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Sample records for contrast agents fdtd

  1. Flow Cytometry with Gold Nanoparticles and their Clusters as scattering Contrast Agents: FDTD Simulation of Light-Cell Interaction

    PubMed Central

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

    2010-01-01

    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 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 a new avenue in the development of advanced cytometric techniques based on scattering effects from nanoscale targets. PMID:19670359

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

    PubMed

    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.

  3. Ultrasound contrast agents

    PubMed Central

    Ignee, Andre; Atkinson, Nathan S. S.; Schuessler, Gudrun; Dietrich, Christoph F.

    2016-01-01

    Endoscopic ultrasound (EUS) plays an important role in imaging of the mediastinum and abdominal organs. Since the introduction of US contrast agents (UCA) for transabdominal US, attempts have been made to apply contrast-enhanced US techniques also to EUS. Since 2003, specific contrast-enhanced imaging was possible using EUS. Important studies have been published regarding contrast-enhanced EUS and the characterization of focal pancreatic lesions, lymph nodes, and subepithelial tumors. In this manuscript, we describe the relevant UCA, their application, and specific image acquisition as well as the principles of image tissue characterization using contrast-enhanced EUS. Safety issues, potential future developments, and EUS-specific issues are reviewed. PMID:27824024

  4. Contrast agents for MRI.

    PubMed

    Shokrollahi, H

    2013-12-01

    Contrast agents are divided into two categories. The first one is paramagnetic compounds, including lanthanides like gadolinium, which mainly reduce the longitudinal (T1) relaxation property and result in a brighter signal. The second class consists of super-paramagnetic magnetic nanoparticles (SPMNPs) such as iron oxides, which have a strong effect on the transversal (T2) relaxation properties. SPMNPs have the potential to be utilized as excellent probes for magnetic resonance imaging (MRI). For instance, clinically benign iron oxide and engineered ferrite nanoparticles provide a good MRI probing capability for clinical applications. Furthermore, the limited magnetic property and inability to escape from the reticuloendothelial system (RES) of the used nanoparticles impede their further advancement. Therefore, it is necessary to develop the engineered magnetic nanoparticle probes for the next-generation molecular MRI. Considering the importance of MRI in diagnosing diseases, this paper presents an overview of recent scientific achievements in the development of new synthetic SPMNP probes whereby the sensitive and target-specific observation of biological events at the molecular and cellular levels is feasible.

  5. Polymeric gastrointestinal MR contrast agents.

    PubMed

    Tilcock, C; Unger, E C; Ahkong, Q F; Fritz, T; Koenig, S H; Brown, R D

    1991-01-01

    Combining either paramagnetic (gadolinium chelates) or superparamagnetic (ferrite) contrast agents with polymers such as polyethylene glycol or cellulose, or with simple sugars such as dextrose, results in mixtures that exhibit improved T1 and/or T2 relaxivity compared with that of the contrast agent alone. It is suggested that the addition of such inexpensive and nontoxic polymers or saccharides may improve the effectiveness and decrease the cost of enteric contrast agents.

  6. Nuclear magnetic resonance contrast agents

    DOEpatents

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

    1997-12-30

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

  7. Nuclear magnetic resonance contrast agents

    DOEpatents

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

    1997-01-01

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

  8. Mechanisms of contrast agent destruction.

    PubMed

    Chomas, J E; Dayton, P; Allen, J; Morgan, K; Ferrara, K W

    2001-01-01

    Various applications of contrast-assisted ultrasound, including blood vessel detection, perfusion estimation, and drug delivery, require controlled destruction of contrast agent microbubbles. The lifetime of a bubble depends on properties of the bubble shell, the gas core, and the acoustic waveform impinging on the bubble. Three mechanisms of microbubble destruction are considered: fragmentation, acoustically driven diffusion, and static diffusion. Fragmentation is responsible for rapid destruction of contrast agents on a time scale of microseconds. The primary characteristics of fragmentation are a very large expansion and subsequent contraction, resulting in instability of the bubble. Optical studies using a novel pulsed-laser optical system show the expansion and contraction of ultrasound contrast agent microbubbles with the ratio of maximum diameter to minimum diameter greater than 10. Fragmentation is dependent on the transmission pressure, occurring in over 55% of bubbles insonified with a peak negative transmission pressure of 2.4 MPa and in less than 10% of bubbles insonified with a peak negative transmission pressure of 0.8 MPa. The echo received from a bubble decorrelates significantly within two pulses when the bubble is fragmented, creating an opportunity for rapid detection of bubbles via a decorrelation-based analysis. Preliminary findings with a mouse tumor model verify the occurrence of fragmentation in vivo. A much slower mechanism of bubble destruction is diffusion, which is driven by both a concentration gradient between the concentration of gas in the bubble compared with the concentration of gas in the liquid, as well as convective effects of motion of the gas-liquid interface. The rate of diffusion increases during insonation, because of acoustically driven diffusion, producing changes in diameter on the time scale of the acoustic pulse length, thus, on the order of microseconds. Gas bubbles diffuse while they are not being insonified, termed

  9. Intraperitoneal contrast agents for computed tomography

    SciTech Connect

    Stork, J.

    1985-08-01

    Intraperitoneal contrast agents have been used to diagnose mass lesions, adhesions, and hernias using conventional radiographic techniques. The use of intraperitoneal contrast agents in conjunction with computed tomography (CT) has been limited and is the subject of this report.

  10. "Basic MR Relaxation Mechanisms & Contrast Agent Design"

    PubMed Central

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

    2015-01-01

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

  11. Status of liposomes as MR contrast agents.

    PubMed

    Unger, E C; Shen, D K; Fritz, T A

    1993-01-01

    Recent work on the development of liposomal magnetic resonance (MR) contrast agents has yielded structures with higher overall relaxivity than that of other nanoparticles of similar diameter. Liposomes incorporating membrane-bound complexes of manganase ("memsomes") produce greater hepatic enhancement per micromole of metal ion than either ferrite particles or paramagnetic chelates. Memsomes also hold promise for targeting of sites outside the liver. Work is in progress to take these agents into clinical trials.

  12. Acoustic response from adherent targeted contrast agents

    PubMed Central

    Zhao, Shukui; Kruse, Dustin E.; Ferrara, Katherine W.; Dayton, Paul A.

    2006-01-01

    In ultrasonic molecular imaging, encapsulated micron-sized gas bubbles are tethered to a blood vessel wall by targeting ligands. A challenging problem is to detect the echoes from adherent microbubbles and distinguish them from echoes from non-adherent agents and tissue. Echoes from adherent contrast agents are observed to include a high amplitude at the fundamental frequency, and significantly different spectral shape compared with free agents (p < 0.0003). Mechanisms for the observed acoustical difference and potential techniques to utilize these differences for molecular imaging are proposed. PMID:17225437

  13. Superhydrophobic silica nanoparticles as ultrasound contrast agents.

    PubMed

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

    2017-05-01

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

  14. Nano/microparticles and ultrasound contrast agents.

    PubMed

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

    2013-12-28

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

  15. Microbubble ultrasound contrast agents: a review.

    PubMed

    Stride, E; Saffari, N

    2003-01-01

    The superior scattering properties of gas bubbles compared with blood cells have made microbubble ultrasound contrast agents important tools in ultrasound diagnosis. Over the past 2 years they have become the focus of a wide and rapidly expanding field of research, with their benefits being repeatedly demonstrated, both in ultrasound image enhancement, and more recently in drug and gene delivery applications. However, despite considerable investigation, their behaviour is by no means fully understood and, while no definite evidence of harmful effects has been obtained, there remain some concerns as to their safety. In this review the existing theoretical and experimental evidence is examined in order to clarify the extent to which contrast agents are currently understood and to identify areas for future research. In particular the disparity between the conditions considered in theoretical models and those encountered both in vitro, and more importantly in vivo is discussed, together with the controversy regarding the risk of harmful bio-effects.

  16. Hypoxia-sensitive NMR contrast agents

    SciTech Connect

    Swartz, H.M.; Chen, K.; Pals, M.; Sentjurc, M.; Morse, P.D. 2d.

    1986-02-01

    The rate of reduction of nitroxides is shown to be more rapid in hypoxic cells. The rate of reduction and the effect of hypoxia on the reduction rate vary for different nitroxides. These findings indicate that it may be feasible to develop in vivo NMR contrast agents that selectively will indicate areas of hypoxia and thereby aid in the detection of disease processes such as neoplasia, ischemia, and inflammation.

  17. Nanoparticle contrast agents for optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Gabriele, Michelle Lynn

    Optical coherence tomography (OCT) provides real-time, objective, in-vivo, optical cross-sectional representations of the retina and optic nerve. Recent innovations in image acquisition, including the incorporation of Fourier/spectral-domain detection, have improved imaging speed, sensitivity and resolution. Still, there remain specific structures within ocular OCT images, such as retinal ganglion cells (RGCs), which are of clinical interest but consistently have low contrast. This makes it difficult to differentiate between surrounding layers and structures. The objectives of this project were: (1) To establish a reliable method for OCT imaging of the healthy and diseased mouse eye in order to provide a platform for testing the utility of OCT contrast agents for ocular imaging, (2) To develop antibody-conjugated gold nanoparticles suitable for targeting specific structures and enhancing OCT image contrast in the mouse eye, and (3) To examine the localized contrast-enhancing ability and biocompatibility of gold nanoparticle contrast agents in-vivo. Our organizing hypotheses were that nanoparticles could improve contrast by modulating the intensity of backscattered light detected by OCT and that they could be directed to ocular structures of interest using antibodies specific to cellular markers. A reproducible method for imaging the mouse retina and quantifying retinal thickness was developed and this technique was then applied to a mouse model for retinal ganglion cell loss, optic nerve crush. Gold nanorods were designed specifically to augment the backscattering OCT signal at the same wavelengths of light used in current ophthalmic OCT imaging schemes (resonant wavelength lambda = 840 nm). Anti-CD90.1 (Thy1.1) antibodies were conjugated to the gold nanorods and a protocol for characterization of the success of antibody conjugation was developed. Upon injection, the gold nanorods were found to remain in the vitreous post-injection, with many consumed by an early

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

    NASA Astrophysics Data System (ADS)

    Sinharay, Sanhita; Pagel, Mark D.

    2016-06-01

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

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

    PubMed Central

    Sinharay, Sanhita; Pagel, Mark D.

    2016-01-01

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

  20. Intraoperative imaging using intravascular contrast agent

    NASA Astrophysics Data System (ADS)

    Watson, Jeffrey R.; Martirosyan, Nikolay; Garland, Summer; Lemole, G. Michael; Romanowski, Marek

    2016-03-01

    Near-infrared (NIR) contrast agents are becoming more frequently studied in medical imaging due to their advantageous characteristics, most notably the ability to capture near-infrared signal across the tissue and the safety of the technique. This produces a need for imaging technology that can be specific for both the NIR dye and medical application. Indocyanine green (ICG) is currently the primary NIR dye used in neurosurgery. Here we report on using the augmented microscope we described previously for image guidance in a rat glioma resection. Luc-C6 cells were implanted in a rat in the left-frontal lobe and grown for 22 days. Surgical resection was performed by a neurosurgeon using augmented microscopy guidance with ICG contrast. Videos and images were acquired to evaluate image quality and resection margins. ICG accumulated in the tumor tissue due to enhanced permeation and retention from the compromised bloodbrain- barrier. The augmented microscope was capable of guiding the rat glioma resection and intraoperatively highlighted tumor tissue regions via ICG fluorescence under normal illumination of the surgical field.

  1. Synthesis of laboratory Ultrasound Contrast Agents.

    PubMed

    Park, Jingam; Park, Donghee; Shin, Unchul; Moon, Sanghyub; Kim, Chihyun; Kim, Han Sung; Park, Hyunjin; Choi, Kiju; Jung, Bongkwang; Oh, Jaemin; Seo, Jongbum

    2013-10-21

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

  2. Temperature dependent behavior of ultrasound contrast agents.

    PubMed

    Mulvana, Helen; Stride, Eleanor; Hajnal, Jo V; Eckersley, Robert J

    2010-06-01

    Recent interest in ultrasound contrast agents (UCAs) as tools for quantitative imaging and therapy has increased the need for accurate characterization. Laboratory investigations are frequently undertaken in a water bath at room temperature; however, implications for in vivo applications are not presented. Acoustic investigation of a bulk suspension of SonoVue (Bracco Research, Geneva, Switzerland) was made in a water bath at temperatures of 20-45 degrees C. UCA characteristics were significantly affected by temperature, particularly between 20 and 40 degrees C, leading to an increase in attenuation from 1.7-2.5 dB, respectively (p = 0.002) and a 2-dB increase in scattered signal over the same range (p = 0.05) at an insonation pressure of 100 kPa. Optical data supported the hypothesis that a temperature-mediated increase in diameter was the dominant cause, and revealed a decrease in bubble stability. In conclusion, measurements made at room temperature require careful interpretation with regard to behavior in vivo.

  3. Gold nanorods: contrast agents for photoacoustic imaging?

    NASA Astrophysics Data System (ADS)

    Ungureanu, C.; Gopal, R. Raja; van Leeuwen, T. G.; Manohar, S.

    2007-07-01

    Gold nanorods are seen as possible contrast agents for photoacoustic imaging since they have strong absorption peaks at near-infrared wavelengths. Also they are easy to conjugate with various proteins. If these particles can be conjugated with cancer affinity proteins then these particles can accumulate specifically at a tumor site. By detecting the presence of accumulation of gold nanorods inside the tissue the indirect detection of tumor can be realized. When these particles are irradiated with light pulses of appropriate temporal properties and energy the temperature around these particles can be high enough to induce apoptosis or necrosis in the surrounding cells. In order to use these particles at their full potential we must determine precisely their optical properties. We simulated the optical properties of gold nanorods synthesized by us using the DDSCAT code. The simulated spectra agree qualitatively with the spectra determined using spectrometry and also determined using photoacoustic spectroscopy. Further the values of molar extinction coefficient derived from the simulations were similar to the data measured experimentally by other groups. These results validated qualitatively the model used in the simulations. During simulations we found that the choice of the dielectric function used in simulations plays an important role in the results.

  4. Contrast agents for cardiac angiography: effects of a nonionic agent vs. a standard ionic agent

    SciTech Connect

    Bettmann, M.A.; Bourdillon, P.D.; Barry, W.H.; Brush, K.A.; Levin, D.C.

    1984-12-01

    The effects on cardiac hemodynamics and of a standard contrast agent, sodium methylglucamine diatrizoate (Renografin 76) were compared with the effects of a new nonionic agent (iohexol) in a double-blind study in 51 patietns undergoing coronary angiography and left ventriculography. No significant alteration in measured blood parameters occurred with either contrast agent. Hemodynamic changes occurred with both, but were significantly greater with the standard renografin than with the low-osmolality, nonionic iohexol. After left ventriculography, heart rate increased and peripheral arterial pressure fell with both agents, but less with iohexol. It is concluded that iohexol causes less alteration in cardiac function than does the agent currently most widely used. Nonionic contrast material is likely to improve the safety of coronary angiography, particularly in those patients at greatest risk.

  5. Nanoparticle Contrast Agents for Computed Tomography: A Focus on Micelles

    PubMed Central

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

    2014-01-01

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

  6. [General adverse reactions to contrast agents. Classification and general concepts].

    PubMed

    Aguilar García, J J; Parada Blázquez, M J; Vargas Serrano, B; Rodríguez Romero, R

    2014-06-01

    General adverse reactions to intravenous contrast agents are uncommon, although relevant due to the growing number of radiologic tests that use iodinated or gadolinium-based contrast agents. Although most of these reactions are mild, some patients can experience significant reactions that radiologists should know how to prevent and treat.

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

    SciTech Connect

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

    1984-10-01

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

  8. Current topics in ultrasound contrast agent application and design

    NASA Astrophysics Data System (ADS)

    Allen, John S.; Kruse, Dustin E.; May, Donovan J.

    2001-05-01

    Ultrasound contrast agents are bubbles, 1-10 microns in radius, encapsulated by a lipid, protein, polymer or fluid shell. The agents have been used to distinguish the acoustic scattering signatures of blood from those of the surrounding tissue. This is possible due to the nonlinear response of the agent, which is similar to that of a free gas bubble. Upon sufficient forcing the agents will oscillate nonlinearly about their equilibrium radius, and for specific conditions, produce nonlinear resonance responses which are integer multiples of the primary resonance. Ultrasound tissue perfusion studies have been developed which are based on the destruction of contract agents coupled to the measurement of blood flow. Nevertheless, many outstanding issues remain in contrast agent design especially with respect to emerging applications. Even with the use of higher order harmonics there is a lack of an acoustic signature or destruction mechanism at frequencies above approximately 5.0 MHz with conventional agents. The design and use of a high frequency contrast agent is addressed by exploiting the multiple scattering response of agents modled as spherical elastic shells. Also considered is the nonlinear response of elastic-shelled agents. The considerations of shells modeled as linear and nonlinear elastic materials are discussed. The use of contrast agents for targeted drug delivery has recently received much attention. More specifically, the ImaRx Corporation (Tucson, Arizona) has developed thick fluid shelled agents, which release suspended taxol-based drugs from their shells upon destruction. Shape instabilities and surface waves correspond with the fragmentation and destruction of the agents. Finally, the interaction of multiple contrast agents has received little attention with respect to these emerging applications.

  9. Iron Oxide as an MRI Contrast Agent for Cell Tracking

    PubMed Central

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

    2015-01-01

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

  10. Manganese-based MRI contrast agents: past, present and future

    PubMed Central

    Pan, Dipanjan; Schmieder, Anne H.; Wickline, Samuel A.; Lanza, Gregory M.

    2011-01-01

    Paramagnetic and superparamagnetic metals are used as contrast materials for magnetic resonance (MR) based techniques. Lanthanide metal gadolinium (Gd) has been the most widely explored, predominant paramagnetic contrast agent until the discovery and association of the metal with nephrogenic systemic fibrosis (NSF), a rare but serious side effects in patients with renal or kidney problems. Manganese was one of the earliest reported examples of paramagnetic contrast material for MRI because of its efficient positive contrast enhancement. In this review, manganese based contrast agent approaches are discussed with a particular emphasis on their synthetic approaches. Both small molecules based typical blood pool contrast agents and more recently developed novel nanometer sized materials are reviewed focusing on a number of successful molecular imaging examples. PMID:22043109

  11. [Contrast agents in magnetic resonance imaging: development and problems].

    PubMed

    Xu, Yi-kai

    2002-09-01

    In spite of the inherent versatility of magnetic resonance imaging (MRI), researchers and clinicians from both home and aboard have made great achievements in developing safe and effective contrast agents. Many new agents are expected to be available for clinical use in the near future. It is of clinical importance that the agents should expand the diagnostic utility of MRI, improve the detection of tiny lesions and help evaluate specific tissue or organ functions. This article aims to examine current status of contrast agents for MRI and the problems waiting for solutions.

  12. A review of responsive MRI contrast agents: 2005–2014

    PubMed Central

    Hingorani, Dina V.; Bernstein, Adam S.; Pagel, Mark D.

    2014-01-01

    This review focuses on MRI contrast agents that are responsive to a change in a physiological biomarker. The response mechanisms are dependent on six physicochemical characteristics, including the accessibility of water to the agent, tumbling time, proton exchange rate, electron spin state, MR frequency, or superparamagnetism of the agent. These characteristics can be affected by changes in concentrations or activities of enzymes, proteins, nucleic acids, metabolites, or metal ions, or changes in redox state, pH, temperature, or light. A total of 117 examples are presented, including examples that employ nuclei other than 1H, which attests to the creativity of multidisciplinary research efforts to develop responsive MRI contrast agents. PMID:25355685

  13. A Brief Account of Nanoparticle Contrast Agents for Photoacoustic Imaging

    PubMed Central

    Pan, Dipanjan; Kim, Benjamin; Wang, Lihong V.; Lanza, Gregory M

    2014-01-01

    Photoacoustic imaging (PAI) is a hybrid, nonionizing modality offering excellent spatial resolution, deep penetration, and high soft tissue contrast. In PAI, signal is generated based on the absorption of laser-generated optical energy by endogenous tissues or exogenous contrast agents leading to acoustic emissions detected by an ultrasound transducer. Research in this area over the years has shown that PAI has the ability to provide both physiological and molecular imaging, which can be viewed alone or used in a hybrid modality fashion to extend the anatomic and hemodynamic sensitivities of clinical ultrasound. PAI may be performed using inherent contrast afforded by light absorbing molecules such as hemoglobin, myoglobin, and melanin or exogenous small molecule contrast agent such as near infrared dyes and porphyrins. However, this review summarizes the potential of exogenous nanoparticle-based agents for PAI applications including contrast based on gold particles, carbon nanotubes, and encapsulated copper compounds. PMID:23983210

  14. A brief account of nanoparticle contrast agents for photoacoustic imaging.

    PubMed

    Pan, Dipanjan; Kim, Benjamin; Wang, Lihong V; Lanza, Gregory M

    2013-01-01

    Photoacoustic imaging (PAI) is a hybrid, nonionizing modality offering excellent spatial resolution, deep penetration, and high soft tissue contrast. In PAI, signal is generated based on the absorption of laser-generated optical energy by endogenous tissues or exogenous contrast agents leading to acoustic emissions detected by an ultrasound transducer. Research in this area over the years has shown that PAI has the ability to provide both physiological and molecular imaging, which can be viewed alone or used in a hybrid modality fashion to extend the anatomic and hemodynamic sensitivities of clinical ultrasound. PAI may be performed using inherent contrast afforded by light absorbing molecules such as hemoglobin, myoglobin, and melanin or exogenous small molecule contrast agent such as near infrared dyes and porphyrins. However, this review summarizes the potential of exogenous nanoparticle-based agents for PAI applications including contrast based on gold particles, carbon nanotubes, and encapsulated copper compounds.

  15. A multimeric MR-optical contrast agent for multimodal imaging†

    PubMed Central

    Harrison, Victoria S. R.; Carney, Christiane E.; Macrenaris, Keith W.

    2015-01-01

    We describe the design, synthesis and in vitro evaluation of a multimodal and multimeric contrast agent. The agent consists of three macrocyclic Gd(III) chelates conjugated to a fluorophore and possesses high relaxivity, water solubility, and is nontoxic. The modular synthesis is amenable for the incorporation of a variety of fluorophores to generate molecular constructs for a number of applications. PMID:25137290

  16. Multiwalled carbon nanotube hybrids as MRI contrast agents.

    PubMed

    Kuźnik, Nikodem; Tomczyk, Mateusz Michał

    2016-01-01

    Magnetic resonance imaging (MRI) is one of the most commonly used tomography techniques in medical diagnosis due to the non-invasive character, the high spatial resolution and the possibility of soft tissue imaging. Contrast agents, such as gadolinium complexes and superparamagnetic iron oxides, are administered to spotlight certain organs and their pathologies. Many new models have been proposed that reduce side effects and required doses of these already clinically approved contrast agents. These new candidates often possess additional functionalities, e.g., the possibility of bioactivation upon action of particular stimuli, thus serving as smart molecular probes, or the coupling with therapeutic agents and therefore combining both a diagnostic and therapeutic role. Nanomaterials have been found to be an excellent scaffold for contrast agents, among which carbon nanotubes offer vast possibilities. The morphology of multiwalled carbon nanotubes (MWCNTs), their magnetic and electronic properties, the possibility of different functionalization and the potential to penetrate cell membranes result in a unique and very attractive candidate for a new MRI contrast agent. In this review we describe the different issues connected with MWCNT hybrids designed for MRI contrast agents, i.e., their synthesis and magnetic and dispersion properties, as well as both in vitro and in vivo behavior, which is important for diagnostic purposes. An introduction to MRI contrast agent theory is elaborated here in order to point to the specific expectations regarding nanomaterials. Finally, we propose a promising, general model of MWCNTs as MRI contrast agent candidates based on the studies presented here and supported by appropriate theories.

  17. Multiwalled carbon nanotube hybrids as MRI contrast agents

    PubMed Central

    Tomczyk, Mateusz Michał

    2016-01-01

    Summary Magnetic resonance imaging (MRI) is one of the most commonly used tomography techniques in medical diagnosis due to the non-invasive character, the high spatial resolution and the possibility of soft tissue imaging. Contrast agents, such as gadolinium complexes and superparamagnetic iron oxides, are administered to spotlight certain organs and their pathologies. Many new models have been proposed that reduce side effects and required doses of these already clinically approved contrast agents. These new candidates often possess additional functionalities, e.g., the possibility of bioactivation upon action of particular stimuli, thus serving as smart molecular probes, or the coupling with therapeutic agents and therefore combining both a diagnostic and therapeutic role. Nanomaterials have been found to be an excellent scaffold for contrast agents, among which carbon nanotubes offer vast possibilities. The morphology of multiwalled carbon nanotubes (MWCNTs), their magnetic and electronic properties, the possibility of different functionalization and the potential to penetrate cell membranes result in a unique and very attractive candidate for a new MRI contrast agent. In this review we describe the different issues connected with MWCNT hybrids designed for MRI contrast agents, i.e., their synthesis and magnetic and dispersion properties, as well as both in vitro and in vivo behavior, which is important for diagnostic purposes. An introduction to MRI contrast agent theory is elaborated here in order to point to the specific expectations regarding nanomaterials. Finally, we propose a promising, general model of MWCNTs as MRI contrast agent candidates based on the studies presented here and supported by appropriate theories. PMID:27547627

  18. Contrast agent enhanced pQCT of articular cartilage

    NASA Astrophysics Data System (ADS)

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

    2007-02-01

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

  19. Cell Labeling via Membrane-Anchored Lipophilic MR Contrast Agents

    PubMed Central

    2015-01-01

    Cell tracking in vivo with MR imaging requires the development of contrast agents with increased sensitivity that effectively label and are retained by cells. Most clinically approved Gd(III)-based contrast agents require high incubation concentrations and prolonged incubation times for cellular internalization. Strategies to increase contrast agent permeability have included conjugating Gd(III) complexes to cell penetrating peptides, nanoparticles, and small molecules which have greatly improved cell labeling but have not resulted in improved cellular retention. To overcome these challenges, we have synthesized a series of lipophilic Gd(III)-based MR contrast agents that label cell membranes in vitro. Two of the agents were synthesized with a multiplexing strategy to contain three Gd(III) chelates (1 and 2) while the third contains a single Gd(III) chelate (3). These new agents exhibit significantly enhanced labeling and retention in HeLa and MDA-MB-231-mcherry cells compared to agents that are internalized by cells (4 and Prohance). PMID:24787689

  20. Methods for blood flow measurements using ultrasound contrast agents

    NASA Astrophysics Data System (ADS)

    Fowlkes, J. Brian

    2003-10-01

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

  1. Contrast agent influences MRI phase-contrast flow measurements in small vessels.

    PubMed

    Lagerstrand, Kerstin M; Vikhoff-Baaz, Barbro; Starck, Göran; Forssell-Aronsson, Eva

    2010-07-01

    Contrast-enhanced MR angiography is often combined with phase contrast (PC) flow measurement to answer a particular clinical question. The contrast agent that is administered during contrast-enhanced MR angiography may still be present in the blood during the consecutive PC flow measurement. The aim of this work was to evaluate the influence of contrast agent on PC flow measurements in small vessels. For that purpose, both in vivo measurements and computer simulations were performed. The dependence of the PC flow quantification on the signal amplitude difference between blood and stationary background tissue for various vessel sizes was characterized. Results show that the partial-volume effect strongly affects the accuracy of the PC flow quantification when the imaged vessel is small compared to the spatial resolution. A higher blood-to-background-contrast level during imaging significantly increases the partial-volume effect and thereby reduces the accuracy of the flow quantification. On the other hand, a higher blood-to-background-contrast level facilitated the segmentation of the vessel for flow rate determination. PC flow measurements should therefore be performed after contrast agent administration in large vessels, but before contrast agent administration in small vessels.

  2. Structure – relaxivity relationships among targeted MR contrast agents

    PubMed Central

    Zhang, Zhaoda

    2012-01-01

    Paramagnetic gadolinium(III) complexes are widely used to increase contrast in magnetic resonance (MR) images. Contrast enhancement depends on the concentration of the gadolinium complex and on its relaxivity, an inherent property of the complex. Increased relaxivity results in greater image contrast or the ability to detect the contrast agent at a lower concentration. Increasing relaxivity enables imaging of abundant molecular targets. Relaxivity depends on the structure of the complex, kinetics of inner-sphere and second sphere water exchange, and on the rotational dynamics of the molecule. The latter, and in some cases the former, properties of the complex change when it is bound to its target. All of these properties can be rationally tuned to enhance relaxivitry. In this Microreview we summarize our efforts in understanding and optimizing the relaxivity of contrast agents targeted to serum albumin and to fibrin. PMID:22745568

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

    PubMed

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

    2014-12-18

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

  4. Contrast agent stability: a continuous B-mode imaging approach.

    PubMed

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

    2001-10-01

    The stability of contrast agents in suspensions with various dissolved gas levels has not been reported in the literature. An in vitro investigation has been carried out that studied the combined effect of varying the acoustic pressure along with degassing the suspension environment. In this study, the contrast agents were introduced into suspensions with different oxygen concentration levels, and their relative performance was assessed in terms of decay rate of their backscatter echoes. The partial pressures of oxygen in those solutions ranged between 1.5 and 26 kPa. Two IV and one arterial contrast agents were used: Definity, Quantison, and Myomap. It was found that Quantison and Myomap released free bubbles at high acoustic pressure that also dissolved faster in degassed suspensions. The backscatter decay for Definity did not depend on the air content of the suspensions. The destruction of bubbles was dependent on acoustic pressure. Different backscatter performance was observed by different populations of bubbles of the last two agents. The physical quantity of "overall backscatter" (OB) was defined as the integral of the decay rate over time of the backscatter of the contrast suspensions, and improved significantly the understanding of the behaviour of the agents. A quantitative analysis of the backscatter properties of contrast agents using a continuous imaging approach was difficult to achieve. This is due to the fact that the backscatter in the field of view is representative of a bubble population affected by the ultrasound (US) field, but this bubble population is not representative of the contrast suspension in the whole tank. Single frame insonation is suggested to avoid the effects of decay due to the ultrasonic field, and to measure a tank-representative backscatter. The definition of OB was useful, however, in understanding the behaviour of the agents.

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

    SciTech Connect

    Ogunlade, Olumide Beard, Paul

    2015-01-15

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

  6. Exceedingly small iron oxide nanoparticles as positive MRI contrast agents.

    PubMed

    Wei, He; Bruns, Oliver T; Kaul, Michael G; Hansen, Eric C; Barch, Mariya; Wiśniowska, Agata; Chen, Ou; Chen, Yue; Li, Nan; Okada, Satoshi; Cordero, Jose M; Heine, Markus; Farrar, Christian T; Montana, Daniel M; Adam, Gerhard; Ittrich, Harald; Jasanoff, Alan; Nielsen, Peter; Bawendi, Moungi G

    2017-02-28

    Medical imaging is routine in the diagnosis and staging of a wide range of medical conditions. In particular, magnetic resonance imaging (MRI) is critical for visualizing soft tissue and organs, with over 60 million MRI procedures performed each year worldwide. About one-third of these procedures are contrast-enhanced MRI, and gadolinium-based contrast agents (GBCAs) are the mainstream MRI contrast agents used in the clinic. GBCAs have shown efficacy and are safe to use with most patients; however, some GBCAs have a small risk of adverse effects, including nephrogenic systemic fibrosis (NSF), the untreatable condition recently linked to gadolinium (Gd) exposure during MRI with contrast. In addition, Gd deposition in the human brain has been reported following contrast, and this is now under investigation by the US Food and Drug Administration (FDA). To address a perceived need for a Gd-free contrast agent with pharmacokinetic and imaging properties comparable to GBCAs, we have designed and developed zwitterion-coated exceedingly small superparamagnetic iron oxide nanoparticles (ZES-SPIONs) consisting of ∼3-nm inorganic cores and ∼1-nm ultrathin hydrophilic shell. These ZES-SPIONs are free of Gd and show a high T1 contrast power. We demonstrate the potential of ZES-SPIONs in preclinical MRI and magnetic resonance angiography.

  7. Blood pool contrast agents for venous magnetic resonance imaging

    PubMed Central

    Oliveira, Irai S.; Li, Weier; Ganguli, Suvranu; Prabhakar, Anand M.

    2016-01-01

    Imaging of the venous system plays a vital role in the diagnosis and management of a wide range of clinically significant disorders. There have been great advances in venous imaging techniques, culminating in the use of magnetic resonance venography (MRV). Although MRV has distinct advantages in anatomic and quantitative cross sectional imaging without ionizing radiation, there are well-known challenges in acquisition timing and contrast administration in patients with renal impairment. The latest advancement involves the addition of new contrast media agents, which have emerged as valuable alternatives in these difficult scenarios. In this review, we will focus on a group of specific contrast agents called blood pool agents and discuss their salient features and clinical applications. PMID:28123972

  8. [Gadolinium-based contrast agents for magnetic resonance imaging].

    PubMed

    Carrasco Muñoz, S; Calles Blanco, C; Marcin, Javier; Fernández Álvarez, C; Lafuente Martínez, J

    2014-06-01

    Gadolinium-based contrast agents are increasingly being used in magnetic resonance imaging. These agents can improve the contrast in images and provide information about function and metabolism, increasing both sensitivity and specificity. We describe the gadolinium-based contrast agents that have been approved for clinical use, detailing their main characteristics based on their chemical structure, stability, and safety. In general terms, these compounds are safe. Nevertheless, adverse reactions, the possibility of nephrotoxicity from these compounds, and the possibility of developing nephrogenic systemic fibrosis will be covered in this article. Lastly, the article will discuss the current guidelines, recommendations, and contraindications for their clinical use, including the management of pregnant and breast-feeding patients.

  9. Geometrical confinement of gadolinium-based contrast agents in nanoporous particles enhances T1 contrast

    PubMed Central

    Ananta, Jeyarama S.; Godin, Biana; Sethi, Richa; Moriggi, Loick; Liu, Xuewu; Serda, Rita E.; Krishnamurthy, Ramkumar; Muthupillai, Raja; Bolskar, Robert D.; Helm, Lothar; Ferrari, Mauro; Wilson, Lon J.; Decuzzi, Paolo

    2010-01-01

    Magnetic resonance imaging contrast agents are currently designed by modifying their structural and physiochemical properties in order to improve relaxivity and to enhance image contrast. Here we show a general method for increasing relaxivity by confining contrast agents inside the nanoporous structure of silicon particles. Magnevist, gadofullerenes and gadonanotubes were loaded inside the pores of quasi-hemispherical and discoidal particles. For all combinations of nanoconstructs, a boost in longitudinal proton relaxivity r1 was observed: for Magnevist, r1~14 mM-1s-1/Gd3+ion (~8.15×10+7 mM-1s-1/construct); for gadofullerenes, r1~200 mM-1s-1/Gd3+ion (~7×10+9 mM-1s-1/construct); for gadonanotubes, r1~150 mM-1s-1/Gd3+ion (~2×10+9 mM-1s-1/construct). These relaxivity values are about 4 to 50 times larger than that of clinically-available gadolinium-based agents (~4 mM-1s-1 /Gd3+ion). The enhancement in contrast is attributed to the geometrical confinement of the agents, which influences the paramagnetic behavior of the Gd3+ions. Thus, nanoscale confinement offers a new and general strategy for enhancing the contrast of gadolinium-based contrast agents. PMID:20972435

  10. Stability analysis of ultrasound thick-shell contrast agents

    PubMed Central

    Lu, Xiaozhen; Chahine, Georges L.; Hsiao, Chao-Tsung

    2012-01-01

    The stability of thick shell encapsulated bubbles is studied analytically. 3-D small perturbations are introduced to the spherical oscillations of a contrast agent bubble in response to a sinusoidal acoustic field with different amplitudes of excitation. The equations of the perturbation amplitudes are derived using asymptotic expansions and linear stability analysis is then applied to the resulting differential equations. The stability of the encapsulated microbubbles to nonspherical small perturbations is examined by solving an eigenvalue problem. The approach then identifies the fastest growing perturbations which could lead to the breakup of the encapsulated microbubble or contrast agent. PMID:22280568

  11. Gd-HOPO Based High Relaxivity MRI Contrast Agents

    SciTech Connect

    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.

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

    PubMed

    Park, Donghee; Song, Gillsoo; Jo, Yongjun; Won, Jongho; Son, Taeyoon; Cha, Ohrum; Kim, Jinho; Jung, Byungjo; Park, Hyunjin; Kim, Chul-Woo; Seo, Jongbum

    2016-01-01

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

  13. Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration

    PubMed Central

    Park, Donghee; Song, Gillsoo; Jo, Yongjun; Won, Jongho; Son, Taeyoon; Cha, Ohrum; Kim, Jinho; Jung, Byungjo; Park, Hyunjin; Kim, Chul-Woo; Seo, Jongbum

    2016-01-01

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

  14. Molecular Imaging and Contrast Agent Database (MICAD): evolution and progress.

    PubMed

    Chopra, Arvind; Shan, Liang; Eckelman, W C; Leung, Kam; Latterner, Martin; Bryant, Stephen H; Menkens, Anne

    2012-02-01

    The purpose of writing this review is to showcase the Molecular Imaging and Contrast Agent Database (MICAD; www.micad.nlm.nih.gov ) to students, researchers, and clinical investigators interested in the different aspects of molecular imaging. This database provides freely accessible, current, online scientific information regarding molecular imaging (MI) probes and contrast agents (CA) used for positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging, X-ray/computed tomography, optical imaging and ultrasound imaging. Detailed information on >1,000 agents in MICAD is provided in a chapter format and can be accessed through PubMed. Lists containing >4,250 unique MI probes and CAs published in peer-reviewed journals and agents approved by the United States Food and Drug Administration as well as a comma separated values file summarizing all chapters in the database can be downloaded from the MICAD homepage. Users can search for agents in MICAD on the basis of imaging modality, source of signal/contrast, agent or target category, pre-clinical or clinical studies, and text words. Chapters in MICAD describe the chemical characteristics (structures linked to PubChem), the in vitro and in vivo activities, and other relevant information regarding an imaging agent. All references in the chapters have links to PubMed. A Supplemental Information Section in each chapter is available to share unpublished information regarding an agent. A Guest Author Program is available to facilitate rapid expansion of the database. Members of the imaging community registered with MICAD periodically receive an e-mail announcement (eAnnouncement) that lists new chapters uploaded to the database. Users of MICAD are encouraged to provide feedback, comments, or suggestions for further improvement of the database by writing to the editors at micad@nlm.nih.gov.

  15. Surface Modified Gadolinium Phosphate Nanoparticles as MRI Contrast Agents

    NASA Astrophysics Data System (ADS)

    Dumont, Matthieu F.; Baligand, Celine; Knowles, Elisabeth S.; Meisel, Mark W.; Walter, Glenn A.; Talham, Daniel R.

    2012-02-01

    Nanoparticles of GdPO4H2O were synthesized in a water/oil microemulsion using IGEPAL CO-520 as surfactant resulting in 50 nm to 100 nm particles that are dispersible and stable in water. Using surface modification chemistry previously established for zirconium phosphonate surfaces,ootnotetext J. Monot et al., J. Am. Chem. Soc. 130 (2008) 6243. the particles are directly modified with 5'-phosphate terminated oligonucleotides, and the specific interaction of the divalent phosphate with Gd^3+ sites at the surface is demonstrated. The ability of the modified nanoparticles to act as MRI contrast agents was determined by performing MR relaxivity measurements at 14 T. Solutions of nanopure water, Feridex and Omniscan (FDA cleared contrast agents) in 0.25% agarose were used for comparison and control purposes. MRI data confirm that GdPO4H2O nanoparticles have relaxivities (r1,r2) comparable to commercially available contrast agents.ootnotetext H. Hifumi et al., J. Am. Chem. Soc. 128 (2006) 15090. In addition, biofunctionalization of the surface of the nanoparticles does not prevent their function as MRI contrast agents.

  16. DNA surface modified gadolinium phosphate nanoparticles as MRI contrast agents.

    PubMed

    Dumont, Matthieu F; Baligand, Celine; Li, Yichen; Knowles, Elisabeth S; Meisel, Mark W; Walter, Glenn A; Talham, Daniel R

    2012-05-16

    Oligonucleotide modified gadolinium phosphate nanoparticles have been prepared and their magnetic resonance relaxivity properties measured. Nanoparticles of GdPO4·H2O were synthesized in a water/oil microemulsion using IGEPAL CO-520 as surfactant, resulting in 50 to 100 nm particles that are highly dispersible and stable in water. Using surface modification chemistry previously established for zirconium phosphonate surfaces, the particles are directly modified with 5'-phosphate terminated oligonucleotides, and the specific interaction of the divalent phosphate with Gd(3+) sites at the surface is demonstrated. The ability of the modified nanoparticles to act as MRI contrast agents was determined by performing MR relaxivity measurements at 14.1 T. Solutions of nanopure water, Feridex, and Omniscan (FDA approved contrast agents) in 0.25% agarose were used for comparison and control purposes. MRI data confirm that GdPO4·H2O nanoparticles have relaxivities (r1, r2) comparable to those of commercially available contrast agents. In addition, the data suggest that biofunctionalization of the surface of the nanoparticles does not prevent their function as MRI contrast agents.

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

    PubMed

    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.

  18. Hyperpolarized water as an authentic magnetic resonance imaging contrast agent

    PubMed Central

    McCarney, Evan R.; Armstrong, Brandon D.; Lingwood, Mark D.; Han, Songi

    2007-01-01

    Pure water in a highly 1H spin-polarized state is proposed as a contrast-agent-free contrast agent to visualize its macroscopic evolution in aqueous media by MRI. Remotely enhanced liquids for image contrast (RELIC) utilizes a 1H signal of water that is enhanced outside the sample in continuous-flow mode and immediately delivered to the sample to obtain maximum contrast between entering and bulk fluids. Hyperpolarization suggests an ideal contrast mechanism to highlight the ubiquitous and specific function of water in physiology, biology, and materials because the physiological, chemical, and macroscopic function of water is not altered by the degree of magnetization. We present an approach that is capable of instantaneously enhancing the 1H MRI signal by up to 2 orders of magnitude through the Overhauser effect under ambient conditions at 0.35 tesla by using highly spin-polarized unpaired electrons that are covalently immobilized onto a porous, water-saturated gel matrix. The continuous polarization of radical-free flowing water allowed us to distinctively visualize vortices in model reactors and dispersion patterns through porous media. A 1H signal enhancement of water by a factor of −10 and −100 provides for an observation time of >4 and 7 s, respectively, upon its injection into fluids with a T1 relaxation time of >1.5 s. The implications for chemical engineering or biomedical applications of using hyperpolarized solvents or physiological fluids to visualize mass transport and perfusion with high and authentic MRI contrast originating from water itself, and not from foreign contrast agents, are immediate. PMID:17264210

  19. Nanoengineered multimodal contrast agent for medical image guidance

    NASA Astrophysics Data System (ADS)

    Perkins, Gregory J.; Zheng, Jinzi; Brock, Kristy; Allen, Christine; Jaffray, David A.

    2005-04-01

    Multimodality imaging has gained momentum in radiation therapy planning and image-guided treatment delivery. Specifically, computed tomography (CT) and magnetic resonance (MR) imaging are two complementary imaging modalities often utilized in radiation therapy for visualization of anatomical structures for tumour delineation and accurate registration of image data sets for volumetric dose calculation. The development of a multimodal contrast agent for CT and MR with prolonged in vivo residence time would provide long-lasting spatial and temporal correspondence of the anatomical features of interest, and therefore facilitate multimodal image registration, treatment planning and delivery. The multimodal contrast agent investigated consists of nano-sized stealth liposomes encapsulating conventional iodine and gadolinium-based contrast agents. The average loading achieved was 33.5 +/- 7.1 mg/mL of iodine for iohexol and 9.8 +/- 2.0 mg/mL of gadolinium for gadoteridol. The average liposome diameter was 46.2 +/- 13.5 nm. The system was found to be stable in physiological buffer over a 15-day period, releasing 11.9 +/- 1.1% and 11.2 +/- 0.9% of the total amounts of iohexol and gadoteridol loaded, respectively. 200 minutes following in vivo administration, the contrast agent maintained a relative contrast enhancement of 81.4 +/- 13.05 differential Hounsfield units (ΔHU) in CT (40% decrease from the peak signal value achieved 3 minutes post-injection) and 731.9 +/- 144.2 differential signal intensity (ΔSI) in MR (46% decrease from the peak signal value achieved 3 minutes post-injection) in the blood (aorta), a relative contrast enhancement of 38.0 +/- 5.1 ΔHU (42% decrease from the peak signal value achieved 3 minutes post-injection) and 178.6 +/- 41.4 ΔSI (62% decrease from the peak signal value achieved 3 minutes post-injection) in the liver (parenchyma), a relative contrast enhancement of 9.1 +/- 1.7 ΔHU (94% decrease from the peak signal value achieved 3 minutes

  20. Redox- and hypoxia-responsive MRI contrast agents.

    PubMed

    Do, Quyen N; Ratnakar, James S; Kovács, Zoltán; Sherry, A Dean

    2014-06-01

    The development of responsive or "smart" magnetic resonance imaging (MRI) contrast agents that can report specific biomarker or biological events has been the focus of MRI contrast agent research over the past 20 years. Among various biological hallmarks of interest, tissue redox and hypoxia are particularly important owing to their roles in disease states and metabolic consequences. Herein we review the development of redox-/hypoxia-sensitive T1 shortening and paramagnetic chemical exchange saturation transfer (PARACEST) MRI contrast agents. Traditionally, the relaxivity of redox-sensitive Gd(3+) -based complexes is modulated through changes in the ligand structure or molecular rotation, while PARACEST sensors exploit the sensitivity of the metal-bound water exchange rate to electronic effects of the ligand-pendant arms and alterations in the coordination geometry. Newer designs involve complexes of redox-active metal ions in which the oxidation states have different magnetic properties. The challenges of translating redox- and hypoxia-sensitive agents in vivo are also addressed.

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

    PubMed

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

    2013-10-22

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

  2. Biodegradable polydisulfide dendrimer nanoclusters as MRI contrast agents.

    PubMed

    Huang, Ching-Hui; Nwe, Kido; Al Zaki, Ajlan; Brechbiel, Martin W; Tsourkas, Andrew

    2012-11-27

    Gadolinium-conjugated dendrimer nanoclusters (DNCs) are a promising platform for the early detection of disease; however, their clinical utility is potentially limited due to safety concerns related to nephrogenic systemic fibrosis (NSF). In this paper, biodegradable DNCs were prepared with polydisulfide linkages between the individual dendrimers to facilitate excretion. Further, DNCs were labeled with premetalated Gd chelates to eliminate the risk of free Gd becoming entrapped in dendrimer cavities. The biodegradable polydisulfide DNCs possessed a circulation half-life of >1.6 h in mice and produced significant contrast enhancement in the abdominal aorta and kidneys for as long as 4 h. The DNCs were reduced in circulation as a result of thiol-disulfide exchange, and the degradation products were rapidly excreted via renal filtration. These agents demonstrated effective and prolonged in vivo contrast enhancement and yet minimized Gd tissue retention. Biodegradable polydisulfide DNCs represent a promising biodegradable macromolecular MRI contrast agent for magnetic resonance angiography and can potentially be further developed into target-specific MRI contrast agents.

  3. Cardiac arrhythmias produced by ultrasound and contrast agents

    NASA Astrophysics Data System (ADS)

    Rota, Claudio

    Ultrasound is used widely in medicine for both diagnostic and therapeutic applications. Ultrasound contrast agents are suspensions of gas-filled microbubbles used to enhance diagnostic imaging. Microbubble contrast agents can increase the likelihood of bioeffects of ultrasound associated with acoustic cavitation. Under certain exposure conditions, the interaction of ultrasound with cardiac tissues can produce cardiac arrhythmias. The general objective of this thesis was to develop a greater understanding of ultrasound-induced premature cardiac beats. The hypothesis guiding this work was that acoustic cavitation is the physical mechanism for the production of arrhythmias with ultrasound. This hypothesis was tested through a series of experiments with mice in vivo and theoretical investigations. Results of this research supported the acoustic cavitation hypothesis. The acoustic pressure threshold for premature beats was significantly lower with microbubble contrast agents present in the blood than without. With microbubbles, the threshold for premature beats was below the current output limits of diagnostic devices. The threshold was not significantly dependent upon contrast agent type and was not influenced by contrast agent dose over three orders of magnitude. Furthermore, the dependence of the threshold on acoustic frequency was consistent with the frequency dependence of acoustic cavitation. Experimentally determined thresholds for premature beats in vivo were in excellent agreement with theoretically estimated thresholds for inertial cavitation. A passive cavitation detector (PCD) was used to measure the acoustic emissions produced by cavitating microbubbles in vivo. A direct correlation between the amplitude of the PCD and the percentage of ultrasound pulses producing a premature beat was consistent with cavitation as a mechanism for this bioeffect. Although this thesis focused on the mechanistic understanding of ultrasound-induced arrhythmias, more persistent

  4. Screening CEST contrast agents using ultrafast CEST imaging

    NASA Astrophysics Data System (ADS)

    Xu, Xiang; Yadav, Nirbhay N.; Song, Xiaolei; McMahon, Michael T.; Jerschow, Alexej; van Zijl, Peter C. M.; Xu, Jiadi

    2016-04-01

    A chemical exchange saturation transfer (CEST) experiment can be performed in an ultrafast fashion if a gradient field is applied simultaneously with the saturation pulse. This approach has been demonstrated for studying dia- and para-magnetic CEST agents, hyperpolarized Xe gas and in vivo spectroscopy. In this study we present a simple method for the simultaneous screening of multiple samples. Furthermore, by interleaving a number of saturation and readout periods within the TR, a series of images with different saturation times can be acquired, allowing for the quantification of exchange rates using the variable saturation time (QUEST) approach in a much accelerated fashion, thus enabling high throughput screening of CEST contrast agents.

  5. Nanoshells as an optical coherence tomography contrast agent

    NASA Astrophysics Data System (ADS)

    Barton, Jennifer K.; Halas, Naomi J.; West, Jennifer L.; Drezek, Rebekah A.

    2004-07-01

    Nanoshells are a layered dielectric core/metal shell composite nanostructure with an optical resonance geometrically tunable through the visible and near infrared. Due to their small size, ability to generate a strong backscattering signal, and potential for surface modification, they may be an ideal in vivo optical coherence tomography contrast agent. We performed a pilot study to assess their capabilities. Images of a cuvette filled with dilute nanoshells, 2 μm polystyrene microspheres, or a combination were obtained. When compared to microspheres, images of the nanoshells where much brighter and attenuation of the bottom cuvette interface less. Injection of micropheres into the tail vein of mice and hamsters caused a noticeable brightening of OCT images of the dorsal skin. These pilot studies indicate that nanoshells may be an excellent OCT contrast agent; work is continuing to determine optimum nanoshell parameters and applications.

  6. Phase-Change Contrast Agents for Imaging and Therapy

    PubMed Central

    Sheeran, Paul S.; Dayton, Paul A.

    2016-01-01

    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. PMID:22352770

  7. A theoretical investigation of chirp insonification of ultrasound contrast agents.

    PubMed

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

    2011-08-01

    A theoretical investigation of second harmonic imaging of an Ultrasound Contrast Agent (UCA) under chirp insonification is considered. By solving the UCA's dynamical equation analytically, the effect that the chirp signal parameters and the UCA shell parameters have on the amplitude of the second harmonic frequency are examined. This allows optimal parameter values to be identified which maximise the UCA's second harmonic response. A relationship is found for the chirp parameters which ensures that a signal can be designed to resonate a UCA for a given set of shell parameters. It is also shown that the shell thickness, shell viscosity and shell elasticity parameter should be as small as realistically possible in order to maximise the second harmonic amplitude. Keller-Herring, Second Harmonic, Chirp, Ultrasound Contrast Agent.

  8. Silver Nanoplate Contrast Agents for In Vivo Molecular Photoacoustic Imaging

    PubMed Central

    Homan, Kimberly A.; Souza, Michael; Truby, Ryan; Luke, Geoffrey P.; Green, Christopher; Vreeland, Erika; Emelianov, Stanislav

    2012-01-01

    Silver nanoplates are introduced as a new photoacoustic contrast agent that can be easily functionalized for molecular photoacoustic imaging in vivo. Methods are described for synthesis, functionalization, and stabilization of silver nanoplates using biocompatible (“green”) reagents. Directional antibody conjugation to the nanoplate surface is presented along with proof of molecular sensitivity in vitro with pancreatic cancer cells. Cell viability tests show the antibody-conjugated silver nanoplates to be nontoxic at concentrations up to 1 mg/ml. Furthermore, the silver nanoplates' potential for in vivo application as a molecularly sensitive photoacoustic contrast agent is demonstrated using an orthotopic mouse model of pancreatic cancer. Results of these studies suggest that the synthesized silver nanoplates are well suited for a host of biomedical imaging and sensing applications. PMID:22188516

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

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

  10. The in vivo relaxivity of MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Shuter, Borys

    1999-11-01

    Post-contrast clinical 1H Magnetic Resonance Images have to date been interpreted with little regard for possible variations in the in-vivo properties of injected magnetic pharmaceuticals (contrast agents), particularly in their relaxivity or ability to alter tissue relaxation rates, T2-1 and T 2-1, per unit concentration. The relaxivities of contrast agents have only rarely been measured in-vivo, measurements usually being performed on excised tissues and at magnetic field strengths lower than used in clinical practice. Some researchers have simply assumed that relaxivities determined in homogeneous tissue phantoms were applicable in-vivo. In this thesis, the relaxivities of two contrast agents, Gd-DTPA and Gd-EOB-DTPA, were measured in simple tissue phantoms and in the kidney and liver of intact, but sacrificed, Wistar rats using a clinical MR scanner with a magnetic field of 1.5 Tesla. T1 and T2 were determined from sets of images acquired using a standard clinical spin-echo pulse sequence. The contrast agent concentration in tissue was assessed by radioassay of 153Gd-DTPA or 153Gd-EOB-DTPA, mixed with the normal compound prior to injection. Relaxivity was taken as the slope of a linear regression fit of relaxation rate against Gd concentration. The relaxivities of Gd-EOB-DTPA were similarly determined in normal and biliary- obstructed guinea pigs. Relaxivities in tissue differed significantly from values obtained in simple phantoms. Kidney T1 relaxivity was reduced for both compounds in normal animals. Three days or more of biliary obstruction produced further reductions in kidney T1 relaxivity of Gd-EOB-DTPA, providing strong evidence that disease affects contrast agent relaxivity. Kidney T2 relaxivity was much greater than T1 relaxivity and was also depressed by biliary obstruction. Liver T1 and T 2 relaxivites were increased above phantom values, but were not affected by the biliary obstruction. Water compartmentalisation, macromolecular binding, proton

  11. Beat frequency ultrasonic microsphere contrast agent detection system

    NASA Technical Reports Server (NTRS)

    Pretlow, III, Robert A. (Inventor); Yost, William T. (Inventor); Cantrell, Jr., John H. (Inventor)

    1997-01-01

    A system for and method of detecting and measuring concentrations of an ultrasonically-reflective microsphere contrast agent involving detecting non-linear sum and difference beat frequencies produced by the microspheres when two impinging signals with non-identical frequencies are combined by mixing. These beat frequencies can be used for a variety of applications such as detecting the presence of and measuring the flow rates of biological fluids and industrial liquids, including determining the concentration level of microspheres in the myocardium.

  12. Site-specific tumor-targeted fluorescent contrast agents

    NASA Astrophysics Data System (ADS)

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

    2001-01-01

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

  13. Vascular flow and perfusion imaging with ultrasound contrast agents.

    PubMed

    Bruce, Matthew; Averkiou, Mike; Tiemann, Klaus; Lohmaier, Stefan; Powers, Jeff; Beach, Kirk

    2004-06-01

    Current techniques for imaging ultrasound (US) contrast agents (UCA) make no distinction between low-velocity microbubbles in the microcirculation and higher-velocity microbubbles in the larger vasculature. A combination of radiofrequency (RF) and Doppler filtering on a low mechanical index (MI) pulse inversion acquisition is presented that differentiates low-velocity microbubbles (on the order of mm/s) associated with perfusion, from the higher-velocity microbubbles (on the order of cm/s) in larger vessels. In vitro experiments demonstrate the ability to separate vascular flow using both harmonic and fundamental Doppler signals. Fundamental and harmonic Doppler signals from microbubbles using a low-MI pulse-inversion acquisition are compared with conventional color Doppler signals in vivo. Due to the lower transmit amplitude and enhanced backscatter from microbubbles, the in vivo signal to clutter ratios for both the fundamental (-11 dB) and harmonic (-4 dB) vascular flow signals were greater than with conventional power Doppler (-51 dB) without contrast agent. The processing investigated here, in parallel with conventional pulse-inversion processing, enables the simultaneous display of both perfusion and vascular flow. In vivo results demonstrating the feasibility and potential utility of the real-time display of both perfusion and vascular flow using US contrast agents are presented and discussed.

  14. Mechanistic investigation of beta-galactosidase-activated MR contrast agents.

    PubMed

    Urbanczyk-Pearson, Lauren M; Femia, Frank J; Smith, Jeffrey; Parigi, Giacomo; Duimstra, Joseph A; Eckermann, Amanda L; Luchinat, Claudio; Meade, Thomas J

    2008-01-07

    We report a mechanistic investigation of an isomeric series of beta-galactosidase-activated magnetic resonance contrast agents. Our strategy focuses on the synthesis of macrocyclic caged-complexes that coordinatively saturate a chelated lanthanide. Enzyme cleavage of the complex results in an open coordination site available for water that creates a detectable MR contrast agent. The complexes consist of a DO3A Gd(III) chelator modified with a galactopyranose at the N-10 position of the macrocycle. We observed significant differences in relaxometric properties and coordination geometry that can be correlated to subtle variations of the linker between the macrocycle and the galactopyranose. After synthesis and purification of the R, S, and racemic mixtures of complexes 1 and 3 and measurement of the hydration number, water residence lifetime, and longitudinal relaxation rates, we propose mechanisms for water exclusion from the lanthanide in the precleavage state. While the stereochemistry of the linker does not influence the agents' properties, the mechanism of water exclusion for each isomer is significantly influenced by the position of modification. Data for one series with a methyl group substituted on the sugar-macrocycle linker at the alpha-position suggests a steric mechanism where the galactopyranose sugar blocks water from the Gd(III) center. In contrast, our observations for a second series with methyl substitution at the beta position of the sugar-macrocycle linker are consistent with a mechanism in which a bidentate anion occupies two available coordination sites of Gd(III) in the precleavage state.

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

    PubMed

    Guo, Caixin; Jin, Yushen; Dai, Zhifei

    2014-05-21

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

  16. Target-specific contrast agents for magnetic resonance microscopy.

    PubMed

    Blackwell, Megan L; Farrar, Christian T; Fischl, Bruce; Rosen, Bruce R

    2009-06-01

    High-resolution ex vivo magnetic resonance (MR) imaging can be used to delineate prominent architectonic features in the human brain, but increased contrast is required to visualize more subtle distinctions. To aid MR sensitivity to cell density and myelination, we have begun the development of target-specific paramagnetic contrast agents. This work details the first application of luxol fast blue (LFB), an optical stain for myelin, as a white matter-selective MR contrast agent for human ex vivo brain tissue. Formalin-fixed human visual cortex was imaged with an isotropic resolution between 80 and 150 microm at 4.7 and 14 T before and after en bloc staining with LFB. Longitudinal (R1) and transverse (R2) relaxation rates in LFB-stained tissue increased proportionally with myelination at both field strengths. Changes in R1 resulted in larger contrast-to-noise ratios (CNR), per unit time, on T1-weighted images between more myelinated cortical layers (IV-VI) and adjacent, superficial layers (I-III) at both field strengths. Specifically, CNR for LFB-treated samples increased by 229 +/- 13% at 4.7 T and 269 +/- 25% at 14 T when compared to controls. Also, additional cortical layers (IVca, IVd, and Va) were resolvable in 14 T-MR images of LFB-treated samples but not in control samples. After imaging, samples were sliced in 40-micron sections, mounted, and photographed. Both the macroscopic and microscopic distributions of LFB were found to mimic those of traditional histological preparations. Our results suggest target-specific contrast agents will enable more detailed MR images with applications in imaging pathological ex vivo samples and constructing better MR atlases from ex vivo brains.

  17. The Paramagnetic Pillared Bentonites as Digestive Tract MRI Contrast Agents

    NASA Astrophysics Data System (ADS)

    Mojović, Miloš; Daković, Marko; Omerašević, Mia; Mojović, Zorica; Banković, Predrag; Milutinović-Nikolić, Aleksandra; Jovanović, Dušan

    The increased use of imaging techniques in diagnostic studies, such as MRI, has contributed to the development of the wide range of new materials which could be successfully used as image improving agents. However, there is a lack of such substances in the area of gastrointestinal tract MRI. Many of the traditionally popular relaxation altering agents show poor results and disadvantages provoking black bowel, side effects of diarrhea and the presence of artifacts arising from clumping. Paramagnetic species seem to be potentially suitable agents for these studies, but contrast opacification has been reported and less than 60% of the gastrointestinal tract magnetic resonance scans showed improved delineation of abdominal pathologies. The new solution has been proposed as zeolites or smectite clays (hectorite and montmorillonite) enclosing of paramagnetic metal ions obtained by ion-exchange methods. However, such materials have problems of leakage of paramagnetic ions causing the appearance of the various side-effects. In this study we show that Co+2 and Dy+3 paramagnetic-pillared bentonites could be successfully used as MRI digestive tract non-leaching contrast agents, altering the longitudinal and transverse relaxation times of fluids in contact with the clay minerals.

  18. MR-angiography: the role of contrast agents.

    PubMed

    Goyen, M; Ruehm, S G; Debatin, J F

    2000-06-01

    Contrast-enhanced 3D MR angiography (MRA) permits comprehensive assessment of the supraaortic arteries as well as the arterial system in the chest, abdomen and lower extremities. 3D MRA combines intravenous injection of a non-nephrotoxic, paramagnetic, extracellular contrast agent that increases the signal intensity of blood by shortening its T1 value with the acquisition of a fast 3D data set. High contrast between the vascular lumen and surrounding tissues, inherent three-dimensionality and the ability to collect image data in the chest and abdomen under apnea conditions all contribute to excellent image quality. This review provides clinical applications of 3D MRA in the chest, abdomen and lower extremities based upon the available literature and several clinical examples.

  19. Nanomaterials incorporated ultrasound contrast agents for cancer theranostics.

    PubMed

    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.

  20. Nanomaterials incorporated ultrasound contrast agents for cancer theranostics

    PubMed Central

    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

  1. Perfusion Imaging with a Freely Diffusible Hyperpolarized Contrast Agent

    PubMed Central

    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 administration of hyperpolarized 2-methylpropan-2-ol show that this agent can be imaged with 2–4s temporal resolution, 2mm slice thickness, and 700 micron in-plane resolution while retaining adequate signal-to-noise ratio. 13C relaxation measurements on 2-methylpropan-2-ol in blood at 9.4T yield T1=46±4s and T2=0.55±0.03s. In the rat brain at 4.7T, analysis of the temporal dynamics of the bSSFP image intensity in tissue and venous blood indicate that 2-methylpropan-2-ol has a T2 of roughly 2–4s and a T1 of 43±24s. 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. PMID:21432901

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

    PubMed

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

    2014-06-18

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

  3. Gadolinium nanoparticles and contrast agent as radiation sensitizers.

    PubMed

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

    2015-06-07

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

  4. Gadolinium nanoparticles and contrast agent as radiation sensitizers

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  5. Acoustic bubble sorting for ultrasound contrast agent enrichment.

    PubMed

    Segers, Tim; Versluis, Michel

    2014-05-21

    An ultrasound contrast agent (UCA) suspension contains encapsulated microbubbles with a wide size distribution, with radii ranging from 1 to 10 μm. Medical transducers typically operate at a single frequency, therefore only a small selection of bubbles will resonate to the driving ultrasound pulse. Thus, the sensitivity can be improved by narrowing down the size distribution. Here, we present a simple lab-on-a-chip method to sort the population of microbubbles on-chip using a traveling ultrasound wave. First, we explore the physical parameter space of acoustic bubble sorting using well-defined bubble sizes formed in a flow-focusing device, then we demonstrate successful acoustic sorting of a commercial UCA. This novel sorting strategy may lead to an overall improvement of the sensitivity of contrast ultrasound by more than 10 dB.

  6. Photoacoustic microscopy using Evans Blue dye as a contrast agent

    NASA Astrophysics Data System (ADS)

    Yao, Junjie; Maslov, Konstantin I.; Hu, Song; Wang, Lihong V.

    2010-02-01

    Complete and continuous imaging of microvascular networks is crucial for a wide variety of biomedical applications. Photoacoustic tomography can provide high resolution microvascular imaging using hemoglobin within red blood cells (RBC) as an endogenous contrast agent. However, intermittent RBC flow in capillaries results in discontinuous and fragmentary capillary images. To overcome this problem, we used Evans Blue (EB) dye as a contrast agent for in vivo photoacoustic imaging. EB has strong optical absorption at 610 nm and distributes uniformly in the blood stream by chemically binding to albumin. By intravenous injection of EB (6%, 200 μL), complete and continuous microvascular networks-especially capillaries-of the ears of nude mice were imaged. The diffusion of EB (3%, 100 μL) leaving the blood stream was monitored for 2 hours. At lower administration dose of EB (3%, 50 μL), the clearance of the EB-albumin complex was imaged for 10 days and quantitatively investigated using a two-compartment model.

  7. Assessment of tumor angiogenesis using fluorescence contrast agents

    NASA Astrophysics Data System (ADS)

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

    2003-12-01

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

  8. Molecular photoacoustic imaging using gold nanoparticles as a contrast agent

    NASA Astrophysics Data System (ADS)

    Kim, Chulhong; Cho, Eun Chul; Chen, Jingyi; Song, Kwang Hyun; Au, Leslie; Favazza, Christopher P.; Zhang, Qiang; Cobley, Claire M.; Xia, Younan; Wang, Lihong V.

    2010-02-01

    Gold nanoparticles have received much attention due to their potential diagnostic and therapeutic applications. Gold nanoparticles are attractive in many biomedical applications because of their biocompatibility, easily modifiable surfaces for targeting, lack of heavy metal toxicity, wide range of sizes (35-100 nm), tunable plasmonic resonance peak, encapsulated site-specific drug delivery, and strong optical absorption in the near-infrared regime. Specifically, due to their strong optical absorption, gold nanoparticles have been used as a contrast agent for molecular photoacoustic (PA) imaging of tumor. The plasmonic resonance peak of the gold nanocages (AuNCs) was tuned to the near-infrared region, and the ratio of the absorption cross-section to the extinction cross-section was approximately ~70%, as measured by PA sensing. We used PEGylated gold nanocages (PEG-AuNCs) as a passive targeting contrast agent on melanomas. After 6-h intravenous injection of PEG-AuNCs, PA amplitude was increased by ~14 %. These results strongly suggest PA imaging paired with AuNCs is a promising diagnostic tool for early cancer detection.

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

    NASA Astrophysics Data System (ADS)

    Dammer, J.; Weyda, F.; Benes, J.; Sopko, V.; Gelbic, I.

    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.

  10. Repositioning Clofazimine as a Macrophage-Targeting Photoacoustic Contrast Agent

    PubMed Central

    Keswani, Rahul K.; Tian, Chao; Peryea, Tyler; Girish, Gandikota; Wang, Xueding; Rosania, Gus R.

    2016-01-01

    Photoacoustic Tomography (PAT) is a deep-tissue imaging modality, with potential clinical applications in the diagnosis of arthritis, cancer and other disease conditions. Here, we identified Clofazimine (CFZ), a red-pigmented dye and anti-inflammatory FDA-approved drug, as a macrophage-targeting photoacoustic (PA) imaging agent. Spectroscopic experiments revealed that CFZ and its various protonated forms yielded optimal PAT signals at wavelengths −450 to 540 nm. CFZ’s macrophage-targeting chemical and structural forms were detected with PA microscopy at a high contrast-to-noise ratio (CNR > 22 dB) as well as with macroscopic imaging using synthetic gelatin phantoms. In vivo, natural and synthetic CFZ formulations also demonstrated significant anti-inflammatory activity. Finally, the injection of CFZ was monitored via a real-time ultrasound-photoacoustic (US-PA) dual imaging system in a live animal and clinically relevant human hand model. These results demonstrate an anti-inflammatory drug repurposing strategy, while identifying a new PA contrast agent with potential applications in the diagnosis and treatment of arthritis. PMID:27000434

  11. Development of Multifunctional Luminomagnetic Nanoparticles as Bioimaging Contrast Agents

    NASA Astrophysics Data System (ADS)

    Mimun, Lawrence C.; Rightsell, Chris; Kumar, G. A.; Pedraza, Francisco; Montelongo, Sergio A.; Guda, Teja; Dravid, Vinayak P.; Sardar, Dhiraj K.

    2015-03-01

    Trivalent rare earth doped nanocrystalline materials with multiple functionalities have drawn special attention in biomedical industry. Current research is focused on the use of various materials with dual functionality for potential multifunctional applications. In this project, we are developing near infrared(NIR) based nanocrystals (NCs) as contrast agents with multimodal features comprising of strong NIR fluorescence, X-ray fluorescence and magnetic properties by utilizing the superparamagnetic features of Gd3+, the high X-ray excitation cross section of Lu3+, and the NIR fluorescence of Nd3+. Halides, such as MGdLuF4 (M=K,Na), were doped with NIR active rare earth ions, Nd3+, where synthesis conditions have been optimized to obtain the brightest phosphor with a size of sub-50 nm. Characterization of the NCs were performed to explore the excitation and emission properties, crystal structure, morphology, magnetization properties, and X-ray fluorescence properties. The potential use of these NCs can be utilized as contrast agents for medical imaging application such as optical imaging, magnetic resonance (MRI) and X-ray imaging. This research was, in part, funded by NIGMS MBRS-RISE GM060655 and from the National Science Foundation Partnerships for Research and Education in Materials (NSF-PREM) Grant N0-DMR-0934218.

  12. Pinched flow fractionation of microbubbles for ultrasound contrast agent enrichment

    NASA Astrophysics Data System (ADS)

    Versluis, Michel; Kok, Maarten; Segers, Tim

    2014-11-01

    An ultrasound contrast agent (UCA) suspension contains a wide size distribution of encapsulated microbubbles (typically 1-10 μm in diameter) that resonate to the driving ultrasound field by the intrinsic relationship between bubble size and ultrasound frequency. Medical transducers, however, operate in a narrow frequency range, which severely limits the number of bubbles that contribute to the echo signal. Thus, the sensitivity can be improved by narrowing down the size distribution of the bubble suspension. Here, we present a novel, low-cost, lab-on-a-chip method for the sorting of contrast microbubbles by size, based on a microfluidic separation technique known as pinched flow fractionation (PFF). We show by experimental and numerical investigation that the inclusion of particle rotation is essential for an accurate physical description of the sorting behavior of the larger bubbles. Successful sorting of a bubble suspension with a narrow size distribution (3.0 +/- 0.6 μm) has been achieved with a PFF microdevice. This sorting technique can be easily parallelized, and may lead to a significant improvement in the sensitivity of contrast-enhanced medical ultrasound. This work is supported by NanoNextNL, a micro and nanotechnology consortium of the Government of the Netherlands and 130 partners.

  13. Optical and acoustical dynamics of microbubble contrast agents inside neutrophils.

    PubMed Central

    Dayton, P A; Chomas, J E; Lum, A F; Allen, J S; Lindner, J R; Simon, S I; Ferrara, K W

    2001-01-01

    Acoustically active microbubbles are used for contrast-enhanced ultrasound assessment of organ perfusion. In regions of inflammation, contrast agents are captured and phagocytosed by activated neutrophils adherent to the venular wall. Using direct optical observation with a high-speed camera and acoustical interrogation of individual bubbles and cells, we assessed the physical and acoustical responses of both phagocytosed and free microbubbles. Optical analysis of bubble radial oscillations during insonation demonstrated that phagocytosed microbubbles experience viscous damping within the cytoplasm and yet remain acoustically active and capable of large volumetric oscillations during an acoustic pulse. Fitting a modified version of the Rayleigh-Plesset equation that describes mechanical properties of thin shells to optical radius-time data of oscillating bubbles provided estimates of the apparent viscosity of the intracellular medium. Phagocytosed microbubbles experienced a viscous damping approximately sevenfold greater than free microbubbles. Acoustical comparison between free and phagocytosed microbubbles indicated that phagocytosed microbubbles produce an echo with a higher mean frequency than free microbubbles in response to a rarefaction-first single-cycle pulse. Moreover, this frequency increase is predicted using the modified Rayleigh-Plesset equation. We conclude that contrast-enhanced ultrasound can detect distinct acoustic signals from microbubbles inside of neutrophils and may provide a unique tool to identify activated neutrophils at sites of inflammation. PMID:11222315

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    In photoacoustic imaging, nanoparticle contrast agents offer strong signal intensity and long-term stability, but are limited by poor biodistribution and clearance profiles. Conversely, small molecules offer renal clearance, but relatively low photoacoustic signal. Here we describe a cellulose-based nanoparticle with photoacoustic signal superior to gold nanorods, but that undergoes enzymatic cleavage into constituent glucose molecules for renal clearance. Cellulose nanoparticles (CNPs) were synthesized through acidic cleavage of cellulose linters and purified with centrifugation. TEM indicated that the nanoparticles were 132 +/- 46 nm; the polydispersity index was 0.138. Ex vivo characterization showed a photoacoustic limit of detection of 0.02 mg/mL CNPs, and the photoacoustic signal of CNPs was 1.5- to 3.0-fold higher than gold nanorods (also at 700 nm resonance) on a particle-to-particle basis. Cell toxicity assays suggested that overnight doses below 0.31 mg/mL CNPs produced no significant (p>0.05) impact on cell metabolism. Intravenous doses up to 0.24 mg were tolerated well in nude mice. Subcutaneous and orthotopic tumor xenografts of the OV2008 ovarian cancer cell line were then created in nude mice. Data was collected with a Nexus128 scanner from Endra LifeSciences. Spectral data used a LAZR system from Visualsonics both at 700 nm excitation. We injected CNPs (0.024 mg, 0.048 mg, and 0.80 mg) via tail vein and showed that the tumor photoacoustic signal reached maximum increase between 10 and 20 minutes. All injected concentrations were statistically (p<0.05) elevated relative to the control group with n=3 mice in each group, and dose and signal had a linear relationship at R2>0.96 suggesting quantitative signal. CNP biodegradation was demonstrated ex vivo with a glucose assay. CNPs in the presence of cellulase were reduced to free glucose in under than four hours. The glucose concentration before addition of cellulase was not detectable, but increased to

  15. The use of contrast agent for imaging biological samples

    NASA Astrophysics Data System (ADS)

    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.

  16. Harmonic chirp imaging method for ultrasound contrast agent.

    PubMed

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

    2005-02-01

    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 compresses and extracts the second harmonic component from the received echo signal. Simulations have shown a clear increase in response for chirp excitation over pulse excitation with the same peak amplitude. This was confirmed by two-dimensional (2-D) optical observations of bubble response with a fast framing camera. To evaluate the harmonic compression method, we applied it to simulated bubble echoes, to measured propagation harmonics, and to B-mode scans of a flow phantom and compared it to regular pulse excitation imaging. An increase of approximately 10 dB in SNR was found for chirp excitation. The compression method was found to perform well in terms of resolution. Axial resolution was in all cases within 10% of the axial resolution from pulse excitation. Range side-lobe levels were 30 dB below the main lobe for the simulated bubble echoes and measured propagation harmonics. However, side-lobes were visible in the B-mode contrast images.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-07-08

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

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

    NASA Astrophysics Data System (ADS)

    Langsner, Robert James

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

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

    PubMed

    Bader, Kenneth B; Holland, Christy K

    2013-01-07

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

  1. Ultrasound Induced Fluorescence of Nanoscale Liposome Contrast Agents

    PubMed Central

    Zhang, Qimei; Morgan, Stephen P.; O’Shea, Paul; Mather, Melissa L.

    2016-01-01

    A new imaging contrast agent is reported that provides an increased fluorescent signal upon application of ultrasound (US). Liposomes containing lipids labelled with pyrene were optically excited and the excimer fluorescence emission intensity was detected in the absence and presence of an ultrasound field using an acousto-fluorescence setup. The acousto-fluorescence dynamics of liposomes containing lipids with pyrene labelled on the fatty acid tail group (PyPC) and the head group (PyPE) were compared. An increase in excimer emission intensity following exposure to US was observed for both cases studied. The increased intensity and time constants were found to be different for the PyPC and PyPE systems, and dependent on the applied US pressure and exposure time. The greatest change in fluorescence intensity (130%) and smallest rise time constant (0.33 s) are achieved through the use of PyPC labelled liposomes. The mechanism underlying the observed increase of the excimer emission intensity in PyPC labelled liposomes is proposed to arise from the “wagging” of acyl chains which involves fast response and requires lower US pressure. This is accompanied by increased lipid lateral diffusivity at higher ultrasound pressures, a mechanism that is also active in the PyPE labelled liposomes. PMID:27467748

  2. Enteric MRI contrast agents: comparative study of five potential agents in humans.

    PubMed

    Tart, R P; Li, K C; Storm, B L; Rolfes, R J; Ang, P G

    1991-01-01

    We compared the effectiveness of 1 mM Geritol, 12% corn oil emulsion, Kaolin-pectin, single contrast oral barium sulfate, and effervescent granules as enteric magnetic resonance imaging (MRI) contrast agents. Five volunteers were recruited. Each volunteer ingested for examinations, separated by at least one week, either 500 ml of each of the liquid preparations or two packets of the CO2 granules (producing 400 ml of CO2 per packet). Abdominal MR images were then obtained using a 1.5 T Magnetom imager and SE 550/22, SE 2000/45/90 and FISP 40/18/40 degrees pulse sequences. The oil emulsions were best tolerated. Barium sulfate caused the greatest amount of nausea, followed by Geritol and Kaolin-pectin. With FISP 40/18/40 degrees, 60%-80% of the small bowel was well delineated using oil emulsion, Kaolin-pectin, or barium sulfate. We conclude that oil emulsion was by far the best enteric MR contrast agent in our study. Good delineation of the small bowel and pancreas can be achieved using oil emulsion and gradient echo pulse sequences. The lack of side-effects and the excellent taste make it highly acceptable to human subjects.

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

    PubMed Central

    2007-01-01

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

  4. Acoustic response of compliable microvessels containing ultrasound contrast agents.

    PubMed

    Qin, Shengping; Ferrara, Katherine W

    2006-10-21

    The existing models of the dynamics of ultrasound contrast agents (UCAs) have largely been focused on an UCA surrounded by an infinite liquid. Preliminary investigations of a microbubble's oscillation in a rigid tube have been performed using linear perturbation, under the assumption that the tube diameter is significantly larger than the UCA diameter. In the potential application of drug and gene delivery, it may be desirable to fragment the agent shell within small blood vessels and in some cases to rupture the vessel wall, releasing drugs and genes at the site. The effect of a compliant small blood vessel on the UCA's oscillation and the microvessel's acoustic response are unknown. The aim of this work is to propose a lumped-parameter model to study the interaction of a microbubble oscillation and compliable microvessels. Numerical results demonstrate that in the presence of UCAs, the transmural pressure through the blood vessel substantially increases and thus the vascular permeability is predicted to be enhanced. For a microbubble within an 8 to 40 microm vessel with a peak negative pressure of 0.1 MPa and a centre frequency of 1 MHz, small changes in the microbubble oscillation frequency and maximum diameter are observed. When the ultrasound pressure increases, strong nonlinear oscillation occurs, with an increased circumferential stress on the vessel. For a compliable vessel with a diameter equal to or greater than 8 microm, 0.2 MPa PNP at 1 MHz is predicted to be sufficient for microbubble fragmentation regardless of the vessel diameter; however, for a rigid vessel 0.5 MPa PNP at 1 MHz may not be sufficient to fragment the bubbles. For a centre frequency of 1 MHz, a peak negative pressure of 0.5 MPa is predicted to be sufficient to exceed the stress threshold for vascular rupture in a small (diameter less than 15 microm) compliant vessel. As the vessel or surrounding tissue becomes more rigid, the UCA oscillation and vessel dilation decrease; however the

  5. Acoustic response of compliable microvessels containing ultrasound contrast agents

    NASA Astrophysics Data System (ADS)

    Qin, Shengping; Ferrara, Katherine W.

    2006-10-01

    The existing models of the dynamics of ultrasound contrast agents (UCAs) have largely been focused on an UCA surrounded by an infinite liquid. Preliminary investigations of a microbubble's oscillation in a rigid tube have been performed using linear perturbation, under the assumption that the tube diameter is significantly larger than the UCA diameter. In the potential application of drug and gene delivery, it may be desirable to fragment the agent shell within small blood vessels and in some cases to rupture the vessel wall, releasing drugs and genes at the site. The effect of a compliant small blood vessel on the UCA's oscillation and the microvessel's acoustic response are unknown. The aim of this work is to propose a lumped-parameter model to study the interaction of a microbubble oscillation and compliable microvessels. Numerical results demonstrate that in the presence of UCAs, the transmural pressure through the blood vessel substantially increases and thus the vascular permeability is predicted to be enhanced. For a microbubble within an 8 to 40 µm vessel with a peak negative pressure of 0.1 MPa and a centre frequency of 1 MHz, small changes in the microbubble oscillation frequency and maximum diameter are observed. When the ultrasound pressure increases, strong nonlinear oscillation occurs, with an increased circumferential stress on the vessel. For a compliable vessel with a diameter equal to or greater than 8 µm, 0.2 MPa PNP at 1 MHz is predicted to be sufficient for microbubble fragmentation regardless of the vessel diameter; however, for a rigid vessel 0.5 MPa PNP at 1 MHz may not be sufficient to fragment the bubbles. For a centre frequency of 1 MHz, a peak negative pressure of 0.5 MPa is predicted to be sufficient to exceed the stress threshold for vascular rupture in a small (diameter less than 15 µm) compliant vessel. As the vessel or surrounding tissue becomes more rigid, the UCA oscillation and vessel dilation decrease; however the

  6. Acoustic response of compliable microvessels containing ultrasound contrast agents

    PubMed Central

    Qin, Shengping; Ferrara, Katherine W.

    2010-01-01

    The existing models of the dynamics of ultrasound contrast agents (UCAs) have largely been focused on an UCA surrounded by an infinite liquid. Preliminary investigations of a microbubble’s oscillation in a rigid tube have been performed using linear perturbation, under the assumption that the tube diameter is significantly larger than UCA size. In the potential application of drug and gene delivery, it may be desirable to fragment the agent shell within small blood vessels and in some cases to rupture the vessel wall, releasing drugs and genes at the site. The effect of a compliant small blood vessel on the UCA’s oscillation and the microvessel’s acoustic response are unknown. The aim of this work is to propose a lumped-parameter model to study the interaction of a microbubble oscillation and compliable microvessels. Numerical results demonstrate that in the presence of UCAs, the transmural pressure through the blood vessel substantially increases and thus the vascular permeability is predicted to be enhanced. For a microbubble within an 8 to 40 micron vessel with a peak negative pressure of 0.1MPa and a center frequency of 1MHz, small changes in the microbubble oscillation frequency and maximum diameter are observed. When the ultrasound pressure increases, strong nonlinear oscillation occurs, with an increased circumferential stress on the vessel. For a compliable vessel with the range of diameters considered in this work, 0.2 MPa PNP at 1 MHz is predicted to be sufficient for microbubble fragmentation regardless the vessel diameter, however, for a rigid vessel 0.5 MPa PNP at 1 MHz may not be sufficient to fragment the bubbles. For a center frequency of 1MHz, a peak negative pressure of 0.5 MPa is predicted to be sufficient to exceed the stress threshold for vascular rupture in a small (diameter less than 15 μm) compliant vessel. As the vessel or surrounding tissue becomes more rigid, the UCA oscillation and vessel dilation decrease, however the

  7. Small-animal microangiography using phase-contrast X-ray imaging and gas as contrast agent

    NASA Astrophysics Data System (ADS)

    Lundström, Ulf; Larsson, Daniel H.; Westermark, Ulrica K.; Burvall, Anna; Hertz, Hans M.

    2014-03-01

    We use propagation-based phase-contrast X-ray imaging with gas as contrast agent to visualize the microvasculature in small animals like mice and rats. The radiation dose required for absorption X-ray imaging is proportional to the minus fourth power of the structure size to be detected. This makes small vessels impossible to image at reasonable radiation doses using the absorption of conventional iodinated contrast agents. Propagation-based phase contrast gives enhanced contrast for high spatial frequencies by moving the detector away from the sample to let phase variations in the transmitted X-rays develop into intensity variations at the detector. Blood vessels are normally difficult to observe in phase contrast even with iodinated contrast agents as the density difference between blood and most tissues is relatively small. By injecting gas into the blood stream this density difference can be greatly enhanced giving strong phase contrast. One possible gas to use is carbon dioxide, which is a clinically accepted X-ray contrast agent. The gas is injected into the blood stream of patients to temporarily displace the blood in a region and thereby reduce the X-ray absorption in the blood vessels. We have shown that this method can be used to image blood vessels down to 8 μm in diameter in mouse ears. The low dose requirements of this method indicate a potential for live small-animal imaging and longitudinal studies of angiogenesis.

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

    PubMed

    Daryaei, Iman; Pagel, Mark D

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-09-01

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

  10. Expanding the potential of MRI contrast agents through multifunctional polymeric nanocarriers.

    PubMed

    Craciun, Ioana; Gunkel-Grabole, Gesine; Belluati, Andrea; Palivan, Cornelia G; Meier, Wolfgang

    2017-04-01

    MRI is a sought-after, noninvasive tool in medical diagnostics, yet the direct application of contrast agents to tissue suffers from several drawbacks. Hosting the contrast agents in polymeric nanocarriers can solve many of these issues while creating additional benefit through exploitation of the intrinsic characteristics of the polymeric carriers. In this report, the versatility is highlighted with recent examples of dendritic and hyperbranched polymers, polymer nanoparticles and micelles, and polymersomes as multifunctional bioresponsive nanocarriers for MRI contrast agents.

  11. Gold Nanoparticle Contrast Agents in Mammography: A Feasibility Study

    DTIC Science & Technology

    2007-08-01

    the detection of a 5 mm dia. tumor at a clinical mammographic dose (1.8 mGy). Using similar agents for thermoacoustic tomography , Copland2...molecular imaging agents for use with emerging breast imaging modalities such as digital breast tomosynthesis (DBT) and breast computed tomography (BCT...Teflon-coated magnetic stir bar was added. The flask was then placed atop a heating mantle and magnetic stirrer and the gold solution was brought to

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

    PubMed Central

    Daryaei, Iman; Pagel, Mark D

    2016-01-01

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

  13. Water-Soluble Lipophilic MR Contrast Agents for Cell Membrane Labeling

    PubMed Central

    Carney, Christiane E.; MacRenaris, Keith W.; Meade, Thomas J.

    2015-01-01

    Long-term cell tracking with MR imaging necessitates the development of contrast agents that both label and are retained by cells. One promising strategy for long-term cell labeling is the development of lipophilic Gd(III)-based contrast agents that anchor into the cell membrane. We have previously reported the efficacy of monomeric and multimeric lipophilic agents and showed that the monomeric agents have improved labeling and contrast enhancement of cell populations. Here, we report on the synthesis, characterization, and in vitro testing of a series of monomeric lipophilic contrast agents with varied alkyl chain compositions. We show that these agents disperse in water, localize to the cell membrane, and label HeLa and MCF7 cells effectively. Additionally, these agents have up to 10-fold improved retention in cells compared to clinically available ProHance®. PMID:26215869

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

    PubMed

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Ma, J.; Chen, K.

    2016-04-01

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

  16. Application of nonlinear sliding mode control to ultrasound contrast agent microbubbles.

    PubMed

    Carroll, James M; Lauderbaugh, Leal K; Calvisi, Michael L

    2013-07-01

    A sliding mode control system is developed and applied to a spherical model of a contrast agent microbubble that simulates its radial response to ultrasound. The model uses a compressible form of the Rayleigh-Plesset equation combined with a thin-shell model. A nonlinear control law for the second-order model is derived and used to design and simulate the controller. The effect of the controller on the contrast agent response is investigated for various control scenarios. This work demonstrates the feasibility of using a nonlinear control system to modulate the dynamic response of ultrasound contrast agents, but highlights the need for improved feedback mechanisms and control input methods. Possible applications of the nonlinear control system to contrast agents illustrated in this work include radius stabilization in the presence of an acoustic wave, radial growth and subsequent collapse, and generation of periodic radial oscillations while a contrast agent is within an acoustic forcing regime known to cause a chaotic response.

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

    PubMed

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

    2014-09-22

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

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

    PubMed

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

    2015-12-01

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

  19. Development of contrast enhancing agents in magnetic resonance imaging.

    PubMed

    Lex, L

    1989-01-01

    Magnetic Resonance Imaging (MRI) is a powerful new diagnostic tool in medicine. In MRI there is a great need to improve the specific identification of different tissues i.e. to enhance the contrast between them. This review tries to cover most of the approaches known for solving this problem.

  20. Development and characterization of a nano-scale contrast agent.

    PubMed

    Oeffinger, Brian E; Wheatley, Margaret A

    2004-04-01

    Agents injected parenterally must be less than approximately 8 microm diameter in order to traverse the capillaries in the pulmonary bed, but these agents remain in the vasculature until they are eliminated from the body by a variety of mechanisms. Targeting of cells outside the capillaries requires agent diameters of less than approximately 700 nm to enable escape through the larger-than-usual pores that have been noted in the leaky vasculature of a tumor. The objective of this study was to test the feasibility of creating a surfactant-stabilized nano-bubble with favorable acoustic properties, and identify the key parameters that influence size, yield and stability. Size distribution was characterized using laser light scattering. In vitro acoustic enhancement was assessed by generation of dose and time response curves. We previously developed a successful protocol to generate gas-filled microbubbles (containing perfluorocarbon, sulfur hexafluoride or air) with mean diameter of 1.5 microm, using sonication of carefully selected surfactant mixtures. This presentation describes generation of nano-bubbles with mean diameters ranging from 700 to 450 nm, depending on process variables. In all cases a centrifugation step was employed to separate the nano-sized particles. The in vitro dose response curves gave a maximum of 23-27 dB enhancement compared to buffer in the absence of agent, with the maximum enhancement and presence of shadowing at higher doses being dependent on the fabrication protocol. The effect of sonication time for solutions containing a mixture of the surfactants (Span 60 and Tween 80) was also tested, but was determined not to be an influencing factor. Future studies will involve development of a mathematical model characterizing the mean size as a function of centrifugal force, spin time and initial size distribution. Future work will also include imaging of tumor-bearing mice and measuring imaging potential in vivo in New Zealand white rabbits

  1. Opportunities for new CT contrast agents to maximize the diagnostic potential of emerging spectral CT technologies.

    PubMed

    Yeh, Benjamin M; FitzGerald, Paul F; Edic, Peter M; Lambert, Jack W; Colborn, Robert E; Marino, Michael E; Evans, Paul M; Roberts, Jeannette C; Wang, Zhen J; Wong, Margaret J; Bonitatibus, Peter J

    2016-09-09

    The introduction of spectral CT imaging in the form of fast clinical dual-energy CT enabled contrast material to be differentiated from other radiodense materials, improved lesion detection in contrast-enhanced scans, and changed the way that existing iodine and barium contrast materials are used in clinical practice. More profoundly, spectral CT can differentiate between individual contrast materials that have different reporter elements such that high-resolution CT imaging of multiple contrast agents can be obtained in a single pass of the CT scanner. These spectral CT capabilities would be even more impactful with the development of contrast materials designed to complement the existing clinical iodine- and barium-based agents. New biocompatible high-atomic number contrast materials with different biodistribution and X-ray attenuation properties than existing agents will expand the diagnostic power of spectral CT imaging without penalties in radiation dose or scan time.

  2. Safe ex vivo coronary angiography with isosmotic contrast agent.

    PubMed

    Schmit, D B; Kern, J A; Mauney, M C; Kron, I L; Tribble, C G

    1996-08-01

    Plain-film coronary angiography of the cardiac explant on the operating table should be considered when conventional cardiac catheterization is desired but unavailable. We compared the effects of three contrast solutions on cold-preserved, isolated guinea pig hearts. Hearts were excised, perfused for 30 minutes, and arrested with Plegisol solution at 7 degree C. Twenty minutes after arrest, experimental hearts were perfused with one of three solutions: hyperosmolar Hexabrix solution (n = 6), hyperosmolar Renografin-76 solution (n = 6), or diluted, isosmotic Omnipaque solution (n = 8). The hearts were flushed with cold Plegisol solution 5 minutes later. Control hearts received no contrast during arrest (n = 9). The hearts were reperfused after 1 hour of arrest, and coronary blood flow (in millimeters per minute), left ventricular developed pressure (in millimeters of mercury), and rate of developed pressure (in millimeters of mercury per second) were measured. Endothelium-dependent smooth muscle relaxation to bradykinin administration and endothelium-independent relaxation to sodium nitroprusside administration were also assessed. No significant difference in myocardial or endothelial function was noted between control hearts and hearts perfused with Omnipaque solution. Hearts perfused with Renografin solution or Hexabrix solution, however, were found to have significantly impaired endothelial and myocardial function. We conclude that an isosmotic contrast solution should be used for ex vivo coronary angiography in cold-preserved hearts to avoid impairment of endothelial and myocardial function.

  3. Gold Nanoparticle Contrast Agents in Mammography: A Feasibility Study

    DTIC Science & Technology

    2008-08-01

    example of such a novel targeted agent, Pittsburg Compound-B (C- PIB ) has been approved for use in Alzheimer’s patients as a PET probe [8]. C- PIB is a... PIB is therefore able to more clearly distinguish between benign cells and tissue that is of interest to the physician. Researchers have found...p. 945-9. 8. Rabinovici, G.D., A.J. Furst, J.P. O’Neil, et al., 11C- PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration

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

    NASA Astrophysics Data System (ADS)

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

    2009-11-01

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

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

    PubMed

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

    2015-02-01

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

  6. Motion corrected photoacoustic difference imaging of fluorescent contrast agents

    NASA Astrophysics Data System (ADS)

    Märk, Julia; Wagener, Asja; Pönick, Sarah; Grötzinger, Carsten; Zhang, Edward; Laufer, Jan

    2016-03-01

    In fluorophores, such as exogenous dyes and genetically expressed proteins, the excited state lifetime can be modulated using pump-probe excitation at wavelengths corresponding to the absorption and fluorescence spectra. Simultaneous pump-probe pulses induce stimulated emission (SE) which, in turn, modulates the thermalized energy, and hence the photoacoustic (PA) signal amplitude. For time-delayed pulses, by contrast, SE is suppressed. Since this is not observed in endogenous chromophores, the location of the fluorophore can be determined by subtracting images acquired using simultaneous and time-delayed pump-probe excitation. This simple experimental approach exploits a fluorophorespecific contrast mechanism, and has the potential to enable deep-tissue molecular imaging at fluences below the MPE. In this study, some of the challenges to its in vivo implementation are addressed. First, the PA signal amplitude generated in fluorophores in vivo is often much smaller than that in blood. Second, tissue motion can give rise to artifacts that correspond to endogenous chromophores in the difference image. This would not allow the unambiguous detection of fluorophores. A method to suppress motion artifacts based on fast switching between simultaneous and time-delayed pump-probe excitation was developed. This enables the acquisition of PA signals using the two excitation modes with minimal time delay (20 ms), thus minimizing the effects of tissue motion. The feasibility of this method is demonstrated by visualizing a fluorophore (Atto680) in tissue phantoms, which were moved during the image acquisition to mimic tissue motion.

  7. Effects of nonlinear propagation in ultrasound contrast agent imaging.

    PubMed

    Tang, Meng-Xing; Kamiyama, Naohisa; Eckersley, Robert J

    2010-03-01

    This paper investigates two types of nonlinear propagation and their effects on image intensity and contrast-to-tissue ratio (CTR) in contrast ultrasound images. Previous studies have shown that nonlinear propagation can occur when ultrasound travels through tissue and microbubble clouds, making tissue farther down the acoustic path appear brighter in pulse inversion (PI) images, thus reducing CTR. In this study, the effect of nonlinear propagation through tissue or microbubbles on PI image intensity and CTR are compared at low mechanical index. A combination of simulation and experiment with SonoVue microbubbles were performed using a microbubble dynamics model, a laboratory ultrasound system and a clinical prototype scanner. The results show that, close to the bubble resonance frequency, nonlinear propagation through a bubble cloud of a few centimeter thickness with a modest concentration (1:10000 dilution of SonoVue microbubbles) is much more significant than through tissue-mimicking material. Consequently, CTR in regions distal to the imaging probe is greatly reduced for nonlinear propagation through the bubble cloud, with as much as a 12-dB reduction compared with nonlinear propagation through tissue-mimicking material. Both types of nonlinear propagation cause only a small change in bubble PI signals at the bubble resonance frequency. When the driving frequency increases beyond bubble resonance, nonlinear propagation through bubbles is greatly reduced in absolute values. However because of a greater reduction in nonlinear scattering from bubbles at higher frequencies, the corresponding CTR is much lower than that at bubble resonance frequency.

  8. Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  9. Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging

    PubMed Central

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

    2016-01-01

    Multiphoton microscopy (MPM) is a nonlinear fluorescence microscopic technique widely used for cellular imaging of thick tissues and live animals in biological studies. However, MPM application to human tissues is limited by weak endogenous fluorescence in tissue and cytotoxicity of exogenous probes. Herein, we describe the applications of moxifloxacin, an FDA-approved antibiotic, as a cell-labeling agent for MPM. Moxifloxacin has bright intrinsic multiphoton fluorescence, good tissue penetration and high intracellular concentration. MPM with moxifloxacin was demonstrated in various cell lines, and animal tissues of cornea, skin, small intestine and bladder. Clinical application is promising since imaging based on moxifloxacin labeling could be 10 times faster than imaging based on endogenous fluorescence. PMID:27283889

  10. Tailored Near-Infrared Contrast Agents for Image Guided Surgery

    PubMed Central

    Njiojob, Costyl N.; Owens, Eric A.; Narayana, Lakshminarayana; Hyun, Hoon; Choi, Hak Soo; Henary, Maged

    2015-01-01

    The success of near-infrared (NIR) fluorescence to be employed for intraoperative imaging relies on the ability to develop a highly stable, NIR fluorescent, nontoxic, biocompatible, and highly excreted compound that retains a reactive functionality for conjugation to a cancer-recognizing peptide. Herein, systematic modifications to previously detailed fluorophore ZW800-1 are explored. Specific modifications, including the isosteric replacement of the O atom of ZW800-1, include nucleophilic amine and sulfur species attached to the heptamethine core. These novel compounds have shown similar satisfactory results in biodistribution and clearance while also expressing increased stability in serum. Most importantly, all of the synthesized and evaluated compounds display a reactive functionality (either a free amino group or carboxylic acid moiety) for further bioconjugation. The results obtained from the newly prepared derivatives demonstrate that the central substitution with the studied linking agents retains the ultralow background in vivo performance of the fluorophores regardless of the total net charge. PMID:25711712

  11. Contrasting actions of pressor agents in severe autonomic failure

    NASA Technical Reports Server (NTRS)

    Jordan, J.; Shannon, J. R.; Biaggioni, I.; Norman, R.; Black, B. K.; Robertson, D.

    1998-01-01

    BACKGROUND: Orthostatic hypotension is the most disabling symptom of autonomic failure. The choice of a pressor agent is largely empiric, and it would be of great value to define predictors of a response. PATIENTS AND METHODS: In 35 patients with severe orthostatic hypotension due to multiple system atrophy or pure autonomic failure, we determined the effect on seated systolic blood pressure (SBP) of placebo, phenylpropanolamine (12.5 mg and 25 mg), yohimbine (5.4 mg), indomethacin (50 mg), ibuprofen (600 mg), caffeine (250 mg), and methylphenidate (5 mg). In a subgroup of patients, we compared the pressor effect of midodrine (5 mg) with the effect of phenylpropanolamine (12.5 mg). RESULTS: There were no significant differences in the pressor responses between patients with multiple system atrophy or pure autonomic failure. When compared with placebo, the pressor response was significant for phenylpropanolamine, yohimbine, and indomethacin. In a subgroup of patients, we confirmed that this pressor effect of phenylpropanolamine, yohimbine, and indomethacin corresponded to a significant increase in standing SBP. The pressor responses to ibuprofen, caffeine, and methylphenidate were not significantly different from placebo. Phenylpropanolamine and midodrine elicited similar pressor responses. There were no significant associations between drug response and autonomic function testing, postprandial hypotension, or plasma catecholamine levels. CONCLUSIONS: We conclude that significant increases in systolic blood pressure can be obtained in patients with orthostatic hypotension due to primary autonomic failure with phenylpropanolamine in low doses or yohimbine or indomethacin in moderate doses. The response to a pressor agent cannot be predicted by autonomic function testing or plasma catecholamines. Therefore, empiric testing with a sequence of medications, based on the risk of side effects in the individual patient and the probability of a response, is a useful approach.

  12. Liver-specific agents for contrast-enhanced MRI: role in oncological imaging

    PubMed Central

    Thian, Yee Liang; Riddell, Angela M.

    2013-01-01

    Abstract Liver-specific magnetic resonance (MR) contrast agents are increasingly used in evaluation of the liver. They are effective in detection and morphological characterization of lesions, and can be useful for evaluation of biliary tree anatomy and liver function. The typical appearances and imaging pitfalls of various tumours at MR imaging performed with these agents can be understood by the interplay of pharmacokinetics of these contrast agents and transporter expression of the tumour. This review focuses on the applications of these agents in oncological imaging. PMID:24434892

  13. Utilization of nanoparticles as X-ray contrast agents for diagnostic imaging applications.

    PubMed

    De La Vega, José Carlos; Häfeli, Urs O

    2015-01-01

    Among all the diagnostic imaging modalities, X-ray imaging techniques are the most commonly used owing to their high resolution and low cost. The improvement of these techniques relies heavily on the development of novel X-ray contrast agents, which are molecules that enhance the visibility of internal structures within the body in X-ray imaging. To date, clinically used X-ray contrast agents consist mainly of small iodinated molecules that might cause severe adverse effects (e.g. allergies, cardiovascular diseases and nephrotoxicity) in some patients owing to the large and repeated doses that are required to achieve good contrast. For this reason, there is an increasing interest in the development of alternative X-ray contrast agents utilizing elements with high atomic numbers (e.g. gold, bismuth, ytterbium and tantalum), which are well known for exhibiting high absorption of X-rays. Nanoparticles (NPs) made from these elements have been reported to have better imaging properties, longer blood circulation times and lower toxicity than conventional iodinated X-ray contrast agents. Additionally, the combination of two or more of these elements into a single carrier allows for the development of multimodal and hybrid contrast agents. Herein, the limitations of iodinated X-ray contrast agents are discussed and the parameters that influence the efficacy of X-ray contrast agents are summarized. Several examples of the design and production of both iodinated and iodine-free NP-based X-ray contrast agents are then provided, emphasizing the studies performed to evaluate their X-ray attenuation capabilities and their toxicity in vitro and in vivo.

  14. Evaluation of microbubble contrast agents for dynamic imaging with x-ray phase contrast.

    PubMed

    Millard, T P; Endrizzi, M; Everdell, N; Rigon, L; Arfelli, F; Menk, R H; Stride, E; Olivo, A

    2015-07-29

    X-rays are commonly used as a means to image the inside of objects opaque to visible light, as their short wavelength allows penetration through matter and the formation of high spatial resolution images. This physical effect has found particular importance in medicine where x-ray based imaging is routinely used as a diagnostic tool. Increasingly, however, imaging modalities that provide functional as well as morphological information are required. In this study the potential to use x-ray phase based imaging as a functional modality through the use of microbubbles that can be targeted to specific biological processes is explored. We show that the concentration of a microbubble suspension can be monitored quantitatively whilst in flow using x-ray phase contrast imaging. This could provide the basis for a dynamic imaging technique that combines the tissue penetration, spatial resolution, and high contrast of x-ray phase based imaging with the functional information offered by targeted imaging modalities.

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

    NASA Astrophysics Data System (ADS)

    Shan, Liang; Gu, Xinbin; Wang, Paul

    2013-09-01

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

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

    PubMed

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

    2015-01-01

    Magnetic resonance imaging (MRI) has become one of the most widely used and powerful tools for noninvasive clinical diagnosis owing to its high degree of soft tissue contrast, spatial resolution, and depth of penetration. MRI signal intensity is related to the relaxation times (T 1, spin-lattice relaxation and T 2, spin-spin relaxation) of in vivo water protons. To increase contrast, various inorganic nanoparticles and complexes (the so-called contrast agents) are administered prior to the scanning. Shortening T 1 and T 2 increases the corresponding relaxation rates, 1/T 1 and 1/T 2, producing hyperintense and hypointense signals respectively in shorter times. Moreover, the signal-to-noise ratio can be improved with the acquisition of a large number of measurements. The contrast agents used are generally based on either iron oxide nanoparticles or ferrites, providing negative contrast in T 2-weighted images; or complexes of lanthanide metals (mostly containing gadolinium ions), providing positive contrast in T 1-weighted images. Recently, lanthanide complexes have been immobilized in nanostructured materials in order to develop a new class of contrast agents with functions including blood-pool and organ (or tumor) targeting. Meanwhile, to overcome the limitations of individual imaging modalities, multimodal imaging techniques have been developed. An important challenge is to design all-in-one contrast agents that can be detected by multimodal techniques. Magnetoliposomes are efficient multimodal contrast agents. They can simultaneously bear both kinds of contrast and can, furthermore, incorporate targeting ligands and chains of polyethylene glycol to enhance the accumulation of nanoparticles at the site of interest and the bioavailability, respectively. Here, we review the most important characteristics of the nanoparticles or complexes used as MRI contrast agents.

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

    PubMed Central

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

    2015-01-01

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

  18. THREE-DIMENSIONAL MODELING OF THE DYNAMICS OF THERAPEUTIC ULTRASOUND CONTRAST AGENTS

    PubMed Central

    Hsiao, Chao-Tsung; Lu, Xiaozhen; Chahine, Georges

    2010-01-01

    A 3-D thick-shell contrast agent dynamics model was developed by coupling a finite volume Navier-Stokes solver and a potential boundary element method flow solver to simulate the dynamics of thick-shelled contrast agents subjected to pressure waves. The 3-D model was validated using a spherical thick-shell model validated by experimental observations. We then used this model to study shell break-up during nonspherical deformations resulting from multiple contrast agent interaction or the presence of a nearby solid wall. Our simulations indicate that the thick viscous shell resists the contrast agent from forming a re-entrant jet, as normally observed for an air bubble oscillating near a solid wall. Instead, the shell thickness varies significantly from location to location during the dynamics, and this could lead to shell break-up caused by local shell thinning and stretching. PMID:20950929

  19. Magnetic resonance contrast media sensing in vivo molecular imaging agents: an overview.

    PubMed

    Amanlou, Massoud; Siadat, Seyed Davar; Norouzian, Dariush; Ebrahimi, Seyed Esmaeil Sadat; Aghasadeghi, Mohammad Reza; Ghorbani, Masoud; Alavidjeh, Mohammad Shafiee; Inanlou, Davoud Nouri; Arabzadeh, Ali Jabbari; Ardestani, Mehdi Shafiee

    2011-01-01

    Metabolic imaging is commonly performed by nuclear medicine facilities such as PET or SPECT, etc. The production and biomedical applications of bio-molecular sensing in vivo MRI metabolic contrast agents has recently become of great universal research interest, which follows its great success as a potential cost effective, less radioactive, nuclear medicine alternative. Temperature, redox potential, enzyme activity, free radial/metal ion responsive and/or pH sensitive molecular metabolic MR contrast agents are among the famous instances exemplified, which basically promote MR image contrast enhancement ability to distinguish molecular metabolic/gene expression features. Overall, these MRI contrast agents provide a framework to achieve a greater degree of accuracy from MRI as a low cost, more available facility, non radioactive radiation producing and highly sensitive biomedical tool to propound as a new suggesting opponent for PET nuclear medicine imaging. In the present review, the design, development, examination and future of the above agents will be discussed in detail.

  20. Acoustic responses of monodisperse lipid-encapsulated microbubble contrast agents produced by flow focusing

    PubMed Central

    Kaya, Mehmet; Feingold, Steven; Hettiarachchi, Kanaka; Lee, Abraham P; Dayton, Paul A

    2010-01-01

    Lipid-encapsulated microbubbles are used as contrast agents in ultrasound imaging. Currently available commercially made contrast agents have a polydisperse size distribution. It has been hypothesised that improved imaging sensitivity could be achieved with a uniform microbubble radius. We have recently developed microfluidics technology to produce contrast agents with a nearly monodisperse distribution. In this manuscript, we analyze echo responses from individual microbubbles from monodisperse populations in order to establish the relationship between scattered echo, microbubble radius, and excitation frequency. Simulations of bubble response from a modified Rayleigh-Plesset type model corroborate experimental data. Results indicate that microbubble echo response can be greatly increased by optimal combinations of microbubble radius and acoustic excitation frequency. These results may have a significant impact in the formulation of contrast agents to improve ultrasonic sensitivity. PMID:21475641

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

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

    PubMed

    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.

  3. Mn12 single-molecule magnet aggregates as magnetic resonance imaging contrast agents.

    PubMed

    Wang, Yinglin; Li, Wen; Zhou, Shengyan; Kong, Daliang; Yang, Haishan; Wu, Lixin

    2011-03-28

    Mn(12) single-molecule magnets have been dispersed in water through an emulsion-assisted self-assembly method with an improved stability in water, in order to investigate the use of Mn(12) as MRI contrast agents.

  4. [Experimental studies of ferrite as a MRI contrast agent].

    PubMed

    Aoki, F

    1992-02-01

    Using a 0.2 T permanent MR imaging system, the gradual changes of signal intensity after intravenous injection of Ferrite suspension were studied in liver of normal rabbits and those with intrahepatic VX2 tumor. After injection of Ferrite suspension, decreased signal intensities of liver were observed on both T1 and T2 weighted images. The decrease on T2 weighted images was more remarkable than that on the T1 weighted image. The image with 8 mg/kg (50 mumol/kg) dose of Ferrite suspension showed significant changes of signal intensity, while, the image with 24 mg/kg (150 mumol/kg) dose was hardly evaluated because of inducing intense artifacts. The decrease of signal intensity in liver was observed immediately after the injection and was lowest after 1 hour. After 48 hours, the signal intensity began to increase. However, a slight loss of signal intensity was visualized even after 4 weeks. A clear MRI of the intrahepatic tumor following injection of Ferrite suspension was acquired especially on T2 weighted image in comparison with MRI after Gd-DTPA administration. In addition, MRI using Ferrite suspension could detect the small intrahepatic tumors which had been unable to be visualized by plain CT or enhanced CT. It is of benefit, furthermore, that Ferrite suspension could be an useful tracer for observing the intrahepatic tumor growth by a first single injection. Histologically, Ferrite particles were accumulated in reticuloendothelial system of liver whereas no accumulated in intrahepatic tumor was verified. The particles produced changes in local magnetic field resulting that signal intensity of liver showed decrease on the image. Subsequently, relatively negative contrast enhancement of liver was displayed. As a result of the present investigation, the MR imaging following injection of Ferrite suspension was found to be useful for detection of intrahepatic tumors, particularly of metastatic tumors which were isointense or hypovascular to the surrounding tissue

  5. Exploring silver as a contrast agent for contrast-enhanced dual-energy X-ray breast imaging

    PubMed Central

    Tsourkas, A; Maidment, A D A

    2014-01-01

    Objective: Through prior monoenergetic modelling, we have identified silver as a potential alternative to iodine in dual-energy (DE) X-ray breast imaging. The purpose of this study was to compare the performance of silver and iodine contrast agents in a commercially available DE imaging system through a quantitative analysis of signal difference-to-noise ratio (SDNR). Methods: A polyenergetic simulation algorithm was developed to model the signal intensity and noise. The model identified the influence of various technique parameters on SDNR. The model was also used to identify the optimal imaging techniques for silver and iodine, so that the two contrast materials could be objectively compared. Results: The major influences on the SDNR were the low-energy dose fraction and breast thickness. An increase in the value of either of these parameters resulted in a decrease in SDNR. The SDNR for silver was on average 43% higher than that for iodine when imaged at their respective optimal conditions, and 40% higher when both were imaged at the optimal conditions for iodine. Conclusion: A silver contrast agent should provide benefit over iodine, even when translated to the clinic without modification of imaging system or protocol. If the system were slightly modified to reflect the lower k-edge of silver, the difference in SDNR between the two materials would be increased. Advances in knowledge: These data are the first to demonstrate the suitability of silver as a contrast material in a clinical contrast-enhanced DE image acquisition system. PMID:24998157

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

    PubMed

    Lancharro Zapata, Á M; Rodríguez, C Marín

    2016-05-01

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

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

    PubMed

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

    2017-04-01

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

  8. Potential of high-Z contrast agents in clinical contrast-enhanced computed tomography

    SciTech Connect

    Nowak, Tristan; Hupfer, Martin; Brauweiler, Robert; Eisa, Fabian; Kalender, Willi A.

    2011-12-15

    Purpose: Currently, only iodine- and barium-based contrast media (CM) are used in clinical contrast-enhanced computed tomography (CE-CT). High-Z metals would produce a higher contrast at equal mass density for the x-ray spectra used in clinical CT. Using such materials might allow for significant dose reductions in CE-CT. The purpose of this study was to quantify the potential for dose reduction when using CM based on heavy metals. Methods: The contrast-to-noise ratio weighted by dose (CNRD) was determined as a function of scan protocol by means of measurements and simulations on a clinical CT scanner. For simulations, water cylinders with diameters 160, 320, 480, and 640 mm were used to cover a broad range of patient sizes. Measurements were conducted with 160 and 320 mm water-equivalent plastic cylinders. A central bore of 13 mm diameter was present in all phantoms. The tube voltage was varied from 80 to 140 kV for measurements and from 60 to 180 kV for simulations. Additional tin filtration of thicknesses 0.4, 0.8, and 1.2 mm was applied in the simulation to evaluate a range of spectral hardness. The bore was filled with a mixture of water and 10 mg/ml of pure iodine, holmium, gadolinium, ytterbium, osmium, tungsten, gold, and bismuth for the simulations and with aqueous solutions of ytterbium, tungsten, gold, and bismuth salts as well as Iopromid containing 10 mg/ml of the pure materials for the measurements. CNRDs were compared to iodine at phantom size-dependent reference voltages for all high-Z materials and the resulting dose reduction was calculated for equal contrast-to-noise ratio. Results: Dose reduction potentials strongly depended on phantom size, spectral hardness, and tube voltage. Depending on the added filtration, a dose reduction of 19%-60% could be reached at 80 kV with gadolinium for the 160 mm phantom, 52%-69% at 100 kV with holmium for the 320 mm phantom, 62%-78% with 120 kV for hafnium and the 480 mm phantom and 74%-86% with 140 kV for gold

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

    PubMed

    Arfelli, F; Rigon, L; Menk, R H

    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.

  10. Formulation of radiographically detectable gastrointestinal contrast agents for magnetic resonance imaging: effects of a barium sulfate additive on MR contrast agent effectiveness.

    PubMed

    Rubin, D L; Muller, H H; Young, S W

    1992-01-01

    Complete and homogeneous distribution of gastrointestinal (GI) contrast media are important factors for their effective use in computed tomography as well as in magnetic resonance (MR) imaging. A radiographic method (using fluoroscopy or spot films) could be effective for monitoring intestinal filling with GI contrast agents for MR imaging (GICMR), but it would require the addition of a radiopaque agent to most GICMR. This study was conducted to determine the minimum amount of barium additive necessary to be radiographically visible and to evaluate whether this additive influences the signal characteristics of the GICMR. A variety of barium sulfate preparations (3-12% wt/vol) were tested in dogs to determine the minimum quantity needed to make the administered agent visible during fluoroscopy and on abdominal radiographs. Solutions of 10 different potential GI contrast agents (Gd-DTPA, ferric ammonium citrate, Mn-DPDP, chromium-EDTA, gadolinium-oxalate, ferrite particles, water, mineral oil, lipid emulsion, and methylcellulose) were prepared without ("nondoped") and with ("doped") the barium sulfate additive. MR images of the solutions in tubes were obtained at 0.38 T using 10 different spin-echo pulse sequences. Region of interest (ROI) measurements of contrast agent signal intensity (SI) were made. In addition, for the paramagnetic contrast media, the longitudinal and transverse relaxivity (R1 and R2) were measured. A 6% wt/vol suspension of barium was the smallest concentration yielding adequate radiopacity in the GI tract. Except for gadolinium-oxalate, there was no statistically significant difference in SI for doped and non-doped solutions with most pulse sequences used. In addition, the doped and nondoped solutions yielded R1 and R2 values which were comparable. We conclude that barium sulfate 6% wt/vol added to MR contrast agents produces a suspension with sufficient radiodensity to be viewed radiographically, and it does not cause significant alteration in

  11. Topical contrast agents to improve soft-tissue contrast in the upper airway using cone beam CT: a pilot study.

    PubMed

    Alsufyani, N A; Noga, M L; Finlay, W H; Major, P W

    2013-01-01

    The purpose of this study is to explore the topical use of radiographic contrast agents to enhance soft-tissue contrast on cone beam CT (CBCT) images. Different barium sulphate concentrations were first tested using an airway phantom. Different methods of barium sulphate application (nasal drops, syringe, spray and sinus wash) were then tested on four volunteers, and nebulized iodine was tested in one volunteer. CBCT images were performed and then assessed subjectively by two examiners for contrast agent uniformity and lack of streak artefact. 25.0% barium sulphate presented adequate viscosity and radiodensity. Barium sulphate administered via nasal drops and sprays showed non-uniform collection at the nostrils, along the inferior and/or middle nasal meatuses and posterior nasal choana. The syringe and sinus wash showed similar results with larger volumes collecting in the naso-oropharynx. Nebulized iodine failed to distribute into the nasal cavity and scarcely collected at the nostrils. All methods of nasal application failed to adequately reach or uniformly coat the nasal cavity beyond the inferior nasal meatuses. The key factors to consider for optimum topical radiographic contrast in the nasal airway are particle size, flow velocity and radio-opacity.

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

    PubMed

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

    2009-06-01

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

  13. Silica-coated super paramagnetic iron oxide nanoparticles (SPION) as biocompatible contrast agent in biomedical photoacoustics.

    PubMed

    Alwi, Rudolf; Telenkov, Sergey; Mandelis, Andreas; Leshuk, Timothy; Gu, Frank; Oladepo, Sulayman; Michaelian, Kirk

    2012-10-01

    In this study, we report for the first time the use of silica-coated superparamagnetic iron oxide nanoparticles (SPION) as contrast agents in biomedical photoacoustic imaging. Using frequency-domain photoacoustic correlation (the photoacoustic radar), we investigated the effects of nanoparticle size, concentration and biological media (e.g. serum, sheep blood) on the photoacoustic response in turbid media. Maximum detection depth and the minimum measurable SPION concentration were determined experimentally. The nanoparticle-induced optical contrast ex vivo in dense muscular tissues (avian pectus and murine quadricept) was evaluated and the strong potential of silica-coated SPION as a possible photoacoustic contrast agents was demonstrated.

  14. Poly(iohexol) nanoparticles as contrast agents for in vivo X-ray computed tomography imaging.

    PubMed

    Yin, Qian; Yap, Felix Y; Yin, Lichen; Ma, Liang; Zhou, Qin; Dobrucki, Lawrence W; Fan, Timothy M; Gaba, Ron C; Cheng, Jianjun

    2013-09-18

    Biocompatible poly(iohexol) nanoparticles, prepared through cross-linking of iohexol and hexamethylene diisocyanate followed by coprecipitation of the resulting cross-linked polymer with mPEG-polylactide, were utilized as contrast agents for in vivo X-ray computed tomography (CT) imaging. Compared to conventional small-molecule contrast agents, poly(iohexol) nanoparticles exhibited substantially protracted retention within the tumor bed and a 36-fold increase in CT contrast 4 h post injection, which makes it possible to acquire CT images with improved diagnosis accuracy over a broad time frame without multiple administrations.

  15. HER2 Targeted Molecular MR Imaging Using a De Novo Designed Protein Contrast Agent

    PubMed Central

    Qiao, Jingjuan; Li, Shunyi; Wei, Lixia; Jiang, Jie; Long, Robert; Mao, Hui; Wei, Ling; Wang, Liya; Yang, Hua; Grossniklaus, Hans E.; Liu, Zhi-Ren; Yang, Jenny J.

    2011-01-01

    The application of magnetic resonance imaging (MRI) to non-invasively assess disease biomarkers has been hampered by the lack of desired contrast agents with high relaxivity, targeting capability, and optimized pharmacokinetics. We have developed a novel MR imaging probe targeting to HER2, a biomarker for various cancer types and a drug target for anti-cancer therapies. This multimodal HER20targeted MR imaging probe integrates a de novo designed protein contrast agent with a high affinity HER2 affibody and a near IR fluorescent dye. Our probe can differentially monitor tumors with different expression levels of HER2 in both human cell lines and xenograft mice models. In addition to its 100-fold higher dose efficiency compared to clinically approved non-targeting contrast agent DTPA, our developed agent also exhibits advantages in crossing the endothelial boundary, tissue distribution, and tumor tissue retention over reported contrast agents as demonstrated by even distribution of the imaging probe across the entire tumor mass. This contrast agent will provide a powerful tool for quantitative assessment of molecular markers, and improved resolution for diagnosis, prognosis and drug discovery. PMID:21455310

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

    PubMed

    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.

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

    PubMed Central

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

    2016-01-01

    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 (Ktrans), efflux rate constant (Kep). 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. PMID:27298076

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

    PubMed Central

    Lalatonne, Y.; Monteil, M.; Jouni, H.; Serfaty, J. M.; Sainte-Catherine, O.; Lièvre, N.; Kusmia, S.; Weinmann, P.; Lecouvey, M.; Motte, L.

    2010-01-01

    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. PMID:20981332

  19. Structural and functional photoacoustic molecular tomography aided by emerging contrast agents

    PubMed Central

    Nie, Liming

    2015-01-01

    Photoacoustic tomography (PAT) can offer structural, functional and molecular contrasts at scalable observation level. By ultrasonically overcoming the strong optical scattering, this imaging technology can reach centimeters penetration depth while retaining high spatial resolution in biological tissue. Recent extensive research has been focused on developing new contrast agents to improve the imaging sensitivity, specificity and efficiency. These emerging materials have substantially accelerated PAT applications in signal sensing, functional imaging, biomarker labeling and therapy monitoring etc. Here, the potentials of different optical probes as PAT contrast agents were elucidated. We first describe the instrumental embodiments and the measured functional parameters, then focus on emerging contrast agent-based PAT applications, and finally discuss the challenges and prospects. PMID:24967718

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

    PubMed

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

    2011-04-01

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

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

    SciTech Connect

    Werner, Eric J.; Datta, Ankona; Jocher, Christoph J.; Raymond, Kenneth N.

    2008-01-15

    The desire to improve and expand the scope of clinical magnetic resonance imaging (MRI) has prompted the search for contrast agents of higher efficiency. The development of better agents requires consideration of the fundamental coordination chemistry of the gadolinium(III) ion and the parameters that affect its efficacy as a proton relaxation agent. In optimizing each parameter, other practical issues such as solubility and in vivo toxicity must also be addressed, making the attainment of safe, high-relaxivity agents a challenging goal. Here we present recent advances in the field, with an emphasis on the hydroxypyridinone family of Gd{sup III} chelates.

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

    PubMed Central

    Fridjhon, Peter; Rubin, David M.

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  5. Optimal Contrast Agent Staining of Ligaments and Tendons for X-Ray Computed Tomography

    PubMed Central

    Balint, Richard; Lowe, Tristan

    2016-01-01

    X-ray computed tomography has become an important tool for studying the microstructures of biological soft tissues, such as ligaments and tendons. Due to the low X-ray attenuation of such tissues, chemical contrast agents are often necessary to enhance contrast during scanning. In this article, the effects of using three different contrast agents—iodine potassium iodide solution, phosphotungstic acid and phosphomolybdic acid—are evaluated and compared. Porcine anterior cruciate ligaments, patellar tendons, medial collateral ligaments and lateral collateral ligaments were used as the basis of the study. Three samples of each of the four ligament/tendon types were each assigned a different contrast agent (giving a total of twelve samples), and the progression of that agent through the tissue was monitored by performing a scan every day for a total period of five days (giving a total of sixty scans). Since the samples were unstained on day one, they had been stained for a total of four days by the time of the final scans. The relative contrast enhancement and tissue deformation were measured. It was observed that the iodine potassium iodide solution penetrated the samples fastest and caused the least sample shrinkage on average (although significant deformation was observed by the time of the final scans), whereas the phosphomolybdic acid caused the greatest sample shrinkage. Equations describing the observed behaviour of the contrast agents, which can be used to predict optimal staining times for ligament and tendon X-ray computed tomography, are presented. PMID:27078030

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

    PubMed Central

    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 increase in the subharmonic and ultraharmonic response (nearly 12–15 and 5–8 dB) after 5–10 minutes of agent preparation. However, the fundamental and the harmonic response remained almost unchanged in this period. During the next 50 minutes, the subharmonic, fundamental, ultraharmonic, and harmonic responses decreased steadily by 2–5 dB. The temporal changes in the nonlinear behavior of the agent appeared to be primarily mediated by gas-exchange through the microbubble shell; temperature and prior acoustic excitation based mechanisms were ruled out. Further, there was no measurable change in the agent size distribution by static diffusion. We envisage that these findings will help obtain reproducible measurements from agent characterization, nonlinear imaging, and fluid-pressure sensing. These findings also suggest the possibility for improving nonlinear imaging by careful design of ultrasound contrast agents. PMID:24582298

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

    NASA Astrophysics Data System (ADS)

    Allen, John

    2016-11-01

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

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

    NASA Astrophysics Data System (ADS)

    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.

  9. Molecular MR Contrast Agents for the Detection of Cancer: Past and Present

    PubMed Central

    Bogdanov, Alexei; Mazzanti, Mary L.

    2011-01-01

    Magnetic resonance imaging (MRI) is a powerful diagnostic tool capable of providing detailed information about the structure and composition of tumors, with unsurpassed spatial resolution. The use of exogenously administered contrast agents allows compartment-specific enhancement of tumors, enabling imaging of functional blood and interstitial volumes. Current efforts are directed at enhancing the capabilities of MRI in oncology to add contrast agents with molecular specificities to the growing armamentarium of diagnostic probes capable of changing local proton relaxation times as a consequence of specific contrast agent binding to cell surface receptors or extracellular matrix components. We review herein the most notable examples, illustrating major trends in the development of specific probes for high-resolution imaging in molecular oncology. PMID:21362515

  10. Plasmon-resonant gold nanorods as low backscattering albedo contrast agents for optical coherence tomography.

    PubMed

    Oldenburg, Amy L; Hansen, Matthew N; Zweifel, Daniel A; Wei, Alexander; Boppart, Stephen A

    2006-07-24

    Plasmon-resonant gold nanorods are demonstrated as low backscattering albedo contrast agents for optical coherence tomography (OCT). We define the backscattering albedo, a', as the ratio of the backscattering to extinction coefficient. Contrast agents which modify a' within the host tissue phantoms are detected with greater sensitivity by the differential OCT measurement of both a' and extinction. Optimum sensitivity is achieved by maximizing the difference between contrast agents and tissue, |a'(ca) - a'(tiss)|. Low backscattering albedo gold nanorods (14x 44 nm; lambda(max) = 780 nm) within a high backscattering albedo tissue phantom with an uncertainty in concentration of 20% (randomized 2+/-0.4% intralipid) were readily detected at 82 ppm (by weight) in a regime where extinction alone could not discriminate nanorods. The estimated threshold of detection was 30 ppm.

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

    NASA Astrophysics Data System (ADS)

    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.

  12. Preclinical evaluation of biodegradable macromolecular contrast agents for magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Feng, Yi

    Macromolecular contrast agents have been shown to be superior to small molecular weight contrast agents for MRI in blood pool imaging, tumor diagnosis and grading. However, none has been approved by the FDA because they circulate in the bloodstream much longer than small molecular weight contrast agents and result in high tissue accumulation of toxic Gd(III) ions. Biodegradable macromolecular contrast agents (BMCA) were invented to alleviate the toxic accumulation. They have a cleavable disulfide bond based backbone that can be degraded in vivo and excreted out of the body via renal filtration. Furthermore, the side chain of the backbone can be modified to achieve various degradation rates. Three BMCA, (Gd-DTPA)-cystamine copolymers (GDCC), Gd-DTPA cystine copolymers (GDCP), and Gd-DTPA cystine diethyl ester copolymers (GDCEP), were evaluated as blood pool contrast agents in a rat model. They have excellent blood pool enhancement, preferred pharmacokinetics, and only minimal long-term tissue retention of toxic Gd(III) ions. GDCC and GDCP, the lead agents with desired degradation rates, with molecular weights of 20 KDa and 70 KDa, were chosen for dynamic contrast enhanced MRI (DCE-MRI) to differentiate human prostate tumor models of different malignancy and growth rates. GDCC and GDCP could differentiate these tumor models, providing more accurate estimations of plasma volume, flow leakage rate, and permeability surface area product than a small molecular weight contrast agent Gd-DTPA-BMA when compared to the prototype macromolecular contrast agent albumin-Gd-DTPA. GDCC was favored for its neutral charge side chain and reasonable uptake rate by the tumors. GDCC with a molecular weight of 40 KDa (GDCC-40, above the renal filtration cutoff size) was used to assess the efficacy of two photothermal therapies (interstitial and indocyanine green enhanced). GDCC-40 provided excellent tumor enhancement shortly after its injection. Acute tumor response (4 hr) after therapies

  13. Intradermal administration of fluorescent contrast agents for delivery to axillary lymph nodes

    NASA Astrophysics Data System (ADS)

    Rasmussen, John C.; Meric-Berstam, Funda; Krishnamurthy, Savitri; Tan, I.-Chih; Zhu, Banghe; Wagner, Jamie L.; Babiera, Gildy V.; Mittendorf, Elizabeth A.; Sevick-Muraca, Eva M.

    2014-05-01

    In this proof-of-concept study we seek to demonstrate the delivery of fluorescent contrast agent to the tumor-draining lymph node basin following intraparenchymal breast injections and intradermal arm injection of micrograms of indocyanine green in 20 breast cancer patients undergoing complete axillary lymph node dissection. Individual lymph nodes were assessed ex vivo for presence of fluorescent signal. In all, 88% of tumor-negative lymph nodes and 81% of tumor-positive lymph nodes were fluorescent. These results indicate that future studies utilizing targeted fluorescent contrast agents may demonstrate improved surgical and therapeutic intervention.

  14. [Case of the month. Acute generalized exanthematous pustulosis due to an iodinated contrast radiodiagnostic agent].

    PubMed

    Paquet, P; Vandenbossche, G; Nikkels, A F; Henry, F; Piérard, G E

    2009-12-01

    Iodinated contrast agents are frequently involved in delayed polymorphic adverse skin reactions. Acute generalized exanthematous pustulosis following administration of iodinated contrast agents is a rare but severe form of such reactions. The disease is characterized by the sudden occurrence of an erosive and pustular erythroderma with fever, leukocytosis and sometimes peripheral adenopathies and liver involvement. This condition is considered as an immunologic reaction, primarily involving T lymphocytes. The overall mortality reaches about 1%. Elucidating the differential diagnosis with other acute paroxysmal drug eruptions (toxic epidermal necrolysis, Steven-Johnson syndrome and drug hypersensitivity syndrome) is of paramount importance for establishing the adequate treatment of PEAG.

  15. Combined ultrasound and photoacoustic imaging of pancreatic cancer using nanocage contrast agents

    NASA Astrophysics Data System (ADS)

    Homan, Kimberly; Shah, Jignesh; Gomez, Sobeyda; Gensler, Heidi; Karpiouk, Andrei; Brannon-Peppas, L.; Emelianov, Stanislav

    2009-02-01

    A new metallodielectric nanoparticle consisting of a silica core and silver outer cage was developed for the purpose of enhancing photoacoustic imaging contrast in pancreatic tissue. These nanocages were injected into an ex vivo porcine pancreas and imaged using a combined photoacoustic and ultrasound (PAUS) assembly. This custom-designed PAUS assembly delivered 800 nm light through a fiber optical light delivery system integrated with 128 element linear array transducer operating at 7.5 MHz center frequency. Imaging results prove that the nanocage contrast agents have the ability to enhance photoacoustic imaging contrast. Furthermore, the value of the combined PAUS imaging modality was demonstrated as the location of nanocages against background native tissue was evident. Future applications of these nanocage contrast agents could include targeting them to pancreatic cancer for enhancement of photoacoustic imaging for diagnosis and therapy.

  16. Improved sensitivity of computed tomography towards iodine and gold nanoparticle contrast agents via iterative reconstruction methods

    NASA Astrophysics Data System (ADS)

    Bernstein, Ally Leigh; Dhanantwari, Amar; Jurcova, Martina; Cheheltani, Rabee; Naha, Pratap Chandra; Ivanc, Thomas; Shefer, Efrat; Cormode, David Peter

    2016-05-01

    Computed tomography is a widely used medical imaging technique that has high spatial and temporal resolution. Its weakness is its low sensitivity towards contrast media. Iterative reconstruction techniques (ITER) have recently become available, which provide reduced image noise compared with traditional filtered back-projection methods (FBP), which may allow the sensitivity of CT to be improved, however this effect has not been studied in detail. We scanned phantoms containing either an iodine contrast agent or gold nanoparticles. We used a range of tube voltages and currents. We performed reconstruction with FBP, ITER and a novel, iterative, modal-based reconstruction (IMR) algorithm. We found that noise decreased in an algorithm dependent manner (FBP > ITER > IMR) for every scan and that no differences were observed in attenuation rates of the agents. The contrast to noise ratio (CNR) of iodine was highest at 80 kV, whilst the CNR for gold was highest at 140 kV. The CNR of IMR images was almost tenfold higher than that of FBP images. Similar trends were found in dual energy images formed using these algorithms. In conclusion, IMR-based reconstruction techniques will allow contrast agents to be detected with greater sensitivity, and may allow lower contrast agent doses to be used.

  17. Improved sensitivity of computed tomography towards iodine and gold nanoparticle contrast agents via iterative reconstruction methods

    PubMed Central

    Bernstein, Ally Leigh; Dhanantwari, Amar; Jurcova, Martina; Cheheltani, Rabee; Naha, Pratap Chandra; Ivanc, Thomas; Shefer, Efrat; Cormode, David Peter

    2016-01-01

    Computed tomography is a widely used medical imaging technique that has high spatial and temporal resolution. Its weakness is its low sensitivity towards contrast media. Iterative reconstruction techniques (ITER) have recently become available, which provide reduced image noise compared with traditional filtered back-projection methods (FBP), which may allow the sensitivity of CT to be improved, however this effect has not been studied in detail. We scanned phantoms containing either an iodine contrast agent or gold nanoparticles. We used a range of tube voltages and currents. We performed reconstruction with FBP, ITER and a novel, iterative, modal-based reconstruction (IMR) algorithm. We found that noise decreased in an algorithm dependent manner (FBP > ITER > IMR) for every scan and that no differences were observed in attenuation rates of the agents. The contrast to noise ratio (CNR) of iodine was highest at 80 kV, whilst the CNR for gold was highest at 140 kV. The CNR of IMR images was almost tenfold higher than that of FBP images. Similar trends were found in dual energy images formed using these algorithms. In conclusion, IMR-based reconstruction techniques will allow contrast agents to be detected with greater sensitivity, and may allow lower contrast agent doses to be used. PMID:27185492

  18. Single-walled carbon nanotubes as a multimodal — thermoacoustic and photoacoustic — contrast agent

    PubMed Central

    Pramanik, Manojit; Swierczewska, Magdalena; Green, Danielle; Sitharaman, Balaji; Wang, Lihong V.

    2009-01-01

    We have developed a novel carbon nanotube-based contrast agent for both thermoacoustic and photoacoustic tomography. In comparison with de-ionized water, single-walled carbon nanotubes exhibited more than two-fold signal enhancement for thermoacoustic tomography at 3 GHz. In comparison with blood, they exhibited more than six-fold signal enhancement for photoacoustic tomography at 1064 nm wavelength. The large contrast enhancement of single-walled carbon nanotubes was further corroborated by tissue phantom imaging studies. PMID:19566311

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

    NASA Astrophysics Data System (ADS)

    Lázaro, Francisco José; Gutiérrez, Lucía; Rosa Abadía, Ana; Soledad Romero, María; López, Antonio; Jesús Muñoz, María

    2007-04-01

    A magnetic AC susceptibility characterisation of rat tissues after intravenous administration of superparamagnetic iron oxide (Endorem ®), 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.

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

    PubMed Central

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

    2016-01-01

    Background The invasiveness and exposure to radiation in voiding cystourethrography led to the introduction of alternative methods of diagnosis of vesicoureteral reflux, including contrast enhanced voiding urosonography. While there is a limited number of studies comparing these methods using new generation ultrasound contrast agents, none of them compared both methods simultaneously. This study is aimed at assessing agreement between contrast enhanced voiding urosonography with second-generation ultrasound contrast agents and voiding cystourethrography. Methods From April 2013 to May 2014, 83 children (37 female and 46 male), mean age 3.5 years, age range from 1 month to 17.5 years, underwent prospective simultaneous assessment by contrast enhanced voiding urosonography and voiding cystourethrography, with a total of 166 uretero-renal units evaluated. Results The sensitivity of voiding cystourethrography and contrast enhanced voiding urosonography were comparable, amounting to 88%, however, neither reached 100% for the entire studied population. The negative predictive value of voiding urosonography and voiding cystourethrography was 97%, and there was no difference between both methods. Conclusion Voiding cystourethrography and contrast enhanced voiding urosonography are comparable methods in diagnosis of vesicoureteral reflux, and can be performed alternatively. However, some limitations of contrast enhanced voiding urosonography must be remembered. PMID:28138405

  1. Evaluation of three effervescent agents for double-contrast upper gastrointestinal radiography.

    PubMed

    Koehler, R E; Weyman, P J; Stanley, R J; Lee, J K; Balfe, D M

    1981-01-01

    The agent used to introduce gas into the stomach is an important factor in determining the quality of double-contrast upper gastrointestinal radiography. The efficacy of 3 effervescent agents formulated for use in double-contract upper gastrointestinal radiography was evaluated in 300 patients. Patients found 2 granular preparations (E-Z-Gas granules and Baros) easier to swallow than a powdered agent (E-Z-Gas powder). Bubble formation and flocculation of barium in the stomach were less of a problem with Baros. Differences in mucosal coating and visualization of area gastricae were not statistically significant.

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

    NASA Astrophysics Data System (ADS)

    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.

  3. Heterogeneous delayed enhancement of the liver after ultrasound contrast agent injection--a normal variant.

    PubMed

    Okada, Masahiro; Albrecht, Thomas; Blomley, Martin J; Heckemann, Rolf A; Cosgrove, David O; Wolf, Karl-Jürgen

    2002-08-01

    We report a characteristic heterogeneous delayed liver enhancement pattern that we have encountered in a total of 6 of approximately 1500 subjects who underwent contrast-enhanced liver ultrasonography. The heterogeneous enhancement occurred several min after contrast injection and persisted for up to 1 h. It was seen in diseased as well as healthy livers and appears to represent a "normal variant" of liver enhancement. It was observed with two different contrast agents. The cause of the described effect is unknown; it may be related to the formation of large bubbles and vascular entrapment of these bubbles in the liver.

  4. Specific binding of molecularly targeted agents to pancreas tumors and impact on observed optical contrast

    NASA Astrophysics Data System (ADS)

    Samkoe, Kimberley S.; Hextrum, Shannon K.; Pardesi, Omar; O'Hara, Julia A.; Hasan, Tayyaba; Pogue, Brian W.

    2010-02-01

    In optical imaging it is thought that optimum tumor contrast can be achieved with the use of small-labeled molecular tracers that have high affinity to their targets and fast clearance rates from the blood stream and healthy tissues. An example of this is fluorescently tagged EGF to monitor the molecular activity of tumors, such as pancreatic cancer. Extensive fluorescence contrast analysis for fluorescence molecular tomography has been performed on the AsPC-1 pancreas tumor, grown orthotopically in mice; yet, the binding dynamics of the EGF-fluorescent agent in vivo is not completely known. The bulk pancreatic tumor displays 3:1 contrast relative to the normal pancreas at long times after injection; however, even higher levels of fluorescence in the liver, kidney and intestine suggest that molecular specificity for the tumor may be low. Mice were administered a fluorescently labeled EGF agent and were sacrificed at various time points post-injection. To analyze the amount of specific binding at each time point frozen tissue samples were fluorescently imaged, washed with saline to remove the interstitially distributed contrast agent, and then imaged again. This technique demonstrated that approximately ~10% of the molecular target was firmly bound to the cell, while 90% was mobile or unbound. This low binding ratio suggests that the contrast observed is from inherent properties of the tumor (i.e. enhanced permeability and retention effect) and not from specific bound contrast as previously anticipated. The use of EGF contrast agents in MRI-guided fluorescence tomography and the impact of low binding specificity are discussed.

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  7. In vivo small animal micro-CT using nanoparticle contrast agents.

    PubMed

    Ashton, Jeffrey R; West, Jennifer L; Badea, Cristian T

    2015-01-01

    Computed tomography (CT) is one of the most valuable modalities for in vivo imaging because it is fast, high-resolution, cost-effective, and non-invasive. Moreover, CT is heavily used not only in the clinic (for both diagnostics and treatment planning) but also in preclinical research as micro-CT. Although CT is inherently effective for lung and bone imaging, soft tissue imaging requires the use of contrast agents. For small animal micro-CT, nanoparticle contrast agents are used in order to avoid rapid renal clearance. A variety of nanoparticles have been used for micro-CT imaging, but the majority of research has focused on the use of iodine-containing nanoparticles and gold nanoparticles. Both nanoparticle types can act as highly effective blood pool contrast agents or can be targeted using a wide variety of targeting mechanisms. CT imaging can be further enhanced by adding spectral capabilities to separate multiple co-injected nanoparticles in vivo. Spectral CT, using both energy-integrating and energy-resolving detectors, has been used with multiple contrast agents to enable functional and molecular imaging. This review focuses on new developments for in vivo small animal micro-CT using novel nanoparticle probes applied in preclinical research.

  8. Ni-Fe2O4 nanoparticles as contrast agents for magnetic resonance imaging.

    PubMed

    Ahmad, Tanveer; Rhee, Ilsu; Hong, Sungwook; Chang, Yongmin; Lee, Jaejun

    2011-07-01

    Reported herein is the synthesis of a dextran coating on nickel ferrite (Ni-Fe2O4) nanoparticles via chemical coprecipitation. The aqueous solution of the synthesized nanoparticles showed good colloidal stability, and no precipitate was observed 20 months after the synthesis. The coated nanoparticles were found to be cylindrical in shape in the TEM images, and showed a uniform size distribution with an average length and diameter of 17 and 4 nm, respectively. The coated particles were evaluated as potential T1 and T2 contrast agents for MRI. The T1 and T2 relaxations of the hydrogen protons in the water molecules in an aqueous solution of dextran-coated Ni-Fe2O4 nanoparticles were studied. It was found that the T1 relaxivity for the aqueous solution of dextran-coated nanoparticles was slightly greater than that of a commercial Gd-DTPA-BMA contrast agent. The T2 relaxivity, however, was almost twice that of the commercial Gd-DTPA-BMA contrast agent. Animal experimentation also demonstrated that the dextran-coated Ni-Fe2O4 nanoparticles are suitable for use as either T1 or T2 contrast agents in MRI.

  9. PSMA-targeted contrast agents for intraoperative imaging of prostate cancer.

    PubMed

    Bao, Kai; Lee, Jeong Heon; Kang, Homan; Park, G Kate; El Fakhri, Georges; Choi, Hak Soo

    2017-02-04

    Prostate-specific membrane antigen (PSMA) can serve as a molecular cell surface target for the detection and treatment of prostate cancer. Near-infrared (NIR) fluorescence imaging enables highly sensitive, rapid, and non-radioactive imaging of PSMA, though specific targeting still remains a challenge because no optimized contrast agents exist.

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

    PubMed

    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.

  11. In vivo small animal micro-CT using nanoparticle contrast agents

    PubMed Central

    Ashton, Jeffrey R.; West, Jennifer L.; Badea, Cristian T.

    2015-01-01

    Computed tomography (CT) is one of the most valuable modalities for in vivo imaging because it is fast, high-resolution, cost-effective, and non-invasive. Moreover, CT is heavily used not only in the clinic (for both diagnostics and treatment planning) but also in preclinical research as micro-CT. Although CT is inherently effective for lung and bone imaging, soft tissue imaging requires the use of contrast agents. For small animal micro-CT, nanoparticle contrast agents are used in order to avoid rapid renal clearance. A variety of nanoparticles have been used for micro-CT imaging, but the majority of research has focused on the use of iodine-containing nanoparticles and gold nanoparticles. Both nanoparticle types can act as highly effective blood pool contrast agents or can be targeted using a wide variety of targeting mechanisms. CT imaging can be further enhanced by adding spectral capabilities to separate multiple co-injected nanoparticles in vivo. Spectral CT, using both energy-integrating and energy-resolving detectors, has been used with multiple contrast agents to enable functional and molecular imaging. This review focuses on new developments for in vivo small animal micro-CT using novel nanoparticle probes applied in preclinical research. PMID:26581654

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

    PubMed

    Sica, Domenic A

    2009-12-01

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

  13. Stabilized porous liposomes with encapsulated Gd-labeled dextran as highly efficient MRI contrast agents

    PubMed Central

    Zaki, Ajlan Al; Jones, Ian W.; Hall, Henry K.; Aspinwall, Craig A; Tsourkas, Andrew

    2014-01-01

    A highly efficient contrast agent for magnetic resonance imaging was developed by encapsulating gadolinium within a stabilized porous liposome. The highly porous membrane leads to a high relaxivity of the encapsulated Gd. The stability of the liposome was improved by forming a polymer network within the bilayer membrane. PMID:24457826

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    2017-01-01

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

  16. Preparation of near-infrared-labeled targeted contrast agents for clinical translation

    NASA Astrophysics Data System (ADS)

    Olive, D. Michael

    2011-03-01

    Targeted fluorophore-labeled contrast agents are moving toward translation to human surgical use. To prepare for future clinical use, we examined the performance of potential ligands targeting the epidermal growth factor receptor, α5β3 integrins, and GLUT transporters for their suitability as directed contrast agents. Each agent was labeled with IRDye 800CW, and near-infrared dye with excitation/emission wavelengths of 789/805 nm, which we determined had favorable toxicity characteristics. The probe molecules examined consisted of Affibodies, nanobodies, peptides, and the sugar 2-deoxy-D-glucose. Each probe was tested for specific and non-specific binding in cell based assays. All probe types showed good performance in mouse models for detecting either spontaneous tumors or tumor xenografts in vivo. Each of the probes tested show promise for future human clinical studies.

  17. Small animal imaging platform for quantitative assessment of short-wave infrared-emitting contrast agents

    NASA Astrophysics Data System (ADS)

    Hu, Philip; Mingozzi, Marco; Higgins, Laura M.; Ganapathy, Vidya; Zevon, Margot; Riman, Richard E.; Roth, Charles M.; Moghe, Prabhas V.; Pierce, Mark C.

    2015-03-01

    We report the design, calibration, and testing of a pre-clinical small animal imaging platform for use with short-wave infrared (SWIR) emitting contrast agents. Unlike materials emitting at visible or near-infrared wavelengths, SWIR-emitting agents require detection systems with sensitivity in the 1-2 μm wavelength region, beyond the range of commercially available small animal imagers. We used a collimated 980 nm laser beam to excite rare-earth-doped NaYF4:Er,Yb nanocomposites, as an example of a SWIR emitting material under development for biomedical imaging applications. This beam was raster scanned across the animal, with fluorescence in the 1550 nm wavelength region detected by an InGaAs area camera. Background adjustment and intensity non-uniformity corrections were applied in software. The final SWIR fluorescence image was overlaid onto a standard white-light image for registration of contrast agent uptake with respect to anatomical features.

  18. Development of nanostars as a biocompatible tumor contrast agent: toward in vivo SERS imaging

    PubMed Central

    D’Hollander, Antoine; Mathieu, Evelien; Jans, Hilde; Vande Velde, Greetje; Stakenborg, Tim; Van Dorpe, Pol; Himmelreich, Uwe; Lagae, Liesbet

    2016-01-01

    The need for sensitive imaging techniques to detect tumor cells is an important issue in cancer diagnosis and therapy. Surface-enhanced Raman scattering (SERS), realized by chemisorption of compounds suitable for Raman spectroscopy onto gold nanoparticles, is a new method for detecting a tumor. As a proof of concept, we studied the use of biocompatible gold nanostars as sensitive SERS contrast agents targeting an ovarian cancer cell line (SKOV3). Due to a high intracellular uptake of gold nanostars after 6 hours of exposure, they could be detected and located with SERS. Using these nanostars for passive targeting after systemic injection in a xenograft mouse model, a detectable signal was measured in the tumor and liver in vivo. These signals were confirmed by ex vivo SERS measurements and darkfield microscopy. In this study, we established SERS nanostars as a highly sensitive contrast agent for tumor detection, which opens the potential for their use as a theranostic agent against cancer. PMID:27536107

  19. Alk5 inhibition increases delivery of macromolecular and protein-bound contrast agents to tumors

    PubMed Central

    Daldrup-Link, Heike E.; Mohanty, Suchismita; Ansari, Celina; Ito, Ken; Hong, Su Hyun; Hoffmann, Matthias; Pisani, Laura; Boudreau, Nancy; Gambhir, Sanjiv Sam; Coussens, Lisa M.

    2016-01-01

    Limited transendothelial permeability across tumor microvessels represents a significant bottleneck in the development of tumor-specific diagnostic agents and theranostic drugs. Here, we show an approach to increase transendothelial permeability of macromolecular and nanoparticle-based contrast agents via inhibition of the type I TGF-β receptor, activin-like kinase 5 (Alk5), in tumors. Alk5 inhibition significantly increased tumor contrast agent delivery and enhancement on imaging studies, while healthy organs remained relatively unaffected. Imaging data correlated with significantly decreased tumor interstitial fluid pressure, while tumor vascular density remained unchanged. This immediately clinically translatable concept involving Alk5 inhibitor pretreatment prior to an imaging study could be leveraged for improved tumor delivery of macromolecular and nanoparticle-based imaging probes and, thereby, facilitate development of more sensitive imaging tests for cancer diagnosis, enhanced tumor characterization, and personalized, image-guided therapies. PMID:27182558

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

    PubMed Central

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

    2016-01-01

    Objective: Photoacoustic (PA) tomography (PAT) has attracted extensive interest because of its optical absorption contrast and ultrasonic detection. This study aims to develop a biocompatible and biodegradable PA contrast agent particularly promising for clinical applications in human body. Methods: In this study, we presented a PA contrast agent: 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine- N-[methoxy (polyethylene glycol)] (DSPE-PEG)-coated superparamagnetic iron oxide (SPIO) nanoparticles (NPs) loaded with indocyanine green (ICG). We used ICG and SPIO NPs because both drugs are approved by the U.S. Food and Drug Administration. Given the strong absorption of near-infrared laser pulses, SPIO@DSPE-PEG/ICG NPs with a uniform diameter of ~28 nm could significantly enhance PA signals. Results: We demonstrated the contrast enhancement of these NPs in phantom and animal experiments, in which the in vivo circulation time of SPIO@DSPE-PEG/ICG NPs was considerably longer than that of free ICG. These novel NPs also displayed a high efficiency of tumor targeting. Conclusions: SPIO@DSPE-PEG/ICG NPs are promising PAT contrast agents for clinical applications. PMID:27807502

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

    PubMed

    Bost, Wolfgang; Lemor, Robert; Fournelle, Marc

    2012-11-20

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

  2. Diagnosis of Popliteal Venous Entrapment Syndrome by Magnetic Resonance Imaging Using Blood-Pool Contrast Agents

    SciTech Connect

    Beitzke, Dietrich Wolf, Florian; Juelg, Gregor; Lammer, Johannes; Loewe, Christian

    2011-02-15

    Popliteal vascular entrapment syndrome is caused by aberrations or hypertrophy of the gastrocnemius muscles, which compress the neurovascular structures of the popliteal fossa, leading to symptoms of vascular and degeneration as well as aneurysm formation. Imaging of popliteal vascular entrapment may be performed with ultrasound, magnetic resonance imaging (MRI), computed tomography angiography, and conventional angiography. The use of blood-pool contrast agents in MRI when popliteal vascular entrapment is suspected offers the possibility to perform vascular imaging with first-pass magnetic resonance angiographic, high-resolution, steady-state imaging and allows functional tests all within one examination with a single dose of contrast agent. We present imaging findings in a case of symptomatic popliteal vein entrapment diagnosed by the use of blood pool contrast-enhanced MRI.

  3. Synthesis of nanoparticle CT contrast agents: in vitro and in vivo studies

    PubMed Central

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

    2015-01-01

    Water-soluble and biocompatible D-glucuronic acid coated Na2WO4 and BaCO3 nanoparticles were synthesized for the first time to be used as x-ray computed tomography (CT) contrast agents. Their average particle diameters were 3.2 ± 0.1 and 2.8 ± 0.1 nm for D-glucuronic acid coated Na2WO4 and BaCO3 nanoparticles, respectively. All the nanoparticles exhibited a strong x-ray attenuation. In vivo CT images were obtained after intravenous injection of an aqueous sample suspension of D-glucuronic acid coated Na2WO4 nanoparticles, and positive contrast enhancements in the kidney were clearly shown. These findings indicate that the nanoparticles reported in this study may be promising CT contrast agents. PMID:27877838

  4. Fe-based nanoparticulate metallic alloys as contrast agents for magnetic resonance imaging.

    PubMed

    Bomatí-Miguel, Oscar; Morales, María P; Tartaj, Pedro; Ruiz-Cabello, Jesús; Bonville, Pierre; Santos, Martín; Zhao, Xinqing; Veintemillas-Verdaguer, Sabino

    2005-10-01

    Pharmaceutical grade magnetic colloidal dispersions have been prepared from iron alloys synthesized by laser pyrolysis. The colloids were obtained by simultaneous dispersion and coating of the particles with dextran in a strong alkaline solution. Both powders and dispersions have been analyzed in terms of microstructural characteristics, chemical composition and magnetic properties. The powders consist of uniform spherical nanoparticles (12 nm of diameter) showing a metallic core encapsulated into an iron-oxide shell. On the other hand, the colloidal dispersions consist of magnetic particles-aggregates with hydrodynamic sizes of approximately 75 nm. Magnetic resonance images of rats were taken after the intravenously administration of the Fe colloidal dispersions, and compared with those obtained using a commercial iron oxide magnetic resonance imaging contrast agent. The results showed a contrast improvement of 60% in the liver with respect to the commercial sample, which suggests that this product could be a suitable contrast agent for NMR imaging of liver and spleen.

  5. Synthesis of nanoparticle CT contrast agents: in vitro and in vivo studies

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

    Water-soluble and biocompatible D-glucuronic acid coated Na2WO4 and BaCO3 nanoparticles were synthesized for the first time to be used as x-ray computed tomography (CT) contrast agents. Their average particle diameters were 3.2 ± 0.1 and 2.8 ± 0.1 nm for D-glucuronic acid coated Na2WO4 and BaCO3 nanoparticles, respectively. All the nanoparticles exhibited a strong x-ray attenuation. In vivo CT images were obtained after intravenous injection of an aqueous sample suspension of D-glucuronic acid coated Na2WO4 nanoparticles, and positive contrast enhancements in the kidney were clearly shown. These findings indicate that the nanoparticles reported in this study may be promising CT contrast agents.

  6. Golden carbon nanotubes as multimodal photoacoustic and photothermal high-contrast molecular agents

    PubMed Central

    Kim, Jin-Woo; Galanzha, Ekaterina I.; Shashkov, Evgeny V.; Moon, Hyung-Mo; Zharov, Vladimir P.

    2012-01-01

    Carbon nanotubes have shown promise as contrast agents for photoacoustic and photothermal imaging of tumours and infections because they offer high resolution and allow deep tissue imaging. However, in vivo applications have been limited by the relatively low absorption displayed by nanotubes at near-infrared wavelengths and concerns over toxicity. Here, we show that gold-plated carbon nanotubes—termed golden carbon nanotubes—can be used as photoacoustic and photothermal contrast agents with enhanced near-infrared contrast (~102-fold) for targeting lymphatic vessels in mice using extremely low laser fluence levels of a few mJ cm−2. Antibody-conjugated golden carbon nanotubes were used to map the lymphatic endothelial receptor, and preliminary in vitro viability tests show golden carbon nanotubes have minimal toxicity. This new nanomaterial could be an effective alternative to existing nanoparticles and fluorescent labels for non-invasive targeted imaging of molecular structures in vivo. PMID:19809462

  7. The influence of agent delivery mode on cardiomyocyte injury induced by myocardial contrast echocardiography in rats.

    PubMed

    Miller, Douglas L; Dou, Chunyan; Armstrong, William F

    2005-09-01

    Myocardial contrast echocardiography (MCE) can induce bioeffects in rat hearts by local activation of the contrast agent gas bodies. This study was designed to examine the influence of agent delivery mode on the magnitude of cardiomyocyte injury. A total of 69 hairless rats were anesthetized and mounted vertically in a water bath. Evans blue dye was injected as vital stain for cardiomyocyte injury. Definity contrast agent was diluted in saline and injected via tail vein at 20 or 80 microL/kg in bolus or infusion mode. In 12 rats, 0.57 mg/kg dipyridamole was given to simulate a stress test. MCE in a short axis view with 1:4 or 1:16 ECG triggering was performed at 1.5 MHz for 5 or 20 min. The peak rarefactional pressure amplitude was set to 1.1 or 2.0 MPa. Premature beats were counted from the ECG record. Evans blue fluorescent cells were counted on frozen sections from the center of the scan plane of heart samples obtained 24 h postMCE. Infusion of the contrast agent led to more cardiomyocyte injury than did bolus injection. Dipyridamole stress also increased the effect. Varying the infusion rate or trigger interval was less important than the overall dosage during scanning. Exposure at 1.1 MPa and 80 microL/kg yielded significant cell killing relative to shams. Premature beats generally followed the same trends as cell injury, except that lower infusion rates tended to increase this effect. Contrast agent delivery mode, as well as dose and peak rarefactional pressure amplitude, has a significant influence on the bioeffects potential of MCE.

  8. MCNP simulation of absorbed energy and dose by iodinated contrast agent

    NASA Astrophysics Data System (ADS)

    He, Wenjun; Mah, Eugene; Huda, Walter; Yao, Hai

    2012-03-01

    The purpose of this study is to investigate the absorbed dose and energy by iodinated contrast medium in diagnostic radiology. A simulation geometry in which an inner sphere (d = 0.2cm, 1cm, 5cm) filled with iodinated contrast medium (or water) is located at the center of a 20cm diameter water sphere was used in simulations performed with MCNP5 codes. Monoenergetic x-rays with energies ranging from 40 to 80keV from a cone beam source were utilized and contrast medium concentration ranged from 100 to 1mg/ml. Absorbed dose ratio (RD) to inner sphere and total absorbed energies ratio (RE) to the whole phantom with and without iodinated contrast medium were investigated. The maximum RD was ~13 for the 0.2cm diameter sphere with 100mg/ml contrast medium. The maximum RE was ~1.05 for the 5cm diameter contrast sphere at 80keV with 100mg/ml contrast medium. Under the same incident photon energy, increasing the inner sphere size from 0.2cm to 5cm caused a ~63% increase in the RD on average. Decreasing the contrast medium concentration from 100 to 10 mg/ml caused a decrease of RD of ~ 76%. A conclusion was reached that although local absorbed dose increase caused by iodinated contrast agent could be high; the increase in total absorbed energy is negligible.

  9. Relative diffusion of paramagnetic metal complexes of MRI contrast agents in an isotropic hydrogel medium.

    PubMed

    Weerakoon, Bimali Sanjeevani; Osuga, Toshiaki

    2017-03-01

    The observation of molecular diffusion by means of magnetic resonance imaging (MRI) is significant in the evaluation of the metabolic activity of living tissues. Series of MRI examinations were conducted on a diffusion model to study the behaviour of the diffusion process of different-molecular-weight (MW) paramagnetic MRI contrast agents in an isotropic agar hydrogel medium. The model consisted of a solidified 1 % agar gel with an initial concentration of 0.5 mmol/L contrast solution layered on top of the gel. The diffusion process was monitored at pre-determined time intervals of immediately, 1, 6, 9, 23, and 48 h after introduction of the contrast agents onto the agar gel with a T1-weighted spin-echo (SE) pulse sequence. Three types of paramagnetic contrast agents, Gd-DTPA with a MW of 547.57 g/mol, Prohance with a MW of 558.69 g/mol and MnCl2 with a MW of 125.84 g/mol, resulted in an approximate average diffusional displacement ratio of 1:1:2 per hour, respectively, within 48 h of the experiment. Therefore, the results of this study supported the hypothesis that the rate of the diffusion process of MRI contrast agents in the agar hydrogel medium is inversely related to their MWs. However, more repetitions are necessary under various types of experimental conditions and also with various types of contrast media of different MWs for further confirmation and validation of these results.

  10. A novel blood-pooling MR contrast agent: Carboxymethyl-diethylaminoethyl dextran magnetite.

    PubMed

    Sonoda, Akinaga; Nitta, Norihisa; Tsuchiya, Keiko; Nitta-Seko, Ayumi; Ohta, Shinichi; Otani, Hideji; Murata, Kiyoshi

    2016-12-01

    Gadofosveset trisodium is available as a prolonged pooling vascular contrast agent for magnetic resonance imaging. As gadolinium (Gd)-based agents may increase the risk for nephrogenic systemic fibrosis in patients with severe renal insufficiency, the present study synthesized carboxymethyl-diethylaminoethyl dextran magnetite (CMEADM) particles as a blood-pooling, non-Gd‑based contrast agent. CMEADM particles carry a negative or positive charge due to the binding of amino and carboxyl groups to the hydroxyl group of dextran. The present study evaluated whether the degree of charge alters the blood‑pooling time. The evaluation was performed by injecting four groups of three Japanese white rabbits each with CMEADM‑, CMEADM2‑, CMEADM+ (surface charges: ‑10.4, ‑41.0 and +9.6 mV, respectively) or with ultrasmall superparamagnetic iron oxide (USPIO; ‑11.5 mV). The relative signal intensity (SIrel) of each was calculated using the following formula: SIrel = (SI post‑contrast ‑ SI pre‑contrast / SI pre‑contrast) x 100. Following injection with the CMEADMs, but not with USPIO, the in vivo pooling time was prolonged to >300 min. No significant differences were attributable to the electric charge among the CMEADM‑, CMEADM2‑ or and CMEADM+ particles when analyzed with analysis of variance and Tukey's HSD test. Taken together, all three differently‑charged CMEADM2 particles exhibited prolonged vascular enhancing effects, compared with the USPIO. The degree of charge of the contrast agents used in the present study did not result in alteration of the prolonged blood pooling time.

  11. Microbubbles as a scattering contrast agent for grating-based x-ray dark-field imaging.

    PubMed

    Velroyen, A; Bech, M; Malecki, A; Tapfer, A; Yaroshenko, A; Ingrisch, M; Cyran, C C; Auweter, S D; Nikolaou, K; Reiser, M; Pfeiffer, F

    2013-02-21

    In clinically established-absorption-based-biomedical x-ray imaging, contrast agents with high atomic numbers (e.g. iodine) are commonly used for contrast enhancement. The development of novel x-ray contrast modalities such as phase contrast and dark-field contrast opens up the possible use of alternative contrast media in x-ray imaging. We investigate using ultrasound contrast agents, which unlike iodine-based contrast agents can also be administered to patients with renal impairment and thyroid dysfunction, for application with a recently developed novel x-ray dark-field imaging modality. To produce contrast from these microbubble-based contrast agents, our method exploits ultra-small-angle coherent x-ray scattering. Such scattering dark-field x-ray images can be obtained with a grating-based x-ray imaging setup, together with refraction-based differential phase-contrast and the conventional attenuation contrast images. In this work we specifically show that ultrasound contrast agents based on microbubbles can be used to produce strongly enhanced dark-field contrast, with superior contrast-to-noise ratio compared to the attenuation signal. We also demonstrate that this method works well with an x-ray tube-based setup and that the relative contrast gain even increases when the pixel size is increased from tenths of microns to clinically compatible detector resolutions about up to a millimetre.

  12. Microbubbles as a scattering contrast agent for grating-based x-ray dark-field imaging

    NASA Astrophysics Data System (ADS)

    Velroyen, A.; Bech, M.; Malecki, A.; Tapfer, A.; Yaroshenko, A.; Ingrisch, M.; Cyran, C. C.; Auweter, S. D.; Nikolaou, K.; Reiser, M.; Pfeiffer, F.

    2013-02-01

    In clinically established—absorption-based—biomedical x-ray imaging, contrast agents with high atomic numbers (e.g. iodine) are commonly used for contrast enhancement. The development of novel x-ray contrast modalities such as phase contrast and dark-field contrast opens up the possible use of alternative contrast media in x-ray imaging. We investigate using ultrasound contrast agents, which unlike iodine-based contrast agents can also be administered to patients with renal impairment and thyroid dysfunction, for application with a recently developed novel x-ray dark-field imaging modality. To produce contrast from these microbubble-based contrast agents, our method exploits ultra-small-angle coherent x-ray scattering. Such scattering dark-field x-ray images can be obtained with a grating-based x-ray imaging setup, together with refraction-based differential phase-contrast and the conventional attenuation contrast images. In this work we specifically show that ultrasound contrast agents based on microbubbles can be used to produce strongly enhanced dark-field contrast, with superior contrast-to-noise ratio compared to the attenuation signal. We also demonstrate that this method works well with an x-ray tube-based setup and that the relative contrast gain even increases when the pixel size is increased from tenths of microns to clinically compatible detector resolutions about up to a millimetre.

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

    PubMed Central

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

    2015-01-01

    It is not known whether administration of contrast agent via retro-orbital injection or the tail vein route affects the efficiency of dynamic contrast-enhanced magnetic resonance imaging (MRI). Therefore, we compared the effects of retro-orbital and tail vein injection on the kinetics of the contrast agent used for MRI in mice. The same group of nine healthy female mice received contrast agent via either route. An extracellular contrast agent was infused via the tail vein and retro-orbital vein, in random order. Dynamic contrast-enhanced MRI was performed before and after administering the contrast agent. The contrast effects in the liver, kidney, lung, and myocardium were assessed. The average total times of venous puncture and mounting of the injection system were about 10 and 4 min for the tail vein and retro-orbital route, respectively. For all organs assessed, the maximum contrast ratio occurred 30 s after administration and the time course of the contrast ratio was similar with either routes. For each organ, the contrast ratios correlated strongly; the contrast ratios were similar. The retro-orbital and tail vein routes afforded similar results in terms of the kinetics of the contrast agent. The retro-orbital route can be used as a simple efficient alternative to tail vein injection for dynamic contrast-enhanced MRI of mice. PMID:26060990

  14. Highly magnetic iron carbide nanoparticles as effective T2 contrast agents

    NASA Astrophysics Data System (ADS)

    Huang, Guoming; Hu, Juan; Zhang, Hui; Zhou, Zijian; Chi, Xiaoqin; Gao, Jinhao

    2013-12-01

    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.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. Electronic supplementary information (ESI) available: Supplementary figures and experimental details. See DOI: 10.1039/c3nr04691e

  15. Multimeric Near IR–MR Contrast Agent for Multimodal In Vivo Imaging

    PubMed Central

    2015-01-01

    Multiple imaging modalities are often required for in vivo imaging applications that require both high probe sensitivity and excellent spatial and temporal resolution. In particular, MR and optical imaging are an attractive combination that can be used to determine both molecular and anatomical information. Herein, we describe the synthesis and in vivo testing of two multimeric NIR–MR contrast agents that contain three Gd(III) chelates and an IR-783 dye moiety. One agent contains a PEG linker and the other a short alkyl linker. These agents label cells with extraordinary efficacy and can be detected in vivo using both imaging modalities. Biodistribution of the PEGylated agent shows observable fluorescence in xenograft MCF7 tumors and renal clearance by MR imaging. PMID:26083313

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

  17. Mesoporous silica nanoparticles as a breast-cancer targeting ultrasound contrast agent

    PubMed Central

    Milgroom, Andrew; Intrator, Miranda; Madhavan, Krishna; Mazzaro, Luciano; Shandas, Robin; Liu, Bolin; Park, Daewon

    2014-01-01

    Ultrasound (US) is used widely in the context of breast cancer. While it is advantageous for a number of reasons, it has low specificity and requires the use of a contrast agent. Its use as a standalone diagnostic and real-time imaging modality could be achieved by development of a tumor-targeted ultrasound contrast agent (UCA); functionalizing the UCA with a tumor-targeting agent would also allow the targeted administration of anti-cancer drugs at the tumor site. In this article, clinical US techniques are used to show that mesoporous silica nanoparticles (MSNs), functionalized with the monoclonal antibody Herceptin®, can be used as an effective UCA by increasing US image contrast. Furthermore, in vitro assays show the successful localization and binding of the MSN-Herceptin conjugate to HER2+ cancer cells, resulting in tumor-specific cytotoxicity. These results demonstrate the potential of MSNs as a stable, biocompatible, and effective therapeutic and diagnostic (“theranostic”) agent for US-based breast cancer imaging, diagnosis, and treatment. PMID:24269054

  18. NOTE: The effects of paramagnetic contrast agents on metabolite protons in aqueous solution

    NASA Astrophysics Data System (ADS)

    Murphy, Philip S.; Leach, Martin O.; Rowland, Ian J.

    2002-03-01

    The longitudinal (R1) and transverse (R2) relaxivities of the clinically used contrast agents Gd(DTPA)2-, Gd(DOTA)- and Gd(DTPA-BMA) have been determined in mixed aqueous metabolite solutions for choline, creatine and N-acetylaspartate. Measurements were performed at 1.5 T using a STEAM sequence on 25 mM metabolite solutions at pH = 7.4 and 22 °C. The data showed that for all the contrast agents and metabolites, R1 ~ R2. The largest range of relaxivity values was found for Gd(DTPA)2-, where R2 = 6.8 +/- 0.3 mM-1 s-1 for choline and 1.5 +/- 0.4 mM-1 s-1 for N-acetylaspartate. Variation in relaxivity values was attributed primarily to differences between the charges of the paramagnetic agent and metabolite. The maximum potential influence of the contrast agents on in vivo metabolite signals was calculated using the measured relaxivities.

  19. Ultrasound guided site specific gene delivery system using adenoviral vectors and commercial ultrasound contrast agents.

    PubMed

    Howard, Candace M; Forsberg, Flemming; Minimo, Corrado; Liu, Ji-Bin; Merton, Daniel A; Claudio, Pier Paolo

    2006-11-01

    We have evaluated if ultrasound imaging (US) and various commercially available contrast microbubbles can serve as a non-invasive systemically administered delivery vehicle for site-specific adenoviral-mediated gene transfer in vitro and in vivo. The contrast agents were tested for their ability to enclose and to protect an adenoviral vector carrying the GFP marker gene (Ad-GFP) into the microbubbles. We have also evaluated the ability of the innate immune system to inactivate free adenoviruses as well as unenclosed viruses adsorbed on the surface of the contrast agents and in turn the ability of the microbubbles to enclose and to protect the viral vectors from such agents. In vitro as well as in vivo, innate components of the immune system were able to serve as inactivating agents to clear free viral particles and unenclosed adenoviruses adsorbed on the microbubbles' surface. Systemic delivery of Ad-GFP enclosed into microbubbles in the tail vein of nude mice resulted in specific targeting of the GFP transgene. Both fluorescence microscopy and GFP immunohistochemistry demonstrated US guided specific transduction in the targeted cells only, with no uptake in either heart, lungs or liver using complement-pretreated Ad-GFP microbubbles. This approach enhances target specificity of US microbubble destruction as a delivery vehicle for viral-mediated gene transfer.

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

    PubMed

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

    2008-11-11

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

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

    NASA Astrophysics Data System (ADS)

    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.

  2. A naturally occurring contrast agent for OCT imaging of smokers' lung

    NASA Astrophysics Data System (ADS)

    Yang, Ying; Bagnaninchi, Pierre O.; Whiteman, Suzanne C.; Gey van Pittius, Daniel; El Haj, Alicia J.; Spiteri, Monica A.; Wang, Ruikang K.

    2005-08-01

    Optical coherence tomography (OCT) offers great potential for clinical applications in terms of its cost, safety and real-time imaging capability. Improvement of its resolution for revealing sub-layers or sub-cellular components within a tissue will further widen its application. In this study we report that carbon pigment, which is frequently present in the lungs of smokers, could be used as a contrast agent to improve the OCT imaging of lung tissue. Carbon produced an intense bright OCT image at a relatively deep location. The parallel histopathological section analysis confirmed the presence of carbon pigment in such tissues. The underlying mechanism of the OCT image formation has been discussed based on a model system in which carbon particles were dispersed in agar gel. Calculations and in-depth intensity profiles of OCT revealed that higher refractive index particles with a size close to or smaller than the wavelength would greatly increase backscattering and generate a sharp contrast, while a particle size several times larger than the wavelength would absorb or obstruct the light path. The naturally occurring contrast agent could provide a diagnostic biomarker of lung tissue in smokers. Furthermore, carbon under such circumstances, can be used as an effective exogenous contrast agent, with which specific components or tissues exhibiting early tumour formation can be optically labelled to delineate the location and boundary, providing potential for early cancer detection and its treatment.

  3. Environmentally sensitive paramagnetic and diamagnetic contrast agents for nuclear magnetic resonance imaging and spectroscopy.

    PubMed

    Pacheco-Torres, Jesus; Calle, Daniel; Lizarbe, Blanca; Negri, Viviana; Ubide, Carmen; Fayos, Rosa; Larrubia, Pilar López; Ballesteros, Paloma; Cerdan, Sebastian

    2011-01-01

    Even though alterations in the microenvironmental properties of tissues underlie the development of the most prevalent and morbid pathologies, they are not directly observable in vivo by Magnetic Resonance Imaging (MRI) or Spectroscopy (MRS) methods. This circumstance has lead to the development of a wide variety of exogenous paramagnetic and diamagnetic MRI and MRS probes able to inform non invasively on microenvironmental variables such as pH, pO(2), ion concentration o even temperature. This review covers the fundamentals of environmental contrast and the current arsenal of endogenous and exogenous MRI and MRS contrast enhancing agents available to visualize it. We begin describing the physicochemical background necessary to understand paramagnetic and diamagnetic contrast enhancement with a special reference to novel magnetization transfer and (13)C hyperpolarization strategies. We describe then the main macrocyclic structures used to support the environmentally sensitive paramagnetic sensors, including CEST and PARACEST pH sensitive probes, temperature probes and enzyme activity or gene expression activatable probes. Finally we address the most commonly used diamagnetic contrast agents including imidazolic derivatives to reveal extracellular pH and tissue pO(2) values by MRS. The potential applications of these agents in multimodal and molecular imaging approaches are discussed.

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  5. Dynamical analysis of the nonlinear response of ultrasound contrast agent microbubbles.

    PubMed

    Carroll, James M; Calvisi, Michael L; Lauderbaugh, Leal K

    2013-05-01

    The nonlinear response of spherical ultrasound contrast agent microbubbles is investigated to understand the effects of common shells on the dynamics. A compressible form of the Rayleigh-Plesset equation is combined with a thin-shell model developed by Lars Hoff to simulate the radial response of contrast agents subject to ultrasound. The responses of Albunex, Sonazoid, and polymer shells are analyzed through the application of techniques from dynamical systems theory such as Poincaré sections, phase portraits, and bifurcation diagrams to illustrate the qualitative dynamics and transition to chaos that occurs under certain changes in system parameters. Corresponding calculations of Lyapunov exponents provide quantitative data on the system dynamics. The results indicate that Albunex and polymer shells sufficiently stabilize the response to prevent transition to the chaotic regime throughout typical clinical ranges of ultrasound pressure and frequency. By contrast, Sonazoid shells delay the onset of chaos relative to an unshelled bubble but do not prevent it. A contour plot identifying regions of periodic and chaotic behavior over clinical ranges of ultrasound pressure and frequency is provided for Sonazoid. This work characterizes the nonlinear response of various ultrasound contrast agents, and shows that shell properties have a profound influence on the dynamics.

  6. Virus-based nanomaterials as PET and MR contrast agents: from technology development to translational medicine

    PubMed Central

    Shukla, Sourabh; Steinmetz, Nicole F.

    2015-01-01

    Viruses have recently emerged as ideal protein scaffolds for a new class of contrast agents that can be used in medical imaging procedures such as positron emission tomography (PET) and magnetic resonance imaging (MRI). Whereas synthetic nanoparticles are difficult to produce as homogeneous formulations due to the inherently stochastic nature of the synthesis process, virus-based nanoparticles are genetically encoded and are therefore produced as homogeneous and monodisperse preparations with a high degree of quality control. Because the virus capsids have a defined chemical structure that has evolved to carry cargoes of nucleic acids, they can be modified to carry precisely defined cargoes of contrast agents and can be decorated with spatially defined contrast reagents on the internal or external surfaces. Viral nanoparticles can also be genetically programed or conjugated with targeting ligands to deliver contrast agents to specific cells, and the natural biocompatibility of viruses means they are cleared rapidly from the body. Nanoparticles based on bacteriophages and plant viruses are safe for use in humans and can be produced inexpensively in large quantities as self-assembling recombinant proteins. Based on these considerations, a new generation of contrast agents has been developed using bacteriophages and plant viruses as scaffolds to carry positron-emitting radioisotopes such as [18F] fluorodeoxyglucose for PET imaging and iron oxide or Gd3+ for MRI. Although challenges such as immunogenicity, loading efficiency and regulatory compliance remain to be address, virus-based nanoparticles represent a promising new enabling technology for a new generation of highly biocompatible and biodegradable targeted imaging reagents. PMID:25683790

  7. Contrast media and glomerular filtration: dose dependence of clearance for three agents

    SciTech Connect

    Baeck, S.E.K.; Krutzen, E.; Nilsson-Ehle, P.

    1988-09-01

    Determination of plasma clearance of contrast agents has been advocated as a means to assess glomerular filtration rate. To evaluate the feasibility of different agents for this purpose, we have compared, in healthy volunteers, the dose dependence of plasma clearance for three contrast media (iohexol, a nonionic agent, and iothalamate and metrizoate, which are ionic substances), with special emphasis on the lower dose range (2-20 mL corresponding to 0.9-12.9 g, depending on dose and agent). Iohexol and iothalamate were cleared at constant rates, irrespective of given dose, whereas metrizoate clearance increased significantly at lower doses. In general, the clearances or iothalamate and metrizoate were, respectively, moderately and markedly higher than that of iohexol. The clearance of different doses of metrizoate (2 mL versus a radiographic dose of 40 mL or more) was also compared with the clearance of (/sup 51/Cr)EDTA in two groups of patients with reduced renal function. When compared with (/sup 51/Cr)EDTA in patients with renal dysfunction, metrizoate was cleared significantly faster after a 2-mL dose, whereas clearances were identical when the metrizoate dose was 40 mL or more. These findings indicate that tubular secretion plays an active role in the elimination of metrizoate. The pharmacokinetic properties of iohexol, in combination with its low toxicity, make it a suitable agent for determination of glomerular filtration rate in clinical practice.

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

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

  9. Research into europium complexes as magnetic resonance imaging contrast agents (Review)

    PubMed Central

    HAN, GUOCAN; DENG, YANGWEI; SUN, JIHONG; LING, JUN; SHEN, ZHIQUAN

    2015-01-01

    Europium (Eu) is a paramagnetic lanthanide element that possesses an outstanding luminescent property. Eu complexes are ideal fluorescence imaging (FI) agents. Eu2+ has satisfactory relaxivity and optical properties, and can realize magnetic resonance (MRI)-FI dual imaging applications when used with appropriate cryptands that render it oxidatively stable. By contrast, based on the chemical exchange saturation transfer (CEST) mechanism, Eu3+ complexes can provide enhanced MRI sensitivity when used with optimal cryptands, incorporated into polymeric CEST agents or blended with Gd3+. Eu complexes are promising in MRI-FI dual imaging applications and have a bright future. PMID:26136858

  10. A Linear Bicharacteristic FDTD Method

    NASA Technical Reports Server (NTRS)

    Beggs, John H.

    2001-01-01

    The linear bicharacteristic scheme (LBS) was originally developed to improve unsteady solutions in computational acoustics and aeroacoustics [1]-[7]. It is a classical leapfrog algorithm, but is combined with upwind bias in the spatial derivatives. This approach preserves the time-reversibility of the leapfrog algorithm, which results in no dissipation, and it permits more flexibility by the ability to adopt a characteristic based method. The use of characteristic variables allows the LBS to treat the outer computational boundaries naturally using the exact compatibility equations. The LBS offers a central storage approach with lower dispersion than the Yee algorithm, plus it generalizes much easier to nonuniform grids. It has previously been applied to two and three-dimensional freespace electromagnetic propagation and scattering problems [3], [6], [7]. This paper extends the LBS to model lossy dielectric and magnetic materials. Results are presented for several one-dimensional model problems, and the FDTD algorithm is chosen as a convenient reference for comparison.

  11. FDTD-ANT User Manual

    NASA Technical Reports Server (NTRS)

    Zimmerman, Martin L.

    1995-01-01

    This manual explains the theory and operation of the finite-difference time domain code FDTD-ANT developed by Analex Corporation at the NASA Lewis Research Center in Cleveland, Ohio. This code can be used for solving electromagnetic problems that are electrically small or medium (on the order of 1 to 50 cubic wavelengths). Calculated parameters include transmission line impedance, relative effective permittivity, antenna input impedance, and far-field patterns in both the time and frequency domains. The maximum problem size may be adjusted according to the computer used. This code has been run on the DEC VAX and 486 PC's and on workstations such as the Sun Sparc and the IBM RS/6000.

  12. Gd-doped BNNTs as T2-weighted MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Ciofani, Gianni; Boni, Adriano; Calucci, Lucia; Forte, Claudia; Gozzi, Alessandro; Mazzolai, Barbara; Mattoli, Virgilio

    2013-08-01

    This work describes, for the first time, doping of boron nitride nanotubes (BNNTs) with gadolinium (Gd@BNNTs), a stable functionalization that permits non-invasive BNNT tracking via magnetic resonance imaging (MRI). We report the structure, Gd loading, and relaxometric properties in water suspension at 7 T of Gd@BNNTs, and show the behaviour of these nanostructures as promising T2-weighted contrast agents. Finally, we demonstrate their complete biocompatibility in vitro on human neuroblastoma cells, together with their ability to effectively label and affect contrast in MRI images at 7 T.

  13. Gadolinium-based contrast agents: did we miss something in the last 25 years?

    PubMed

    Beomonte Zobel, Bruno; Quattrocchi, Carlo Cosimo; Errante, Yuri; Grasso, Rosario Francesco

    2016-06-01

    In the last 24 months, several clinical and experimental studies, suggested first and demonstrated later, a progressive concentration of Gadolinium in the brain of normal renal function patients, following repeated injections of some of the commercially approved Gadolinium-Based Contrast Agents. Although, till now, Gadolinium brain deposits have not been associated to any kind of neurological signs or symptoms, they oblige the radiology community to modify the actual approach in using Gadolinium contrast media in daily practice, to reduce unknown possible risks for patients.

  14. Imaging translucent cell bodies in the living mouse retina without contrast agents

    PubMed Central

    Guevara-Torres, A.; Williams, D. R.; Schallek, J. B.

    2015-01-01

    The transparency of most retinal cell classes typically precludes imaging them in the living eye; unless invasive methods are used that deploy extrinsic contrast agents. Using an adaptive optics scanning light ophthalmoscope (AOSLO) and capitalizing on the large numerical aperture of the mouse eye, we enhanced the contrast from otherwise transparent cells by subtracting the left from the right half of the light distribution in the detector plane. With this approach, it is possible to image the distal processes of photoreceptors, their more proximal cell bodies and the mosaic of horizontal cells in the living mouse retina. PMID:26114032

  15. Imaging translucent cell bodies in the living mouse retina without contrast agents.

    PubMed

    Guevara-Torres, A; Williams, D R; Schallek, J B

    2015-06-01

    The transparency of most retinal cell classes typically precludes imaging them in the living eye; unless invasive methods are used that deploy extrinsic contrast agents. Using an adaptive optics scanning light ophthalmoscope (AOSLO) and capitalizing on the large numerical aperture of the mouse eye, we enhanced the contrast from otherwise transparent cells by subtracting the left from the right half of the light distribution in the detector plane. With this approach, it is possible to image the distal processes of photoreceptors, their more proximal cell bodies and the mosaic of horizontal cells in the living mouse retina.

  16. Efficient, non-iterative estimator for imaging contrast agents with spectral x-ray detectors.

    PubMed

    Alvarez, Robert E

    2015-12-22

    This paper describes an estimator to image contrast agents and body materials with x-ray spectral measurements. Previous implementations were limited to a two function basis set but the new implementation is usable with the three or more basis functions that are required with high atomic number contrast materials. The estimator variance is equal to the Cramèr-Rao lower bound (CRLB) and it is unbiased. Its parameters can be computed from measurements of a calibration phantom with the clinical x-ray system and it is non-iterative. The estimator is compared with an iterative maximum likelihood estimator.

  17. Modifying the size distribution of microbubble contrast agents for high-frequency subharmonic imaging

    PubMed Central

    Shekhar, Himanshu; Rychak, Joshua J.; Doyley, Marvin M.

    2013-01-01

    Purpose: Subharmonic imaging is of interest for high frequency (>10 MHz) nonlinear imaging, because it can specifically detect the response of ultrasound contrast agents (UCA). However, conventional UCA produce a weak subharmonic response at high frequencies, which limits the sensitivity of subharmonic imaging. We hypothesized that modifying the size distribution of the agent can enhance its high-frequency subharmonic response. The overall goal of this study was to investigate size-manipulated populations of the agent to determine the range of sizes that produce the strongest subharmonic response at high frequencies (in this case, 20 MHz). A secondary goal was to assess whether the number or the volume-weighted size distribution better represents the efficacy of the agent for high-frequency subharmonic imaging. Methods: The authors created six distinct agent size distributions from the native distribution of a commercially available UCA (Targestar-P®). The median (number-weighted) diameter of the native agent was 1.63 μm, while the median diameters of the size-manipulated populations ranged from 1.35 to 2.99 μm. The authors conducted acoustic measurements with native and size-manipulated agent populations to assess their subharmonic response to 20 MHz excitation (pulse duration 1.5 μs, pressure amplitudes 100–398 kPa). Results: The results showed a considerable difference between the subharmonic response of the agent populations that were investigated. The subharmonic response peaked for the agent population with a median diameter of 2.15 μm, which demonstrated a subharmonic signal that was 8 dB higher than the native agent. Comparing the subharmonic response of different UCA populations indicated that microbubbles with diameters between 1.3 and 3 μm are the dominant contributors to the subharmonic response at 20 MHz. Additionally, a better correlation was observed between the subharmonic response of the agent and the number-weighted size-distribution (R2

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  19. Optimization of oral contrast agents for MR imaging of the small bowel.

    PubMed

    Lauenstein, Thomas C; Schneemann, Herbert; Vogt, Florian M; Herborn, Christoph U; Ruhm, Stefan G; Debatin, Jorg F

    2003-07-01

    Effect on small-bowel distention of additives to water as contrast agents for magnetic resonance (MR) imaging was assessed. Oral contrast agents included water and water in combination with mannitol, a bulk fiber laxative, locust bean gum, and a combination of mannitol and locust bean gum. Filling of the small bowel was quantified on coronal images obtained with two-dimensional true fast imaging with steady-state precession sequence; bowel diameters were measured. Ingestion of water with locust bean gum and mannitol provided the best distention of the small bowel. MR imaging of the small bowel with oral administration of water can be improved with addition of osmotic and nonosmotic substances that lead to decreased water resorption.

  20. Hepatobiliary contrast agents: differential diagnosis of focal hepatic lesions, pitfalls and other indications.

    PubMed

    Francisco, Flávia Angélica Ferreira; de Araújo, Antonio Luis Eiras; Oliveira Neto, Jaime Araújo; Parente, Daniella Braz

    2014-01-01

    The characterization of focal liver lesions is very important. Magnetic resonance imaging is considered the best imaging method for evaluating such lesions, but does not allow for the diagnosis in all cases. The use of hepatobiliary contrast agents increases the diagnostic accuracy of magnetic resonance imaging and reduces the number of non-specific liver lesions. The main indications for the method include: differentiation between focal nodular hyperplasia and adenoma; characterization of hepatocellular carcinomas in cirrhotic patients; detection of small liver metastases; evaluation of biliary anatomy; and characterization of postoperative biliary fistulas. The use of hepatobiliary contrast agents may reduce the need for invasive diagnostic procedures and further investigations with other imaging methods, besides the need for imaging follow-up.

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

    NASA Astrophysics Data System (ADS)

    Yazdani, Farshad; Fattahi, Bahare; Azizi, Najmodin

    2016-05-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  3. Synthesis and Relaxometric Studies of a Dendrimer-Based pH-Responsive MRI Contrast Agent

    PubMed Central

    Ali, M. Meser; Woods, Mark; Caravan, Peter; Opina, Ana C. L.; Spiller, Marga; Fettinger, James C.

    2009-01-01

    The design of effective pH responsive MRI contrast agents is a key goal in the development of new diagnostic methods for conditions such as kidney disease and cancer. A key factor determining the effectiveness of an agent is the difference between the relaxivity of the “on” state compared to that of the “off” state. In this paper, we demonstrate that it is possible to improve the pH-responsive action of a low molecular weight agent by conjugating it to a macromolecular construct. The synthesis of a bifunctional pH responsive agent is reported. As part of that synthetic pathway we examine the Ing–Manske reaction, identifying an undesirable by-product and establishing effective conditions for promoting a clean and effective reaction. Reaction of the bifunctional pH responsive agent with a G5-PAMAM dendrimer yielded a product with an average of 96 chelates per dendrimer. The relaxivity of the dendrimer conjugate rises from 10.8 mm−1 s−1 (pH 9) to 24.0 mm−1 s−1 (pH 6) per Gd3+ ion. This more than doubles the relaxivity pH response, Δr1, of our agent from just 51% for the original low molecular weight chelate to 122% for the dendrimer. PMID:18601236

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

    DTIC Science & Technology

    2008-01-01

    Dextran coatings have been used to stabilize super - paramagnetic iron oxide nanoparticles used as an MRI contrast agent [1-3]. For a detailed description...that serves to stabilize the particle dispersions. • Dextran coatings have been used to stabilize super - paramagnetic iron oxide nanoparticles for MRI...CT was demonstrated using a barium sulfate (BaSO4) stain. Gold nanoparticles (Au NPs) were prepared and functionalized with L-glutamic acid for

  5. Highly relaxing gadolinium based MRI contrast agents responsive to Mg2+ sensing.

    PubMed

    Abada, Sabah; Lecointre, Alexandre; Elhabiri, Mourad; Esteban-Gómez, David; Platas-Iglesias, Carlos; Tallec, Gaylord; Mazzanti, Marinella; Charbonnière, Loïc J

    2012-04-28

    A Gd complex based on a polyphosphonated pyridyl ligand shows a very high stability in aqueous solution (log K(EuL) = 25.7), a high relaxivity (8.5 mM(-1) s(-1) at 25 °C and 20 MHz) and a marked and selective relaxivity enhancement (37%) in the presence of Mg(2+), opening interesting perspectives for the design of cation responsive contrast agents.

  6. Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent.

    PubMed

    Zhao, M; Beauregard, D A; Loizou, L; Davletov, B; Brindle, K M

    2001-11-01

    The C2 domain of synaptotagmin I, which binds to anionic phospholipids in cell membranes, was shown to bind to the plasma membrane of apoptotic cells by both flow cytometry and confocal microscopy. Conjugation of the protein to superparamagnetic iron oxide nanoparticles allowed detection of this binding using magnetic resonance imaging. Detection of apoptotic cells, using this novel contrast agent, was demonstrated both in vitro, with isolated apoptotic tumor cells, and in vivo, in a tumor treated with chemotherapeutic drugs.

  7. A new macromolecular paramagnetic MR contrast agent binds to activated human platelets.

    PubMed

    Chaubet, Frédéric; Bertholon, Isabelle; Serfaty, Jean-Michel; Bazeli, Ramin; Alsaid, Hasan; Jandrot-Perrus, Martine; Zahir, Charaf; Even, Pascale; Bachelet, Laure; Touat, Ziad; Lancelot, Eric; Corot, Claire; Canet-Soulas, Emmanuelle; Letourneur, Didier

    2007-07-01

    A new functionalized macromolecular magnetic resonance (MR) contrast agent has been developed from a carboxymethyldextran-Gd(DOTA) devoid of biospecificity. The functionalized contrast agent was synthesized in order to mimic PSGL-1, the main ligand of P-selectin, a glycoprotein mainly expressed on the surface of activated platelets. The starting compound, CM1, was first carboxymethylated by monochloroacetic acid leading to a series of 10 derivatives varying in their carboxymethyl content. CM8 derivative, with a degree of substitution in carboxymethyl of 0.84, was chosen for subsequent fluorolabeling and sulfation to give CM8FS. CM8FS has an average number molecular weight of 27 000 +/- 500 g/mol, a hydrodynamic radius of 5.7 +/- 0.2 nm and a high relaxivity (r(1) = 11.2/mM (Gd)/s at 60 MHz). Flow cytometry experiments on whole human blood or on isolated platelets evidenced in vitro a preferential binding of CM8FS on TRAP-activated human platelets. Interestingly, CM8FS did not bind to other blood cells or to resting platelets. Pellets of TRAP-activated human platelets have also been imaged in tubes with a 1.5 T MR imager. A MR signal was observed for activated platelets incubated with CM8FS. Altogether, these in vitro results evidenced the recognition of activated human platelets by a fluorescent paramagnetic contrast agent grafted with carboxyl and sulfate groups. This biomimetic approach associated with the versatile macromolecular platform appears promising for the development of new contrast agents for molecular imaging of activated platelets in cardiovascular diseases such as atherosclerosis and aneurysms.

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

    NASA Astrophysics Data System (ADS)

    Pablico, Michele Huelar

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

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

    PubMed

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

    2011-05-01

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

  10. NIR-activated iron oxides as a new multi-functional contrast agent of photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Ting, Pei-Hsien; Huang, Chih-Chia; Li, Meng-Lin

    2014-03-01

    Iron oxide nanoparticles are commonly used contrast agents for theranostic nanomedicines because of their advantages of good biocompatibility, high stability in physiological conditions, low cytotoxicity and excellent safety record in clinical settings for human use. In this study, we developed a NIR-activated iron oxide (NIR-Fe3O4) nanoparticle as a new multi-functional contrast agent of photoacoustic (PA) imaging. Unlike traditional iron oxides, the developed NIR-Fe3O4 owns biocompatibility and optical tunability capable of providing strong optical absorption in the NIR range for PA signal generation. Its intrinsic magnetic property enables the active magnetic tumor targeting. Phantom experiments were performed to confirm the tunability of NIR-Fe3O4's optical absorption in NIR and demonstrate its magnetic targeting capability. The PA signal response of NIR-Fe3O4 as a function of concentration was also investigated. The results showed that the PA signal of NIR-Fe3O4 with OD=1.25 was comparable to that of blood at 715 nm - the wavelength of peak absorption of the used NIR-Fe3O4. Moreover, the PA signal from NIR-Fe3O4 could be further improved by magnetic targeting. Overall, we proved that the potential of the developed NIR-Fe3O4 as a good tumor targeting contrast agent of PA imaging.

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

    PubMed

    Xing, Zhanwen; Wang, Jinrui; Ke, Hengte; Zhao, Bo; Yue, Xiuli; Dai, Zhifei; Liu, Jibin

    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.

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

    PubMed Central

    Zehri, Aqib H.; Ramey, Wyatt; Georges, Joseph F.; Mooney, Michael A.; Martirosyan, Nikolay L.; Preul, Mark C.; Nakaji, Peter

    2014-01-01

    Background: The clinical application of fluorescent contrast agents (fluorescein, indocyanine green, and aminolevulinic acid) with intraoperative microscopy has led to advances in intraoperative brain tumor imaging. Their properties, mechanism of action, history of use, and safety are analyzed in this report along with a review of current laser scanning confocal endomicroscopy systems. Additional imaging modalities with potential neurosurgical utility are also analyzed. Methods: A comprehensive literature search was performed utilizing PubMed and key words: In vivo confocal microscopy, confocal endomicroscopy, fluorescence imaging, in vivo diagnostics/neoplasm, in vivo molecular imaging, and optical imaging. Articles were reviewed that discussed clinically available fluorophores in neurosurgery, confocal endomicroscopy instrumentation, confocal microscopy systems, and intraoperative cancer diagnostics. Results: Current clinically available fluorescent contrast agents have specific properties that provide microscopic delineation of tumors when imaged with laser scanning confocal endomicroscopes. Other imaging modalities such as coherent anti-Stokes Raman scattering (CARS) microscopy, confocal reflectance microscopy, fluorescent lifetime imaging (FLIM), two-photon microscopy, and second harmonic generation may also have potential in neurosurgical applications. Conclusion: In addition to guiding tumor resection, intraoperative fluorescence and microscopy have the potential to facilitate tumor identification and complement frozen section analysis during surgery by providing real-time histological assessment. Further research, including clinical trials, is necessary to test the efficacy of fluorescent contrast agents and optical imaging instrumentation in order to establish their role in neurosurgery. PMID:24872922

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

    PubMed

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

    2015-10-07

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

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

    NASA Astrophysics Data System (ADS)

    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.

  15. Injectable microbubbles as contrast agents for diagnostic ultrasound imaging: the key role of perfluorochemicals.

    PubMed

    Schutt, Ernest G; Klein, David H; Mattrey, Robert M; Riess, Jean G

    2003-07-21

    Ultrasonography has, until recently, lacked effective contrast-enhancing agents. Micrometer-sized gas bubbles that resonate at a diagnostic frequency are ideal reflectors for ultrasound. However, simple air bubbles, when injected into the blood stream, disappear within seconds through the combined effects of Laplace pressure, blood pressure, and exposure to ultrasound energy. Use of fluorocarbon vapor, by extending the persistence of microbubbles in vivo from seconds to minutes, propelled contrast ultrasonography into clinical practice. Imaging techniques that selectively suppress tissue, but not microbubble signal, further increase image contrast. Approved products consist of C3F8 or SF6 microbubbles, and N2 microbubbles osmotically stabilized with C6F14. These agents allow the detection and characterization of cardiovascular abnormalities and solid organ lesions, such as tumors. By providing higher quality images, they improve the accuracy and confidence of disease diagnosis, and can play a decisive role in clinical decision making. New objectives include agents that target specific cells for the molecular imaging of disease, and drug and gene delivery, including ultrasound-triggered delivery.

  16. Development of Ultrasound-switchable Fluorescence Imaging Contrast Agents based on Thermosensitive Polymers and Nanoparticles

    PubMed Central

    Cheng, Bingbing; Wei, Ming-Yuan; Liu, Yuan; Pitta, Harish; Xie, Zhiwei; Hong, Yi; Nguyen, Kytai T.; Yuan, Baohong

    2015-01-01

    In this work we first introduced a recently developed high-resolution, deep-tissue imaging technique, ultrasound-switchable fluorescence (USF). The imaging principles based on two types of USF contrast agents were reviewed. To improve USF imaging techniques further, excellent USF contrast agents were developed based on high-performance thermoresponsive polymers and environment-sensitive fluorophores. Herein, such contrast agents were synthesized and characterized with five key parameters: (1) peak excitation and emission wavelengths (λex and λem), (2) the fluorescence intensity ratio between on and off states (IOn/IOff), (3) the fluorescence lifetime ratio between on and off states (τOn/τOff), (4) the temperature threshold to switch on fluorophores (Tth), and (5) the temperature transition bandwidth (TBW). We mainly investigated fluorescence intensity and lifetime changes of four environment-sensitive dyes [7-(2-Aminoethylamino)-N,N-dimethyl-4-benzofurazansulfonamide (DBD-ED), St633, Sq660, and St700] as a function of temperature, while the dye was attached to poly(N-isopropylacrylamide) linear polymers or encapsulated in nanoparticles. Six fluorescence resonance energy transfer systems were invented in which both the donor (DBD-ED or ST425) and the acceptor (Sq660) were adopted. Our results indicate that three Förster resonance energy transfer systems, where both IOn/IOff and τOn/τOff are larger than 2.5, are promising for application in future surface tissue bioimaging by USF technique. PMID:26052192

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

    NASA Astrophysics Data System (ADS)

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

    2004-01-01

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

  18. Iodixanol, a new isosmotic nonionic contrast agent compared with iohexol in cardiac angiography.

    PubMed

    Hill, J A; Cohen, M B; Kou, W H; Mancini, G B; Mansour, M; Fountaine, H; Brinker, J A

    1994-07-01

    Iodixanol, a new ratio 6 nonionic iodinated contrast agent with an osmolality equal to serum, was compared with iohexol in a randomized, double-blind, parallel study. Two hundred patients undergoing elective diagnostic cardiac angiography were randomized to iodixanol (n = 101) or iohexol (n = 99). There were no differences noted between the 2 agents in the mean changes in systolic or diastolic blood pressure or heart rate during or immediately after any angiography. However, significantly more patients had a decrease in diastolic blood pressure of > 20 mm Hg during left coronary angiography with iodixanol. The only significant differences in any electrophysiologic parameter were slightly more PR prolongation during left coronary angiography with iodixanol and more ST-segment depression with iohexol during coronary angiography. Neither was clinically significant. Injection-associated discomfort occurred with both agents, but more patients experienced moderate to severe discomfort with iohexol (52%) than with iodixanol (17%) (p < 0.001). Only 1 potentially serious adverse event, ventricular fibrillation with iohexol, was considered related to contrast, and there were no differences noted between the agents. Overall, angiographic quality was equal with all angiograms being assessed as good or excellent in both groups (p = 0.885). In this low-risk population undergoing cardiac angiography, iodixanol is safe and effective without clinically important differences from iohexol. Additional studies in patients at high risk for complications should help further define the role of iodixanol in cardiac angiography.

  19. Multispectral photoacoustic decomposition with localized regularization for detecting targeted contrast agent

    NASA Astrophysics Data System (ADS)

    Tavakoli, Behnoosh; Chen, Ying; Guo, Xiaoyu; Kang, Hyun Jae; Pomper, Martin; Boctor, Emad M.

    2015-03-01

    Targeted contrast agents can improve the sensitivity of imaging systems for cancer detection and monitoring the treatment. In order to accurately detect contrast agent concentration from photoacoustic images, we developed a decomposition algorithm to separate photoacoustic absorption spectrum into components from individual absorbers. In this study, we evaluated novel prostate-specific membrane antigen (PSMA) targeted agents for imaging prostate cancer. Three agents were synthesized through conjugating PSMA-targeting urea with optical dyes ICG, IRDye800CW and ATTO740 respectively. In our preliminary PA study, dyes were injected in a thin wall plastic tube embedded in water tank. The tube was illuminated with pulsed laser light using a tunable Q-switch ND-YAG laser. PA signal along with the B-mode ultrasound images were detected with a diagnostic ultrasound probe in orthogonal mode. PA spectrums of each dye at 0.5 to 20 μM concentrations were estimated using the maximum PA signal extracted from images which are obtained at illumination wavelengths of 700nm-850nm. Subsequently, we developed nonnegative linear least square optimization method along with localized regularization to solve the spectral unmixing. The algorithm was tested by imaging mixture of those dyes. The concentration of each dye was estimated with about 20% error on average from almost all mixtures albeit the small separation between dyes spectrums.

  20. Comparison of two effervescent agents for double-contrast upper gastrointestinal tract radiography.

    PubMed

    Agha, F P; Trenkner, S W; Woolsey, E J; Hayes, D

    1985-11-01

    We prospectively evaluated the efficacy in 100 patients of two effervescent contrast agents commonly used in routine double-contrast upper gastrointestinal (GI) tract examinations: Baros and E-Z-Gas II granules. The study was double blinded. Two radiologists, who were not aware of which effervescent agent was being used, objectively evaluated the radiographic studies. Patient ease in swallowing and acceptance of the effervescent granules was 94% for Baros and 68% for E-Z-Gas II granules. The objective evaluation of the radiographs showed adequate gastric distension (Baros, 94%; E-Z-Gas II, 90%) and adequate to excellent mucosal coating for both agents (Baros, 92%, E-Z-Gas II, 94%). Areae gastricae were better seen with Baros (64% vs. 30%), and air bubbles were less of a problem with Baros. We conclude that Baros effervescent granules have certain distinct advantages over E-Z-Gas II granules regarding patient tolerance and acceptance, better visualization of the areae gastricae, and less degradation of the quality of the radiographs by air bubbles. The differences in mucosal coatings for the two agents was insignificant.

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

    PubMed Central

    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

  2. Pump-probe optical coherence tomography using microencapsulated methylene blue as a contrast agent (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Kim, Wihan; Zebrowski, Erin; Lopez, Hazel C.; Applegate, Brian E.; Charoenphol, Phapanin; Jo, Javier A.

    2016-03-01

    Molecular contrast imaging can target specific molecules or receptors to provide detailed information on the local biochemistry and yield enhanced visualization of pathological and physiological processes. When paired with Optical Coherence Tomography (OCT) it can simultaneously supply the morphological context for the molecular information. We recently demonstrated in vivo molecular contrast imaging of methylene blue (MB) using a 663 nm diode laser as a pump in a Pump-Probe OCT (PPOCT) system. The simple addition of a dichroic mirror in the sample arm enabled PPOCT imaging with a typical 830-nm band spectral-domain OCT system. Here we report on the development of a microencapsulated MB contrast agent. The poly lactic-co-glycolic acid (PLGA) microspheres loaded with MB offer several advantages over bare MB. The microsphere encapsulation improves the PPOCT signal both by enhancing the scattering and preventing the reduction of MB to leucomethylene blue. The surface of the microsphere can readily be functionalized to enable active targeting of the contrast agent without modifying the excited state dynamics of MB that enable PPOCT imaging. Both MB and PLGA are used clinically. PLGA is FDA approved and used in drug delivery and tissue engineering applications. 2.5 μm diameter microspheres were synthesized with an inner core containing 0.01% (w/v) aqueous MB. As an initial demonstration the MB microspheres were imaged in a 100 μm diameter capillary tube submerged in a 1% intralipid emulsion.

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

    PubMed

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

    2013-09-01

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

  4. Assessment of the viscoelastic and oscillation properties of a nano-engineered multimodality contrast agent.

    PubMed

    Kothapalli, Satya V V N; Oddo, Letizia; Paradossi, Gaio; Brodin, Lars-Åke; Grishenkov, Dmitry

    2014-10-01

    Combinations of microbubbles (MBs) and superparamagnetic iron oxide nanoparticles (SPIONs) are used to fabricate dual contrast agents for ultrasound and MRI. This study examines the viscoelastic and oscillation characteristics of two MB types that are manufactured with SPIONs and either anchored chemically on the surface (MBs-chem) or physically embedded (MBs-phys) into a polymer shell. A linearized Church model was employed to simultaneously fit attenuation coefficients and phase velocity spectra that were acquired experimentally. The model predicted lower viscoelastic modulus values, undamped resonance frequencies and total damping ratios for MBs-chem. MBs-chem had a resonance frequency of approximately 13 MHz and a damping ratio of approximately 0.9; thus, MBs-chem can potentially be used as a conventional ultrasound contrast agent with the combined functionality of MRI detection. In contrast, MBs-phys had a resonance frequency and damping of 28 MHz and 1.2, respectively, and requires further modification of clinically available contrast pulse sequences to be visualized.

  5. Biocompatible polypyrrole nanoparticles as a novel organic photoacoustic contrast agent for deep tissue imaging

    NASA Astrophysics Data System (ADS)

    Zha, Zhengbao; Deng, Zijian; Li, Yanyan; Li, Changhui; Wang, Jinrui; Wang, Shumin; Qu, Enze; Dai, Zhifei

    2013-05-01

    Photoacoustic tomography (PAT) has emerged as a hybrid, nonionizing imaging modality because of its satisfactory spatial resolution and high soft tissue contrast. Here, we demonstrate the application of a novel organic PAT contrast agent based on polypyrrole nanoparticles (PPy NPs). Monodisperse PPy NPs are ~46 nm in diameter with strong absorption in the near-infrared (NIR) range, which allowed visualization of PPy NP-containing agar gel embedded in chicken breast muscle at a depth of ~4.3 cm. Compared with PAT images based on the intrinsic optical contrast in mice, the PAT images acquired within 1 h after intravenous administration of PPy NPs showed the brain vasculature with greater clarity than hemoglobin in blood. Preliminary results showed no acute toxicity to the vital organs (heart, liver, spleen, lungs and kidneys) in mice following a single imaging dose of PPy NPs. Our results indicate that PPy NPs are promising contrast agents for PAT with good biocompatibility, high spatial resolution and enhanced sensitivity.

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

    PubMed

    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

    2013-10-07

    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.

  7. Highly magnetic iron carbide nanoparticles as effective T(2) contrast agents.

    PubMed

    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.

  8. Differential structured illumination microendoscopy for in vivo imaging of molecular contrast agents

    PubMed Central

    Keahey, Pelham; Ramalingam, Preetha; Schmeler, Kathleen

    2016-01-01

    Fiber optic microendoscopy has shown promise for visualization of molecular contrast agents used to study disease in vivo. However, fiber optic microendoscopes have limited optical sectioning capability, and image contrast is limited by out-of-focus light generated in highly scattering tissue. Optical sectioning techniques have been used in microendoscopes to remove out-of-focus light but reduce imaging speed or rely on bulky optical elements that prevent in vivo imaging. Here, we present differential structured illumination microendoscopy (DSIMe), a fiber optic system that can perform structured illumination in real time for optical sectioning without any opto-mechanical components attached to the distal tip of the fiber bundle. We demonstrate the use of DSIMe during in vivo fluorescence imaging in patients undergoing surgery for cervical adenocarcinoma in situ. Images acquired using DSIMe show greater contrast than standard microendoscopy, improving the ability to detect cellular atypia associated with neoplasia. PMID:27621464

  9. Design of a Modular Protein-Based MRI Contrast Agent for Targeted Application

    PubMed Central

    Kraff, Oliver; Heider, Dominik; Schramm, Alexander; Hoffmann, Daniel; Bayer, Peter

    2013-01-01

    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 Gd3+. 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. PMID:23762349

  10. Measurement of the contrast agent intrinsic and native harmonic response with single transducer pulse waved ultrasound systems.

    PubMed

    Verbeek, X A; Willigers, J M; Brands, P J; Ledoux, L A; Hoeks, A P

    1999-01-01

    Ultrasound contrast agents, i.e., small gas filled microbubbles, enhance the echogenicity of blood and have the potential to be used for tissue perfusion assessment. The contrast agents scatter ultrasound in a nonlinear manner and thereby introduce harmonics in the ultrasound signal. This property is exploited in new ultrasound techniques like harmonic imaging, which aims to display only the contrast agent presence. Much attention has already been given to the physical properties of the contrast agent. The present study focuses on practical aspects of the measurement of the intrinsic harmonic response of ultrasound contrast agents with single transducer pulse waved ultrasound systems. Furthermore, the consequences of two other sources of harmonics are discussed. These sources are the nonlinear distortion of ultrasound in a medium generating native harmonics, and the emitted signal itself which might contain contaminating harmonics. It is demonstrated conceptually and by experiments that optimization of the contrast agent harmonic response measured with a single transducer is governed by the transducer spectral sensitivity distribution rather than the resonance properties of the contrast agent. Both native and contaminating harmonics may be of considerable strength and can be misinterpreted as intrinsic harmonics of the contrast agent. Practical difficulties to filter out the harmonic component selectively, without deteriorating the image, may cause misinterpretation of the fundamental as a harmonic.

  11. Evaluation of chirp reversal power modulation sequence for contrast agent imaging.

    PubMed

    Novell, A; Sennoga, C A; Escoffre, J M; Chaline, J; Bouakaz, A

    2014-09-07

    Over the last decade, significant research effort has been focused on the use of chirp for contrast agent imaging because chirps are known to significantly increase imaging contrast-to-noise ratio (CNR). New imaging schemes, such as chirp reversal (CR), have been developed to improve contrast detection by increasing non-linear microbubble responses. In this study we evaluated the contrast enhancement efficiency of various chirped imaging sequences in combination with well-established imaging schemes such as power modulation (PM) and pulse inversion (PI). The imaging schemes tested were implemented on a fully programmable open scanner and evaluated by ultrasonically scanning (excitation frequency of 2.5 MHz; amplitude of 350 kPa) a tissue-mimicking flow phantom comprising a 4 mm diameter tube through which aqueous dispersions (dilution fraction of 1/2000) of the commercial ultrasound contrast agent, SonoVue(®) were continuously circulated. The recovery of non-linear microbubble responses after chirp compression requires the development and the optimization of a specific filter. A compression filter was therefore designed and used to compress and extract several non-linear components from the received microbubble responses. The results showed that using chirps increased the image CNR by approximately 10 dB, as compared to conventional Gaussian apodized sine burst excitation but degraded the axial resolution by a factor of 1.4, at -3 dB. We demonstrated that the highest CNR and contrast-to-noise ratio (CTR) were achievable when CR was combined with PM as compared to other imaging schemes such as PI.

  12. Dendritic iodinated contrast agents with PEG-cores for CT imaging: synthesis and preliminary characterization.

    PubMed

    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. Magnetic red blood cells as new contrast agents for MRI applications

    NASA Astrophysics Data System (ADS)

    Antonelli, Antonella; Sfara, Carla; Manuali, Elisabetta; Salamida, Sonia; Louin, Gaëlle; Magnani, Mauro

    2013-03-01

    Superparamagnetic iron oxide (SPIO) nanoparticles have been produced and used successfully as potent contrast agents for Magnetic Resonance Imaging (MRI). However, a significant challenge associated with the biological application of SPIO-tracer agents is their behavior in vivo since their efficacy is often compromised due to a rapid recognition and clearance by the reticuloendothelial system (RES) which limits the applicability of such compounds in MRI. The advances in nanotechnology and molecular cell biology had lead to improve stability and biocompatibility of these nanoparticles, but despite a number of efforts, the SPIO half-life in blood circulation is very short. In this contest, the potential of red blood cells (RBCs) loaded with SPIO nanoparticles as a tracer material for MRI has been investigated in order to realize a blood pool tracer with longer blood retention time. Previously, we have proposed the encapsulation into RBCs of superparamagnetic iron oxide nanoparticles carboxydextran coated, such as Resovist contrast agent. This approach led to a nanoparticle reduction in uptake by the RES, increasing the blood circulation half-life of nanoparticles. Recently, the loading procedure was applied to a new contrast agent, the P904 ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles coated by hydrophilic derivatives of glucose, recently developed by Guerbet Laboratories. The results evidenced that this nanomaterial can be efficiently loaded into human and murine RBCs at concentrations ranging from 1.5 to 12 mM Fe. In vivo experiments performed in mice have showed an increased survival in the mouse vascular system of P904 encapsulated into RBCs respect to free P904 sample intravenously injected at the equivalent amounts.

  14. Phantom studies with gold nanorods as contrast agents for photoacoustic imaging: novel and old approaches

    NASA Astrophysics Data System (ADS)

    Avigo, Cinzia; Di Lascio, Nicole; Armanetti, Paolo; Stea, Francesco; Cavigli, Lucia; Ratto, Fulvio; Pini, Roberto; Meucci, Sandro; Cecchini, Marco; Kusmic, Claudia; Faita, Francesco; Menichetti, Luca

    2015-03-01

    Photoacoustic imaging is emerging as a bioimaging technique. The development of contrast agents extend the potential towards novel application. The design of stable phantoms is needed to achieve a semi-quantitative evaluation of the performance of contrast agents. The aim of this study was to investigate the PA signal generated from gold nanorods (GNRs) loaded in custom made phantoms. VevoLAZR (VisualSonics Inc., Toronto) was used with custom made agar phantom, with 5 parallel polyethylene tubes (with 0.58mm internal and 0.99mm external diameter), and a PDMS phantom, with six parallel channels with sizes from 50 μm to 500 μm, loaded with two different types of GNRs: PEGGNRs (53nm length and 11nm axial diameter, plasmon resonance at 840nm, 87nM (15mM Au equivalent)); and gold nanorods (NPZ) coated in a dense layer of hydrophilic polymers by Nanopartz Inc., Loveland, CO (41nm length and 10nm axial diameter, plasmon resonance at 808nm, 83 nM (14mM Au equivalent)). The absorption spectra acquired with the PA system and the spectrophotometer were compared. The reproducibility and stability of the PA signal were evaluated at different dilutions. The dynamic variation of the PA signal was evaluated as function of the number of the GNRs. The SNR and the contrast were measured across the range of concentrations studied. The custom made agar phantom demonstrated suitable for the characterization of PA contrast agents such as PEG-GNRs and NPZ. The PDMS phantom is promising in the field of photoacoustics, therefore future works will conducted exploiting its precise and controlled geometry.

  15. Photoacoustic imaging and surface-enhanced Raman spectroscopy using dual modal contrast agents

    NASA Astrophysics Data System (ADS)

    Park, Sungjo; Lee, Seunghyun; Cha, Myeonggeun; Jeong, Cheolhwan; Kang, Homan; Park, So Yeon; Lee, Yoon-sik; Jeong, Daehong; Kim, Chulhong

    2016-03-01

    Recently, photoacoustic tomography (PAT) has emerged as a remarkable non-invasive imaging modality that provides a strong optical absorption contrast, high ultrasonic resolution, and great penetration depth. Thus, PAT has been widely used as an in vivo preclinical imaging tool. Surface-enhanced Raman spectroscopy (SERS) is another attractive sensing technology in biological research because it offers highly sensitive chemical analyses and multiplexed detection. By performing dual-modal imaging of SERS and PAT, high-resolution structural PAT imaging and high-sensitivity SERS sensing can be achieved. At the same time, it is equally important to develop a dual modal contrast agent for this purpose. To perform both PAT and SERS, we synthesized PEGylated silver bumpy nanoshells (AgBSs). The AgBSs generate strong PA signals owing to their strong optical absorption properties as well as sensitive SERS signals because of the surface plasmon resonance effect. Then, multiplexed Raman chemicals were synthesized to enhance the sensitivity of Raman. We have photoacoustically imaged the sentinel lymph nodes of small animals after intradermal injection of multiplexed agents. Furthermore, the chemical composition of each agent has been distinguished through SERS.

  16. Palladium nanosheets as highly stable and effective contrast agents for in vivo photoacoustic molecular imaging

    NASA Astrophysics Data System (ADS)

    Nie, Liming; Chen, Mei; Sun, Xiaolian; Rong, Pengfei; Zheng, Nanfeng; Chen, Xiaoyuan

    2014-01-01

    A stable and efficient contrast agent is highly desirable for photoacoustic (PA) imaging applications. Recently gold nanostructures have been widely reported and studied for PA imaging and photothermal therapy. However, the structures of the nonspherical gold nanoparticles are easily destroyed after laser irradiation and thus may fail to complete the intended tasks. In this study, we propose to apply palladium nanosheets (PNSs), with strong optical absorption in the near-infrared (NIR) region, as a new class of exogenous PA contrast agents. PA and ultrasound (US) images were acquired sequentially by a portable and fast photoacoustic tomography (PAT) system with a hand-held transducer. Significant and long-lasting imaging enhancement in SCC7 head and neck squamous cell carcinoma was successfully observed in mice by PAT over time after tail vein administration of PNSs. The morphology and functional perfusion of the tumors were delineated in PA images due to the nanoparticle accumulation. PAT of the main organs was also conducted ex vivo to trace the fate of PNSs, which was further validated by inductively coupled plasma atomic emission spectrometry (ICP-AES). No obvious toxic effect was observed by in vitro MTT assay and ex vivo histological examination 7 days after PNS administration. With the combination of a portable imaging instrument and signal specificity, PNSs might be applied as stable and effective agents for photoacoustic cancer detection, diagnosis and treatment guidance.

  17. Facile Synthesis of Gd-Functionalized Gold Nanoclusters as Potential MRI/CT Contrast Agents

    PubMed Central

    Le, Wenjun; Cui, Shaobin; Chen, Xin; Zhu, Huanhuan; Chen, Bingdi; Cui, Zheng

    2016-01-01

    Multi-modal imaging plays a key role in the earlier detection of disease. In this work, a facile bioinspired method was developed to synthesize Gd-functionalized gold nanoclusters (Gd-Au NCs). The Gd-Au NCs exhibit a uniform size, with an average size of 5.6 nm in dynamic light scattering (DLS), which is a bit bigger than gold clusters (3.74 nm, DLS), while the fluorescent properties of Gd-Au NCs are almost the same as that of Au NCs. Moreover, the Gd-Au NCs exhibit a high longitudinal relaxivity value (r1) of 22.111 s−1 per mM of Gd in phosphate-buffered saline (PBS), which is six times higher than that of commercial Magnevist (A complex of gadolinium with a chelating agent, diethylenetriamine penta-acetic acid, Gd-DTPA, r1 = 3.56 mM−1·s−1). Besides, as evaluated by nano single photon emission computed tomography (SPECT) and computed tomography (CT) the Gd-Au NCs have a potential application as CT contrast agents because of the Au element. Finally, the Gd-Au NCs show little cytotoxicity, even when the Au concentration is up to 250 μM. Thus, the Gd-Au NCs can act as multi-modal imaging contrast agents.

  18. The Effectiveness of Ferritin as a Contrast Agent for Cell Tracking MRI in Mouse Cancer Models

    PubMed Central

    Lee, Chan Wha; Choi, Sun Il; Lee, Sang Jin; Oh, Young Taek; Park, Gunwoo; Park, Na Yeon; Yoon, Kyoung-Ah; Kim, Sunshin; Suh, Jin-Suck

    2017-01-01

    Purpose We aimed to investigate the effectiveness of ferritin as a contrast agent and a potential reporter gene for tracking tumor cells or macrophages in mouse cancer models. Materials and Methods Adenoviral human ferritin heavy chain (Ad-hFTH) was administrated to orthotopic glioma models and subcutaneous colon cancer mouse models using U87MG and HCT116 cells, respectively. Brain MR images were acquired before and daily for up to 6 days after the intracranial injection of Ad-hFTH. In the HCT116 tumor model, MR examinations were performed before and at 6, 24, and 48 h after intratumoral injection of Ad-hFTH, as well as before and every two days after intravenous injection of ferritin-labeled macrophages. The contrast effect of ferritin in vitro was measured by MR imaging of cell pellets. MRI examinations using a 7T MR scanner comprised a T1-weighted (T1w) spin-echo sequence, T2-weighted (T2w) relaxation enhancement sequence, and T2*-weighted (T2*w) fast low angle shot sequence. Results Cell pellet imaging of Ad-hFTH in vitro showed a strong negatively enhanced contrast in T2w and T2*w images, presenting with darker signal intensity in high concentrations of Fe. T2w images of glioma and subcutaneous HCT116 tumor models showed a dark signal intensity around or within the Ad-hFTH tumor, which was distinct with time and apparent in T2*w images. After injection of ferritin-labeled macrophages, negative contrast enhancement was identified within the tumor. Conclusion Ferritin could be a good candidate as an endogenous MR contrast agent and a potential reporter gene that is capable of maintaining cell labeling stability and cellular safety. PMID:27873495

  19. On-chip preparation of nanoscale contrast agents towards high-resolution ultrasound imaging.

    PubMed

    Peyman, Sally A; McLaughlan, James R; Abou-Saleh, Radwa H; Marston, Gemma; Johnson, Benjamin R G; Freear, Steven; Coletta, P Louise; Markham, Alexander F; Evans, Stephen D

    2016-02-21

    Micron-sized lipid-stabilised bubbles of heavy gas have been utilised as contrast agents for diagnostic ultrasound (US) imaging for many years. Typically bubbles between 1 and 8 μm in diameter are produced to enhance imaging in US by scattering sound waves more efficiently than surrounding tissue. A potential area of interest for Contrast Enhanced Ultrasound (CEUS) are bubbles with diameters <1 μm or 'nanobubbles.' As bubble diameter decreases, ultrasonic resonant frequency increases, which could lead to an improvement in resolution for high-frequency imaging applications when using nanobubbles. In addition, current US contrast agents are limited by their size to the vasculature in vivo. However, molecular-targeted nanobubbles could penetrate into the extra-vascular space of cancerous tissue providing contrast in regions inaccessible to traditional microbubbles. This paper reports a new microfluidic method for the generation of sub-micron sized lipid stabilised particles containing perfluorocarbon (PFC). The nanoparticles are produced in a unique atomisation-like flow regime at high production rates, in excess of 10(6) particles per s and at high concentration, typically >10(11) particles per mL. The average particle diameter appears to be around 100-200 nm. These particles, suspected of being a mix of liquid and gaseous C4F10 due to Laplace pressure, then phase convert into nanometer sized bubbles on the application of US. In vitro ultrasound characterisation from these nanoparticle populations showed strong backscattering compared to aqueous filled liposomes of a similar size. The nanoparticles were stable upon injection and gave excellent contrast enhancement when used for in vivo imaging, compared to microbubbles with an equivalent shell composition.

  20. Saline as the Sole Contrast Agent for Successful MRI-guided Epidural Injections

    SciTech Connect

    Deli, Martin; Mateiescu, Serban Busch, Martin; Becker, Jan Garmer, Marietta Groenemeyer, Dietrich

    2013-06-15

    Purpose. To assess the performance of sterile saline solution as the sole contrast agent for percutaneous magnetic resonance imaging (MRI)-guided epidural injections at 1.5 T. Methods. A retrospective analysis of two different techniques of MRI-guided epidural injections was performed with either gadolinium-enhanced saline solution or sterile saline solution for documentation of the epidural location of the needle tip. T1-weighted spoiled gradient echo (FLASH) images or T2-weighted single-shot turbo spin echo (HASTE) images visualized the test injectants. Methods were compared by technical success rate, image quality, table time, and rate of complications. Results. 105 MRI-guided epidural injections (12 of 105 with gadolinium-enhanced saline solution and 93 of 105 with sterile saline solution) were performed successfully and without complications. Visualization of sterile saline solution and gadolinium-enhanced saline solution was sufficient, good, or excellent in all 105 interventions. For either test injectant, quantitative image analysis demonstrated comparable high contrast-to-noise ratios of test injectants to adjacent body substances with reliable statistical significance levels (p < 0.001). The mean table time was 22 {+-} 9 min in the gadolinium-enhanced saline solution group and 22 {+-} 8 min in the saline solution group (p = 0.75). Conclusion. Sterile saline is suitable as the sole contrast agent for successful and safe percutaneous MRI-guided epidural drug delivery at 1.5 T.

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

    PubMed Central

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

    2016-01-01

    Recently, we developed a new technology, ultrasound-switchable fluorescence (USF), for high-resolution imaging in centimeter-deep tissues via fluorescence contrast. The success of USF imaging highly relies on excellent contrast agents. ICG-encapsulated poly(N-isopropylacrylamide) nanoparticles (ICG-NPs) are one of the families of the most successful near-infrared (NIR) USF contrast agents. However, the first-generation ICG-NPs have a short shelf life (<1 month). This work significantly increases the shelf life of the new-generation ICG-NPs (>6 months). In addition, we have conjugated hydroxyl or carboxyl function groups on the ICG-NPs for future molecular targeting. Finally, we have demonstrated the effect of temperature-switching threshold (Tth) and the background temperature (TBG) on the quality of USF images. We estimated that the Tth of the ICG-NPs should be controlled at ~38–40 °C (slightly above the body temperature of 37 °C) for future in vivo USF imaging. Addressing these challenges further reduces the application barriers of USF imaging. PMID:27775014

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

    PubMed Central

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

    2013-01-01

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

  3. Tracking contrast agents using real-time 2D photoacoustic imaging system for cardiac applications

    NASA Astrophysics Data System (ADS)

    Olafsson, Ragnar; Montilla, Leonardo; Ingram, Pier; Witte, Russell S.

    2009-02-01

    Photoacoustic (PA) imaging is a rapidly developing imaging modality that can detect optical contrast agents with high sensitivity. While detectors in PA imaging have traditionally been single element ultrasound transducers, use of array systems is desirable because they potentially provide high frame rates to capture dynamic events, such as injection and distribution of contrast in clinical applications. We present preliminary data consisting of 40 second sequences of coregistered pulse-echo (PE) and PA images acquired simultaneously in real time using a clinical ultrasonic machine. Using a 7 MHz linear array, the scanner allowed simultaneous acquisition of inphase-quadrature (IQ) data on 64 elements at a rate limited by the illumination source (Q-switched laser at 20 Hz) with spatial resolution determined to be 0.6 mm (axial) and 0.4 mm (lateral). PA images had a signal-to-noise ratio of approximately 35 dB without averaging. The sequences captured the injection and distribution of an infrared-absorbing contrast agent into a cadaver rat heart. From these data, a perfusion time constant of 0.23 s-1 was estimated. After further refinement, the system will be tested in live animals. Ultimately, an integrated system in the clinic could facilitate inexpensive molecular screening for coronary artery disease.

  4. Low-Density Lipoprotein Nanoparticles as Magnetic Resonance Imaging Contrast Agents1

    PubMed Central

    Corbin, Ian R; Li, Hui; Chen, Juan; Lund-Katz, Sissel; Zhou, Rong; Glickson, Jerry D; Zheng, Gang

    2006-01-01

    Abstract Low-density lipoproteins (LDLs) are a naturally occurring endogenous nanoplatform in mammalian systems. These nanoparticles (22 nm) specifically transport cholesterol to cells expressing the LDL receptor (LDLR). Several tumors overexpress LDLRs presumably to provide cholesterol to sustain a high rate of membrane synthesis. Amphiphilic gadolinium (Gd)-diethylenetria-minepentaacetic acid chelates have been incorporated into the LDL to produce a novel LDLR-targeted magnetic resonance imaging (MRI) contrast agent. The number of Gd chelates per LDL particle ranged between 150 and 496 Gd(III). In vitro studies demonstrated that Gd-labeled LDL retained a similar diameter and surface charge as the native LDL particle. In addition, Gd-labeled LDL retained selective cellular binding and uptake through LDLR-mediated endocytosis. Finally, Gd-labeled LDLs exhibited significant contrast enhancement 24 hours after administration in nude mice with human hepatoblastoma G2 xenografts. Thus, Gd-labeled LDL demonstrates potential use as a targeted MRI contrast agent for in vivo tumor detection. PMID:16820095

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

    PubMed

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

    2005-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

    Recently, we developed a new technology, ultrasound-switchable fluorescence (USF), for high-resolution imaging in centimeter-deep tissues via fluorescence contrast. The success of USF imaging highly relies on excellent contrast agents. ICG-encapsulated poly(N-isopropylacrylamide) nanoparticles (ICG-NPs) are one of the families of the most successful near-infrared (NIR) USF contrast agents. However, the first-generation ICG-NPs have a short shelf life (<1 month). This work significantly increases the shelf life of the new-generation ICG-NPs (>6 months). In addition, we have conjugated hydroxyl or carboxyl function groups on the ICG-NPs for future molecular targeting. Finally, we have demonstrated the effect of temperature-switching threshold (Tth) and the background temperature (TBG) on the quality of USF images. We estimated that the Tth of the ICG-NPs should be controlled at ~38–40 °C (slightly above the body temperature of 37 °C) for future in vivo USF imaging. Addressing these challenges further reduces the application barriers of USF imaging.

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

    NASA Astrophysics Data System (ADS)

    Makuta, T.; Tamakawa, Y.

    2012-04-01

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

  8. Mesoporous silica nanoparticles as a breast cancer targeting contrast agent for ultrasound imaging

    NASA Astrophysics Data System (ADS)

    Milgroom, Andrew Carson

    Current clinical use of ultrasound for breast cancer diagnostics is strictly limited to a role as a supplementary detection method to other modalities, such as mammography or MRI. A major reason for ultrasound’s role as a secondary method is its inability to discern between cancerous and non-cancerous bodies of similar density, like dense calcifications or benign fibroadenomas. Its detection capabilities are further diminished by the variable density of the surrounding breast tissue with the progression of age. Preliminary studies suggest that mesoporous silica nanoparticles (MSNs) are a good candidate as an in situ contrast agent for ultrasound. By tagging the silica particle surface with the cancer-targeting antibody trastuzumab (Herceptin), suspect regions of interest can be better identified in real time with standard ultrasound equipment. Once the silica-antibody conjugate is injected into the bloodstream and enters the cancerous growth’s vasculature, the antibody arm will bind to HER2, a cell surface receptor known to be dysfunctional or overexpressed in certain types of breast cancer. As more particles aggregate at the cell surface, backscatter of the ultrasonic waves increases as a result of the higher porous silica concentration. This translates to an increased contrast around the lesion boundary. Tumor detection through ultrasound contrast enhancement provides a tremendous advantage over current cancer diagnostics because is it significantly cheaper and can be monitored in real time. Characterization of MCM-41 type MSNs suggests that these particles have sufficient stability and particle size distribution to penetrate through fenestrated tumor vasculature and accumulate in HER2+ breast cancer cells through the enhanced permeation and retention (EPR) effect. A study of acoustic properties showed that particle concentration is linearly correlated to image contrast in clinical frequency-range ultrasound, although less pronounced than typical microbubble

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

    PubMed

    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

  10. Modeling of the acoustic response from contrast agent microbubbles near a rigid wall

    PubMed Central

    Doinikov, Alexander A.; Zhao, Shukui; Dayton, Paul A.

    2009-01-01

    In ultrasonic targeted imaging, specially designed encapsulated microbubbles are used, which are capable of selectively adhering to the target site in the body. A challenging problem is to distinguish the echoes from such adherent agents from echoes produced by freely circulating agents. In the present paper, an equation of radial oscillation for an encapsulated bubble near a plane rigid wall is derived. The equation is then used to simulate the echo from a layer of contrast agents localized on a wall. The echo spectrum of adherent microbubbles is compared to that of free, randomly distributed microbubbles inside a vessel, in order to examine differences between the acoustic responses of free and adherent agents. It is shown that the fundamental spectral component of adherent bubbles is perceptibly stronger than that of free bubbles. This increase is accounted for by a more coherent summation of echoes from adherent agents and the acoustic interaction between the agents and the wall. For cases tested, the increase of the fundamental component caused by the above two effects is on the order of 8-9 dB. Bubble aggregates, which are observed experimentally to form near a wall due to secondary Bjerknes forces, increase the intensity of the fundamental component only if they are formed by bubbles whose radii are well below the resonant radius. If the formation of aggregates contributes to the growth of the fundamental component, the increase can exceed 17 dB. Statistical analysis for the comparison between adhering and free bubbles, performed over random space bubble distributions, gives p-values much smaller than 0.05. PMID:18789469

  11. MR imaging of pulmonary parenchyma and emboli by paramagnetic and superparamagnetic contrast agents.

    PubMed

    Thakur, M L; Vinitski, S; Mitchell, D G; Consigny, P M; Lin, S; DeFulvio, J; Rifkin, M

    1990-01-01

    Using experimentally induced pulmonary emboli in an animal model, three intravenously administered contrast agents, Gd-DTPA-albumin microspheres (8-15 microns, 0.2 M particles/mg protein, 39-106 micrograms Gd/mg, 50 mg/ml), Gd-DTPA-liposomes (15-30 microns, 130 micrograms/mg lipid, 6 mg Gd/ml) and superparamagnetic ferrosome, (60 nm, 100 mM iron and 20 mg lipid/ml) were examined for MR imaging. Gd-DTPA entrapped in lung capillaries did not enhance the signal intensity of lung parenchyma, but liposomes (5 ml) served as better Gd-DTPA carriers and increased the parenchymal signal intensity by up to a factor of 2.3. However, neither agent improved delineation of pulmonary emboli. Ferrosome decreased the intensity of lung parenchyma, improving detectability of pulmonary emboli by several factors.

  12. T₁ and T₂ dual-mode MRI contrast agent for enhancing accuracy by engineered nanomaterials.

    PubMed

    Shin, Tae-Hyun; Choi, Jin-sil; Yun, Seokhwan; Kim, Il-Sun; Song, Ho-Taek; Kim, Youngmee; Park, Kook In; Cheon, Jinwoo

    2014-04-22

    One of the holy grails in biomedical imaging technology is to achieve accurate imaging of biological targets. The development of sophisticated instrumentation and the use of contrast agents have improved the accuracy of biomedical imaging. However, the issue of false imaging remains a problem. Here, we developed a dual-mode artifact filtering nanoparticle imaging agent (AFIA) that comprises a combination of paramagnetic and superparamagnetic nanomaterials. This AFIA has the ability to perform "AND logic gate" algorithm to eliminate false errors (artifacts) from the raw images to enhance accuracy of the MRI. We confirm the artifact filtering capability of AFIA in MRI phantoms and further demonstrate that artifact-free imaging of stem cell migration is possible in vivo.

  13. Speciation and isotope dilution analysis of gadolinium-based contrast agents in wastewater.

    PubMed

    Telgmann, Lena; Wehe, Christoph A; Birka, Marvin; Künnemeyer, Jens; Nowak, Sascha; Sperling, Michael; Karst, Uwe

    2012-11-06

    The fate of Gadolinium (Gd)-based contrast agents for magnetic resonance imaging (MRI) during sewage treatment was investigated. The total concentration of Gd in influent and effluent 2 and 24 h composite samples was determined by means of isotope dilution analysis. The balancing of Gd input and output of a sewage plant over seven days indicated that approximately 10% of the Gd is removed during treatment. Batch experiments simulating the aeration tank of a sewage treatment plant confirmed the Gd complex removal during activated sludge treatment. For speciation analysis of the Gd complexes in wastewater samples, high performance liquid chromatography (HPLC) was hyphenated to inductively coupled plasma sector field mass spectrometry (ICP-SFMS). Separation of the five predominantly used contrast agents was carried out on a new hydrophilic interaction liquid chromatography stationary phase in less than 15 min. A limit of detection (LOD) of 0.13 μg/L and a limit of quantification of 0.43 μg/L could be achieved for the Gd chelates without having to apply enrichment techniques. Speciation analysis of the 24 h composite samples revealed that 80% of the Gd complexes are present as Gd-BT-DO3A in the sampled treatment plant. The day-of-week dependent variation of the complex load followed the variation of the total Gd load, indicating a similar behavior. The analysis of sewage sludge did not prove the presence of anthropogenic Gd. However, in the effluent of the chamber filter press, which was used for sludge dewatering, two of the contrast agents and three other unknown Gd species were observed. This indicates that species transformation took place during anaerobic sludge treatment.

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

    PubMed

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

    2016-03-15

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

  15. Safety assessment of nanoparamagnetic contrast agents with different coatings for molecular MRI

    NASA Astrophysics Data System (ADS)

    Azizian, Gholamreza; Riyahi-Alam, Nader; Haghgoo, Soheila; Saffari, Mojtaba; Zohdiaghdam, Reza; Gorji, Ensieh

    2013-04-01

    Despite the wide application of gadolinium as a contrast agent for magnetic resonance imaging (MRI), there is a serious lack of information on its toxicity. Gadolinium and gadolinium oxide (Gd-oxide) are used as contrast agents for magnetic resonance imaging (MRI). There are methods for reducing toxicity of these materials, such as core nanoparticles coating or conjugating. Therefore, for toxicity evaluation, we compared the viability of commercial contrast agents in MRI (Gd-DTPA) and three nanoparticles with the same core Gd2O3 and small particulate gadolinium oxide or SPGO (< 40 nm) but different coatings of diethyleneglycol (DEG) as Gd2O3-DEG and methoxy polyethylene glycol-silane (mPEG-silane: 550 and 2000 Dalton) as SPGO-mPEG-silane550 and SPGO-mPEG-silane2000, respectively, in the SK-MEL3 cell line, by light microscopy, MTT assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, and the LDH assay detecting lactate dehydrogenase activity. The viability values were not statistically different between the three nanoparticles and Gd-DTPA. The MTT and LDH assay results showed that Gd2O3-DEG nanoparticles were more toxic than Gd-DTPA and other nanoparticles. Also, SPGO-mPEG-silane2000 was more biocompatible than other nanoparticles. The obtained results did not show any significant increase in cytotoxicity of the nanoparticles and Gd-DTPA, neither dose-dependent nor time-dependent. Therefore, DEG and PEG, due to their considerable properties and irregular sizes (different molecular weights), were selected as the useful surface covering materials of nanomagnetic particles that could reveal noticeable relaxivity and biocompatibility characteristics.

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

    NASA Astrophysics Data System (ADS)

    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

  17. Gold nanoclusters as contrast agents for fluorescent and X-ray dual-modality imaging.

    PubMed

    Zhang, Aili; Tu, Yu; Qin, Songbing; Li, Yan; Zhou, Juying; Chen, Na; Lu, Qiang; Zhang, Bingbo

    2012-04-15

    Multimodal imaging technique is an alternative approach to improve sensitivity of early cancer diagnosis. In this study, highly fluorescent and strong X-ray absorption coefficient gold nanoclusters (Au NCs) are synthesized as dual-modality imaging contrast agents (CAs) for fluorescent and X-ray dual-modality imaging. The experimental results show that the as-prepared Au NCs are well constructed with ultrasmall sizes, reliable fluorescent emission, high computed tomography (CT) value and fine biocompatibility. In vivo imaging results indicate that the obtained Au NCs are capable of fluorescent and X-ray enhanced imaging.

  18. ParaCEST MRI contrast agents capable of derivatization via"click" chemistry.

    PubMed

    Milne, Mark; Chicas, Kirby; Li, Alex; Bartha, Robert; Hudson, Robert H E

    2012-01-14

    A comprehensive series of lanthanide chelates has been prepared with a tetrapropargyl DOTAM type ligand. The complexes have been characterized by a combination of (1)H NMR, single-crystal X-ray crystallography, CEST and relaxation studies and have also been evaluated for potential use as paramagnetic chemical exchange saturation transfer (ParaCEST) contrast agents in magnetic resonance imaging (MRI). We demonstrate the functionalization of several chelates by means of alkyne-azide "click" chemistry in which a glucosyl azide is used to produce a tetra-substituted carbohydrate-decorated lanthanide complex. The carbohydrate periphery of the chelates has a potent influence on the CEST properties as described herein.

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

    PubMed Central

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

    2016-01-01

    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. PMID:28335240

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2017-01-01

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

  2. Modeling of the dynamics of microbubble contrast agents in ultrasonic medicine: Survey

    NASA Astrophysics Data System (ADS)

    Doinikov, A. A.; Bouakaz, A.

    2013-11-01

    The survey is devoted to a new field of bubble dynamics that studies the behavior of ultrasound contrast agents. This name denotes man-made encapsulated microbubbles applied in diagnostic and therapeutic ultrasonic medicine to enhance the quality of ultrasonic images and to deliver drugs to target sites in the human body. The survey analyzes theoretical models that are currently applied for the description of the bubble shell, the interaction of bubbles with blood vessel walls, and the acoustical action of bubbles on the cell membrane.

  3. Hydrogels incorporating GdDOTA: towards highly efficient dual T1/T2 MRI contrast agents.

    PubMed

    Courant, Thomas; Roullin, Valérie Gaëlle; Cadiou, Cyril; Callewaert, Maïté; Andry, Marie Christine; Portefaix, Christophe; Hoeffel, Christine; de Goltstein, Marie Christine; Port, Marc; Laurent, Sophie; Elst, Luce Vander; Muller, Robert; Molinari, Michaël; Chuburu, Françoise

    2012-09-03

    Do not tumble dry: Gadolinium-DOTA encapsulated into polysaccharide nanoparticles (GdDOTA NPs) exhibited high relaxivity (r(1) =101.7 s(-1) mM(-1) per Gd(3+) ion at 37 °C and 20 MHz). This high relaxation rate is due to efficient Gd loading, reduced tumbling of the Gd complex, and the hydrogel nature of the nanoparticles. The efficacy of the nanoparticles as a T(1)/T(2) dual-mode contrast agent was studied in C6 cells.

  4. Contrast Agent Ultrasonography before and after HIFU Treatment of Parathyroid Glands

    NASA Astrophysics Data System (ADS)

    Kovatcheva, Roussanka; Arnaud, Françoise; Lacoste, François

    2010-03-01

    OBJECTIVES: To observe changes in the parathyroid tissue treated by extracorporeal HIFU. MATERIAL AND METHODS: 5 patients were treated for primary hyperparathyroidism by thermally ablating enlarged parathyroid glands using an external HIFU applicator. The treated glands were visualized with B-Mode and contrast enhanced ultrasonography (CEUS) before, 1 week and 4 weeks post HIFU. Serum iPTH, calcium, and phosphorus levels were monitored before and after the treatment. RESULTS: The initial results showed a correlation between contrast agent uptake of treated parathyroid tissue, the reduction of volume of the gland and the decrease of iPTH levels. CONCLUSIONS These results show it is possible to use CEUS to monitor the thermal ablation of parathyroid glands.

  5. Porous silicon nanoparticles as biocompatible contrast agents for magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Gongalsky, M. B.; Kargina, Yu. V.; Osminkina, L. A.; Perepukhov, A. M.; Gulyaev, M. V.; Vasiliev, A. N.; Pirogov, Yu. A.; Maximychev, A. V.; Timoshenko, V. Yu.

    2015-12-01

    We propose porous silicon nanoparticles (PSi NPs) with natural oxide coating as biocompatible and bioresorbable contrast agents for magnetic resonant imaging (MRI). A strong shortening of the transversal proton relaxation time (T2) was observed for aqueous suspensions of PSi NPs, whereas the longitudinal relaxation time (T1) changed moderately. The longitudinal and transversal relaxivities are estimated to be 0.03 and 0.4 l/(g.s), respectively, which are promising for biomedical studies. The proton relaxation is suggested to undergo via the magnetic dipole-dipole interaction with Si dangling bonds on surfaces of PSi NPs. MRI experiments with phantoms have revealed the remarkable contrasting properties of PSi NPs for medical diagnostics.

  6. Porous silicon nanoparticles as biocompatible contrast agents for magnetic resonance imaging

    SciTech Connect

    Gongalsky, M. B. Kargina, Yu. V.; Osminkina, L. A.; Perepukhov, A. M.; Maximychev, A. V.; Gulyaev, M. V.; Vasiliev, A. N.; Pirogov, Yu. A.; Timoshenko, V. Yu.

    2015-12-07

    We propose porous silicon nanoparticles (PSi NPs) with natural oxide coating as biocompatible and bioresorbable contrast agents for magnetic resonant imaging (MRI). A strong shortening of the transversal proton relaxation time (T{sub 2}) was observed for aqueous suspensions of PSi NPs, whereas the longitudinal relaxation time (T{sub 1}) changed moderately. The longitudinal and transversal relaxivities are estimated to be 0.03 and 0.4 l/(g·s), respectively, which are promising for biomedical studies. The proton relaxation is suggested to undergo via the magnetic dipole-dipole interaction with Si dangling bonds on surfaces of PSi NPs. MRI experiments with phantoms have revealed the remarkable contrasting properties of PSi NPs for medical diagnostics.

  7. In vitro study of the antimicrobial effects of radiological contrast agents used in arthrography.

    PubMed

    Bruins, M J; Zwiers, J H; Verheyen, C C P M; Wolfhagen, M J H M

    2011-01-01

    Aspiration arthrography using an iodinated contrast medium is a useful tool for the investigation of septic or aseptic loosening of arthroplasties and of septic arthritis. Previously, the contrast media have been thought to cause false negative results in cultures when present in aspirated samples of synovial fluid, probably because free iodine is bactericidal, but reports have been inconclusive. We examined the influence of the older, high osmolar contrast agents and the low osmolar media used currently on the growth of ten different micro-organisms capable of causing deep infection around a prosthesis. Five media were tested, using a disc diffusion technique and a time-killing curve method in which high and low inocula of micro-organisms were incubated in undiluted media. The only bactericidal effects were found with low inocula of Escherichia coli and Pseudomonas aeruginosa in ioxithalamate, one of the older ionic media. The low and iso-osmolar iodinated contrast media used currently do not impede culture. Future study must assess other causes of false negative cultures of synovial fluid and new developments in enhancing microbial recovery from aspirated samples.

  8. An in vitro system for the study of ultrasound contrast agents using a commercial imaging system.

    PubMed

    Sboros, V; Moran, C M; Anderson, T; Gatzoulis, L; Criton, A; Averkiou, M; Pye, S D; McDicken, W N

    2001-12-01

    An in vitro system for the investigation of the behaviour of contrast microbubbles in an ultrasound field, that provides a full diagnostic range of settings, is yet to be presented in the literature. The evaluation of a good compromise of such a system is presented in this paper. It is based on (a) an HD13000 ATL scanner (Bothell, WA, USA) externally controlled by a PC and (b) on the use of well-defined reference materials. The suspensions of the reference ultrasonic scattering material are placed in an anechoic tank. The pulse length ranges from 2 to 10 cycles, the acoustic pressure from 0.08 to 1.8 MPa, the transmit frequency from 1 to 4.3 MHz, and the receive frequency from 1 to 8 MHz. The collection of 256 samples of RF data, at an offset distance from the transducer face, was performed at 20 MHz digitization rate, which corresponds to approximately 1 cm depth in water. Two particle suspensions are also presented for use as reference scatterers for contrast studies: (a) a suspension of Orgasol (ELF Atochem, Paris, France) particles (approximately 5 microm mean diameter) and (b) a suspension of Eccosphere (New Metals & Chemicals Ltd, Essex, UK) particles (approximately 50 microm mean diameter). A preliminary experiment with the contrast agent Definity (DuPont Pharmaceutical Co, Waltham, MA) showed that the above two materials are suitable for use as a reference for contrast backscatter.

  9. Development and evaluation of a novel VEGFR2-targeted nanoscale ultrasound contrast agents

    NASA Astrophysics Data System (ADS)

    Yu, Houqiang; Li, Chunfang; He, Xiaoling; Zhou, Qibing; Ding, Mingyue

    2016-04-01

    Recent literatures have reported that the targeted nanoscale ultrasound contrast agents are becoming more and more important in medical application, like ultrasound imaging, detection of perfusion, drug delivery and molecular imaging and so on. In this study, we fabricated an uniform nanoscale bubbles (257 nm with the polydispersity index of 0.458) by incorporation of antibody targeted to vascular endothelial growth factor receptor 2 (VEGFR2) into the nanobubbles membrane by using avidin-biotin interaction. Some fundamental characterizations such as nanobubble suspension, surface morphology, particle size distribution and zeta potential were investigated. The concentration and time-intensity curves (TICs) were obtained with a self-made ultrasound experimental setup in vitro evaluation. In addition, in order to evaluate the contrast enhancement ability and the potential tumor-targeted ability in vivo, normal Wistar rats and nude female BALB/c mice were intravascular administration of the nanobubbles via tail vein injection, respectively. Significant contrast enhancement of ultrasound imaging within liver and tumor were visualized. These experiments demonstrated that the targeted nanobubbles is efficient in ultrasound molecular imaging by enhancement of the contrast effect and have potential capacity for targeted tumor diagnosis and therapy in the future.

  10. Transdermal Drug Delivery Aided by an Ultrasound Contrast Agent: An In Vitro Experimental Study

    PubMed Central

    Park, Donghee; Yoon, Jinhee; Park, Jingam; Jung, Byungjo; Park, Hyunjin; Seo, Jongbum

    2010-01-01

    Sonophoresis temporarily increases skin permeability such that medicine can be delivered transdermally. Cavitation is believed to be the predominant mechanism in sonophoresis. In this study, an ultrasound contrast agent (UCA) strategy was adopted instead of low frequency ultrasound to assure that cavitation occurred, and the efficacy of sonophoresis with UCA was quantitatively analyzed by optical measurements. The target drug used in this study was 0.1 % Definity® in 70% glycerol, which was delivered into porcine skin samples. Glycerol was used because it is an optical clearing agent, and the efficiency of glycerol delivery could be analyzed with optical measurements. The applied acoustic pressure was approximately 600 kPa at 1 MHz ultrasound with a 10% duty cycle for 60 minutes. Experimental results indicated that the measured relative contrast (RC) after sonophoresis with UCA was approximately 80% higher than RC after sonophoresis without UCA. In addition, the variance of RC was also reduced by more than 50% with the addition of a UCA. The use of a UCA appeared to increase cavitation, demonstrating that the use of a UCA can be effective in transdermal drug delivery (TDD). PMID:20448793

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

    PubMed

    Paefgen, Vera; Doleschel, Dennis; Kiessling, Fabian

    2015-01-01

    Ultrasound (US) 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 (CAs). 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 CAs 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 US pulses to locally release the entrapped agent. Recent studies show that US CAs 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 US CAs and introduces the current clinical applications of contrast-enhanced US. Additionally, an overview of the recent developments in US probe design for functional and molecular diagnosis as well as for drug delivery is given.

  12. Porphyrin Nanodroplets: Sub-micrometer Ultrasound and Photoacoustic Contrast Imaging Agents.

    PubMed

    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.

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

    PubMed Central

    Paefgen, Vera; Doleschel, Dennis; Kiessling, Fabian

    2015-01-01

    Ultrasound (US) 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 (CAs). 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 CAs 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 US pulses to locally release the entrapped agent. Recent studies show that US CAs 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 US CAs and introduces the current clinical applications of contrast-enhanced US. Additionally, an overview of the recent developments in US probe design for functional and molecular diagnosis as well as for drug delivery is given. PMID:26441654

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

    PubMed

    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.

  15. Material characterization of poly-lactic acid shelled ultrasound contrast agent and their dynamics

    NASA Astrophysics Data System (ADS)

    Paul, Shirshendu; Russakow, Daniel; Rodgers, Tyler; Sarkar, Kausik; Cochran, Michael; Wheatley, Margaret

    2011-11-01

    Micron-size gas bubbles encapsulated with lipids and proteins are used as contrast enhancing agents for ultrasound imaging. Biodegradable polymer poly-lactic acid (PLA) has recently been suggested as a possible means of encapsulation. Here, we report in vitro measurement of attenuation and scattering of ultrasound through an emulsion of PLA agent as well as theoretical modeling of the encapsulated bubble dynamics. The attenuation measured with three different transducers of central frequencies 2.25, 3.5 and 5 MHz, shows a peak around 2-3 MHz. These bubbles also show themselves to possess excellent scattering characteristics including strong non-linear response that can be used for harmonic and sub-harmonic contrast imaging. Our recently developed interfacial rheological models are applied to describe the dynamics of these bubbles; rheological model properties are estimated using measured attenuation data. The model is then applied to predict nonlinear scattered response, and the prediction is compared against experimental observation. Partially supported by NSF and NIH.

  16. Transdermal drug delivery aided by an ultrasound contrast agent: an in vitro experimental study.

    PubMed

    Park, Donghee; Yoon, Jinhee; Park, Jingam; Jung, Byungjo; Park, Hyunjin; Seo, Jongbum

    2010-02-11

    Sonophoresis temporarily increases skin permeability such that medicine can be delivered transdermally. Cavitation is believed to be the predominant mechanism in sonophoresis. In this study, an ultrasound contrast agent (UCA) strategy was adopted instead of low frequency ultrasound to assure that cavitation occurred, and the efficacy of sonophoresis with UCA was quantitatively analyzed by optical measurements. The target drug used in this study was 0.1 % Definity(R) in 70% glycerol, which was delivered into porcine skin samples. Glycerol was used because it is an optical clearing agent, and the efficiency of glycerol delivery could be analyzed with optical measurements. The applied acoustic pressure was approximately 600 kPa at 1 MHz ultrasound with a 10% duty cycle for 60 minutes. Experimental results indicated that the measured relative contrast (RC) after sonophoresis with UCA was approximately 80% higher than RC after sonophoresis without UCA. In addition, the variance of RC was also reduced by more than 50% with the addition of a UCA. The use of a UCA appeared to increase cavitation, demonstrating that the use of a UCA can be effective in transdermal drug delivery (TDD).

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

    We developed a new and improved Laser Optoacoustic Imaging System, LOIS-3D for preclinical research applications in small animal models. The advancements include (i) a new stabilized imaging module with a more homogeneous illumination of the mouse yielding a better spatial resolution (<0.2 mm) and (ii) a new low noise amplifier incorporated into the ultrasonic probe and providing the noise equivalent pressure around 2 Pa resulting in increased signal-to-noise ratio and the optical absorption sensitivity of about 0.15 cm-1. We also improved scan time and the image reconstruction times. This prototype has been commercialized for a number of biomedical research applications, such as imaging vascularization and measuring hemoglobin / oxyhemoglobin distribution in the organs as well as imaging exogenous or endogenous optoacoustic contrast agents. As examples, we present in vivo experiments using phantoms and mice with and without tumor injected with contrast agents with indocyanine green (ICG). LOIS-3D was capable of detecting ~1-2 pmole of the ICG, in tissues with relatively low blood content. With its high sensitivity and excellent spatial resolution LOIS-3D is an advanced alternative to fluorescence and bioluminescence based modalities for molecular imaging in live mice.

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

    NASA Astrophysics Data System (ADS)

    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.

  19. Quantitative photoacoustic measurement of tissue optical absorption spectrum aided by an optical contrast agent.

    PubMed

    Rajian, Justin Rajesh; Carson, Paul L; Wang, Xueding

    2009-03-16

    In photoacoustic imaging, the intensity of photoacoustic signal induced by optical absorption in biological tissue is proportional to light energy deposition, which is the product of the absorption coefficient and the local light fluence. Because tissue optical properties are highly dependent on the wavelength, the spectrum of the local light fluence at a target tissue beneath the sample surface is different than the spectrum of the incident light fluence. Therefore, quantifying the tissue optical absorption spectrum by using a photoacoustic technique is not feasible without the knowledge of the local light fluence. In this work, a highly accurate photoacoustic measurement of the subsurface tissue optical absorption spectrum has been achieved for the first time by introducing an extrinsic optical contrast agent with known optical properties. From the photoacoustic measurements with and without the contrast agent, a quantified measurement of the chromophore absorption spectrum can be realized in a strongly scattering medium. Experiments on micro-flow vessels containing fresh canine blood buried in phantoms and chicken breast tissues were carried out in a wavelength range from 680 nm to 950 nm. Spectroscopic photoacoustic measurements of both oxygenated and deoxygenated blood specimens presented an improved match with the references when employing this technique.

  20. Structural and Magnetic Characterization of Superparamagnetic Iron Platinum Nanoparticle Contrast Agents for Magnetic Resonance Imaging

    PubMed Central

    Taylor, Robert M.; Huber, Dale L.; Monson, Todd C.; Esch, Victor; Sillerud, Laurel O.

    2012-01-01

    We report the synthesis, from simple salts, and the physical characterization of superparamagnetic iron platinum nanoparticles (SIPPs) suitable for use as contrast agents in magnetic resonance imaging. The properties of these particles were determined by means of transmission electron microscopy (TEM), thermogravimetric analysis (TGA), inductively coupled plasma-optical emission spectroscopy (ICP-OES), superconducting quantum interference device (SQUID) magnetometry, and nuclear magnetic resonance (NMR) relaxivity at 4.7 Tesla. TEM showed that the diameters of the particles ranged from 9.3 nm to 10 nm, depending on the mole ratio of iron to platinum precursors, and on the concentration of Octadecylamine (ODA) used in their preparation. The iron to platinum stoichiometry determined by ICP-OES varied from 1.4:1 to 3.7:1 and was similarly dependant on the initial mole ratios of iron and platinum salts, as well as on the concentration of ODA in the reaction. SQUID magnetometry showed that the SIPPs were superparamagnetic and had magnetic moments that increased with increasing iron content from 62 to 72 A•m2/kg Fe. The measured relaxivities of the SIPPs at 4.7 Tesla were higher than commercially available superparamagnetic iron oxide nanoparticles (SPIONs), suggesting that these particles may be superior contrast agents in T2-weighted magnetic resonance imaging (MRI). PMID:22872817

  1. Structural and magnetic characterization of superparamagnetic iron platinum nanoparticle contrast agents for magnetic resonance imaging

    PubMed Central

    Taylor, Robert M.; Huber, Dale L.; Monson, Todd C.; Esch, Victor; Sillerud, Laurel O.

    2012-01-01

    The authors report the synthesis, from simple salts, and the physical characterization of superparamagnetic iron platinum nanoparticles (SIPPs) suitable for use as contrast agents in magnetic resonance imaging. The properties of these particles were determined by means of transmission electron microscopy (TEM), thermogravimetric analysis, inductively coupled plasma-optical emission spectroscopy (ICP-OES), superconducting quantum interference device (SQUID) magnetometry, and nuclear magnetic resonance relaxivity at 4.7 T. TEM showed that the diameters of the particles ranged from 9.3 to 10 nm, depending on the mole ratio of iron to platinum precursors, and on the concentration of octadecylamine (ODA) used in their preparation. The iron to platinum stoichiometry determined by ICP-OES varied from 1.4:1 to 3.7:1 and was similarly dependent on the initial mole ratios of iron and platinum salts, as well as on the concentration of ODA in the reaction. SQUID magnetometry showed that the SIPPs were superparamagnetic and had magnetic moments that increased with increasing iron content from 62 to 72 A·m2/kg Fe. The measured relaxivities of the SIPPs at 4.7 T were higher than commercially available superparamagnetic iron oxide nanoparticles, suggesting that these particles may be superior contrast agents in T2-weighted magnetic resonance imaging. PMID:25317380

  2. Antiferromagnetic iron nanocolloids: a new generation in vivo T1 MRI contrast agent.

    PubMed

    Peng, Yung-Kang; Liu, Chien-Liang; Chen, Hsieh-Chih; Chou, Shang-Wei; Tseng, Wei-Hsuan; Tseng, Yu-Jui; Kang, Chia-Cheng; Hsiao, Jong-Kai; Chou, Pi-Tai

    2013-12-11

    A novel T1 agent, antiferromagnetic α-iron oxide-hydroxide (α-FeOOH) nanocolloids with a diameter of 2-3 nm, has been successfully prepared. These nanocolloids, together with a post synthetic strategy performed in mesoporous silica, are a great improvement over the low T1-weighted contrast common in traditional magnetic silica nanocomposites. The intrinsic antiferromagnetic goethite (α-FeOOH) shows very low magnetization (M(z)) of 0.05 emu g(-1) at H = 2 T at 300 K (0.0006 emu g(-1) for FeOOH/WMSN-PEG), which is 2 orders of magnitude smaller than any current ultrasmall iron oxide NPs (>5 emu g(-1)) reported to date, hence ensuring the low r2 (∝ Mz) (7.64 mM(-1) s(-1)) and r2/r1 ratio (2.03) at 4.7 T. These biodegradable α-FeOOH nanocolloids also demonstrate excellent in vitro cellular imaging and in vivo MR vascular and urinary trace imaging capability with outstanding biocompatibility, which is exceptionally well secreted by the kidney and not the liver as with most nanoparticles, opening up a new avenue for designing powerful antiferromagnetic iron T1 contrast agents.

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

    PubMed Central

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

    2017-01-01

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

  4. Removal of magnetic resonance imaging contrast agents through advanced water treatment plants.

    PubMed

    Lawrence, Michael G; Keller, Jurg; Poussade, Yvan

    2010-01-01

    Stable gadolinium (Gd) complexes have been used as paramagnetic contrast agents for magnetic resonance imaging (MRI) for over 20 years, and have recently been identified as environmental contaminants. As the rare earth elements (REE), which include Gd, are able to be measured accurately at very low concentrations (e.g. Tb is measured at 7 fmol/kg in this study) using inductively coupled plasma mass spectrometry (ICP-MS), it is possible to determine the fate of this class of compounds during the production of purified recycled water from effluent. Coagulation and microfiltration have negligible removal, with the major removal step occurring across the reverse osmosis membrane where anthropogenic Gd (the amount of Gd attributable to MRI contrast agents) is reduced from 0.39 nmol/kg to 0.59 pmol/kg, a reduction of 99.85%. The RO concentrate has anthropogenic Gd concentrations of 2.6 nmol/kg, an increase in concentration in line with the design characteristics of the plant. The increased concentration in the RO concentrate may allow further development of anthropogenic Gd as a tracer of the fate of the RO concentrate in the environment.

  5. Virus-mimicking nano-constructs as a contrast agent for near infrared photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Gupta, Sharad; Chatni, Muhammad R.; Rao, Ayala L. N.; Vullev, Valentine I.; Wang, Lihong V.; Anvari, Bahman

    2013-02-01

    We report the first proof-of-principle demonstration of photoacoustic imaging using a contrast agent composed of a plant virus protein shell, which encapsulates indocyanine green (ICG), the only FDA-approved near infrared chromophore. These nano-constructs can provide higher photoacoustic signals than blood in tissue phantoms, and display superior photostability compared to non-encapsulated ICG. Our preliminary results suggest that the constructs do not elicit an acute immunogenic response in healthy mice.We report the first proof-of-principle demonstration of photoacoustic imaging using a contrast agent composed of a plant virus protein shell, which encapsulates indocyanine green (ICG), the only FDA-approved near infrared chromophore. These nano-constructs can provide higher photoacoustic signals than blood in tissue phantoms, and display superior photostability compared to non-encapsulated ICG. Our preliminary results suggest that the constructs do not elicit an acute immunogenic response in healthy mice. Electronic supplemental information (ESI) available: Information on experimental procedure for fabrication of the nano-constructs, photoacoustic imaging, and immunogenic studies. See DOI: 10.1039/c3nr34124k

  6. Optimization of the protocols for the use of contrast agents in PET/CT studies.

    PubMed

    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.

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

    PubMed

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

    2015-10-29

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is almost uniformly fatal. Current methods of detection include ultrasound examination and imaging by CT scan or MRI; however, these techniques are problematic in terms of sensitivity and specificity, and the detection of early tumors (<1 cm diameter) has proven elusive. Better, more specific, and more sensitive detection methods are therefore urgently needed. Here we discuss the application of a newly developed x-ray imaging technique called Spatial Frequency Heterodyne Imaging (SFHI) for the early detection of HCC. SFHI uses x-rays scattered by an object to form an image and is more sensitive than conventional absorption-based x-radiography. We show that tissues labeled in vivo with gold nanoparticle contrast agents can be detected using SFHI. We also demonstrate that directed targeting and SFHI of HCC tumors in a mouse model is possible through the use of HCC-specific antibodies. The enhanced sensitivity of SFHI relative to currently available techniques enables the x-ray imaging of tumors that are just a few millimeters in diameter and substantially reduces the amount of nanoparticle contrast agent required for intravenous injection relative to absorption-based x-ray imaging.

  8. X-ray scatter imaging of hepatocellular carcinoma in a mouse model using nanoparticle contrast agents

    DOE PAGES

    Rand, Danielle; Derdak, Zoltan; Carlson, Rolf; ...

    2015-10-29

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is almost uniformly fatal. Current methods of detection include ultrasound examination and imaging by CT scan or MRI; however, these techniques are problematic in terms of sensitivity and specificity, and the detection of early tumors (<1 cm diameter) has proven elusive. Better, more specific, and more sensitive detection methods are therefore urgently needed. Here we discuss the application of a newly developed x-ray imaging technique called Spatial Frequency Heterodyne Imaging (SFHI) for the early detection of HCC. SFHI uses x-rays scattered by an object to form anmore » image and is more sensitive than conventional absorption-based x-radiography. We show that tissues labeled in vivo with gold nanoparticle contrast agents can be detected using SFHI. We also demonstrate that directed targeting and SFHI of HCC tumors in a mouse model is possible through the use of HCC-specific antibodies. As a result, the enhanced sensitivity of SFHI relative to currently available techniques enables the x-ray imaging of tumors that are just a few millimeters in diameter and substantially reduces the amount of nanoparticle contrast agent required for intravenous injection relative to absorption-based x-ray imaging.« less

  9. X-ray scatter imaging of hepatocellular carcinoma in a mouse model using nanoparticle contrast agents

    SciTech Connect

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

    2015-10-29

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is almost uniformly fatal. Current methods of detection include ultrasound examination and imaging by CT scan or MRI; however, these techniques are problematic in terms of sensitivity and specificity, and the detection of early tumors (<1 cm diameter) has proven elusive. Better, more specific, and more sensitive detection methods are therefore urgently needed. Here we discuss the application of a newly developed x-ray imaging technique called Spatial Frequency Heterodyne Imaging (SFHI) for the early detection of HCC. SFHI uses x-rays scattered by an object to form an image and is more sensitive than conventional absorption-based x-radiography. We show that tissues labeled in vivo with gold nanoparticle contrast agents can be detected using SFHI. We also demonstrate that directed targeting and SFHI of HCC tumors in a mouse model is possible through the use of HCC-specific antibodies. As a result, the enhanced sensitivity of SFHI relative to currently available techniques enables the x-ray imaging of tumors that are just a few millimeters in diameter and substantially reduces the amount of nanoparticle contrast agent required for intravenous injection relative to absorption-based x-ray imaging.

  10. Targeted Nanodiamonds as Phenotype Specific Photoacoustic Contrast Agents for Breast Cancer

    PubMed Central

    Zhang, Ti; Cui, Huizhong; Fang, Chia-Yi; Cheng, Kun; Yang, Xinmai; Chang, Huan-Cheng; Forrest, M. Laird

    2015-01-01

    Aim The aim is to develop irradiated nanodiamonds (INDs) as a molecularly-targeted contrast agent for high resolution and phenotype-specific detection of breast cancer with photoacoustic (PA) imaging. Materials & Methods The surface of acid treated radiation-damaged nanodiamonds was grafted with polyethylene glycol (PEG) to improve its stability and circulation time in blood, followed by conjugation to an anti-Human epidermal growth factor receptor-2 (HER2) peptide (KCCYSL) with a final nanoparticle size of ca. 92 nm. Immunocompetent mice bearing orthotopic HER2 positive or negative tumors were administered INDs and PA imaged using an 820-nm near infrared laser. Results PA images demonstrated that INDs accumulate in tumors and completely delineated the entire tumor within 10 hours. HER2 targeting significantly enhanced imaging of HER2-positive tumors. Pathological examination demonstrated INDs are non-toxic. Conclusions PA technology is adaptable to low-cost bedside medicine, and with new contrast agents described herein, PA can achieve high resolution (sub-mm) and phenotype specific monitoring of cancer growth. PMID:25723091

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

    PubMed

    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.

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

    SciTech Connect

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

    2007-08-29

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

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

    PubMed

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

    2017-01-31

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

  14. Maxwell rheological model for lipid-shelled ultrasound microbubble contrast agents.

    PubMed

    Doinikov, Alexander A; Dayton, Paul A

    2007-06-01

    The present paper proposes a model that describes the encapsulation of microbubble contrast agents by the linear Maxwell constitutive equation. The model also incorporates the translational motion of contrast agent microbubbles and takes into account radiation losses due to the compressibility of the surrounding liquid. To establish physical features of the proposed model, comparative analysis is performed between this model and two existing models, one of which treats the encapsulation as a viscoelastic solid following the Kelvin-Voigt constitutive equation and the other assumes that the encapsulating layer behaves as a viscous Newtonian fluid. Resonance frequencies, damping coefficients, and scattering cross sections for the three shell models are compared in the regime of linear oscillation. Translational displacements predicted by the three shell models are examined by numerically calculating the general, nonlinearized equations of motion for weakly nonlinear excitation. Analogous results for free bubbles are also presented as a basis to which calculations made for encapsulated bubbles can be related. It is shown that the Maxwell shell model possesses specific physical features that are unavailable in the two other models.

  15. Nonlinear behaviors of contrast agents relevant to diagnostic and therapeutic applications.

    PubMed

    Wu, Junru; Pepe, Jason; Dewitt, William

    2003-04-01

    The nonlinear properties of an encapsulated microbubble of a contrast agent were studied theoretically and experimentally. A modified nonlinear differential equation (Herring equation) was used to describe the radial oscillation of the microbubble and solved numerically. It was found that the nonlinear resonance frequency, at which the peak radial oscillation amplitude occurs, was a decreasing function of the acoustic amplitude of a driving ultrasonic pulse. Optical images of the contrast agent microbubbles under various ultrasonic exposure conditions: 1. sham exposure; 2. 2-MHz spatial peak acoustic pressure = 200 kPa, I(SATA) = 260 mW/cm(2), duty cycle = 7.5%, repetition period = 0.0266 ms; 3. 0.5-MHz spatial peak acoustic pressure = 200 kPa, I(SATA) = 130 mW/cm(2), duty cycle = 7.5%, repetition period = 0.1067 ms; have also shown that the lower-frequency ultrasound (US) excitation (0.5 MHz) is more effective in disruption of the microbubbles due to acoustic inertial cavitation than the higher frequency US (2 MHz).

  16. Analysis of flash echo from contrast agent for designing optimal ultrasound diagnostic systems.

    PubMed

    Kamiyama, N; Moriyasu, F; Mine, Y; Goto, Y

    1999-03-01

    Microbubble-based contrast agents can enhance echoes in areas of low blood flow, but the bubbles are extremely sensitive and collapse easily when exposed to ultrasound (US) irradiation. An experimental study of bubble collapse was carried out to design new functions for US diagnostic systems to detect echoes from microbubbles more efficiently. For contrast agent (Levovist) solution, a high-intensity, but momentary, echo (flash echo), was observed in the first frame image after a several-second suspension of transmission, but was not seen in the second frame image. These "flash echo" signals were analyzed and categorized based on microscopic observation, and the results showed that the longevity of the microbubbles was reduced by conditions such as B-mode imaging. Next, a numerical simulation of the bubbles in liquid was performed under the same conditions as in the in vitro experiment. The results showed that even bubbles less than 1 microm in diameter expand and collapse within one pulse drive, which would generate flash echoes. The flash echo imaging system described here permits flexible intermittent scanning with variable intervals, with a variable number of frames at the trigger, and with simultaneous monitoring at low power output. Animal experiments were also conducted to evaluate the system. As the interval between frames was increased, the flash echoes gradually increased, and perfusion in the parenchyma was clearly observed with an interval of 4 s.

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

    PubMed

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

    2015-12-22

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

  18. High relaxivity MRI contrast agents part 2: Optimization of inner- and second-sphere relaxivity

    PubMed Central

    Jacques, Vincent; Dumas, Stephane; Sun, Wei-Chuan; Troughton, Jeffrey S.; Greenfield, Matthew T.; Caravan, Peter

    2011-01-01

    Rationale and objectives The observed relaxivity of gadolinium based contrast agents has contributions from the water molecule(s) that bind directly to the gadolinium ion (inner-sphere water), long lived water molecules and exchangeable protons that make up the second-sphere of coordination, and water molecules that diffuse near the contrast agent (outer-sphere). Inner- and second-sphere relaxivity can both be increased by optimization of the lifetimes of the water molecules and protons in these coordination spheres, the rotational motion of the complex, and the electronic relaxation of the gadolinium ion. We sought to identify new high relaxivity contrast agents by systematically varying the donor atoms that bind directly to gadolinium to increase inner-sphere relaxivity and concurrently including substituents that influence the second-sphere relaxivity. Methods Twenty GdDOTA derivatives were prepared and their relaxivity determined in presence and absence of human serum albumin as a function of temperature and magnetic field. Data was analyzed to extract the underlying molecular parameters influencing relaxivity. Each compound had a common albumin-binding group and an inner-sphere donor set comprising the 4 tertiary amine N atoms from cyclen, an α-substituted acetate oxygen atom, two amide oxygen atoms, an inner-sphere water oxygen atom, and a variable donor group. Each amide nitrogen was substituted with different groups to promote hydrogen bonding with second-sphere water molecules. Results Relaxivites at 0.47T and 1.4T, 37 °C, in serum albumin ranged from 16.0 to 58.1 mM−1s−1 and from 12.3 to 34.8 mM−1s−1 respectively. The reduction of inner-sphere water exchange typical of amide donor groups could be offset by incorporating a phosphonate or phenolate oxygen atom donor in the first coordination sphere resulting in higher relaxivity. Amide nitrogen substitution with pendant phosphonate or carboxylate groups increased relaxivity by as much as 88

  19. Impact of Filling Gas on Subharmonic Emissions of Phospholipid Ultrasound Contrast Agents.

    PubMed

    Kanbar, Emma; Fouan, Damien; Sennoga, Charles A; Doinikov, Alexander A; Bouakaz, Ayache

    2017-02-14

    Subharmonic signals backscattered from gas-filled lipid-shelled microbubbles have generated significant research interest because they can improve the detection and sensitivity of contrast-enhanced ultrasound imaging. However, the emission of subharmonic signals is strongly characterized by a temporal dependence, the origins of which have not been sufficiently elucidated. The features that influence subharmonic emissions need to be identified not only to better develop next-generation microbubble contrast agents, but also to develop more efficient subharmonic imaging (SHI) modes and therapeutic strategies. We examined the effect of microbubble filling gas on subharmonic emissions. Phospholipid shelled-microbubbles with different gaseous compositions such as sulfur hexafluoride (SF6), octafluoropropane (C3F8) or decafluorobutane (C4F10), nitrogen (N2)/C4F10 or air were insonated using a driving frequency of 10 MHz and peak negative pressure of 450 kPa, and their acoustic responses were tracked by monitoring both second harmonic and subharmonic emissions. Microbubbles were first acoustically characterized with their original gas and then re-characterized after substitution of the original gas with air, SF6 or C4F10. A measureable change in intensity of the subharmonic emissions with a 20- to 40-min delayed onset and increasing subharmonic emissions of the order 12-18 dB was recorded for microbubbles filled with C4F10. Substitution of C4F10 with air eliminated the earlier observed delay in subharmonic emissions. Significantly, substitution of SF6 for C4F10 successfully triggered a delay in the subharmonic emissions of the resultant agents, whereas substitution of C4F10 for SF6 eliminated the earlier observed suppression of subharmonic emissions, clearly suggesting that the type of filling gas contained in the microbubble agent influences subharmonic emissions in a time-dependent manner. Because our agents were dispersed in air-stabilized phosphate-buffered saline

  20. Metal-substituted protein MRI contrast agents engineered for enhanced relaxivity and ligand sensitivity.

    PubMed

    Lelyveld, Victor S; Brustad, Eric; Arnold, Frances H; Jasanoff, Alan

    2011-02-02

    Engineered metalloproteins constitute a flexible new class of analyte-sensitive molecular imaging agents detectable by magnetic resonance imaging (MRI), but their contrast effects are generally weaker than synthetic agents. To augment the proton relaxivity of agents derived from the heme domain of cytochrome P450 BM3 (BM3h), we formed manganese(III)-containing proteins that have higher electron spin than their native ferric iron counterparts. Metal substitution was achieved by coexpressing BM3h variants with the bacterial heme transporter ChuA in Escherichia coli and supplementing the growth medium with Mn3+-protoporphyrin IX. Manganic BM3h variants exhibited up to 2.6-fold higher T1 relaxivities relative to native BM3h at 4.7 T. Application of ChuA-mediated porphyrin substitution to a collection of thermostable chimeric P450 domains resulted in a stable, high-relaxivity BM3h derivative displaying a 63% relaxivity change upon binding of arachidonic acid, a natural ligand for the P450 enzyme and an important component of biological signaling pathways. This work demonstrates that protein-based MRI sensors with robust ligand sensitivity may be created with ease by including metal substitution among the toolkit of methods available to the protein engineer.

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

    PubMed

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

    2015-06-01

    Ultrasound contrast agents (UCAs) are currently used throughout the world in both clinical and research settings. The concept of contrast-enhanced ultrasound imaging originated in the late 1960s, and the first commercially available agents were initially developed in the 1980s. Today's microbubbles are designed for greater utility and are used for both approved and off-label indications. In October 2007, the US Food and Drug Administration (FDA) imposed additional product label warnings that included serious cardiopulmonary reactions, several new disease-state contraindications, and a mandated 30 min post-procedure monitoring period for the agents Optison and Definity. These additional warnings were prompted by reports of cardiopulmonary reactions that were temporally related but were not clearly attributable to these UCAs. Subsequent published reports over the following months established not only the safety but also the improved efficacy of clinical ultrasound applications with UCAs. The FDA consequently updated the product labeling in June 2008 and reduced contraindications, although it continued to monitor select patients. In addition, a post-marketing program was proposed to the sponsors for a series of safety studies to further assess the risk of UCAs. Then in October 2011, the FDA leadership further downgraded the warnings after hearing the results of the post-marketing data, which revealed continued safety and improved efficacy. The present review focuses on the use of UCAs in today's clinical practice, including the approved indications, a variety of off-label uses, and the most recent data, which affirms the safety and efficacy of UCAs.

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

    PubMed Central

    Tracy, Melissa J; Feinstein, Steven B

    2015-01-01

    Ultrasound contrast agents (UCAs) are currently used throughout the world in both clinical and research settings. The concept of contrast-enhanced ultrasound imaging originated in the late 1960s, and the first commercially available agents were initially developed in the 1980s. Today's microbubbles are designed for greater utility and are used for both approved and off-label indications. In October 2007, the US Food and Drug Administration (FDA) imposed additional product label warnings that included serious cardiopulmonary reactions, several new disease-state contraindications, and a mandated 30 min post-procedure monitoring period for the agents Optison and Definity. These additional warnings were prompted by reports of cardiopulmonary reactions that were temporally related but were not clearly attributable to these UCAs. Subsequent published reports over the following months established not only the safety but also the improved efficacy of clinical ultrasound applications with UCAs. The FDA consequently updated the product labeling in June 2008 and reduced contraindications, although it continued to monitor select patients. In addition, a post-marketing program was proposed to the sponsors for a series of safety studies to further assess the risk of UCAs. Then in October 2011, the FDA leadership further downgraded the warnings after hearing the results of the post-marketing data, which revealed continued safety and improved efficacy. The present review focuses on the use of UCAs in today's clinical practice, including the approved indications, a variety of off-label uses, and the most recent data, which affirms the safety and efficacy of UCAs. PMID:26693339

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

    PubMed Central

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

    2015-01-01

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

  4. Paramagnetic dysprosium oxide nanoparticles and dysprosium hydroxide nanorods as T₂ MRI contrast agents.

    PubMed

    Kattel, Krishna; Park, Ja Young; Xu, Wenlong; Kim, Han Gyeol; Lee, Eun Jung; Bony, Badrul Alam; Heo, Woo Choul; Jin, Seonguk; Baeck, Jong Su; Chang, Yongmin; Kim, Tae Jeong; Bae, Ji Eun; Chae, Kwon Seok; Lee, Gang Ho

    2012-04-01

    We report here paramagnetic dysprosium nanomaterial-based T(2) MRI contrast agents. A large r(2) and a negligible r(1) is an ideal condition for T(2) MR imaging. At this condition, protons are strongly and nearly exclusively induced for T(2) MR imaging. The dysprosium nanomaterials fairly satisfy this because they are found to possess a decent r(2) but a negligible r(1) arising from L + S state 4f-electrons in Dy(III) ion ((6)H(15/2)). Their r(2) will also further increase with increasing applied field because of unsaturated magnetization at room temperature. Therefore, MR imaging and various physical properties of the synthesized d-glucuronic acid coated ultrasmall dysprosium oxide nanoparticles (d(avg) = 3.2 nm) and dysprosium hydroxide nanorods (20 × 300 nm) are investigated. These include hydrodynamic diameters, magnetic properties, MR relaxivities, cytotoxicities, and 3 tesla in vivo T(2) MR images. Here, MR imaging properties of dysprosium hydroxide nanorods have not been reported so far. These two samples show r(2)s of 65.04 and 181.57 s(-1)mM(-1), respectively, with negligible r(1)s at 1.5 tesla and at room temperature, no in vitro cytotoxicity up to 100 μM Dy, and clear negative contrast enhancements in 3 tesla in vivo T(2) MR images of a mouse liver, which will be even more improved at higher MR fields. Therefore, d-glucuronic acid coated ultrasmall dysprosium oxide nanoparticles with renal excretion can be a potential candidate as a sensitive T(2) MRI contrast agent at MR field greater than 3 tesla.

  5. The Natural Frequency of Nonlinear Oscillation of Ultrasound Contrast Agents in Microvessels

    PubMed Central

    Qin, Shengping; Ferrara, Katherine W.

    2009-01-01

    Ultrasound Contrast Agent (UCAs) are under intensive investigation for their applications in physiological and molecular imaging and drug delivery. Prediction of the natural frequency of the oscillation of UCAs in microvessels has drawn increasing attention. To our knowledge, the existing models to predict the natural frequency of oscillation of UCAs in microvessels all apply the linear approximation and treat the blood vessel wall as a rigid boundary. In the potential applications of ultrasound imaging drug and gene delivery, the compliance of small vessels may play an important role in the bubble’s oscillation. The goal of this work is to provide a lumped-parameter model to study the natural frequency of nonlinear oscillation of UCAs in microvessels. Three types of the blood vessel conditions have been considered. i.e. rigid vessels, normal compliable vessels and vessels with increasing stiffness that could correspond to tumor vasculature. The corresponding bubble oscillation frequencies in the vessels with radius less than 100 μm are examined in detail. When a bubble with a radius of 4 μm is confined in a compliable vessel (inner radius 5 μm and length 100μm), the natural frequency of bubble oscillation increases by a factor of 1.7 as compared with a bubble in an unbounded field. The natural frequency of oscillation of a bubble in a compliable vessel increases with decreasing vessel size while decreasing with increasing values of vessel rigidity. This model suggests that contrast agent size, blood vessel size distribution and the type of vasculature should be comprehensively considered for choosing the transmitted frequency in ultrasound contrast imaging and drug delivery. PMID:17478030

  6. Stimulus-Responsive Ultrasound Contrast Agents for Clinical Imaging: Motivations, Demonstrations, and Future Directions

    PubMed Central

    Goodwin, Andrew P.; Nakatsuka, Matthew A.; Mattrey, Robert F.

    2014-01-01

    Microbubble ultrasound contrast agents allow imaging of the vasculature with excellent resolution and signal-to-noise ratios. Contrast in microbubbles derives from their interaction with an ultrasound wave to generate signal at harmonic frequencies of the stimulating pulse; subtracting the elastic echo caused by the surrounding tissue can enhance the specificity of these harmonic signals significantly. The nonlinear acoustic emission is caused by pressure-driven microbubble size fluctuations, which in both theoretical descriptions and empirical measurements was found to depend on the mechanical properties of the shell that encapsulates the microbubble as well as stabilizes it against the surrounding aqueous environment. Thus biochemically-induced switching between a rigid “off” state and a flexible “on” state provides a mechanism for sensing chemical markers for disease. In our research, we coupled DNA oligonucleotides to a stabilizing lipid monolayer to modulate stiffness of the shell and thereby induce stimulus-responsive behavior. In initial proof-of-principle studies, it was found that signal modulation came primarily from DNA crosslinks preventing the microbubble size oscillations rather than merely damping the signal. Next, these microbubbles were redesigned to include an aptamer sequence in the crosslinking strand, which not only allowed the sensing of the clotting enzyme thrombin but also provided a general strategy for sensing other soluble biomarkers in the bloodstream. Finally, the thrombin-sensitive microbubbles were validated in a rabbit model, presenting the first example of an ultrasound contrast agent that could differentiate between active and inactive clots for the diagnosis of Deep Venous Thrombosis. PMID:25195785

  7. Evaluation of Gd-DTPA-monophytanyl and phytantriol nanoassemblies as potential MRI contrast agents.

    PubMed

    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.

  8. TREG coated iron oxide nanoparticles as contrast agent for MRI in-vivo use

    NASA Astrophysics Data System (ADS)

    Gutierrez-Garcia, Eric; Hidalgo-Tobon, Silvia; Lopez, Ciro; Gonzalez-Rodriguez, Roberto; Coffer, Jeffery; De Celis Alonso, Benito; Dies Suarez, Pilar; Obregon, Manuel; Perez-Pena, Mario; Platas-Neri, Diana; Mendez-Rojas, Miguel

    2014-11-01

    Super-paramagnetic iron oxide nanoparticles (SPIONs) are of interest due to their great potential applications in diverse fields such as biomedicine. In this work we have prepared SPION nanoparticles using the polyol technique and characterized the magnetic properties of them for MRI in-vivo use. Nanoparticle preparation: All reagents were purchased from commercial sources (Sigma-Aldrich, St. Louis, USA) Iron (III) acetylacetonate, [Fe(acac)3], was used as the iron oxide precursor and thermally decomposed at high temperatures in triethyleneglycol (TREG). Nano-sized magnetite particles were prepared by an adaptation of the method proposed by Wei Cai et al[1-3]. A healthy rabbit was scanned on a clinical 1.5 T Philips MR scanner. Images were taken in 2D mode with a mFFE sequence. Relaxation time T2 was obtained from the MR images using a Matlab algorithm where the signal intensity decay was calculated at each image and then adjusted to a mono-exponential curve. Images were obtained before contrast injection, 24 hours and 36 hours following SPIONs administration. Signal decay at different Echo times for the prepared magnetic SPIONs, before and after contrast injection was measured. It was visualized a concentration of the agent contrast in brain and liver and the results were compared with images obtained from histopathology.

  9. Liposomes Loaded with Hydrophobic Iron Oxide Nanoparticles: Suitable T₂ Contrast Agents for MRI.

    PubMed

    Martínez-González, Raquel; Estelrich, Joan; Busquets, Maria Antònia

    2016-07-27

    There has been a recent surge of interest in the use of superparamagnetic iron oxide nanoparticles (SPIONs) as contrast agents (CAs) for magnetic resonance imaging (MRI), due to their tunable properties and their low toxicity compared with other CAs such as gadolinium. SPIONs exert a strong influence on spin-spin T₂ relaxation times by decreasing the MR signal in the regions to which they are delivered, consequently yielding darker images or negative contrast. Given the potential of these nanoparticles to enhance detection of alterations in soft tissues, we studied the MRI response of hydrophobic or hydrophilic SPIONs loaded into liposomes (magnetoliposomes) of different lipid composition obtained by sonication. These hybrid nanostructures were characterized by measuring several parameters such as size and polydispersity, and number of SPIONs encapsulated or embedded into the lipid systems. We then studied the influence of acyl chain length as well as its unsaturation, charge, and presence of cholesterol in the lipid bilayer at high field strength (7 T) to mimic the conditions used in preclinical assays. Our results showed a high variability depending on the nature of the magnetic particles. Focusing on the hydrophobic SPIONs, the cholesterol-containing samples showed a slight reduction in r₂, while unsaturation of the lipid acyl chain and inclusion of a negatively charged lipid into the bilayer appeared to yield a marked increase in negative contrast, thus rendering these magnetoliposomes suitable candidates as CAs, especially as a liver CA.

  10. Liposomes Loaded with Hydrophobic Iron Oxide Nanoparticles: Suitable T2 Contrast Agents for MRI

    PubMed Central

    Martínez-González, Raquel; Estelrich, Joan; Busquets, Maria Antònia

    2016-01-01

    There has been a recent surge of interest in the use of superparamagnetic iron oxide nanoparticles (SPIONs) as contrast agents (CAs) for magnetic resonance imaging (MRI), due to their tunable properties and their low toxicity compared with other CAs such as gadolinium. SPIONs exert a strong influence on spin-spin T2 relaxation times by decreasing the MR signal in the regions to which they are delivered, consequently yielding darker images or negative contrast. Given the potential of these nanoparticles to enhance detection of alterations in soft tissues, we studied the MRI response of hydrophobic or hydrophilic SPIONs loaded into liposomes (magnetoliposomes) of different lipid composition obtained by sonication. These hybrid nanostructures were characterized by measuring several parameters such as size and polydispersity, and number of SPIONs encapsulated or embedded into the lipid systems. We then studied the influence of acyl chain length as well as its unsaturation, charge, and presence of cholesterol in the lipid bilayer at high field strength (7 T) to mimic the conditions used in preclinical assays. Our results showed a high variability depending on the nature of the magnetic particles. Focusing on the hydrophobic SPIONs, the cholesterol-containing samples showed a slight reduction in r2, while unsaturation of the lipid acyl chain and inclusion of a negatively charged lipid into the bilayer appeared to yield a marked increase in negative contrast, thus rendering these magnetoliposomes suitable candidates as CAs, especially as a liver CA. PMID:27472319

  11. Aggregates dynamic in contrasting soils with different fertilizations and role of humic carbon as binding agent

    NASA Astrophysics Data System (ADS)

    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 <53 mm) in contrasting soil (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, <30 KDa). The aim were to evaluate the effect of the different fertilisations type in the aggregate and 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. Oxidation-Responsive, EuII/III-Based, Multimodal Contrast Agent for Magnetic Resonance and Photoacoustic Imaging

    PubMed Central

    2017-01-01

    We report, for the first time, a multimodal, oxidation-responsive contrast agent for magnetic resonance imaging and photoacoustic imaging that uses the differences in the properties between Eu in the +2 and +3 oxidation states. The enhancement of contrast in T1-weighted magnetic resonance and photoacoustic imaging was observed in the +2 but not in the +3 oxidation state, and the complex is a known chemical exchange saturation transfer agent for magnetic resonance imaging in the +3 oxidation state. PMID:28393130

  13. Recent advances in ytterbium-based contrast agents for in vivo X-ray computed tomography imaging: promises and prospects.

    PubMed

    Liu, Yanlan; Liu, Jianhua; Ai, Kelong; Yuan, Qinghai; Lu, Lehui

    2014-01-01

    X-ray computed tomography (CT) imaging is one of the most widely used diagnostic imaging techniques in the clinic, and has raised significant interest in recent years both in research and practice owing to its many advantages such as deep penetration depth, high resolution and facile image processing. Developing heavy metal-based CT contrast agents, especially heavy metal-containing nanoparticulate CT contrast agents, has become a key focus in research fields to address issues of clinical iodinated agents involving short circulation time, low contrast efficiency and potential renal toxicity. In this review, we summarize the development of ytterbium (Yb)-based CT contrast agents and highlight the design and applications of Yb-based nanoparticulate CT contrast agents. Yb has high atomic number and higher abundance in the earth's crust relative to Au, Ta and Bi, which have received much attention as a CT contrast agents. In particular, in contrast to these metal elements, as well as I, Yb has K-edge energy that is located just within the higher-intensity region of X-ray spectra, which can induce significant enhancement in the contrast efficiency. When encapsulated in nanoparticles, Yb can remain in the circulation for a long time. This long in vivo circulation time, combined with the proper K-edge energy and a large absorption cross-section of Yb in the near-infrared region, makes Yb-based nanoparticles particularly promising in angiography, 'multicolor' spectral CT imaging, and multimodal imaging. Finally, we also discuss the prospects and the challenges in the development of Yb-based CT contrast agents.

  14. FDTD simulation tools for UWB antenna analysis.

    SciTech Connect

    Brocato, Robert Wesley

    2005-02-01

    This paper describes the development of a set of software tools useful for analyzing ultra-wideband (UWB) antennas and structures. These tools are used to perform finite difference time domain (FDTD) simulation of a conical antenna with continuous wave (CW) and UWB pulsed excitations. The antenna is analyzed using spherical coordinate-based FDTD equations that are derived from first principles. The simulation results for CW excitation are compared to simulation and measured results from published sources; the results for UWB excitation are new.

  15. FDTD simulation tools for UWB antenna analysis.

    SciTech Connect

    Brocato, Robert Wesley

    2004-12-01

    This paper describes the development of a set of software tools useful for analyzing ultra-wideband (UWB) antennas and structures. These tools are used to perform finite difference time domain (FDTD) simulation of a conical antenna with continuous wave (CW) and UWB pulsed excitations. The antenna is analyzed using spherical coordinate-based FDTD equations that are derived from first principles. The simulation results for CW excitation are compared to simulation and measured results from published sources; the results for UWB excitation are new.

  16. Is bacteriostatic saline superior to normal saline as an echocardiographic contrast agent?

    PubMed

    Cardozo, Shaun; Gunasekaran, Prasad; Patel, Hena; McGorisk, Timothy; Toosi, Mehrdad; Faraz, Haroon; Zalawadiya, Sandip; Alesh, Issa; Kottam, Anupama; Afonso, Luis

    2014-12-01

    Objective data on the performance characteristics and physical properties of commercially available saline formulations [normal saline (NS) vs. bacteriostatic normal saline (bNS)] are sparse. This study sought to compare the in vitro physical properties and in vivo characteristics of two commonly employed echocardiographic saline contrast agents in an attempt to assess superiority. Nineteen patients undergoing transesophageal echocardiograms were each administered agitated regular NS and bNS injections in random order and in a blinded manner according to a standardized protocol. Video time-intensity (TI) curves were constructed from a representative region of interest, placed paraseptally within the right atrium, in the bicaval view. TI curves were analyzed for maximal plateau acoustic intensity (Vmax, dB) and dwell time (DT, s), defined as time duration between onset of Vmax and decay of video intensity below clinically useful levels, reflecting the duration of homogenous opacification of the right atrium. To further characterize the physical properties of the bubbles in vitro, fixed aliquots of similarly agitated saline were injected into a glass well slide-cover slip assembly and examined using an optical microscope to determine bubble diameter in microns (µm) and concentration [bubble count/high power field (hpf)]. A higher acoustic intensity (a less negative dB level), higher bubble concentration and longer DT were considered properties of a superior contrast agent. For statistical analysis, a paired t test was conducted to evaluate the differences in means of Vmax and DT. Compared to NS, bNS administration was associated with superior opacification (video intensity -8.69 ± 4.7 vs. -10.46 ± 4.1 dB, P = 0.002), longer DT (17.3 ± 6.1 vs. 10.2 ± 3.7 s) in vivo and smaller mean bubble size (43.4 vs. 58.6 μm) and higher bubble concentration (1,002 vs. 298 bubble/hpf) in vitro. bNS provides higher intensity and more sustained opacification of the right atrium

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

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

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

    SciTech Connect

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

    2015-10-28

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

  19. Vascular imaging with ultrasound contrast agents: Characterization of pharmaceutical, physiological, and instrumentation parameters that influence clinical efficacy

    NASA Astrophysics Data System (ADS)

    Steinbach, Gregory Curtis

    Over the last decade, ultrasound contrast media have become important diagnostic tools. Their development lagged behind that of some of the other imaging modalities, even though ultrasound is used worldwide and is a technology that would benefit from an increased signal-to-noise ratio. Ultrasound contrast agents, used as a tool to improve signal, could have global diagnostic applications as well as the possibility of extending the diagnostic capabilities of outdated or inexpensive instruments, which often have poor sensitivity. Part of the lag in contrast agent development was due to the pharmaceutical challenge of creating a safe material that effectively scattered ultrasound. The challenge was further increased by the difficulty of reproducibly predicting and characterizing the properties of these materials in-vitro with results that correlated with clinical data. Additional significant problems included demonstrating the benefits of contrast agents and teaching the clinicians about the interactions between instrumentation and contrast materials so that they could use both tools synergistically to derive maximum diagnostic benefit. The purpose of this work is to reduce these challenges by characterizing the clinically relevant enhancement properties of two different classes of ultrasound contrast materials. The enhancement mechanisms of these agents differ considerably and will be discussed in detail. These differences provide a unique view of the variety of physical characteristics that can be utilized to design ultrasound contrast agents for a range of applications. The in-vitro characterization requirements of the agents differ, and the experimental model characteristics for each are described and demonstrated. The clinical enhancement characteristics are also described, as well as the differing impact of contrast- instrumentation interactions on the efficacy of the agents. Understanding these principles is important because ultrasound contrast agents are

  20. The study of N-isopropylacrylamide gel dosimeter doped iodinated contrast agents

    NASA Astrophysics Data System (ADS)

    Chang, Y. J.; Hsieh, L. L.; Liu, M. H.; Liu, J. S.; Hsieh, B. T.

    2013-06-01

    Low toxicity of N-isopropylacrylamide (NIPAM) dosimeter was doped with clinical iodinated contrast medium agents(Iobitridol (Xenetix® 350) and organically bound iodine (Conray® 60) as radiation sensitizers; The suitable gel dosimeter preparation formula in this research was 5 w/w% gelatin, 5 w/w% N-isopropylacrylamide, 3 w/w% N,N-methylene-bis-acrylamide, and 5 mM Tetrakis phosphonium chloride. The spiral CT was irradiator, and 120 kVp was the operating tube voltage. The maximum radiation dose was 0.6 Gy, and optical CT was the gel measurement device used. The results showed SERs with the addition of radiosensitizers were 10.70 (Xenetix® 350) and 9.67 (Conray® 60), respectively. Thus, the polymerized gel dosimeter could be used in the efficacy evaluation of low-energy and low-radiation dose.

  1. Cellulose nanoparticles are a biodegradable photoacoustic contrast agent for use in living mice

    PubMed Central

    Jokerst, Jesse V.; Van de Sompel, Dominique; Bohndiek, Sarah E.; Gambhir, Sanjiv S.

    2014-01-01

    Molecular imaging with photoacoustic ultrasound is an emerging field that combines the spatial and temporal resolution of ultrasound with the contrast of optical imaging. However, there are few imaging agents that offer both high signal intensity and biodegradation into small molecules. Here we describe a cellulose-based nanoparticle with peak photoacoustic signal at 700 nm and an in vitro limit of detection of 6 pM (0.02 mg/mL). Doses down to 0.35 nM (1.2 mg/mL) were used to image mouse models of ovarian cancer. Most importantly, the nanoparticles were shown to biodegrade in the presence of cellulase both through a glucose assay and electron microscopy. PMID:25225633

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

    NASA Astrophysics Data System (ADS)

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

    2016-12-01

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

  3. Fluorine-19 MRI Contrast Agents for Cell Tracking and Lung Imaging

    PubMed Central

    Fox, Matthew S.; Gaudet, Jeffrey M.; Foster, Paula J.

    2015-01-01

    Fluorine-19 (19F)-based contrast agents for magnetic resonance imaging stand to revolutionize imaging-based research and clinical trials in several fields of medical intervention. First, their use in characterizing in vivo cell behavior may help bring cellular therapy closer to clinical acceptance. Second, their use in lung imaging provides novel noninvasive interrogation of the ventilated airspaces without the need for complicated, hard-to-distribute hardware. This article reviews the current state of 19F-based cell tracking and lung imaging using magnetic resonance imaging and describes the link between the methods across these fields and how they may mutually benefit from solutions to mutual problems encountered when imaging 19F-containing compounds, as well as hardware and software advancements. PMID:27042089

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

    NASA Astrophysics Data System (ADS)

    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.

  5. Detection of brain tumors using fluorescence diffuse optical tomography and nanoparticles as contrast agents

    NASA Astrophysics Data System (ADS)

    Fortin, Pierre-Yves; Genevois, Coralie; Koenig, Anne; Heinrich, Emilie; Texier, Isabelle; Couillaud, Franck

    2012-12-01

    Near-infrared fluorescence-enhanced diffuse optical tomography (fDOT) is used to localize tumors in mice using fluorescent nanoparticles as a blood pool contrast agent. The infrared dye DiR is loaded in the lipid core of nontargeted nanoparticles (DiR-lipidots) and injected systemically via the tail vein in mice bearing U87 tumors. Distribution and time-course of DiR-lipidots are followed using in vivo fluorescence reflectance imaging and reveal enhanced fluorescent signal within the subcutaneous tumors up to seven days due to the enhanced permeability and retention effect. Tumor growth into the brain is followed using bioluminescent imaging, and tumor localization is further determined by magnetic resonance imaging. The fDOT provides three-dimensional fluorescent maps that allow for consistent localization for both subcutaneous and brain tumors.

  6. Thoracic duct lymphography by subcutaneous contrast agent injection in a dog with chylothorax

    PubMed Central

    Iwanaga, T.; Tokunaga, S.; Momoi, Y.

    2016-01-01

    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 an open thoracotomy. Pleural effusion improved but relapsed a week after the surgery. A second lymphography revealed a collateral thoracic duct that was not detected during the first lymphography. The collateral duct was ligated and chylothorax was resolved after the second surgery. The lymphography applied in this study was minimally-invasive and easily provided images of the thoracic duct in a dog with chylothorax. PMID:27995081

  7. Gadolinium(III) complexes as MRI contrast agents: ligand design and properties of the complexes.

    PubMed

    Hermann, Petr; Kotek, Jan; Kubícek, Vojtech; Lukes, Ivan

    2008-06-21

    Magnetic resonance imaging is a commonly used diagnostic method in medicinal practice as well as in biological and preclinical research. Contrast agents (CAs), which are often applied are mostly based on Gd(III) complexes. In this paper, the ligand types and structures of their complexes on one side and a set of the physico-chemical parameters governing properties of the CAs on the other side are discussed. The solid-state structures of lanthanide(III) complexes of open-chain and macrocyclic ligands and their structural features are compared. Examples of tuning of ligand structures to alter the relaxometric properties of gadolinium(III) complexes as a number of coordinated water molecules, their residence time (exchange rate) or reorientation time of the complexes are given. Influence of the structural changes of the ligands on thermodynamic stability and kinetic inertness/lability of their lanthanide(III) complexes is discussed.

  8. Iodinated α-tocopherol nano-emulsions as non-toxic contrast agents for preclinical X-ray imaging.

    PubMed

    Li, Xiang; Anton, Nicolas; Zuber, Guy; Zhao, Minjie; Messaddeq, Nadia; Hallouard, François; Fessi, Hatem; Vandamme, Thierry F

    2013-01-01

    Micro-computed tomography (micro-CT) is an emerging imaging modality, due to the low cost of the imagers as well as their efficiency in establishing high-resolution (1-100 μm) three-dimensional images of small laboratory animals and facilitating rapid, structural and functional in vivo visualization. However use of a contrast agent is absolutely necessary when imaging soft tissues. The main limitation of micro-CT is the low efficiency and toxicity of the commercially available blood pool contrast agents. This study proposes new, efficient and non-toxic contrast agents for micro-CT imaging. This formulation consists of iodinated vitamin E (α-tocopheryl 2,3,5-triiodobenzoate) as an oily phase, formulated as liquid nano-emulsion droplets (by low-energy nano-emulsification), surrounded by a hairy PEG layer to confer stealth properties. The originality and strength of these new contrast agents lie not only in their outstanding contrasting properties, biocompatibility and low toxicity, but also in the simplicity of their fabrication: one-step synthesis of highly iodinated oil (iodine constitutes 41.7% of the oil molecule weight) and its spontaneous emulsification. After i.v. administration in mice (8.5% of blood volume), the product shows stealth properties towards the immune system and thus acts as an efficient blood pool contrast agent (t(1/2) = 9.0 h), exhibiting blood clearance following mono-exponential decay. A gradual accumulation predominantly due to hepatocyte uptake is observed and measured in the liver, establishing a strong hepatic contrast, persistent for more than four months. To summarize, in the current range of available or developed contrast agents for preclinical X-ray imaging, this agent appears to be one of the most efficient.

  9. Bioconjugated gold nanoparticles as a contrast agent for detection of small tumors

    NASA Astrophysics Data System (ADS)

    Eghtedari, Mohammad A.; Copland, John A.; Popov, Vsevolod L.; Kotov, Nicholas A.; Motamedi, Massoud; Oraevsky, Alexander A.

    2003-06-01

    Optoacoustic tomography (OAT) is a medical imaging method for detection of cancerous tumors that uses laser pulses to produce transi ultrasonic waves with spatial profiles replicating distribution of absorbed optical energy. Unlike conventional ultrasonography that uses an external source of acoustic waves, OAT uses transient acoustic waves generated as result of thermal expansion of tissue preferentially heated with short laser pulses. Tissues with different optical properties have different optoacoustic profiles and this enables reconstruction of an acoustic image based on distribution of optical absorption. It is anticipated that the difference in optical absorption between very early tumors and normal tissues might be minimal, justifying application of a contrast agent. Gold Nanoparticles (NP) can be designed to strongly absorb desirable color of laser pulses and effectively produce acoustic waves. Therefore, gold NP can be potentially employed as an optoacoustic contrast agent. We studied sensitivity of optoacoustic imaging in phantoms resembling dimensions and properties of the breast with small objects loaded with gold NPs of various concentrations. Targeted selective loading of breast cancer cells in culture with 40-nm diameter NPs was experimentally demonstrated with electron microscopy and fluorescence labeling techniques. To achieve selective targeting, Herceptin, a monoclonal antibody raised against Her2 receptor was conjugated to NPs using streptavidin-biotin conjugation as a linker. Targeting experiments simultaneously demonstrated that Mab/NPs conjugates inhibit cell proliferation of Her/neu positive cells. These data present the first step in development of a new technology for highly selective cancer chemotherapy with capability to diagnose the presence of malignant tumors and monitor the effects of the treatment.

  10. Biocompatible nanotemplate-engineered nanoparticles containing gadolinium: stability and relaxivity of a potential MRI contrast agent.

    PubMed

    Zhu, Donghua; White, R D; Hardy, Peter A; Weerapreeyakul, Natthida; Sutthanut, Khaetthareeya; Jay, Michael

    2006-04-01

    In this article, we use a nanotemplate engineering approach to prepare biodegradable nanoparticles composed of FDA-approved materials and possessing accessible gadolinium (Gd) atoms and demonstrate their potential as a Magnetic Resonance Imaging (MRI) contrast agent. Nanoparticles containing dimyristoyl phosphoethanolamine diethylene triamine penta acetate (PE-DTPA) were prepared using 3.5 mg of Brij 78, 2.0 mg of emulsifying wax and 0.5 mg of PE-DTPA/ml from a microemulsion precursor. After the addition of GdCl3, the presence of Gd on the surface of nanoparticles was characterized using inductively coupled plasma atomic emission spectroscopy and Scanning Transmission Electron Microscopy (STEM). The in vitro relaxivities of the PE-DTPA-Gd nanoparticles in different media were assessed at different field strengths. The conditional stability constant of Gd binding to the nanoparticles was determined using competitive spectrophotometric titration. Transmetallation kinetics of the gadolinium ion from PE-DTPA-Gd nanoparticles with zinc as the competing ionic was measured using the relaxivity evolution method. Nanoparticles with a diameter of approximately 130 nm possessing surface chelating functions were made from GRAS (Generally Regarded As Safe) materials. STEM demonstrated the uniform distribution of Gd3+ on the surface of the nanoparticles. The thermodynamic binding constant for Gd3+ to the nanoparticles was approximately 10(18) M(-1) and transmetallation studies with Zn2+ yielded kinetic constants K1 and K(-1) of 0.033 and 0.022 1/h, respectively, with an equilibrium constant of 1.5. A payload of approximately 10(5) Gd/nanoparticle was achieved; enhanced relaxivities were observed, including a pH dependence of the transverse relaxivity (r2). Nanoparticles composed of materials that have been demonstrated to be hemocompatible and enzymatically metabolized and possessing accessible Gd ions on their surface induce relaxivities in the bulk water signal that make them

  11. Confocal Microscopy and Molecular-Specific Optical Contrast Agents for the Detection of Oral Neoplasia

    PubMed Central

    Carlson, Alicia L.; Gillenwater, Ann M.; Williams, Michelle D.; El-Naggar, Adel K.; Richards-Kortum, R. R.

    2009-01-01

    Using current clinical diagnostic techniques, it is difficult to visualize tumor morphology and architecture at the cellular level, which is necessary for diagnostic localization of pathologic lesions. Optical imaging techniques have the potential to address this clinical need by providing real-time, sub-cellular resolution images. This paper describes the use of dual mode confocal microscopy and optical molecular-specific contrast agents to image tissue architecture, cellular morphology, and sub-cellular molecular features of normal and neoplastic oral tissues. Fresh tissue slices were prepared from 33 biopsies of clinically normal and abnormal oral mucosa obtained from 14 patients. Reflectance confocal images were acquired after the application of 6% acetic acid, and fluorescence confocal images were acquired after the application of a fluorescence contrast agent targeting the epidermal growth factor receptor (EGFR). The dual imaging modes provided images similar to light microscopy of hematoxylin and eosin and immunohistochemistry staining, but from thick fresh tissue slices. Reflectance images provided information on the architecture of the tissue and the cellular morphology. The nuclear-to-cytoplasmic (N/C) ratio from the reflectance images was at least 7.5 times greater for the carcinoma than the corresponding normal samples, except for one case of highly keratinized carcinoma. Separation of carcinoma from normal and mild dysplasia was achieved using this ratio (p<0.01). Fluorescence images of EGFR expression yielded a mean fluorescence labeling intensity (FLI) that was at least 2.7 times higher for severe dysplasia and carcinoma samples than for the corresponding normal sample, and could be used to distinguish carcinoma from normal and mild dysplasia (p<0.01). Analyzed together, the N/C ratio and the mean FLI may improve the ability to distinguish carcinoma from normal squamous epithelium. PMID:17877424

  12. Experimental evaluation of a hyperspectral imager for near-infrared fluorescent contrast agent studies

    NASA Astrophysics Data System (ADS)

    Luthman, A. S.; Bohndiek, Sarah E.

    2015-03-01

    Hyperspectral imaging (HSI) systems have the potential to combine morphological and spectral information to provide detailed and high sensitivity readouts in biological and medical applications. As HSI enables simultaneous detection in several spectral bands, the technology has significant potential for use in real-time multiplexed contrast agent studies. Examples include tumor detection in intraoperative and endoscopic imaging as well as histopathology. A multiplexed readout from multiple disease targets, such as cell surface receptors overexpressed in cancer cells, could improve both sensitivity and specificity of tumor identification. Here, we evaluate a commercial, compact, near-infrared HSI sensor that has the potential to enable low cost, video rate HSI for multiplexed fluorescent contrast agent studies in biomedical applications. The hyperspectral imager, based on a monolithically integrated Fabry-Perot etalon, has 70 spectral bands between 600-900 nm, making it ideal for this application. Initial calibration of the imager was performed to determine wavelength band response, quantum efficiency and the effect of F-number on the spectral response. A platform for wide-field fluorescence imaging in reflectance using fluorophore specific LED excitation was then developed. The applicability of the imaging platform for simultaneous readout of multiple fluorophore signals was demonstrated using a dilution series of Alexa Fluor 594 and Alexa Fluor 647, showing that nanomolar fluorophore concentrations can be detected. Our results show that the HSI system can clearly resolve the emission spectra of the two fluorophores in mixtures of concentrations across several orders of magnitude, indicating a high dynamic range performance. We therefore conclude that the HSI sensor tested here is suitable for detecting fluorescence in biomedical imaging applications.

  13. Dimethyl sulfoxide (DMSO) as a potential contrast agent for brain tumors.

    PubMed

    Delgado-Goñi, T; Martín-Sitjar, J; Simões, R V; Acosta, M; Lope-Piedrafita, S; Arús, C

    2013-02-01

    Dimethyl sulfoxide (DMSO) is commonly used in preclinical studies of animal models of high-grade glioma as a solvent for chemotherapeutic agents. A strong DMSO signal was detected by single-voxel MRS in the brain of three C57BL/6 control mice during a pilot study of DMSO tolerance after intragastric administration. This led us to investigate the accumulation and wash-out kinetics of DMSO in both normal brain parenchyma (n=3 control mice) by single-voxel MRS, and in 12 GL261 glioblastomas (GBMs) by single-voxel MRS (n=3) and MRSI (n=9). DMSO accumulated differently in each tissue type, reaching its highest concentration in tumors: 6.18 ± 0.85 µmol/g water, 1.5-fold higher than in control mouse brain (p<0.05). A faster wash-out was detected in normal brain parenchyma with respect to GBM tissue: half-lives of 2.06 ± 0.58 and 4.57 ± 1.15 h, respectively. MRSI maps of time-course DMSO changes revealed clear hotspots of differential spatial accumulation in GL261 tumors. Additional MRSI studies with four mice bearing oligodendrogliomas (ODs) revealed similar results as in GBM tumors. The lack of T(1) contrast enhancement post-gadolinium (gadopentetate dimeglumine, Gd-DTPA) in control mouse brain and mice with ODs suggested that DMSO was fully able to cross the intact blood-brain barrier in both normal brain parenchyma and in low-grade tumors. Our results indicate a potential role for DMSO as a contrast agent for brain tumor detection, even in those tumors 'invisible' to standard gadolinium-enhanced MRI, and possibly for monitoring heterogeneities associated with progression or with therapeutic response.

  14. Brain gadolinium deposition after administration of gadolinium-based contrast agents.

    PubMed

    Kanda, Tomonori; Oba, Hiroshi; Toyoda, Keiko; Kitajima, Kazuhiro; Furui, Shigeru

    2016-01-01

    Gadolinium-based contrast agents (GBCAs) consist of gadolinium ions and a chelating agent that binds the gadolinium ion tightly so that its toxicity is not manifested. However, in 2013, an association between brain MRI abnormalities and a history of GBCA administration was first reported. Even in patients with normal renal function, increased signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted images showed a positive correlation with previous exposure to linear chelate type GBCAs, but not to macrocyclic chelate type ones. This difference of GBCAs is speculated to reflect the stability of GBCAs, and de-chelated gadolinium deposition has been strongly suspected. Using inductively coupled plasma mass spectroscopy, gadolinium was detected from patients' brains with a history of repeated GBCA administration. In some cases, the gadolinium concentration of a patient's brain with normal renal function exceeded the gadolinium concentration of the skin in nephrogenic systemic fibrosis patients, but without any histological change. The actual risk has not been documented yet, but it seems important to consider the potential unknown risks of residual gadolinium in our decisions regarding GBCA administration, and to make efforts to minimize any residual gadolinium in the patient's body.

  15. Octreotide Functionalized Nano-Contrast Agent for Targeted Magnetic Resonance Imaging.

    PubMed

    Jackson, Alexander W; Chandrasekharan, Prashant; Ramasamy, Boominathan; Goggi, Julian; Chuang, Kai-Hsiang; He, Tao; Robins, Edward G

    2016-12-12

    Reversible addition-fragmentation chain transfer (RAFT) polymerization has been employed to synthesize branched block copolymer nanoparticles possessing 1,4,7,10-tetraazacyclododecane-N,N,'N,″N,‴-tetraacetic acid (DO3A) macrocycles within their cores and octreotide (somatostatin mimic) cyclic peptides at their periphery. These polymeric nanoparticles have been chelated with Gd(3+) and applied as magnetic resonance imaging (MRI) nanocontrast agents. This nanoparticle system has an r1 relaxivity of 8.3 mM(-1) s(-1), which is 3 times the r1 of commercial gadolinium-based contrast agents (GBCAs). The in vitro targeted binding efficiency of these nanoparticles shows 5 times greater affinity to somatostatin receptor type 2 (SSTR2) with Ki = 77 pM (compared to somatostatin with Ki = 0.385 nM). We have also evaluated the tumor targeting molecular imaging ability of these branched copolymer nanoparticle in vivo using nude/NCr mice bearing AR42J rat pancreatic tumor (SSTR2 positive) and A549 human lung carcinoma tumor (SSTR2 negative) xenografts.

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

    PubMed

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

    2013-12-23

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

  17. A targeted contrast agent for magnetic resonance imaging of thrombus: implications of spatial resolution.

    PubMed

    Johansson, L O; Bjørnerud, A; Ahlström, H K; Ladd, D L; Fujii, D K

    2001-04-01

    A preparation of ultra-small superparamagnetic iron oxide (USPIO) particles coupled to an RGD peptide (RGD-USPIO) was investigated as an MR contrast agent, targeted to activated platelets, in both ex vivo and in vivo thrombus models. Thrombus visualization ex vivo was compared using RGD-USPIO and a non-targeted UPSIO. The influence of thrombus visualization on thrombus exposure time to RGD-USPIO (ex vivo) and on the spatial resolution of the MR image (ex vivo and in vivo) was assessed. RGD-USPIO resulted in better thrombus visualization than non-targeted USPIO ex vivo, and maximum enhancement was achieved after approximately one hour exposure time of the thrombus to RGD-USPIO. The ability to visualize the clots was highly dependent on the spatial resolution of the image. In vivo, an in-plane resolution of less than 0.2 x 0.2 mm(2) was required for good clot visualization after contrast enhancement. It is concluded that the achievable resolution and sensitivity is a potential limitation to the usefulness of active vascular targeting in MRI.

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

    PubMed

    Braz, Ana K S; de Araujo, Renato E; 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.

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

    NASA Astrophysics Data System (ADS)

    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.

  20. Water-Soluble Spinel Ferrites by a Modified Polyol Process as Contrast Agents in MRI

    SciTech Connect

    Basina, Georgia; Tzitzios, Vasilis; Niarchos, Dimitris; Li Wanfeng; Khurshid, Hafsa; Hadjipanayis, George; Mao Hui; Hadjipanayis, Costas

    2010-12-02

    Magnetic nanoparticles have recently been very attractive for biomedical applications. In this study, we have synthesized ferrite nanoparticles for application as contrast agents in MRI experiments. Fe{sub 3}O{sub 4} and MnFe{sub 2}O{sub 4} spinel ferrites with a mean size of 11-12 nm, were prepared by a modified polyol route in commercially available polyethylene glycol with molecular weight 600 (PEG-600). The reaction takes place in the presence of water soluble and non-toxic tri-block copolymer known as Pluronic registered F-127 (PEO{sub 100}-PPO{sub 65}-PEO{sub 100}). The nanoparticles have saturation magnetization values of 52 and 68 emu/g for MnFe{sub 2}O{sub 4} and Fe{sub 3}O{sub 4}, respectively. Both the Fe{sub 3}O{sub 4}, and MnFe{sub 2}O{sub 4} nanoparticles make stable solutions in water known as ferrofluids. Preliminary data demonstrated the capability of these nanoparticles to induce imaging contrast in T{sub 2} weighted MRI experiments, making these materials suitable for biomedical applications such as medical MRI.

  1. In vitro characterization of an Fe(8) cluster as potential MRI contrast agent.

    PubMed

    Rodríguez, Elisenda; Roig, Anna; Molins, Elies; Arús, Carles; Quintero, María Rosa; Cabañas, Miquel E; Cerdán, Sebastián; Lopez-Larrubia, Pilar; Sanfeliu, Coral

    2005-08-01

    The complex [(tacn)(6)Fe(8)(micro(3)-O)(2)(micro(2)-OH)(12)]Br(8).9H(2)O (Fe(8)) was evaluated in vitro as a new kind of possible MRI contrast agent. Relaxivities were measured at 1.41 and 9.4 T for Fe(8) and commercial Gd-DTPA dissolved in PBS. There was significant difference for r(1) and r(2) values between Fe(8) and Gd-DTPA at high field (9.4 T) and for r(1) at low field (1.4 T) (p<0.05). Phantom studies with T(1)-weighted MRI at 9.4 T suggest T(1) contrast potential for Fe(8). That is, up to 5.2 times higher intensity enhancement with respect to that of equimolar Gd-DTPA was obtained with an Fe(8) concentration, referred to the whole molecule, of 0.2 mM, for which no toxicity on C6 cells could be detected. No toxic effects on cultured C6 cells were observed up to a concentration of 1 mM Fe(8).

  2. Nanobubble-Affibody: Novel ultrasound contrast agents for targeted molecular ultrasound imaging of tumor.

    PubMed

    Yang, Hengli; Cai, Wenbin; Xu, Lei; Lv, Xiuhua; Qiao, Youbei; Li, Pan; Wu, Hong; Yang, Yilin; Zhang, Li; Duan, Yunyou

    2015-01-01

    Nanobubbles (NBs), as novel ultrasound contrast agents (UCAs), have attracted increasing attention in the field of molecular ultrasound imaging for tumors. However, the preparation of uniform-sized NBs is considered to be controversial, and poor tumor selectivity in in vivo imaging has been reported. In this study, we fabricated uniform nano-sized NBs (478.2 ± 29.7 nm with polydispersity index of 0.164 ± 0.044, n = 3) using a thin-film hydration method by controlling the thickness of phospholipid films; we then conjugated the NBs with Affibody molecules to produce nano-sized UCAs referred to as NB-Affibody with specific affinity to human epidermal growth factor receptor type 2 (HER2)-overexpressing tumors. NB-Affibody presented good ultrasound enhancement, demonstrating a peak intensity of 104.5 ± 2.1 dB under ultrasound contrast scanning. Ex vivo experiments further confirmed that the NB-Affibody conjugates were capable of targeting HER2-expressing tumor cells in vivo with high affinity. The newly prepared nano-sized NB-Affibody conjugates were observed to be novel targeted UCAs for efficient and safe specific molecular imaging and may have potential applications in early cancer quantitative diagnosis and targeted therapy in the future.

  3. Hyaluronic acid-functionalized single-walled carbon nanotubes as tumor-targeting MRI contrast agent

    PubMed Central

    Hou, Lin; Zhang, Huijuan; Wang, Yating; Wang, Lili; Yang, Xiaomin; Zhang, Zhenzhong

    2015-01-01

    A tumor-targeting carrier, hyaluronic acid (HA)-functionalized single-walled carbon nanotubes (SWCNTs), was explored to deliver magnetic resonance imaging (MRI) contrast agents (CAs) targeting to the tumor cells specifically. In this system, HA surface modification for SWCNTs was simply accomplished by amidation process and could make this nanomaterial highly hydrophilic. Cellular uptake was performed to evaluate the intracellular transport capabilities of HA-SWCNTs for tumor cells and the uptake rank was HA-SWCNTs> SWCNTs owing to the presence of HA, which was also evidenced by flow cytometry. The safety evaluation of this MRI CAs was investigated in vitro and in vivo. It revealed that HA-SWCNTs could stand as a biocompatible nanocarrier and gadolinium (Gd)/HA-SWCNTs demonstrated almost no toxicity compared with free GdCl3. Moreover, GdCl3 bearing HA-SWCNTs could significantly increase the circulation time for MRI. Finally, to investigate the MRI contrast enhancing capabilities of Gd/HA-SWCNTs, T1-weighted MR images of tumor-bearing mice were acquired. The results suggested Gd/HA-SWCNTs had the highest tumor-targeting efficiency and T1-relaxivity enhancement, indicating HA-SWCNTs could be developed as a tumor-targeting carrier to deliver the CAs, GdCl3, for the identifiable diagnosis of tumor. PMID:26213465

  4. Demeclocycline as a contrast agent for detecting brain neoplasms using confocal microscopy

    NASA Astrophysics Data System (ADS)

    Wirth, Dennis; Smith, Thomas W.; Moser, Richard; Yaroslavsky, Anna N.

    2015-04-01

    Complete resection of brain tumors improves life expectancy and quality. Thus, there is a strong need for high-resolution detection and microscopically controlled removal of brain neoplasms. The goal of this study was to test demeclocycline as a contrast enhancer for the intraoperative detection of brain tumors. We have imaged benign and cancerous brain tumors using multimodal confocal microscopy. The tumors investigated included pituitary adenoma, meningiomas, glioblastomas, and metastatic brain cancers. Freshly excised brain tissues were stained in 0.75 mg ml-1 aqueous solution of demeclocyline. Reflectance images were acquired at 402 nm. Fluorescence signals were excited at 402 nm and registered between 500 and 540 nm. After imaging, histological sections were processed from the imaged specimens and compared to the optical images. Fluorescence images highlighted normal and cancerous brain cells, while reflectance images emphasized the morphology of connective tissue. The optical and histological images were in accordance with each other for all types of tumors investigated. Demeclocyline shows promise as a contrast agent for intraoperative detection of brain tumors.

  5. Anthranilic acid analogs as diamagnetic CEST MRI contrast agents that feature an intramolecular-bond shifted hydrogen.

    PubMed

    Song, Xiaolei; Yang, Xing; Ray Banerjee, Sangeeta; Pomper, Martin G; McMahon, Michael T

    2015-01-01

    Diamagnetic chemical exchange saturation transfer (diaCEST) agents are a new class of imaging agents, which have unique magnetic resonance (MR) properties similar to agents used for optical imaging. Here we present a series of anthranilic acid analogs as examples of diaCEST agents that feature an exchangeable proton shifted downfield, namely, an intramolecular-bond shifted hydrogen (IM-SHY), which produces significant and tunable contrast at frequencies of 4.8-9.3 ppm from water. Five analogs of N-sulfonyl anthranilic acids are all highly soluble and produced similar CEST contrast at ~6-8 ppm. We also discovered that flufenamic acid, a commercial nonsteroidal anti-inflammatory drug, displayed CEST contrast at 4.8 ppm. For these N-H IM-SHY agents, the contrast produced was insensitive to pH, making them complementary to existing diaCEST probes. This initial IM-SHY library includes the largest reported shifts for N-H protons on small organic diaCEST agents, and should find use as multifrequency MR agents for in vivo applications.

  6. High-performance dendritic contrast agents for X-ray computed tomography imaging using potent tetraiodobenzene derivatives.

    PubMed

    You, Suyeon; Jung, Hye-Youn; Lee, Chaewoon; Choe, Yun Hui; Heo, Ju Young; Gang, Gil-Tae; Byun, Sang-Kyung; Kim, Won Kon; Lee, Chul-Ho; Kim, Dong-Eog; Kim, Young Il; Kim, Yoonkyung

    2016-03-28

    The use of computed tomography (CT) for vascular imaging is critical in medical emergencies requiring urgent diagnostic decisions, such as cerebral ischemia and many cardiovascular diseases. Small-molecule iodinated contrast media are often injected intravenously as radiopaque agents during CT imaging to achieve high contrast enhancement of vascular systems. The rapid excretion rate of these agents is overcome by injecting a significantly high dose of iodine, which can have serious side effects. Here we report a simple method to prepare blood-pool contrast agents for CT based on dendrimers for the first time using tetraiodobenzene derivatives as potent radiopaque moieties. Excellent in vivo safety has been demonstrated for these small (13-22nm) unimolecular water-soluble dendritic contrast agents, which exhibit high contrast enhancement in the blood-pool and effectively extend their blood half-lives. Our method is applicable to virtually any scaffold with suitable surface groups and may fulfill the current need for safer, next-generation iodinated CT contrast agents.

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

    NASA Astrophysics Data System (ADS)

    Vairapperumal, Tamilmani; Saraswathy, Ariya; Ramapurath, Jayasree S.; Kalarical Janardhanan, Sreeram; Balachandran Unni, Nair

    2016-10-01

    Tetragonal (t)-LaVO4 has turned out to be a potential host for luminescent materials. Synthesis of t-LaVO4 till date has been based on chelating effect of EDTA making it not ideal for bioimaging applications. An alternative was proposed by us through the use of catechin. In recent times there is interest for new MRI contrast agents that can through appropriate doping function both as MRI contrast and optical/upconversion materials. It is generally believed that under appropriate doping, t-LaVO4 would be a better upconversion material than monoclinic (m)-LaVO4. Based on these postulations, this work explores the use of gadolinium doped t-LaVO4 as an MRI contrast agent. From literature, gadolinium oxide is a good T1 contrast agent. Through this work, using catechin as a template for the synthesis of Gd doped t-LaVO4, we demonstrate the possible use as a T1 contrast agent. Interestingly, as the catechin concentration changes, morphology changes from nanorods to square nanoplates and spheres. In this process, a switch from T1 to T2 contrast agent was also observed. Under optimal concentration of catechin, with a rod shaped Gd doped t-LaVO4 an r2/r1 value of 21.30 was observed. Similarly, with a spherical shape had an r2/r1 value of 1.48 was observed.

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

    PubMed Central

    Vairapperumal, Tamilmani; Saraswathy, Ariya; Ramapurath, Jayasree S.; Kalarical Janardhanan, Sreeram; Balachandran Unni, Nair

    2016-01-01

    Tetragonal (t)-LaVO4 has turned out to be a potential host for luminescent materials. Synthesis of t-LaVO4 till date has been based on chelating effect of EDTA making it not ideal for bioimaging applications. An alternative was proposed by us through the use of catechin. In recent times there is interest for new MRI contrast agents that can through appropriate doping function both as MRI contrast and optical/upconversion materials. It is generally believed that under appropriate doping, t-LaVO4 would be a better upconversion material than monoclinic (m)-LaVO4. Based on these postulations, this work explores the use of gadolinium doped t-LaVO4 as an MRI contrast agent. From literature, gadolinium oxide is a good T1 contrast agent. Through this work, using catechin as a template for the synthesis of Gd doped t-LaVO4, we demonstrate the possible use as a T1 contrast agent. Interestingly, as the catechin concentration changes, morphology changes from nanorods to square nanoplates and spheres. In this process, a switch from T1 to T2 contrast agent was also observed. Under optimal concentration of catechin, with a rod shaped Gd doped t-LaVO4 an r2/r1 value of 21.30 was observed. Similarly, with a spherical shape had an r2/r1 value of 1.48 was observed. PMID:27752038

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

    NASA Astrophysics Data System (ADS)

    Horsfield, Mark A.; Thornton, John S.; Gill, Andrew; Jager, H. Rolf; Priest, Andrew N.; Morgan, Bruno

    2009-05-01

    A functional form for the vascular concentration of MRI contrast agent after intravenous bolus injection was developed that can be used to model the concentration at any vascular site at which contrast concentration can be measured. The form is based on previous models of blood circulation, and is consistent with previously measured data at long post-injection times, when the contrast agent is fully and evenly dispersed in the blood. It allows the first-pass and recirculation peaks of contrast agent to be modelled, and measurement of the absolute concentration of contrast agent at a single time point allows the whole time course to be rescaled to give absolute contrast agent concentration values. This measure of absolute concentration could be performed at a long post-injection time using either MRI or blood-sampling methods. In order to provide a model that is consistent with measured data, it was necessary to include both rapid and slow extravasation, together with excretion via the kidneys. The model was tested on T1-weighted data from the descending aorta and hepatic portal vein, and on T*2-weighted data from the cerebral arteries. Fitting of the model was successful for all datasets, but there was a considerable variation in fit parameters between subjects, which suggests that the formation of a meaningful population-averaged vascular concentration function is precluded.

  10. The nonlinear dynamics of microbubble contrast agents used in medical ultrasound

    NASA Astrophysics Data System (ADS)

    Reddy, Anil J.

    Microbubbles are used as contrast agents in diagnostic ultrasound, and as transport agents or to engender physical effects in therapeutic ultrasound. The distinguishing characteristic of bubbles is their small size, on the order of microns, which allows them to traverse the smallest capillaries in the human body. Furthermore, when subject to acoustic forcing (ultrasound), the oscillations of bubbles become highly nonlinear, leading to a unique echo characteristic. Bubble echo improves the clinician's ability to distinguish between blood carrying contrast agent from the surrounding tissue. Present ultrasound techniques, however, do not take full advantage of the nonlinear properties of oscillating microbubbles. In this work, a novel method to maximize the bubble echo, thereby improving image quality, is suggested. Pulse-inversion imaging is utilized as a means of filtering out the linear echo of surrounding tissue. A norm is defined for the nonlinear bubble echo and it is shown how the norm may be maximized, given a limit on ultrasound intensity, by optimizing the acoustic pulse shape using optimal control theory. The optimization is performed for a single bubble of a particular size. The optimal pulse yields a several-fold increase in the echo norm over conventional pulse driving. It is also shown that the optimal pulse effectively maximizes the echo of a bubble cloud with mean size equal to that of the single bubble. Increased bubble response comes as a result of severe radial collapse, which in turn drives the translation dynamics of the bubble. These motions have been observed by others in experiment, but have, up this point, been inadequately explained. The erratic translation of a bubble is found to be intimately coupled to the radial dynamics, especially in the case of violent oscillations. The assumption of spherical symmetry is relaxed and it is considered how bubble translation can be a mechanism for shape instability, thereby leading to bubble destruction

  11. Biologically-compatible gadolinium(at)(carbon nanostructures) as advanced contrast agents for magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Sitharaman, Balaji

    2005-11-01

    Paramagnetic gadolinium-based carbon nanostructures are introduced as a new paradigm in high-performance magnetic resonance imaging (MRI) contrast agent (CA) design. Two Gd C60-based nanomaterials, Gd C60 [C(COOH)2]10 and Gd C60(OH)x are shown to have MRI efficacies (relaxivities) 5 to 20 times larger than any current Gd3+-based CA in clinical use. The first detailed and systematic physicochemical characterization was performed on these materials using the same experimental techniques usually applied to traditional Gd 3+-based CAs. Water-proton relaxivities were measured for the first time on these materials, as a function of magnetic field (5 x 10-4--9.4 T) to elucidate the different interaction mechanisms and dynamic processes influencing the relaxation behavior. These studies attribute the observed enhanced relaxivities completely to the "outer sphere" proton relaxation mechanism. These "outer sphere" relaxation effects are the largest reported for any Gd3+-based agent without inner-sphere water molecules. The proton relaxivities displayed a remarkable pH-dependency, increasing dramatically with decreasing pH (pH: 3--12). The increase in relaxivity resulted mainly from aggregation and subsequent three-order-of-magnitude increase in tauR, the rotational correlation time. Water-soluble fullerene materials (such as the neuroprotective fullerene drug, C3) readily cross cell membranes, suggesting an application for these gadofullerenes as the first intracellular, as well as pH-responsive MRI CAs. Studies performed at 60 MHz in the presence of phosphate-buffered saline (PBS, mice serum pH: 7.4) to mimic physiological conditions demonstrated that the aggregates can be disrupted by addition of salts, leading to a decrease in relaxivity. Biological fluids present a high salt concentration and should strongly modify the behavior of any fullerenes/metallofullerene-based drug in vivo. Gd C60[C(COOH)2]10 also showed enhanced relaxivity (23% increase) in the presence of the

  12. FDTD modeling of thin impedance sheets

    NASA Technical Reports Server (NTRS)

    Luebbers, Raymond J.; Kunz, Karl S.

    1991-01-01

    Thin sheets of resistive or dielectric material are commonly encountered in radar cross section calculations. Analysis of such sheets is simplified by using sheet impedances. In this paper it is shown that sheet impedances can be modeled easily and accurately using Finite Difference Time Domain (FDTD) methods.

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

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

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

    NASA Astrophysics Data System (ADS)

    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

  16. Ultrasound Molecular Imaging of Tumor Angiogenesis with an Integrin Targeted Microbubble Contrast Agent

    PubMed Central

    Anderson, Christopher R.; Hu, Xiaowen; Tlaxca, Jose; Decleves, Anne-Emilie; Houghtaling, Robert; Sharma, Kumar; Lawrence, Michael; Ferrara, Katherine; Rychak, Joshua J.

    2010-01-01

    Rationale and Objectives Ultrasound molecular imaging is an emerging technique for sensitive detection of intravascular targets. Molecular imaging of angiogenesis has strong potential for both clinical use and as a research tool in tumor biology and the development of anti-angiogenic therapies. Our objective is to develop a robust microbubble (MB) ultrasound contrast agent platform to which targeting ligands can be conjugated by biocompatible, covalent conjugation chemistry, and to develop a pure low mechanical index imaging processing method and corresponding quantifying method. The microbubbles and the imaging methods were evaluated in a mouse model of breast cancer in vivo. Materials and Methods We utilized a cyclic RGD (cRGD) pentapeptide containing a terminal cysteine group conjugated to the surface of MB bearing pyridyldithio-propionate (PDP) for targeting αvβ3 integrins. As negative controls, MB without a ligand or MB bearing a scrambled sequence (cRAD) were prepared. To enable characterization of peptides bound to MB surfaces, the cRGD peptide was labeled with FITC and detected by plate fluorometry, flow cytometry, and fluorescence microscopy. Targeted adhesion of cRGD-MB was demonstrated in an in vitro flow adhesion assay against recombinant murine αvβ3 integrin protein and αvβ3 integrin-expressing endothelial cells (bEnd.3). The specificity of cRGD-MB for αvβ3 integrin was demonstrated by treating bEnd.3 EC with a blocking antibody. A murine model of mammary carcinoma was used to assess targeted adhesion and ultrasound molecular imaging in vivo. The targeted microbubbles were visualized using a low mechanical index contrast imaging pulse sequence, and quantified by intensity normalization and two-dimensional Fourier transform analysis, Results The cRGD ligand concentration on the MB surface was ~8.2 × 106 molecules/MB. At a wall shear stress of 1.0 dynes/cm2, cRGD-MB exhibited 5-fold higher adhesion to immobilized recombinant αvβ3 integrin

  17. Arterial double-contrast dual-energy MDCT: in-vivo rabbit atherosclerosis with iodinated nanoparticles and gadolinium agents

    NASA Astrophysics Data System (ADS)

    Carmi, Raz; Kafri, Galit; Altman, Ami; Goshen, Liran; Planer, David; Sosna, Jacob

    2010-03-01

    An in-vivo feasibility study of potentially improved atherosclerosis CT imaging is presented. By administration of two different contrast agents to rabbits with induced atherosclerotic plaques we aim at identifying both soft plaque and vessel lumen simultaneously. Initial injection of iodinated nanoparticle (INP) contrast agent (N1177 - Nanoscan Imaging), two to four hours before scan, leads to its later accumulation in macrophage-rich soft plaque, while a second gadolinium contrast agent (Magnevist) injected immediately prior to the scan blends with the aortic blood. The distinction between the two agents in a single scan is achieved with a double-layer dual-energy MDCT (Philips Healthcare) following material separation analysis using the reconstructed images of the different x-ray spectra. A single contrast agent injection scan, where only INP was injected two hours prior to the scan, was compared to a double-contrast scan taken four hours after INP injection and immediately after gadolinium injection. On the single contrast agent scan we observed along the aorta walls, localized iodine accumulation which can point on INP uptake by atherosclerotic plaque. In the double-contrast scan the gadolinium contributes a clearer depiction of the vessel lumen in addition to the lasting INP presence. The material separation shows a good correlation to the pathologies inferred from the conventional CT images of the two different scans while performing only a single scan prevents miss-registration problems and reduces radiation dose. These results suggest that a double-contrast dual-energy CT may be used for advanced clinical diagnostic applications.

  18. New oil-in-water magnetic emulsion as contrast agent for in vivo magnetic resonance imaging (MRI).

    PubMed

    Ahmed, Naveed; Jaafar-Maalej, Chiraz; Eissa, Mohamed Mahmoud; Fessi, Hatem; Elaissari, Abdelhamid

    2013-09-01

    Nowadays, bio-imaging techniques are widely applied for the diagnosis of various diseased/tumoral tissues in the body using different contrast agents. Accordingly, the advancement in bionanotechnology research is enhanced in this regard. Among contrast agents used, superparamagnetic iron oxide nanoparticles were developed by many researchers and applied for in vive magnetic resonance imaging (MRI). In this study, a new oil-in-water magnetic emulsion was used as contrast agent in MRI, after being characterized in terms of particle size, iron oxide content, magnetic properties and colloidal stability using dynamic light scattering (DLS), thermal gravimetric analysis (TGA), vibrating sample magnetometer (VSM) and zeta potential measurement techniques, respectively. The hydrodynamic size and magnetic content of the magnetic colloidal particles were found to be 250 nm and 75 wt%, respectively. In addition, the used magnetic emulsion possesses superparamagentic properties and high colloidal stability in aqueous medium. Then, the magnetic emulsion was highly diluted and administered intravenously to the Sprague dawley rats to be tested as contrast agent for in vivo MRI. In this preliminary study, MRI images showed significant enhancement in contrast, especially for T2 (relaxation time) contrast enhancement, indicating the distribution of magnetic colloidal nanoparticles within organs, like liver, spleen and kidneys of the Sprague dawley rats. In addition, it was found that 500 microL of the highly diluted magnetic emulsion (0.05 wt%) was found adequate for MRI analysis. This seems to be useful for further investigations especially in theranostic applications of magnetic emulsion.

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

    NASA Astrophysics Data System (ADS)

    Nakatsuka, Matthew Allan Masao

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

  20. Incorporation of paramagnetic, fluorescent and PET/SPECT contrast agents into liposomes for multimodal imaging

    PubMed Central

    Mitchell, Nick; Kalber, Tammy L.; Cooper, Margaret S.; Sunassee, Kavitha; Chalker, Samantha L.; Shaw, Karen P.; Ordidge, Katherine L.; Badar, Adam; Janes, Samuel M.; Blower, Philip J.; Lythgoe, Mark F.; Hailes, Helen C.; Tabor, Alethea B.

    2013-01-01

    A series of metal-chelating lipid conjugates has been designed and synthesized. Each member of the series bears a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) macrocycle attached to the lipid head group, using short n-ethylene glycol (n-EG) spacers of varying length. Liposomes incorporating these lipids, chelated to Gd3+, 64Cu2+, or 111In3+, and also incorporating fluorescent lipids, have been prepared, and their application in optical, magnetic resonance (MR) and single-photon emission tomography (SPECT) imaging of cellular uptake and distribution investigated in vitro and in vivo. We have shown that these multimodal liposomes can be used as functional MR contrast agents as well as radionuclide tracers for SPECT, and that they can be optimized for each application. When shielded liposomes were formulated incorporating 50% of a lipid with a short n-EG spacer, to give nanoparticles with a shallow but even coverage of n-EG, they showed good cellular internalization in a range of tumour cells, compared to the limited cellular uptake of conventional shielded liposomes formulated with 7% 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethyleneglycol)2000] (DSPE-PEG2000). Moreover, by matching the depth of n-EG coverage to the length of the n-EG spacers of the DOTA lipids, we have shown that similar distributions and blood half lives to DSPE-PEG2000-stabilized liposomes can be achieved. The ability to tune the imaging properties and distribution of these liposomes allows for the future development of a flexible tri-modal imaging agent. PMID:23131536

  1. Probing the Chemical Stability of Mixed Ferrites: Implications for Magnetic Resonance Contrast Agent Design

    SciTech Connect

    Schultz-Sikma, Elise A.; Joshi, Hrushikesh M.; Ma, Qing; MacRenaris, Keith W.; Eckermann, Amanda L.; Dravid, Vinayak P.; Meade, Thomas J.

    2011-09-16

    Nanomaterials with mixed composition, in particular magnetic spinel ferrites, are emerging as efficient contrast agents for magnetic resonance imaging. Many factors, including size, composition, atomic structure, and surface properties, are crucial in the design of such nanoparticle-based probes because of their influence on the magnetic properties. Silica-coated iron oxide (IO-SiO{sub 2}) and cobalt ferrite (CoIO-SiO{sub 2}) nanoparticles were synthesized using standard high-temperature thermal decomposition and base-catalyzed water-in-oil microemulsion techniques. Under neutral aqueous conditions, it was found that 50-75% of the cobalt content in the CoIO-SiO{sub 2} nanoparticles leached out of the core structure. Leaching caused a 7.2-fold increase in the longitudinal relaxivity and an increase in the saturation magnetization from {approx}48 to {approx}65 emu/g of the core. X-ray absorption fine structure studies confirmed that the atomic structure of the ferrite core was altered following leaching, while transmission electron microscopy and dynamic light scattering confirmed that the morphology and size of the nanoparticle remained unchanged. The CoIO-SiO{sub 2} nanoparticles converted from a partially inverted spinel cation arrangement (unleached state) to an inverse spinel arrangement (leached state). The control IO-SiO{sub 2} nanoparticles remained stable with no change in the structure and negligible changes in the magnetic behavior. This detailed analysis highlights how important understanding the properties of nanomaterials is in the development of reliable agents for diagnostic and therapeutic applications.

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

    PubMed

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

    2012-11-01

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

  3. Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Hachani, Roxanne; Lowdell, Mark; Birchall, Martin; Hervault, Aziliz; Mertz, Damien; Begin-Colin, Sylvie; Thanh, Nguy&Ecirtil; N. Thi&Cmb. B. Dot; Kim

    2016-02-01

    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.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

  4. Cerenkov specific contrast agents for detection of pH in vivo

    PubMed Central

    Czupryna, Julie; Kachur, Alexander V.; Blankemeyer, Eric; Popov, Anatoliy V.; Karp, Joel S.; Delikatny, E. James

    2015-01-01

    We report the design, testing and in vivo application of pH sensitive contrast agents designed specifically for Cerenkov imaging. Radioisotopes used for positron emission tomography (PET) emit photons via Cerenkov radiation. The multispectral emission of Cerenkov radiation allows for selective bandwidth quenching, where a band of photons are quenched by absorption by a functional dye. Under acidic conditions, 18F-labeled derivatives emit the full spectrum of Cerenkov light. Under basic conditions, the dyes change color and a wavelength-dependent quenching of Cerenkov emission is observed. METHODS Mono and di-18F-labeled derivatives of phenolsulfonphthalein (phenol red) and meta-cresolsulfonphthalein (cresol purple) were synthesized by electrophilic fluorination. Cerenkov emission was measured at different wavelengths as a function of pH in vitro. Intramolecular response was measured in fluorinated probes; intermolecular quenching by mixing phenolphthalein with 18F FDG. Monofluorocresol purple (MFCP) was tested in mice treated with acetazolamide to cause urinary alkalinization and Cerenkov images compared to PET images. RESULTS Fluorinated pH indicators were produced with radiochemical yields of 4-11% at >90% purity. Selective Cerenkov quenching was observed intramolecularly with difluorophenol red or MFCP, and intermolecularly in phenolphthalein 18F-FDG mixtures. The probes were selectively quenched in the bandwidth closest to the indicator’s absorption maximum (λmax) at pHs above the indicator pKa. Addition of acid or base to the probes resulted in reversible switching from unquenched to quenched emission. In vivo, the bladders of acetazolamide-treated mice exhibited a wavelength-dependent quenching in Cerenkov emission, with the greatest reduction occurring near the λmax. Ratiometric imaging at two wavelengths showed significant decreases in Cerenkov emission at basic pH and allowed the estimation of absolute pH in vivo. CONCLUSIONS We have created contrast

  5. Cancer diagnostics using dynamic near-infrared optical imaging and fluorescent contrast agents

    NASA Astrophysics Data System (ADS)

    Gurfinkel, Mikhail

    2004-12-01

    A new optical imaging modality has been developed for small animal in vivo imaging of near-infrared fluorescence resulting from fluorescent contrast agents specifically targeted to molecular markers of cancer. The imaging system is comprised of an intensified charge-coupled device (ICCD) for the detection of ultra-low levels of re-emitted fluorescence following the delivery of an expanded beam of excitation light. The design of the ICCD detection system allows for both continuous wave (CW) and frequency-domain modes of operation. Since the accurate acquisition of frequency-domain photon migration (FDPM) data is important for tomographic imaging, the imaging system was also validated using experimentally obtained FDPM measurements of homogenous turbid media and diffusion theory to obtain estimates of the optical properties characteristic of the media. The experiments demonstrated that the absorption and reduced scattering coefficients are determined least accurately when relative measurements of average light intensity IrelDC are employed either alone or in a combination with relative modulation amplitude data IrelAC and/or relative phase shift data thetarel. However, when FDPM measurements of thetarel are employed either alone or in combination with IrelAC data, the absorption and reduced scattering coefficients may be found accurate to within 15% and I1%, respectively, of the values obtained from standard single-pixel measurements; a result that suggests that FDPM data obtained from an ICCD detection system may in fact be useful in tomographic imaging. Furthermore, intensified-detection allows for sub-second exposure times, permitting the acquisition of dynamic fluorescence images immediately following administration of the contrast agent. Experimental results demonstrate that when coupled with a suitable pharmacokinetic model describing targeted dye distribution throughout the body, dynamic fluorescence imaging may be used to discriminate spontaneous canine

  6. Magnetic protein microspheres as dynamic contrast agents for magnetomotive optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Nguyen, Freddy T.; Dibbern, Elizabeth M.; Chaney, Eric J.; Oldenburg, Amy L.; Suslick, Kenneth S.; Boppart, Stephen A.

    2008-02-01

    Optical coherence tomography (OCT) is an emerging biomedical imaging modality that has been developed over the last 15 years. More recently, OCT has been used for the intraoperative imaging of tumor margins in breast cancer and axillary lymph nodes providing a real time in-vivo assessment of the tissue morphology. Traditional OCT images are limited by only being able to observe morphological structures. As diagnostic medicine continues to push for earlier detection, one must develop functional imaging modalities that would detect molecular information in-vivo allowing a real-time microscopic analysis of the tissue specimen. A novel modality of OCT called magnetomotive-OCT (MMOCT) has been developed by our group, employing an induced modulated magnetic field with a magnetic contrast agent to create the added contrast to structural OCT images. Modified protein microspheres with a BSA protein shell functionalized with RGD peptide sequences for targeting and an oil core have been designed and synthesized. Magnetic nanoparticles (Fe3O4) and Nile Red dye have been encapsulated into its oil core. These microspheres have previously been demonstrated to target cancer cells by functionalizing them with a layer of RGD peptides and could be functionalized with monoclonal antibodies. Preliminary results show that these magnetic microspheres, which are 2.0- 5.0 microns in size, are readily detectable under MM-OCT when embedded in a 5% agarose gel, in a 3-D scaffold of macrophage cells previously incubated with the microspheres, and when injected in-vivo into a tumor from an NMUcarcinogen rat animal model for breast cancer.

  7. Evaluation of Perfusion Quantification Methods with Ultrasound Contrast Agents in a Machine-Perfused Pig Liver.

    PubMed

    Averkiou, M; Keravnou, C P; Izamis, M L; Leen, E

    2016-05-03

    Purpose: To evaluate dynamic contrast-enhanced ultrasound (DCEUS) as a tool for measuring blood flow in the macro- and microcirculation of an ex-vivo machine-perfused pig liver and to confirm the ability of DCEUS to accurately detect induced flow rate changes so that it could then be used clinically for monitoring flow changes in liver tumors. Materials and Methods: Bolus injections of contrast agents in the hepatic artery (HA) and portal vein (PV) were administered to 3 machine-perfused pig livers. Flow changes were induced by the pump of the machine perfusion system. The induced flow rates were of clinical relevance (150 - 400 ml/min for HA and 400 - 1400 ml/min for PV). Quantification parameters from time-intensity curves [rise time (RT), mean transit time (MTT), area under the curve (AUC) and peak intensity (PI)] were extracted in order to evaluate whether the induced flow changes were reflected in these parameters. Results: A linear relationship between the image intensity and the microbubble concentration was confirmed first, while time parameters (RT and MMT) were found to be independent of concentration. The induced flow changes which propagated from the larger vessels to the parenchyma were reflected in the quantification parameters. Specifically, RT, MTT and AUC correlated with flow rate changes. Conclusion Machine-perfused pig liver is an excellent test bed for DCEUS quantification approaches for the study of the hepatic vascular networks. DCEUS quantification parameters (RT, MTT, and AUC) can measure relative flow changes of about 20 % and above in the liver vasculature. DCEUS quantification is a promising tool for real-time monitoring of the vascular network of tumors.

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

    PubMed

    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

    2014-08-21

    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.

  9. Biocompatible magnetite/gold nanohybrid contrast agents via green chemistry for MRI and CT bioimaging.

    PubMed

    Narayanan, Sreeja; Sathy, Binulal N; Mony, Ullas; Koyakutty, Manzoor; Nair, Shantikumar V; Menon, Deepthy

    2012-01-01

    Magnetite/gold (Fe(3)O(4)/Au) hybrid nanoparticles were synthesized from a single iron precursor (ferric chloride) through a green chemistry route using grape seed proanthocyanidin as the reducing agent. Structural and physicochemical characterization proved the nanohybrid to be crystalline, with spherical morphology and size ~35 nm. Magnetic resonance imaging and magnetization studies revealed that the Fe(3)O(4) component of the hybrid provided superparamagnetism, with dark T(2) contrast and high relaxivity (124.2 ± 3.02 mM(-1) s(-1)). Phantom computed tomographic imaging demonstrated good X-ray contrast, which can be attributed to the presence of the nanogold component in the hybrid. Considering the potential application of this bimodal nanoconstruct for stem cell tracking and imaging, we have conducted compatibility studies on human Mesenchymal Stem Cells (hMSCs), wherein cell viability, apoptosis, and intracellular reactive oxygen species (ROS) generation due to the particle-cell interaction were asessed. It was noted that the material showed good biocompatibility even for high concentrations of 500 μg/mL and up to 48 h incubation, with no apoptotic signals or ROS generation. Cellular uptake of the nanomaterial was visualized using confocal microscopy and prussian blue staining. The presence of the nanohybrids were clearly visualized in the intracytoplasmic region of the cell, which is desirable for efficient imaging of stem cells in addition to the cytocompatible nature of the hybrids. Our work is a good demonstrative example of the use of green aqueous chemistry through the employment of phytochemicals for the room temperature synthesis of complex hybrid nanomaterials with multimodal functionalities.

  10. Nonlinear Imaging of Microbubble Contrast Agent Using the Volterra Filter: In Vivo Results.

    PubMed

    Du, Juan; Liu, Dalong; Ebbini, Emad S

    2016-12-01

    A nonlinear filtering approach to imaging the dynamics of microbubble ultrasound contrast agents (UCAs) in microvessels is presented. The approach is based on the adaptive third-order Volterra filter (TVF), which separates the linear, quadratic, and cubic components from beamformed pulse-echo ultrasound data. The TVF captures polynomial nonlinearities utilizing the full spectral components of the echo data and not from prespecified bands, e.g., second or third harmonics. This allows for imaging using broadband pulse transmission to preserve the axial resolution and the SNR. In this paper, we present the results from imaging the UCA activity in a 200- [Formula: see text] cellulose tube embedded in a tissue-mimicking phantom using a linear array diagnostic probe. The contrast enhancement was quantified by computing the contrast-to-tissue ratio (CTR) for the different imaging components, i.e., B-mode, pulse inversion (PI), and the TVF components. The temporal mean and standard deviation of the CTR values were computed for all frames in a given data set. Quadratic and cubic images, referred to as QB-mode and CB-mode, produced higher mean CTR values than B-mode, which showed improved sensitivity. Compared with PI, they produced similar or higher mean CTR values with greater spatial specificity. We also report in vivo results from imaging UCA activity in an implanted LNCaP tumor with heterogeneous perfusion. The temporal means and standard deviations of the echogenicity were evaluated in small regions with different perfusion levels in the presence and absence of UCA. The in vivo measurements behaved consistently with the corresponding calculations obtained under microflow conditions in vitro. Specifically, the nonlinear VF components produced larger increases in the temporal mean and standard deviation values compared with B-mode in regions with low to relatively high perfusion. These results showed that polynomial filters such as the TVF can provide an important tool

  11. Estrogen Receptor-Targeted Contrast Agents for Molecular Magnetic Resonance Imaging of Breast Cancer Hormonal Status

    PubMed Central

    Pais, Adi; Degani, Hadassa

    2016-01-01

    The estrogen receptor (ER) α is overexpressed in most breast cancers, and its level serves as a major prognostic factor. It is important to develop quantitative molecular imaging methods that specifically detect ER in vivo and assess its function throughout the entire primary breast cancer and in metastatic breast cancer lesions. This study presents the biochemical and molecular features, as well as the magnetic resonance imaging (MRI) effects of two novel ER-targeted contrast agents (CAs), based on pyridine-tetra-acetate-Gd(III) chelate conjugated to 17β-estradiol (EPTA-Gd) or to tamoxifen (TPTA-Gd). The experiments were conducted in solution, in human breast cancer cells, and in severe combined immunodeficient mice implanted with transfected ER-positive and ER-negative MDA-MB-231 human breast cancer xenografts. Binding studies with ER in solution and in human breast cancer cells indicated affinities in the micromolar range of both CAs. Biochemical and molecular studies in breast cancer cell cultures showed that both CAs exhibit estrogen-like agonistic activity, enhancing cell proliferation, as well as upregulating cMyc oncogene and downregulating ER expression levels. The MRI longitudinal relaxivity was significantly augmented by EPTA-Gd in ER-positive cells as compared to ER-negative cells. Dynamic contrast-enhanced studies with EPTA-Gd in vivo indicated specific augmentation of the MRI water signal in the ER-positive versus ER-negative xenografts, confirming EPTA-Gd-specific interaction with ER. In contrast, TPTA-Gd did not show increased enhancement in ER-positive tumors and did not appear to interact in vivo with the tumors’ ER. However, TPTA-Gd was found to interact strongly with muscle tissue, enhancing muscle signal intensity in a mechanism independent of the presence of ER. The specificity of EPTA-Gd interaction with ER in vivo was further verified by acute and chronic competition with tamoxifen. The chronic tamoxifen treatment also revealed that this

  12. Ultrasound contrast agent loaded with nitric oxide as a theranostic microdevice

    PubMed Central

    Grishenkov, Dmitry; Gonon, Adrian; Weitzberg, Eddie; Lundberg, Jon O; Harmark, Johan; Cerroni, Barbara; Paradossi, Gaio; Janerot-Sjoberg, Birgitta

    2015-01-01

    The current study describes novel multifunctional polymer-shelled microbubbles (MBs) loaded with nitric oxide (NO) for integrated therapeutic and diagnostic applications (ie, theranostics) of myocardial ischemia. We used gas-filled MBs with an average diameter of 4 μm stabilized by a biocompatible shell of polyvinyl alcohol. In vitro acoustic tests showed sufficient enhancement of the backscattered power (20 dB) acquired from the MBs’ suspension. The values of attenuation coefficient (0.8 dB/cm MHz) and phase velocities (1,517 m/s) were comparable with those reported for the soft tissue. Moreover, polymer MBs demonstrate increased stability compared with clinically approved contrast agents with a fracture threshold of about 900 kPa. In vitro chemiluminescence measurements demonstrated that dry powder of NO-loaded MBs releases its gas content in about 2 hours following an exponential decay profile with an exponential time constant equal to 36 minutes. The application of high-power ultrasound pulse (mechanical index =1.2) on the MBs resuspended in saline decreases the exponential time constant from 55 to 4 minutes in air-saturated solution and from 17 to 10 minutes in degassed solution. Thus, ultrasound-triggered release of NO is achieved. Cytotoxicity tests indicate that phagocytosis of the MBs by macrophages starts within 6–8 hours. This is a suitable time for initial diagnostics, treatment, and monitoring of the therapeutic effect using a single injection of the proposed multifunctional MBs. PMID:25995614

  13. Physicochemical characterization of ultrasmall superparamagnetic iron oxide particles (USPIO) for biomedical application as MRI contrast agents.

    PubMed

    Di Marco, Mariagrazia; Sadun, Claudia; Port, Marc; Guilbert, Irene; Couvreur, Patrick; Dubernet, Catherine

    2007-01-01

    Ultrasmall superparamagnetic iron oxide (USPIO) particles are maghemite or magnetite nanoparticles currently used as contrast agent in magnetic resonance imaging. The coatings surrounding the USPIO inorganic core play a major role in both the in vitro stability and, over all, USPIO's in vivo fate. Different physicochemical properties such as final size, surface charge and coating density are key factors in this respect. Up to now no precise structure--activity relationship has been described to predict entirely the USPIOs stability, as well as their pharmacokinetics and their safety. This review is focused on both the classical and the latest available techniques allowing a better insight in the magnetic core structure and the organic surface of these particles. Concurrently, this work clearly shows the difficulty to obtain a complete physicochemical characterization of USPIOs particles owing to their small dimensions, reaching the analytical resolution limits of many commercial instruments. An extended characterization is therefore necessary to improve the understanding of the properties of USPIOs when dispersed in an aqueous environment and to set the specifications and limits for their conception.

  14. Erythrocytes and microbubble contrast agents, improve the therapeutic efficiency of high intensity focused ultrasound

    NASA Astrophysics Data System (ADS)

    Takegami, Kenji; Kaneko, Yukio; Watanabe, Toshiaki; Maruyama, Toshiyuki; Matsumoto, Yoichiro; Nagawa, Hirokazu

    2005-03-01

    Erythrocytes, an well as Levovist microbubble contrast agent, enhance the heating effect of high intensity focused ultrasound (HIFU) and increase the coagulation volume produced by HIFU irradiation. In vitro experiments used human plasma with various concentrations of human erythrocytes in combination with or without Levovist. In vivo experiments used eight Japan white rabbits with three levels of anaemia. Using a 2.17 MHz transducer, HIFU was applied for 60 seconds, and the temperature rise and the volume of coagulation necrosis was evaluated. There was a significant correlation between the HIFU-induced temperature rise and hematocrit, with a correlation coefficient of 0.998 (p=0.0001). Although the temperature rise was smaller at low hematocrit, it was significantly increased by adding Levovist to the suspension (p<0.01). The mean volume of coagulation necrosis was significantly higher in the rabbits with higher hematocrit (p<0.01), and that in the moderate anaemia group was significantly increased by using Levovist (p<0.01).

  15. Physicochemical characterization of a novel graphene-based magnetic resonance imaging contrast agent

    PubMed Central

    Kanakia, Shruti; Toussaint, Jimmy D; Chowdhury, Sayan Mullick; Lalwani, Gaurav; Tembulkar, Tanuf; Button, Terry; Shroyer, Kenneth R; Moore, William; Sitharaman, Balaji

    2013-01-01

    We report the synthesis and characterization of a novel carbon nanostructure-based magnetic resonance imaging contrast agent (MRI CA); graphene nanoplatelets intercalated with manganese (Mn2+) ions, functionalized with dextran (GNP-Dex); and the in vitro assessment of its essential preclinical physicochemical properties: osmolality, viscosity, partition coefficient, protein binding, thermostability, histamine release, and relaxivity. The results indicate that, at concentrations between 0.1 and 100.0 mg/mL, the GNP-Dex formulations are hydrophilic, highly soluble, and stable in deionized water, as well as iso-osmolar (upon addition of mannitol) and iso-viscous to blood. At potential steady-state equilibrium concentrations in blood (0.1–10.0 mg/mL), the thermostability, protein-binding, and histamine-release studies indicate that the GNP-Dex formulations are thermally stable (with no Mn2+ ion dissociation), do not allow non-specific protein adsorption, and elicit negligible allergic response. The r1 relaxivity of GNP-Dex was 92 mM−1s−1 (per-Mn2+ ion, 22 MHz proton Larmor frequency); ~20- to 30-fold greater than that of clinical gadolinium (Gd3+)- and Mn2+-based MRI CAs. The results open avenues for preclinical in vivo safety and efficacy studies with GNP-Dex toward its development as a clinical MRI CA. PMID:23946653

  16. Ultrasound contrast agent loaded with nitric oxide as a theranostic microdevice.

    PubMed

    Grishenkov, Dmitry; Gonon, Adrian; Weitzberg, Eddie; Lundberg, Jon O; Harmark, Johan; Cerroni, Barbara; Paradossi, Gaio; Janerot-Sjoberg, Birgitta

    2015-01-01

    The current study describes novel multifunctional polymer-shelled microbubbles (MBs) loaded with nitric oxide (NO) for integrated therapeutic and diagnostic applications (ie, theranostics) of myocardial ischemia. We used gas-filled MBs with an average diameter of 4 μm stabilized by a biocompatible shell of polyvinyl alcohol. In vitro acoustic tests showed sufficient enhancement of the backscattered power (20 dB) acquired from the MBs' suspension. The values of attenuation coefficient (0.8 dB/cm MHz) and phase velocities (1,517 m/s) were comparable with those reported for the soft tissue. Moreover, polymer MBs demonstrate increased stability compared with clinically approved contrast agents with a fracture threshold of about 900 kPa. In vitro chemiluminescence measurements demonstrated that dry powder of NO-loaded MBs releases its gas content in about 2 hours following an exponential decay profile with an exponential time constant equal to 36 minutes. The application of high-power ultrasound pulse (mechanical index =1.2) on the MBs resuspended in saline decreases the exponential time constant from 55 to 4 minutes in air-saturated solution and from 17 to 10 minutes in degassed solution. Thus, ultrasound-triggered release of NO is achieved. Cytotoxicity tests indicate that phagocytosis of the MBs by macrophages starts within 6-8 hours. This is a suitable time for initial diagnostics, treatment, and monitoring of the therapeutic effect using a single injection of the proposed multifunctional MBs.

  17. 1,2-hydroxypyridonates as contrast agents for magnetic resonance imaging: TREN-1,2-HOPO.

    PubMed

    Jocher, Christoph J; Moore, Evan G; Xu, Jide; Avedano, Stefano; Botta, Mauro; Aime, Silvio; Raymond, Kenneth N

    2007-10-29

    1,2-Hydroxypyridinones (1,2-HOPO) form very stable lanthanide complexes that may be useful as contrast agents for magnetic resonance imaging (MRI). X-ray diffraction of single crystals established that the solid-state structures of the Eu(III) and the previously reported [Inorg. Chem. 2004, 43, 5452] Gd(III) complex are identical. The recently discovered sensitizing properties of 1,2-HOPO chelates for Eu(III) luminescence [J. Am. Chem. Soc. 2006, 128, 10 067] allow for direct measurement of the number of water molecules coordinated to the metal center. Fluorescence measurements of the Eu(III) complex corroborate that, in solution, two water molecules coordinate the lanthanide (q = 2) as proposed from the analysis of NMRD profiles. In addition, fluorescence measurements have verified the anion binding interactions of lanthanide TREN-1,2-HOPO complexes in solution, studied by relaxivity, revealing only very weak oxalate binding (KA = 82.7 +/- 6.5 M-1). Solution thermodynamic studies of the metal complex and free ligand have been carried out using potentiometry, spectrophotometry, and fluorescence spectroscopy. The metal ion selectivity of TREN-1,2-HOPO supports the feasibility of using 1,2-HOPO ligands for selective lanthanide binding [pGd = 19.3 (2), pZn = 15.2 (2), pCa = 8.8 (3)].

  18. Aptamer-conjugated Magnetic Nanoparticles as Targeted Magnetic Resonance Imaging Contrast Agent for Breast Cancer

    PubMed Central

    Keshtkar, Mohammad; Shahbazi-Gahrouei, Daryoush; Khoshfetrat, Seyyed Mehdi; Mehrgardi, Masoud A.; Aghaei, Mahmoud

    2016-01-01

    Early detection of breast cancer is the most effective way to improve the survival rate in women. Magnetic resonance imaging (MRI) offers high spatial resolution and good anatomic details, and its lower sensitivity can be improved by using targeted molecular imaging. In this study, AS1411 aptamer was conjugated to Fe3O4@Au nanoparticles for specific targeting of mouse mammary carcinoma (4T1) cells that overexpress nucleolin. In vitro cytotoxicity of aptamer-conjugated nanoparticles was assessed on 4T1 and HFFF-PI6 (control) cells. The ability of the synthesized nanoprobe to target specifically the nucleolin overexpressed cells was assessed with the MRI technique. Results show that the synthesized nanoprobe produced strongly darkened T2-weighted magnetic resonance (MR) images with 4T1 cells, whereas the MR images of HFFF-PI6 cells incubated with the nanoprobe are brighter, showing small changes compared to water. The results demonstrate that in a Fe concentration of 45 μg/mL, the nanoprobe reduced by 90% MR image intensity in 4T1 cells compared with the 27% reduction in HFFF-PI6 cells. Analysis of MR signal intensity showed statistically significant signal intensity difference between 4T1 and HFFF-PI6 cells treated with the nanoprobe. MRI experiments demonstrate the high potential of the synthesized nanoprobe as a specific MRI contrast agent for detection of nucleolin-expressing breast cancer cells. PMID:28028501

  19. Oral manganese as an MRI contrast agent for the detection of nociceptive activity.

    PubMed

    Jacobs, Kathleen E; Behera, Deepak; Rosenberg, Jarrett; Gold, Garry; Moseley, Michael; Yeomans, David; Biswal, Sandip

    2012-04-01

    The ability of divalent manganese to enter neurons via calcium channels makes manganese an excellent MRI contrast agent for the imaging of nociception, the afferent neuronal encoding of pain perception. There is growing evidence that nociceptive neurons possess increased expression and activity of calcium channels, which would allow for the selective accumulation of manganese at these sites. In this study, we show that oral manganese chloride leads to increased enhancement of peripheral nerves involved in nociception on T(1)-weighted MRI. Oral rather than intravenous administration was chosen for its potentially better safety profile, making it a better candidate for clinical translation with important applications, such as pain diagnosis, therapy and research. The spared nerve injury (SNI) model of neuropathic pain was used for the purposes of this study. SNI rats were given, sequentially, increasing amounts of manganese chloride (lowest, 2.29 mg/100 g weight; highest, 20.6 mg/100 g weight) with alanine and vitamin D(3) by oral gavage. Compared with controls, SNI rats demonstrated increased signal-to-background ratios on T(1)-weighted fast spin echo MRI, which was confirmed by and correlated strongly with spectrometry measurements of nerve manganese concentration. We also found the difference between SNI and control rats to be greater at 48 h than at 24 h after dosing, indicating increased manganese retention in addition to increased manganese uptake in nociceptive nerves. This study demonstrates that oral manganese is a viable method for the imaging of nerves associated with increased nociceptive activity.

  20. Sonophoresis using ultrasound contrast agents for transdermal drug delivery: an in vivo experimental study.

    PubMed

    Park, Donghee; Ryu, Heungil; Kim, Han Sung; Kim, Young-Sun; Choi, Kyu-Sil; Park, Hyunjin; Seo, Jongbum

    2012-04-01

    Sonophoresis temporally increases skin permeability such that various medications can be delivered noninvasively. Previous sonophoresis studies have suggested that cavitation plays an important role in enhancing transdermal drug delivery (TDD). In this study, the feasibility of controlled cavitation using ultrasound contrast agents (UCAs) at high frequency was explored through in vivo experiments in a rat model. Two commercially available UCAs, SonoVue® and Definity®, were used at 2.47 MHz and 1.12 MHz, respectively. Fluorescein isothiocyanate (FITC)-dextran with 0.1% UCA was used as the drug to be delivered through the skin. Ultrasound with a 10 ms pulse and a 1% duty cycle at 1 MPa acoustic pressure for 30 min was applied in all sonication sessions. The efficacy of sonophoresis with UCAs was quantitatively analyzed using an optical imaging system that was used to count photons emitted from fluorescein. The results showed that the proposed sonophoresis method significantly improved drug penetration compared with the traditional sonophoresis method with 4 kD, 20 kD and 150 kD FITC-dextrans at 1.12 MHz, and with 4 kD and 20 kD FITC-dextrans at 2.47 MHz. Sonophoresis for TDD was performed more effectively with the aid of UCAs. Sonophoresis with UCAs has excellent potential for broad applications in drug delivery for diseases requiring the chronic administration of medications such as diabetes.

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

    PubMed

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

    2015-07-01

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

  2. Evaluation of different small bowel contrast agents by multi - detector row CT

    PubMed Central

    Wang, Yong-Ren; Yu, Xiao-Li; Peng, Zhi-Yi

    2015-01-01

    Objective: This study aims to evaluate the effects of different oral small bowel contrast agents towards the intestinal dilatation and intestinal wall structure exhibition by the abdominal multi - detector row CT (MDCT) examination. Methods: 80 patients were performed the whole abdominal CT examination, then randomly divided into four groups, with 20 patients in each group. 45 minutes before the CT examination, the patients were served with a total of 1800 ml pure water, pure milk, dilute lactulose solution and isotonic mannitol solution, respectively. Results: The images were blinded read by two experienced abdominal radiologists in the workstation, the cross-sectional diameters of duodenum, jejunum, proximal and terminal ends of ileum of each patient were measured, then the analysis of variance was performed to analyze the differences in the intestinal dilatation among the experimental groups. The scoring method was used to score the intestinal dilatation and intestinal structure exhibition. The diluted lactulose solution and 2.5% mannitol exhibited the best intestinal dilation degrees. Similarly, the diluted lactulose solution and 2.5% mannitol exhibited the highest scores in the entire small bowel dilatation degree and intestinal structure exhibition. Conclusions: 2.5% osmotic mannitol and the diluted lactulose solution enabled the full dilatation of small bowel, and could clearly exhibit the wall structure. PMID:26629131

  3. Measurement of absolute arterial cerebral blood volume in human brain without using a contrast agent.

    PubMed

    Hua, Jun; Qin, Qin; Pekar, James J; van Zijl, Peter C M

    2011-12-01

    Arterial cerebral blood volume (CBV(a) ) is a vital indicator of tissue perfusion and vascular reactivity. We extended the recently developed inflow vascular-space-occupancy (iVASO) MRI technique, which uses spatially selective inversion to suppress the signal from blood flowing into a slice, with a control scan to measure absolute CBV(a) using cerebrospinal fluid (CSF) for signal normalization. Images were acquired at multiple blood nulling times to account for the heterogeneity of arterial transit times across the brain, from which both CBV(a) and arterial transit times were quantified. Arteriolar CBV(a) was determined separately by incorporating velocity-dependent bipolar crusher gradients. Gray matter (GM) CBV(a) values (n=11) were 2.04 ± 0.27 and 0.76 ± 0.17 ml blood/100 ml tissue without and with crusher gradients (b=1.8 s/mm(2) ), respectively. Arterial transit times were 671 ± 43 and 785 ± 69 ms, respectively. The arterial origin of the signal was validated by measuring its T(2) , which was within the arterial range. The proposed approach does not require exogenous contrast agent administration, and provides a non-invasive alternative to existing blood volume techniques for mapping absolute CBV(a) in studies of brain physiology and neurovascular diseases.

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

    PubMed

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

    2015-02-01

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

  5. A model for the dynamics of ultrasound contrast agents in vivo

    PubMed Central

    Qin, Shengping; Ferrara, Katherine W.

    2010-01-01

    The Rayleigh-Plesset (RP) equation for a clean gas bubble in an incompressible and infinite liquid has previously been applied to approximately simulate the behavior of ultrasound contrast agents (UCA) in vivo, and extended RP equations have been proposed to account for the effects of the UCA shell or surrounding soft tissue. These models produce results that are consistent with experimental measurements for low acoustic pressure scenarios. For applications of UCAs in therapeutic medicine, the transmitted acoustic pulse can have a peak negative pressure (PNP) up to a few megapascals, resulting in discrepancies between measurements and predictions using these extended RP equations. Here, a model was developed to describe the dynamics of UCAs in vivo while taking account of the effects of liquid compressibility, the shell and the surrounding tissue. Liquid compressibility is approximated to first order and the shell is treated either as a Voigt viscoelastic solid or a Newtonian viscous liquid. Finite deformation of the shell and tissue is derived. Dynamics of UCAs with a shell of lipid, polymer, albumin and liquid are investigated for typical therapeutic ultrasound pulses. The effects of liquid compressibility and shell and tissue parameters are analyzed. PMID:20815486

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

    PubMed

    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.

  7. DECAFLUOROBUTANE AS A PHASE-CHANGE CONTRAST AGENT FOR LOW-ENERGY EXTRAVASCULAR ULTRASONIC IMAGING

    PubMed Central

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

    2015-01-01

    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. (E-mail: padayton@bme.unc.edu) PMID:21775049

  8. Efficient, Non-Iterative Estimator for Imaging Contrast Agents With Spectral X-Ray Detectors.

    PubMed

    Alvarez, Robert E

    2016-04-01

    An estimator to image contrast agents and body materials with x-ray spectral measurements is described. The estimator is usable with the three or more basis functions that are required to represent the attenuation coefficient of high atomic number materials. The estimator variance is equal to the Cramèr-Rao lower bound (CRLB) and it is unbiased. Its parameters are computed from measurements of a calibration phantom with the clinical x-ray system and it is non-iterative. The estimator is compared with an iterative maximum likelihood estimator. The estimator first computes a linearized maximum likelihood estimate of the line integrals of the basis set coefficients. Corrections for errors in the initial estimates are computed by interpolation with calibration phantom data. The final estimate is the initial estimate plus the correction. The performance of the estimator is measured using a Monte Carlo simulation. Random photon counting with pulse height analysis data are generated. The mean squared errors of the estimates are compared to the CRLB. The random data are also processed with an iterative maximum likelihood estimator. Previous implementations of iterative estimators required advanced physics instruments not usually available in clinical institutions. The estimator mean squared error is essentially equal to the CRLB. The estimator outputs are close to those of the iterative estimator but the computation time is approximately 180 times shorter. The estimator is efficient and has advantages over alternate approaches such as iterative estimators.

  9. In vivo detection of cucurbit[6]uril, a hyperpolarized xenon contrast agent for a xenon magnetic resonance imaging biosensor

    NASA Astrophysics Data System (ADS)

    Hane, Francis T.; Li, Tao; Smylie, Peter; Pellizzari, Raiili M.; Plata, Jennifer A.; Deboef, Brenton; Albert, Mitchell S.

    2017-01-01

    The Hyperpolarized gas Chemical Exchange Saturation Transfer (HyperCEST) Magnetic Resonance (MR) technique has the potential to increase the sensitivity of a hyperpolarized xenon-129 MRI contrast agent. Signal enhancement is accomplished by selectively depolarizing the xenon within a cage molecule which, upon exchange, reduces the signal in the dissolved phase pool. Herein we demonstrate the in vivo detection of the cucurbit[6]uril (CB6) contrast agent within the vasculature of a living rat. Our work may be used as a stepping stone towards using the HyperCEST technique as a molecular imaging modality.

  10. In vivo detection of cucurbit[6]uril, a hyperpolarized xenon contrast agent for a xenon magnetic resonance imaging biosensor

    PubMed Central

    Hane, Francis T.; Li, Tao; Smylie, Peter; Pellizzari, Raiili M.; Plata, Jennifer A.; DeBoef, Brenton; Albert, Mitchell S.

    2017-01-01

    The Hyperpolarized gas Chemical Exchange Saturation Transfer (HyperCEST) Magnetic Resonance (MR) technique has the potential to increase the sensitivity of a hyperpolarized xenon-129 MRI contrast agent. Signal enhancement is accomplished by selectively depolarizing the xenon within a cage molecule which, upon exchange, reduces the signal in the dissolved phase pool. Herein we demonstrate the in vivo detection of the cucurbit[6]uril (CB6) contrast agent within the vasculature of a living rat. Our work may be used as a stepping stone towards using the HyperCEST technique as a molecular imaging modality. PMID:28106110

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

    NASA Astrophysics Data System (ADS)

    Chiriac, L. B.; Trandafir, D. L.; Turcu, R. V. F.; Todea, M.; Simon, S.

    2016-11-01

    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, 29Si 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-T1 and RARE-T2 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 T2-weighted MRI contrast properties.

  12. Methylene blue microbubbles as a model dual-modality contrast agent for ultrasound and activatable photoacoustic imaging.

    PubMed

    Jeon, Mansik; Song, Wentao; Huynh, Elizabeth; Kim, Jungho; Kim, Jeesu; Helfield, Brandon L; Leung, Ben Y C; Goertz, David E; Zheng, Gang; Oh, Jungtaek; Lovell, Jonathan F; Kim, Chulhong

    2014-01-01

    Ultrasound and photoacoustic imaging are highly complementary modalities since both use ultrasonic detection for operation. Increasingly, photoacoustic and ultrasound have been integrated in terms of hardware instrumentation. To generate a broadly accessible dual-modality contrast agent, we generated microbubbles (a standard ultrasound contrast agent) in a solution of methylene blue (a standard photoacoustic dye). This MB2 solution was formed effectively and was optimized as a dual-modality contrast solution. As microbubble concentration increased (with methylene blue concentration constant), photoacoustic signal was attenuated in the MB2 solution. When methylene blue concentration increased (with microbubble concentration held constant), no ultrasonic interference was observed. Using an MB2 solution that strongly attenuated all photoacoustic signal, high powered ultrasound could be used to burst the microbubbles and dramatically enhance photoacoustic contrast (>800-fold increase), providing a new method for spatiotemporal control of photoacoustic signal generation.

  13. Methylene blue microbubbles as a model dual-modality contrast agent for ultrasound and activatable photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Jeon, Mansik; Song, Wentao; Huynh, Elizabeth; Kim, Jungho; Kim, Jeesu; Helfield, Brandon L.; Leung, Ben Y. C.; Goertz, David E.; Zheng, Gang; Oh, Jungtaek; Lovell, Jonathan F.; Kim, Chulhong

    2014-01-01

    Ultrasound and photoacoustic imaging are highly complementary modalities since both use ultrasonic detection for operation. Increasingly, photoacoustic and ultrasound have been integrated in terms of hardware instrumentation. To generate a broadly accessible dual-modality contrast agent, we generated microbubbles (a standard ultrasound contrast agent) in a solution of methylene blue (a standard photoacoustic dye). This MB2 solution was formed effectively and was optimized as a dual-modality contrast solution. As microbubble concentration increased (with methylene blue concentration constant), photoacoustic signal was attenuated in the MB2 solution. When methylene blue concentration increased (with microbubble concentration held constant), no ultrasonic interference was observed. Using an MB2 solution that strongly attenuated all photoacoustic signal, high powered ultrasound could be used to burst the microbubbles and dramatically enhance photoacoustic contrast (>800-fold increase), providing a new method for spatiotemporal control of photoacoustic signal generation.

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

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

    PubMed

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

    2014-11-07

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

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

    PubMed Central

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

    2014-01-01

    Here we present a new optical contrast agent, based on silver nanoplate clusters embedded inside a polymer nano matrix. Unlike nanosphere clusters, which have been well studied, nanoplate clusters have unique properties due to the different possible orientations of interaction between the individual plates, resulting in a significant broadening of the absorption spectra. These nanoclusters were immobilized inside a polymer cladding, so as to maintain their stability and optical properties under in vivo conditions. The polymer coated silver nanoplate clusters show a lower toxicity, compared to the uncoated nanoparticles. At high nanoparticle concentrations, cell death occurs mostly due to apoptosis. These nanoparticles were used for targeted fluorescence imaging in a rat glioma cell line by incorporating a fluorescent dye into the matrix, followed by conjugation of a tumor targeting F3 peptide. We further used these nanoparticles as photoacoustic contrast agents in vivo, to enhance the contrast of the vasculature structures in a rat ear model. We observed a contrast enhancement of over 90%, following nanoparticle injection. It is also shown that these NP’s can serve as efficient contrast agents, with specific targeting abilities, for broadband multimodal imaging, usable for diagnostic applications and extendable into use as therapeutic agents as well. PMID:25325364

  17. Evaluation of Tumor Micro-Environment in an Animal Model using a Nanoparticle Contrast Agent in Computed Tomography Imaging

    PubMed Central

    Ghaghada, Ketan B.; Badea, Cristian T.; Karumbaiah, Lohitash; Fettig, Nicole; Bellamkonda, Ravi V.; Johnson, G A; Annapragada, Ananth

    2010-01-01

    RATIONALE AND OBJECTIVES Non-invasive longitudinal imaging of tumor vasculature could provide new insights into the development of solid tumors, facilitating efficient delivery of therapeutics. In this study, we report three-dimensional imaging and characterization of tumor vascular architecture using a nanoparticle contrast agent and high-resolution computed tomography (CT) imaging. MATERIALS AND METHODS Five Balb/c mice implanted with 4T1/Luc syngeneic breast tumors cells were used for the study. The nanoparticle contrast agent was systemically administered and longitudinal CT imaging was performed pre-contrast and at serial time-points post-contrast, for up to 7 days for studying the characteristics of tumor-associated blood vessels. Gene-expression of tumor angiogenic biomarkers was measured using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS Early-phase imaging demonstrated the presence of co-opted and newly developed tumor vessels. The co-opted vessels demonstrated wall-permeability and ‘leakiness’ characteristics evident by an increase in extra-vascular nanoparticle-based signal enhancement visible well beyond the margins of tumor. Diameters of tumor-associated vessels were larger than the contra-lateral normal vessels. Delayed-phase imaging also demonstrated significant accumulation of nanoparticle contrast agent both within and in areas surrounding the tumor. A heterogeneous pattern of signal enhancement was observed both within and among individual tumors. Gene-expression profiling demonstrated significant variability in several angiogenic biomarkers both within and among individual tumors. CONCLUSIONS The nanoparticle contrast agent and high-resolution CT imaging facilitated visualization of co-opted and newly developed tumors vessels as well as imaging of nanoparticle accumulation within tumors. The use of this agent could provide novel insights into tumor vascular biology and could have implications on the monitoring of tumor

  18. Crucial Roles of Systemic and Tissue Lipid Peroxidation Levels and Anti-Oxidant Defences Following Contrast Agent Application

    PubMed Central

    Sitar, Gungor; Kucuk, Mehmet; Erinc Sitar, Mustafa; Yasar, Ozgur; Aydin, Seval; Yanar, Karolin; Cakatay, Ufuk; Buyukpınarbasili, Nur

    2016-01-01

    Background One of the most important side effects of contrast pharmaceutical agents, which are used very common in routine radiology practice, is contrast induced nephropathy. Even ischemia, oxidative stress and osmolality related cytotoxic effects are considered, the molecular mechanisms underlying this pathology have not been identified completely yet. Objectives The aim of the current study was to reveal the role of oxidative stress and antioxidant enzymatic defence mechanisms in the aetiopathogenesis of contrast-induced nephropathy. We also studied possible alleviating effects of N-acetylcysteine (NAC), a potent antioxidant, to obtain extra information regarding the molecular mechanisms underlying this pathology. Materials and Methods This is an clinical-experimental study, This study was conducted of Istanbul/Turkey between September 15, 2012 and April 15, 2013. Three groups of male rats were randomly set up as a control group (C), a 100 mg/kg intraperitoneal NAC + 7 mL/kg contrast agent group (N + CIN) and a 7 mL/kg intraperitoneal contrast agent group (CIN). They were placed in individual metabolic cages 48 hours after agent administration to obtain 24-hour urine samples. Renal function tests (albumin, urea, creatinine, total protein) were conducted, oxidative stress parameters (Cu, Zn superoxide dismutase activity - Cu, Zn-SOD; advanced oxidation protein products - AOPP; protein carbonyls - PCO; total thiol groups - T-SH; and lipid hydroperoxides -LHP) were measured and tissues were analysed histopathologically. Results Compared with the control group, groups CIN and N + CIN had significantly higher urea and LHP levels (P < 0.05 and P < 0.001, respectively) and significantly lower Cu, Zn-SOD activity and creatinine clearance (P < 0.05). There was no statistically significant difference between the groups in PCO or AOPP levels despite differences in descriptive statistics. Conclusions Contrast-agent-induced nephropathic changes are more closely related to

  19. FDTD analysis of the light extraction efficiency of OLEDs with a random scattering layer.

    PubMed

    Kim, Jun-Whee; Jang, Ji-Hyang; Oh, Min-Cheol; Shin, Jin-Wook; Cho, Doo-Hee; Moon, Jae-Hyun; Lee, Jeong-Ik

    2014-01-13

    The light extraction efficiency of OLEDs with a nano-sized random scattering layer (RSL-OLEDs) was analyzed using the Finite Difference Time Domain (FDTD) method. In contrast to periodic diffraction patterns, the presence of an RSL suppresses the spectral shift with respect to the viewing angle. For FDTD simulation of RSL-OLEDs, a planar light source with a certain spatial and temporal coherence was incorporated, and the light extraction efficiency with respect to the fill factor of the RSL and the absorption coefficient of the material was investigated. The design results were compared to the experimental results of the RSL-OLEDs in order to confirm the usefulness of FDTD in predicting experimental results. According to our FDTD simulations, the light confined within the ITO-organic waveguide was quickly absorbed, and the absorption coefficients of ITO and RSL materials should be reduced in order to obtain significant improvement in the external quantum efficiency (EQE). When the extinction coefficient of ITO was 0.01, the EQE in the RSL-OLED was simulated to be enhanced by a factor of 1.8.

  20. Estimation of contrast agent bolus arrival delays for improved reproducibility of liver DCE MRI

    NASA Astrophysics Data System (ADS)

    Chouhan, Manil D.; Bainbridge, Alan; Atkinson, David; Punwani, Shonit; Mookerjee, Rajeshwar P.; Lythgoe, Mark F.; Taylor, Stuart A.

    2016-10-01

    Delays between contrast agent (CA) arrival at the site of vascular input function (VIF) sampling and the tissue of interest affect dynamic contrast enhanced (DCE) MRI pharmacokinetic modelling. We investigate effects of altering VIF CA bolus arrival delays on liver DCE MRI perfusion parameters, propose an alternative approach to estimating delays and evaluate reproducibility. Thirteen healthy volunteers (28.7  ±  1.9 years, seven males) underwent liver DCE MRI using dual-input single compartment modelling, with reproducibility (n  =  9) measured at 7 days. Effects of VIF CA bolus arrival delays were assessed for arterial and portal venous input functions. Delays were pre-estimated using linear regression, with restricted free modelling around the pre-estimated delay. Perfusion parameters and 7 days reproducibility were compared using this method, freely modelled delays and no delays using one-way ANOVA. Reproducibility was assessed using Bland-Altman analysis of agreement. Maximum percent change relative to parameters obtained using zero delays, were  -31% for portal venous (PV) perfusion, +43% for total liver blood flow (TLBF), +3247% for hepatic arterial (HA) fraction, +150% for mean transit time and  -10% for distribution volume. Differences were demonstrated between the 3 methods for PV perfusion (p  =  0.0085) and HA fraction (p  <  0.0001), but not other parameters. Improved mean differences and Bland-Altman 95% Limits-of-Agreement for reproducibility of PV perfusion (9.3 ml/min/100 g, ±506.1 ml/min/100 g) and TLBF (43.8 ml/min/100 g, ±586.7 ml/min/100 g) were demonstrated using pre-estimated delays with constrained free modelling. CA bolus arrival delays cause profound differences in liver DCE MRI quantification. Pre-estimation of delays with constrained free modelling improved 7 days reproducibility of perfusion parameters in volunteers.

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

    PubMed Central

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

    2013-01-01

    Gadolinium chelates, which are currently approved for clinical MRI use, provide relaxivities well below their theoretical limit, and they also lack tissue specificity. Recently, the geometrical confinement of Gd3+-based contrast agents (CAs) within porous structures has been proposed as a novel, alternative strategy to improve relaxivity without chemical modification of the CA. Here, we have characterized and optimized the performance of MRI nanoconstructs obtained by loading [Gd(DTPA)(H2O)]2− (Magnevist®) into the pores of injectable mesoporous silicon particles. Nanoconstructs with three different pore sizes were studied, and at 60 MHz, they exhibited longitudinal relaxivities of ~ 24 mM−1s−1 for 5 – 10 nm pores and ~ 10 mM−1s−1 for 30 – 40 nm pores. No enhancement in relaxivity was observed for larger pores sizes. Using an outer-sphere compound, [GdTTHA]−3, and mathematical modeling, it was demonstrated that the relaxivity enhancement is due to the increase in rotational correlation times (CA adsorbed on the pore walls) and diffusion correlation times (reduced mobility of the water molecules), as the pore sizes decreases. It was also observed that extensive CA adsorption on the outer surface of the silicon particles negates the advantages offered by nanoscale confinement. Upon incubation with HeLa cells, the nanoconstructs did not demonstrate significant cytotoxicity for up to 3 days post incubation, at different particle/cell ratios. In addition, the nanoconstructs showed complete degradation after 24h of continuous agitation in PBS. These data support and confirm the hypothesis that the geometrical confinement of Gd3+-chelate compounds into porous structures offers MRI nanoconstructs with enhanced relaxivity (up to 6 times for [Gd(DTPA)(H2O)]2−, and 4 times for [GdTTHA]−3) and, potentially, improved stability, reduced toxicity and tissue specificity. PMID:22991316

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

    PubMed

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

    2013-08-01

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

  3. Relationship between cavitation and loss of echogenicity from ultrasound contrast agents.

    PubMed

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

    2013-09-21

    Ultrasound contrast agents (UCAs) have the potential to nucleate cavitation and promote both beneficial and deleterious bioeffects in vivo. Previous studies have elucidated the pulse-duration-dependent pressure amplitude threshold for rapid loss of echogenicity due to UCA fragmentation. Previous studies have demonstrated that UCA fragmentation was concomitant with inertial cavitation. The purpose of this study was to evaluate the relationship between stable and inertial cavitation thresholds and loss of echogenicity of UCAs as a function of pulse duration. Determining the relationship between cavitation thresholds and loss of echogenicity of UCAs would enable monitoring of cavitation based upon the onscreen echogenicity in clinical applications. Two lipid-shelled UCAs, echogenic liposomes (ELIP) and Definity®, were insonified by a clinical ultrasound scanner in duplex spectral Doppler mode at four pulse durations ('sample volumes') in both a static system and a flow system. Cavitation emissions from the UCAs insonified by Doppler pulses were recorded using a passive cavitation detection system and stable and inertial cavitation thresholds ascertained. Loss of echogenicity from ELIP and Definity® was assessed within regions of interest on B-mode images. A numerical model based on UCA rupture predicted the functional form of the loss of echogenicity from ELIP and Definity®. Stable and inertial cavitation thresholds were found to have a weak dependence on pulse duration. Stable cavitation thresholds were lower than inertial cavitation thresholds. The power of cavitation emissions was an exponential function of the loss of echogenicity over the investigated range of acoustic pressures. Both ELIP and Definity® lost more than 80% echogenicity before the onset of stable or inertial cavitation. Once this level of echogenicity loss occurred, both stable and inertial cavitation were detected in the physiologic flow phantom. These results imply that stable and inertial

  4. Dual-energy subtraction imaging utilizing indium as a contrast agent

    SciTech Connect

    Le Duc, G.; Zhong, Z.; Warkentien, L.; Laster, B.; Thomlinson, W.

    1997-10-01

    The purpose of our current work is to establish the minimum detection, of indium contrast agent using dual-energy subtraction imaging above and below indium K-edge. Experiments were performed on the X12 and X17B2 beamlines at the National Synchrotron Light Source using the same method but with two different set-ups. Experiments were first carried out on InCl{sub 3} solutions, then on V79 Chinese hamster cells and on BALB/c mice excised tumors, labeled with indium. For each experiment, several layers of Lucite were placed in front of the phantom to ensure a 43 mm thickness, dose to that of a mammography examination. Results were the same on X12 and X17B2. As expected, indium-free materials disappeared on subtracted images (water, steel reference and screw). Indium samples were easily distinguishable for the following concentrations: 10-5-2-1 mg/cm{sup 2}. Smaller concentrations were not clearly distinguishable and we were unable to see cell samples and tumors. To conclude, the lowest concentration we can image is around 1 mg/cm{sup 2}. These results agree with theoretical results. Such results also suggest that indium concentration in both cells and tumors is lower than 0.5 mg/cm{sup 2}. Since the current detection is dose to optimum, we conclude that dual energy subtraction imaging using indium to label tumors cells and tumors is not possible unless the indium uptake is increased by more than an order of magnitude.

  5. Multifunctional rare-Earth vanadate nanoparticles: luminescent labels, oxidant sensors, and MRI contrast agents.

    PubMed

    Abdesselem, Mouna; Schoeffel, Markus; Maurin, Isabelle; Ramodiharilafy, Rivo; Autret, Gwennhael; Clément, Olivier; Tharaux, Pierre-Louis; Boilot, Jean-Pierre; Gacoin, Thierry; Bouzigues, Cedric; Alexandrou, Antigoni

    2014-11-25

    Collecting information on multiple pathophysiological parameters is essential for understanding complex pathologies, especially given the large interindividual variability. We report here multifunctional nanoparticles which are luminescent probes, oxidant sensors, and contrast agents in magnetic resonance imaging (MRI). Eu(3+) ions in an yttrium vanadate matrix have been demonstrated to emit strong, nonblinking, and stable luminescence. Time- and space-resolved optical oxidant detection is feasible after reversible photoreduction of Eu(3+) to Eu(2+) and reoxidation by oxidants, such as H2O2, leading to a modulation of the luminescence emission. The incorporation of paramagnetic Gd(3+) confers in addition proton relaxation enhancing properties to the system. We synthesized and characterized nanoparticles of either 5 or 30 nm diameter with compositions of GdVO4 and Gd0.6Eu0.4VO4. These particles retain the luminescence and oxidant detection properties of YVO4:Eu. Moreover, the proton relaxivity of GdVO4 and Gd0.6Eu0.4VO4 nanoparticles of 5 nm diameter is higher than that of the commercial Gd(3+) chelate compound Dotarem at 20 MHz. Nuclear magnetic resonance dispersion spectroscopy showed a relaxivity increase above 10 MHz. Complexometric titration indicated that rare-earth leaching is negligible. The 5 nm nanoparticles injected in mice were observed with MRI to concentrate in the liver and the bladder after 30 min. Thus, these multifunctional rare-earth vanadate nanoparticles pave the way for simultaneous optical and magnetic resonance detection, in particular, for in vivo localization evolution and reactive oxygen species detection in a broad range of physiological and pathophysiological conditions.

  6. Enhanced Thermal Ablation by Combining Ultrasound Contrast Agents with a Miniature Flat Transducer

    NASA Astrophysics Data System (ADS)

    Murillo, A.; Goldendstedt, C.; Lafon, C.; Cathignol, D.; Chapelon, J.-Y.

    2007-05-01

    Miniature transducers can be used for performing interstitial thermal ablation. Increasing the frequency of non-focused transducers enhances energy deposition but limits the therapeutic range. In order to treat extended tumors, new therapeutic strategies must be explored. This work aimed to combine ultrasound contrast agents (UCA) with flat transducers for increasing the treatment depth. The idea consists in increasing attenuation away from the transducer to favor remote heat deposition. Thermal ablation is induced in three steps. 1- Attenuation raises by injecting UCA; 2- Destruction of bubbles next to the transducer by pulsed high intensity bursts, results in a gradient of attenuation; 3- Continuous ultrasound are applied for generating a localized thermal lesion. In vitro tests were performed on temperature-sensitive tissue phantoms in which the UCA BR14 (Bracco) was injected during the liquid phase. The feasibility of the idea was demonstrated in three stages. 1- The coefficient of attenuation was measured with the force balance as a function of the concentration of BR14. For 0.8 and 4.8% attenuation at 10MHz was found to be 0.35 and 1.33 Np/cm respectively. 2- Pulsed ultrasound was applied on phantoms to destroy UCA. Based on the echogenicity decay evidenced on ultrasound images, a 1MPa-pressure was required at 10MHz. 3- Heating beams were applied on phantoms presenting a gradient in attenuation. Lesions were 1.5 times larger than in phantoms with constant attenuation. This study demonstrates that UCA can be selectively destroyed in order to generate a gradient of attenuation and extended thermal lesions.

  7. Quantitative ultrasound molecular imaging by modeling the binding kinetics of targeted contrast agent

    NASA Astrophysics Data System (ADS)

    Turco, Simona; Tardy, Isabelle; Frinking, Peter; Wijkstra, Hessel; Mischi, Massimo

    2017-03-01

    Ultrasound molecular imaging (USMI) is an emerging technique to monitor diseases at the molecular level by the use of novel targeted ultrasound contrast agents (tUCA). These consist of microbubbles functionalized with targeting ligands with high-affinity for molecular markers of specific disease processes, such as cancer-related angiogenesis. Among the molecular markers of angiogenesis, the vascular endothelial growth factor receptor 2 (VEGFR2) is recognized to play a major role. In response, the clinical-grade tUCA BR55 was recently developed, consisting of VEGFR2-targeting microbubbles which can flow through the entire circulation and accumulate where VEGFR2 is over-expressed, thus causing selective enhancement in areas of active angiogenesis. Discrimination between bound and free microbubbles is crucial to assess cancer angiogenesis. Currently, this is done non-quantitatively by looking at the late enhancement, about 10 min after injection, or by calculation of the differential targeted enhancement, requiring the application of a high-pressure ultrasound (US) burst to destroy all the microbubbles in the acoustic field and isolate the signal coming only from bound microbubbles. In this work, we propose a novel method based on mathematical modeling of the binding kinetics during the tUCA first pass, thus reducing the acquisition time and with no need for a destructive US burst. Fitting time-intensity curves measured with USMI by the proposed model enables the assessment of cancer angiogenesis at both the vascular and molecular levels. This is achieved by estimation of quantitative parameters related to the microvascular architecture and microbubble binding. The proposed method was tested in 11 prostate-tumor bearing rats by performing USMI after injection of BR55, and showed good agreement with current USMI methods. The novel information provided by the proposed method, possibly combined with the current non-quantitative methods, may bring deeper insight into

  8. Iodixanol as a Contrast Agent in a Fibrin Hydrogel for Endodontic Applications

    PubMed Central

    Hertig, Gabriel; Zehnder, Matthias; Woloszyk, Anna; Mitsiadis, Thimios A.; Ivica, Anja; Weber, Franz E.

    2017-01-01

    The application of biomaterials used in regenerative endodontics should be traceable. In this study, we checked some basic effects of rendering a fibrin hydrogel radiopaque using an iodine-based contrast agent (iodixanol) approved for systemic application. Fibrin hydrogels were prepared from a fibrin sealant (Tisseel) using either an isotonic iodixanol solution (Visipaque 320, test) or Tris buffer (control) as a diluent. Gelation kinetics, radiopacity, and swelling of lyophilized hydrogels were tested using standard methods. Hydrogel structure was evaluated using scanning electron microscopy (SEM). Furthermore, iodixanol release from the test gels was assessed using spectrophotometry, and tissue compatibility was compared between test and control hydrogels using the chick chorioallantoic membrane (CAM) assay. Results were compared using pairwise t-test, p < 0.05. Iodixanol caused a 70-fold delay in gelation to 26 min in the test compared to the control hydrogels (22 ± 1 s). Radiopacity of the test gels was 1.9 ± 0.2 mm Al/mm, compared to zero in the control hydrogels. Lyophilized hydrogel swelling was strongly reduced when iodixanol was added to the hydrogel (p < 0.05). Test hydrogels had an altered SEM appearance compared to controls, and exhibited a reduced porosity. Iodixanol release from the test hydrogels reached 14.5 ± 0.5% after 120 h and then ceased. This release did not have any apparent toxic effect and neither affected the viability, nor the physiology or vascularization of the CAM of fertilized chicken eggs. Iodixanol can render a fibrin hydrogel radiopaque and maintains its tissue compatibility, yet impacts gelation kinetics and hydrogel porosity. PMID:28360862

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

    PubMed

    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 < 0.05) and 80.77 ± 6.60% (p < 0.01) in the UCA subharmonic frequency and subharmonic imaging, respectively. However, corresponding resolutions were 0.78 ± 0.07 (p < 0.05) and 0.72 ± 0.12 (p < 0.01) times those without guided 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.

  10. New functional handle for use as a self-reporting contrast and delivery agent in nanomedicine.

    PubMed

    Robin, Mathew P; Mabire, Anne B; Damborsky, Joanne C; Thom, Elizabeth S; Winzer-Serhan, Ursula H; Raymond, Jeffery E; O'Reilly, Rachel K

    2013-06-26

    The synthesis and photophysical characterization of a chromophore-bridged block copolymer system is presented. This system is based on a dithiomaleimide (DTM) functional group as a highly emissive functionality which can readily be incorporated into polymeric scaffolds. A key advantage of this new reporter group is its versatile chemistry, ease of further functionalization, and notably small size, which allows for ready incorporation without affecting or disrupting the self-assembly process critical to the formation of core-shell polymeric contrast and drug delivery agents. We demonstrate the potential of this functionality with a diblock system which has been shown to be appropriate for micellization and, when in the micellar state, does not self-quench. The block copolymer is shown to be significantly more emissive than the lone dye, with a concentration-independent emission and anisotropy profile from 1.5 mM to 0.15 μM. An emission lifetime and anisotropy decay comparison of the block copolymer to its micelle displays that time-domain fluorescence lifetime imaging (FLIM) is able to rapidly resolve differences in the supramolecular state of this block-dye-block polymer system. Furthermore, the ability to resolve these differences in the supramolecular state means that the DTM micelles are capable of self-reporting when disassembly occurs, simply by monitoring with FLIM. We demonstrate the great potential for in vitro applications that this system provides by using FLIM to observe micelle disassembly in different vascular components of rat hippocampal tissue. In total this system represents a new class of in-chain emitter which is appropriate for application in quantitative imaging and the tracking of particle degradation/disassembly events in biological environments.

  11. Nonspherical dynamics and shape mode stability of ultrasound contrast agent microbubbles

    NASA Astrophysics Data System (ADS)

    Calvisi, Michael

    2016-11-01

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

  12. Investigations on the destruction of ultrasound contrast agents: Fragmentation thresholds, inertial cavitation, and bioeffects

    NASA Astrophysics Data System (ADS)

    Chen, Wen-Shiang

    Ultrasound contrast agents (UCA) have shown great potential in both diagnostic and therapeutic applications recently. To fully explore the possible applications and the safety concerns of using UCA, a complete understanding of the UCA responses to various acoustic fields is necessary. Therefore, we performed a series of experiments and simulations to investigate the various acoustic properties of UCA with different gases and shells. We also investigated the mechanisms of some UCA-enhanced bioeffects including thrombolysis, hemolysis and high-intensity focused ultrasound (HIFU) tumor ablation. Two pressure thresholds were found: the fragmentation threshold and continuous inertial cavitation (IC) threshold. At the fragmentation threshold, bubbles were destroyed and the released gas dissolved in the surrounding solution at a rate which depended on the bubble's initial size and type of gas. The continuous IC threshold occurred at a higher pressure, where fragments of destroyed UCA (derivative bubbles) underwent violent inertial collapse; the period of activity depending on acoustic parameters such as frequency, pressure, pulse length, and pulse repetition frequency (PRF). Different UCA had different threshold pressures and demonstrated different magnitudes of IC activity after destruction. The amount of derivative bubbles generated by IC was determined by several acoustic parameters including pressure, pulse length and PRE For the same acoustic energy delivered, longer pulses generated more bubbles. More IC could be induced if the derivative bubbles could survive through the 'off' period of the pulsed ultrasound waves, and served as nuclei for the subsequent IC. In therapeutic applications, evidences of IC activity were recorded during the hemolysis, thrombolysis, and the lesion-formation processes with UCA. Hemolysis and thrombolysis were highly correlated to the presence of ultrasound and UCA, and correlated well with the amount of the IC activity. Finally, the

  13. Micro-Computed Tomography of Fatigue Microdamage in Cortical Bone Using a Barium Sulfate Contrast Agent

    PubMed Central

    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 (BaSO4) 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 BaSO4 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 BaSO4, 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. PMID:18443659

  14. A neutral polydisulfide containing Gd(III) DOTA monoamide as a redox-sensitive biodegradable macromolecular MRI contrast agent.

    PubMed

    Ye, Zhen; Zhou, Zhuxian; Ayat, Nadia; Wu, Xueming; Jin, Erlei; Shi, Xiaoyue; Lu, Zheng-Rong

    2016-01-01

    This work aims to develop safe and effective gadolinium (III)-based biodegradable macromolecular MRI contrast agents for blood pool and cancer imaging. A neutral polydisulfide containing macrocyclic Gd-DOTA monoamide (GOLS) was synthesized and characterized. In addition to studying the in vitro degradation of GOLS, its kinetic stability was also investigated in an in vivo model. The efficacy of GOLS for contrast-enhanced MRI was examined with female BALB/c mice bearing 4T1 breast cancer xenografts. The pharmacokinetics, biodistribution, and metabolism of GOLS were also determined in mice. GOLS has an apparent molecular weight of 23.0 kDa with T1 relaxivities of 7.20 mM(-1) s(-1) per Gd at 1.5 T, and 6.62 mM(-1) s(-1) at 7.0 T. GOLS had high kinetic inertness against transmetallation with Zn(2+) ions, and its polymer backbone was readily cleaved by L-cysteine. The agent showed improved efficacy for blood pool and tumor MR imaging. The structural effect on biodistribution and in vivo chelation stability was assessed by comparing GOLS with Gd(HP-DO3A), a negatively charged polydisulfide containing Gd-DOTA monoamide GODC, and a polydisulfide containing Gd-DTPA-bisamide (GDCC). GOLS showed high in vivo chelation stability and minimal tissue deposition of gadolinium. The biodegradable macromolecular contrast agent GOLS is a promising polymeric contrast agent for clinical MR cardiovascular imaging and cancer imaging.

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

    PubMed

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

    2016-04-01

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

  16. Dual-modal MRI contrast agent with aggregation-induced emission characteristic for liver specific imaging with long circulation lifetime.

    PubMed

    Chen, Yilong; Li, Min; Hong, Yuning; Lam, Jacky W Y; Zheng, Qichang; Tang, Ben Zhong

    2014-07-09

    We herein report a novel dual-modal MRI contrast agent, TPE-2Gd, for both magnetic and fluorescence imaging. TPE-2Gd consists of a hydrophobic tetraphenylethene (TPE) fluorophore and two hydrophilic gadolinium (Gd) diethylenetriaminepentaacetic acid moieties. As an amphiphilic molecule, TPE-2Gd aggregates into micelles at a high concentration in aqueous medium. These aggregates are highly emissive, showing an aggregation-induced emission (AIE) characteristic. TPE-2Gd is used as a fluorescent agent for cell imaging, which demonstrates negligible cytotoxicity and excellent photostability owing to its AIE property. As a magnetic resonance imaging (MRI) contrast agent, TPE-2Gd exhibits similar longitudinal relaxivity in water (R1,TPE-2Gd = 3.36 ± 0.10 s(-1) per mM of Gd(3+)) as those commercial agents (e.g., Magnevist, R1,magnevist = 3.70 ± 0.02 s(-1) per mM of Gd(3+)). Compared with Magnevist, the circulation lifetime of TPE-2Gd nanoaggregates in living rats is extended from 10 min to 1 h. With relatively high specificity to the liver, the MR imaging could remain hyperintense in liver even after 150 min post injection. These TPE-2Gd nanoparticles can be excreted gradually via renal filtration due to the disassembly of the nanoparticles into small molecules during circulation. TPE-2Gd could thus potentially be used as a liver specific MRI contrast agent for clinical diagnosis.

  17. Delivery of optical contrast agents using Triton-X100, part 1: reversible permeabilization of live cells for intracellular labeling

    NASA Astrophysics Data System (ADS)

    van de Ven, Anne L.; Adler-Storthz, Karen; Richards-Kortum, Rebecca

    2009-03-01

    Effective delivery of optical contrast agents into live cells remains a significant challenge. We sought to determine whether Triton-X100, a detergent commonly used for membrane isolation and protein purification, could be used to effectively and reversibly permeabilize live cells for delivery of targeted optical contrast agents. Although Triton-X100 is widely recognized as a good cell permeabilization agent, no systematic study has evaluated the efficiency, reproducibility, and reversibility of Triton-X100-mediated permeabilization in live mammalian cells. We report a series of studies to characterize macromolecule delivery in cells following Triton-X100 treatment. Using this approach, we demonstrate that molecules ranging from 1 to 150 kDa in molecular weight can be reproducibly delivered into live cells by controlling the moles of Triton-X100 relative to the number of cells to be treated. When Triton-X100 is administered at or near the minimum effective concentration, cell permeabilization is generally reversed within 24 h, and treated cells continue to proliferate and show metabolic activity during the restoration of membrane integrity. We conclude that Triton-X100 is a promising permeabilization agent for efficient and reproducible delivery of optical contrast agents into live mammalian cells.

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

    PubMed Central

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

    2009-01-01

    A general theoretical approach to the development of zero-thickness encapsulation models for contrast microbubbles is proposed. The approach describes a procedure that allows one to recast available rheological laws from the bulk form to a surface form which is used in a modified Rayleigh-Plesset equation governing the radial dynamics of a contrast microbubble. By the use of the proposed procedure, the testing of different rheological laws for encapsulation can be carried out. Challenges of existing shell models for lipid-encapsulated microbubbles, such as the dependence of shell parameters on the initial bubble radius and the “compression-only” behavior, are discussed. Analysis of the rheological behavior of lipid encapsulation is made by using experimental radius-time curves for lipid-coated microbubbles with radii in the range 1.2 – 2.5 μm. The curves were acquired for a research phospholipid-coated contrast agent insonified with a 20-cycle, 3.0 MHz, 100 kPa acoustic pulse. The fitting of the experimental data by a model which treats the shell as a viscoelastic solid gives the values of the shell surface viscosity increasing from 0.30×10-8 kg/s to 2.63×10-8 kg/s for the range of bubble radii indicated above. The shell surface elastic modulus increases from 0.054 N/m to 0.37 N/m. It is proposed that this increase may be a result of the lipid coating possessing the properties of both a shear-thinning and a strain-softening material. We hypothesize that these complicated rheological properties do not allow the existing shell models to satisfactorily describe the dynamics of lipid encapsulation. In the existing shell models, the viscous and the elastic shell terms have the linear form which assumes that the viscous and the elastic stresses acting inside the lipid shell are proportional to the shell shear rate and the shell strain, respectively, with constant coefficients of proportionality. The analysis performed in the present paper suggests that a more

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

    PubMed

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

    2009-02-01

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

  20. ADE-FDTD Scattered-Field Formulation for Dispersive Materials.

    PubMed

    Kong, Soon-Cheol; Simpson, Jamesina J; Backman, Vadim

    2008-01-01

    This Letter presents a scattered-field formulation for modeling dispersive media using the finite-difference time-domain (FDTD) method. Specifically, the auxiliary differential equation method is applied to Drude and Lorentz media for a scattered field FDTD model. The present technique can also be applied in a straightforward manner to Debye media. Excellent agreement is achieved between the FDTD-calculated and exact theoretical results for the reflection coefficient in half-space problems.

  1. Quantum dots targeted to vascular endothelial growth factor receptor 2 as a contrast agent for the detection of colorectal cancer

    NASA Astrophysics Data System (ADS)

    Carbary-Ganz, Jordan L.; Barton, Jennifer K.; Utzinger, Urs

    2014-08-01

    We successfully labeled colorectal cancer in vivo using quantum dots targeted to vascular endothelial growth factor receptor 2 (VEGFR2). Quantum dots with emission centered at 655 nm were bioconjugated to anti-VEGFR2 antibodies through streptavidin/biotin linking. The resulting QD655-VEGFR2 contrast agent was appli