Stability analysis of ultrasound thick-shell contrast agents.

PubMed

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. © 2012 Acoustical Society of America.

In vitro and ex vivo evaluation of silica-coated super paramagnetic iron oxide nanoparticles (SPION) as biomedical photoacoustic contrast agent

NASA Astrophysics Data System (ADS)

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

2013-03-01

The employment of contrast agents in photoacoustic imaging has gained significant attention within the past few years for their biomedical applications. In this study, the use of silica-coated superparamagnetic iron oxide (Fe3O4) nanoparticles (SPION) was investigated as a contrast agent in biomedical photoacoustic imaging. SPIONs have been widely used as Food-and-Drug-Administration (FDA)-approved contrast agents for magnetic resonance imaging (MRI) and are known to have an excellent safety profile. Using our frequency-domain photoacoustic correlation technique ("the photoacoustic radar") with modulated laser excitation, we examined the effects of nanoparticle size, concentration and biological medium (e.g. serum, sheep blood) on its photoacoustic response in turbid media (intralipid solution). Maximum detection depth and minimum measurable SPION concentration were determined experimentally. The detection was performed using a single element transducer. The nanoparticle-induced optical contrast ex vivo in dense muscular tissues (avian pectus) was evaluated using a phased array photoacoustic probe and the strong potential of silicacoated SPION as a possible photoacoustic contrast agent was demonstrated. This study opens the way for future clinical applications of nanoparticle-enhanced photoacoustic imaging in cancer therapy.

A smart magnetic resonance imaging contrast agent responsive to adenosine based on a DNA aptamer-conjugated gadolinium complex.

PubMed

Xu, Weichen; Lu, Yi

2011-05-07

We report a general strategy for developing a smart MRI contrast agent for the sensing of small molecules such as adenosine based on a DNA aptamer that is conjugated to a Gd compound and a protein streptavidin. The binding of adenosine to its aptamer results in the dissociation of the Gd compound from the large protein, leading to decreases in the rotational correlation time and thus change of MRI contrast. © The Royal Society of Chemistry 2011

Screening and Monitoring Response to Treatment Using Subsecond Molecular Imaging and Hyperpolarized Contrast Agents

DTIC Science & Technology

2013-05-01

Magnetization transfer MRI in multiple sclerosis . J Neuroimaging. 2007;17 Suppl 1:S22–S26. 82. Filippi M, Rocca MA. Magnetization transfer magnetic resonance... multiple sclerosis . Neuroimaging Clin N Am. 2009;19(1):27–36. 84. Lundbom N. Determination of magnetization transfer contrast in tissue: an MR... multiple RF coils intended for optimal direct and indirect detection of hyperpolarized contrast agents in vivo. 4.b. Y1Q3-Y1Q4. Low field MRI: pre

Nano-sized Contrast Agents to Non-Invasively Detect Renal Inflammation by Magnetic Resonance Imaging

PubMed Central

Thurman, Joshua M.; Serkova, Natalie J.

2013-01-01

Several molecular imaging methods have been developed that employ nano-sized contrast agents to detect markers of inflammation within tissues. Renal inflammation contributes to disease progression in a wide range of autoimmune and inflammatory diseases, and a biopsy is currently the only method of definitively diagnosing active renal inflammation. However, the development of new molecular imaging methods that employ contrast agents capable of detecting particular immune cells or protein biomarkers will allow clinicians to evaluate inflammation throughout the kidneys, and to assess a patient's response to immunomodulatory drugs. These imaging tools will improve our ability to validate new therapies and to optimize the treatment of individual patients with existing therapies. This review describes the clinical need for new methods of monitoring renal inflammation, and recent advances in the development of nano-sized contrast agents for detection of inflammatory markers of renal disease. PMID:24206601

Advantages of paramagnetic CEST complexes having slow-to-intermediate water exchange properties as responsive MRI agents

PubMed Central

Soesbe, Todd C.; Wu, Yunkou; Sherry, A. Dean

2012-01-01

Paramagnetic saturation transfer chemical exchange (PARACEST) complexes are exogenous contrast agents that have great potential to further extend the functional and molecular imaging capabilities of magnetic resonance. Due to the presence of a central paramagnetic lanthanide ion (Ln3+ ≠ La3+, Gd3+, Lu3+) within the chelate, the resonance frequencies of protons and water molecules bound to the PARACEST agent are shifted far away from the bulk water frequency. This large chemical shift combined with an extreme sensitivity to the chemical exchange rate make PARACEST agents ideally suited for reporting significant biological metrics such as temperature, pH, and the presence of metabolites. Also, the ability to turn PARACEST agents “off” and “on” using a frequency selective saturation pulse gives them a distinct advantage over Gd3+-based contrast agents. A current challenge for PARACEST research is translating the promising in vitro results into in vivo systems. This short review article first describes the basic theory behind PARACEST contrast agents, their benefits over other contrast agents, and their applications to magnetic resonance imaging. It then describes some of the recent PARACEST research results. Specifically, pH measurements using water molecule exchange rate modulation, T2-exchange contrast due to water molecule exchange, the use of ultra-short echo times (TE<10 μs) to overcome T2-exchange line-broadening, and the potential application of T2-exchange as a new contrast mechanism for magnetic resonance imaging. PMID:23055299

Smart Contrast Agents for Magnetic Resonance Imaging.

PubMed

Bonnet, Célia S; Tóth, Éva

2016-01-01

By visualizing bioactive molecules or biological parameters in vivo, molecular imaging is searching for information at the molecular level in living organisms. In addition to contributing to earlier and more personalized diagnosis in medicine, it also helps understand and rationalize the molecular factors underlying physiological and pathological processes. In magnetic resonance imaging (MRI), complexes of paramagnetic metal ions, mostly lanthanides, are commonly used to enhance the intrinsic image contrast. They rely either on the relaxation effect of these metal chelates (T(1) agents), or on the phenomenon of paramagnetic chemical exchange saturation transfer (PARACEST agents). In both cases, responsive molecular magnetic resonance imaging probes can be designed to report on various biomarkers of biological interest. In this context, we review recent work in the literature and from our group on responsive T(1) and PARACEST MRI agents for the detection of biogenic metal ions (such as calcium or zinc), enzymatic activities, or neurotransmitter release. These examples illustrate the general strategies that can be applied to create molecular imaging agents with an MRI detectable response to biologically relevant parameters.

Subharmonic Imaging and Pressure Estimation for Monitoring Neoadjuvant Chemotherapy

DTIC Science & Technology

2015-11-01

ultrasound contrast agents to improve the monitoring of breast cancer treatment response to neoadjuvant therapies in women diagnosed with LABC by imaging...estimation (SHAPE). Software for analyzing RF data from a Logiq 9 ultrasound scanner (GE Healthcare, Milwauke, WI) to produce 3D SHAPE pressure...responders; albeit not statistically significant (p > 0.19). 14. SUBJECT TERMS Breast Cancer, Ultrasound Imaging, Ultrasound Contrast Agent, Pressure

Acoustic fingerprints of photoacoustic contrast agents for molecular imaging

NASA Astrophysics Data System (ADS)

McDonald, Michael A.; Jankovic, Ladislav; Shahzad, Khalid; Burcher, Michael; Li, King C. P.

2007-02-01

Protein nanospheres capable of frequency controlled oscillation in response to laser stimulation are presented as contrast agents for photoacoustic imaging. Incident laser energy absorbed by dye-labeled protein nanospheres causes thermoelastically generated sound production. Plotted A-line graphs reveal a distinctive morphology and greater than 2 orders of magnitude increase in signal amplitude subsequent to converting labeled proteins into nanospheres. Evidence of nonlinearity and enhancement of ultrasound backscatter indicate a potential use in contrast-enhanced harmonic imaging. Photoacoustic and ultrasound imaging of protein nanospheres in phantom vessels show enhanced contrast at low concentration and clear delineation of the phantom vessel wall.

Redox-activated MRI contrast agents based on lanthanide and transition metal ions.

PubMed

Tsitovich, Pavel B; Burns, Patrick J; McKay, Adam M; Morrow, Janet R

2014-04-01

The reduction/oxidation (redox) potential of tissue is tightly regulated in order to maintain normal physiological processes, but is disrupted in disease states. Thus, the development of new tools to map tissue redox potential may be clinically important for the diagnosis of diseases that lead to redox imbalances. One promising area of chemical research is the development of redox-activated probes for mapping tissue through magnetic resonance imaging (MRI). In this review, we summarize several strategies for the design of redox-responsive MRI contrast agents. Our emphasis is on both lanthanide(III) and transition metal(II/III) ion complexes that provide contrast either as T1 relaxivity MRI contrast agents or as paramagnetic chemical exchange saturation transfer (PARACEST) contrast agents. These agents are redox-triggered by a variety of chemical reactions or switches including redox-activated thiol groups, and heterocyclic groups that interact with the metal ion or influence properties of other ancillary ligands. Metal ion centered redox is an approach which is ripe for development by coordination chemists. Redox-triggered metal ion approaches have great potential for creating large differences in magnetic properties that lead to changes in contrast. An attractive feature of these agents is the ease of fine-tuning the metal ion redox potential over a biologically relevant range. Copyright © 2014 Elsevier Inc. All rights reserved.

Stimuli-disassembling gold nanoclusters for diagnosis of early stage oral cancer by optical coherence tomography

NASA Astrophysics Data System (ADS)

Kim, Chang Soo; Ingato, Dominique; Wilder-Smith, Petra; Chen, Zhongping; Kwon, Young Jik

2018-01-01

A key design consideration in developing contrast agents is obtaining distinct, multiple signal changes in diseased tissue. Plasmonic gold nanoparticles (Au NPs) have been developed as contrast agents due to their strong surface plasmon resonance (SPR). This study aims to demonstrate that stimuli-responsive plasmonic Au nanoclusters (Au NCs) can be used as a contrast agent for optical coherence tomography (OCT) in detecting early-stage cancer. Au NPs were clustered via acid-cleavable linkers to synthesize Au NCs that disassemble under mildly acidic conditions into individual Au NPs, simultaneously diminishing SPR effect (quantified by scattering intensity) and increasing Brownian motion (quantified by Doppler variance). The acid-triggered morphological and accompanying optico-physical property changes of the acid-disassembling Au NCs were confirmed by TEM, DLS, UV/Vis, and OCT. Stimuli-responsive Au NCs were applied in a hamster check pouch model carrying early-stage squamous carcinoma tissue. The tissue was visualized by OCT imaging, which showed reduced scattering intensity and increased Doppler variance in the dysplastic tissue. This study demonstrates the promise of diagnosing early-stage cancer using molecularly programmable, inorganic nanomaterial-based contrast agents that are capable of generating multiple, stimuli-triggered diagnostic signals in early-stage cancer.[Figure not available: see fulltext.

Advantages of paramagnetic chemical exchange saturation transfer (CEST) complexes having slow to intermediate water exchange properties as responsive MRI agents.

PubMed

Soesbe, Todd C; Wu, Yunkou; Dean Sherry, A

2013-07-01

Paramagnetic chemical exchange saturation transfer (PARACEST) complexes are exogenous contrast agents that have great potential to further extend the functional and molecular imaging capabilities of magnetic resonance. As a result of the presence of a central paramagnetic lanthanide ion (Ln(3+) ≠ La(3+) , Gd(3+) , Lu(3+) ) within the chelate, the resonance frequencies of exchangeable protons bound to the PARACEST agent are shifted far away from the bulk water frequency. This large chemical shift, combined with an extreme sensitivity to the chemical exchange rate, make PARACEST agents ideally suited for the reporting of significant biological metrics, such as temperature, pH and the presence of metabolites. In addition, the ability to turn PARACEST agents 'off' and 'on' using a frequency-selective saturation pulse gives them a distinct advantage over Gd(3+) -based contrast agents. A current challenge for PARACEST research is the translation of the promising in vitro results into in vivo systems. This short review article first describes the basic theory behind PARACEST contrast agents, their benefits over other contrast agents and their applications to MRI. It then describes some of the recent PARACEST research results: specifically, pH measurements using water molecule exchange rate modulation, T2 exchange contrast caused by water molecule exchange, the use of ultrashort TEs (TE < 10 µs) to overcome T2 exchange line broadening and the potential application of T2 exchange as a new contrast mechanism for MRI. Copyright © 2012 John Wiley & Sons, Ltd.

Comparison of the nonionic contrast agents, iopromide and iotrolan, for positive-contrast arthrography of the scapulohumeral joint in dogs.

PubMed

van Bree, H; Van Rijssen, B; Tshamala, M; Maenhout, T

1992-09-01

Arthrographic quality and synovial inflammatory response were examined to compare the use of iopromide with that of iotrolan for arthrography of the scapulohumeral joint in 6 dogs. Radiographs obtained 1 and 3 minutes after injection of either nonionic compound were of similar quality, but radiographs obtained 5 minutes after injection of iotrolan were significantly (P less than 0.05) better than those obtained after injection of iopromide. Results of analysis of synovial fluid samples obtained at 1, 3, 7, and 14 days after injection of contrast media were not significantly different between the 2 groups. Histologic examination of synovium and articular cartilage 2 weeks after injection of iopromide or iotrolan revealed minimal inflammatory response for both contrast agents. Injection of iopromide and iotrolan into the scapulohumeral joints of dogs had less effect on synovial fluid than that reported after injection of ionic compounds.

Preclinical evaluation of biodegradable macromolecular contrast agents for magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Feng, Yi

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

Surface Modification of Gd Nanoparticles with pH-Responsive Block Copolymers for Use As Smart MRI Contrast Agents.

PubMed

Zhu, Liping; Yang, Yuan; Farquhar, Kirsten; Wang, Jingjing; Tian, Chixia; Ranville, James; Boyes, Stephen G

2016-02-01

Despite recent advances in the understanding of fundamental cancer biology, cancer remains the second most common cause of death in the United States. One of the primary factors indicative of high cancer morbidity and mortality and aggressive cancer phenotypes is tumors with a low extracellular pH (pHe). Thus, the ability to measure tumor pHe in vivo using noninvasive and accurate techniques that also provide high spatiotemporal resolution has become increasingly important and is of great interest to researchers and clinicians. In an effort to develop a pH-responsive magnetic resonance imaging (MRI) contrast agent (CA) that has the potential to be used to measure tumor pHe, well-defined pH-responsive polymers, synthesized via reversible addition-fragmentation chain transfer polymerization, were attached to the surface of gadolinium-based nanoparticles (GdNPs) via a "grafting to" method after reduction of the thiocarbonylthio end groups. The successful modification of the GdNPs was verified by transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis and dynamic light scattering. The performance of the pH-responsive polymer modified GdNPs was then evaluated for potential use as smart MRI CAs via monitoring the relaxivity changes with changing environmental pH. The results suggested that the pH-responsive polymers can be used to effectively modify the GdNPs surface to prepare a smart contrast agent for MRI.

The Controlling Function of the Agent in the Analysis of Question-Response Relationships.

ERIC Educational Resources Information Center

Bierschenk, Inger

In contrast to traditional linguistic analysis, a model based on the empirical agent is presented and tested. A text is regarded as an intentionally produced cognitive process. The analysis has to take the agent (perspective) into account to facilitate an adequate processing of its objectives (viewpoints). Moreover, the model is surface-oriented…

In vivo characterization of a smart MRI agent that displays an inverse response to calcium concentration.

PubMed

Mamedov, Ilgar; Canals, Santiago; Henig, Jörg; Beyerlein, Michael; Murayama, Yusuke; Mayer, Hermann A; Logothetis, Nikos K; Angelovski, Goran

2010-12-15

Contrast agents for magnetic resonance imaging (MRI) that exhibit sensitivity toward specific ions or molecules represent a challenging but attractive direction of research. Here a Gd(3+) complex linked to an aminobis(methylenephosphonate) group for chelating Ca(2+) was synthesized and investigated. The longitudinal relaxivity (r(1)) of this complex decreases during the relaxometric titration with Ca(2+) from 5.76 to 3.57 mM(-1) s(-1) upon saturation. The r(1) is modulated by changes in the hydration number, which was confirmed by determination of the luminescence emission lifetimes of the analogous Eu(3+) complex. The initial in vivo characterization of this responsive contrast agent was performed by means of electrophysiology and MRI experiments. The investigated complex is fully biocompatible, having no observable effect on neuronal function after administration into the brain ventricles or parenchyma. Distribution studies demonstrated that the diffusivity of this agent is significantly lower compared with that of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA).

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

NASA Astrophysics Data System (ADS)

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

2017-11-01

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

Multi-modality imaging of tumor phenotype and response to therapy

NASA Astrophysics Data System (ADS)

Nyflot, Matthew J.

2011-12-01

Imaging and radiation oncology have historically been closely linked. However, the vast majority of techniques used in the clinic involve anatomical imaging. Biological imaging offers the potential for innovation in the areas of cancer diagnosis and staging, radiotherapy target definition, and treatment response assessment. Some relevant imaging techniques are FDG PET (for imaging cellular metabolism), FLT PET (proliferation), CuATSM PET (hypoxia), and contrast-enhanced CT (vasculature and perfusion). Here, a technique for quantitative spatial correlation of tumor phenotype is presented for FDG PET, FLT PET, and CuATSM PET images. Additionally, multimodality imaging of treatment response with FLT PET, CuATSM, and dynamic contrast-enhanced CT is presented, in a trial of patients receiving an antiangiogenic agent (Avastin) combined with cisplatin and radiotherapy. Results are also presented for translational applications in animal models, including quantitative assessment of proliferative response to cetuximab with FLT PET and quantification of vascular volume with a blood-pool contrast agent (Fenestra). These techniques have clear applications to radiobiological research and optimized treatment strategies, and may eventually be used for personalized therapy for patients.

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.

Acoustic fingerprints of dye-labeled protein submicrosphere photoacoustic contrast agents

NASA Astrophysics Data System (ADS)

McDonald, Michael A.; Jankovic, Ladislav; Shahzad, Khalid; Burcher, Michael; Li, King C. P.

2009-05-01

Dye-labeled protein microspheres, submicron in size and capable of producing thermoelastically generated ultrasound in response to laser stimulation, are presented as contrast agents for photoacoustic imaging. Incident laser energy absorbed by fluorescein isothiocyanate (FITC)-labeled elastin submicrospheres results in thermoelastically generated sound production. Plotted A-line graphs reveal a distinctive morphology and a greater than two orders of magnitude increase in signal amplitude subsequent to converting FITC elastin into submicrospheres (despite a four orders of magnitude decrease in concentration). Evidence of nonlinearity and enhancement of ultrasound backscatter indicate a potential use in contrast-enhanced harmonic imaging. Photoacoustic and ultrasound imaging of FITC-elastin submicrospheres in a water-filled phantom vessel shows enhanced contrast at low concentration and clear delineation of the phantom vessel wall.

On the interplay of shell structure with low- and high-frequency mechanics of multifunctional magnetic microbubbles.

PubMed

Poehlmann, Melanie; Grishenkov, Dmitry; Kothapalli, Satya V V N; Härmark, Johan; Hebert, Hans; Philipp, Alexandra; Hoeller, Roland; Seuss, Maximilian; Kuttner, Christian; Margheritelli, Silvia; Paradossi, Gaio; Fery, Andreas

2014-01-07

Polymer-shelled magnetic microbubbles have great potential as hybrid contrast agents for ultrasound and magnetic resonance imaging. In this work, we studied US/MRI contrast agents based on air-filled poly(vinyl alcohol)-shelled microbubbles combined with superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs are integrated either physically or chemically into the polymeric shell of the microbubbles (MBs). As a result, two different designs of a hybrid contrast agent are obtained. With the physical approach, SPIONs are embedded inside the polymeric shell and with the chemical approach SPIONs are covalently linked to the shell surface. The structural design of hybrid probes is important, because it strongly determines the contrast agent's response in the considered imaging methods. In particular, we were interested how structural differences affect the shell's mechanical properties, which play a key role for the MBs' US imaging performance. Therefore, we thoroughly characterized the MBs' geometric features and investigated low-frequency mechanics by using atomic force microscopy (AFM) and high-frequency mechanics by using acoustic tests. Thus, we were able to quantify the impact of the used SPIONs integration method on the shell's elastic modulus, shear modulus and shear viscosity. In summary, the suggested approach contributes to an improved understanding of structure-property relations in US-active hybrid contrast agents and thus provides the basis for their sustainable development and optimization.

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

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. Copyright © 2011 Elsevier B.V. All rights reserved.

"Smart" gold nanoparticles for photoacoustic imaging: an imaging contrast agent responsive to the cancer microenvironment and signal amplification via pH-induced aggregation.

PubMed

Song, Jaejung; Kim, Jeesu; Hwang, Sekyu; Jeon, Mansik; Jeong, Sanghwa; Kim, Chulhong; Kim, Sungjee

2016-07-07

'Smart' gold nanoparticles can respond to mild acidic environments, rapidly form aggregates, and shift the absorption to red and near-infrared. They were used as a photoacoustic imaging agent responsive to the cancer microenvironment, and have demonstrated the cancer-specific accumulation at the cellular level and an amplified signal which is twice higher than the control in vivo.

Copper sulfide nanodisk as photoacoustic contrast agent for ovarian tumor detection

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

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

PubMed

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

2016-08-01

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

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

NASA Astrophysics Data System (ADS)

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

2016-08-01

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

Potential for differentiation of pseudoprogression from true tumor progression with dynamic susceptibility-weighted contrast-enhanced magnetic resonance imaging using ferumoxytol versus gadoteridol: A pilot study

PubMed Central

Gahramanov, Seymur; Raslan, Ahmed; Muldoon, Leslie L.; Hamilton, Bronwyn E.; Rooney, William D.; Varallyay, Csanad G.; Njus, Jeffrey M.; Haluska, Marianne; Neuwelt, Edward A.

2010-01-01

Purpose We evaluated dynamic susceptibility-weighted contrast-enhanced magnetic resonance imaging (DSC-MRI) using gadoteridol in comparison to the iron oxide nanoparticle blood pool agent, ferumoxytol in patients with glioblastoma multiforme (GBM) who received standard radiochemotherapy (RCT). Methods and Materials Fourteen patients with GBM received standard RCT and underwent 19 MRI sessions that included DSC-MRI acquisitions with gadoteridol on day 1 and ferumoxytol on day 2. Relative cerebral blood volume (rCBV) values were calculated from DSC data obtained from each contrast agent. T1-weighted acquisition post-gadoteridol administration was used to identify enhancing regions. Results In 7 MRI sessions of clinically presumptive active tumor, gadoteridol-DSC showed low rCBV in 3 and high rCBV in 4, while ferumoxytol-DSC showed high rCBV in all 7 sessions (p=0.002). After RCT, 7 MRI sessions showed increased gadoteridol contrast enhancement on T1-weighted scans coupled with low rCBV without significant differences between contrast agents (p=0.9). Based on post-gadoteridol T1-weighted scans, DSC-MRI, and clinical presentation four patterns of response to RCT were observed: 1) regression, 2) pseudoprogression, 3) true progression, and 4) mixed response. Conclusion We conclude that DSC-MRI with a blood-pool agent such as ferumoxytol may provide a better monitor of tumor rCBV than DSC-MRI with gadoteridol. Lesions demonstrating increased enhancement on T1-weighted MRI coupled with low ferumoxytol rCBV, are likely exhibiting pseudoprogression, while high rCBV with ferumoxytol is a better marker than gadoteridol for determining active tumor. These interesting pilot observations suggest that ferumoxytol may differentiate tumor progression from pseudoprogression, and warrant further investigation. PMID:20395065

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.; Dubois, L.; Jakubek, J.; Le Pape, A.; Sefc, L.; 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.

Simple method for quantification of gadolinium magnetic resonance imaging contrast agents using ESR spectroscopy.

PubMed

Takeshita, Keizo; Kinoshita, Shota; Okazaki, Shoko

2012-01-01

To develop an estimation method of gadolinium magnetic resonance imaging (MRI) contrast agents, the effect of concentration of Gd compounds on the ESR spectrum of nitroxyl radical was examined. A solution of either 4-oxo-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPONE) or 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) was mixed with a solution of Gd compound and the ESR spectrum was recorded. Increased concentration of gadolinium-diethylenetriamine pentaacetic acid chelate (Gd-DTPA), an MRI contrast agent, increased the peak-to-peak line widths of ESR spectra of the nitroxyl radicals, in accordance with a decrease of their signal heights. A linear relationship was observed between concentration of Gd-DTPA and line width of ESR signal, up to approximately 50 mmol/L Gd-DTPA, with a high correlation coefficient. Response of TEMPONE was 1.4-times higher than that of TEMPOL as evaluated from the slopes of the lines. The response was slightly different among Gd compounds; the slopes of calibration curves for acua[N,N-bis[2-[(carboxymethyl)[(methylcarbamoyl)methyl]amino]ethyl]glycinato(3-)]gadolinium hydrate (Gd-DTPA-BMA) (6.22 μT·L/mmol) and gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid chelate (Gd-DOTA) (6.62 μT·L/mmol) were steeper than the slope for Gd-DTPA (5.45 μT·L/mmol), whereas the slope for gadolinium chloride (4.94 μT·L/mmol) was less steep than that for Gd-DTPA. This method is simple to apply. The results indicate that this method is useful for rough estimation of the concentration of Gd contrast agents if calibration is carried out with each standard compound. It was also found that the plot of the reciprocal square root of signal height against concentrations of contrast agents could be useful for the estimation if a constant volume of sample solution is taken and measured at the same position in the ESR cavity every time.

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

PubMed

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

2013-09-01

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

Bimodal MR-PET agent for quantitative pH imaging

PubMed Central

Frullano, Luca; Catana, Ciprian; Benner, Thomas; Sherry, A. Dean; Caravan, Peter

2010-01-01

Activatable or “smart” magnetic resonance contrast agents have relaxivities that depend on environmental factors such as pH or enzymatic activity, but the MR signal depends on relaxivity and agent concentration – two unknowns. A bimodal approach, incorporating a positron emitter, solves this problem. Simultaneous positron emission tomography (PET) and MR imaging with the biomodal, pH-responsive MR-PET agent GdDOTA-4AMP-F allows direct determination of both concentration (PET) and T1 (MRI), and hence pH. PMID:20191650

Facile solvothermal synthesis of mesostructured Fe3O4/chitosan nanoparticles as delivery vehicles for pH-responsive drug delivery and magnetic resonance imaging contrast agents.

PubMed

Zhao, Guanghui; Wang, Jianzhi; Peng, Xiaomen; Li, Yanfeng; Yuan, Xuemei; Ma, Yingxia

2014-02-01

We report a facile fabrication of a host-metal-guest coordination-bonding system in a mesostructured Fe3O4/chitosan nanoparticle that can act as a pH-responsive drug-delivery system. The mesostructured Fe3O4/chitosan was synthesized by a solvothermal approach with iron(III) chloride hexahydrate as a precursor, ethylene glycol as a reducing agent, ammonium acetate as a porogen, and chitosan as a surface-modification agent. Subsequently, doxorubicin (DOX), acting as a model drug (guest), was loaded onto the mesostructured Fe3O4/chitosan nanoparticles, with chitosan acting as a host molecule to form the NH2-Zn(II)-DOX coordination architecture. The release of DOX can be achieved through the cleavage of coordination bonds that are sensitive to variations in external pH under weakly acidic conditions. The pH-responsive nature of the nanoparticles was confirmed by in vitro releases and cell assay tests. Furthermore, the relaxation efficiency of the nanoparticles as high-performance magnetic resonance imaging contrast agents was also investigated. Experimental results confirm that the synthesized mesostructured Fe3O4/chitosan is a smart nanovehicle for drug delivery owing to both its pH-responsive nature and relaxation efficiency. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Impact of myocardial contrast echocardiography on vascular permeability: an in vivo dose response study of delivery mode, pressure amplitude and contrast dose.

PubMed

Li, Peng; Cao, Lu-qin; Dou, Chun-Yan; Armstrong, William F; Miller, Douglas

2003-09-01

An in vivo rat model of myocardial contrast echocardiography (MCE) was defined and used to examine the dose range response of microvascular permeabilization and premature ventricular contractions (PVCs) with respect to method of imaging, peak rarefactional pressure amplitude (PRPA) and agent dose. A left ventricular short axis view was obtained on anesthetized rats at 1.7 MHz using a diagnostic ultrasound system with simultaneous ECG recording. Evans blue dye, a marker for microvascular leakage, and a bolus of Optison were injected i.v. Counts of PVCs were made from video tape during the 3 min of MCE. Hearts were excised 5 min after imaging and petechial hemorrhages, Evans blue colored area and Evans blue content were determined. No PVCs or microvascular leakage were seen in rats imaged without contrast agent followed by contrast agent injection without imaging. When PVCs were detected during MCE, petechial hemorrhages and Evans blue leakage were also found in the myocardium. Triggering 1:4 at end-systole produced the most PVCs per frame and most microvascular leakage, followed by end-systole 1:1, continuous scanning and end-diastole triggering 1:1. All effects increased with increasing Optison dosage in the range 25 to 500 microL kg(-1). Ultrasound PRPA was important, with apparent thresholds for PVCs at 1.0 MPa and for petechiae at 0.54 MPa. PVCs, petechial hemorrhages and microvascular leakage in the myocardium occur as a result of MCE in rats.

Tumor-Microenvironment Relaxivity-Changeable Gd-Loaded Poly(L-lysine)/Carboxymethyl Chitosan Nanoparticles as Cancer-Recognizable Magnetic Resonance Imaging Contrast Agents.

PubMed

Jiang, Dandan; Zhang, Xiaopeng; Yu, Dexin; Xiao, Yanan; Wang, Tianqi; Su, Zhihui; Liu, Yongjun; Zhang, Na

2017-03-01

Magnetic resonance imaging (MRI) contrast agents with tumor-microenvironment changeable relaxivity are effective to increase the sensitivity and selectivity of MRI in tumor diagnosis. In this study, pH-sensitive Gd-loaded Poly(L-lysine)/ Carboxymethyl Chitosan Nanoparticles (Gd-PCNPs) were developed as relaxivity-changeable MRI contrast agents based on the "on–off" switchable strategy. The "on–off" switchable nano-contrast agents were capable of releasing Gd3+ in response to physical stimulation, with structure transformed. Gd-PCNPs could responsively disassemble in an acidic tumor-microenvironment and increase the exchange of protons between water molecules and Gd3+ ions, thus selectively enhance the relaxivity in tumor area. Gd-PCNPs were self-assembled via electrostatic interaction between poly(L-lysine)-diethylenetriamine pentaacetic acid-gadolinium and pH-sensitive carboxymethyl chitosan (CMCS). Gd-PCNPs exhibited spherical shape with uniform particle size distribution (166.00 ± 1 .71 nm) and negative zeta potential (–13.2 ± 4.7 mV). The relaxivity of Gd-PCNPs increased from 6.618 mM–1 · s–1 to 10.008 mM–1 · s–1 when the pH values decrease from 7.4 to 6.0, which was higher than Magnevist® (3.924 mM–1 · s–1 at both pH 7.4 and 6.0 (p <0 05). The changeable relaxivity of Gd/PCNPs would result in enhanced tumor/normal tissue signal contrast, which was verified by in vivo MRI test. In vivo MRI test showed that the signal of Gd-PCNPs was significantly enhanced with prolonged imaging time in tumor tissue compared to Magnevist® (p <0 05). Furthermore, Gd-PCNPs exhibited unobvious in vitro cytotoxicity under the experimental concentrations in B16 cells. No obvious damage was observed in the different tissues of mice. These results indicated that the relaxivity-changeable Gd-PCNPs exhibited demonstrated sensitivity and selectivity in tumor diagnosis with a great potential as a novel MRI contrast agent.

Advances in Magnetic Resonance Imaging Contrast Agents for Biomarker Detection

PubMed Central

Sinharay, Sanhita; Pagel, Mark D.

2016-01-01

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

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

PubMed

Sharma, Samin K

2008-05-01

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

Multi-stimuli responsive Cu2S nanocrystals as trimodal imaging and synergistic chemo-photothermal therapy agents

NASA Astrophysics Data System (ADS)

Poulose, Aby Cheruvathoor; Veeranarayanan, Srivani; Mohamed, M. Sheikh; Nagaoka, Yutaka; Romero Aburto, Rebeca; Mitcham, Trevor; Ajayan, Pulickel M.; Bouchard, Richard R.; Sakamoto, Yasushi; Yoshida, Yasuhiko; Maekawa, Toru; Sakthi Kumar, D.

2015-04-01

A size and shape tuned, multifunctional metal chalcogenide, Cu2S-based nanotheranostic agent is developed for trimodal imaging and multimodal therapeutics against brain cancer cells. This theranostic agent was highly efficient in optical, photoacoustic and X-ray contrast imaging systems. The folate targeted NIR-responsive photothermal ablation in synergism with the chemotherapeutic action of doxorubicin proved to be a rapid precision guided cancer-killing module. The multi-stimuli, i.e., pH-, thermo- and photo-responsive drug release behavior of the nanoconjugates opens up a wider corridor for on-demand triggered drug administration. The simple synthesis protocol, combined with the multitudes of interesting features packed into a single nanoformulation, clearly demonstrates the competing role of this Cu2S nanosystem in future cancer treatment strategies.A size and shape tuned, multifunctional metal chalcogenide, Cu2S-based nanotheranostic agent is developed for trimodal imaging and multimodal therapeutics against brain cancer cells. This theranostic agent was highly efficient in optical, photoacoustic and X-ray contrast imaging systems. The folate targeted NIR-responsive photothermal ablation in synergism with the chemotherapeutic action of doxorubicin proved to be a rapid precision guided cancer-killing module. The multi-stimuli, i.e., pH-, thermo- and photo-responsive drug release behavior of the nanoconjugates opens up a wider corridor for on-demand triggered drug administration. The simple synthesis protocol, combined with the multitudes of interesting features packed into a single nanoformulation, clearly demonstrates the competing role of this Cu2S nanosystem in future cancer treatment strategies. Electronic supplementary information (ESI) available: Methodology and additional experimental results. See DOI: 10.1039/c4nr07139e

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Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-21

... their legally authorized agent and not from associations acting on their behalf. The FAA will adhere to... data feed.\\12\\ By contrast, the responsibilities of ASDI subscribers with respect to handling ASDI and... request on their own behalf, or they may do so through a legally authorized agent, including an attorney...

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

PubMed

Shiraishi, Kouichi

2013-01-01

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

Imaging angiogenesis.

PubMed

Charnley, Natalie; Donaldson, Stephanie; Price, Pat

2009-01-01

There is a need for direct imaging of effects on tumor vasculature in assessment of response to antiangiogenic drugs and vascular disrupting agents. Imaging tumor vasculature depends on differences in permeability of vasculature of tumor and normal tissue, which cause changes in penetration of contrast agents. Angiogenesis imaging may be defined in terms of measurement of tumor perfusion and direct imaging of the molecules involved in angiogenesis. In addition, assessment of tumor hypoxia will give an indication of tumor vasculature. The range of imaging techniques available for these processes includes positron emission tomography (PET), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), perfusion computed tomography (CT), and ultrasound (US).

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

PubMed

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

2017-08-16

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

Biocompatible astaxanthin as novel contrast agent for biomedical imaging.

PubMed

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

2017-08-01

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

Analysis of image heterogeneity using 2D Minkowski functionals detects tumor responses to treatment.

PubMed

Larkin, Timothy J; Canuto, Holly C; Kettunen, Mikko I; Booth, Thomas C; Hu, De-En; Krishnan, Anant S; Bohndiek, Sarah E; Neves, André A; McLachlan, Charles; Hobson, Michael P; Brindle, Kevin M

2014-01-01

The acquisition of ever increasing volumes of high resolution magnetic resonance imaging (MRI) data has created an urgent need to develop automated and objective image analysis algorithms that can assist in determining tumor margins, diagnosing tumor stage, and detecting treatment response. We have shown previously that Minkowski functionals, which are precise morphological and structural descriptors of image heterogeneity, can be used to enhance the detection, in T1 -weighted images, of a targeted Gd(3+) -chelate-based contrast agent for detecting tumor cell death. We have used Minkowski functionals here to characterize heterogeneity in T2 -weighted images acquired before and after drug treatment, and obtained without contrast agent administration. We show that Minkowski functionals can be used to characterize the changes in image heterogeneity that accompany treatment of tumors with a vascular disrupting agent, combretastatin A4-phosphate, and with a cytotoxic drug, etoposide. Parameterizing changes in the heterogeneity of T2 -weighted images can be used to detect early responses of tumors to drug treatment, even when there is no change in tumor size. The approach provides a quantitative and therefore objective assessment of treatment response that could be used with other types of MR image and also with other imaging modalities. Copyright © 2013 Wiley Periodicals, Inc.

Ultrasound Contrast Agents

NASA Astrophysics Data System (ADS)

Cachard, Christian; Basset, Olivier

While the use of contrast agents in other imaging modalities (X ray, MRI, PET, …) has been routinely accepted for many years, the development and commercialization of contrast agents designed specifically for ultrasound imaging has occurred only very recently. As in the other imaging modalities, the injection of contrast agents during an ultrasound examination is intended to facilitate the detection and diagnosis of specific pathologies. Contrast agents efficiency is based on the backscattering of ultrasound by microbubbles. These microparticules are intravenously injected in the blood flow. After an introduction and generalities on ultrasound contrast agents (UCA) the microbubble physics in an acoustic field will be developed. Second, physics characteristics of contrast agents will be compared (bubbles with or without shell, gas nature, size distribution). Influence of acoustic pressure on the behaviour of the microparticules (linear, non linear and destruction) will be discussed. Finally, a review of specific imaging adapted to contrast agent properties as harmonic imaging, pulse inversion imaging will be presented.

Gadolinium-Based Contrast Agents for MR Cancer Imaging

PubMed Central

Zhou, Zhuxian; Lu, Zheng-Rong

2013-01-01

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

Novel Fe3+-Based 1H MRI β-Galactosidase Reporter Molecules**

PubMed Central

Yu, Jian-Xin; Gulaka, Praveen K.; Liu, Li; Kodibagkar, Vikram D.; Mason, Ralph P.

2012-01-01

There is increasing interest in the development of reporter agents to reveal enzyme activity in vivo using small animal imaging. We have previously demonstrated the feasibility of detecting lacZ gene activity using the commercially available 3,4-cyclohexenoesculetin-β-D-galactopyranoside (S-Gal™) as a 1H MRI reporter. Specifically, β-galactosidase (β-gal) releases the aglycone, which forms an MR contrast-inducing paramagnetic precipitate in the presence of Fe3+. Contrast was primarily T2-weighted signal loss, but T1 effects were also observed. Since T1-contrast generally provides signal enhancement as opposed to loss, it appeared attractive to explore whether analogues could be generated with enhanced characteristics. We now report the design and successful synthesis of novel analogues together with characterization of 1H MRI contrast based on both T1 and T2 response to β-gal activity in vitro for the lead agent. PMID:23807909

Intracellular bimodal nanoparticles based on quantum dots for high-field MRI at 21.1 T.

PubMed

Rosenberg, Jens T; Kogot, Joshua M; Lovingood, Derek D; Strouse, Geoffrey F; Grant, Samuel C

2010-09-01

Multimodal, biocompatible contrast agents for high magnetic field applications represent a new class of nanomaterials with significant potential for tracking of fluorescence and MR in vitro and vivo. Optimized for high-field MR applications-including biomedical imaging at 21.1 T, the highest magnetic field available for MRI-these nanoparticles capitalize on the improved performance of chelated Dy(3+) with increasing magnetic field coupled to a noncytotoxic Indium Phosphide/Zinc Sulfide (InP/ZnS) quantum dot that provides fluorescence detection, MR responsiveness, and payload delivery. By surface modifying the quantum dot with a cell-penetrating peptide sequence coupled to an MR contrast agent, the bimodal nanomaterial functions as a self-transfecting high-field MR/optical contrast agent for nonspecific intracellular labeling. Fluorescent images confirm sequestration in perinuclear vesicles of labeled cells, with no apparent cytotoxicity. These techniques can be extended to impart cell selectivity or act as a delivery vehicle for genetic or pharmaceutical interventions. 2010 Wiley-Liss, Inc.

Nonlinear pulse compression in pulse-inversion fundamental imaging.

PubMed

Cheng, Yun-Chien; Shen, Che-Chou; Li, Pai-Chi

2007-04-01

Coded excitation can be applied in ultrasound contrast agent imaging to enhance the signal-to-noise ratio with minimal destruction of the microbubbles. Although the axial resolution is usually compromised by the requirement for a long coded transmit waveforms, this can be restored by using a compression filter to compress the received echo. However, nonlinear responses from microbubbles may cause difficulties in pulse compression and result in severe range side-lobe artifacts, particularly in pulse-inversion-based (PI) fundamental imaging. The efficacy of pulse compression in nonlinear contrast imaging was evaluated by investigating several factors relevant to PI fundamental generation using both in-vitro experiments and simulations. The results indicate that the acoustic pressure and the bubble size can alter the nonlinear characteristics of microbubbles and change the performance of the compression filter. When nonlinear responses from contrast agents are enhanced by using a higher acoustic pressure or when more microbubbles are near the resonance size of the transmit frequency, higher range side lobes are produced in both linear imaging and PI fundamental imaging. On the other hand, contrast detection in PI fundamental imaging significantly depends on the magnitude of the nonlinear responses of the bubbles and thus the resultant contrast-to-tissue ratio (CTR) still increases with acoustic pressure and the nonlinear resonance of microbubbles. It should be noted, however, that the CTR in PI fundamental imaging after compression is consistently lower than that before compression due to obvious side-lobe artifacts. Therefore, the use of coded excitation is not beneficial in PI fundamental contrast detection.

Integrin Targeted MR Imaging

PubMed Central

Tan, Mingqian; Lu, Zheng-Rong

2011-01-01

Magnetic resonance imaging (MRI) is a powerful medical diagnostic imaging modality for integrin targeted imaging, which uses the magnetic resonance of tissue water protons to display tissue anatomic structures with high spatial resolution. Contrast agents are often used in MRI to highlight specific regions of the body and make them easier to visualize. There are four main classes of MRI contrast agents based on their different contrast mechanisms, including T1, T2, chemical exchange saturation transfer (CEST) agents, and heteronuclear contrast agents. Integrins are an important family of heterodimeric transmembrane glycoproteins that function as mediators of cell-cell and cell-extracellular matrix interactions. The overexpressed integrins can be used as the molecular targets for designing suitable integrin targeted contrast agents for MR molecular imaging. Integrin targeted contrast agent includes a targeting agent specific to a target integrin, a paramagnetic agent and a linker connecting the targeting agent with the paramagnetic agent. Proper selection of targeting agents is critical for targeted MRI contrast agents to effectively bind to integrins for in vivo imaging. An ideal integrin targeted MR contrast agent should be non-toxic, provide strong contrast enhancement at the target sites and can be completely excreted from the body after MR imaging. An overview of integrin targeted MR contrast agents based on small molecular and macromolecular Gd(III) complexes, lipid nanoparticles and superparamagnetic nanoparticles is provided for MR molecular imaging. By using proper delivery systems for loading sufficient Gd(III) chelates or superparamagnetic nanoparticles, effective molecular imaging of integrins with MRI has been demonstrated in animal models. PMID:21547154

Convertible MRI contrast: Sensing the delivery and release of anti-glioma nano-drugs

NASA Astrophysics Data System (ADS)

Zhang, Liang; Zhang, Zhongwei; Mason, Ralph P.; Sarkaria, Jann N.; Zhao, Dawen

2015-05-01

There is considerable interest in developing nanohybrids of imaging contrast agents and drugs for image-guided drug delivery. We have developed a strategy of utilizing manganese (Mn) to enhance the nano-encapsulation of arsenic trioxide (ATO). Formation of arsenite (As3+)-Mn precipitates in liposomes generates magnetic susceptibility effects, reflected as dark contrast on T2-weighted MRI. Intriguingly, following cell uptake, the As-Mn complex decomposes in response to low pH in endosome-lysosome releasing ionic As3+, the active form of ATO, and Mn2+, the T1 contrast agent that gives a bright signal. Glioblastoma (GBM) is well known for its high resistance to chemotherapy, e.g., temozolomide (TMZ). Building upon the previously established phosphatidylserine (PS)-targeted nanoplatform that has excellent GBM-targeting specificity, we now demonstrate the effectiveness of the targeted nanoformulated ATO for treating TMZ-resistant GBM cells and the ability of the convertible Mn contrast as a surrogate revealing the delivery and release of ATO.

How do we think machines think? An fMRI study of alleged competition with an artificial intelligence

PubMed Central

Chaminade, Thierry; Rosset, Delphine; Da Fonseca, David; Nazarian, Bruno; Lutcher, Ewald; Cheng, Gordon; Deruelle, Christine

2012-01-01

Mentalizing is defined as the inference of mental states of fellow humans, and is a particularly important skill for social interactions. Here we assessed whether activity in brain areas involved in mentalizing is specific to the processing of mental states or can be generalized to the inference of non-mental states by comparing brain responses during the interaction with an intentional and an artificial agent. Participants were scanned using fMRI during interactive rock-paper-scissors games while believing their opponent was a fellow human (Intentional agent, Int), a humanoid robot endowed with an artificial intelligence (Artificial agent, Art), or a computer playing randomly (Random agent, Rnd). Participants' subjective reports indicated that they adopted different stances against the three agents. The contrast of brain activity during interaction with the artificial and the random agents didn't yield any cluster at the threshold used, suggesting the absence of a reproducible stance when interacting with an artificial intelligence. We probed response to the artificial agent in regions of interest corresponding to clusters found in the contrast between the intentional and the random agents. In the precuneus involved in working memory, the posterior intraparietal suclus, in the control of attention and the dorsolateral prefrontal cortex, in executive functions, brain activity for Art was larger than for Rnd but lower than for Int, supporting the intrinsically engaging nature of social interactions. A similar pattern in the left premotor cortex and anterior intraparietal sulcus involved in motor resonance suggested that participants simulated human, and to a lesser extend humanoid robot actions, when playing the game. Finally, mentalizing regions, the medial prefrontal cortex and right temporoparietal junction, responded to the human only, supporting the specificity of mentalizing areas for interactions with intentional agents. PMID:22586381

How do we think machines think? An fMRI study of alleged competition with an artificial intelligence.

PubMed

Chaminade, Thierry; Rosset, Delphine; Da Fonseca, David; Nazarian, Bruno; Lutcher, Ewald; Cheng, Gordon; Deruelle, Christine

2012-01-01

Mentalizing is defined as the inference of mental states of fellow humans, and is a particularly important skill for social interactions. Here we assessed whether activity in brain areas involved in mentalizing is specific to the processing of mental states or can be generalized to the inference of non-mental states by comparing brain responses during the interaction with an intentional and an artificial agent. Participants were scanned using fMRI during interactive rock-paper-scissors games while believing their opponent was a fellow human (Intentional agent, Int), a humanoid robot endowed with an artificial intelligence (Artificial agent, Art), or a computer playing randomly (Random agent, Rnd). Participants' subjective reports indicated that they adopted different stances against the three agents. The contrast of brain activity during interaction with the artificial and the random agents didn't yield any cluster at the threshold used, suggesting the absence of a reproducible stance when interacting with an artificial intelligence. We probed response to the artificial agent in regions of interest corresponding to clusters found in the contrast between the intentional and the random agents. In the precuneus involved in working memory, the posterior intraparietal suclus, in the control of attention and the dorsolateral prefrontal cortex, in executive functions, brain activity for Art was larger than for Rnd but lower than for Int, supporting the intrinsically engaging nature of social interactions. A similar pattern in the left premotor cortex and anterior intraparietal sulcus involved in motor resonance suggested that participants simulated human, and to a lesser extend humanoid robot actions, when playing the game. Finally, mentalizing regions, the medial prefrontal cortex and right temporoparietal junction, responded to the human only, supporting the specificity of mentalizing areas for interactions with intentional agents.

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

PubMed

Runge, Val M

2017-06-01

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

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

PubMed

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

2017-04-01

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

Properties of iopamidol-incorporated poly(vinyl alcohol) microparticle as an X-ray imaging flow tracer.

PubMed

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

2011-02-10

We have recently reported on poly(vinyl alcohol) microparticles containing X-ray contrast agent, iopamidol, designed as a flow tracer working in synchrotron X-ray imaging ( Biosens. Bioelectron. 2010 , 25 , 1571 ). Although iopamidol is physically encapsulated in the microparticles, it displays a great contrast enhancement and stable feasibility in in vitro human blood pool. Nonetheless, a direct relation between the absolute amount of incorporated iopamidol and the enhancement in imaging efficiency was not observed. In this study, physical properties of the designed microparticle are systematically investigated experimentally with theoretical interpretation to correlate an enhancement in X-ray imaging efficiency. The compositional ratio of X-ray contrast agent in polymeric microparticle is controlled as 1/1 and 10/1 [contrast agent/polymer microparticle (w/w)] with changed degree of cross-linkings. Flory-Huggins interaction parameter (χ), retractive force (τ) and degree of swelling of the designed polymeric microparticles are investigated. In addition, the hydrodynamic size (D(H)) and ζ-potential are evaluated in terms of environment responsiveness. The physical properties of the designed flow tracer microparticles under a given condition are observed to be strongly related with the X-ray absorption efficiency, which are also supported by the Beer-Lambert-Bouguer law. The designed microparticles are almost nontoxic with a reasonable concentration and time period, enough to be utilized as a flow tracer in various biomedical applications. This study would contribute to the basic understanding on the physical property connected with the imaging efficiency of contrast agents.

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

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

Wang, Hui; Mu, Qingxin; Revia, Richard

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

Contrast enhanced spectroscopic optical coherence tomography

NASA Technical Reports Server (NTRS)

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

2010-01-01

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

Blood-pool contrast agent for pre-clinical computed tomography

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

Nanoparticle Contrast Agents for Computed Tomography: A Focus on Micelles

PubMed Central

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

2014-01-01

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

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

NASA Astrophysics Data System (ADS)

Shekhar, Himanshu; Doyley, Marvin M.

2013-03-01

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

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

PubMed

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

2014-04-18

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

Thermal- and pH-Dependent Size Variable Radical Nanoparticles and Its Water Proton Relaxivity for Metal-Free MRI Functional Contrast Agents.

PubMed

Morishita, Kosuke; Murayama, Shuhei; Araki, Takeru; Aoki, Ichio; Karasawa, Satoru

2016-09-16

For development of the metal-free MRI contrast agents, we prepared the supra-molecular organic radical, TEMPO-UBD, carrying TEMPO radical, as well as the urea, alkyl group, and phenyl ring, which demonstrate self-assembly behaviors using noncovalent bonds in an aqueous solution. In addition, TEMPO-UBD has the tertiary amine and the oligoethylene glycol chains (OEGs) for the function of pH and thermal responsiveness. By dynamic light scattering and transmission electron microscopy imaging, the resulting self-assembly was seen to form the spherical nanoparticles 10-150 nm in size. On heating, interestingly, the nanoparticles showed a lower critical solution temperature (LCST) behavior having two-step variation. This double-LCST behavior is the first such example among the supra-molecules. To evaluate of the ability as MRI contrast agents, the values of proton ((1)H) longitudinal relaxivity (r1) were determined using MRI apparatus. In conditions below and above CAC at pH 7.0, the distinguishable r1 values were estimated to be 0.17 and 0.21 mM(-1) s(1), indicating the suppression of fast tumbling motion of TEMPO moiety in a nanoparticle. Furthermore, r1 values became larger in the order of pH 7.0 > 9.0 > 5.0. Those thermal and pH dependencies indicated the possibility of metal-fee MRI functional contrast agents in the future.

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

PubMed

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

2015-01-01

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

Ferrimagnetic susceptibility contrast agents.

PubMed

Bach-Gansmo, T

1993-01-01

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

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

PubMed

Mithal, Leena B; Patel, Payal S; Mithal, Divakar; Palac, Hannah L; Rozenfeld, Michael N

2017-05-01

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

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.

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

PubMed

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

2015-11-04

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

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

PubMed

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

2006-05-01

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

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

NASA Astrophysics Data System (ADS)

Hu, Fengqin; Zhao, Yong Sheng

2012-09-01

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

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

PubMed Central

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

2013-01-01

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

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

Treesearch

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

2009-01-01

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

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

PubMed

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

2015-09-01

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

Recent Advances in Molecular, Multimodal and Theranostic Ultrasound Imaging

PubMed Central

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

2014-01-01

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

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

PubMed Central

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

2017-01-01

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

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

PubMed Central

2007-01-01

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

Effects of encapsulation damping on the excitation threshold for subharmonic generation from contrast microbubbles.

PubMed

Katiyar, Amit; Sarkar, Kausik

2012-11-01

A recent study [Katiyar and Sarkar (2011). J. Acoust. Soc. Am. 130, 3137-3147] showed that in contrast to the analytical result for free bubbles, the minimum threshold for subharmonic generation for contrast microbubbles does not necessarily occur at twice the resonance frequency. Here increased damping-either due to the small radius or the encapsulation-is shown to shift the minimum threshold away from twice the resonance frequency. Free bubbles as well as four models of the contrast agent encapsulation are investigated varying the surface dilatational viscosity. Encapsulation properties are determined using measured attenuation data for a commercial contrast agent. For sufficiently small damping, models predict two minima for the threshold curve-one at twice the resonance frequency being lower than the other at resonance frequency-in accord with the classical analytical result. However, increased damping damps the bubble response more at twice the resonance than at resonance, leading to a flattening of the threshold curve and a gradual shift of the absolute minimum from twice the resonance frequency toward the resonance frequency. The deviation from the classical result stems from the fact that the perturbation analysis employed to obtain it assumes small damping, not always applicable for contrast microbubbles.

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

PubMed Central

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

2013-01-01

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

Preliminary studies of enhanced contrast radiography in anatomy and embryology of insects with Elettra synchrotron light

NASA Astrophysics Data System (ADS)

Hönnicke, M. G.; Foerster, L. A.; Navarro-Silva, M. A.; Menk, R.-H.; Rigon, L.; Cusatis, C.

2005-08-01

Enhanced contrast X-ray imaging is achieved by exploiting the real part of the refraction index, which is responsible for the phase shifts, in addition to the imaginary part, which is responsible for the absorption. Such techniques are called X-ray phase contrast imaging. An analyzer-based X-ray phase contrast imaging set-up with Diffraction Enhanced Imaging processing (DEI) were used for preliminary studies in anatomy and embryology of insects. Parasitized stinkbug and moth eggs used as control agents of pests in vegetables and adult stinkbugs and mosquitoes ( Aedes aegypti) were used as samples. The experimental setup was mounted in the SYRMEP beamline at ELETTRA. Images were obtained using a high spatial resolution CCD detector (pixel size 14×14 μm 2) coupled with magnifying optics. Analyzer-based X-ray phase contrast images (PCI) and edge detection images show contrast and details not observed with conventional synchrotron radiography and open the possibility for future study in the embryonic development of insects.

Cognitive conflict without explicit conflict monitoring in a dynamical agent.

PubMed

Ward, Robert; Ward, Ronnie

2006-11-01

We examine mechanisms for resolving cognitive conflict in an embodied, situated, and dynamic agent, developed through an evolutionary learning process. The agent was required to solve problems of response conflict in a dual-target "catching" task, focusing response on one of the targets while ignoring the other. Conflict in the agent was revealed at the behavioral level in terms of increased latencies to the second target. This behavioral interference was correlated to peak violations of the network's stable state equation. At the level of the agent's neural network, peak violations were also correlated to periods of disagreement in source inputs to the agent's motor effectors. Despite observing conflict at these numerous levels, we did not find any explicit conflict monitoring mechanisms within the agent. We instead found evidence of a distributed conflict management system, characterized by competitive sources within the network. In contrast to the conflict monitoring hypothesis [Botvinick, M. M., Braver, T. S., Barch, D. M., Carter, C. S., & Cohen, J. D. (2001). Conflict monitoring and cognitive control. Psychological Review, 108(3), 624-652], this agent demonstrates that resolution of cognitive conflict does not require explicit conflict monitoring. We consider the implications of our results for the conflict monitoring hypothesis.

Gd-labeled glycol chitosan as a pH-responsive magnetic resonance imaging agent for detecting acidic tumor microenvironments.

PubMed

Nwe, Kido; Huang, Ching-Hui; Tsourkas, Andrew

2013-10-24

Neoplastic lesions can create a hostile tumor microenvironment with low extracellular pH. It is commonly believed that these conditions can contribute to tumor progression as well as resistance to therapy. We report the development and characterization of a pH-responsive magnetic resonance imaging contrast agent for imaging the acidic tumor microenvironment. The preparation included the conjugation of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid 1-(2,5-dioxo-1-pyrrolidinyl) ester (DOTA-NHS) to the surface of a water-soluble glycol chitosan (GC) polymer, which contains pH-titrable primary amines, followed by gadolinium complexation (GC-NH2-GdDOTA). GC-NH2-GdDOTA had a chelate-to-polymer ratio of approximately1:24 and a molar relaxivity of 9.1 mM(-1) s(-1). GC-NH2-GdDOTA demonstrated pH-dependent cellular association in vitro compared to the control. It also generated a 2.4-fold enhancement in signal in tumor-bearing mice 2 h postinjection. These findings suggest that glycol chitosan coupled with contrast agents can provide important diagnostic information about the tumor microenvironment.

Colorectal liver metastases: contrast agent diffusion coefficient for quantification of contrast enhancement heterogeneity at MR imaging.

PubMed

Jia, Guang; O'Dell, Craig; Heverhagen, Johannes T; Yang, Xiangyu; Liang, Jiachao; Jacko, Richard V; Sammet, Steffen; Pellas, Theodore; Cole, Patricia; Knopp, Michael V

2008-09-01

To describe and determine the reproducibility of a simplified model to quantitatively measure heterogeneous intralesion contrast agent diffusion in colorectal liver metastases. This HIPAA-compliant retrospective study received institutional review board approval, and written informed consent was obtained from 14 patients (mean age, 61 years +/- 9 [standard deviation]; range, 41-78 years), including 10 men (mean age, 65 years +/- 8; range, 47-78 years) and four women (mean age, 54 years +/- 9; range, 41-59 years), with colorectal liver metastases. Magnetic resonance (MR) imaging was performed twice (first baseline MR image [B(1)] and second baseline MR image [B(2)]) in a single target lesion prior to therapy. Dynamic contrast material-enhanced MR imaging was performed by using a saturation-recovery fast gradient-echo sequence. A simplified contrast agent diffusion model was proposed, and a contrast agent diffusion coefficient (CDC) was calculated. The reproducibility of the CDC measurement was evaluated by using the Bland-Altman plot and a linear regression model. The mean CDC was 0.22 mm(2)/sec (range, 0.01-0.73 mm(2)/sec) on B(1) and 0.24 mm(2)/sec (range, 0.01-0.71 mm(2)/sec) on B(2), with an intraclass correlation coefficient of 0.91 (P < .0001). Bland-Altman plot showed good agreement, with a mean difference in measurement pairs of 0.017 mm(2)/sec +/- 0.096. The slope from the linear regression model was 0.89 (95% confidence interval: 0.63, 1.15) and the intercept was 0.01 (95% confidence interval: -0.08, 0.09). The CDC enables a quantitative description of contrast enhancement heterogeneity in lesions. Given the high reproducibility of the CDC metric, CDC appears promising for further qualification as an imaging biomarker of change measurement in response assessment. http://radiology.rsnajnls.org/cgi/content/full/248/3/901/DC1. RSNA, 2008

Contrast echocardiography: new agents.

PubMed

Miller, Andrew P; Nanda, Navin C

2004-04-01

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

Developmental Thyroid Hormone Insufficiency Impairs Visual Contrast Sensitivity in Adult Male Offspring.

EPA Science Inventory

Severe thyroid hormone (TH) insufficiency during early development results in alterations in brain structure and function. Many environmental agents produce subtle alterations in TH status, but the dose-response relationships for such effects are unclear. We have previously demon...

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

NASA Astrophysics Data System (ADS)

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

2009-01-01

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

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

PubMed Central

2017-01-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2015-12-01

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

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

PubMed Central

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

2011-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2016-02-01

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

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

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

PubMed Central

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

2009-01-01

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

Blood oxygenation level-dependent (BOLD) contrast magnetic resonance imaging (MRI) for prediction of breast cancer chemotherapy response: a pilot study.

PubMed

Jiang, Lan; Weatherall, Paul T; McColl, Roderick W; Tripathy, Debu; Mason, Ralph P

2013-05-01

To determine whether a simple noninvasive method of assessing tumor oxygenation is feasible in the clinical setting and can provide useful, potentially predictive information. Tumor microcirculation and oxygenation play critical roles in tumor growth and responsiveness to cytotoxic treatment and may provide prognostic indicators for cancer therapy. Deoxyhemoglobin is paramagnetic and can serve as an endogenous contrast agent causing signal loss in echo planar magnetic resonance imaging (MRI) (blood oxygenation level-dependent [BOLD]-MRI). We used BOLD-MRI to provide early evaluation of response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. MRI was performed on 11 patients with biopsy-proven malignancy. MRI exams were scheduled before, during, and after chemotherapy. The BOLD study applied a 6-minute oxygen breathing challenge. Seven patients successfully completed the exams. Before chemotherapy, BOLD contrast enhancement was observed in all tumors, but the patients, who ultimately had complete pathological response, exhibited a significantly higher BOLD response to oxygen breathing. We have successfully implemented an oxygen-breathing challenge BOLD contrast technique as part of the standard breast MRI exam in patients with locally advanced breast cancer. The preliminary observation that a large BOLD response correlated with better treatment response suggests a predictive capability for BOLD MRI. Copyright © 2012 Wiley Periodicals, Inc.

Contrast agent enhanced pQCT of articular cartilage

NASA Astrophysics Data System (ADS)

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

2007-02-01

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

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

PubMed

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

2015-10-01

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

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

PubMed Central

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

2008-01-01

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

Contrast-enhanced peripheral MRA: technique and contrast agents.

PubMed

Nielsen, Yousef W; Thomsen, Henrik S

2012-09-01

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

Nuclear magnetic resonance contrast agents

DOEpatents

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

1997-12-30

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

Nuclear magnetic resonance contrast agents

DOEpatents

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

1997-01-01

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

DCE-MRI Parameters Have Potential to Predict Response of Locally Advanced Breast Cancer Patients to Neoadjuvant Chemotherapy and Hyperthermia: A Pilot Study

PubMed Central

Craciunescu, Oana I.; Blackwell, Kimberly L.; Jones, Ellen L.; MacFall, James R.; Yu, Daohai; Vujaskovic, Zeljko; Wong, Terence Z.; Liotcheva, Vlayka; Rosen, Eric L.; Prosnitz, Leonard R.; Samulski, Thaddeus V.; Dewhirst, Mark W.

2009-01-01

Purpose To use a novel Morpho-Physiological Tumor Score (MPTS) generated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict response to treatment. Materials and Methods A protocol was designed to acquire DCE-MRI images of 20 locally advanced breast cancer (LABC) patients treated with neoadjuvant chemotherapy (NA ChT) and hyperthermia (HT). Imaging was done over 30 minutes following bolus injection of Gd-based contrast agent. Parametric maps were generated by fitting the signal intensity to a double exponential curve and were used to derive a morphological characterization of the lesions. Enhancement-variance dynamics parameters, washin and washout parameters (WiP, WoP) were extracted. The morphological characterization and the WiP and WoP were combined into a MPTS with the intent of achieving better prognostic efficacy. The MPTS was correlated with response to NA therapy as determined by pathologic residual tumor and MRI imaging. Results The contrast agent in all tumors typically peaked in the first 1–4 minutes. The tumors WiP and WoP varied considerably. The MPTS was highly correlated with whether the patients had a pathologic response. This scoring system has a specificity of 78% and a sensitivity of 91% for predicting response to NA chemotherapy. The kappa was 0.69 with a 95% confidence interval of [0.38, 1.0] and a p-value of 0.002. Conclusions This pilot study shows that the MPTS derived using pre-treatment MRI images has the potential to predict response to NA ChT and HT in LABC patients. Further prospective studies are needed to confirm the validity of these results. PMID:19657852

Iopamidol as a responsive MRI-chemical exchange saturation transfer contrast agent for pH mapping of kidneys: In vivo studies in mice at 7 T.

PubMed

Longo, Dario Livio; Dastrù, Walter; Digilio, Giuseppe; Keupp, Jochen; Langereis, Sander; Lanzardo, Stefania; Prestigio, Simone; Steinbach, Oliver; Terreno, Enzo; Uggeri, Fulvio; Aime, Silvio

2011-01-01

Iopamidol (Isovue®-Bracco Diagnostic Inc.) is a clinically approved X-Ray contrast agent used in the last 30 years for a wide variety of diagnostic applications with a very good clinical acceptance. Iopamidol contains two types of amide functionalities that can be exploited for the generation of chemical exchange saturation transfer effect. The exchange rate of the two amide proton pools is markedly pH-dependent. Thus, a ratiometric method for pH assessment has been set-up based on the comparison of the saturation transfer effects induced by selective irradiation of the two resonances. This ratiometric approach allows to rule out the concentration effect of the contrast agent and provides accurate pH measurements in the 5.5-7.4 range. Upon injection of Iopamidol into healthy mice, it has been possible to acquire pH maps of kidney regions. Furthermore, it has been also shown that the proposed method is able to report about pH-changes induced in control mice fed with acidified or basified water for a period of a week before image acquisition. © 2010 Wiley-Liss, Inc.

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

PubMed

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

2016-11-01

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

Effect of contrast leakage on the detection of abnormal brain tumor vasculature in high-grade glioma.

PubMed

LaViolette, Peter S; Daun, Mitchell K; Paulson, Eric S; Schmainda, Kathleen M

2014-02-01

Abnormal brain tumor vasculature has recently been highlighted by a dynamic susceptibility contrast (DSC) MRI processing technique. The technique uses independent component analysis (ICA) to separate arterial and venous perfusion. The overlap of the two, i.e. arterio-venous overlap or AVOL, preferentially occurs in brain tumors and predicts response to anti-angiogenic therapy. The effects of contrast agent leakage on the AVOL biomarker have yet to be established. DSC was acquired during two separate contrast boluses in ten patients undergoing clinical imaging for brain tumor diagnosis. Three components were modeled with ICA, which included the arterial and venous components. The percentage of each component as well as a third component were determined within contrast enhancing tumor and compared. AVOL within enhancing tumor was also compared between doses. The percentage of enhancing tumor classified as not arterial or venous and instead into a third component with contrast agent leakage apparent in the time-series was significantly greater for the first contrast dose compared to the second. The amount of AVOL detected within enhancing tumor was also significantly greater with the second dose compared to the first. Contrast leakage results in large signal variance classified as a separate component by the ICA algorithm. The use of a second dose mitigates the effect and allows measurement of AVOL within enhancement.

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

PubMed

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

2016-04-01

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

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

NASA Astrophysics Data System (ADS)

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

2016-05-01

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

Imaging-related medications: a class overview

PubMed Central

2007-01-01

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

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

PubMed

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

2017-08-01

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

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

PubMed

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

2015-12-01

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

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

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

PubMed

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

2017-12-01

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

Superparamagnetic Nanoparticles as High Efficiency Magnetic Resonance Imaging T2 Contrast Agent.

PubMed

Sousa, Fernanda; Sanavio, Barbara; Saccani, Alessandra; Tang, Yun; Zucca, Ileana; Carney, Tamara M; Mastropietro, Alfonso; Jacob Silva, Paulo H; Carney, Randy P; Schenk, Kurt; Omrani, Arash O; Huang, Ping; Yang, Lin; Rønnow, Henrik M; Stellacci, Francesco; Krol, Silke

2017-01-18

Nanoparticle-based magnetic resonance imaging T 2 negative agents are of great interest, and much effort is devoted to increasing cell-loading capability while maintaining low cytotoxicity. Herein, two classes of mixed-ligand protected magnetic-responsive, bimetallic gold/iron nanoparticles (Au/Fe NPs) synthesized by a two-step method are presented. Their structure, surface composition, and magnetic properties are characterized. The two classes of sulfonated Au/Fe NPs, with an average diameter of 4 nm, have an average atomic ratio of Au to Fe equal to 7 or 8, which enables the Au/Fe NPs to be superparamagnetic with a blocking temperature of 56 K and 96 K. Furthermore, preliminary cellular studies reveal that both Au/Fe NPs show very limited toxicity. MRI phantom experiments show that r 2 /r 1 ratio of Au/Fe NPs is as high as 670, leading to a 66% reduction in T 2 relaxation time. These nanoparticles provide great versatility and potential for nanoparticle-based diagnostics and therapeutic applications and as imaging contrast agents.

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

PubMed

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

2016-01-01

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

Distinct Gene Expression Profiles in Peripheral Blood Mononuclear Cells from Patients Infected with Vaccinia Virus, Yellow Fever 17D Virus, or Upper Respiratory Infections Running Title: PBMC Expression Response to Viral Agents

PubMed Central

Scherer, Christina A.; Magness, Charles L.; Steiger, Kathryn V.; Poitinger, Nicholas D.; Caputo, Christine M.; Miner, Douglas G.; Winokur, Patricia L.; Klinzman, Donna; McKee, Janice; Pilar, Christine; Ward, Patricia A.; Gillham, Martha H.; Haulman, N. Jean; Stapleton, Jack T.; Iadonato, Shawn P.

2007-01-01

Gene expression in human peripheral blood mononuclear cells was systematically evaluated following smallpox and yellow fever vaccination, and naturally occurring upper respiratory infection (URI). All three infections were characterized by the induction of many interferon stimulated genes, as well as enhanced expression of genes involved in proteolysis and antigen presentation. Vaccinia infection was also characterized by a distinct expression signature composed of up-regulation of monocyte response genes, with repression of genes expressed by B and T-cells. In contrast, the yellow fever host response was characterized by a suppression of ribosomal and translation factors, distinguishing this infection from vaccinia and URI. No significant URI-specific signature was observed, perhaps reflecting greater heterogeneity in the study population and etiological agents. Taken together, these data suggest that specific host gene expression signatures may be identified that distinguish one or a small number of virus agents. PMID:17651872

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

PubMed Central

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

2014-01-01

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

Acoustic characterization of ultrasound contrast microbubbles and echogenic liposomes: Applications to imaging and drug-delivery

NASA Astrophysics Data System (ADS)

Paul, Shirshendu

Micron- to nanometer - sized ultrasound agents, like encapsulated microbubbles and echogenic liposomes (ELIPs), are being actively developed for possible clinical implementations in diagnostic imaging and ultrasound mediated drug/gene delivery. The primary objective of this thesis is to characterize the acoustic behavior of and the ultrasound-mediated contents release from these contrast agents for developing multi-functional ultrasound contrast agents. Subharmonic imaging using contrast microbubbles can improve image quality by providing a higher signal to noise ratio. However, the design and development of contrast microbubbles with favorable subharmonic behavior requires accurate mathematical models capable of predicting their nonlinear dynamics. To this goal, 'strain-softening' viscoelastic interfacial models of the encapsulation were developed and subsequently utilized to simulate the dynamics of encapsulated microbubbles. A hierarchical two-pronged approach of modeling --- a model is applied to one set of experimental data to obtain the model parameters (material characterization), and then the model is validated against a second independent experiment --- is demonstrated in this thesis for two lipid coated (SonazoidRTM and DefinityRTM) and a few polymer (polylactide) encapsulated microbubbles. The proposed models were successful in predicting several experimentally observed behaviors e.g., low subharmonic thresholds and "compression-only" radial oscillations. Results indicate that neglecting the polydisperse size distribution of contrast agent suspensions, a common practice in the literature, can lead to inaccurate results. In vitro experimental investigation of the dependence of subharmonic response from these microbubbles on the ambient pressure is also in conformity with the recent numerical investigations, showing both increase or decrease under appropriate excitation conditions. Experimental characterization of the ELIPs and polymersomes was performed with the goal of demonstrating their potential as ultrasound agents with simultaneous imaging and drug/gene delivery applications --- 'dual-purpose' contrast agents. Both in vitro acoustic studies and ultrasound imaging (performed in NDSU by our collaborators) showed the echogenicity of the various formulations studied. We believe that this echogenicity results from the larger diameter liposomes present in the polydisperse suspension obtained after reconstitution of the lyophilized powders. Although, ultrasound excitation (< 5 MHz) alone was incapable of causing optimal release of contents, a dual-triggering strategy (with enzymes or redox) proved successful, resulting in a total release of up to 80-90%. Considering these experimental results, it can be concluded that these novel formulations hold the potential of providing powerful treatment strategies for many diseases, including cardiovascular ones and various cancers.

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

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

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

2015-01-15

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

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

PubMed

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

2017-04-01

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

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

PubMed

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

2016-12-01

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

Molecular Contrast Optical Coherence Tomography: A Review¶

PubMed Central

Yang, Changhuei

2005-01-01

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

Annexin V conjugated nanobubbles: A novel ultrasound contrast agent for in vivo assessment of the apoptotic response in cancer therapy.

PubMed

Zhou, Tian; Cai, Wenbin; Yang, Hengli; Zhang, Huizhong; Hao, Minghua; Yuan, Lijun; Liu, Jie; Zhang, Li; Yang, Yilin; Liu, Xi; Deng, Jianling; Zhao, Ping; Yang, Guodong; Duan, Yunyou

2018-04-28

In vivo assessment of apoptotic response to cancer therapy is believed to be very important for optimizing management of treatment. However, few noninvasive strategies are currently available to monitor the therapeutic response in vivo. Ultrasonography has been used to detect apoptotic cell death in vivo, but a high-frequency transducer is needed. Fortunately, the capability of ultrasound contrast agents (UCAs) to exit the leaky vasculature of tumors enables ultrasound-targeted imaging of molecular events in response to cancer therapy. In this study, we prepared a novel nano-sized UCA, namely, Annexin V-conjugated nanobubbles (AV-NBs, 635.5 ± 25.4 nm). In vitro studies revealed that AV-NBs were relatively stable and highly echogenic. Moreover, these AV-NBs could easily extravasate into the tumor vasculature and recognize the apoptotic cells with high specificity and affinity in tumors sensitive to chemotherapy. Ultrasound imaging results demonstrated that AV-NBs had higher echogenicity and significantly greater enhancement compared with the untargeted control NBs (P < 0.01) inside the tumors after chemotherapy. Taken together, this study provides a promising method to accurately evaluate therapeutic effects at the molecular level to support cancer management. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

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

PubMed

Greis, C

2014-01-01

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

Contrast media enhancement reduction predicts tumor response to presurgical molecular-targeting therapy in patients with advanced renal cell carcinoma.

PubMed

Hosogoe, Shogo; Hatakeyama, Shingo; Kusaka, Ayumu; Hamano, Itsuto; Tanaka, Yoshimi; Hagiwara, Kazuhisa; Hirai, Hideaki; Morohashi, Satoko; Kijima, Hiroshi; Yamamoto, Hayato; Tobisawa, Yuki; Yoneyama, Tohru; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Koie, Takuya; Ohyama, Chikara

2017-07-25

A quantitative tumor response evaluation to molecular-targeting agents in advanced renal cell carcinoma (RCC) is debatable. We aimed to evaluate the relationship between radiologic tumor response and pathological response in patients with advanced RCC who underwent presurgical therapy. Of 34 patients, 31 underwent scheduled radical nephrectomy. Presurgical therapy agents included axitinib (n = 26), everolimus (n = 3), sunitinib (n = 1), and axitinib followed by temsirolimus (n = 1). The major presurgical treatment-related adverse event was grade 2 or 3 hypertension (44%). The median radiologic tumor response by RECIST, Choi, and CMER were -19%, -24%, and -49%, respectively. Among the radiologic tumor response tests, CMER showed a higher association with tumor necrosis in surgical specimens than others. Ki67/MIB1 status was significantly decreased in surgical specimens than in biopsy specimens. The magnitude of the slope of the regression line associated with the tumor necrosis percentage was greater in CMER than in Choi and RECIST. Between March 2012 and December 2016, we prospectively enrolled 34 locally advanced and/or metastatic RCC who underwent presurgical molecular-targeting therapy followed by radical nephrectomy. Primary endpoint was comparison of radiologic tumor response among Response Evaluation Criteria in Solid Tumors (RECIST), Choi, and contrast media enhancement reduction (CMER). Secondary endpoint included pathological downstaging, treatment related adverse events, postoperative complications, Ki67/MIB1 status, and tumor necrosis. CMER may predict tumor response after presurgical molecular-targeting therapy. Larger prospective studies are needed to develop an optimal tumor response evaluation for molecular-targeting therapy.

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

PubMed

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

2017-09-01

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

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

PubMed Central

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

2012-01-01

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

Geometrically confined ultrasmall gadolinium oxide nanoparticles boost the T1 contrast ability

NASA Astrophysics Data System (ADS)

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

2016-02-01

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

Response assessment challenges in clinical trials of gliomas.

PubMed

Wen, Patrick Y; Norden, Andrew D; Drappatz, Jan; Quant, Eudocia

2010-01-01

Accurate, reproducible criteria for determining tumor response and progression after therapy are critical for optimal patient care and effective evaluation of novel therapeutic agents. Currently, the most widely used criteria for determining treatment response in gliomas is based on two-dimensional tumor measurements using neuroimaging studies (Macdonald criteria). In recent years, the limitation of these criteria, which only address the contrast-enhancing component of the tumor, have become increasingly apparent. This review discusses challenges that have emerged in assessing response in patients with gliomas and approaches being introduced to address them.

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

PubMed

Atar, Eli

2004-07-01

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

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

PubMed

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

2013-12-01

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

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

Counter-propagating wave interaction for contrast-enhanced ultrasound imaging

NASA Astrophysics Data System (ADS)

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

2012-11-01

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

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

NASA Astrophysics Data System (ADS)

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

2011-02-01

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

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

PubMed

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

2015-12-01

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

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

PubMed

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

2017-02-01

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

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

PubMed

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

2008-01-01

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

Assessment of Myocardial Remodeling Using an Elastin/Tropoelastin Specific Agent with High Field Magnetic Resonance Imaging (MRI).

PubMed

Protti, Andrea; Lavin, Begoña; Dong, Xuebin; Lorrio, Silvia; Robinson, Simon; Onthank, David; Shah, Ajay M; Botnar, Rene M

2015-08-13

Well-defined inflammation, proliferation, and maturation phases orchestrate the remodeling of the injured myocardium after myocardial infarction (MI) by controlling the formation of new extracellular matrix. The extracellular matrix consists mainly of collagen but also fractions of elastin. It is thought that elastin is responsible for maintaining elastic properties of the myocardium, thus reducing the risk of premature rupture. An elastin/tropoelastin-specific contrast agent (Gd-ESMA) was used to image tropoelastin and mature elastin fibers for in vivo assessment of extracellular matrix remodeling post-MI. Gd-ESMA enhancement was studied in a mouse model of myocardial infarction using a 7 T MRI scanner and results were compared to those achieved after injection of a nonspecific control contrast agent, gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). In the infarcted tissue, Gd-ESMA uptake (measured as R1 relaxation rate) steadily increased from day 3 to day 21 as a result of the synthesis of elastin/tropoelastin. R1 values were in good agreement with histological findings. A similar R1 behavior was observed in the remote myocardium. No mature cross-linked elastin was found at any time point. In contrast, Gd-DTPA uptake was only observed in the infarct with no changes in R1 values between 3 and 21 days post-MI. We demonstrate the feasibility of in vivo imaging of extracellular matrix remodeling post-MI using a tropoelastin/elastin binding MR contrast agent, Gd-ESMA. We found that tropoelastin is the main contributor to the increased MRI signal at late stages of MI where its augmentation in areas of infarction was in good agreement with the R1 increase. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Influence of contrast agent dose and ultrasound exposure on cardiomyocyte injury induced by myocardial contrast echocardiography in rats.

PubMed

Miller, Douglas L; Li, Peng; Dou, Chunyan; Gordon, David; Edwards, Chris A; Armstrong, William F

2005-10-01

To detect specific cardiomyocyte injury induced by myocardial contrast material-enhanced echocardiography (ie, myocardial contrast echocardiography) in rats and to ascertain the influences of contrast material dose and ultrasound exposure on this injury. All animal procedures were approved by the university committee for the use and care of animals. Myocardial contrast echocardiography with 1:4 electrocardiographic (ECG) triggering was performed at 1.5 MHz in 61 anesthetized rats. Evans blue (EB) dye was injected as the vital stain for cardiomyocyte injury. At the start of myocardial contrast echocardiography, which lasted 10 minutes, perflutren lipid microsphere-based contrast material was infused through the tail vein for 5 minutes. Premature heartbeats were counted from the ECG record. The numbers of EB-stained cells counted on sections of heart specimens obtained 24 hours after myocardial contrast echocardiography and then either fresh frozen or embedded in paraffin were determined by using fluorescence microscopy. Results were compared statistically by using t tests and Mann-Whitney rank sum tests. EB-stained cells were concentrated in the anterior region of the myocardium. In the paraffin-embedded specimens, EB-stained cells were often accompanied by but largely separate from areas of inflammatory cell infiltration. At end-systolic triggering with a 50 microL/kg dose of microsphere contrast material, the EB-stained cell count increased with increasing peak rarefactional pressure amplitude, with significantly increased cell counts at 1.6 MPa (P < .02) and 2.0 MPa (P < .005) relative to the cell counts at sham myocardial contrast echocardiography. Premature heartbeats had a similar exposure-response relationship; however, number of premature heartbeats and EB-stained cell count did not appear to be directly related (coefficient of determination r2 = 0.03). The EB-stained cell counts at end-diastolic triggering were not significantly different from those at end-systolic triggering (P > .1). EB-stained cell counts increased with increasing contrast material dose, from 10 to 50 microL/kg, at 2.0 MPa. Cardiomyocyte injury was induced by the interaction of ultrasound pulses with contrast agent microbubbles during myocardial contrast echocardiography in rats, and the numbers of injured cells increased with increasing contrast agent dose and ultrasound exposure. RSNA, 2005

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

PubMed

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

2010-09-01

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

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

NASA Astrophysics Data System (ADS)

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

1988-06-01

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

Element-specific spectral imaging of multiple contrast agents: a phantom study

NASA Astrophysics Data System (ADS)

Panta, R. K.; Bell, S. T.; Healy, J. L.; Aamir, R.; Bateman, C. J.; Moghiseh, M.; Butler, A. P. H.; Anderson, N. G.

2018-02-01

This work demonstrates the feasibility of simultaneous discrimination of multiple contrast agents based on their element-specific and energy-dependent X-ray attenuation properties using a pre-clinical photon-counting spectral CT. We used a photon-counting based pre-clinical spectral CT scanner with four energy thresholds to measure the X-ray attenuation properties of various concentrations of iodine (9, 18 and 36 mg/ml), gadolinium (2, 4 and 8 mg/ml) and gold (2, 4 and 8 mg/ml) based contrast agents, calcium chloride (140 and 280 mg/ml) and water. We evaluated the spectral imaging performances of different energy threshold schemes between 25 to 82 keV at 118 kVp, based on K-factor and signal-to-noise ratio and ranked them. K-factor was defined as the X-ray attenuation in the K-edge containing energy range divided by the X-ray attenuation in the preceding energy range, expressed as a percentage. We evaluated the effectiveness of the optimised energy selection to discriminate all three contrast agents in a phantom of 33 mm diameter. A photon-counting spectral CT using four energy thresholds of 27, 33, 49 and 81 keV at 118 kVp simultaneously discriminated three contrast agents based on iodine, gadolinium and gold at various concentrations using their K-edge and energy-dependent X-ray attenuation features in a single scan. A ranking method to evaluate spectral imaging performance enabled energy thresholds to be optimised to discriminate iodine, gadolinium and gold contrast agents in a single spectral CT scan. Simultaneous discrimination of multiple contrast agents in a single scan is likely to open up new possibilities of improving the accuracy of disease diagnosis by simultaneously imaging multiple bio-markers each labelled with a nano-contrast agent.

MRI mediated, non-invasive tracking of intratumoral distribution of nanocarriers in rat glioma

NASA Astrophysics Data System (ADS)

Karathanasis, Efstathios; Park, Jaekeun; Agarwal, Abhiruchi; Patel, Vijal; Zhao, Fuqiang; Annapragada, Ananth V.; Hu, Xiaoping; Bellamkonda, Ravi V.

2008-08-01

Nanocarrier mediated therapy of gliomas has shown promise. The success of systemic nanocarrier-based chemotherapy is critically dependent on the so-called leaky vasculature to permit drug extravasation across the blood-brain barrier. Yet, the extent of vascular permeability in individual tumors varies widely, resulting in a correspondingly wide range of responses to the therapy. However, there exist no tools currently for rationally determining whether tumor blood vessels are amenable to nanocarrier mediated therapy in an individualized, patient specific manner today. To address this need for brain tumor therapy, we have developed a multifunctional 100 nm scale liposomal agent encapsulating a gadolinium-based contrast agent for contrast-enhanced magnetic resonance imaging with prolonged blood circulation. Using a 9.4 T MRI system, we were able to track the intratumoral distribution of the gadolinium-loaded nanocarrier in a rat glioma model for a period of three days due to improved magnetic properties of the contrast agent being packaged in a nanocarrier. Such a nanocarrier provides a tool for non-invasively assessing the suitability of tumors for nanocarrier mediated therapy and then optimizing the treatment protocol for each individual tumor. Additionally, the ability to image the tumor in high resolution can potentially constitute a surgical planning tool for tumor resection.

MRI mediated, non-invasive tracking of intratumoral distribution of nanocarriers in rat glioma.

PubMed

Karathanasis, Efstathios; Park, Jaekeun; Agarwal, Abhiruchi; Patel, Vijal; Zhao, Fuqiang; Annapragada, Ananth V; Hu, Xiaoping; Bellamkonda, Ravi V

2008-08-06

Nanocarrier mediated therapy of gliomas has shown promise. The success of systemic nanocarrier-based chemotherapy is critically dependent on the so-called leaky vasculature to permit drug extravasation across the blood-brain barrier. Yet, the extent of vascular permeability in individual tumors varies widely, resulting in a correspondingly wide range of responses to the therapy. However, there exist no tools currently for rationally determining whether tumor blood vessels are amenable to nanocarrier mediated therapy in an individualized, patient specific manner today. To address this need for brain tumor therapy, we have developed a multifunctional 100 nm scale liposomal agent encapsulating a gadolinium-based contrast agent for contrast-enhanced magnetic resonance imaging with prolonged blood circulation. Using a 9.4 T MRI system, we were able to track the intratumoral distribution of the gadolinium-loaded nanocarrier in a rat glioma model for a period of three days due to improved magnetic properties of the contrast agent being packaged in a nanocarrier. Such a nanocarrier provides a tool for non-invasively assessing the suitability of tumors for nanocarrier mediated therapy and then optimizing the treatment protocol for each individual tumor. Additionally, the ability to image the tumor in high resolution can potentially constitute a surgical planning tool for tumor resection.

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

Contrast changes in fluoroscopic imaging systems and statistical variations of these changes

NASA Technical Reports Server (NTRS)

Bailey, N. A.

1973-01-01

Experimental studies have indicated that: (1) The response of digitized fluoroscopic imaging systems is linear systems is linear with contrast over a rather wide range of absorber and cavity thicknesses. (2) Contrast changes associated with the addition of aluminum, iodine containing contrast agents and air of thicknesses 1mm or less can be detected with a 95% confidence level. (3) The standard deviation associated with such determination using clinically available X-ray generators and video disc recording is less than 1 percent. A large flat screen X-ray image intensifier has been constructed and some preliminary results obtained. Sensitivity achieved makes dose reduction a factor often greater than previously reported for a system using a conventional X-ray image intensifier.

Tumor environment changed by combretastatin derivative (Cderiv) pretreatment that leads to effective tumor targeting, MRI studies, and antitumor activity of polymeric micelle carrier systems.

PubMed

Shiraishi, Kouichi; Harada, Yoshiko; Kawano, Kumi; Maitani, Yoshie; Hori, Katsuyoshi; Yanagihara, Kazuyoshi; Takigahira, Misato; Yokoyama, Masayuki

2012-01-01

To evaluate effect of a vascular disrupting agent, a combretastatin derivative (Cderiv), on tumor targeting for polymeric micelle carrier systems, containing either a diagnostic MRI contrast agent or a therapeutic anticancer drug. Cderiv was pre-administered 72 h before polymeric micelle MRI contrast agent injection. Accumulation of the MRI contrast agent in colon 26 murine tumor was evaluated with or without pretreatment of Cderiv by ICP and MRI. Significantly higher accumulation of the MRI contrast agent was found in tumor tissues when Cderiv was administered at 72 h before MRI contrast agent injection. T(1)-weighted images of the tumor exhibited substantial signal enhancement in tumor area at 24 h after the contrast agent injection. In T(1)-weighted images, remarkable T(1)-signal enhancements were observed in part of tumor, not in whole tumor. These results indicate that Cderiv pretreatment considerably enhanced the permeability of the tumor blood vessels. Antitumor activity of adriamycin encapsulated polymeric micelles with the Cderiv pretreatment suppressed tumor growth in 44As3 human gastric scirrhous carcinoma-bearing nude mice. Pretreatment of Cderiv enhanced tumor permeability, resulting in higher accumulation of polymeric micelle carrier systems in solid tumors.

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

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

NASA Astrophysics Data System (ADS)

Ng, Thian C.

2012-06-01

It is known that one strength of MRI is its excellent soft tissue discrimination. It naturally provides sufficient contrast between the structural differences of normal and pathological tissues, their spatial extent and progression. However, to further extend its applications and enhance even more contrast for clinical studies, various Gadolinium (Gd)-based contrast agents have been developed for different organs (brain strokes, cancer, cardio-MRI, etc). These Gd-based contrast agents are paramagnetic compounds that have strong T1-effect for enhancing the contrast between tissue types. Gd-contrast can also enhance magnetic resonance angiography (CE-MRA) for studying stenosis and for measuring perfusion, vascular susceptibility, interstitial space, etc. Another class of contrast agents makes use of ferrite iron oxide nanoparticles (including Superparamagnetic Ion Oxide (SPIO) and Ultrasmall Superparamagnetic Iron Oxide (USPIO)). These nanoparticles have superior magnetic susceptibility effect and produce a drop in signal, namely in T2*-weighted images, useful for the determination of lymph nodes metastases, angiogenesis and arteriosclerosis plaques.

Structural and functional photoacoustic molecular tomography aided by emerging contrast agents

PubMed Central

Nie, Liming

2015-01-01

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

Biocompatible and high-performance amino acids-capped MnWO4 nanocasting as a novel non-lanthanide contrast agent for X-ray computed tomography and T1-weighted magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Dong, Kai; Liu, Zhen; Liu, Jianhua; Huang, Sa; Li, Zhenhua; Yuan, Qinghai; Ren, Jinsong; Qu, Xiaogang

2014-01-01

In the present work, a novel non-lanthanide dual-modality contrast agent, manganese tungstate (MnWO4), has been successfully constructed by a facile and versatile hydrothermal route. With the merits of a high atomic number and a well-positioned K-edge energy of tungsten, our well-prepared non-lanthanide nanoprobes provide a higher contrast efficacy than routine iodine-based agents in clinics. Additionally, the presence of Mn in these nanoparticles endow them with excellent T1-weighted MR imaging capabilities. As an alternative to T2-weighted MRI and CT dual-modality contrast agents, the nanoprobes can provide a positive contrast signal, which prevents confusion with the dark signals from hemorrhage and blood clots. To the best of our knowledge, this is the first report that a non-lanthanide imaging nanoprobe is applied for CT and T1-weighted MRI simultaneously. Moreover, comparing with gadolinium-based T1-weighted MRI and CT dual-modality contrast agents that were associated with nephrogenic systemic fibrosis (NSF), our contrast agents have superior biocompatibility, which is proved by a detailed study of the pharmacokinetics, biodistribution, and in vivo toxicology. Together with excellent dispersibility, high biocompatibility and superior contrast efficacy, these nanoprobes provide detailed and complementary information from dual-modality imaging over traditional single-mode imaging and bring more opportunities to the new generation of non-lanthanide nanoparticulate-based contrast agents.In the present work, a novel non-lanthanide dual-modality contrast agent, manganese tungstate (MnWO4), has been successfully constructed by a facile and versatile hydrothermal route. With the merits of a high atomic number and a well-positioned K-edge energy of tungsten, our well-prepared non-lanthanide nanoprobes provide a higher contrast efficacy than routine iodine-based agents in clinics. Additionally, the presence of Mn in these nanoparticles endow them with excellent T1-weighted MR imaging capabilities. As an alternative to T2-weighted MRI and CT dual-modality contrast agents, the nanoprobes can provide a positive contrast signal, which prevents confusion with the dark signals from hemorrhage and blood clots. To the best of our knowledge, this is the first report that a non-lanthanide imaging nanoprobe is applied for CT and T1-weighted MRI simultaneously. Moreover, comparing with gadolinium-based T1-weighted MRI and CT dual-modality contrast agents that were associated with nephrogenic systemic fibrosis (NSF), our contrast agents have superior biocompatibility, which is proved by a detailed study of the pharmacokinetics, biodistribution, and in vivo toxicology. Together with excellent dispersibility, high biocompatibility and superior contrast efficacy, these nanoprobes provide detailed and complementary information from dual-modality imaging over traditional single-mode imaging and bring more opportunities to the new generation of non-lanthanide nanoparticulate-based contrast agents. Electronic supplementary information (ESI) available: TEM images of MnWO4 nanoparticles synthesized at pH = 7, 180 °C pH = 9, 180 °C pH = 6, 200 °C with various amino acid molecules as capped agents, survey XPS spectra, FTIR spectrum of glycine capped MnWO4 nanorods, photos of glycine capped MnWO4 nanorods in various solutions including PBS, DMEM cell medium, and FBS, in vivo coronal view CT images of a rat before and after intravenous injection of iobitridol at different timed intervals, in vivo CT imaging of the rat one month after intravenous injection of MnWO4 nanorods, CT values of the heart, liver, spleen and kidney of a rat before and after intravenous administration of MnWO4 nanorods and iobitridol at different time intervals, hematology analysis and blood biochemical assay. See DOI: 10.1039/c3nr05455a

Cationic Contrast Agent Diffusion Differs Between Cartilage and Meniscus.

PubMed

Honkanen, Juuso T J; Turunen, Mikael J; Freedman, Jonathan D; Saarakkala, Simo; Grinstaff, Mark W; Ylärinne, Janne H; Jurvelin, Jukka S; Töyräs, Juha

2016-10-01

Contrast enhanced computed tomography (CECT) is a non-destructive imaging technique used for the assessment of composition and structure of articular cartilage and meniscus. Due to structural and compositional differences between these tissues, diffusion and distribution of contrast agents may differ in cartilage and meniscus. The aim of this study is to determine the diffusion kinematics of a novel iodine based cationic contrast agent (CA(2+)) in cartilage and meniscus. Cylindrical cartilage and meniscus samples (d = 6 mm, h ≈ 2 mm) were harvested from healthy bovine knee joints (n = 10), immersed in isotonic cationic contrast agent (20 mgI/mL), and imaged using a micro-CT scanner at 26 time points up to 48 h. Subsequently, normalized X-ray attenuation and contrast agent diffusion flux, as well as water, collagen and proteoglycan (PG) contents in the tissues were determined. The contrast agent distributions within cartilage and meniscus were different. In addition, the normalized attenuation and diffusion flux were higher (p < 0.05) in cartilage. Based on these results, diffusion kinematics vary between cartilage and meniscus. These tissue specific variations can affect the interpretation of CECT images and should be considered when cartilage and meniscus are assessed simultaneously.

Contrast-enhanced and targeted ultrasound.

PubMed

Postema, Michiel; Gilja, Odd Helge

2011-01-07

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

Contrast-enhanced and targeted ultrasound

PubMed Central

Postema, Michiel; Gilja, Odd Helge

2011-01-01

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

Renal contrast-enhanced MR angiography: timing errors and accurate depiction of renal artery origins.

PubMed

Schmidt, Maria A; Morgan, Robert

2008-10-01

To investigate bolus timing artifacts that impair depiction of renal arteries at contrast material-enhanced magnetic resonance (MR) angiography and to determine the effect of contrast agent infusion rates on artifact generation. Renal contrast-enhanced MR angiography was simulated for a variety of infusion schemes, assuming both correct and incorrect timing between data acquisition and contrast agent injection. In addition, the ethics committee approved the retrospective evaluation of clinical breath-hold renal contrast-enhanced MR angiographic studies obtained with automated detection of contrast agent arrival. Twenty-two studies were evaluated for their ability to depict the origin of renal arteries in patent vessels and for any signs of timing errors. Simulations showed that a completely artifactual stenosis or an artifactual overestimation of an existing stenosis at the renal artery origin can be caused by timing errors of the order of 5 seconds in examinations performed with contrast agent infusion rates compatible with or higher than those of hand injections. Lower infusion rates make the studies more likely to accurately depict the origin of the renal arteries. In approximately one-third of all clinical examinations, different contrast agent uptake rates were detected on the left and right sides of the body, and thus allowed us to confirm that it is often impossible to optimize depiction of both renal arteries. In three renal arteries, a signal void was found at the origin in a patent vessel, and delayed contrast agent arrival was confirmed. Computer simulations and clinical examinations showed that timing errors impair the accurate depiction of renal artery origins. (c) RSNA, 2008.

[Adult transient intestinal intussusception: can abdominal CT guide resolution?].

PubMed

Stabile Ianora, Amato Antonio; Telegrafo, Michele; Lorusso, Valentina; Rella, Leonarda; Niccoli Asabella, Artor; La Porta, Michele; Moschetta, Marco

2013-01-01

The purpose of this study was to evaluate the adult transient intestinal intussusceptions on CT before and after the administration of gastrointestinal contrast material. We evaluated two different gastrointestinal contrast materials: hyperdense and hypodense. In all cases the gastrointestinal contrast agent solved the invaginations. In the group of patients treated with hypodense contrast medium relapses occurred in the short and long term; no recurrence was observed in the other group. CT is useful in the recognition of intestinal intussusception. The gastrointestinal contrast agent could define the real transience of intussusceptions and hyperdense contrast agent could be more effective in short and long term resolution.

Biological and Clinical Aspects of Lanthanide Coordination Compounds

PubMed Central

Misra, Sudhindra N.; M., Indira Devi; Shukla, Ram S.

2004-01-01

The coordinating chemistry of lanthanides, relevant to the biological, biochemical and medical aspects, makes a significant contribution to understanding the basis of application of lanthanides, particularly in biological and medical systems. The importance of the applications of lanthanides, as an excellent diagnostic and prognostic probe in clinical diagnostics, and an anticancer material, is remarkably increasing. Lanthanide complexes based X-ray contrast imaging and lanthanide chelates based contrast enhancing agents for magnetic resonance imaging (MRI) are being excessively used in radiological analysis in our body systems. The most important property of the chelating agents, in lanthanide chelate complex, is its ability to alter the behaviour of lanthanide ion with which it binds in biological systems, and the chelation markedly modifies the biodistribution and excretion profile of the lanthanide ions. The chelating agents, especially aminopoly carboxylic acids, being hydrophilic, increase the proportion of their complex excreted from complexed lanthanide ion form biological systems. Lanthanide polyamino carboxylate-chelate complexes are used as contrast enhancing agents for Magnetic Resonance Imaging. Conjugation of antibodies and other tissue specific molecules to lanthanide chelates has led to a new type of specific MRI contrast agents and their conjugated MRI contrast agents with improved relaxivity, functioning in the body similar to drugs. Many specific features of contrast agent assisted MRI make it particularly effective for musculoskeletal and cerebrospinal imaging. Lanthanide-chelate contrast agents are effectively used in clinical diagnostic investigations involving cerebrospinal diseases and in evaluation of central nervous system. Chelated lanthanide complexes shift reagent aided 23Na NMR spectroscopic analysis is used in cellular, tissue and whole organ systems. PMID:18365075

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

NASA Astrophysics Data System (ADS)

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

2017-09-01

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

Anti-EpCAM scFv gadolinium chelate: a novel targeted MRI contrast agent for imaging of colorectal cancer.

PubMed

Khantasup, Kannika; Saiviroonporn, Pairash; Jarussophon, Suwatchai; Chantima, Warangkana; Dharakul, Tararaj

2018-05-08

The development of targeted contrast agents for magnetic resonance imaging (MRI) facilitates enhanced cancer imaging and more accurate diagnosis. In the present study, a novel contrast agent was developed by conjugating anti-EpCAM humanized scFv with gadolinium chelate to achieve target specificity. The material design strategy involved site-specific conjugation of the chelating agent to scFv. The scFv monomer was linked to maleimide-DTPA via unpaired cysteine at the scFv C-terminus, followed by chelation with gadolinium (Gd). Successful scFv-DTPA conjugation was achieved at 1:10 molar ratio of scFv to maleimide-DTPA at pH 6.5. The developed anti-EpCAM-Gd-DTPA MRI contrast agent was evaluated for cell targeting ability, in vitro serum stability, cell cytotoxicity, relaxivity, and MR contrast enhancement. A high level of targeting efficacy of anti-EpCAM-Gd-DTPA to an EpCAM-overexpressing HT29 colorectal cell was demonstrated by confocal microscopy. Good stability of the contrast agent was obtained and no cytotoxicity was observed in HT29 cells after 48 h incubation with 25-100 µM of Gd. Favorable imaging was obtained using anti-EpCAM-Gd-DTPA, including 1.8-fold enhanced relaxivity compared with Gd-DTPA, and MR contrast enhancement observed after binding to HT29. The potential benefit of this contrast agent for in vivo MR imaging of colorectal cancer, as well as other EpCAM positive cancers, is suggested and warrants further investigation.

Effect of iodinated low-osmolar contrast media on the hemostatic system after intraarterial and intravenous contrast administration.

PubMed

Lukasiewicz, A; Lebkowska, U; Galar, M

2012-01-01

Some of the adverse clinical effects of intravascular radiological contrast agents include the interference of these contrast media with normal hemostatic processes. The aim of this report was to investigate in vivo whether a non-ionic iodinated contrast agent possess prothrombotic or anticoagulant properties. Hemostatic parameters: vWF (von Willebrand factor), F1+2 (prothrombin fragments 1+2), TAT (thrombin-antithrombin complexes), D-Dimer, β-TG (beta-thromboglobulin) were measured in a group of 35 patients. Blood samples for laboratory investigations were collected before and 30 min after the administration of a iodine contrast agent. There was observed statistically highly significant contrast-induced increase in TAT and F1+2 (p = 0.005 and p = 0.008, respectively). D-Dimer increase and decrease of β-TG and vWF after contrast medium administration were non significant. The volume of contrast medium has no influence on the assessed hemostatic parameters, while the type of contrast medium and/or the route of the contrast administration may significantly affect hemostatic parameters. We found significant effects of non-ionic agents on hemostatic activation. These effects may be important for adverse reactions and for thromboembolic complications.

Development and Applications of Photo-triggered Theranostic Agents

PubMed Central

Rai, Prakash; Mallidi, Srivallesha; Zheng, Xiang; Rahmanzadeh, Ramtin; Mir, Youssef; Elrington, Stefan; Khurshid, Ahmat; Hasan, Tayyaba

2010-01-01

Theranostics, the fusion of therapy and diagnostics for optimizing efficacy and safety of therapeutic regimes, is a growing field that is paving the way towards the goal of personalized medicine for the benefit of patients. The use of light as a remote-activation mechanism for drug delivery has received increased attention due to its advantages in highly specific spatial and temporal control of compound release. Photo-triggered theranostic constructs could facilitate an entirely new category of clinical solutions which permit early recognition of the disease by enhancing contrast in various imaging modalities followed by the tailored guidance of therapy. Finally, such theranostic agents could aid imaging modalities in monitoring response to therapy. This article reviews recent developments in the use of light-triggered theranostic agents for simultaneous imaging and photoactivation of therapeutic agents. Specifically, we discuss recent developments in the use of theranostic agents for photodynamic-, photothermal- or photo-triggered chemo-therapy for several diseases. PMID:20858520

[Complications due to contrast agent administration: what has been confirmed in prevention?].

PubMed

Schönenberger, E; Mühler, M; Dewey, M

2010-12-01

Computed tomography (CT) and magnetic resonance imaging (MRI) have been evaluated by internists to be the most important medical innovations. Often, intravenous contrast agent administration is required for answering the clinical questions to CT and MRI. In this review we present an overview of the most common and most important aspects that need to be considered prior to intravenous contrast agent administration. We discuss aspects of renal impairment (contrast-induced nephropathy, nephrogenic systemic fibrosis), allergy-like reactions, hyperthyroidism, and pregnancy and breast-feeding.

Image reconstruction for x-ray K-edge imaging with a photon counting detector

NASA Astrophysics Data System (ADS)

Meng, Bo; Cong, Wenxiang; Xi, Yan; Wang, Ge

2014-09-01

Contrast agents with high-Z elements have K-absorption edges which significantly change X-ray attenuation coefficients. The K-edge characteristics is different for various kinds of contrast agents, which offers opportunities for material decomposition in biomedical applications. In this paper, we propose a new K-edge imaging method, which not only quantifies a distribution of a contrast agent but also provides an optimized contrast ratio. Our numerical simulation tests demonstrate the feasibility and merits of the proposed methodology.

Contrast-enhanced CT with a High-Affinity Cationic Contrast Agent for Imaging ex Vivo Bovine, Intact ex Vivo Rabbit, and in Vivo Rabbit Cartilage

PubMed Central

Stewart, Rachel C.; Bansal, Prashant N.; Entezari, Vahid; Lusic, Hrvoje; Nazarian, Rosalynn M.; Snyder, Brian D.

2013-01-01

Purpose: To quantify the affinity of a cationic computed tomography (CT) contrast agent (CA4+) and that of an anionic contrast agent (ioxaglate) to glycosaminoglycans (GAGs) in ex vivo cartilage tissue explants and to characterize the in vivo diffusion kinetics of CA4+ and ioxaglate in a rabbit model. Materials and Methods: All in vivo procedures were approved by the institutional animal care and use committee. The affinities of ioxaglate and CA4+ to GAGs in cartilage (six bovine osteochondral plugs) were quantified by means of a modified binding assay using micro-CT after plug equilibration in serial dilutions of each agent. The contrast agents were administered intraarticularly to the knee joints of five New Zealand white rabbits to determine the in vivo diffusion kinetics and cartilage tissue imaging capabilities. Kinetics of diffusion into the femoral groove cartilage and relative contrast agent uptake into bovine plugs were characterized by means of nonlinear mixed-effects models. Diffusion time constants (τ) were compared by using a Student t test. Results: The uptake of CA4+ in cartilage was consistently over 100% of the reservoir concentration, whereas it was only 59% for ioxaglate. In vivo, the contrast material–enhanced cartilage reached a steady CT attenuation for both CA4+ and ioxaglate, with τ values of 13.8 and 6.5 minutes, respectively (P = .04). The cartilage was easily distinguishable from the surrounding tissues for CA4+ (12 mg of iodine per milliliter); comparatively, the anionic contrast agent provided less favorable imaging results, even when a higher concentration was used (80 mg of iodine per milliliter). Conclusion: The affinity of the cationic contrast agent CA4+ to GAGs enables high-quality imaging and segmentation of ex vivo bovine and rabbit cartilage, as well as in vivo rabbit cartilage. © RSNA, 2012 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112246/-/DC1 PMID:23192774

Preclinical evaluation of Gd-DTPA and gadomelitol as contrast agents in DCE-MRI of cervical carcinoma interstitial fluid pressure.

PubMed

Hompland, Tord; Ellingsen, Christine; Rofstad, Einar K

2012-11-22

High interstitial fluid pressure (IFP) in the primary tumor is associated with poor disease-free survival in locally advanced cervical carcinoma. A noninvasive assay is needed to identify cervical cancer patients with highly elevated tumor IFP because these patients may benefit from particularly aggressive treatment. It has been suggested that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) as contrast agent may provide useful information on the IFP of cervical carcinomas. In this preclinical study, we investigated whether DCE-MRI with contrast agents with higher molecular weights (MW) than Gd-DTPA would be superior to Gd-DTPA-based DCE-MRI. CK-160 human cervical carcinoma xenografts were subjected to DCE-MRI with Gd-DTPA (MW of 0.55 kDa) or gadomelitol (MW of 6.5 kDa) as contrast agent before tumor IFP was measured invasively with a Millar SPC 320 catheter. The DCE-MRI was carried out at a spatial resolution of 0.23 × 0.23 × 2.0 mm³ and a time resolution of 14 s by using a 1.5-T whole-body scanner and a slotted tube resonator transceiver coil constructed for mice. Parametric images were derived from the DCE-MRI recordings by using the Tofts iso-directional transport model and the Patlak uni-directional transport model. When gadomelitol was used as contrast agent, significant positive correlations were found between the parameters of both pharmacokinetic models and tumor IFP. On the other hand, significant correlations between DCE-MRI-derived parameters and IFP could not be detected with Gd-DTPA as contrast agent. Gadomelitol is a superior contrast agent to Gd-DTPA in DCE-MRI of the IFP of CK-160 cervical carcinoma xenografts. Clinical studies attempting to develop DCE-MRI-based assays of the IFP of cervical carcinomas should involve contrast agents with higher MW than Gd-DTPA.

Aptamer-Targeted Gold Nanoparticles As Molecular-Specific Contrast Agents for Reflectance Imaging

PubMed Central

2008-01-01

Targeted metallic nanoparticles have shown potential as a platform for development of molecular-specific contrast agents. Aptamers have recently been demonstrated as ideal candidates for molecular targeting applications. In this study, we investigated the development of aptamer-based gold nanoparticles as contrast agents, using aptamers as targeting agents and gold nanoparticles as imaging agents. We devised a novel conjugation approach using an extended aptamer design where the extension is complementary to an oligonucleotide sequence attached to the surface of the gold nanoparticles. The chemical and optical properties of the aptamer−gold conjugates were characterized using size measurements and oligonucleotide quantitation assays. We demonstrate this conjugation approach to create a contrast agent designed for detection of prostate-specific membrane antigen (PSMA), obtaining reflectance images of PSMA(+) and PSMA(−) cell lines treated with the anti-PSMA aptamer−gold conjugates. This design strategy can easily be modified to incorporate multifunctional agents as part of a multimodal platform for reflectance imaging applications. PMID:18512972

Validation of dynamic contrast-enhanced ultrasound in predicting outcomes of antiangiogenic therapy for solid tumors: the French multicenter support for innovative and expensive techniques study.

PubMed

Lassau, Nathalie; Bonastre, Julia; Kind, Michèle; Vilgrain, Valérie; Lacroix, Joëlle; Cuinet, Marie; Taieb, Sophie; Aziza, Richard; Sarran, Antony; Labbe-Devilliers, Catherine; Gallix, Benoit; Lucidarme, Olivier; Ptak, Yvette; Rocher, Laurence; Caquot, Louis-Michel; Chagnon, Sophie; Marion, Denis; Luciani, Alain; Feutray, Sylvaine; Uzan-Augui, Joëlle; Coiffier, Benedicte; Benastou, Baya; Koscielny, Serge

2014-12-01

Dynamic contrast-enhanced ultrasound (DCE-US) has been used in single-center studies to evaluate tumor response to antiangiogenic treatments: the change of area under the perfusion curve (AUC), a criterion linked to blood volume, was consistently correlated with the Response Evaluation Criteria in Solid Tumors response. The main objective here was to do a multicentric validation of the use of DCE-US to evaluate tumor response in different solid tumor types treated by several antiangiogenic agents. A secondary objective was to evaluate the costs of the procedure. This prospective study included patients from 2007 to 2010 in 19 centers (8 teaching hospitals and 11 comprehensive cancer centers). All patients treated with antiangiogenic therapy were eligible. Dynamic contrast-enhanced ultrasound examinations were performed at baseline as well as on days 7, 15, 30, and 60. For each examination, a perfusion curve was recorded during 3 minutes after injection of a contrast agent. Change from baseline at each time point was estimated for each of 7 fitted criteria. The main end point was freedom from progression (FFP). Criterion/time-point combinations with the strongest correlation with FFP were analyzed further to estimate an optimal cutoff point. A total of 1968 DCE-US examinations in 539 patients were analyzed. The median follow-up was 1.65 years. Variations from baseline were significant at day 30 for several criteria, with AUC having the most significant association with FFP (P = 0.00002). Patients with a greater than 40% decrease in AUC at day 30 had better FFP (P = 0.005) and overall survival (P = 0.05). The mean cost of each DCE-US was 180&OV0556;, which corresponds to $250 using the current exchange rate. Dynamic contrast-enhanced ultrasound is a new functional imaging technique that provides a validated criterion, namely, the change of AUC from baseline to day 30, which is predictive of tumor progression in a large multicenter cohort. Because of its low cost, it should be considered in the routine evaluation of solid tumors treated with antiangiogenic therapy.

Sexual dysfunction with antihypertensive and antipsychotic agents.

PubMed

Smith, P J; Talbert, R L

1986-05-01

The physiology of the normal sexual response, epidemiology of sexual dysfunction, and the pharmacologic mechanisms involved in antihypertensive- and antipsychotic-induced problems with sexual function are discussed, with recommendations for patient management. The physiologic mechanisms involved in the normal sexual response include neurogenic, psychogenic, vascular, and hormonal factors that are coordinated by centers in the hypothalamus, limbic system, and cerebral cortex. Sexual dysfunction is frequently attributed to antihypertensive and antipsychotic agents and is a cause of noncompliance. Drug-induced effects include diminished libido, delayed orgasm, ejaculatory disturbances, gynecomastia, impotence, and priapism. The pharmacologic mechanisms proposed to account for these adverse effects include adrenergic inhibition, adrenergic-receptor blockade, anticholinergic properties, and endocrine and sedative effects. The most frequently reported adverse effect on sexual function with the antihypertensive agents is impotence. It is seen most often with methyldopa, guanethidine, clonidine, and propranolol. In contrast, the most common adverse effect on sexual function with the antipsychotic agents involves ejaculatory disturbances. Thioridazine, with its potent anticholinergic and alpha-blocking properties, is cited most often. Drug-induced sexual dysfunction may be alleviated by switching to agents with dissimilar mechanisms to alter the observed adverse effect while maintaining adequate control of the patient's disease state.

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

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

PubMed

Lancharro Zapata, Á M; Rodríguez, C Marín

2016-05-01

It is essential to minimize exposure to ionizing radiation in children for various reasons. The risk of developing a tumor from exposure to a given dose of radiation is greater in childhood. Various strategies can be used to reduce exposure to ionizing radiation. It is fundamental to avoid unnecessary tests and tests that are not indicated, to choose an alternative test that does not use ionizing radiation, and/or to take a series of measures that minimize the dose of radiation that the patient receives, such as avoiding having to repeat tests, using the appropriate projections, using shields, adjusting the protocol (mAs, Kv, or pitch) to the patient's body volume, etc… When contrast agents are necessary, intracavitary ultrasound agents can be used, although the use of ultrasound agents is also being extended to include intravenous administration. In fluoroscopy, contrast agents with low osmolarity must be used, as in CT where we must adjust the dose and speed of injection to the patient's weight and to the caliber of the peripheral line, respectively. In MRI, only three types of contrast agents have been approved for pediatric use. It is sometimes necessary to use double doses or organ-specific contrast agents in certain clinical situations; the safety of contrast agents for these indications has not been proven, so they must be used off label. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Pattern of Retained Contrast on Immediate Postprocedure Computed tomography (CT) After Particle Embolization of Liver Tumors Predicts Subsequent Treatment Response

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

Wang Xiaodong, E-mail: wangxde@gmail.com; Erinjeri, Joseph P., E-mail: erinjerj@mskcc.org; Jia Xiaoyu, E-mail: jiax@mskcc.org

2013-08-01

PurposeTo determine if the pattern of retained contrast on immediate postprocedure computed tomography (CT) after particle embolization of hepatic tumors predicts modified Response Evaluation Criteria in Solid Tumors (mRECIST) response.Materials and MethodsThis study was approved by the Institutional Review Board with a waiver of authorization. One hundred four liver tumors were embolized with spherical embolic agents (Embospheres, Bead Block, LC Bead) and polyvinyl alcohol. Noncontrast CT was performed immediately after embolization to assess contrast retention in the targeted tumors, and treatment response was assessed by mRECIST criteria on follow-up CT (average time 9.0 {+-} 7.7 weeks after embolization). Tumor contrastmore » retention (TCR) was determined based on change in Hounsfield units (HUs) of the index tumors between the preprocedure and immediate postprocedure scans; vascular contrast retention (VCR) was rated; and defects in contrast retention (DCR) were also documented. The morphology of residual enhancing tumor on follow-up CT was described as partial, circumferential, or total. Association between TCR variables and tumor response were assessed using multivariate logistic regression.ResultsOf 104 hepatic tumors, 51 (49 %) tumors had complete response (CR) by mRECIST criteria; 23 (22.1 %) had partial response (PR); 21 (20.2 %) had stable disease (SD); and 9 (8.7 %) had progressive disease (PD). By multivariate analysis, TCR, VCR, and tumor size are independent predictors of CR (p = 0.02, 0.05, and 0.005 respectively). In 75 tumors, DCR was found to be an independent predictor of failure to achieve complete response (p < 0.0001) by imaging criteria.ConclusionTCR, VCR, and DCR on immediate posttreatment CT are independent predictors of CR by mRECIST criteria.« less

Electric-field responsive contrast agent based on liquid crystals and magnetic nanoparticles

NASA Astrophysics Data System (ADS)

Mair, Lamar O.; Martinez-Miranda, Luz J.; Kurihara, Lynn K.; Nacev, Aleksandar; Hilaman, Ryan; Chowdhury, Sagar; Jafari, Sahar; Ijanaten, Said; da Silva, Claudian; Baker-McKee, James; Stepanov, Pavel Y.; Weinberg, Irving N.

2018-05-01

The properties of liquid crystal-magnetic nanoparticle composites have potential for sensing in the body. We study the response of a liquid crystal-magnetic nanoparticle (LC-MNP) composite to applied potentials of hundreds of volts per meter. Measuring samples using X-ray diffraction (XRD) and imaging composites using magnetic resonance imaging (MRI), we demonstrate that electric potentials applied across centimeter scale LC-MNP composite samples can be detected using XRD and MRI techniques.

Contrast agent choice for intravenous coronary angiography

NASA Astrophysics Data System (ADS)

Zeman, H. D.; Siddons, D. P.

1990-05-01

The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with monochromatic synchrotron radiation X-rays and an iodine-containing contrast agent at the Stanford Synchrotron Radiation Laboratory have shown that such an intravenous angiography procedure would be possible with an adequately intense monochromatic X-ray source. Because of the size and cost of synchrotron radiation facilities it would be desirable to make the most efficient use of the intensity available, while reducing as much as possible the radiation dose experienced by the patient. By choosing contrast agents containing elements with a higher atomic number than iodine, it is possible to both improve the image quality and reduce the patient radiation dose, while using the same synchrotron radiation source. By using Si monochromator crystals with a small mosaic spread, it is possible to increase the X-ray flux available for imaging by over an order of magnitude, without any changes in the storage ring or wiggler magnet. The most critical imaging task for intravenous coronary angiography utilizing synchrotron radiation X-rays is visualizing a coronary artery through the left ventricle or aorta which also contain contrast agent. Calculations have been made of the signal to noise ratio expected for this imaging task for various contrast agents with atomic numbers between that of iodine and bismuth. The X-ray energy spectrum of the X-17 superconduction wiggler beam line at the National Synchrotron Light Source at Brookhaven National Laboratory has been used for these calculations. Both perfect Si crystals and Si crystals with a small mosaic spread are considered as monochromators. Contrast agents containing Gd or Yb seem to have about the optimal calculated signal to noise ratio. Gd-DTPA is already approved for use as a contrast agent for magnetic resonance imaging. Experiments have already been performed with Yb-DTPA in animals, and it appears to have a lower toxicity than that of Gd-DTPA. Reported animal experiments with Gd-DOTA contrast agent show no toxicity at all.

Advancement of multifunctional hybrid nanogel systems: Construction and application in drug co-delivery and imaging technique.

PubMed

Ma, Yakun; Ge, Yanxiu; Li, Lingbing

2017-02-01

Nanogel-based multifunctional drug delivery systems, especially hybrid nanogels and multicompartment nanogels have drawn more and more extensive attention from the researchers in pharmacy because it can result in achieving a superior functionality through the synergistic property enhancement of each component. The unique hybrid and compartmentalized structures provide the great potential for co-delivery of multiple agents even the multiple agents with different physicochemical properties. Otherwise the hybrid nanogel encapsulating optical and magnetic resonance imaging contrast can be utilized in imaging technique for disease diagnosis. More importantly through nanogel-based multifunctional drug delivery systems the stimuli-responsive features might be easily employed for the design of targeted release of drug. This review summarizes the construction of diverse hybrid nanogels and multicompartment nanogels. The application in co-delivery of multiple agents and imaging agents for diagnosis as well as the application in the design of stimuli-responsive multifunctional nanogels as drug delivery are also reviewed and discussed. The future prospects in application of multifunctional nanogels will be also discussed in this review. Copyright © 2016 Elsevier B.V. All rights reserved.

Enhanced Positive-Contrast Visualization of Paramagnetic Contrast Agents Using Phase Images

PubMed Central

Mills, Parker H.; Ahrens, Eric T.

2009-01-01

Iron oxide–based MRI contrast agents are increasingly being used to noninvasively track cells, target molecular epitopes, and monitor gene expression in vivo. Detecting regions of contrast agent accumulation can be challenging if resulting contrast is subtle relative to endogenous tissue hypointensities. A postprocessing method is presented that yields enhanced positive-contrast images from the phase map associated with T2*-weighted MRI data. As examples, the method was applied to an agarose gel phantom doped with superparamagnetic iron-oxide nanoparticles and in vivo and ex vivo mouse brains inoculated with recombinant viruses delivering transgenes that induce overexpression of paramagnetic ferritin. Overall, this approach generates images that exhibit a 1- to 8-fold improvement in contrast-to-noise ratio in regions where paramagnetic agents are present compared to conventional magnitude images. This approach can be used in conjunction with conventional T2* pulse sequences, requires no prescans or increased scan time, and can be applied retrospectively to previously acquired data. PMID:19780169

Magnetic nanoparticles in magnetic resonance imaging and diagnostics.

PubMed

Rümenapp, Christine; Gleich, Bernhard; Haase, Axel

2012-05-01

Magnetic nanoparticles are useful as contrast agents for magnetic resonance imaging (MRI). Paramagnetic contrast agents have been used for a long time, but more recently superparamagnetic iron oxide nanoparticles (SPIOs) have been discovered to influence MRI contrast as well. In contrast to paramagnetic contrast agents, SPIOs can be functionalized and size-tailored in order to adapt to various kinds of soft tissues. Although both types of contrast agents have a inducible magnetization, their mechanisms of influence on spin-spin and spin-lattice relaxation of protons are different. A special emphasis on the basic magnetism of nanoparticles and their structures as well as on the principle of nuclear magnetic resonance is made. Examples of different contrast-enhanced magnetic resonance images are given. The potential use of magnetic nanoparticles as diagnostic tracers is explored. Additionally, SPIOs can be used in diagnostic magnetic resonance, since the spin relaxation time of water protons differs, whether magnetic nanoparticles are bound to a target or not.

Surface impact on nanoparticle-based magnetic resonance imaging contrast agents

PubMed Central

Zhang, Weizhong; Liu, Lin; Chen, Hongmin; Hu, Kai; Delahunty, Ian; Gao, Shi; Xie, Jin

2018-01-01

Magnetic resonance imaging (MRI) is one of the most widely used diagnostic tools in the clinic. To improve imaging quality, MRI contrast agents, which can modulate local T1 and T2 relaxation times, are often injected prior to or during MRI scans. However, clinically used contrast agents, including Gd3+-based chelates and iron oxide nanoparticles (IONPs), afford mediocre contrast abilities. To address this issue, there has been extensive research on developing alternative MRI contrast agents with superior r1 and r2 relaxivities. These efforts are facilitated by the fast progress in nanotechnology, which allows for preparation of magnetic nanoparticles (NPs) with varied size, shape, crystallinity, and composition. Studies suggest that surface coatings can also largely affect T1 and T2 relaxations and can be tailored in favor of a high r1 or r2. However, the surface impact of NPs has been less emphasized. Herein, we review recent progress on developing NP-based T1 and T2 contrast agents, with a focus on the surface impact. PMID:29721097

Optimizing radiologist e-prescribing of CT oral contrast agent using a protocoling portal.

PubMed

Wasser, Elliot J; Galante, Nicholas J; Andriole, Katherine P; Farkas, Cameron; Khorasani, Ramin

2013-12-01

The purpose of this study is to quantify the time expenditure associated with radiologist ordering of CT oral contrast media when using an integrated protocoling portal and to determine radiologists' perceptions of the ordering process. This prospective study was performed at a large academic tertiary care facility. Detailed timing information for CT inpatient oral contrast orders placed via the computerized physician order entry (CPOE) system was gathered over a 14-day period. Analyses evaluated the amount of physician time required for each component of the ordering process. Radiologists' perceptions of the ordering process were assessed by survey. Descriptive statistics and chi-square analysis were performed. A total of 96 oral contrast agent orders were placed by 13 radiologists during the study period. The average time necessary to create a protocol for each case was 40.4 seconds (average range by subject, 20.0-130.0 seconds; SD, 37.1 seconds), and the average total time to create and sign each contrast agent order was 27.2 seconds (range, 10.0-50.0 seconds; SD, 22.4 seconds). Overall, 52.5% (21/40) of survey respondents indicated that radiologist entry of oral contrast agent orders improved patient safety. A minority of respondents (15% [6/40]) indicated that contrast agent order entry was either very or extremely disruptive to workflow. Radiologist e-prescribing of CT oral contrast agents using CPOE can be embedded in a protocol workflow. Integration of health IT tools can help to optimize user acceptance and adoption.

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

PubMed

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

2017-10-15

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

Adverse reactions of low osmolar non-ionic and ionic contrast media when used together or separately during percutaneous coronary intervention.

PubMed

Juergens, Craig P; Khaing, Aye Mi; McIntyre, Geraldine J; Leung, Dominic Y C; Lo, Sidney T H; Fernandes, Clyne; Hopkins, Andrew P

2005-09-01

Due to perceived advantages in the use of non-ionic contrast agents for diagnostic angiography and ionic agents for percutaneous coronary intervention (PCI), patients often receive various combinations of both types of agents. To assess potential adverse effects of non-ionic and ionic contrast media when used together or separately during percutaneous coronary intervention. We retrospectively evaluated the outcomes of 532 patients undergoing percutaneous coronary intervention in our institution. Patients were divided into two groups: those that underwent diagnostic angiography and "follow on" PCI; and those that underwent "planned" PCI. The groups were subdivided on the basis of the use of the ionic agent ioxaglate or the non-ionic agent iopromide during PCI. The frequency of allergic reactions and major adverse cardiac events (MACE) were noted. With respect to the "follow on" group, allergic reactions occurred in 9 of 150 patients (6.0%) who received the combination of ioxaglate and iopromide versus 1 of 93 (1.1%) who only received iopromide (p=0.094). There was no difference with respect to MACE [6 (4.0%) ioxaglate and iopromide versus 4 (4.3%) iopromide alone, p=1.00]. In the "planned" group, 7 of 165 patients (4.2%) receiving ioxaglate had an allergic reaction as opposed 0.0% (0 of 124 patients) in the iopromide group (p=0.021). All contrast reactions were mild. The incidence of a MACE was similar in both groups [1 (0.6%) ioxaglate versus 2 (1.6%) iopromide, p=0.579]. The incidence of allergic reactions was similar if ioxaglate was used alone or in combination with iopromide (p=0.478). Whilst combining ionic and non-ionic contrast agents in the same procedure was not associated with any more adverse reactions than using an ionic contrast agent alone, the ionic contrast agent ioxaglate was associated with the majority of allergic reactions. With respect to choice of contrast agent, using the non-ionic agent iopromide alone for coronary intervention is associated with the lowest risk of an adverse event.

Interleukin 16- (IL-16-) Targeted Ultrasound Imaging Agent Improves Detection of Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

PubMed

Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Adur, Malavika K; Utterback, Chet W; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

2015-01-01

Limited resolution of transvaginal ultrasound (TVUS) scanning is a significant barrier to early detection of ovarian cancer (OVCA). Contrast agents have been suggested to improve the resolution of TVUS scanning. Emerging evidence suggests that expression of interleukin 16 (IL-16) by the tumor epithelium and microvessels increases in association with OVCA development and offers a potential target for early OVCA detection. The goal of this study was to examine the feasibility of IL-16-targeted contrast agents in enhancing the intensity of ultrasound imaging from ovarian tumors in hens, a model of spontaneous OVCA. Contrast agents were developed by conjugating biotinylated anti-IL-16 antibodies with streptavidin coated microbubbles. Enhancement of ultrasound signal intensity was determined before and after injection of contrast agents. Following scanning, ovarian tissues were processed for the detection of IL-16 expressing cells and microvessels. Compared with precontrast, contrast imaging enhanced ultrasound signal intensity significantly in OVCA hens at early (P < 0.05) and late stages (P < 0.001). Higher intensities of ultrasound signals in OVCA hens were associated with increased frequencies of IL-16 expressing cells and microvessels. These results suggest that IL-16-targeted contrast agents improve the visualization of ovarian tumors. The laying hen may be a suitable model to test new imaging agents and develop targeted anti-OVCA therapeutics.

Contrast-enhanced sonography in pediatrics.

PubMed

McCarville, M Beth

2011-05-01

Microbubble US contrast agents are composed of an outer shell of protein, phospholipid or polymer that encase air or perfluorocarbon gas. These contrast agents have been widely used in adult cardiology patients to improve endocardial border delineation and have been proved safe and well tolerated in this patient population. There is also a growing body of literature elucidating the value of contrast-enhanced sonography to distinguish benign from malignant liver lesions in adults and to characterize non-hepatic adult malignancies. Because these agents have not been approved for pediatric use in many countries, less is known of the value of contrast-enhanced sonography in children. In this review I will discuss several proven and potential pediatric applications of contrast-enhanced sonography.

Direct visualization of gastrointestinal tract with lanthanide-doped BaYbF5 upconversion nanoprobes.

PubMed

Liu, Zhen; Ju, Enguo; Liu, Jianhua; Du, Yingda; Li, Zhengqiang; Yuan, Qinghai; Ren, Jinsong; Qu, Xiaogang

2013-10-01

Nanoparticulate contrast agents have attracted a great deal of attention along with the rapid development of modern medicine. Here, a binary contrast agent based on PAA modified BaYbF5:Tm nanoparticles for direct visualization of gastrointestinal (GI) tract has been designed and developed via a one-pot solvothermal route. By taking advantages of excellent colloidal stability, low cytotoxicity, and neglectable hemolysis of these well-designed nanoparticles, their feasibility as a multi-modal contrast agent for GI tract was intensively investigated. Significant enhancement of contrast efficacy relative to clinical barium meal and iodine-based contrast agent was evaluated via X-ray imaging and CT imaging in vivo. By doping Tm(3+) ions into these nanoprobes, in vivo NIR-NIR imaging was then demonstrated. Unlike some invasive imaging modalities, non-invasive imaging strategy including X-ray imaging, CT imaging, and UCL imaging for GI tract could extremely reduce the painlessness to patients, effectively facilitate imaging procedure, as well as rationality economize diagnostic time. Critical to clinical applications, long-term toxicity of our contrast agent was additionally investigated in detail, indicating their overall safety. Based on our results, PAA-BaYbF5:Tm nanoparticles were the excellent multi-modal contrast agent to integrate X-ray imaging, CT imaging, and UCL imaging for direct visualization of GI tract with low systemic toxicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

Horsfield, Mark A.; Thornton, John S.; Gill, Andrew; Jager, H. Rolf; Priest, Andrew N.; Morgan, Bruno

2009-05-01

A functional form for the vascular concentration of MRI contrast agent after intravenous bolus injection was developed that can be used to model the concentration at any vascular site at which contrast concentration can be measured. The form is based on previous models of blood circulation, and is consistent with previously measured data at long post-injection times, when the contrast agent is fully and evenly dispersed in the blood. It allows the first-pass and recirculation peaks of contrast agent to be modelled, and measurement of the absolute concentration of contrast agent at a single time point allows the whole time course to be rescaled to give absolute contrast agent concentration values. This measure of absolute concentration could be performed at a long post-injection time using either MRI or blood-sampling methods. In order to provide a model that is consistent with measured data, it was necessary to include both rapid and slow extravasation, together with excretion via the kidneys. The model was tested on T1-weighted data from the descending aorta and hepatic portal vein, and on T*2-weighted data from the cerebral arteries. Fitting of the model was successful for all datasets, but there was a considerable variation in fit parameters between subjects, which suggests that the formation of a meaningful population-averaged vascular concentration function is precluded.

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

PubMed

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

2016-01-01

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

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

PubMed

Carrel, Maxence; Beltran, Mario A; Morales, Verónica L; Derlon, Nicolas; Morgenroth, Eberhard; Kaufmann, Rolf; Holzner, Markus

2017-01-01

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

75 FR 875 - Guidance for Industry on New Contrast Imaging Indication Considerations for Devices and Approved...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-06

... imaging devices for use with imaging contrast agents or radiopharmaceuticals. FDA intends this guidance to..., for medical imaging devices for use with imaging contrast agents or radiopharmaceuticals. Further, the...] Guidance for Industry on New Contrast Imaging Indication Considerations for Devices and Approved Drug and...

Investigation of X-ray permeability of surgical gloves coated with different contrast agents

PubMed Central

Kayan, Mustafa; Yaşar, Selçuk; Saygın, Mustafa; Yılmaz, Ömer; Aktaş, Aykut Recep; Kayan, Fatmanur; Türker, Yasin; Çetinkaya, Gürsel

2016-01-01

Objective: We aimed to investigate the effectiveness and radiation protection capability of latex gloves coated with various contrast agents as an alternative to lead gloves. Methods: The following six groups were created to evaluate the permeability of X-ray in this experimental study: lead gloves, two different non-ionic contrast media (iopromide 370/100 mg I/mL and iomeprol 400/100 mg I/mL), 10% povidone–iodine (PV–I), 240/240 g/mL barium sulphate and a mixture of equal amounts of all contrast agents. A radiation dose detector was placed in coated latex gloves for each one. The absorption values of radiation from latex gloves coated with various contrast agents were measured and compared with the absorption of radiation from lead gloves. This study was designed as an ‘experimental study’. Results: The mean absorption value of X-ray from lead gloves was 3.0±0.08 µG/s. The mean absorption values of X-ray from latex gloves coated with various contrast agents were 3.7±0.09 µG/s (iopromide 370/100 mg I/mL), 3.6±0.09 µG/s (iomeprol 400/100 mg I/mL), 3.7±0.04 µG/s (PV–I), 3.1±0.07 µG/s (barium sulphate) and 3.8±0.05 µG/s (mixture of all contrast agents). Latex gloves coated with barium sulphate provided the best radiation absorption compared with latex gloves coated with other radiodense contrast agents. Conclusion: Latex gloves coated with barium sulphate may provide protection equivalent to lead gloves. PMID:26680548

VEGFR2-Targeted Ultrasound Imaging Agent Enhances the Detection of Ovarian Tumors at Early Stage in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

PubMed

Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Machado, Sergio A; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

2015-07-01

Tumor-associated neoangiogenesis (TAN) is an early event in ovarian cancer (OVCA) development. Increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) by TAN vessels presents a potential target for early detection by ultrasound imaging. The goal of this study was to examine the suitability of VEGFR2-targeted ultrasound contrast agents in detecting spontaneous OVCA in laying hens. Effects of VEGFR2-targeted contrast agents in enhancing the intensity of ultrasound imaging from spontaneous ovarian tumors in hens were examined in a cross-sectional study. Enhancement in the intensity of ultrasound imaging was determined before and after injection of VEGFR2-targeted contrast agents. All ultrasound images were digitally stored and analyzed off-line. Following scanning, ovarian tissues were collected and processed for histology and detection of VEGFR2-expressing microvessels. Enhancement in visualization of ovarian morphology was detected by gray-scale imaging following injection of VEGFR2-targeted contrast agents. Compared with pre-contrast, contrast imaging enhanced the intensities of ultrasound imaging significantly (p < 0.0001) irrespective of the pathological status of ovaries. In contrast to normal hens, the intensity of ultrasound imaging was significantly (p < 0.0001) higher in hens with early stage OVCA and increased further in hens with late stage OVCA. Higher intensities of ultrasound imaging in hens with OVCA were positively correlated with increased (p < 0.0001) frequencies of VEGFR2-expressing microvessels. The results of this study suggest that VEGFR2-targeted contrast agents enhance the visualization of spontaneous ovarian tumors in hens at early and late stages of OVCA. The laying hen may be a suitable model to test new imaging agents and develop targeted therapeutics. © The Author(s) 2014.

Spectral response model for a multibin photon-counting spectral computed tomography detector and its applications.

PubMed

Liu, Xuejin; Persson, Mats; Bornefalk, Hans; Karlsson, Staffan; Xu, Cheng; Danielsson, Mats; Huber, Ben

2015-07-01

Variations among detector channels in computed tomography can lead to ring artifacts in the reconstructed images and biased estimates in projection-based material decomposition. Typically, the ring artifacts are corrected by compensation methods based on flat fielding, where transmission measurements are required for a number of material-thickness combinations. Phantoms used in these methods can be rather complex and require an extensive number of transmission measurements. Moreover, material decomposition needs knowledge of the individual response of each detector channel to account for the detector inhomogeneities. For this purpose, we have developed a spectral response model that binwise predicts the response of a multibin photon-counting detector individually for each detector channel. The spectral response model is performed in two steps. The first step employs a forward model to predict the expected numbers of photon counts, taking into account parameters such as the incident x-ray spectrum, absorption efficiency, and energy response of the detector. The second step utilizes a limited number of transmission measurements with a set of flat slabs of two absorber materials to fine-tune the model predictions, resulting in a good correspondence with the physical measurements. To verify the response model, we apply the model in two cases. First, the model is used in combination with a compensation method which requires an extensive number of transmission measurements to determine the necessary parameters. Our spectral response model successfully replaces these measurements by simulations, saving a significant amount of measurement time. Second, the spectral response model is used as the basis of the maximum likelihood approach for projection-based material decomposition. The reconstructed basis images show a good separation between the calcium-like material and the contrast agents, iodine and gadolinium. The contrast agent concentrations are reconstructed with more than 94% accuracy.

Spectral response model for a multibin photon-counting spectral computed tomography detector and its applications

PubMed Central

Liu, Xuejin; Persson, Mats; Bornefalk, Hans; Karlsson, Staffan; Xu, Cheng; Danielsson, Mats; Huber, Ben

2015-01-01

Abstract. Variations among detector channels in computed tomography can lead to ring artifacts in the reconstructed images and biased estimates in projection-based material decomposition. Typically, the ring artifacts are corrected by compensation methods based on flat fielding, where transmission measurements are required for a number of material-thickness combinations. Phantoms used in these methods can be rather complex and require an extensive number of transmission measurements. Moreover, material decomposition needs knowledge of the individual response of each detector channel to account for the detector inhomogeneities. For this purpose, we have developed a spectral response model that binwise predicts the response of a multibin photon-counting detector individually for each detector channel. The spectral response model is performed in two steps. The first step employs a forward model to predict the expected numbers of photon counts, taking into account parameters such as the incident x-ray spectrum, absorption efficiency, and energy response of the detector. The second step utilizes a limited number of transmission measurements with a set of flat slabs of two absorber materials to fine-tune the model predictions, resulting in a good correspondence with the physical measurements. To verify the response model, we apply the model in two cases. First, the model is used in combination with a compensation method which requires an extensive number of transmission measurements to determine the necessary parameters. Our spectral response model successfully replaces these measurements by simulations, saving a significant amount of measurement time. Second, the spectral response model is used as the basis of the maximum likelihood approach for projection-based material decomposition. The reconstructed basis images show a good separation between the calcium-like material and the contrast agents, iodine and gadolinium. The contrast agent concentrations are reconstructed with more than 94% accuracy. PMID:26839904

Synthesis and characterization of a smart contrast agent sensitive to calcium.

PubMed

Dhingra, Kirti; Maier, Martin E; Beyerlein, Michael; Angelovski, Goran; Logothetis, Nikos K

2008-08-07

A novel first-generation Ca2+ sensitive contrast agent, Gd-DOPTRA has been synthesized and characterized. The agent shows approximately 100% relaxivity enhancement upon addition of Ca2+. The agent is selective and sensitive to Ca2+ also in the presence of Mg2+ and Zn2+. The relaxivity studies carried out in physiological fluids prove the prospects of the agent for in vivo measurements.

Targeted Gold Nanoparticle Contrast Agent for Digital Breast Tomosynthesis and Computed Tomography

DTIC Science & Technology

2011-03-01

injection series was repeated with an iodinated contrast agent, Omnipaque 320 (320 mg I/mL). Iodine enhancement was observed immediately post-injection...shape, size, growth rate, and expression level of cell-surface markers. Today, the most commonly used x-ray contrast agents are iodine-based...structural and radiographic properties of the AuNP. (iii) Evaluate the in vivo effect of the nanoparticles: tumor- enhancement , biodistribution, and

Penetrating Colorectal Injuries: Diagnostic Performance of Multidetector CT with Trajectography.

PubMed

Dreizin, David; Boscak, Alexis R; Anstadt, Michael J; Tirada, Nikki; Chiu, William C; Munera, Felipe; Bodanapally, Uttam K; Hornick, Michael; Stein, Deborah M

2016-12-01

Purpose To determine the diagnostic performance of multidetector computed tomography (CT) with trajectography for penetrating colorectal injuries. Materials and Methods This institutional review board-approved and HIPAA-compliant study was a 6-year blinded retrospective review by two independent readers of 182 consecutive patients who preoperatively underwent 40- or 64-row multidetector CT for penetrating torso trauma below the diaphragm and had surgically confirmed findings. Colorectal perforation was present in 42 patients. Trajectory analysis with postprocessing software was used for all studies. Additional signs evaluated were rectal contrast agent leak, collections of extruded fecal material, mural defect, wall thickening, abnormal enhancement, free fluid or stranding, and free air. The quality of the colorectal contrast agent administration was recorded. Sensitivity, specificity, predictive values, areas under the receiver operating characteristic curves (AUCs), and Cohen κ were determined. Results In patients with rectal contrast agent administration (n = 151), AUCs were 0.90-0.91, which indicated excellent accuracy. Trajectory was sensitive (88%-91%). For single wounds (n = 104), sensitivity of trajectory was 96% for both readers, but was only 80% for multiple wounds (n = 47). Contrast agent leak was highly specific (96%-98%), but insensitive (42%-46%). Improved diagnostic performance was observed in patients with poor colonic distension or opacification. Accuracy remained high (AUC, 0.86-0.99) in the group without rectal contrast agent administration (n = 31). Conclusion Trajectory had excellent sensitivity, while rectal contrast agent leak was specific but insensitive. Sensitivity of trajectory was lower for multiple wounds. Accuracy remained high in patients without rectal contrast agent administration. © RSNA, 2016.

Acoustic Studies on Nanodroplets, Microbubbles and Liposomes

NASA Astrophysics Data System (ADS)

Kumar, Krishna Nandan

Microbubbles and droplets are nanometer to micron size biocompatible particles which are primarily used for drug delivery and contrast imaging. Our aim is to broaden the use of microbubbles from contrast imaging to other applications such as measuring blood pressure. The other goal is to develop in situ contrast agents (phase shift droplets) which can be used for applications such as cancer tumor imaging. Therefore, the focus is on developing and validating the concept using experimental and theoretical methods. Below is an overview of each of the projects performed on droplets and microbubbles. Phase shift droplets vaporizable by acoustic stimulation offer many advantages over microbubbles as contrast agents due to their higher stability and possibility of smaller sizes. In this study, the acoustic droplet vaporization (ADV) threshold of a suspension of PFP droplets (400-3000nm) was acoustically measured as a function of the excitation frequency by examining the scattered signals, fundamental, sub- and second-harmonic. This work presents the experimental methodology to determine ADV threshold. The threshold increases with frequency: 1.25 MPa at 2.25 MHz, 2.0 MPa at 5 MHz and 2.5 MPa at 10 MHz. The scattered response from droplets was also found to match well with that of independently prepared lipid-coated microbubble suspension in magnitude as well as trends above the threshold value. Additionally, we have employed classical nucleation theory (CNT) to investigate the ADV, specifically the threshold value of the peak negative pressure required for vaporization. The theoretical analysis predicts that the ADV threshold increases with increasing surface tension of the droplet core and frequency of excitation, while it decreases with increasing temperature and droplet size. The predictions are in qualitative agreement with experimental observations. A technique to measure the ambient pressure using microbubbles was developed. Here we are presenting the results of an in vitro study aimed at developing an ultrasound-aided noninvasive pressure estimation technique using contrast agents-DefinityRTM, a lipid coated microbubble, and an experimental PLA (Poly lactic acid) microbubbles. Scattered responses from these bubbles have been measured in vitro as a function of ambient pressure using a 3.5 MHz acoustic excitation of varying amplitude. At an acoustic pressure of 670 kPa, Definity RTM microbubbles showed a linear decrease in subharmonic signal with increasing ambient pressure, registering a 12dB reduction at an overpressure of 120 mm Hg. Ultrasound contrast microbubbles experience widely varying ambient blood pressure in different organs, which can also change due to diseases. Pressure change can alter the material properties of the encapsulation of these microbubbles. Here the characteristic rheological parameters of contrast agent Definity and Targestar are determined by varying the ambient pressure (in a physiologically relevant range 0-200 mmHg). Four different interfacial rheological models are used to characterize the microbubbles. Both the contrast agents show an increase in their interfacial dilatational viscosity and interfacial dilatational elasticity with ambient pressure. It has been well established that liposomes prepared following a careful multi-step procedure can be made echogenic. Our group as well as others experimentally demonstrated that freeze-drying in the presence of mannitol is a crucial component to ensure echogenicity. Here, we showed that freeze-dried aqueous solutions of excipients such as mannitol, meso-erythritol, glycine, and glucose that assume a crystalline state, when dispersed in water creates bubbles and are echogenic even without any lipids. We also present an explanation for the bubble generation process because of dissolution of mannitol.

PDT: loss of autophagic cytoprotection after lysosomal photodamage

NASA Astrophysics Data System (ADS)

Kessel, David; Price, Michael

2012-02-01

Photodynamic therapy is known to evoke both autophagy and apoptosis. Apoptosis is an irreversible death pathway while autophagy can serve a cytoprotective function. In this study, we examined two photosensitizing agents that target lysosomes, although they differ in the reactive oxygen species (ROS) formed during irradiation. With both agents, the 'shoulder' on the PDT dose-response curve was substantially attenuated, consistent with loss of a cytoprotective pathway. In contrast, this 'shoulder' is commonly observed when PDT targets mitochondria or the ER. We propose that lysosomal targets may offer the possibility of promoting PDT efficacy by eliminating a potentially protective pathway.

Diffusion properties of conventional and calcium-sensitive MRI contrast agents in the rat cerebral cortex.

PubMed

Hagberg, Gisela E; Mamedov, Ilgar; Power, Anthony; Beyerlein, Michael; Merkle, Hellmut; Kiselev, Valerij G; Dhingra, Kirti; Kubìček, Vojtĕch; Angelovski, Goran; Logothetis, Nikos K

2014-01-01

Calcium-sensitive MRI contrast agents can only yield quantitative results if the agent concentration in the tissue is known. The agent concentration could be determined by diffusion modeling, if relevant parameters were available. We have established an MRI-based method capable of determining diffusion properties of conventional and calcium-sensitive agents. Simulations and experiments demonstrate that the method is applicable both for conventional contrast agents with a fixed relaxivity value and for calcium-sensitive contrast agents. The full pharmacokinetic time-course of gadolinium concentration estimates was observed by MRI before, during and after intracerebral administration of the agent, and the effective diffusion coefficient D* was determined by voxel-wise fitting of the solution to the diffusion equation. The method yielded whole brain coverage with a high spatial and temporal sampling. The use of two types of MRI sequences for sampling of the diffusion time courses was investigated: Look-Locker-based quantitative T(1) mapping, and T(1) -weighted MRI. The observation times of the proposed MRI method is long (up to 20 h) and consequently the diffusion distances covered are also long (2-4 mm). Despite this difference, the D* values in vivo were in agreement with previous findings using optical measurement techniques, based on observation times of a few minutes. The effective diffusion coefficient determined for the calcium-sensitive contrast agents may be used to determine local tissue concentrations and to design infusion protocols that maintain the agent concentration at a steady state, thereby enabling quantitative sensing of the local calcium concentration. Copyright © 2014 John Wiley & Sons, Ltd.

Synthesis and Preclinical Characterization of a Cationic Iodinated Imaging Contrast Agent (CA4+) and Its Use for Quantitative Computed Tomography of Ex Vivo Human Hip Cartilage.

PubMed

Stewart, Rachel C; Patwa, Amit N; Lusic, Hrvoje; Freedman, Jonathan D; Wathier, Michel; Snyder, Brian D; Guermazi, Ali; Grinstaff, Mark W

2017-07-13

Contrast agents that go beyond qualitative visualization and enable quantitative assessments of functional tissue performance represent the next generation of clinically useful imaging tools. An optimized and efficient large-scale synthesis of a cationic iodinated contrast agent (CA4+) is described for imaging articular cartilage. Contrast-enhanced CT (CECT) using CA4+ reveals significantly greater agent uptake of CA4+ in articular cartilage compared to that of similar anionic or nonionic agents, and CA4+ uptake follows Donnan equilibrium theory. The CA4+ CECT attenuation obtained from imaging ex vivo human hip cartilage correlates with the glycosaminoglycan content, equilibrium modulus, and coefficient of friction, which are key indicators of cartilage functional performance and osteoarthritis stage. Finally, preliminary toxicity studies in a rat model show no adverse events, and a pharmacokinetics study documents a peak plasma concentration 30 min after dosing, with the agent no longer present in vivo at 96 h via excretion in the urine.

Magnetic and Plasmonic Contrast Agents in Optical Coherence Tomography

PubMed Central

Oldenburg, Amy L.; Blackmon, Richard L.; Sierchio, Justin M.

2016-01-01

Optical coherence tomography (OCT) has gained widespread application for many biomedical applications, yet the traditional array of contrast agents used in incoherent imaging modalities do not provide contrast in OCT. Owing to the high biocompatibility of iron oxides and noble metals, magnetic and plasmonic nanoparticles, respectively, have been developed as OCT contrast agents to enable a range of biological and pre-clinical studies. Here we provide a review of these developments within the past decade, including an overview of the physical contrast mechanisms and classes of OCT system hardware addons needed for magnetic and plasmonic nanoparticle contrast. A comparison of the wide variety of nanoparticle systems is also presented, where the figures of merit depend strongly upon the choice of biological application. PMID:27429543

Iodinated contrast media and the role of renal replacement therapy.

PubMed

Weisbord, Steven D; Palevsky, Paul M

2011-05-01

Iodinated contrast media are among the most commonly used pharmacologic agents in medicine. Although generally highly safe, iodinated contrast media are associated with several adverse effects, most significantly the risk of acute kidney injury, particularly in patients with underlying renal dysfunction. By virtue of their pharmacokinetic characteristics, these contrast agents are efficiently cleared by hemodialysis and to a lesser extent, hemofiltration. This has led to research into the capacity for renal replacement therapies to prevent certain adverse effects of iodinated contrast. This review examines the molecular and pharmacokinetic characteristics of iodinated contrast media and critically analyzes data from past studies on the role of renal replacement therapy to prevent adverse effects of these diagnostic agents. Published by Elsevier Inc.

Contrast-Enhanced Sonography Depicts Spontaneous Ovarian Cancer at Early Stages in a Preclinical Animal Model

PubMed Central

Barua, Animesh; Bitterman, Pincas; Bahr, Janice M.; Basu, Sanjib; Sheiner, Eyal; Bradaric, Michael J.; Hales, Dale B.; Luborsky, Judith L.; Abramowicz, Jacques S.

2011-01-01

Objective Our goal was to examine the feasibility of using laying hens, a preclinical model of human spontaneous ovarian cancer, in determining the kinetics of an ultrasound contrast agent indicative of ovarian tumor-associated neoangiogenesis in early-stage ovarian cancer. Methods Three-year-old White Leghorn laying hens with decreased ovarian function were scanned before and after intravenous injection of a human serum albumin–perflutren contrast agent at a dose of 5 µL/kg body weight. Gray scale morphologic characteristics, Doppler indices, the arrival time, peak intensity, and wash-out of the contrast agent were recorded and archived on still images and video clips. Hens were euthanized thereafter; sonographic predictions were compared at gross examination; and ovarian tissues were collected. Archived clips were analyzed to determine contrast parameters and Doppler intensities of vessels. A time-intensity curve per hen was drawn, and the area under the curve was derived. Tumor types and the density of ovarian microvessels were determined by histologic examination and immunohistochemistry and compared to sonographic predictions. Results The contrast agent significantly (P < .05) enhanced the visualization of microvessels, which was confirmed by immunohistochemistry. Contrast parameters, including the time of wash-out and area under the curve, were significantly different (P < .05) between ovaries of normal hens and hens with ovarian cancer and correctly detected cancer at earlier stages than the time of peak intensity. Conclusions The laying hen may be a useful animal model for determining ovarian tumor-associated vascular kinetics diagnostic of early-stage ovarian cancer using a contrast agent. This model may also be useful for testing the efficacy of different contrast agents in a preclinical setting. PMID:21357555

Immediate reactions following iodinated contrast media injection: a study of 38 cases.

PubMed

Dewachter, Pascale; Laroche, Dominique; Mouton-Faivre, Claudie; Bloch-Morot, Evelyne; Cercueil, Jean-Pierre; Metge, Liliane; Carette, Marie-France; Vergnaud, Marie-Claude; Clément, Olivier

2011-03-01

To investigate the pathomechanisms involved in cases of immediate hypersensitivity reactions occurring after the administration of iodinated contrast media. Patients having presented clinical signs of immediate hypersensitivity suggesting allergy after iodinated contrast medium were investigated. Histamine and tryptase concentrations were measured, and/or skin tests were performed. Patients with positive skin tests to the culprit contrast agent were classified as IgE-mediated allergic hypersensitivity (Group I) and patients with negative skin tests as non-allergic hypersensitivity (Group II). 38 patients were included. Most reactions appeared after non-ionic (n = 32). Reactions were more frequently severe following ionic than non-ionic (p = 0.014). Skin testing was not performed in 11 patients. Skin tests with the culprit contrast agent were negative in 26% of the patients (Group II, n = 7) whereas they were found positive with the contrast agent in 73% of the patients (Group I, n = 19). Latex-induced reaction was diagnosed in one patient, and was consequently excluded from the cohort. In Group I, the frequency of cross-reactivity with the other commercialized iodinated contrast media was low (7%). Cardiovascular signs were present in Group I (52.6%, n = 10), and absent in Group II (p = 0.023). Histamine and tryptase concentrations were higher in patients who had cardiovascular signs (p < 0.02). Immediate reactions with clinical signs suggesting allergy along with positive skin tests with the administered contrast agent confirm immediate allergic hypersensitivity (anaphylaxis) to this agent. Consequently, the culprit contrast agent should be definitely avoided as well as cross-reactive ICM in order to prevent further recurrences. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Near infrared spectral polarization imaging of prostate cancer tissues using Cybesin: a receptor-targeted contrast agent

NASA Astrophysics Data System (ADS)

Pu, Yang; Wang, W. B.; Tang, G. C.; Liang, Kexian; Achilefu, S.; Alfano, R. R.

2013-03-01

Cybesin, a smart contrast agent to target cancer cells, was investigated using a near infrared (NIR) spectral polarization imaging technique for prostate cancer detection. The approach relies on applying a contrast agent that can target cancer cells. Cybesin, as a small ICG-derivative dye-peptide, emit fluorescence between 750 nm and 900 nm, which is in the "tissue optical window". Cybesin was reported targeting the over-expressed bombesin receptors in cancer cells in animal model and the human prostate cancers over-expressing bombesin receptors. The NIR spectral polarization imaging study reported here demonstrated that Cybesin can be used as a smart optical biomarker and as a prostate cancer receptor targeted contrast agent.

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

PubMed

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

2014-06-01

Gadolinium-based contrast agents are increasingly being used in magnetic resonance imaging. These agents can improve the contrast in images and provide information about function and metabolism, increasing both sensitivity and specificity. We describe the gadolinium-based contrast agents that have been approved for clinical use, detailing their main characteristics based on their chemical structure, stability, and safety. In general terms, these compounds are safe. Nevertheless, adverse reactions, the possibility of nephrotoxicity from these compounds, and the possibility of developing nephrogenic systemic fibrosis will be covered in this article. Lastly, the article will discuss the current guidelines, recommendations, and contraindications for their clinical use, including the management of pregnant and breast-feeding patients. Copyright © 2014 SERAM. Published by Elsevier Espana. All rights reserved.

Hybrid gold-iron oxide nanoparticles as a multifunctional platform for biomedical application

PubMed Central

2012-01-01

Background Iron oxide nanoparticles (IONPs) have increasing applications in biomedicine, however fears over long term stability of polymer coated particles have arisen. Gold coating IONPs results in particles of increased stability and robustness. The unique properties of both the iron oxide (magnetic) and gold (surface plasmon resonance) result in a multimodal platform for use as MRI contrast agents and as a nano-heater. Results Here we synthesize IONPs of core diameter 30 nm and gold coat using the seeding method with a poly(ethylenimine) intermediate layer. The final particles were coated in poly(ethylene glycol) to ensure biocompatibility and increase retention times in vivo. The particle coating was monitored using FTIR, PCS, UV–vis absorption, TEM, and EDX. The particles appeared to have little cytotoxic effect when incubated with A375M cells. The resultant hybrid nanoparticles (HNPs) possessed a maximal absorbance at 600 nm. After laser irradiation in agar phantom a ΔT of 32°C was achieved after only 90 s exposure (50 μgmL-1). The HNPs appeared to decrease T2 values in line with previously clinically used MRI contrast agent Feridex®. Conclusions The data highlights the potential of these HNPs as dual function MRI contrast agents and nano-heaters for therapies such as cellular hyperthermia or thermo-responsive drug delivery. PMID:22731703

Antibody Conjugated, Raman Tagged Hollow Gold-Silver Nanospheres for Specific Targeting and Multimodal Dark-Field/SERS/Two Photon-FLIM Imaging of CD19(+) B Lymphoblasts.

PubMed

Nagy-Simon, Timea; Tatar, Andra-Sorina; Craciun, Ana-Maria; Vulpoi, Adriana; Jurj, Maria-Ancuta; Florea, Adrian; Tomuleasa, Ciprian; Berindan-Neagoe, Ioana; Astilean, Simion; Boca, Sanda

2017-06-28

In this Research Article, we propose a new class of contrast agents for the detection and multimodal imaging of CD19(+) cancer lymphoblasts. The agents are based on NIR responsive hollow gold-silver nanospheres conjugated with antiCD19 monoclonal antibodies and marked with Nile Blue (NB) SERS active molecules (HNS-NB-PEG-antiCD19). Proof of concept experiments on specificity of the complex for the investigated cells was achieved by transmission electron microscopy (TEM). The microspectroscopic investigations via dark field (DF), surface-enhanced Raman spectroscopy (SERS), and two-photon excited fluorescence lifetime imaging microscopy (TPE-FLIM) corroborate with TEM and demonstrate successful and preferential internalization of the antibody-nanocomplex. The combination of the microspectroscopic techniques enables contrast and sensitivity that competes with more invasive and time demanding cell imaging modalities, while depth sectioning images provide real time localization of the nanoparticles in the whole cytoplasm at the entire depth of the cells. Our findings prove that HNS-NB-PEG-antiCD19 represent a promising type of new contrast agents with great possibility of being detected by multiple, non invasive, rapid and accessible microspectroscopic techniques and real applicability for specific targeting of CD19(+) cancer cells. Such versatile nanocomplexes combine in one single platform the detection and imaging of cancer lymphoblasts by DF, SERS, and TPE-FLIM microspectroscopy.

In vivo tumor characterization using both MR and optical contrast agents with a hybrid MRI-DOT system

NASA Astrophysics Data System (ADS)

Lin, Yuting; Ghijsen, Michael; Thayer, David; Nalcioglu, Orhan; Gulsen, Gultekin

2011-03-01

Dynamic contrast enhanced MRI (DCE-MRI) has been proven to be the most sensitive modality in detecting breast lesions. Currently available MR contrast agent, Gd-DTPA, is a low molecular weight extracellular agent and can diffuse freely from the vascular space into interstitial space. Due to this reason, DCE-MRI has low sensitivity in differentiating benign and malignant tumors. Meanwhile, diffuse optical tomography (DOT) can be used to provide enhancement kinetics of an FDA approved optical contrast agent, ICG, which behaves like a large molecular weight optical agent due to its binding to albumin. The enhancement kinetics of ICG may have a potential to distinguish between the malignant and benign tumors and hence improve the specificity. Our group has developed a high speed hybrid MRI-DOT system. The DOT is a fully automated, MR-compatible, multi-frequency and multi-spectral imaging system. Fischer-344 rats bearing subcutaneous R3230 tumor are injected simultaneously with Gd-DTPA (0.1nmol/kg) and IC-Green (2.5mg/kg). The enhancement kinetics of both contrast agents are recorded simultaneously with this hybrid MRI-DOT system and evaluated for different tumors.

Gadolinium Endohedral Metallofullerene-Based MRI Contrast Agents

NASA Astrophysics Data System (ADS)

Bolskar, Robert D.

With the ability to encapsulate and carry the highly paramagnetic Gd3+ ion, gadolinium endohedral metallofullerenes or "gadofullerenes" are being explored as alternatives to the chelate complexes that are currently used for contrast-enhanced magnetic resonance imaging (MRI). Reviewed here are the various water-soluble derivatives of the gadofullerenes Gd@C82, Gd@C60, and Gd3N@C80 that have been investigated as MRI contrast agents. The water proton r1 relaxivities of gadofullerenes can be more than an order of magnitude higher than those of clinically used chelate agents. Gadofullerene relaxivity mechanisms have been studied, and multiple factors are found to contribute to their high relaxivities. In vitro and in vivoT1-weighted MRI tests of gadofullerene derivatives have shown their utility as bright image-enhancing agents. The gadofullerene MRI contrast agents are a promising new and unique style of gadolinium carrier for advanced imaging applications, including cellular and molecular imaging.

Nephrogenic systemic fibrosis (NSF): a late adverse reaction to some of the gadolinium based contrast agents

PubMed Central

Marckmann, Peter; Logager, Vibeke B.

2007-01-01

Abstract Until recently it was believed that extracellular gadolinium based contrast agents were safe for both the kidneys and all other organs within the dose range up to 0.3 mmol/kg body weight. However, in 2006, it was demonstrated that some gadolinium based contrast agents may trigger the development of nephrogenic systemic fibrosis, a generalised fibrotic disorder, in renal failure patients. Accordingly, the use of gadodiamide and gadopentate dimeglumine for renal failure patients was banned in Europe in spring 2007. The same two compounds should only be used cautiously in patients with moderate renal dysfunction. The current paper reviews the situation (July 2007) regarding gadolinium based contrast agent and the severe delayed reaction to some of these agents. The fear of nephrogenic systemic fibrosis should not lead to a denial of a well indicated enhanced magnetic resonance imaging examination. PMID:17905680

Characterization of image heterogeneity using 2D Minkowski functionals increases the sensitivity of detection of a targeted MRI contrast agent.

PubMed

Canuto, Holly C; McLachlan, Charles; Kettunen, Mikko I; Velic, Marko; Krishnan, Anant S; Neves, Andre' A; de Backer, Maaike; Hu, D-E; Hobson, Michael P; Brindle, Kevin M

2009-05-01

A targeted Gd(3+)-based contrast agent has been developed that detects tumor cell death by binding to the phosphatidylserine (PS) exposed on the plasma membrane of dying cells. Although this agent has been used to detect tumor cell death in vivo, the differences in signal intensity between treated and untreated tumors was relatively small. As cell death is often spatially heterogeneous within tumors, we investigated whether an image analysis technique that parameterizes heterogeneity could be used to increase the sensitivity of detection of this targeted contrast agent. Two-dimensional (2D) Minkowski functionals (MFs) provided an automated and reliable method for parameterization of image heterogeneity, which does not require prior assumptions about the number of regions or features in the image, and were shown to increase the sensitivity of detection of the contrast agent as compared to simple signal intensity analysis. (c) 2009 Wiley-Liss, Inc.

MRI contrast agent concentration and tumor interstitial fluid pressure.

PubMed

Liu, L J; Schlesinger, M

2016-10-07

The present work describes the relationship between tumor interstitial fluid pressure (TIFP) and the concentration of contrast agent for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). We predict the spatial distribution of TIFP based on that of contrast agent concentration. We also discuss the cases for estimating tumor interstitial volume fraction (void fraction or porosity of porous medium), ve, and contrast volume transfer constant, K(trans), by measuring the ratio of contrast agent concentration in tissue to that in plasma. A linear fluid velocity distribution may reflect a quadratic function of TIFP distribution and lead to a practical method for TIFP estimation. To calculate TIFP, the parameters or variables should preferably be measured along the direction of the linear fluid velocity (this is in the same direction as the gray value distribution of the image, which is also linear). This method may simplify the calculation for estimating TIFP. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2013-02-01

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

Comparison of colonic transit between polyethylene glycol and water as oral contrast vehicles in the CT evaluation of acute appendicitis.

PubMed

Hebert, Jeffrey J; Taylor, Andrew J; Winter, Thomas C

2006-11-01

The objective of our study was to assess the efficacy of a new positive oral contrast agent's ability to reach the colon during CT evaluation of acute appendicitis. Eighty adult emergency department patients who underwent abdominal CT to evaluate for appendicitis were studied. Forty patients received the department's standard dose of 1,600 mL of a water-iodinated contrast mixture (ratio of 2 mL of iodinated contrast material to 100 mL of water) with a standard delay time of 2-2.5 hours from the beginning of contrast medium ingestion. Forty patients were given a new oral contrast mixture of 1,000 mL of polyethylene glycol (PEG) mixed with 30 mL of iodinated contrast agent, and the examination was conducted only 1 hour from inception of contrast administration. Examinations were reviewed for the presence of contrast medium in the cecum and the presence of appendicitis or other abdominal abnormality. Thirty-eight of 40 patients in the PEG group had contrast medium in the colon at 1 hour after contrast administration, 20 of whom had surgically confirmed cases of appendicitis. In five other patients in that group, another cause to explain the patient's complaints was identified on imaging. Only 18 of the 40 patients who received the standard oral preparation had contrast material present in the cecum. Eleven patients in that group had confirmed appendicitis, and four others had another abnormal finding detected at CT. There was a significant difference in the success of contrast medium transit to the colon with these two agents (p < 0.0001). The use of an oral contrast agent composed of PEG and iodinated contrast material provided a marked improvement in oral agent transit to the colon even in patients with intraabdominal inflammation.

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.

Magnetic Responsive Hydrogel Material Delivery System II

DTIC Science & Technology

2010-08-29

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

Copper complexes as a source of redox active MRI contrast agents.

PubMed

Dunbar, Lynsey; Sowden, Rebecca J; Trotter, Katherine D; Taylor, Michelle K; Smith, David; Kennedy, Alan R; Reglinski, John; Spickett, Corinne M

2015-10-01

The study reports an advance in designing copper-based redox sensing MRI contrast agents. Although the data demonstrate that copper(II) complexes are not able to compete with lanthanoids species in terms of contrast, the redox-dependent switch between diamagnetic copper(I) and paramagnetic copper(II) yields a novel redox-sensitive contrast moiety with potential for reversibility.

Hyperspectral fluorescence imaging with multi wavelength LED excitation

NASA Astrophysics Data System (ADS)

Luthman, A. Siri; Dumitru, Sebastian; Quirós-Gonzalez, Isabel; Bohndiek, Sarah E.

2016-04-01

Hyperspectral imaging (HSI) can combine morphological and molecular information, yielding potential for real-time and high throughput multiplexed fluorescent contrast agent imaging. Multiplexed readout from targets, such as cell surface receptors overexpressed in cancer cells, could improve both sensitivity and specificity of tumor identification. There remains, however, a need for compact and cost effective implementations of the technology. We have implemented a low-cost wide-field multiplexed fluorescence imaging system, which combines LED excitation at 590, 655 and 740 nm with a compact commercial solid state HSI system operating in the range 600 - 1000 nm. A key challenge for using reflectance-based HSI is the separation of contrast agent fluorescence from the reflectance of the excitation light. Here, we illustrate how it is possible to address this challenge in software, using two offline reflectance removal methods, prior to least-squares spectral unmixing. We made a quantitative comparison of the methods using data acquired from dilutions of contrast agents prepared in well-plates. We then established the capability of our HSI system for non-invasive in vivo fluorescence imaging in small animals using the optimal reflectance removal method. The HSI presented here enables quantitative unmixing of at least four fluorescent contrast agents (Alexa Fluor 610, 647, 700 and 750) simultaneously in living mice. A successful unmixing of the four fluorescent contrast agents was possible both using the pure contrast agents and with mixtures. The system could in principle also be applied to imaging of ex vivo tissue or intraoperative imaging in a clinical setting. These data suggest a promising approach for developing clinical applications of HSI based on multiplexed fluorescence contrast agent imaging.

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

PubMed

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

2015-07-01

Gd(III) chelate is currently used as positive magnetic resonance imaging (MRI) contrast agent in clinical diagnosis, but generally induces the risk of nephrogenic systemic fibrosis (NSF) due to the dissociated Gd(3+) from Gd(III) chelates. To develop a novel positive MRI contrast agent with low toxicity and high sensitivity, ultrasmall MnO nanoparticles were PEGylated via catechol-Mn chelation and conjugated with cRGD as active targeting function to tumor. Particularly, the MnO nanoparticles with a size of ca. 5nm were modified by α,β-poly(aspartic acid)-based graft polymer containing PEG and DOPA moieties and, meanwhile, conjugated with cRGD to produce the contrast agent with a size of ca. 100nm and a longitudinal relaxivity (r1) of 10.2mM(-1)S(-1). Such nanoscaled contrast agent integrated passive- and active-targeting function to tumor, and its efficient accumulation behavior in tumor was verified by in vivo distribution study. At the same time, the PEG moiety played a role of hydrophilic coating to improve the biocompatibility and stability under storing and physiological conditions, and especially might guarantee enough circulation time in blood. Moreover, in vivo MRI revealed a good and long-term effect of enhancing MRI signal for as-fabricated contrast agent while cell viability assay proved its acceptable cytotoxicity for MRI application. On the whole, the as-fabricated PEGylated and cRGD-functionalized contrast agent based on ultrasmall MnO nanoparticles showed a great potential to the T1-weighted MRI diagnosis of tumor. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Synthesis and characterization of a porphyrazine-Gd(III) MRI contrast agent and in vivo imaging of a breast cancer xenograft model.

PubMed

Trivedi, Evan R; Ma, Zhidong; Waters, Emily A; Macrenaris, Keith W; Subramanian, Rohit; Barrett, Anthony G M; Meade, Thomas J; Hoffman, Brian M

2014-01-01

Porphyrazines (Pz), or tetraazaporphyrins, are being studied for their potential use in detection and treatment of cancer. Here, an amphiphilic Cu-Pz-Gd(III) conjugate has been prepared via azide-alkyne Huisgen cycloaddition or 'click' chemistry between an azide functionalized Pz and alkyne functionalized DOTA-Gd(III) analog for use as an MRI contrast agent. This agent, Cu-Pz-Gd(III), is synthesized in good yield and exhibits solution-phase ionic relaxivity (r1  = 11.5 mM(-1) s(-1)) that is approximately four times higher than that of a clinically used monomeric Gd(III) contrast agent, DOTA-Gd(III). Breast tumor cells (MDA-MB-231) associate with Cu-Pz-Gd(III) in vitro, where significant contrast enhancement (9.336 ± 0.335 contrast-to-noise ratio) is observed in phantom cell pellet MR images. This novel contrast agent was administered in vivo to an orthotopic breast tumor model in athymic nude mice and MR images were collected. The average T1 of tumor regions in mice treated with 50 mg kg(-1) Cu-Pz-Gd(III) decreased relative to saline-treated controls. Furthermore, the decrease in T1 was persistent relative to mice treated with the monomeric Gd(III) contrast agent. An ex vivo biodistribution study confirmed that Cu-Pz-Gd(III) accumulates in the tumors and is rapidly cleared, primarily through the kidneys. Differential accumulation and T1 enhancement by Cu-Pz-Gd(III) in the tumor's core relative to the periphery offer preliminary evidence that this agent would find application in the imaging of necrotic tissue. Copyright © 2014 John Wiley & Sons, Ltd.

Spectral Imaging Technology-Based Evaluation of Radiation Treatment Planning to Remove Contrast Agent Artifacts.

PubMed

Yi-Qun, Xu; Wei, Liu; Xin-Ye, Ni

2016-10-01

This study employs dual-source computed tomography single-spectrum imaging to evaluate the effects of contrast agent artifact removal and the computational accuracy of radiotherapy treatment planning improvement. The phantom, including the contrast agent, was used in all experiments. The amounts of iodine in the contrast agent were 30, 15, 7.5, and 0.75 g/100 mL. Two images with different energy values were scanned and captured using dual-source computed tomography (80 and 140 kV). To obtain a fused image, 2 groups of images were processed using single-energy spectrum imaging technology. The Pinnacle planning system was used to measure the computed tomography values of the contrast agent and the surrounding phantom tissue. The difference between radiotherapy treatment planning based on 80 kV, 140 kV, and energy spectrum image was analyzed. For the image with high iodine concentration, the quality of the energy spectrum-fused image was the highest, followed by that of the 140-kV image. That of the 80-kV image was the worst. The difference in the radiotherapy treatment results among the 3 models was significant. When the concentration of iodine was 30 g/100 mL and the distance from the contrast agent at the dose measurement point was 1 cm, the deviation values (P) were 5.95% and 2.20% when image treatment planning was based on 80 and 140 kV, respectively. When the concentration of iodine was 15 g/100 mL, deviation values (P) were -2.64% and -1.69%. Dual-source computed tomography single-energy spectral imaging technology can remove contrast agent artifacts to improve the calculated dose accuracy in radiotherapy treatment planning. © The Author(s) 2015.

Gadolinium-Loaded Solid Lipid Nanoparticles as a Tumor-Absorbable Contrast Agent for Early Diagnosis of Colorectal Tumors Using Magnetic Resonance Colonography.

PubMed

Sun, Jihong; Zhang, Shizheng; Jiang, Shaojie; Bai, Weixian; Liu, Fei; Yuan, Hong; Ji, Jiansong; Luo, Jingfeng; Han, Guocan; Chen, Lumin; Jin, Yin; Hu, Peng; Yu, Lei; Yang, Xiaoming

2016-09-01

Magnetic resonance (MR) contrast agents focusing on special functions are required to improve cancer diagnosis, particularly in the early stages. Here, we designed multifunctional solid lipid nanoparticles (SLNs) with simultaneous loading of gadolinium (Gd) diethylenetriaminepentaacetic acid (Gd-DTPA) and octadecylamine fluorescein isothiocyanate (FITC) to obtain Gd-FITC-SLNs as a tumor-absorbable nanoparticle contrast agent for the histological confirmation of MR imaging (MRI) findings. Colorectal tumors were evaluated in vitro and in vivo via direct uptake of this contrast agent, which displayed reasonable T1 relaxivity and no significant cytotoxicity at the experimental concentrations in human colon carcinoma cells (HT29) and mouse colon carcinoma cells (CT26). In vitro cell uptake experiments demonstrated that contrast agent absorption by the two types of cancer cells was concentration-dependent in the safe concentration range. During in vivo MRI, transrectal infusion of Gd-FITC-SLNs showed more significant enhancement at the tumor site compared with the infusion of Gd-DTPA in female C57/BL mice with azoxymethane/dextran sulfate sodium-induced colorectal highgrade intraepithelial neoplasia. Subsequent confocal fluorescence microscopy demonstrated Gd-FITC-SLNs as highly concentrated green fluorescent spots distributed from the tumor capsule into the tumor. This study establishes the "proof-of-principle" of a new MRI technique wherein colorectal tumors are enhanced via direct absorption or uptake of the nanoparticle contrast agent.

Dynamic contrast-enhanced optical imaging of in vivo organ function

NASA Astrophysics Data System (ADS)

Amoozegar, Cyrus B.; Wang, Tracy; Bouchard, Matthew B.; McCaslin, Addason F. H.; Blaner, William S.; Levenson, Richard M.; Hillman, Elizabeth M. C.

2012-09-01

Conventional approaches to optical small animal molecular imaging suffer from poor resolution, limited sensitivity, and unreliable quantitation, often reducing their utility in practice. We previously demonstrated that the in vivo dynamics of an injected contrast agent could be exploited to provide high-contrast anatomical registration, owing to the temporal differences in each organ's response to the circulating fluorophore. This study extends this approach to explore whether dynamic contrast-enhanced optical imaging (DyCE) can allow noninvasive, in vivo assessment of organ function by quantifying the differing cellular uptake or wash-out dynamics of an agent in healthy and damaged organs. Specifically, we used DyCE to visualize and measure the organ-specific uptake dynamics of indocyanine green before and after induction of transient liver damage. DyCE imaging was performed longitudinally over nine days, and blood samples collected at each imaging session were analyzed for alanine aminotransferase (ALT), a liver enzyme assessed clinically as a measure of liver damage. We show that changes in DyCE-derived dynamics of liver and kidney dye uptake caused by liver damage correlate linearly with ALT concentrations, with an r2 value of 0.91. Our results demonstrate that DyCE can provide quantitative, in vivo, longitudinal measures of organ function with inexpensive and simple data acquisition.

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

PubMed Central

Beltran, Mario A.; Morales, Verónica L.; Derlon, Nicolas; Morgenroth, Eberhard; Kaufmann, Rolf; Holzner, Markus

2017-01-01

X-ray tomography is a powerful tool giving access to the morphology of biofilms, in 3D porous media, at the mesoscale. Due to the high water content of biofilms, the attenuation coefficient of biofilms and water are very close, hindering the distinction between biofilms and water without the use of contrast agents. Until now, the use of contrast agents such as barium sulfate, silver-coated micro-particles or 1-chloronaphtalene added to the liquid phase allowed imaging the biofilm 3D morphology. However, these contrast agents are not passive and potentially interact with the biofilm when injected into the sample. Here, we use a natural inorganic compound, namely iron sulfate, as a contrast agent progressively bounded in dilute or colloidal form into the EPS matrix during biofilm growth. By combining a very long source-to-detector distance on a X-ray laboratory source with a Lorentzian filter implemented prior to tomographic reconstruction, we substantially increase the contrast between the biofilm and the surrounding liquid, which allows revealing the 3D biofilm morphology. A comparison of this new method with the method proposed by Davit et al (Davit et al., 2011), which uses barium sulfate as a contrast agent to mark the liquid phase was performed. Quantitative evaluations between the methods revealed substantial differences for the volumetric fractions obtained from both methods. Namely, contrast agent—biofilm interactions (e.g. biofilm detachment) occurring during barium sulfate injection caused a reduction of the biofilm volumetric fraction of more than 50% and displacement of biofilm patches elsewhere in the column. Two key advantages of the newly proposed method are that passive addition of iron sulfate maintains the integrity of the biofilm prior to imaging, and that the biofilm itself is marked by the contrast agent, rather than the liquid phase as in other available methods. The iron sulfate method presented can be applied to understand biofilm development and bioclogging mechanisms in porous materials and the obtained biofilm morphology could be an ideal basis for 3D numerical calculations of hydrodynamic conditions to investigate biofilm-flow coupling. PMID:28732010

Dose Reduction Study in Vaginal Balloon Packing Filled With Contrast for HDR Brachytherapy Treatment;HDR; Uterine cervix cancer; Vaginal balloon packing; Contrast; Monte Carlo

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

Saini, Amarjit S.; Zhang, Geoffrey G., E-mail: geoffrey.zhang@moffitt.org; Finkelstein, Steven E.

2011-07-15

Purpose: Vaginal balloon packing is a means to displace organs at risk during high dose rate brachytherapy of the uterine cervix. We tested the hypothesis that contrast-filled vaginal balloon packing reduces radiation dose to organs at risk, such as the bladder and rectum, in comparison to water- or air-filled balloons. Methods and Materials: In a phantom study, semispherical vaginal packing balloons were filled with air, saline solution, and contrast agents. A high dose rate iridium-192 source was placed on the anterior surface of the balloon, and the diode detector was placed on the posterior surface. Dose ratios were taken withmore » each material in the balloon. Monte Carlo (MC) simulations, by use of the MC computer program DOSXYZnrc, were performed to study dose reduction vs. balloon size and contrast material, including commercially available iodine- and gadolinium-based contrast agents. Results: Measured dose ratios on the phantom with the balloon radius of 3.4 cm were 0.922 {+-} 0.002 for contrast/saline solution and 0.808 {+-} 0.001 for contrast/air. The corresponding ratios by MC simulations were 0.895 {+-} 0.010 and 0.781 {+-} 0.010. The iodine concentration in the contrast was 23.3% by weight. The dose reduction of contrast-filled balloon ranges from 6% to 15% compared with water-filled balloon and 11% to 26% compared with air-filled balloon, with a balloon size range between 1.4 and 3.8 cm, and iodine concentration in contrast of 24.9%. The dose reduction was proportional to the contrast agent concentration. The gadolinium-based contrast agents showed less dose reduction because of much lower concentrations in their solutions. Conclusions: The dose to the posterior wall of the bladder and the anterior wall of the rectum can be reduced if the vaginal balloon is filled with contrast agent in comparison to vaginal balloons filled with saline solution or air.« less

Effects of ketamine, thiopental sodium and propofol on muscle contractures in rat diaphragm in vitro.

PubMed Central

Ulker, S.; Tok, D.; Kosay, S.; Oyman, S.

1991-01-01

The effects of commonly used intravenous anaesthetic agents ketamine, thiopental sodium and propofol on the caffeine-alone or halothane-plus-caffeine-induced muscle contractures were investigated to determine safety for use in patients susceptible to malignant hyperthermia (MH). The muscle strips from rat diaphragm were exposed to one of these anaesthetic agents prior to challenge with caffeine 8 mmol/l alone or halothane 3% plus caffeine 8 mmol/l together. None of the three agents induced contractures when added alone. Ketamine 100 mumol/l and thiopental sodium 300 mumol/l augmented neither caffeine-alone nor caffeine-with-halothane contractures significantly and these two agents appear to be safe for use in MH-susceptible patients. In contrast, propofol 150 mumol/l augmented these contractile responses significantly and may not be recommended for use in patients known to be susceptible to this anaesthetic complication. PMID:1742205

EFSUMB guidelines 2011: comment on emergent indications and visions.

PubMed

Dietrich, C F; Cui, X W; Barreiros, A P; Hocke, M; Ignee, A

2012-07-01

The focus of this article is the emergent and potential indications of contrast-enhanced ultrasound (CEUS). Emergent applications of CEUS techniques include extravascular and intracavitary contrast-enhanced ultrasound, quantitative assessment of microvascular circulation for tumor response assessment, and tumor characterization using dynamic contrast-enhanced ultrasound (DCE-US). Potential indications for microbubble agents include novel molecular imaging and drug and gene delivery techniques, which have been successfully tested in animal models. "Comments and Illustrations of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Non-Liver Guidelines 2011" which focus more on established applications are published in the same supplement to Ultraschall in der Medizin (European Journal of Ultrasound). © Georg Thieme Verlag KG Stuttgart · New York.

5-HT has contrasting effects in the frontal cortex, but not the hypothalamus, on changes in noradrenaline efflux induced by the monoamine releasing-agent, d-amphetamine, and the reuptake inhibitor, BTS 54 354.

PubMed

Géranton, Sandrine M; Heal, David J; Stanford, S Clare

2004-03-01

There is extensive evidence for functional interactions between central noradrenergic and serotonergic neurones. Here, dual-probe microdialysis was used in freely-moving rats to compare the effects of 5-HT on noradrenergic transmission in the rat frontal cortex and hypothalamus. We studied the effects of the 5-HT synthesis inhibitor, para-chlorophenylalanine (pCPA; which depleted 5-HT stores in both the frontal cortex and the hypothalamus), on spontaneous efflux of noradrenaline and on the noradrenergic responses to d-amphetamine, and the monoamine reuptake inhibitor, BTS 54 354. pCPA pretreatment alone did not affect spontaneous noradrenaline efflux in either brain region, whether or not alpha2-autoreceptors were inactivated by administration of the alpha2-antagonist, atipamezole (1 mg/kg i.p). However, in the frontal cortex, pCPA pretreatment augmented the amplitude of, and prolonged, the noradrenergic response to local infusion of d-amphetamine (10 microM). In contrast, pCPA abolished the increase in cortical noradrenaline efflux induced by local infusion of BTS 54 354 (50 microM). In the hypothalamus, pCPA did not affect the amplitude of the response to either of these agents but did prolong the effects of d-amphetamine on noradrenaline efflux. These findings suggest that serotonergic transmission has complex effects on the noradrenergic response to drugs that increase noradrenergic transmission in the frontal cortex, but has less influence in the hypothalamus.

Brain tumor enhancement in magnetic resonance imaging at 3 tesla: intraindividual comparison of two high relaxivity macromolecular contrast media with a standard extracellular gd-chelate in a rat brain tumor model.

PubMed

Fries, Peter; Runge, Val M; Bücker, Arno; Schürholz, Hellmut; Reith, Wolfgang; Robert, Philippe; Jackson, Carney; Lanz, Titus; Schneider, Günther

2009-04-01

The aim of this study was to evaluate lesion enhancement (LE) and contrast-to-noise ratio (CNR) properties of P846, a new intermediate sized, high relaxivity Gd-based contrast agent at 3 Tesla in a rat brain glioma model, and to compare this contrast agent with a high relaxivity, macromolecular compound (P792), and a standard extracellular Gd-chelate (Gd-DOTA). Seven rats with experimental induced brain glioma were evaluated using 3 different contrast agents, with each MR examination separated by at least 24 hours. The time between injections assured sufficient clearance of the agent from the tumor, before the next examination. P792 (Gadomelitol, Guerbet, France) and P846 (a new compound from Guerbet Research) are macromolecular and high relaxivity contrast agents with no protein binding, and were compared with the extracellular agent Gd-DOTA (Dotarem, Guerbet, France). T1w gradient echo sequences (TR/TE 200 milliseconds/7.38 milliseconds, flip angle = 90 degrees , acquisition time: 1:42 minutes:sec, voxel size: 0.2 x 0.2 x 2.0 mm, FOV = 40 mm, acquisition matrix: 256 x 256) were acquired before and at 5 consecutive time points after each intravenous contrast injection in the identical slice orientation, using a dedicated 4-channel head array animal coil. The order of contrast media injection was randomized, with however Gd-DOTA used either as the first or second contrast agent. Contrast agent dose was adjusted to compensate for the different T1 relaxivities of the 3 agents. Signal-to-noise ratio, CNR, and LE were evaluated using region-of-interest analysis. A veterinary histopathologist confirmed the presence of a glioma in each subject, after completion of the imaging study. P792 showed significantly less LE as compared with Gd-DOTA within the first 7 minutes after contrast agent injection (P < 0.05) with, however, reaching comparable LE values at 9 minutes after injection (P = 0.07). However, P792 provided significantly less CNR as compared with Gd-DOTA (P < 0.05) for all examination time points. P846 provided comparable but persistent LE as compared with Gd-DOTA (P < 0.05) and demonstrated significantly greater LE and CNR when compared with P792 (P < 0.05). No statistically significant differences between CNR values for Gd-DOTA and P846 were noted for all examination time points (P < 0.05), with P846 administered at one-fourth the dose as compared with Gd-DOTA. The intravascular contrast medium P792 showed significantly less LE and CNR in comparison to Gd-DOTA and P846, suggesting that it does not show marked extravasation from tumor neocapillaries and does not significantly cross the disrupted blood brain-barrier in this rat glioma model. In distinction, P846 provides comparable enhancement properties at a field strength of 3 Tesla to the extracellular contrast agent Gd-DOTA, using the adjusted dose, suggesting that it crosses the disrupted blood-brain-barrier and tumor capillaries, most likely based on the decreased molecular weight as compared with P792. At the same time, the high relaxivity of this compound allows for decreasing the injected gadolinium dose by a factor of 4 whereas providing comparable enhancement properties when compared with a standard extracellular Gd-chelate (Gd-DOTA) at a dose of 0.1 mmol/kg body weight.

Cystogram

MedlinePlus

... showing the bladder (solid arrow) filling with a contrast agent. The catheter used to fill the bladder also ... taken. This final radiograph will show whether any contrast agent stays in your bladder following urina- tion. Any ...

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

PubMed

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

2012-11-01

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

Development of a Gd(III)-based receptor-induced magnetization enhancement (RIME) contrast agent for β-glucuronidase activity profiling.

PubMed

Chen, Shih-Hsien; Kuo, Yu-Ting; Singh, Gyan; Cheng, Tian-Lu; Su, Yu-Zheng; Wang, Tzu-Pin; Chiu, Yen-Yu; Lai, Jui-Jen; Chang, Chih-Ching; Jaw, Twei-Shiun; Tzou, Shey-Cherng; Liu, Gin-Chung; Wang, Yun-Ming

2012-11-19

β-Glucuronidase is a key lysosomal enzyme and is often overexpressed in necrotic tumor masses. We report here the synthesis of a pro receptor-induced magnetization enhancement (pro-RIME) magnetic resonance imaging (MRI) contrast agent ([Gd(DOTA-FPβGu)]) for molecular imaging of β-glucuronidase activity in tumor tissues. The contrast agent consists of two parts, a gadolinium complex and a β-glucuronidase substrate (β-d-glucopyranuronic acid). The binding association constant (KA) of [Gd(DOTA-FPβGu)] is 7.42 × 10(2), which is significantly lower than that of a commercially available MS-325 (KA = 3.0 × 10(4)) RIME contrast agent. The low KA value of [Gd(DOTA-FPβGu)] is due to the pendant β-d-glucopyranuronic acid moiety. Therefore, [Gd(DOTA-FPβGu)] can be used for detection of β-glucuronidase through RIME modulation. The detail mechanism of enzymatic activation of [Gd(DOTA-FPβGu)] was elucidated by LC-MS. The kinetics of β-glucuronidase catalyzed hydrolysis of [Eu(DOTA-FPβGu)] at pH 7.4 best fit the Miechalis-Menten kinetic mode with Km = 1.38 mM, kcat = 3.76 × 10(3), and kcat/Km = 2.72 × 10(3) M(-1) s(-1). The low Km value indicates high affinity of β-glucuronidase for [Gd(DOTA-FPβGu)] at physiological pH. Relaxometric studies revealed that T1 relaxivity of [Gd(DOTA-FPβGu)] changes in response to the concentration of β-glucuronidase. Consistent with the relaxometric studies, [Gd(DOTA-FPβGu)] showed significant change in MR image signal in the presence of β-glucuronidase and HSA. In vitro and in vivo MR images demonstrated appreciable differences in signal enhancement in the cell lines and tumor xenografts in accordance to their expression levels of β-glucuronidase.

Cardiotonic agent milrinone stimulates resorption in rodent bone organ culture.

PubMed Central

Krieger, N S; Stappenbeck, T S; Stern, P H

1987-01-01

The cardiotonic agent amrinone inhibits bone resorption in vitro. Milrinone, an amrinone analog, is a more potent cardiotonic agent with lower toxicity. In contrast to amrinone, milrinone stimulated resorption in cultures of neonatal mouse calvaria and fetal rat limb bones. Threshold doses were 0.1 microM in calvaria and 0.1 mM in limb bones; maximal stimulation occurred in calvaria at 0.1 mM. Maximal responses to milrinone and parathyroid hormone were comparable. Milrinone concentrations below 0.1 mM did not affect calvarial cyclic AMP. 0.5 microM indomethacin inhibited milrinone effects in calvaria but usually not in limb bones. 3 nM calcitonin inhibited milrinone-stimulated resorption and there was no escape from this inhibition. Structural homology between milrinone and thyroxine has been reported. We find similarities between milrinone and thyroxine actions on bone, because prostaglandin production was crucial for the effects of both agents in calvaria but not in limb bones, and neither agent exhibited escape from calcitonin inhibition. PMID:3027124

High Energy Resolution Hyperspectral X-Ray Imaging for Low-Dose Contrast-Enhanced Digital Mammography.

PubMed

Pani, Silvia; Saifuddin, Sarene C; Ferreira, Filipa I M; Henthorn, Nicholas; Seller, Paul; Sellin, Paul J; Stratmann, Philipp; Veale, Matthew C; Wilson, Matthew D; Cernik, Robert J

2017-09-01

Contrast-enhanced digital mammography (CEDM) is an alternative to conventional X-ray mammography for imaging dense breasts. However, conventional approaches to CEDM require a double exposure of the patient, implying higher dose, and risk of incorrect image registration due to motion artifacts. A novel approach is presented, based on hyperspectral imaging, where a detector combining positional and high-resolution spectral information (in this case based on Cadmium Telluride) is used. This allows simultaneous acquisition of the two images required for CEDM. The approach was tested on a custom breast-equivalent phantom containing iodinated contrast agent (Niopam 150®). Two algorithms were used to obtain images of the contrast agent distribution: K-edge subtraction (KES), providing images of the distribution of the contrast agent with the background structures removed, and a dual-energy (DE) algorithm, providing an iodine-equivalent image and a water-equivalent image. The high energy resolution of the detector allowed the selection of two close-by energies, maximising the signal in KES images, and enhancing the visibility of details with the low surface concentration of contrast agent. DE performed consistently better than KES in terms of contrast-to-noise ratio of the details; moreover, it allowed a correct reconstruction of the surface concentration of the contrast agent in the iodine image. Comparison with CEDM with a conventional detector proved the superior performance of hyperspectral CEDM in terms of the image quality/dose tradeoff.

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

PubMed

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

2016-09-01

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

Dual PET and Near-Infrared Fluorescence Imaging Probes as Tools for Imaging in Oncology

PubMed Central

An, Fei-Fei; Chan, Mark; Kommidi, Harikrishna; Ting, Richard

2016-01-01

OBJECTIVE The purpose of this article is to summarize advances in PET fluorescence resolution, agent design, and preclinical imaging that make a growing case for clinical PET fluorescence imaging. CONCLUSION Existing SPECT, PET, fluorescence, and MRI contrast imaging techniques are already deeply integrated into the management of cancer, from initial diagnosis to the observation and management of metastases. Combined positron-emitting fluorescent contrast agents can convey new or substantial benefits that improve on these proven clinical contrast agents. PMID:27223168

Glomerular filtration rate in evaluation of the effect of iodinated contrast media on renal function.

PubMed

Becker, Joshua; Babb, James; Serrano, Manuel

2013-04-01

The purpose of this study was to use measured glomerular filtration rate (GFR), the reference standard of renal function, to assess the deleterious effect of iodinated contrast media on renal function. Such an effect has been traditionally defined as a greater than 0.5-mg/dL increase in serum creatinine concentration or a 25% or greater increase 24-72 hours after the injection of iodinated contrast medium. This pilot investigation was focused on the consequences of clinically indicated IV injection of iodinated contrast media; intraarterial injection was excluded. One hundred thirteen patients with normal serum creatinine concentrations were enrolled in an approved protocol. At random, as chosen by one of the investigators, patients underwent imaging with one of three monomeric agents (iopamidol 300, iopromide 300, iohexol 300) and one dimeric agent (iodixanol 320). Measured GFR was determined immediately before CT and approximately 3 and 72 hours after the contrast injection for the CT examination. Iodinated contrast medium, a glomerular filtrate with no tubular excretion or reabsorption, was the GFR marker. Measured GFR was determined by x-ray fluorescence analysis with nonisotopic iodinated contrast media. Monomeric and dimeric contrast agents in diagnostic CT volumes (based on bodyweight and imaging protocol) did not induce a significant change in measured GFR (95% confidence by Wilcoxon test), suggesting that use of the evaluated contrast media will not lead to more than a 12% variation. The three monomeric agents studied and the one dimeric agent were equivalent in terms of lack of a significant effect on measured GFR when administered to patients with a normal GFR.

Noninvasive visualization of in vivo release and intratumoral distribution of surrogate MR contrast agent using the dual MR contrast technique.

PubMed

Onuki, Yoshinori; Jacobs, Igor; Artemov, Dmitri; Kato, Yoshinori

2010-09-01

A direct evaluation of the in vivo release profile of drugs from carriers is a clinical demand in drug delivery systems, because drug release characterized in vitro correlates poorly with in vivo release. The purpose of this study is to demonstrate the in vivo applicability of the dual MR contrast technique as a useful tool for noninvasive monitoring of the stability and the release profile of drug carriers, by visualizing in vivo release of the encapsulated surrogate MR contrast agent from carriers and its subsequent intratumoral distribution profile. The important aspect of this technique is that it incorporates both positive and negative contrast agents within a single carrier. GdDTPA, superparamagnetic iron oxide nanoparticles, and 5-fluorouracil were encapsulated in nano- and microspheres composed of poly(D,L-lactide-co-glycolide), which was used as a model carrier. In vivo studies were performed with orthotopic xenograft of human breast cancer. The MR-based technique demonstrated here has enabled visualization of the delivery of carriers, and release and intratumoral distribution of the encapsulated positive contrast agent. This study demonstrated proof-of-principle results for the noninvasive monitoring of in vivo release and distribution profiles of MR contrast agents, and thus, this technique will make a great contribution to the field. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

A Magnetic Chameleon: Biocompatible Lanthanide Fluoride Nanoparticles with Magnetic Field Dependent Tunable Contrast Properties as a Versatile Contrast Agent for Low to Ultrahigh Field MRI and Optical Imaging in Biological Window.

PubMed

Biju, Silvanose; Gallo, Juan; Bañobre-López, M; Manshian, Bella B; Soenen, Stefaan J; Himmelreich, Uwe; Vander Elst, Luce; Parac-Vogt, Tatjana N

2018-05-23

A novel type of multimodal, magnetic resonance imaging/optical imaging (MRI/OI) contrast agent was developed, based on core-shell lanthanide fluoride nanoparticles composed of a β-NaHoF4 core plus a β-NaGdF4:Yb 3+ , Tm 3+ shell with an average size of ∼24 nm. The biocompatibility of the particles was ensured by a surface modification with poly acrylic acid (PAA) and further functionalization with an affinity ligand, folic acid (FA). When excited using 980 nm near infrared (NIR) radiation, the contrast agent (CA) shows intense emission at 802 nm with lifetime of 791±3 μs, due to the transition 3 H 4 → 3 H 6 of Tm 3+ . Proton nuclear magnetic relaxation dispersion ( 1 H-NMRD) studies and magnetic resonance (MR) phantom imaging showed that the newly synthesized nanoparticles, decorated with poly(acrylic acid) and folic acid on the surface (NP-PAA-FA), can act mainly as a T 1 -weighted contrast agent below 1.5 T, a T 1 /T 2 dual-weighted contrast agent at 3 T, and as highly efficient T 2 -weighted contrast agent at ultrahigh fields. In addition, NP-PAA-FA showed very low cytotoxicity and no detectable cellular damage up to a dose of 500 μg mL -1 . © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antibiofouling polymer-coated gold nanoparticles as a contrast agent for in vivo X-ray computed tomography imaging.

PubMed

Kim, Dongkyu; Park, Sangjin; Lee, Jae Hyuk; Jeong, Yong Yeon; Jon, Sangyong

2007-06-20

Current computed tomography (CT) contrast agents such as iodine-based compounds have several limitations, including short imaging times due to rapid renal clearance, renal toxicity, and vascular permeation. Here, we describe a new CT contrast agent based on gold nanoparticles (GNPs) that overcomes these limitations. Because gold has a higher atomic number and X-ray absorption coefficient than iodine, we expected that GNPs can be used as CT contrast agents. We prepared uniform GNPs ( approximately 30 nm in diameter) by general reduction of HAuCl4 by boiling with sodium citrate. The resulting GNPs were coated with polyethylene glycol (PEG) to impart antibiofouling properties, which extends their lifetime in the bloodstream. Measurement of the X-ray absorption coefficient in vitro revealed that the attenuation of PEG-coated GNPs is 5.7 times higher than that of the current iodine-based CT contrast agent, Ultravist. Furthermore, when injected intravenously into rats, the PEG-coated GNPs had a much longer blood circulation time (>4 h) than Ultravist (<10 min). Consequently, CT images of rats using PEG-coated GNPs showed a clear delineation of cardiac ventricles and great vessels. On the other hand, relatively high levels of GNPs accumulated in the spleen and liver, which contain phagocytic cells. Intravenous injection of PEG-coated GNPs into hepatoma-bearing rats resulted in a high contrast ( approximately 2-fold) between hepatoma and normal liver tissue on CT images. These results suggest that PEG-coated GNPs can be useful as a CT contrast agent for a blood pool and hepatoma imaging.

Quality of abdominal computed tomography angiography: hand versus mechanical intravenous contrast administration in children.

PubMed

Ayyala, Rama S; Zurakowski, David; Lee, Edward Y

2015-11-01

Abdominal CT angiography has been increasingly used for evaluation of various conditions related to abdominal vasculature in the pediatric population. However, no direct comparison has evaluated the quality of abdominal CT angiography in children using hand versus mechanical administration of intravenous (IV) contrast agent. To compare hand versus mechanical administration of IV contrast agent in the quality of abdominal CT angiography in the pediatric population. We retrospectively reviewed the electronic medical record to identify pediatric patients (≤18 years) who had abdominal CT angiography between August 2012 and August 2013. The information obtained includes: (1) type of administration of IV contrast agent (hand [group 1] versus mechanical [group 2]), (2) size (gauge) of IV catheter, (3) amount of contrast agent administered and (4) rate of contrast agent administration (ml/s). Two reviewers independently performed qualitative and quantitative evaluation of abdominal CT angiography image quality. Qualitative evaluation of abdominal CT angiography image quality was performed by visual assessment of the degree of contrast enhancement in the region of interest (ROI) based on a 4-point scale. Quantitative evaluation of each CT angiography examination was performed by measuring the Hounsfield unit (HU) using an ROI within the abdominal aorta at two levels (celiac axis and the inferior mesenteric artery) for each child. Analysis of variance (ANOVA) using the F-test was applied to compare contrast enhancement within the abdominal aorta at two levels (celiac axis and inferior mesenteric artery) between hand administration and mechanical administration of IV contrast methods with adjustment for age. We identified 46 pediatric patients (24 male, 22 female; mean age 7.3 ± 5.5 years; range 5 weeks to 18 years) with abdominal CT angiography performed during the study period. Of these patients, 16 (35%; 1.7 ± 2.2 years; range 5 weeks to 5 years) had hand administration of IV contrast agent and 30 (65%; 10.2 ± 4.2 years; range 4-18 years) had mechanical administration of IV contrast agent. All 46 abdominal CT angiography studies were of diagnostic quality based on qualitative evaluation (all ≥3). All abdominal CT angiography studies from both groups showed diagnostic quality of contrast enhancement (>150 HU) at both the celiac axis and the inferior mesenteric artery (IMA) levels. The contrast enhancement of the abdominal aorta was not significantly different between the IV contrast administration methods at either the celiac axis level (360 ± 158 vs. 353 ± 116, P = 0.24) or the IMA level (340 ± 140 vs. 351 ± 90, P = 0.27), adjusting for age. Diagnostic-quality abdominal CT angiography can be achieved using hand administration of IV contrast agent in infants and young children (≤5 years).

Prospective randomized trial of iohexol 350 versus meglumine sodium diatrizoate as an oral contrast agent for abdominopelvic computed tomography.

PubMed

Peterson, Christine M; Lin, Michael; Pilgram, Thomas; Heiken, Jay P

2011-01-01

To compare the efficacy and patient tolerance of iohexol and meglumine sodium diatrizoate as oral contrast agents for computed tomography (CT). One hundred patients were randomly assigned to drink 1000 mL of either meglumine sodium diatrizoate or iohexol 350 before their abdominopelvic CT examination. The images were evaluated independently and in a blinded fashion by 2 radiologists who scored the extent and density of bowel opacification. Attenuation value measurements were obtained in representative areas of each gastrointestinal tract segment (stomach, duodenum, jejunum, ileum, and colon) by a research technologist. Patients' tolerance of the oral contrast agent was assessed through a questionnaire administered immediately after the CT and with a follow-up phone call 2 to 3 days later. For most of the bowel, there was no statistically significant difference in the extent or degree of opacification between the 2 contrast agents. Opacification of the ileum was better with iohexol. There was no statistically significant difference between the 2 agents in adverse effects. Patients had a small but statistically significant preference for the taste of iohexol. Iohexol 350 is a satisfactory oral contrast agent for abdominopelvic CT. It opacifies the gastrointestinal tract as well as meglumine sodium diatrizoate does, and patients prefer the taste of iohexol to that of diatrizoate.

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

PubMed

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

2006-11-01

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

An exploratory study of contrast agents for soft tissue visualization by means of high resolution X-ray computed tomography imaging.

PubMed

Pauwels, E; Van Loo, D; Cornillie, P; Brabant, L; Van Hoorebeke, L

2013-04-01

High resolution X-ray computed tomography (CT), or microCT, is a promising and already widely used technique in various scientific fields. Also for histological purposes it has great potential. Although microCT has proven to be a valuable technique for the imaging of bone structures, the visualization of soft tissue structures is still an important challenge due to their low inherent X-ray contrast. One way to achieve contrast enhancement is to make use of contrast agents. However, contrary to light and electron microscopy, knowledge about contrast agents and staining procedures is limited for X-ray CT. The purpose of this paper is to identify useful X-ray contrast agents for soft tissue visualization, which can be applied in a simple way and are also suited for samples larger than (1 cm)(3) . And 28 chemical substances have been investigated. All chemicals were applied in the form of concentrated aqueous solutions in which the samples were immersed. First, strips of green Bacon were stained to evaluate contrast enhancement between muscle and adipose tissue. Furthermore it was also tested whether the contrast agents remained fixed in the tissue after staining by re-immersing them in water. Based on the results, 12 contrast agents were selected for further testing on postmortem mice hind legs, containing a variety of different tissues, including muscle, fat, bone, cartilage and tendons. It was evaluated whether the contrast agents allowed a clearer distinction between the different soft tissue structures present. Finally also penetration depth was measured. And 26 chemicals resulted in contrast enhancement between muscle and adipose tissue in the Bacon strips. Mercury(II)chloride (HgCl2 ), phosphotungstic acid (PTA), phosphomolybdic acid (PMA) and ammonium orthomolybdate ((NH4 )2 MoO4 ) remained fixed after re-immersion in water. The penetration tests showed that potassium iodide (KI) and sodium tungstate can be most efficiently used for large samples of the order of several tens of cm(3) . PMA, PTA, HgCl2 and also to a lesser extent Na2 WO4 and (NH4 )2 MoO4 allowed a clearer distinction between the different soft tissue structures present. © 2013 The Authors Journal of Microscopy © 2013 Royal Microscopical Society.

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

Peripheral Artery Disease

MedlinePlus

... This minimally invasive imaging exam relies on a contrast agent and x-rays to show blood flow in ... pinpoint any blockages that may be present. The contrast agent is injected through a tube or catheter that ...

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

PubMed

Blumfield, Einat; Moore, Michael M; Drake, Mary K; Goodman, Thomas R; Lewis, Kristopher N; Meyer, Laura T; Ngo, Thang D; Sammet, Christina; Stanescu, Arta Luana; Swenson, David W; Slovis, Thomas L; Iyer, Ramesh S

2017-05-01

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

T1-T2 dual-modal MRI of brain gliomas using PEGylated Gd-doped iron oxide nanoparticles.

PubMed

Xiao, Ning; Gu, Wei; Wang, Hao; Deng, Yunlong; Shi, Xin; Ye, Ling

2014-03-01

To overcome the negative contrast limitations of iron oxide-based contrast agents and to improve the biocompatibility of Gd-chelate contrast agents, PEGylated Gd-doped iron oxide (PEG-GdIO) NPs as a T1-T2 dual-modal contrast agent were synthesized by the polyol method. The transverse relaxivity (r2) and longitudinal relaxivity (r1) of PEG-GdIO were determined to be 66.9 and 65.9 mM(-1) s(-1), respectively. The high r1 value and low r2/r1 ratio make PEG-GdIO NPs suitable as a T1-T2 dual-modal contrast agent. The in vivo MRI demonstrated a brighter contrast enhancement in T1-weighted image and a simultaneous darken effect in T2-weighted MR image compared to the pre-contrast image in the region of glioma. Furthermore, the biocompatibility of PEG-GdIO NPs was confirmed by the in vitro MTT cytotoxicity and in vivo histological analyses (H&E). Therefore, PEG-GdIO NPs hold great potential in T1-T2 dual-modal imaging for the diagnosis of brain glioma. Copyright © 2013 Elsevier Inc. All rights reserved.

Mouse blood vessel imaging by in-line x-ray phase-contrast imaging

NASA Astrophysics Data System (ADS)

Zhang, Xi; Liu, Xiao-Song; Yang, Xin-Rong; Chen, Shao-Liang; Zhu, Pei-Ping; Yuan, Qing-Xi

2008-10-01

It is virtually impossible to observe blood vessels by conventional x-ray imaging techniques without using contrast agents. In addition, such x-ray systems are typically incapable of detecting vessels with diameters less than 200 µm. Here we show that vessels as small as 30 µm could be detected using in-line phase-contrast x-ray imaging without the use of contrast agents. Image quality was greatly improved by replacing resident blood with physiological saline. Furthermore, an entire branch of the portal vein from the main axial portal vein to the eighth generation of branching could be captured in a single phase-contrast image. Prior to our work, detection of 30 µm diameter blood vessels could only be achieved using x-ray interferometry, which requires sophisticated x-ray optics. Our results thus demonstrate that in-line phase-contrast x-ray imaging, using physiological saline as a contrast agent, provides an alternative to the interferometric method that can be much more easily implemented and also offers the advantage of a larger field of view. A possible application of this methodology is in animal tumor models, where it can be used to observe tumor angiogenesis and the treatment effects of antineoplastic agents.

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 applied in vivo to the colon of azoxymethane (AOM) treated mice via lavage and allowed to incubate. The colons were then excised, cut longitudinally, opened to expose the lumen, and imaged en face using a fluorescence stereoscope. The QD655-VEGFR2 contrast agent produced a significant increase in contrast between diseased and undiseased tissues, allowing for fluorescence-based visualization of the diseased areas of the colon. Specificity was assessed by observing insignificant contrast increase when labeling colons of AOM-treated mice with quantum dots bioconjugated to isotype control antibodies, and by labeling the colons of saline-treated control mice. This contrast agent has a great potential for in vivo imaging of the colon through endoscopy.

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.

The anarchic hand syndrome and utilization behavior: a window onto agentive self-awareness.

PubMed

Pacherie, Elisabeth

2007-01-01

Two main approaches can be discerned in the literature on agentive self-awareness: a top-down approach, according to which agentive self-awareness is fundamentally holistic in nature and involves the operations of a central-systems narrator, and a bottom-up approach that sees agentive self-awareness as produced by lowlevel processes grounded in the very machinery responsible for motor production and control. Neither approach is entirely satisfactory if taken in isolation; however, the question of whether their combination would yield a full account of agentive self-awareness remains very much open. In this paper, I contrast two disorders affecting the control of voluntary action: the anarchic hand syndrome and utilization behavior. Although in both conditions patients fail to inhibit actions that are elicited by objects in the environment but inappropriate with respect to the wider context, these actions are experienced in radically different ways by the two groups of patients. I discuss how top-down and bottom-up processes involved in the generation of agentive self-awareness would have to be related in order to account for these differences.

Dual-Frequency Piezoelectric Transducers for Contrast Enhanced Ultrasound Imaging

PubMed Central

Martin, K. Heath; Lindsey, Brooks D.; Ma, Jianguo; Lee, Mike; Li, Sibo; Foster, F. Stuart; Jiang, Xiaoning; Dayton, Paul A.

2014-01-01

For many years, ultrasound has provided clinicians with an affordable and effective imaging tool for applications ranging from cardiology to obstetrics. Development of microbubble contrast agents over the past several decades has enabled ultrasound to distinguish between blood flow and surrounding tissue. Current clinical practices using microbubble contrast agents rely heavily on user training to evaluate degree of localized perfusion. Advances in separating the signals produced from contrast agents versus surrounding tissue backscatter provide unique opportunities for specialized sensors designed to image microbubbles with higher signal to noise and resolution than previously possible. In this review article, we describe the background principles and recent developments of ultrasound transducer technology for receiving signals produced by contrast agents while rejecting signals arising from soft tissue. This approach relies on transmitting at a low-frequency and receiving microbubble harmonic signals at frequencies many times higher than the transmitted frequency. Design and fabrication of dual-frequency transducers and the extension of recent developments in transducer technology for dual-frequency harmonic imaging are discussed. PMID:25375755

Gold nanoparticles as a contrast agent for in vivo tumor imaging with photoacoustic tomography

NASA Astrophysics Data System (ADS)

Zhang, Q.; Iwakuma, N.; Sharma, P.; Moudgil, B. M.; Wu, C.; McNeill, J.; Jiang, H.; Grobmyer, S. R.

2009-09-01

Photoacoustic tomography (PAT) is a rapidly emerging non-invasive imaging technology that integrates the merits of high optical contrast with high ultrasound resolution. The ability to quantitatively and non-invasively image nanoparticles has important implications for the development of nanoparticles as in vivo cancer diagnostic and therapeutic agents. In this study, the ability of systemically administered poly(ethylene glycol)-coated (PEGylated) gold nanoparticles as a contrast agent for in vivo tumor imaging with PAT has been evaluated. We demonstrate that gold nanoparticles (20 and 50 nm) have high photoacoustic contrast as compared to mouse tissue ex vivo. Gold nanoparticles can be visualized in mice in vivo following subcutaneous administration using PAT. Following intravenous administration of PEGylated gold nanoparticles to tumor-bearing mice, accumulation of gold nanoparticles in tumors can be effectively imaged with PAT. With gold nanoparticles as a contrast agent, PAT has important potential applications in the image guided therapy of superficial tumors such as breast cancer, melanoma and Merkel cell carcinoma.

Dual-frequency piezoelectric transducers for contrast enhanced ultrasound imaging.

PubMed

Martin, K Heath; Lindsey, Brooks D; Ma, Jianguo; Lee, Mike; Li, Sibo; Foster, F Stuart; Jiang, Xiaoning; Dayton, Paul A

2014-11-04

For many years, ultrasound has provided clinicians with an affordable and effective imaging tool for applications ranging from cardiology to obstetrics. Development of microbubble contrast agents over the past several decades has enabled ultrasound to distinguish between blood flow and surrounding tissue. Current clinical practices using microbubble contrast agents rely heavily on user training to evaluate degree of localized perfusion. Advances in separating the signals produced from contrast agents versus surrounding tissue backscatter provide unique opportunities for specialized sensors designed to image microbubbles with higher signal to noise and resolution than previously possible. In this review article, we describe the background principles and recent developments of ultrasound transducer technology for receiving signals produced by contrast agents while rejecting signals arising from soft tissue. This approach relies on transmitting at a low-frequency and receiving microbubble harmonic signals at frequencies many times higher than the transmitted frequency. Design and fabrication of dual-frequency transducers and the extension of recent developments in transducer technology for dual-frequency harmonic imaging are discussed.

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

PubMed Central

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

2014-01-01

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

Development of PEGylated KMnF3 nanoparticles as a T1-weighted contrast agent: chemical synthesis, in vivo brain MR imaging, and accounting for high relaxivity

NASA Astrophysics Data System (ADS)

Liu, Zhi-Jun; Song, Xiao-Xia; Tang, Qun

2013-05-01

Magnetic nanoparticles consisting of manganese-based T1-weighted contrast agents have rapidly achieved clinical application, however low proton relaxivity impedes further development. In this report, by analyzing nanoparticles' surface oxidation states we propose the possible reason for the low r1 relaxivity of common MnO nanoparticles and develop PEGylated fluoroperovskite KMnF3 nanoparticles as new T1-weighted contrast agents, which exhibit the highest longitudinal relaxivity (r1 = 23.15 mM-1 s-1) among all the reported manganese-based T1-weighted contrast agents. We, for the first time, illustrate a typical example showing that the surface oxidation states of metal ions exposed on the nanoparticles' surfaces are able to influence not only the optical, magnetic, electronic or catalytic properties but also water proton longitudinal relaxivity when applied as an MRI contrast agent. Cytotoxicity tests demonstrate that the PEGylated KMnF3 nanoparticles are free from toxicity. Further in vivo MRI experiments distinctively depict fine anatomical features in brain imaging at a low dose of 5 mg of Mn per kg and possible removal from the kidneys due to their small size and biocompatibility.Magnetic nanoparticles consisting of manganese-based T1-weighted contrast agents have rapidly achieved clinical application, however low proton relaxivity impedes further development. In this report, by analyzing nanoparticles' surface oxidation states we propose the possible reason for the low r1 relaxivity of common MnO nanoparticles and develop PEGylated fluoroperovskite KMnF3 nanoparticles as new T1-weighted contrast agents, which exhibit the highest longitudinal relaxivity (r1 = 23.15 mM-1 s-1) among all the reported manganese-based T1-weighted contrast agents. We, for the first time, illustrate a typical example showing that the surface oxidation states of metal ions exposed on the nanoparticles' surfaces are able to influence not only the optical, magnetic, electronic or catalytic properties but also water proton longitudinal relaxivity when applied as an MRI contrast agent. Cytotoxicity tests demonstrate that the PEGylated KMnF3 nanoparticles are free from toxicity. Further in vivo MRI experiments distinctively depict fine anatomical features in brain imaging at a low dose of 5 mg of Mn per kg and possible removal from the kidneys due to their small size and biocompatibility. Electronic supplementary information (ESI) available: Experimental procedure for two types of MnO nanoparticles, T1-weighted mapping. See DOI: 10.1039/c3nr00721a

In Vivo Visualization of Alzheimer’s Amyloid Plaques by MRI in Transgenic Mice Without a Contrast Agent

PubMed Central

Jack, Clifford R.; Garwood, Michael; Wengenack, Thomas M.; Borowski, Bret; Curran, Geoffrey L.; Lin, Joseph; Adriany, Gregor; Grohn, Olli H.J.; Grimm, Roger; Poduslo, Joseph F.

2009-01-01

One of the cardinal pathologic features of Alzheimer’s disease (AD) is formation of senile, or amyloid, plaques. Transgenic mice have been developed that express one or more of the genes responsible for familial AD in humans. Doubly transgenic mice develop “human-like” plaques, providing a mechanism to study amyloid plaque biology in a controlled manner. Imaging of labeled plaques has been accomplished with other modalities, but only MRI has sufficient spatial and contrast resolution to visualize individual plaques non-invasively. Methods to optimize visualization of plaques in vivo in transgenic mice at 9.4 T using a spin echo sequence based on adiabatic pulses are described. Preliminary results indicate that a spin echo acquisition more accurately reflects plaque size, while a T2* weighted gradient echo sequence reflects plaque iron content not plaque size. In vivo MRI – ex vivo MRI – in vitro histological correlations are provided. Histologically verified plaques as small as 50 μm in diameter were visualized in the living animal. To our knowledge this work represents the first demonstration of non-invasive in vivo visualization of individual AD plaques without the use of a contrast agent. PMID:15562496

Contrast-enhanced digital mammography (CEDM): imaging modeling, computer simulations, and phantom study

NASA Astrophysics Data System (ADS)

Chen, Biao; Jing, Zhenxue; Smith, Andrew

2005-04-01

Contrast enhanced digital mammography (CEDM), which is based upon the analysis of a series of x-ray projection images acquired before/after the administration of contrast agents, may provide physicians critical physiologic and morphologic information of breast lesions to determine the malignancy of lesions. This paper proposes to combine the kinetic analysis (KA) of contrast agent uptake/washout process and the dual-energy (DE) contrast enhancement together to formulate a hybrid contrast enhanced breast-imaging framework. The quantitative characteristics of materials and imaging components in the x-ray imaging chain, including x-ray tube (tungsten) spectrum, filter, breast tissues/lesions, contrast agents (non-ionized iodine solution), and selenium detector, were systematically modeled. The contrast-noise-ration (CNR) of iodinated lesions and mean absorbed glandular dose were estimated mathematically. The x-ray techniques optimization was conducted through a series of computer simulations to find the optimal tube voltage, filter thickness, and exposure levels for various breast thicknesses, breast density, and detectable contrast agent concentration levels in terms of detection efficiency (CNR2/dose). A phantom study was performed on a modified Selenia full field digital mammography system to verify the simulated results. The dose level was comparable to the dose in diagnostic mode (less than 4 mGy for an average 4.2 cm compressed breast). The results from the computer simulations and phantom study are being used to optimize an ongoing clinical study.

Materials Chemistry of Nanoultrasonic Biomedicine.

PubMed

Tang, Hailin; Zheng, Yuanyi; Chen, Yu

2017-03-01

As a special cross-disciplinary research frontier, nanoultrasonic biomedicine refers to the design and synthesis of nanomaterials to solve some critical issues of ultrasound (US)-based biomedicine. The concept of nanoultrasonic biomedicine can also overcome the drawbacks of traditional microbubbles and promote the generation of novel US-based contrast agents or synergistic agents for US theranostics. Here, we discuss the recent developments of material chemistry in advancing the nanoultrasonic biomedicine for diverse US-based bio-applications. We initially introduce the design principles of novel nanoplatforms for serving the nanoultrasonic biomedicine, from the viewpoint of synthetic material chemistry. Based on these principles and diverse US-based bio-application backgrounds, the representative proof-of-concept paradigms on this topic are clarified in detail, including nanodroplet vaporization for intelligent/responsive US imaging, multifunctional nano-contrast agents for US-based multi-modality imaging, activatable synergistic agents for US-based therapy, US-triggered on-demand drug releasing, US-enhanced gene transfection, US-based synergistic therapy on combating the cancer and potential toxicity issue of screening various nanosystems suitable for nanoultrasonic biomedicine. It is highly expected that this novel nanoultrasonic biomedicine and corresponding high performance in US imaging and therapy can significantly promote the generation of new sub-discipline of US-based biomedicine by rationally integrating material chemistry and theranostic nanomedicine with clinical US-based biomedicine. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of PEGylated KMnF3 nanoparticles as a T1-weighted contrast agent: chemical synthesis, in vivo brain MR imaging, and accounting for high relaxivity.

PubMed

Liu, Zhi-jun; Song, Xiao-xia; Tang, Qun

2013-06-07

Magnetic nanoparticles consisting of manganese-based T1-weighted contrast agents have rapidly achieved clinical application, however low proton relaxivity impedes further development. In this report, by analyzing nanoparticles' surface oxidation states we propose the possible reason for the low r1 relaxivity of common MnO nanoparticles and develop PEGylated fluoroperovskite KMnF3 nanoparticles as new T1-weighted contrast agents, which exhibit the highest longitudinal relaxivity (r1 = 23.15 mM(-1) s(-1)) among all the reported manganese-based T1-weighted contrast agents. We, for the first time, illustrate a typical example showing that the surface oxidation states of metal ions exposed on the nanoparticles' surfaces are able to influence not only the optical, magnetic, electronic or catalytic properties but also water proton longitudinal relaxivity when applied as an MRI contrast agent. Cytotoxicity tests demonstrate that the PEGylated KMnF3 nanoparticles are free from toxicity. Further in vivo MRI experiments distinctively depict fine anatomical features in brain imaging at a low dose of 5 mg of Mn per kg and possible removal from the kidneys due to their small size and biocompatibility.

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

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.

Quantitation of MRI sensitivity to quasi-monodisperse microbubble contrast agents for spatially resolved manometry.

PubMed

Bencsik, Martin; Al-Rwaili, Amgad; Morris, Robert; Fairhurst, David J; Mundell, Victoria; Cave, Gareth; McKendry, Jonathan; Evans, Stephen

2013-11-01

The direct in-vivo measurement of fluid pressure cannot be achieved with MRI unless it is done with the contribution of a contrast agent. No such contrast agents are currently available commercially, whilst those demonstrated previously only produced qualitative results due to their broad size distribution. Our aim is to quantitate then model the MR sensitivity to the presence of quasi-monodisperse microbubble populations. Lipid stabilised microbubble populations with mean radius 1.2 ± 0.8 μm have been produced by mechanical agitation. Contrast agents with increasing volume fraction of bubbles up to 4% were formed and the contribution the bubbles bring to the relaxation rate was quantitated. A periodic pressure change was also continuously applied to the same contrast agent, until MR signal changes were only due to bubble radius change and not due to a change in bubble density. The MR data compared favourably with the prediction of an improved numerical simulation. An excellent MR sensitivity of 23 % bar(-1) has been demonstrated. This work opens up the possibility of generating microbubble preparations tailored to specific applications with optimised MR sensitivity, in particular MRI based in-vivo manometry. Copyright © 2012 Wiley Periodicals, Inc.

Design of a novel class of protein-based magnetic resonance imaging contrast agents for the molecular imaging of cancer biomarkers

PubMed Central

Xue, Shenghui; Qiao, Jingjuan; Pu, Fan; Cameron, Mathew; Yang, Jenny J.

2014-01-01

Magnetic resonance imaging (MRI) of disease biomarkers, especially cancer biomarkers, could potentially improve our understanding of the disease and drug activity during preclinical and clinical drug treatment and patient stratification. MRI contrast agents with high relaxivity and targeting capability to tumor biomarkers are highly required. Extensive work has been done to develop MRI contrast agents. However, only a few limited literatures report that protein residues can function as ligands to bind Gd3+ with high binding affinity, selectivity, and relaxivity. In this paper, we focus on reporting our current progress on designing a novel class of protein-based Gd3+ MRI contrast agents (ProCAs) equipped with several desirable capabilities for in vivo application of MRI of tumor biomarkers. We will first discuss our strategy for improving the relaxivity by a novel protein-based design. We then discuss the effect of increased relaxivity of ProCAs on improving the detection limits for MRI contrast agent, especially for in vivo application. We will further report our efforts to improve in vivo imaging capability and our achievement in molecular imaging of cancer biomarkers with potential preclinical and clinical applications. PMID:23335551

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 concentration of microbubbles in case stable cavitation is predominant.

Macromolecular and Dendrimer Based Magnetic Resonance Contrast Agents

PubMed Central

Bumb, Ambika; Brechbiel, Martin W.; Choyke, Peter

2010-01-01

Magnetic resonance imaging (MRI) is a powerful imaging modality that can provide an assessment of function or molecular expression in tandem with anatomic detail. Over the last 20–25 years, a number of gadolinium based MR contrast agents have been developed to enhance signal by altering proton relaxation properties. This review explores a range of these agents from small molecule chelates, such as Gd-DTPA and Gd-DOTA, to macromolecular structures composed of albumin, polylysine, polysaccharides (dextran, inulin, starch), poly(ethylene glycol), copolymers of cystamine and cystine with GD-DTPA, and various dendritic structures based on polyamidoamine and polylysine (Gadomers). The synthesis, structure, biodistribution and targeting of dendrimer-based MR contrast agents are also discussed. PMID:20590365

NIR to NIR upconversion in KYb2F7: RE3+ (RE = Tm, Er) nanoparticles for biological imaging

NASA Astrophysics Data System (ADS)

Pedraza, F.; Yust, B.; Tsin, A.; Sardar, D.

2014-03-01

Until recently, many contrast agents widely used in biological imaging have absorbed and emitted in the visible region, limiting their usefulness for deeper tissue imaging. In order to push the boundaries of deep tissue imaging with non-ionizing radiation, contrast agents in the near infrared (NIR) regime, which is not strongly absorbed or scattered by most tissues, are being sought after. Upconverting nanoparticles (UCNPs) are attractive candidates since their upconversion emission is tunable with a very narrow bandwidth and they do not photobleach or blink. The upconversion produced by the nanoparticles can be tailored for NIR to NIR by carefully choosing the lanthanide dopants and dopant ratios such as KYb2F7: RE3+ (RE = Tm, Er). Spectroscopic characterization was done by analyzing absorption, fluorescence, and quantum yield data. In order to study the toxicity of the nanoparticles Monkey Retinal Endothelial Cells (MREC) were cultivated in 24 well plates and then treated with nanoparticles at different concentrations in triplicate to obtain the optimal concentration for in vivo experiments. It will be shown that these UCNPs do not elicit a strong toxic response such as quantum dots and some noble metal nanoparticles. 3-D optical slices of nanoparticle treated fibroblast cells were imaged using a confocal microscope where the nucleus and cytoplasm were stained with DAPI and Alexa Fluor respectively. These results presented support the initial assumption, which suggests that KYb2F7: RE3+ would be excellent candidates for NIR contrast agents.

2, 3-dimercaptosuccinic acid-modified iron oxide clusters for magnetic resonance imaging.

PubMed

Xiong, Fei; Yan, Caiyun; Tian, Jilai; Geng, Kunkun; Zhu, Ziyi; Song, Lina; Zhang, Yu; Mulvale, Matthew; Gu, Ning

2014-12-01

Over the last decade, various magnetic nanomaterials have been developed as magnetic resonance imaging (MRI) contrast agents; the greatest challenges encountered for clinical application have been insufficient stability. In this paper, a lyophilization method for 2, 3-dimercaptosuccinic acid-modified iron oxide (γ-Fe2 O3 @DMSA) nanoparticles was developed to simultaneously overcome two disadvantages; these include insufficient stability and low-magnetic response. After lyophilization, the clusters of γ-Fe2 O3 @DMSA with the size of 156.7 ± 15.3 nm were formed, and the stability of the lyophilized powder (γ-Fe2 O3 @DMSA-LP) increased up to over 3 years. It was also found that rehydrated γ-Fe2 O3 @DMSA-LP could be ingested by RAW264.7 cells in very large quantities. Results of pharmacokinetics and biodistribution studies in vivo indicated that γ-Fe2 O3 @DMSA-LP is a promising liver-targeted material. Furthermore, it also exhibited higher MRI efficiency and longer imaging time in the liver than the well-known product Feridex(®) . Moreover, results of vascular irritation and long-term toxicity experiments demonstrated γ-Fe2 O3 @DMSA-LP could be a nontoxic, biocompatible contrast agent in vivo. Therefore, the proposed γ-Fe2 O3 @DMSA-LP can be used as a potential MRI contrast agent in clinic for hepatic diseases. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Multipixel frequency-domain imaging of spontaneous canine breast disease using fluorescent contrast agents

NASA Astrophysics Data System (ADS)

Reynolds, Jeffery S.; Thompson, Alan B.; Troy, Tamara L.; Mayer, Ralf H.; Waters, David J.; Sevick-Muraca, Eva M.

1999-07-01

In this paper we demonstrate the ability to detect the frequency-domain fluorescent signal from the contrast agent indocyanine green within the mammary chain of dogs with spontaneous mammary tumors. We use a gain-modulated image intensifier to rapidly capture multi-pixel images of the fluorescent modulation amplitude, modulation phase, and average intensity signals. Excitation is provided by a 100 MHz amplitude-modulated, 780 nm laser diode. Time series images of the uptake and clearance of the contrast agent in the diseased tissue are also presented.

Nanoparticle Based Contrast Enhancement for Discriminating Indolent From Aggressive Prostate Cancer

DTIC Science & Technology

2016-06-01

contrast agent Major Task 1: Evaluate nanoparticle contrast in a saline model Milestones: Relationship between electrical properties and NP concentration...by Jan 2017 5 What was accomplished under these goals? 1) Major Activities ( Saline Model) – Our major focus of the 1st year of this program was to...develop an electrode array for saline tests and to begin evaluation of using nanoparticles as a contrast agent for electrical impedance measurements

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 MnCl 2 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.

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.

Polyelectrolyte coating of ferumoxytol nanoparticles for labeling of dendritic cells

NASA Astrophysics Data System (ADS)

Celikkin, Nehar; Jakubcová, Lucie; Zenke, Martin; Hoss, Mareike; Wong, John Erik; Hieronymus, Thomas

2015-04-01

Engineered magnetic nanoparticles (MNPs) are emerging to be used as cell tracers, drug delivery vehicles, and contrast agents for magnetic resonance imaging (MRI) for enhanced theragnostic applications in biomedicine. In vitro labeling of target cell populations with MNPs and their implantation into animal models and patients shows promising outcomes in monitoring successful cell engraftment, differentiation and migration by using MRI. Dendritic cells (DCs) are professional antigen-presenting cells that initiate adaptive immune responses. Thus, DCs have been the focus of cellular immunotherapy and are increasingly applied in clinical trials. Here, we addressed the coating of different polyelectrolytes (PE) around ferumoxytol particles using the layer-by-layer technique. The impact of PE-coated ferumoxytol particles for labeling of DCs and Flt3+ DC progenitors was then investigated. The results from our studies revealed that PE-coated ferumoxytol particles can be readily employed for labeling of DC and DC progenitors and thus are potentially suitable as contrast agents for MRI tracking.

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.

Calcium-sensitive MRI contrast agents based on superparamagnetic iron oxide nanoparticles and calmodulin

PubMed Central

Atanasijevic, Tatjana; Shusteff, Maxim; Fam, Peter; Jasanoff, Alan

2006-01-01

We describe a family of calcium indicators for magnetic resonance imaging (MRI), formed by combining a powerful iron oxide nanoparticle-based contrast mechanism with the versatile calcium-sensing protein calmodulin and its targets. Calcium-dependent protein–protein interactions drive particle clustering and produce up to 5-fold changes in T2 relaxivity, an indication of the sensors' potency. A variant based on conjugates of wild-type calmodulin and the peptide M13 reports concentration changes near 1 μM Ca2+, suitable for detection of elevated intracellular calcium levels. The midpoint and cooperativity of the response can be tuned by mutating the protein domains that actuate the sensor. Robust MRI signal changes are achieved even at nanomolar particle concentrations (<1 μM in calmodulin) that are unlikely to buffer calcium levels. When combined with technologies for cellular delivery of nanoparticulate agents, these sensors and their derivatives may be useful for functional molecular imaging of biological signaling networks in live, opaque specimens. PMID:17003117

Calcium-sensitive MRI contrast agents based on superparamagnetic iron oxide nanoparticles and calmodulin.

PubMed

Atanasijevic, Tatjana; Shusteff, Maxim; Fam, Peter; Jasanoff, Alan

2006-10-03

We describe a family of calcium indicators for magnetic resonance imaging (MRI), formed by combining a powerful iron oxide nanoparticle-based contrast mechanism with the versatile calcium-sensing protein calmodulin and its targets. Calcium-dependent protein-protein interactions drive particle clustering and produce up to 5-fold changes in T2 relaxivity, an indication of the sensors' potency. A variant based on conjugates of wild-type calmodulin and the peptide M13 reports concentration changes near 1 microM Ca(2+), suitable for detection of elevated intracellular calcium levels. The midpoint and cooperativity of the response can be tuned by mutating the protein domains that actuate the sensor. Robust MRI signal changes are achieved even at nanomolar particle concentrations (<1 microM in calmodulin) that are unlikely to buffer calcium levels. When combined with technologies for cellular delivery of nanoparticulate agents, these sensors and their derivatives may be useful for functional molecular imaging of biological signaling networks in live, opaque specimens.

Lung imaging of laboratory rodents in vivo

NASA Astrophysics Data System (ADS)

Cody, Dianna D.; Cavanaugh, Dawn; Price, Roger E.; Rivera, Belinda; Gladish, Gregory; Travis, Elizabeth

2004-10-01

We have been acquiring respiratory-gated micro-CT images of live mice and rats for over a year with our General Electric (formerly Enhanced Vision Systems) hybrid scanner. This technique is especially well suited for the lung due to the inherent high tissue contrast. Our current studies focus on the assessment of lung tumors and their response to experimental agents, and the assessment of lung damage due to chemotherapy agents. We have recently installed a custom-built dual flat-panel cone-beam CT scanner with the ability to scan laboratory animals that vary in size from mice to large dogs. A breath-hold technique is used in place of respiratory gating on this scanner. The objective of this pilot study was to converge on scan acquisition parameters and optimize the visualization of lung damage in a mouse model of fibrosis. Example images from both the micro-CT scanner and the flat-panel CT scanner will be presented, as well as preliminary data describing spatial resolution, low contrast resolution, and radiation dose parameters.

Acute side effects of three commonly used gadolinium contrast agents in the paediatric population.

PubMed

Neeley, Chris; Moritz, Michael; Brown, Jeffrey J; Zhou, Yihua

2016-07-01

To determine the incidence of acute side effects of three commonly used gadolinium contrast agents in the paediatric population. A retrospective review of medical records was performed to determine the incidence of acute adverse side effects of i.v. gadolinium contrast agents [MultiHance(®) (Bracco Diagnostics Inc., Princeton, NJ), Magnevist(®) (Bayer Healthcare Pharmaceuticals, Wayne, NJ) or Gadavist(®) (Bayer HealthCare Pharmaceuticals)] in paediatric patients. 40 of the 2393 patients who received gadolinium contrast agents experienced acute side effects, representing an incidence of 1.7%. The majority of the acute side effects (in 30 patients) were nausea and vomiting. The incidence was significantly higher in non-sedated patients (2.37% vs 0.7%; p = 0.0018). Furthermore, without sedation, the incidence of both nausea and vomiting was significantly higher in children receiving MultiHance, with a 4.48% incidence of nausea when compared with Magnevist (0.33%, p < 0.0001) and Gadavist (0.28%, p < 0.0001) and a 2.36% incidence of vomiting compared with those for Magnevist (0.50%, p = 0.0054) and Gadavist (0.28%, p = 0.014), whereas no difference was observed between Magnevist and Gadavist within the power of the study. In addition, there was no apparent difference between any of the three contrast agents for the incidence of allergy or other acute side effects detected, given the sample size. The gadolinium contrast agents MultiHance, Magnevist and Gadavist have a low incidence of acute side effects in the paediatric population, a rate that is further reduced in moderately sedated patients. MultiHance demonstrated significantly increased incidence of gastrointestinal symptoms compared with Magnevist and Gadavist. The incidence of acute side effects of three commonly used gadolinium contrast agents was determined in the paediatric population, which can have clinical implications.

Differential effects of two MRI contrast agents on the integrity and distribution of rAAV2 and rAAV5 in the rat striatum

PubMed Central

Osting, Sue; Bennett, Antonette; Power, Shelby; Wackett, Jordan; Hurley, Samuel A; Alexander, Andrew L; Agbandje-Mckena, Mavis; Burger, Corinna

2014-01-01

Intraoperative magnetic resonance imaging (MRI) has been proposed as a method to optimize intracerebral targeting and for tracking infusate distribution in gene therapy trials for nervous system disorders. We thus investigated possible effects of two MRI contrast agents, gadoteridol (Gd) and galbumin (Gab), on the distribution and levels of transgene expression in the rat striatum and their effect on integrity and stability of recombinant adeno-associated virus (rAAV) particles. MRI studies showed that contrast agent distribution did not predict rAAV distribution. However, green fluorescent protein (GFP) immunoreactivity revealed an increase in distribution of rAAV5-GFP, but not rAAV2-GFP, in the presence of Gd when compared with viral vector injected alone. In contrast, Gab increased the distribution of rAAV2-GFP not rAAV5-GFP. These observations pointed to a direct effect of infused contrast agent on the rAAV particles. Negative-stain electron microscopy (EM), DNAase treatment, and differential scanning calorimetry (DSC) were used to monitor rAAV2 and rAAV5 particle integrity and stability following contrast agent incubation. EMs of rAAV2-GFP and rAAV5-GFP particles pretreated with Gd appear morphologically similar to the untreated sample; however, Gab treatment resulted in surface morphology changes and aggregation. A compromise of particle integrity was suggested by sensitivity of the packaged genome to DNAase treatment following Gab incubation but not Gd for both vectors. However, neither agent significantly affected particle stability when analyzed by DSC. An increase in Tm was observed for AAV2 in lactated Ringer’s buffer. These results thus highlight potential interactions between MRI contrast agents and AAV that might affect vector distribution and stability, as well as the stabilizing effect of lactated Ringer’s solution on AAV2. PMID:26015943

Retention of Gadolinium-Based Contrast Agents in Multiple Sclerosis: Retrospective Analysis of an 18-Year Longitudinal Study.

PubMed

Forslin, Y; Shams, S; Hashim, F; Aspelin, P; Bergendal, G; Martola, J; Fredrikson, S; Kristoffersen-Wiberg, M; Granberg, T

2017-07-01

Gadolinium-based contrast agents have been associated with lasting high T1-weighted signal intensity in the dentate nucleus and globus pallidus, with histopathologically confirmed gadolinium retention. We aimed to longitudinally investigate the relationship of multiple gadolinium-based contrast agent administrations to the Signal Intensity Index in the dentate nucleus and globus pallidus and any associations with cognitive function in multiple sclerosis. The Signal Intensity Index in the dentate nucleus and globus pallidus was retrospectively evaluated on T1-weighted MR imaging in an 18-year longitudinal cohort study of 23 patients with MS receiving multiple gadolinium-based contrast agent administrations and 23 healthy age- and sex-matched controls. Participants also underwent comprehensive neuropsychological testing. Patients with MS had a higher Signal Intensity Index in the dentate nucleus ( P < .001), but not in the globus pallidus ( P = .19), compared with non-gadolinium-based contrast agent-exposed healthy controls by an unpaired t test. Increasing numbers of gadolinium-based contrast agent administrations were associated with an increased Signal Intensity Index in the dentate nucleus (β = 0.45, P < .001) and globus pallidus (β = 0.60, P < .001). This association remained stable with corrections for the age, disease duration, and physical disability for both the dentate nucleus (β = 0.43, P = .001) and globus pallidus (β = 0.58, P < .001). An increased Signal Intensity Index in the dentate nucleus among patients with MS was associated with lower verbal fluency scores, which remained significant after correction for several aspects of disease severity (β = -0.40 P = .013). Our data corroborate previous reports of lasting gadolinium retention in brain tissues. An increased Signal Intensity Index in the dentate nucleus and globus pallidus was associated with lower verbal fluency, which does not prove causality but encourages further studies on cognition and gadolinium-based contrast agent administration. © 2017 by American Journal of Neuroradiology.

Europium-engineered iron oxide nanocubes with high T1 and T2 contrast abilities for MRI in living subjects

NASA Astrophysics Data System (ADS)

Yang, Lijiao; Zhou, Zijian; Liu, Hanyu; Wu, Changqiang; Zhang, Hui; Huang, Guoming; Ai, Hua; Gao, Jinhao

2015-04-01

Magnetic resonance imaging (MRI) contrast agents with both positive (T1) and negative (T2) contrast abilities are needed in clinical diagnosis for fault-free accurate detection of lesions. We report a facile synthesis of europium-engineered iron oxide (EuIO) nanocubes as T1 and T2 contrast agents for MRI in living subjects. The Eu(iii) oxide-embedded iron oxide nanoparticles significantly increase the T1 relaxivity with an enhanced positive contrast effect. EuIO nanocubes with 14 nm in diameter showed a high r1 value of 36.8 mM-1 s-1 with respect to total metal ions (Fe + Eu), which is about 3 times higher than that of Fe3O4 nanoparticles with similar size. Moreover, both r1 and r2 values of EuIO nanocubes can be tuned by varying their sizes and Eu doping ratios. After citrate coating, EuIO nanocubes can provide enhanced T1 and T2 contrast effects in small animals, particularly in the cardiac and liver regions. This work may provide an insightful strategy to design MRI contrast agents with both positive and negative contrast abilities for biomedical applications.Magnetic resonance imaging (MRI) contrast agents with both positive (T1) and negative (T2) contrast abilities are needed in clinical diagnosis for fault-free accurate detection of lesions. We report a facile synthesis of europium-engineered iron oxide (EuIO) nanocubes as T1 and T2 contrast agents for MRI in living subjects. The Eu(iii) oxide-embedded iron oxide nanoparticles significantly increase the T1 relaxivity with an enhanced positive contrast effect. EuIO nanocubes with 14 nm in diameter showed a high r1 value of 36.8 mM-1 s-1 with respect to total metal ions (Fe + Eu), which is about 3 times higher than that of Fe3O4 nanoparticles with similar size. Moreover, both r1 and r2 values of EuIO nanocubes can be tuned by varying their sizes and Eu doping ratios. After citrate coating, EuIO nanocubes can provide enhanced T1 and T2 contrast effects in small animals, particularly in the cardiac and liver regions. This work may provide an insightful strategy to design MRI contrast agents with both positive and negative contrast abilities for biomedical applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr00774g

Speak Up: Prevent Errors in Your Child's Care

MedlinePlus

... Ask if your child will be given a contrast agent. This is a liquid that makes organs and ... staff if your child has had problems with contrast agents before. Immediately alert staff if your child begins ...

Utility of a prototype liposomal contrast agent for x-ray imaging of breast cancer: a proof of concept using micro-CT in small animals

NASA Astrophysics Data System (ADS)

Badea, C. T.; Samei, E.; Ghaghada, K.; Saunders, R.; Yuan, H.; Qi, Y.; Hedlund, L. W.; Mukundan, S.

2008-03-01

Imaging tumor angiogenesis in small animals is extremely challenging due to the size of the tumor vessels. Consequently, both dedicated small animal imaging systems and specialized intravascular contrast agents are required. The goal of this study was to investigate the use of a liposomal contrast agent for high-resolution micro-CT imaging of breast tumors in small animals. A liposomal blood pool agent encapsulating iodine with a concentration of 65.5 mg/ml was used with a Duke Center for In Vivo Microscopy (CIVM) prototype micro-computed tomography (micro-CT) system to image the R3230AC mammary carcinoma implanted in rats. The animals were injected with equivalent volume doses (0.02 ml/kg) of contrast agent. Micro-CT with the liposomal blood pool contrast agent ensured a signal difference between the blood and the muscle higher than 450 HU allowing the visualization of the tumors 3D vascular architecture in exquisite detail at 100-micron resolution. The micro-CT data correlated well with the histological examination of tumor tissue. We also studied the ability to detect vascular enhancement with limited angle based reconstruction, i.e. tomosynthesis. Tumor volumes and their regional vascular percentage were estimated. This imaging approach could be used to better understand tumor angiogenesis and be the basis for evaluating anti-angiogenic therapies.

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

PubMed

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

2006-01-01

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

Doxorubicin Delivery into Tumor Cells by Stable Cavitation without Contrast Agents.

PubMed

Chettab, Kamel; Mestas, Jean-Louis; Lafond, Maxime; Saadna, Djamel Eddine; Lafon, Cyril; Dumontet, Charles

2017-02-06

Doxorubicin, alone or in combination with other anticancer agents, is one of the most widely used chemotherapeutic agents and is administered in a wide range of cancers. However, the use of doxorubicin is limited due to its potential serious adverse reactions. Previous studies have established the ability of high intensity focused ultrasound (HIFU) in combination with various contrast agents to increase intracellular doxorubicin delivery in a targeted and noninvasive manner. In this study, we developed a new sonoporation device generating and monitoring acoustic cavitation bubbles without any addition of contrast agents. The device was used to potentiate the delivery of active doxorubicin into both adherent and suspended cell lines. Combining doxorubicin with ultrasound resulted in a significant enhancement of doxorubicin intracellular delivery and a decrease in cell viability at 48 and 72 h, in comparison to doxorubicin alone. More importantly and unlike previous investigations, our procedure does not require the addition of contrast agents to generate acoustic cavitation and to achieve high levels of doxorubicin delivery. The successful translation of this approach for an in vivo application may allow a significant reduction in the dosage and the adverse effects of doxorubicin therapy in patients.

Usefulness of high-density barium for detection of leaks after esophagogastrectomy, total gastrectomy, and total laryngectomy.

PubMed

Swanson, Jonathan O; Levine, Marc S; Redfern, Regina O; Rubesin, Stephen E

2003-08-01

The purpose of this study was to determine the usefulness of a high-density (250% weight/volume) barium compared with a water-soluble contrast agent for the detection of esophageal leaks in patients who had undergone esophagogastrectomy, total gastrectomy, or total laryngectomy. A search of our radiology database from 1998 to 2001 revealed 46 eligible radiographic studies performed using a water-soluble contrast agent alone or a water-soluble contrast agent followed by barium that showed leaks in patients who had undergone esophagogastrectomy, total gastrectomy, or total laryngectomy. The images were reviewed to determine the morphology of the leaks (i.e., blind-ending tracks, sealed-off collections, or free extravasation of contrast material). Medical records were also reviewed to determine whether detection of the leaks seen on the radiographic studies affected patient management. Of the 46 leaks seen on radiographic studies, 23 (50%) were detected with a water-soluble contrast agent and 23 (50%) were detected only with high-density barium. Of the 23 leaks visualized with water-soluble contrast media, six (26%) were characterized by blind-ending tracks, 14 (61%) by sealed-off collections, and three (13%) by free extravasation of contrast material into the mediastinum or neck. Of the 23 leaks visualized only with high-density barium, 19 (83%) were characterized by blind-ending tracks and four (17%) by sealed-off collections. Thus, leaks detected only on images obtained with high-density barium were significantly more likely to be characterized by blind-ending tracks than those detected on images obtained with a water-soluble contrast agent (p = 0.0007). Of the 33 patients with clinical follow-up, the findings seen on these imaging studies affected management in 12 (86%) of 14 patients with leaks depicted by water-soluble contrast media and in 10 (53%) of 19 with leaks depicted only by high-density barium. Our findings support the use of high-density barium as part of the routine postoperative radiographic examination when no leaks are detected on images obtained with a water-soluble contrast agent.

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

PubMed

Wiener, Edzard; Settles, Marcus; Diederichs, Gerd

2010-01-01

The transverse relaxation time, T(2), of native cartilage is used to quantify cartilage degradation. T(2) is frequently measured after contrast administration, assuming that the impact of gadolinium-based contrast agents on cartilage T(2) is negligible. To verify this assumption the depth-dependent variation of T(2) in the presence of gadopentetate dimeglumine, gadobenate dimeglumine and gadoteridol was investigated. Furthermore, the r(2)/r(1) relaxivity ratios were quantified in different cartilage layers to demonstrate differences between T(2) and T(1) relaxation effects. Transverse high-spatial-resolution T(1)- and T(2)-maps were simultaneously acquired on a 1.5 T MR scanner before and after contrast administration in nine bovine patellae using a turbo-mixed sequence. The r(2)/r(1) ratios were calculated for each contrast agent in cartilage. Profiles of T(1), T(2) and r(2)/r(1) across cartilage thickness were generated in the absence and presence of contrast agent. The mean values in different cartilage layers were compared for global variance using the Kruskal-Wallis test and pairwise using the Mann-Whitney U-test. T(2) of unenhanced cartilage was 98 +/- 5 ms at 1 mm and 65 +/- 4 ms at 3 mm depth. Eleven hours after contrast administration significant differences (p < 0.001) were measurable for all three contrast agents. T(2) values were 58 +/- 2 and 62 +/- 3 ms for gadopentetate dimeglumine, 46 +/- 2 and 57 +/- 2 ms for gadobenate dimeglumine, and 38 +/- 2 and 42 +/- 2 ms for gadoteridol at 1 and 3 mm depths, respectively. The r(2)/r(1) relaxivity ratios across cartilage thickness were close to 1.0 (range 0.9-1.3). At 1.5 T, T(2) decreased significantly in the presence of contrast agents, more pronounced in superficial than in deep cartilage. The change in T(2) relaxation rate was similar to the change in T(1). Cartilage T(2) measurements after contrast administration will lead to systematic errors in the quantification of cartilage degradation. 2010 John Wiley & Sons, Ltd.

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

NASA Astrophysics Data System (ADS)

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

2015-09-01

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

Early detection of osteoarthritis in rabbits using MRI with a double-contrast agent.

PubMed

Onishi, Okihiro; Ikoma, Kazuya; Kido, Masamitsu; Kabuto, Yukichi; Ueshima, Keiichiro; Matsuda, Ken-Ichi; Tanaka, Masaki; Kubo, Toshikazu

2018-03-13

Articular cartilage degeneration has been evaluated by magnetic resonance imaging (MRI). However, this method has several problems, including its time-consuming nature and the requirement of a high magnetic field or specialized hardware. The purpose of this study was to sequentially assess early degenerative changes in rabbit knee articular cartilage using MRI with a new double-contrast agent. We induced osteoarthritis (OA) in the right knee of rabbits by anterior cruciate ligament transection and partial medial meniscectomy. Proton density-weighted images and T 2 -calculated images were obtained before and after contrast agent injection into the knee. The signal intensity ratio (SIR) values on the proton density-weighted images were calculated by dividing the signal intensity of the articular cartilage by that of joint fluid. Six rabbits were examined using MRI at 2 (designated 2-w OA) and 4 weeks (4-w OA) after the operation. Histological examination was performed 4 weeks after the operation. One rabbit was histologically examined 2 weeks after the operation. The control consisted of six rabbits that were not subjected to the operation. The SIR values, T 2 values and the thicknesses of the cartilage of the 2-w OA, 4-w OA and the control before and after contrast agent injection were analyzed. The Mankin score and OARSI (Osteoarthritis Research Society International) score were used for the histological evaluation. Significant differences in the SIR and T 2 values of the medial and lateral condyles of the femur were found between the control and the 4-w OA only after contrast agent injection. No significant differences were found in the SIR and T 2 values before contrast agent injection between the control, the 2-w OA and 4-w OA. The thickness of the articular cartilage revealed no significant differences. In the histological assessment, the Mankin score and OARSI score sequentially increased from the control to the 4-w OA. We evaluated the SIR and T 2 values of the knees in a rabbit OA model and a control model using a new double-contrast agent. MRI with this agent enabled OA detection earlier than using conventional MRI.

Patent foramen ovale: diagnosis with multidetector CT--comparison with transesophageal echocardiography.

PubMed

Kim, Young Jin; Hur, Jin; Shim, Chi-Young; Lee, Hye-Jeong; Ha, Jong-Won; Choe, Kyu Ok; Heo, Ji Hoe; Choi, Eui-Young; Choi, Byoung Wook

2009-01-01

To evaluate the clinical feasibility and accuracy of 64-section multidetector computed tomography (CT) compared with transesophageal echocardiography (TEE) for diagnosis of a patent foramen ovale (PFO). Institutional review board approval was obtained for this retrospective study. The study included 152 consecutive stroke patients (mean age, 61.7 years; 98 men, 54 women) who underwent both cardiac multidetector CT and TEE. Electrocardiographically gated cardiac CT was performed with a 64-section CT scanner by using a saline-chaser contrast agent injection technique. A contrast agent jet from the contrast agent-filled left atrium (LA) to the saline-filled right atrium (RA) and channel-like appearance of the interatrial septum (IAS) were evaluated on axial and oblique sagittal CT images. Two-dimensional and Doppler TEE were performed to detect PFO. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CT were obtained with TEE as the reference standard. A PFO was present in 26 patients at TEE. On CT images, a left-to-right contrast agent jet toward the inferior vena cava was noted in 21 patients (sensitivity, 73.1%; specificity, 98.4%; PPV, 90.5%; NPV, 94.7%). Channel-like appearance of the IAS was detected in 38 patients (sensitivity, 76.9%; specificity, 85.7%; PPV, 52.6%; NPV, 94.7%). Channel-like appearance of the IAS was noted in all patients who had a contrast agent jet. A contrast agent jet from LA to RA toward the inferior vena cava with channel-like appearance of the IAS on CT images confirms the presence of a PFO. (c) RSNA, 2008.

Clinical development of BLZ-100 for real-time optical imaging of tumors during resection

NASA Astrophysics Data System (ADS)

Franklin, Heather L.; Miller, Dennis M.; Hedges, Teresa; Perry, Jeff; Parrish-Novak, Julia

2016-03-01

Complete initial resection can give cancer patients the best opportunity for long-term survival. There is unmet need in surgical oncology for optical imaging that enables simple and precise visualization of tumors and consistent contrast with surrounding normal tissues. Near-infrared (NIR) contrast agents and camera systems that can detect them represent an area of active research and development. The investigational Tumor Paint agent BLZ-100 is a conjugate of a chlorotoxin peptide and the NIR dye indocyanine green (ICG) that has been shown to specifically bind to a broad range of solid tumors. Clinical efficacy studies with BLZ-100 are in progress, a necessary step in bringing the product into clinical practice. To ensure a product that will be useful for and accepted by surgeons, the early clinical development of BLZ- 100 incorporates multiple tumor types and imaging devices so that surgeon feedback covers the range of anticipated clinical uses. Key contrast agent characteristics include safety, specificity, flexibility in timing between dose and surgery, and breadth of tumor types recognized. Imaging devices should use wavelengths that are optimal for the contrast agent, be sensitive enough that contrast agent dosing can be adjusted for optimal contrast, include real-time video display of fluorescence and white light image, and be simple for surgeons to use with minimal disruption of surgical flow. Rapid entry into clinical studies provides the best opportunity for early surgeon feedback, enabling development of agents and devices that will gain broad acceptance and provide information that helps surgeons achieve more complete and precise resections.

A theoretical framework to model DSC-MRI data acquired in the presence of contrast agent extravasation

NASA Astrophysics Data System (ADS)

Quarles, C. C.; Gochberg, D. F.; Gore, J. C.; Yankeelov, T. E.

2009-10-01

Dynamic susceptibility contrast (DSC) MRI methods rely on compartmentalization of the contrast agent such that a susceptibility gradient can be induced between the contrast-containing compartment and adjacent spaces, such as between intravascular and extravascular spaces. When there is a disruption of the blood-brain barrier, as is frequently the case with brain tumors, a contrast agent leaks out of the vasculature, resulting in additional T1, T2 and T*2 relaxation effects in the extravascular space, thereby affecting the signal intensity time course and reducing the reliability of the computed hemodynamic parameters. In this study, a theoretical model describing these dynamic intra- and extravascular T1, T2 and T*2 relaxation interactions is proposed. The applicability of using the proposed model to investigate the influence of relevant MRI pulse sequences (e.g. echo time, flip angle), and physical (e.g. susceptibility calibration factors, pre-contrast relaxation rates) and physiological parameters (e.g. permeability, blood flow, compartmental volume fractions) on DSC-MRI signal time curves is demonstrated. Such a model could yield important insights into the biophysical basis of contrast-agent-extravasastion-induced effects on measured DSC-MRI signals and provide a means to investigate pulse sequence optimization and appropriate data analysis methods for the extraction of physiologically relevant imaging metrics.

Application of a biodegradable macromolecular contrast agent in dynamic contrast enhanced MRI for assessing the efficacy of indocyanine green enhanced photothermal cancer therapy

PubMed Central

Feng, Yi; Emerson, Lyska; Jeong, Eun-Kee; Parker, Dennis L.; Lu, Zheng-Rong

2009-01-01

Purpose To investigate the effectiveness of a polydisulfide-based biodegradable macromolecular contrast agent, (Gd-DTPA)-cystamine copolymers (GDCC), in assessing the efficacy of indocyanine green enhanced photothermal cancer therapy using dynamic contrast enhanced MRI (DCE-MRI). Materials and Methods Breast cancer xenografts in mice were injected with indocyanine green and irradiated with laser. The efficacy was assessed using DCE-MRI with GDCC of 40 KDa (GDCC-40) at 4 hours and 7 days after the treatment. The uptake of GDCC-40 by the tumors was fit to a two-compartment model to obtain tumor vascular parameters, including fractional plasma volume (fPV), endothelium transfer coefficient (KPS), and permeability surface area product (PS). Results GDCC-40 resulted in similar tumor vascular parameters at three doses with larger standard deviations at lower doses. The values of fPV, KPS and PS of the treated tumors were smaller (p < 0.05) than those of untreated tumors at 4 hours after the treatment and recovered to pretreatment values (p > 0.05) at 7 days after the treatment. Conclusion DCE-MRI with GDCC-40 is effective for assessing tumor early response to dye-enhanced photothermal therapy and detecting tumor relapse after the treatment. GDCC-40 has a potential to non-invasively monitor anticancer therapies with DCE-MRI. PMID:19629979

Evaluation of simethicone-coated cellulose as a negative oral contrast agent for abdominal CT.

PubMed

Sahani, Dushyant V; Jhaveri, Kartik S; D'souza, Roy V; Varghese, Jose C; Halpern, Elkan; Harisinghani, Mukesh G; Hahn, Peter F; Saini, Sanjay

2003-05-01

Because of the increased clinical use of computed tomography (CT) for imaging the abdominal vasculature and urinary tract, there is a need for negative contrast agents. The authors undertook this study to assess the suitability of simethicone-coated cellulose (SCC), which is approved for use as an oral contrast agent in sonography, for use as a negative oral contrast agent in abdominal CT. This prospective study involved 40 adult patients scheduled to undergo abdominal CT for the evaluation of hematuria. Prior to scanning, 20 subjects received 800 mL of SCC and 20 received 800 mL of water as an oral contrast agent. Imaging was performed with a multi-detector row helical scanner in two phases, according to the abdominal CT protocol used for hematuria evaluation at the authors' institution. The first, "early" phase began an average of 15 minutes after the ingestion of contrast material; the second, "late" phase began an average of 45 minutes after the ingestion of contrast material. Blinded analysis was performed by three abdominal radiologists separately, using a three-point scale (0 = poor, 1 = acceptable, 2 = excellent) to assess the effectiveness of SCC for marking the proximal, middle, and distal small bowel. Average scores for enhancement with SCC and with water were obtained and compared. Statistical analysis was performed with a Wilcoxon signed-rank test. SCC was assigned higher mean scores than water for enhancement in each segment of the bowel, both on early-phase images (0.8-1.35 for SCC vs 0.6-1.1 for water) and on late-phase images (1.1-1.4 vs 0.81-0.96). Bowel marking with SCC, particularly in the jejunum and ileum, also was rated better than that with water in a high percentage of patients. The differences between the scores for water and for SCC, however, were not statistically significant (P > .05). SCC is effective as a negative oral contrast agent for small bowel marking at CT.

L-DOPA-Coated Manganese Oxide Nanoparticles as Dual MRI Contrast Agents and Drug-Delivery Vehicles.

PubMed

McDonagh, Birgitte Hjelmeland; Singh, Gurvinder; Hak, Sjoerd; Bandyopadhyay, Sulalit; Augestad, Ingrid Lovise; Peddis, Davide; Sandvig, Ioanna; Sandvig, Axel; Glomm, Wilhelm Robert

2016-01-20

Manganese oxide nanoparticles (MONPs) are capable of time-dependent magnetic resonance imaging contrast switching as well as releasing a surface-bound drug. MONPs give T2/T2* contrast, but dissolve and release T1-active Mn(2+) and L-3,4-dihydroxyphenylalanine. Complementary images are acquired with a single contrast agent, and applications toward Parkinson's disease are suggested. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison of Different Contrast Agents in Detecting Cardiac Right-to-Left Shunt in Patients with a Patent Foramen Ovale during Contrast-Transthoracic Echocardiography

PubMed Central

Zhao, Enfa; Cheng, Gesheng; Wang, Yingli

2017-01-01

The aim of this study is to evaluate the ability of two different contrast agents to detect cardiac right-to-left shunting in patients with a patent foramen ovale during contrast transthoracic echocardiography and transesophageal echocardiography. Eighty-four patients who had migraines or experienced cryptogenic stroke were prospectively enrolled. Contrast echocardiography of the right portion of the heart was performed using an injection of either (i) 8 ml of agitated saline, 1 ml of blood, and 1 ml of air (ASB) or (ii) 4 ml of vitamin B6 and 6 ml of sodium bicarbonate solution (VSBS). All patients underwent contrast echocardiography with different contrast agents successively before undergoing transesophageal echocardiography. The diagnostic sensitivity of VSBS and ASB for cardiac shunting diagnosis was 94.23% and 78.85%, respectively. The diagnostic sensitivity in the VSBS group was significantly higher than that in the ASB group (χ2 = 5.283, P = 0.022). The observed semiquantitative shunt grading suggests that the positive rate in the VSBS group was higher than that in the ASB group (Z = −1.998, P = 0.046). The use of vitamin B6 and sodium bicarbonate solution as a TTE contrast agent yielded a high sensitivity compared with ASB. However, further trials with large sample size are required to confirm this finding. PMID:29333447

Artifacts in Sonography - Part 3.

PubMed

Bönhof, Jörg A; McLaughlin, Glen

2018-06-01

As a continuation of parts 1 1 and 2 2, this article discusses artifacts as caused by insufficient temporal resolution, artifacts in color and spectral Doppler sonography, and information regarding artifacts in sonography with contrast agents. There are artifacts that occur in B-mode sonography as well as in Doppler imaging methods and sonography with contrast agents, such as slice thickness artifacts and bow artifacts, shadows, mirroring, and artifacts due to refraction that appear, for example, as double images, because they are based on the same formation mechanisms. In addition, there are artifacts specific to Doppler sonography, such as the twinkling artifact, and method-based motion artifacts, such as aliasing, the ureteric jet, and due to tissue vibration. The artifacts specific to contrast mode include echoes from usually highly reflective structures that are not contrast bubbles ("leakage"). Contrast agent can also change the transmitting signal so that even structures not containing contrast agent are echogenic ("pseudoenhancement"). While artifacts can cause problems regarding differential diagnosis, they can also be useful for determining the diagnosis. Therefore, effective use of sonography requires both profound knowledge and skilled interpretation of artifacts. © Georg Thieme Verlag KG Stuttgart · New York.

In vivo photoacoustic tumor tomography using a quinoline-annulated porphyrin as NIR molecular contrast agent.

PubMed

Luciano, Michael; Erfanzadeh, Mohsen; Zhou, Feifei; Zhu, Hua; Bornhütter, Tobias; Röder, Beate; Zhu, Quing; Brückner, Christian

2017-01-25

The synthesis and photophysical properties of a tetra-PEG-modified and freely water-soluble quinoline-annulated porphyrin are described. We previously demonstrated the ability of quinoline-annulated porphyrins to act as an in vitro NIR photoacoustic imaging (PAI) contrast agent. The solubility of the quinoline-annulated porphyrin derivative in serum now allowed the assessment of the efficacy of the PEGylated derivative as an in vivo NIR contrast agent for the PAI of an implanted tumor in a mouse model. A multi-fold contrast enhancement when compared to the benchmark dye ICG could be shown, a finding that could be traced to its photophysical properties (short triplet lifetimes, low fluorescence and singlet oxygen sensitization quantum yields). A NIR excitation wavelength of 790 nm could be used, fully taking advantage of the optical window of tissue. Rapid renal clearance of the dye was observed. Its straight-forward synthesis, optical properties with the possibility for further optical fine-tuning, nontoxicity, favorable elimination rates, and contrast enhancement make this a promising PAI contrast agent. The ability to conjugate the PAI chromophore with a fluorescent tag using a facile and general conjugation strategy was also demonstrated.

Integrin αvβ3-targeted dynamic contrast-enhanced magnetic resonance imaging using a gadolinium-loaded polyethylene gycol-dendrimer-cyclic RGD conjugate to evaluate tumor angiogenesis and to assess early antiangiogenic treatment response in a mouse xenograft tumor model.

PubMed

Chen, Wei-Tsung; Shih, Tiffany Ting Fang; Chen, Ran-Chou; Tu, Shin-Yang; Hsieh, Wen-Yuen; Yang, Pang-Chyr

2012-01-01

The purpose of this study was to validate an integrin αvβ3-targeted magnetic resonance contrast agent, PEG-G3-(Gd-DTPA)6-(cRGD-DTPA)2, for its ability to detect tumor angiogenesis and assess early response to antiangiogenic therapy using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). Integrin αvβ3-positive U87 cells and control groups were incubated with fluorescein-labeled cRGD-conjugated dendrimer, and the cellular attachment of the dendrimer was observed. DCE MRI was performed on mice bearing KB xenograft tumors using either PEG-G3-(Gd-DTPA)6-(cRGD-DTPA)2 or PEG-G3-(Gd-DTPA)6-(cRAD-DTPA)2. DCE MRI was also performed 2 hours after anti-integrin αvβ3 monoclonal antibody treatment and after bevacizumab treatment on days 3 and 6t. Using DCE MRI, the 30-minute contrast washout percentage was significantly lower in the cRGD-conjugate injection groups. The enhancement patterns were different between the two contrast injection groups. In the antiangiogenic therapy groups, a rapid increase in 30-minute contrast washout percentage was observed in both the LM609 and bevacizumab treatment groups, and this occurred before there was an observable decrease in tumor size. The integrin αvβ3 targeting ability of PEG-G3-(Gd-DTPA)6-(cRGD-DTPA)2 in vitro and in vivo was demonstrated. The 30-minute contrast washout percentage is a useful parameter for examining tumor angiogenesis and for the early assessment of antiangiogenic treatment response.

A hyaluronic acid nanogel for photo-chemo theranostics of lung cancer with simultaneous light-responsive controlled release of doxorubicin

NASA Astrophysics Data System (ADS)

Khatun, Zehedina; Nurunnabi, Md; Nafiujjaman, Md; Reeck, Gerald R.; Khan, Haseeb A.; Cho, Kwang Jae; Lee, Yong-Kyu

2015-06-01

The combined delivery of photo- and chemo-therapeutic agents is an emerging strategy to overcome drug resistance in treating cancer, and controlled light-responsive drug release is a proven tactic to produce a continuous therapeutic effect for a prolonged duration. Here, a combination of light-responsive graphene, chemo-agent doxorubicin and pH-sensitive disulfide-bond linked hyaluronic acid form a nanogel (called a graphene-doxorubicin conjugate in a hyaluronic acid nanogel) that exerts an activity with multiple effects: thermo and chemotherapeutic, real-time noninvasive imaging, and light-glutathione-responsive controlled drug release. The nanogel is mono-dispersed with an average diameter of 120 nm as observed by using TEM and a hydrodynamic size analyzer. It has excellent photo-luminescence properties and good stability in buffer and serum solutions. Graphene itself, being photoluminescent, can be considered an optical imaging contrast agent as well as a heat source when excited by laser irradiation. Thus the nanogel shows simultaneous thermo-chemotherapeutic effects on noninvasive optical imaging. We have also found that irradiation enhances the release of doxorubicin in a controlled manner. This release synergizes therapeutic activity of the nanogel in killing tumor cells. Our findings demonstrate that the graphene-doxorubicin conjugate in the hyaluronic acid nanogel is very effective in killing the human lung cancer cell line (A549) with limited toxicity in the non-cancerous cell line (MDCK).The combined delivery of photo- and chemo-therapeutic agents is an emerging strategy to overcome drug resistance in treating cancer, and controlled light-responsive drug release is a proven tactic to produce a continuous therapeutic effect for a prolonged duration. Here, a combination of light-responsive graphene, chemo-agent doxorubicin and pH-sensitive disulfide-bond linked hyaluronic acid form a nanogel (called a graphene-doxorubicin conjugate in a hyaluronic acid nanogel) that exerts an activity with multiple effects: thermo and chemotherapeutic, real-time noninvasive imaging, and light-glutathione-responsive controlled drug release. The nanogel is mono-dispersed with an average diameter of 120 nm as observed by using TEM and a hydrodynamic size analyzer. It has excellent photo-luminescence properties and good stability in buffer and serum solutions. Graphene itself, being photoluminescent, can be considered an optical imaging contrast agent as well as a heat source when excited by laser irradiation. Thus the nanogel shows simultaneous thermo-chemotherapeutic effects on noninvasive optical imaging. We have also found that irradiation enhances the release of doxorubicin in a controlled manner. This release synergizes therapeutic activity of the nanogel in killing tumor cells. Our findings demonstrate that the graphene-doxorubicin conjugate in the hyaluronic acid nanogel is very effective in killing the human lung cancer cell line (A549) with limited toxicity in the non-cancerous cell line (MDCK). Electronic supplementary information (ESI) available: In vitro stability study method and results, FT-IR data, optical properties and thermal stability (TGA and DTA), cell image and in vivo optical image and histological images. See DOI: 10.1039/c5nr01075f

Instrumentation for contrast echocardiography: technology and techniques.

PubMed

Kaul, Sanjiv

2002-11-18

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

[Contrast medium enhanced magnetic resonance tomography of liver metastases: positive versus negative contrast media].

PubMed

Hammerstingl, R M; Schwarz, W; Hochmuth, K; Staib-Sebler, E; Lorenz, M; Vogl, T J

2001-01-01

The development in oncologic liver surgery as well as modified interventional therapy strategies of the liver have resulted in improved diagnostic imaging. The evolution of contrast agents for MR imaging of the liver has proceeded along several different paths with the common goal of improving liver-lesion contrast. In MRI contrast agents act indirectly by their effects on relaxation times. Contrast agents used for hepatic MR imaging can be categorized in those that target the extracellular space, the hepatobiliary system, and the reticuloendothelial system. The first two result in a positive enhancement, the last one in a negative enhancement. Positive enhancers allow a better characterization of liver metastases using dynamic sequence protocols. Detection rate of liver metastases is increased using hepatobiliary contrast-enhanced MRI compared to unenhanced MRI. Negative enhancers, iron oxide particles, significantly increase tumor-to-liver contrast and allow detection of more lesions than other diagnostic methods. Iron-oxide enhanced MRI enables differential diagnosis of liver metastases comparing morphologic features using T2 and T1-weighted sequences.

Neutral vs positive oral contrast in diagnosing acute appendicitis with contrast-enhanced CT: sensitivity, specificity, reader confidence and interpretation time

PubMed Central

Naeger, D M; Chang, S D; Kolli, P; Shah, V; Huang, W; Thoeni, R F

2011-01-01

Objective The study compared the sensitivity, specificity, confidence and interpretation time of readers of differing experience in diagnosing acute appendicitis with contrast-enhanced CT using neutral vs positive oral contrast agents. Methods Contrast-enhanced CT for right lower quadrant or right flank pain was performed in 200 patients with neutral and 200 with positive oral contrast including 199 with proven acute appendicitis and 201 with other diagnoses. Test set disease prevalence was 50%. Two experienced gastrointestinal radiologists, one fellow and two first-year residents blindly assessed all studies for appendicitis (2000 readings) and assigned confidence scores (1=poor to 4=excellent). Receiver operating characteristic (ROC) curves were generated. Total interpretation time was recorded. Each reader's interpretation with the two agents was compared using standard statistical methods. Results Average reader sensitivity was found to be 96% (range 91–99%) with positive and 95% (89–98%) with neutral oral contrast; specificity was 96% (92–98%) and 94% (90–97%). For each reader, no statistically significant difference was found between the two agents (sensitivities p-values >0.6; specificities p-values>0.08), in the area under the ROC curve (range 0.95–0.99) or in average interpretation times. In cases without appendicitis, positive oral contrast demonstrated improved appendix identification (average 90% vs 78%) and higher confidence scores for three readers. Average interpretation times showed no statistically significant differences between the agents. Conclusion Neutral vs positive oral contrast does not affect the accuracy of contrast-enhanced CT for diagnosing acute appendicitis. Although positive oral contrast might help to identify normal appendices, we continue to use neutral oral contrast given its other potential benefits. PMID:20959365

Effects of the magnetic resonance imaging contrast agent Gd-DTPA on plant growth and root imaging in rice.

PubMed

Liu, Zan; Qian, Junchao; Liu, Binmei; Wang, Qi; Ni, Xiaoyu; Dong, Yaling; Zhong, Kai; Wu, Yuejin

2014-01-01

Although paramagnetic contrast agents have a wide range of applications in medical studies involving magnetic resonance imaging (MRI), these agents are seldom used to enhance MRI images of plant root systems. To extend the application of MRI contrast agents to plant research and to develop related techniques to study root systems, we examined the applicability of the MRI contrast agent Gd-DTPA to the imaging of rice roots. Specifically, we examined the biological effects of various concentrations of Gd-DTPA on rice growth and MRI images. Analysis of electrical conductivity and plant height demonstrated that 5 mmol Gd-DTPA had little impact on rice in the short-term. The results of signal intensity and spin-lattice relaxation time (T1) analysis suggested that 5 mmol Gd-DTPA was the appropriate concentration for enhancing MRI signals. In addition, examination of the long-term effects of Gd-DTPA on plant height showed that levels of this compound up to 5 mmol had little impact on rice growth and (to some extent) increased the biomass of rice.

Validation of diffuse optical tomography using a bi-functional optical-MRI contrast agent and a hybrid MRI-DOT system

NASA Astrophysics Data System (ADS)

Luk, Alex T.; Lin, Yuting; Grimmond, Brian; Sood, Anup; Uzgiris, Egidijus E.; Nalcioglu, Orhan; Gulsen, Gultekin

2013-03-01

Since diffuse optical tomography (DOT) is a low spatial resolution modality, it is desirable to validate its quantitative accuracy with another well-established imaging modality, such as magnetic resonance imaging (MRI). In this work, we have used a polymer based bi-functional MRI-optical contrast agent (Gd-DTPA-polylysine-IR800) in collaboration with GE Global Research. This multi-modality contrast agent provided not only co-localization but also the same kinetics, to cross-validate two imaging modalities. Bi-functional agents are injected to the rats and pharmacokinetics at the bladder are recovered using both optical and MR imaging. DOT results are validated using MRI results as "gold standard"

Optoacoustic detection of viral antigens using targeted gold nanorods

NASA Astrophysics Data System (ADS)

Maswadi, Saher; Woodward, Lee; Glickman, Randolph D.; Barsalou, Norman

2009-02-01

We are detecting antigens (Ag), isolated from infectious organisms, utilizing laser optoacoustic spectroscopy and antibody-coupled gold nanorod (NR) contrast agents specifically targeted to the antigen of interest. We have detected, in clinical ocular samples, both Herpes Simplex Virus Type 1 and 2 (HSV-1 and HSV-2) . A monoclonal antibody (Ab) specific to both HSV-1 and HSV-2 was conjugated to gold nanorods to produce a targeted contrast agent with a strong optoacoustic signal. Elutions obtained from patient corneal swabs were adsorbed in standard plastic micro-wells. An immunoaffinity reaction was then performed with the functionalized gold nanorods, and the results were probed with an OPO laser, emitting wavelengths at the peak absorptions of the nanorods. Positive optoacoustic responses were obtained from samples containing authentic (microbiologically confirmed) HSV-1 and HSV-2. To obtain an estimate of the sensitivity of the technique, serial dilutions from 1 mg/ml to 1 pg/ml of a C. trachomatis surface Ag were prepared, and were probed with a monoclonal Ab, specific to the C. trachomatis surface Ag, conjugated to gold nanorods. An optoacoustic response was obtained, proportional to the concentration of antigen, and with a limit of detection of about 5 pg/ml. The optoacoustic signals generated from micro-wells containing albumin or saline were similar to those from blank wells. The potential benefit of this method is identify viral agents more rapidly than with existing techniques. In addition, the sensitivity of the assay is comparable or superior to existing colorimetric- or fluorometric-linked immunoaffinity assays.

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. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Linking MODFLOW with an agent-based land-use model to support decision making

USGS Publications Warehouse

Reeves, H.W.; Zellner, M.L.

2010-01-01

The U.S. Geological Survey numerical groundwater flow model, MODFLOW, was integrated with an agent-based land-use model to yield a simulator for environmental planning studies. Ultimately, this integrated simulator will be used as a means to organize information, illustrate potential system responses, and facilitate communication within a participatory modeling framework. Initial results show the potential system response to different zoning policy scenarios in terms of the spatial patterns of development, which is referred to as urban form, and consequent impacts on groundwater levels. These results illustrate how the integrated simulator is capable of representing the complexity of the system. From a groundwater modeling perspective, the most important aspect of the integration is that the simulator generates stresses on the groundwater system within the simulation in contrast to the traditional approach that requires the user to specify the stresses through time. Copyright ?? 2010 The Author(s). Journal compilation ?? 2010 National Ground Water Association.

Brain Response to a Humanoid Robot in Areas Implicated in the Perception of Human Emotional Gestures

PubMed Central

Chaminade, Thierry; Zecca, Massimiliano; Blakemore, Sarah-Jayne; Takanishi, Atsuo; Frith, Chris D.; Micera, Silvestro; Dario, Paolo; Rizzolatti, Giacomo; Gallese, Vittorio; Umiltà, Maria Alessandra

2010-01-01

Background The humanoid robot WE4-RII was designed to express human emotions in order to improve human-robot interaction. We can read the emotions depicted in its gestures, yet might utilize different neural processes than those used for reading the emotions in human agents. Methodology Here, fMRI was used to assess how brain areas activated by the perception of human basic emotions (facial expression of Anger, Joy, Disgust) and silent speech respond to a humanoid robot impersonating the same emotions, while participants were instructed to attend either to the emotion or to the motion depicted. Principal Findings Increased responses to robot compared to human stimuli in the occipital and posterior temporal cortices suggest additional visual processing when perceiving a mechanical anthropomorphic agent. In contrast, activity in cortical areas endowed with mirror properties, like left Broca's area for the perception of speech, and in the processing of emotions like the left anterior insula for the perception of disgust and the orbitofrontal cortex for the perception of anger, is reduced for robot stimuli, suggesting lesser resonance with the mechanical agent. Finally, instructions to explicitly attend to the emotion significantly increased response to robot, but not human facial expressions in the anterior part of the left inferior frontal gyrus, a neural marker of motor resonance. Conclusions Motor resonance towards a humanoid robot, but not a human, display of facial emotion is increased when attention is directed towards judging emotions. Significance Artificial agents can be used to assess how factors like anthropomorphism affect neural response to the perception of human actions. PMID:20657777

Dual-contrast agent photon-counting computed tomography of the heart: initial experience.

PubMed

Symons, Rolf; Cork, Tyler E; Lakshmanan, Manu N; Evers, Robert; Davies-Venn, Cynthia; Rice, Kelly A; Thomas, Marvin L; Liu, Chia-Ying; Kappler, Steffen; Ulzheimer, Stefan; Sandfort, Veit; Bluemke, David A; Pourmorteza, Amir

2017-08-01

To determine the feasibility of dual-contrast agent imaging of the heart using photon-counting detector (PCD) computed tomography (CT) to simultaneously assess both first-pass and late enhancement of the myocardium. An occlusion-reperfusion canine model of myocardial infarction was used. Gadolinium-based contrast was injected 10 min prior to PCD CT. Iodinated contrast was infused immediately prior to PCD CT, thus capturing late gadolinium enhancement as well as first-pass iodine enhancement. Gadolinium and iodine maps were calculated using a linear material decomposition technique and compared to single-energy (conventional) images. PCD images were compared to in vivo and ex vivo magnetic resonance imaging (MRI) and histology. For infarct versus remote myocardium, contrast-to-noise ratio (CNR) was maximal on late enhancement gadolinium maps (CNR 9.0 ± 0.8, 6.6 ± 0.7, and 0.4 ± 0.4, p < 0.001 for gadolinium maps, single-energy images, and iodine maps, respectively). For infarct versus blood pool, CNR was maximum for iodine maps (CNR 11.8 ± 1.3, 3.8 ± 1.0, and 1.3 ± 0.4, p < 0.001 for iodine maps, gadolinium maps, and single-energy images, respectively). Combined first-pass iodine and late gadolinium maps allowed quantitative separation of blood pool, scar, and remote myocardium. MRI and histology analysis confirmed accurate PCD CT delineation of scar. Simultaneous multi-contrast agent cardiac imaging is feasible with photon-counting detector CT. These initial proof-of-concept results may provide incentives to develop new k-edge contrast agents, to investigate possible interactions between multiple simultaneously administered contrast agents, and to ultimately bring them to clinical practice.

Influence of different iodinated contrast media on the induction of DNA double-strand breaks after in vitro X-ray irradiation.

PubMed

Deinzer, Christoph K W; Danova, Daniela; Kleb, Beate; Klose, Klaus J; Heverhagen, Johannes T

2014-01-01

The objective of this work was to examine differences in DNA double-strand break induction in peripheral blood lymphocytes after in vitro X-ray irradiation between iodinated contrast agents. Four different iodinated X-ray contrast agents--three of them with two different iodine concentrations--and mannitol (negative control; concentration of 150 mg mannitol per ml blood) were pipetted into blood samples so that there was a concentration of 0, 7.5 or 15 mg of iodine per ml blood in the samples. Negative controls without contrast medium (0 mg of iodine per ml blood) were also processed for every irradiation dose. The tubes were exposed to 0, 20 or 500 mGy in vitro X-ray irradiation. After that, the lymphocytes were separated by using density-gradient centrifugation. Fluorescence microscopy was applied to determine the average number of γH2AX-foci per lymphocyte in the presence or absence of different contrast media or mannitol. Differences in the number of γH2AX-foci were statistically analysed by one-way ANOVA and post-hoc Tukey's honestly significant difference test. Iodinated contrast agents led to a statistically significant increase in DNA double-strand breaks after in vitro irradiation. This effect increased statistically significant with rising radiation dose and appeared independent of the contrast agent used (iopromid, iodixanol, iomeprol, iopamidol). A statistically significant difference in DNA damage between the different tested contrast agents was not found. Therefore, the increase in DNA double-strand breaks depends solely on the amount of iodine applied. For evaluation of clinical consequences, our findings could be tested in further animal studies. Copyright © 2014 John Wiley & Sons, Ltd.

Molecular nanomagnets as contrast agents for Magnetic Resonance Imaging

NASA Astrophysics Data System (ADS)

Rodríguez, Elisenda; Roig, Anna; Molins, Elies; Arús, Carles; Cabañas, Miquel; Quintero, María Rosa; Cerdán, Sebastián; Sanfeliu, Coral

2003-03-01

Magnetic resonance imaging (MRI) is a non-invasive technique used in medicine to produce high quality images of human body slices. In order to enhance the contrast between different organs or to reveal altered portions of them such necrosis or tumors, the administration of a contrast agent is highly convenient. Currently Gd-DTPA, a paramagnetic complex, is the most widely administered compound. In this context, we have assayed molecular nanomagnets as MRI contrast agents. The complex [(tacn)_6Fe_8(μ_3-O)_2(μ_2-OH)_12]Br_8·9H_2O^1(Fe8 in brief) has been evaluated and shorter relaxation times, T1 and T_2, have been obtained for Fe8 than those obtained for the commercial Gd-DTPA. No toxic effects have been observed at concentrations up to 1 mM of Fe8 in cultured cells. Phantom studies with T_1-weighted MRI at 9.4 Tesla suggest that Fe8 can have potentiality as T_1-contrast agent. ^1Wieghardt K Angew Chem Intl Ed Engl 23 1 (1984) 77

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

PubMed

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

2012-04-01

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

Gadofosveset-enhanced magnetic resonance angiography as a means of evaluating pulmonary arteriovenous malformation: a case report.

PubMed

Pressacco, Josephine; Papas, Konstantin

2012-07-01

This case report is a unique presentation of a new potential indication for Gadofosvest (Ablavar), a blood pool contrast agent for magnetic resonance angiography (MRA). Ablavar is an excellent MRA contrast agent because it provides optimal contrast opacification of both the arterial and venous system, unlike the conventional extracellular agents that are used for arterial imaging only. The present case report demonstrates the ability of Ablavar to demonstrate pulmonary arteriovenous malformation (AVM), showing both its arterial feeders as well as its venous drainage tract. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Synchrotron-based intra-venous K-edge digital subtraction angiography in a pig model: a feasibility study.

PubMed

Schültke, Elisabeth; Fiedler, Stefan; Nemoz, Christian; Ogieglo, Lissa; Kelly, Michael E; Crawford, Paul; Esteve, Francois; Brochard, Thierry; Renier, Michel; Requardt, Herwig; Le Duc, Geraldine; Juurlink, Bernhard; Meguro, Kotoo

2010-03-01

K-edge digital subtraction angiography (KEDSA) combined with the tunability of synchrotron beam yields an imaging technique that is highly sensitive to low concentrations of contrast agents. Thus, contrast agent can be administered intravenously, obviating the need for insertion of a guided catheter to deliver a bolus of contrast agent close to the target tissue. With the high-resolution detectors used at synchrotron facilities, images can be acquired at high spatial resolution. Thus, the KEDSA appears particularly suited for studies of neurovascular pathology in animal models, where the vascular diameters are significantly smaller than in human patients. This feasibility study was designed to test the suitability of KEDSA after intravenous injection of iodine-based contrast agent for use in a pig model. Four adult male pigs were used for our experiments. Neurovascular angiographic images were acquired using KEDSA with a solid state Germanium (Ge) detector at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. After intravenous injection of 0.9 ml/kg iodinated contrast agent (Xenetix), the peak iodine concentrations in the internal carotid and middle cerebral arteries reached 35 mg/ml. KEDSA images in radiography mode allowed the visualization of intracranial arteries of less than 1.5mm diameter. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Dual-mode imaging with radiolabeled gold nanorods

NASA Astrophysics Data System (ADS)

Agarwal, Ashish; Shao, Xia; Rajian, Justin R.; Zhang, Huanan; Chamberland, David L.; Kotov, Nicholas A.; Wang, Xueding

2011-05-01

Many nanoparticle contrast agents have difficulties with deep tissue and near-bone imaging due to limited penetration of visible photons in the body and mineralized tissues. We are looking into the possibility of mediating this problem while retaining the capabilities of the high spatial resolution associated with optical imaging. As such, the potential combination of emerging photoacoustic imaging and nuclear imaging in monitoring of antirheumatic drug delivery by using a newly developed dual-modality contrast agent is investigated. The contrast agent is composed of gold nanorods (GNRs) conjugated to the tumor necrosis factor (TNF-α) antibody and is subsequently radiolabeled by 125I. ELISA experiments designed to test TNF-α binding are performed to prove the specificity and biological activity of the radiolabeled conjugated contrast agent. Photoacoustic and nuclear imaging are performed to visualize the distribution of GNRs in articular tissues of the rat tail joints in situ. Findings from the two imaging modalities correspond well with each other in all experiments. Our system can image GNRs down to a concentration of 10 pM in biological tissues and with a radioactive label of 5 μCi. This study demonstrates the potential of combining photoacoustic and nuclear imaging modalities through one targeted contrast agent for noninvasive monitoring of drug delivery as well as deep and mineralized tissue imaging.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2017-08-07

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

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

PubMed Central

Longo, Dario Livio; Aime, Silvio

2017-01-01

Optoacoustic imaging emerged in early 1990s as a new biomedical imaging technology that generates images by illuminating tissues with short laser pulses and detecting resulting ultrasound waves. This technique takes advantage of the spectroscopic approach to molecular imaging, and delivers high-resolution images in the depth of tissue. Resolution of the optoacoustic imaging is scalable, so that biomedical systems from cellular organelles to large organs can be visualized and, more importantly, characterized based on their optical absorption coefficient, which is proportional to the concentration of absorbing chromophores. Optoacoustic imaging was shown to be useful in both preclinical research using small animal models and in clinical applications. Applications in the field of molecular imaging offer abundant opportunities for the development of highly specific and effective contrast agents for quantitative optoacoustic imaging. Recent efforts are being made in the direction of nontoxic biodegradable contrast agents (such as nanoparticles made of melanin) that are potentially applicable in clinical optoacoustic imaging. In order to increase the efficiency and specificity of contrast agents and probes, they need to be made smart and capable of controlled accumulation in the target cells. This review was written in recognition of the potential breakthroughs in medical optoacoustic imaging that can be enabled by efficient and nontoxic melanin-based optoacoustic contrast agents. PMID:28783106

Radiation exposure and contrast agent use related to radial versus femoral arterial access during percutaneous coronary intervention (PCI)-Results of the FERARI study.

PubMed

Becher, Tobias; Behnes, Michael; Ünsal, Melike; Baumann, Stefan; El-Battrawy, Ibrahim; Fastner, Christian; Kuschyk, Jürgen; Papavassiliu, Theano; Hoffmann, Ursula; Mashayekhi, Kambis; Borggrefe, Martin; Akin, Ibrahim

2016-12-01

Data regarding radiation exposure related to radial versus femoral arterial access in patients undergoing percutaneous coronary intervention (PCI) remain controversial. This study aims to evaluate patients enrolled in the FERARI study regarding radiation exposure, fluoroscopy time and contrast agent use. The Femoral Closure versus Radial Compression Devices Related to Percutaneous Coronary Interventions (FERARI) study evaluated prospectively 400 patients between February 2014 and May 2015 undergoing PCI either using the radial or femoral access. In these 400 patients, baseline characteristics, procedural data such as procedural duration, fluoroscopy time, dose-area product (DAP) as well as the amount of contrast agent used were documented and analyzed. Median fluoroscopy time was not significantly different in patients undergoing radial versus femoral access (12.2 vs. 9.8min, p=0.507). Furthermore, median DAP (54.5 vs. 52.0 Gycm2, p=0.826), procedural duration (46.0 vs. 45.0min, p=0.363) and contrast agent use (185.5 vs. 199.5ml, p=0.742) were also similar in radial and femoral PCI. There was no difference regarding median fluoroscopy time, procedural duration, radiation dose or contrast agent use between radial versus femoral arterial access in PCI. Copyright © 2016 Elsevier Inc. All rights reserved.

Aptamer-Targeted Magnetic Resonance Imaging Contrast Agents and Their Applications.

PubMed

Zhang, Yajie; Zhang, Tingting; Liu, Min; Kuang, Ye; Zu, Guangyue; Zhang, Kunchi; Cao, Yi; Pei, Renjun

2018-06-01

Magnetic resonance imaging is a powerful diagnostic technology with high spatial resolution and non-invasion. The contrast agents have significant effect on the resolution of the MR imaging. However, the commercial contrast agents (CAs) usually consist of individual Gd3+ chelated with a low molecular weight acyclic or cyclic ligand, and these small-molecule CAs are usually subjected to nonspecificity, thus leading to rapid renal clearance and modest contrast enhancement for tumor imaging. In recent years, the nanostructured materials conjugated with aptamers were widely used and opened a new door in biomedical imaging due to excellent specificity, non-immunogenicity, easily synthesis and chemical modification of aptamers. This review summarizes all kinds of aptamertargeted MRI CAs and their applications.

Biocompatible blood pool MRI contrast agents based on hyaluronan

PubMed Central

Zhu, Wenlian; Artemov, Dmitri

2010-01-01

Biocompatible gadolinium blood pool contrast agents based on a biopolymer, hyaluronan, were investigated for magnetic resonance angiography application. Hyaluronan, a non-sulfated linear glucosaminoglycan composed of 2000–25,000 repeating disaccharide subunits of D-glucuronic acid and N-acetylglucosamine with molecular weight up to 20 MDa, is a major component of the extracellular matrix. Two gadolinium contrast agents based on 16 and 74 kDa hyaluronan were synthesized, both with R1 relaxivity around 5 mM−1 s−1 per gadolinium at 9.4 T at 25°C. These two hyaluronan based agents show significant enhancement of the vasculature for an extended period of time. Initial excretion was primarily through the renal system. Later uptake was observed in the stomach and lower gastrointestinal tract. Macromolecular hyaluronan-based gadolinium agents have a high clinical translation potential as hyaluronan is already approved by FDA for a variety of medical applications. PMID:21504061

The potential for neurovascular intravenous angiography using K-edge digital subtraction angiography

NASA Astrophysics Data System (ADS)

Schültke, E.; Fiedler, S.; Kelly, M.; Griebel, R.; Juurlink, B.; LeDuc, G.; Estève, F.; Le Bas, J.-F.; Renier, M.; Nemoz, C.; Meguro, K.

2005-08-01

Background: Catheterization of small-caliber blood vessels in the central nervous system can be extremely challenging. Alternatively, intravenous (i.v.) administration of contrast agent is minimally invasive and therefore carries a much lower risk for the patient. With conventional X-ray equipment, volumes of contrast agent that could be safely administered to the patient do not allow acquisition of high-quality images after i.v. injection, because the contrast bolus is extremely diluted by passage through the heart. However, synchrotron-based digital K-edge subtraction angiography does allow acquisition of high-quality images after i.v. administration of relatively small doses of contrast agent. Materials and methods: Eight adult male New Zealand rabbits were used for our experiments. Animals were submitted to both angiography with conventional X-ray equipment and synchrotron-based digital subtraction angiography. Results: With conventional X-ray equipment, no contrast was seen in either cerebral or spinal blood vessels after i.v. injection of iodinated contrast agent. However, using K-edge digital subtraction angiography, as little as 1 ml iodinated contrast agent, when administered as i.v. bolus, yielded images of small-caliber blood vessels in the central nervous system (both brain and spinal cord). Conclusions: If it would be possible to image blood vessels of the same diameter in the central nervous system of human patients, the synchrotron-based technique could yield high-quality images at a significantly lower risk for the patient than conventional X-ray imaging. Images could be acquired where catheterization of feeding blood vessels has proven impossible.

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.

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

PubMed

Lv, Peijie; Liu, Jie; Chai, Yaru; Yan, Xiaopeng; Gao, Jianbo; Dong, Junqiang

2017-01-01

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

A predictive software tool for optimal timing in contrast enhanced carotid MR angiography

NASA Astrophysics Data System (ADS)

Moghaddam, Abbas N.; Balawi, Tariq; Habibi, Reza; Panknin, Christoph; Laub, Gerhard; Ruehm, Stefan; Finn, J. Paul

2008-03-01

A clear understanding of the first pass dynamics of contrast agents in the vascular system is crucial in synchronizing data acquisition of 3D MR angiography (MRA) with arrival of the contrast bolus in the vessels of interest. We implemented a computational model to simulate contrast dynamics in the vessels using the theory of linear time-invariant systems. The algorithm calculates a patient-specific impulse response for the contrast concentration from time-resolved images following a small test bolus injection. This is performed for a specific region of interest and through deconvolution of the intensity curve using the long division method. Since high spatial resolution 3D MRA is not time-resolved, the method was validated on time-resolved arterial contrast enhancement in Multi Slice CT angiography. For 20 patients, the timing of the contrast enhancement of the main bolus was predicted by our algorithm from the response to the test bolus, and then for each case the predicted time of maximum intensity was compared to the corresponding time in the actual scan which resulted in an acceptable agreement. Furthermore, as a qualitative validation, the algorithm's predictions of the timing of the carotid MRA in 20 patients with high quality MRA were correlated with the actual timing of those studies. We conclude that the above algorithm can be used as a practical clinical tool to eliminate guesswork and to replace empiric formulae by a priori computation of patient-specific timing of data acquisition for MR angiography.

Modeling and Visualizing Flow of Chemical Agents Across Complex Terrain

NASA Technical Reports Server (NTRS)

Kao, David; Kramer, Marc; Chaderjian, Neal

2005-01-01

Release of chemical agents across complex terrain presents a real threat to homeland security. Modeling and visualization tools are being developed that capture flow fluid terrain interaction as well as point dispersal downstream flow paths. These analytic tools when coupled with UAV atmospheric observations provide predictive capabilities to allow for rapid emergency response as well as developing a comprehensive preemptive counter-threat evacuation plan. The visualization tools involve high-end computing and massive parallel processing combined with texture mapping. We demonstrate our approach across a mountainous portion of North California under two contrasting meteorological conditions. Animations depicting flow over this geographical location provide immediate assistance in decision support and crisis management.

Self-demodulation effect on subharmonic response of ultrasound contrast agent

NASA Astrophysics Data System (ADS)

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

2012-03-01

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

Spin-lock imaging of exogenous exchange-based contrast agents to assess tissue pH.

PubMed

Zu, Zhongliang; Li, Hua; Jiang, Xiaoyu; Gore, John C

2018-01-01

Some X-ray contrast agents contain exchangeable protons that give rise to exchange-based effects on MRI, including chemical exchange saturation transfer (CEST). However, CEST has poor specificity to explicit exchange parameters. Spin-lock sequences at high field are also sensitive to chemical exchange. Here, we evaluate whether spin-locking techniques can detect the contrast agent iohexol in vivo after intravenous administration, and their potential for measuring changes in tissue pH. Two metrics of contrast based on R 1ρ , the spin lattice relaxation rate in the rotating frame, were derived from the behavior of R 1ρ at different locking fields. Solutions containing iohexol at different concentrations and pH were used to evaluate the ability of the two metrics to quantify exchange effects. Images were also acquired from rat brains bearing tumors before and after intravenous injections of iohexol to evaluate the potential of spin-lock techniques for detecting the agent and pH variations. The two metrics were found to depend separately on either agent concentration or pH. Spin-lock imaging may therefore provide specific quantification of iohexol concentration and the iohexol-water exchange rate, which reports on pH. Spin-lock techniques may be used to assess the dynamics of intravenous contrast agents and detect extracellular acidification. Magn Reson Med 79:298-305, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Effect of capping agent on selectivity and sensitivity of CdTe quantum dots optical sensor for detection of mercury ions

NASA Astrophysics Data System (ADS)

Labeb, Mohmed; Sakr, Abdel-Hamed; Soliman, Moataz; Abdel-Fettah, Tarek M.; Ebrahim, Shaker

2018-05-01

Cadmium telluride (CdTe) quantum dots (QDs) were prepared from an aqueous solution containing CdCl2 and Te precursor in the presence of thioglycolic acid (TGA) or L-cysteine as capping agents. Two optical sensors have been developed for Hg2+ ions with very low concentration in the range of nanomolar (nM) or picomolar (pM) depending on the type of capping agents and based on photoluminescence (PL) quenching of CdTe QDs. It was observed that low concentrations of Hg2+ ions quench the fluorescence spectra of CdTe QDs and TGA capped CdTe QDs exhibited a linear response to Hg2+ ions in the concentration range from 1.25 to 10 nM. Moreover, it was found that L-cysteine capped CdTe QDs optical sensor with a sensitivity of 6 × 109 M-1, exhibited a linear coefficient of 0.99 and showed a detection limit of 2.7 pM in range from 5 to 25 pM of Hg2+ ions was achieved. In contrast to the significant response that was observed for Hg2+, a weak signal response was noted upon the addition of other metal ions indicating an excellent selectivity of CdTe QDs towards Hg2+.

Gd-DTPA T1 relaxivity in brain tissue obtained by convection-enhanced delivery, magnetic resonance imaging and emission spectroscopy

NASA Astrophysics Data System (ADS)

Haar, Peter J.; Broaddus, William C.; Chen, Zhi-jian; Fatouros, Panos P.; Gillies, George T.; Corwin, Frank D.

2010-06-01

A common approach to quantify gadolinium (Gd) contrast agents involves measuring the post-contrast change in T1 rate and then using the constant T1 relaxivity R to determine the contrast agent concentration. Because this method is fast and non-invasive, it could be potentially valuable in many areas of brain research. However, to accurately measure contrast agent concentrations in the brain, the T1 relaxivity R of the specific agent must be accurately known. Furthermore, the macromolecular content and compartmentalization of the brain extracellular space (ECS) are expected to significantly alter R from values measured in aqueous solutions. In this study, the T1 relaxivity R of gadolinium-diethylene-triamine penta-acetic acid (Gd-DTPA) was measured following direct interstitial infusions of three different contrast agent concentrations to the parenchyma of rat brains. Changes in magnetic resonance (MR) T1 values were compared to brain slice concentrations determined with inductively coupled plasma atomic emission spectroscopy (ICP-AES) to determine R in 15 rats. Additionally, samples of cerebrospinal fluid, blood and urine were analyzed to evaluate possible Gd-DTPA clearance from the brain. The T1 relaxivity R of Gd-DTPA in the brain ECS was measured to be 5.35 (mM s)-1 in a 2.4 T field. This value is considerably higher than estimations used in studies by other groups. Measurements of brain Gd-DTPA tissue concentrations using MRI and ICP-AES demonstrated a high degree of coincidence. Clearance of Gd-DTPA was minimal at the time point immediately after infusion. These results suggest that the environment of the brain does in fact significantly affect Gd T1 relaxivity, and that MRI can accurately measure contrast agent concentrations when this relaxivity is well characterized.

MRI ductography of contrast agent distribution and leakage in normal mouse mammary ducts and ducts with in situ cancer.

PubMed

Markiewicz, Erica; Fan, Xiaobing; Mustafi, Devkumar; Zamora, Marta; Conzen, Suzanne D; Karczmar, Gregory S

2017-07-01

High resolution 3D MRI was used to study contrast agent distribution and leakage in normal mouse mammary glands and glands containing in situ cancer after intra-ductal injection. Five female FVB/N mice (~19weeks old) with no detectable mammary cancer and eight C3(1) SV40 Tag virgin female mice (~15weeks old) with extensive in situ cancer were studied. A 34G, 45° tip Hamilton needle with a 25μL Hamilton syringe was inserted into the tip of the nipple and approximately 15μL of a Gadodiamide was injected slowly over 1min into the nipple and throughout the duct on one side of the inguinal gland. Following injection, the mouse was placed in a 9.4T MRI scanner, and a series of high resolution 3D T1-weighted images was acquired with a temporal resolution of 9.1min to follow contrast agent leakage from the ducts. The first image was acquired at about 12min after injection. Ductal enhancement regions detected in images acquired between 12 and 21min after contrast agent injection was five times smaller in SV40 mouse mammary ducts (p<0.001) than in non-cancerous FVB/N mouse mammary ducts, perhaps due to rapid washout of contrast agent from the SV40 ducts. The contrast agent washout rate measured between 12min and 90min after injection was ~20% faster (p<0.004) in SV40 mammary ducts than in FVB/N mammary ducts. These results may be due to higher permeability of the SV40 ducts, likely due to the presence of in situ cancers. Therefore, increased permeability of ducts may indicate early stage breast cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of diatrizoate and iopamidol on spermatogenesis.

PubMed

Yaghmai, V; Harapanhalli, R S; Patel, Y D; Baker, S R; Rao, D V

1993-12-01

The biological effects of iodinated contrast media were examined by using spermatogenesis in mouse testis as the experimental model. Spermhead survival and abnormality assays were used as the biological end points. Diatrizoate meglumine/diatrizoate sodium and iopamidol were administered intravenously at equal rates and concentrations. Testicular uptake and clearance of these contrast agents were examined by high-performance liquid chromatography techniques. Appropriate mannitol solutions were employed as osmolality controls. Intravenous administration of the contrast agent or its respective mannitol control resulted in approximately a 30% decrease in spermhead count. A dose-related experiment with mannitol demonstrated that the spermhead count decreased rapidly until 600 mOsm/kg was reached, beyond which this decrease was minimal. Clearance of both contrast media was complete in approximately 4 hours. No significant increase in the induction of spermhead abnormalities was observed. Osmotic substances, such as iodinated contrast agents, affect the process of spermatogenesis.

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.

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.

Translational Applications of Nanodiamonds: From Biocompatibility to Theranostics

NASA Astrophysics Data System (ADS)

Moore, Laura Kent

Nanotechnology marks the next phase of development for drug delivery, contrast agents and gene therapy. For these novel systems to achieve success in clinical translation we must see that they are both effective and safe. Diamond nanoparticles, also known as nanodiamonds (NDs), have been gaining popularity as molecular delivery vehicles over the last decade. The uniquely faceted, carbon nanoparticles possess a number of beneficial properties that are being harnessed for applications ranging from small-molecule drug delivery to biomedical imaging and gene therapy. In addition to improving the effectiveness of a variety of therapeutics and contrast agents, initial studies indicate that NDs are biocompatible. In this work we evaluate the translational potential of NDs by demonstrating efficacy in molecular delivery and scrutinizing particle tolerance. Previous work has demonstrated that NDs are effective vehicles for the delivery of anthracycline chemotherapeutics and gadolinium(III) based contrast agents. We have sought to enhance the gains made in both areas through the addition of active targeting. We find that ND-mediated targeted delivery of epirubicin to triple negative breast cancers induces tumor regression and virtually eliminates drug toxicities. Additionally, ND-mediated delivery of the MRI contrast agent ProGlo boosts the per gadolinium relaxivity four fold, eliminates water solubility issues and effectively labels progesterone receptor expressing breast cancer cells. Both strategies open the door to the development of targeted, theranostic constructs based on NDs, capable of treating and labeling breast cancers at the same time. Although we have seen that NDs are effective vehicles for molecular delivery, for any nanoparticle to achieve clinical utility it must be biocompatible. Preliminary research has shown that NDs are non-toxic, however only a fraction of the ND-subtypes have been evaluated. Here we present an in depth analysis of the cellular response to multiple subtypes of NDs, including pristine, amine functionalized, fluorescent and daunorubicin-loaded NDs. Furthermore, we present the most comprehensive analysis of in vivo tolerance of nanodiamonds to date. We find that NDs, regardless of subtype, are non-toxic to multiple cell types. Furthermore, we find that NDs are well tolerated by mice and rats at both acute and sub-acute time frames. These results indicate that NDs are biocompatible and will serve as the foundation for future clinical translation of diamond-based imaging, therapeutic or theranostic agents.

3D widefield light microscope image reconstruction without dyes

NASA Astrophysics Data System (ADS)

Larkin, S.; Larson, J.; Holmes, C.; Vaicik, M.; Turturro, M.; Jurkevich, A.; Sinha, S.; Ezashi, T.; Papavasiliou, G.; Brey, E.; Holmes, T.

2015-03-01

3D image reconstruction using light microscope modalities without exogenous contrast agents is proposed and investigated as an approach to produce 3D images of biological samples for live imaging applications. Multimodality and multispectral imaging, used in concert with this 3D optical sectioning approach is also proposed as a way to further produce contrast that could be specific to components in the sample. The methods avoid usage of contrast agents. Contrast agents, such as fluorescent or absorbing dyes, can be toxic to cells or alter cell behavior. Current modes of producing 3D image sets from a light microscope, such as 3D deconvolution algorithms and confocal microscopy generally require contrast agents. Zernike phase contrast (ZPC), transmitted light brightfield (TLB), darkfield microscopy and others can produce contrast without dyes. Some of these modalities have not previously benefitted from 3D image reconstruction algorithms, however. The 3D image reconstruction algorithm is based on an underlying physical model of scattering potential, expressed as the sample's 3D absorption and phase quantities. The algorithm is based upon optimizing an objective function - the I-divergence - while solving for the 3D absorption and phase quantities. Unlike typical deconvolution algorithms, each microscope modality, such as ZPC or TLB, produces two output image sets instead of one. Contrast in the displayed image and 3D renderings is further enabled by treating the multispectral/multimodal data as a feature set in a mathematical formulation that uses the principal component method of statistics.

Passive microlesion detection and mapping for treatment of hypertrophic cardiomyopathy

NASA Astrophysics Data System (ADS)

Zhu, Yiying I.; Miller, Douglas L.; Dou, Chunyan; Kripfgans, Oliver D.

2017-03-01

Intermittent high intensity ultrasound pulses with circulating contrast agent microbubbles can induce scattered microlesions of potential value for myocardial reduction therapy. This paper presents an in vitro setup imitating the treatment for monitoring development. A preclinical imaging system with a single element transducer, synchronization and receive-only imaging transducer array has been implemented on a research platform. Contrast agent microbubbles pumped in a dialysis tubing setup were exposed to high intensity focused ultrasound at 1.0/3.5 MHz center frequencies. Polystyrene spheres were employed as linear scatterers compared to contrast agents for system transfer function equalization. A cavitation mapping technique was employed to spatially locate and depict microbubble activity during treatment. For high acoustic pressure amplitudes a 5 dB difference between contrast agent and solid spheres was observed and spatially mapped. The in-plane resolution was 4.5 mm for axial and 1.5 mm laterally. In the future, this cavitation detection scheme will be applied to monitor in vivo microlesioning in real-time.

Introductory Chemistry: A Molar Relaxivity Experiment in the High School Classroom.

PubMed

Dawsey, Anna C; Hathaway, Kathryn L; Kim, Susie; Williams, Travis J

2013-07-09

Dotarem and Magnevist, two clinically available magnetic resonance imaging (MRI) contrast agents, were assessed in a high school science classroom with respect to which is the better contrast agent. Magnevist, the more efficacious contrast agent, has negative side effects because its gadolinium center can escape from its ligand. However, Dotarem, though a less efficacious contrast agent, is a safer drug choice. After the experiment, students are confronted with the FDA warning on Magnevist, which enabled a discussion of drug efficacy versus safety. We describe a laboratory experiment in which NMR spin lattice relaxation rate measurements are used to quantify the relaxivities of the active ingredients of Dotarem and Magnevist. The spin lattice relaxation rate gives the average amount of time it takes the excited nucleus to relax back to the original state. Students learn by constructing molar relaxivity curves based on inversion recovery data sets that Magnevist is more relaxive than Dotarem. This experiment is suitable for any analytical chemistry laboratory with access to NMR.

Synthesis and in vitro evaluation of bone-seeking superparamagnetic iron oxide nanoparticles as contrast agents for imaging bone metabolic activity.

PubMed

Panahifar, Arash; Mahmoudi, Morteza; Doschak, Michael R

2013-06-12

In this article, we report the synthesis and in vitro evaluation of a new class of nonionizing bone-targeting contrast agents based on bisphosphonate-conjugated superparamagnetic iron oxide nanoparticles (SPIONs), for use in imaging of bone turnover with magnetic resonance imaging (MRI). Similar to bone-targeting (99m)Technetium medronate, our novel contrast agent uses bisphosphonates to impart bone-seeking properties, but replaces the former radioisotope with nonionizing SPIONs which enables their subsequent detection using MRI. Our reported method is relatively simple, quick and cost-effective and results in BP-SPIONs with a final nanoparticle size of 17 nm under electron microscopy technique (i.e., TEM). In-vitro binding studies of our novel bone tracer have shown selective binding affinity (around 65%) for hydroxyapatite, the principal mineral of bone. Bone-targeting SPIONs offer the potential for use as nonionizing MRI contrast agents capable of imaging dynamic bone turnover, for use in the diagnosis and monitoring of metabolic bone diseases and related bone pathology.

On-chip generation of microbubbles as a practical technology for manufacturing contrast agents for ultrasonic imaging

PubMed Central

Hettiarachchi, Kanaka; Talu, Esra; Longo, Marjorie L.; Dayton, Paul A.; Lee, Abraham P.

2007-01-01

This paper presents a new manufacturing method to generate monodisperse microbubble contrast agents with polydispersity index (σ) values of <2% through microfluidic flow-focusing. Micron-sized lipid shell-based perfluorocarbon (PFC) gas microbubbles for use as ultrasound contrast agents were produced using this method. The poly(dimethylsiloxane) (PDMS)-based devices feature expanding nozzle geometry with a 7 μm orifice width, and are robust enough for consistent production of microbubbles with runtimes lasting several hours. With high-speed imaging, we characterized relationships between channel geometry, liquid flow rate Q, and gas pressure P in controlling bubble sizes. By a simple optimization of the channel geometry and Q and P, bubbles with a mean diameter of <5 μm can be obtained, ideal for various ultrasonic imaging applications. This method demonstrates the potential of microfluidics as an efficient means for custom-designing ultrasound contrast agents with precise size distributions, different gas compositions and new shell materials for stabilization, and for future targeted imaging and therapeutic applications. PMID:17389962

Photoacoustic imaging at 1064nm wavelength with exogenous contrast agents

NASA Astrophysics Data System (ADS)

Upputuri, Paul Kumar; Jiang, Yuyan; Pu, Kanyi; Pramanik, Manojit

2018-02-01

Photoacoustic (PA) imaging is a promising imaging modality for both preclinical research and clinical practices. Laser wavelengths in the first near infrared window (NIR-I, 650-950 nm) have been widely used for photoacoustic imaging. As compared with NIR-I window, scattering of photons by biological tissues is largely reduced in the second NIR (NIR-II) window, leading to enhanced imaging fidelity. However, the lack of biocompatible NIR-II absorbing exogenous agents prevented the use of this window for in vivo imaging. In recent years, few studies have been reported on photoacoustic imaging in NIR-II window using exogenous contrast agents. In this work, we discuss the recent work on PA imaging using 1064 nm wavelength, the fundamental of Nd:YAG laser, as an excitation wavelength. The PA imaging at 1064 nm is advantageous because of the low and homogeneous signal from tissue background, enabling high contrast in PA imaging when NIR-II absorbing contrast agents are employed.

Subharmonic Imaging and Pressure Estimation for Monitoring Neoadjuvant Chemotherapy

DTIC Science & Technology

2013-09-01

10]. However, the level of IFP has been shown to predict disease free survival for cervix cancer (34% disease free survival (DFS) if IFP > 19 mmHg...in patients with cervix cancer independent of clinical prognostic factors and tumor oxygen measurements. Cancer Res, 2001. 61(17): p. 6400-5. 12... cancer (LABC). Monitoring tumor response is advantageous for patients. This project aims to using the subharmonic signals from ultrasound contrast agents

Tunable Semiconducting Polymer Nanoparticles with INDT-Based Conjugated Polymers for Photoacoustic Molecular Imaging.

PubMed

Stahl, Thomas; Bofinger, Robin; Lam, Ivan; Fallon, Kealan J; Johnson, Peter; Ogunlade, Olumide; Vassileva, Vessela; Pedley, R Barbara; Beard, Paul C; Hailes, Helen C; Bronstein, Hugo; Tabor, Alethea B

2017-06-21

Photoacoustic imaging combines both excellent spatial resolution with high contrast and specificity, without the need for patients to be exposed to ionizing radiation. This makes it ideal for the study of physiological changes occurring during tumorigenesis and cardiovascular disease. In order to fully exploit the potential of this technique, new exogenous contrast agents with strong absorbance in the near-infrared range, good stability and biocompatibility, are required. In this paper, we report the formulation and characterization of a novel series of endogenous contrast agents for photoacoustic imaging in vivo. These contrast agents are based on a recently reported series of indigoid π-conjugated organic semiconductors, coformulated with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, to give semiconducting polymer nanoparticles of about 150 nm diameter. These nanoparticles exhibited excellent absorption in the near-infrared region, with good photoacoustic signal generation efficiencies, high photostability, and extinction coefficients of up to three times higher than those previously reported. The absorption maximum is conveniently located in the spectral region of low absorption of chromophores within human tissue. Using the most promising semiconducting polymer nanoparticle, we have demonstrated wavelength-dependent differential contrast between vasculature and the nanoparticles, which can be used to unambiguously discriminate the presence of the contrast agent in vivo.

ACOUSTIC CHARACTERIZATION AND PHARAMACOKINETIC ANALYSES OF NEW NANOBUBBLE ULTRASOUND CONTRAST AGENTS

PubMed Central

Wu, Hanping; Rognin, Nicolas G.; Krupka, Tianyi M.; Solorio, Luis; Yoshiara, Hiroki; Guenette, Gilles; Sanders, Christoher; Kamiyama, Naohisa; Exner, Agata A.

2013-01-01

In contrast to the clinically used microbubble ultrasound contrast agents, nanoscale bubbles (or nanobubbles) may potentially extravasate into tumors that exhibit more permeable vasculature, facilitating targeted molecular imaging and drug delivery. Our group recently presented a simple strategy using the non-ionic surfactant Pluronic as a size control excipient to produce nanobubbles with a mean diameter of 200 nm that exhibited stability and echogenicity on par with microbubbles. The objective of this study was to carry out an in-depth characterization of nanobubble properties as compared with Definity microbubbles, both in vitro and in vivo. Through use of a tissue-mimicking phantom, in vitro experiments measured the echogenicity of the contrast agent solutions and the contrast agent dissolution rate over time. Nanobubbles were found to be more echogenic than Definity microbubbles at three different harmonic frequencies (8, 6.2 and 3.5 MHz). Definity microbubbles also dissolved 1.67 times faster than nanobubbles. Pharmacokinetic studies were then performed in vivo in a subcutaneous human colorectal adenocarcinoma (LS174T) in mice. The peak enhancement and decay rates of contrast agents after bolus injection in the liver, kidney and tumor were analyzed. No significant differences were observed in peak enhancement between the nanobubble and Definity groups in the three tested regions (tumor, liver and kidney). However, the decay rates of nanobubbles in tumor and kidney were significantly slower than those of Definity in the first 200-s fast initial phase. There were no significant differences in the decay rate in the liver in the initial phase or in three regions of interest in the terminal phase. Our results suggest that the stability and acoustic properties of the new nanobubble contrast agents are superior to those of the clinically used Definity microbubbles. The slower washout of nanobubbles in tumors suggests potential entrapment of the bubbles within the tumor parenchyma. PMID:23932272

Acoustic characterization and pharmacokinetic analyses of new nanobubble ultrasound contrast agents.

PubMed

Wu, Hanping; Rognin, Nicolas G; Krupka, Tianyi M; Solorio, Luis; Yoshiara, Hiroki; Guenette, Gilles; Sanders, Christopher; Kamiyama, Naohisa; Exner, Agata A

2013-11-01

In contrast to the clinically used microbubble ultrasound contrast agents, nanoscale bubbles (or nanobubbles) may potentially extravasate into tumors that exhibit more permeable vasculature, facilitating targeted molecular imaging and drug delivery. Our group recently presented a simple strategy using the non-ionic surfactant Pluronic as a size control excipient to produce nanobubbles with a mean diameter of 200 nm that exhibited stability and echogenicity on par with microbubbles. The objective of this study was to carry out an in-depth characterization of nanobubble properties as compared with Definity microbubbles, both in vitro and in vivo. Through use of a tissue-mimicking phantom, in vitro experiments measured the echogenicity of the contrast agent solutions and the contrast agent dissolution rate over time. Nanobubbles were found to be more echogenic than Definity microbubbles at three different harmonic frequencies (8, 6.2 and 3.5 MHz). Definity microbubbles also dissolved 1.67 times faster than nanobubbles. Pharmacokinetic studies were then performed in vivo in a subcutaneous human colorectal adenocarcinoma (LS174T) in mice. The peak enhancement and decay rates of contrast agents after bolus injection in the liver, kidney and tumor were analyzed. No significant differences were observed in peak enhancement between the nanobubble and Definity groups in the three tested regions (tumor, liver and kidney). However, the decay rates of nanobubbles in tumor and kidney were significantly slower than those of Definity in the first 200-s fast initial phase. There were no significant differences in the decay rates in the liver in the initial phase or in three regions of interest in the terminal phase. Our results suggest that the stability and acoustic properties of the new nanobubble contrast agents are superior to those of the clinically used Definity microbubbles. The slower washout of nanobubbles in tumors suggests potential entrapment of the bubbles within the tumor parenchyma. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

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.

Determination of the interfacial rheological properties of a PLA encapsulated contrast agent using in vitro attenuation and scattering

PubMed Central

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

2013-01-01

The stabilizing encapsulation of a microbubble based ultrasound contrast agent (UCA) critically affects its acoustic properties. Polymers, which behave differently from commonly used materials—e.g. lipids or proteins—for the monolayer encapsulation, hold potential for better stability and control over encapsulation properties. Air-filled microbubbles coated with Poly (D, L-lactide) (PLA) are characterized here using in vitro acoustic experiments and several models of encapsulation. The interfacial rheological properties of the encapsulation are determined according to each of these models using attenuation of ultrasound through a suspension of these microbubbles. Then the model predictions are compared with scattered nonlinear—sub- and second harmonic—responses. For this microbubble population (average diameter 1.9 μm), the peak in attenuation measurement indicates a weighted average resonance frequency of 2.5–3 MHz, which, in contrast to other encapsulated microbubbles, is lower than the resonance frequency of a free bubble of similar size (diameter 1.9 μm). This apparently contradictory result stems from the extremely low surface dilatational elasticity (around 0.01–0.07 N/m) and the reduced surface tension of the PLA encapsulation as well as the polydispersity of the bubble population. All models considered here are shown to behave similarly even in the nonlinear regime because of the low value of the surface dilatational elasticity. Pressure dependent scattering measurements at two different excitation frequencies (2.25 and 3 MHz) show strongly non-linear behavior with 25–30 dB and 5–20 dB enhancements in fundamental and second-harmonic responses respectively for a concentration of 1.33 μg/mL of suspension. Subharmonic responses are registered above a relatively low generation threshold of 100–150 kPa with up to 20 dB enhancement beyond that pressure. Numerical predictions from all models show good agreement with the experimentally measured fundamental response, but not with the second harmonic response. The characteristic features of subharmonic response and the steady response beyond the threshold are matched well by model predictions. However, prediction of the threshold value depends on property values and the size distribution. The variation in size distribution from sample to sample leads to variation in estimated encapsulation property values—the lowest estimated value of surface dilatational viscosity better predicts the subharmonic threshold. PMID:23643050

Near-infrared light-responsive liposomal contrast agent for photoacoustic imaging and drug release applications.

PubMed

Sivasubramanian, Kathyayini; Mathiyazhakan, Malathi; Wiraja, Christian; Upputuri, Paul Kumar; Xu, Chenjie; Pramanik, Manojit

2017-04-01

Photoacoustic imaging has become an emerging tool for theranostic applications. Not only does it help in

Near-infrared light-responsive liposomal contrast agent for photoacoustic imaging and drug release applications

NASA Astrophysics Data System (ADS)

Sivasubramanian, Kathyayini; Mathiyazhakan, Malathi; Wiraja, Christian; Upputuri, Paul Kumar; Xu, Chenjie; Pramanik, Manojit

2017-04-01

Photoacoustic imaging has become an emerging tool for theranostic applications. Not only does it help in in vivo, noninvasive imaging of biological structures at depths but it can also be used for drug release and therapeutic applications. We explore near-infrared light-sensitive liposomes coated with gold nanostars (AuNSs) for both imaging and drug release applications using a photoacoustic imaging system. Being amphiphilic, the liposomes lipid bilayer and the aqueous core enable encapsulation of both hydrophobic and hydrophilic drugs. The AuNSs on the surface of the liposomes act as photon absorbers due to their intrinsic surface plasmon resonance. Upon excitation by laser light at specific wavelength, AuNSs facilitate rapid release of the contents encapsulated in the liposomes due to local heating and pressure wave formation (photoacoustic wave). Herein, we describe the design and optimization of the AuNSs-coated liposomes and demonstrate the release of both hydrophobic and hydrophilic model drugs (paclitaxel and calcein, respectively) through laser excitation at near-infrared wavelength. The use of AuNSs-coated liposomes as contrast agents for photoacoustic imaging is also explored with tissue phantom experiments. In comparison to blood, the AuNSs-coated liposomes have better contrast (approximately two times) at 2-cm imaging depth.

Demonstration of a bronchobiliary fistula using magnetic resonance image with hepatospecific contrast agent.

PubMed

Baleato-González, S; Vieira-Leite, C; Alvárez-Castro, A M; García-Figueiras, R

Bronchobiliary fistulas are a rare entity of difficult diagnosis. The utility of magnetic resonance image (MRI) with hepatospecific contrast agents to demonstrate such condition is seldom described in the literature. This case reports a patient with pulmonary infection with a past history of hepatic surgery for hydatid disease in whom the presence of bile in the sputum rose the suspicious of a bronchobiliary fistula. MRI with hepatospecific contrast agents showed the communication between the biliary and bronchial tree and provided anatomic data to allow a therapeutic approach. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Studies of MRI relaxivities of gadolinium-labeled dendrons

NASA Astrophysics Data System (ADS)

Pan, Hongmu; Daniel, Marie-Christine

2011-05-01

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

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

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.

Infections in patients with chronic lymphocytic leukaemia: Mitigating risk in the era of targeted therapies.

PubMed

Teh, Benjamin W; Tam, Constantine S; Handunnetti, Sasanka; Worth, Leon J; Slavin, Monica A

2018-04-23

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia with infections a leading cause of morbidity and mortality. Recently there has been a paradigm shift from the use of chemo-immunotherapies to agents targeting specific B-lymphocyte pathways. These agents include ibrutinib, idelalisib and venetoclax. In this review, the risks and timing of infections associated with these agents are described, taking into account disease and treatment status. Treatment with ibrutinib as monotherapy or in combination with chemo-immunotherapies is not associated with additional risk for infection. In contrast, the use of idelalisib is associated with a 2-fold risk for severe infection and opportunistic infections. Venetoclax does not appear to be associated with additional infection risk. The evolving spectrum of pathogens responsible infections in CLL patients, especially those with relapsed and refractory disease are described, and prevention strategies (prophylaxis, monitoring and vaccination) are proposed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Magnetic resonance angiography: current status and future directions

PubMed Central

2011-01-01

With recent improvement in hardware and software techniques, magnetic resonance angiography (MRA) has undergone significant changes in technique and approach. The advent of 3.0 T magnets has allowed reduction in exogenous contrast dose without compromising overall image quality. The use of novel intravascular contrast agents substantially increases the image windows and decreases contrast dose. Additionally, the lower risk and cost in non-contrast enhanced (NCE) MRA has sparked renewed interest in these methods. This article discusses the current state of both contrast-enhanced (CE) and NCE-MRA. New CE-MRA methods take advantage of dose reduction at 3.0 T, novel contrast agents, and parallel imaging methods. The risks of gadolinium-based contrast media, and the NCE-MRA methods of time-of-flight, steady-state free precession, and phase contrast are discussed. PMID:21388544

Microenvironment-Sensitive Multimodal Contrast Agent for Prostate Cancer Diagnosis

DTIC Science & Technology

2014-10-01

which serve as a contrast agent for Magnetic Resonance Imaging (MRI), coated with a biopolymer (i.e. starch ) to improve biocompatibility, and...size stability (i.e. resisted aggregation) and lower protein binding than the unmodified MNP. The MNPs were also incubated for varying time periods with

An albumin-based gold nanocomposites as potential dual mode CT/MRI contrast agent

NASA Astrophysics Data System (ADS)

Zhao, Wenjing; Chen, Lina; Wang, Zhiming; Huang, Yuankui; Jia, Nengqin

2018-02-01

In pursuit of the biological detection applications, recent years have witnessed the prosperity of novel multi-modal nanoprobes. In this study, biocompatible bovine serum albumin (BSA)-coated gold nanoparticles (Au NPs) containing Gd (III) as the contrast agent for both X-ray CT and T1-weighted MR imaging is reported. Firstly, the Au NPs with BSA coating (Au@BSA) was prepared through a moderate one-pot reduction route in the presence of hydrazine hydrate as reducer. Sequentially, the BSA coating enables modification of diethylenetriaminepentaacetic acid (DTPA) as well as targeting reagent hyaluronic acid (HA), and further chelation of Gd (III) ions led to the formation of biomimetic nanoagent HA-targeted Gd-Au NPs (HA-targeted Au@BSA-Gd-DTPA). Several techniques were used to thoroughly characterize the formed HA-targeted Gd-Au NPs. As expected, the as-prepared nanoagent with mean diameter of 13.82 nm exhibits not only good colloid stablility and water dispersibility, but also satisfying low cytotoxicity and hemocompatibility in the tested concentration range. Additionally, for the CT phantoms, the obtained nanocomplex shows an improved contrast in CT scanning than that of Au@BSA as well as small molecule iodine-based CT contrast agents such as iopromide. Meanwhile, for the T1-weighted MRI images, there is a linear increase of contrast with concentration of Gd for the two cases of HA-targeted Gd-Au NPs and Magnevist. Strikingly, the nanoagent we explored displays a relatively higher r1 relaxivity than that of commercial MR contrast agents. Therefore, this newly constructed nanoagent could be used as contrast agents for synergistically enhanced X-ray CT and MR phantoms, holding promising potential for future biomedical applications.

Comparison of transducers with different frequencies in breast contrast-enhanced ultrasound (CEUS) using SonoVue as contrast agent.

PubMed

Wang, Yong-Mei; Fan, Wei; Zhang, Kai; Zhang, Li; Tan, Zhen; Ma, Rong

2016-07-01

To explore the effectiveness of different transducers in breast contrast-enhanced ultrasound (CEUS) using SonoVue(®) (Bracco, Plan-Les-Ouates, Switzerland) as the contrast agent. Breast CEUS was performed in 51 patients with 51 breast lesions using a low-frequency transducer (probe C5-1) and a high-frequency transducer (probe L12-5) separately. All image processes were reviewed for the presence of local blood perfusion defects and surrounding vessels. McNemar's test was conducted to compare the detection effectiveness between these two transducers. Pathological results revealed 38 malignant and 13 benign lesions. The two transducers showed no difference in detecting benign lesions. Among malignant lesions, CEUS conducted by probe C5-1 (frequency range from 1 to 5 MHz) presented 23 (60.5%) lesions with local blood perfusion defects and 26 (68.4%) lesions with surrounding vessels. Meanwhile, probe L12-5 (frequency range from 5 to 12 MHz) showed only 12 (31.6%) lesions with local blood perfusion defects and 12 (31.6%) lesions with surrounding vessel. Probe C5-1 was more sensitive than probe L12-5 in detecting malignant CEUS characteristics (p-value < 0.05). The low-frequency transducer was more sensitive than the high-frequency transducer in breast CEUS using SonoVue as the contrast agent. A new contrast agent with a higher resonance frequency, specially designed for high-frequency transducers, may be helpful in improving the clinical value of breast CEUS. The first study comparing different frequency transducers in breast CEUS of the same patient lesions. We brought out the requirement for CEUS contrast agents which are more suitable for high-frequency examinations.

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

PubMed

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

2017-08-01

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

MRI contrast agent for targeting glioma: interleukin-13 labeled liposome encapsulating gadolinium-DTPA

PubMed Central

Liu, Xiaoli; Madhankumar, Achuthamangalam B.; Miller, Patti A.; Duck, Kari A.; Hafenstein, Susan; Rizk, Elias; Slagle-Webb, Becky; Sheehan, Jonas M.; Connor, James R.; Yang, Qing X.

2016-01-01

Background Detection of glioma with MRI contrast agent is limited to cases in which the blood-brain barrier (BBB) is compromised as contrast agents cannot cross the BBB. Thus, an early-stage infiltrating tumor is not detectable. Interleukin-13 receptor alpha 2 (IL-13Rα2), which has been shown to be overexpressed in glioma, can be used as a target moiety. We hypothesized that liposomes conjugated with IL-13 and encapsulating MRI contrast agent are capable of passing through an intact BBB and producing MRI contrast with greater sensitivity. Methods The targeted MRI contrast agent was created by encapsulating Magnevist (Gd-DTPA) into liposomes conjugated with IL-13 and characterized by particle size distribution, cytotoxicity, and MRI relaxivity. MR image intensity was evaluated in the brain in normal mice post injection of Gd-DTPA and IL-13-liposome-Gd-DTPA one day apart. The specificity for glioma detection by IL-13-liposome-Gd-DTPA was demonstrated in an intracranial glioma mouse model and validated histologically. Results The average size of IL-13-liposome-Gd-DTPA was 137 ± 43 nm with relaxivity of 4.0 ± 0.4 L/mmole-s at 7 Tesla. No significant cytotoxicity was observed with MTS assay and serum chemistry in mice. The MRI signal intensity was enhanced up to 15% post injection of IL-13-liposome-Gd-DTPA in normal brain tissue following a similar time course as that for the pituitary gland outside of the BBB. MRI enhanced by IL-13-liposome-Gd-DTPA detected small tumor masses in addition to those seen with Magnevist-enhanced MRI. Conclusions IL-13-liposome-Gd-DTPA is able to pass through the uncompromised BBB and detect an early stage glioma that cannot be seen with conventional contrast-enhanced MRI. PMID:26519740

Dynamic fractal signature dissimilarity analysis for therapeutic response assessment using dynamic contrast-enhanced MRI

PubMed Central

Wang, Chunhao; Subashi, Ergys; Yin, Fang-Fang; Chang, Zheng

2016-01-01

Purpose: To develop a dynamic fractal signature dissimilarity (FSD) method as a novel image texture analysis technique for the quantification of tumor heterogeneity information for better therapeutic response assessment with dynamic contrast-enhanced (DCE)-MRI. Methods: A small animal antiangiogenesis drug treatment experiment was used to demonstrate the proposed method. Sixteen LS-174T implanted mice were randomly assigned into treatment and control groups (n = 8/group). All mice received bevacizumab (treatment) or saline (control) three times in two weeks, and one pretreatment and two post-treatment DCE-MRI scans were performed. In the proposed dynamic FSD method, a dynamic FSD curve was generated to characterize the heterogeneity evolution during the contrast agent uptake, and the area under FSD curve (AUCFSD) and the maximum enhancement (MEFSD) were selected as representative parameters. As for comparison, the pharmacokinetic parameter Ktrans map and area under MR intensity enhancement curve AUCMR map were calculated. Besides the tumor’s mean value and coefficient of variation, the kurtosis, skewness, and classic Rényi dimensions d1 and d2 of Ktrans and AUCMR maps were evaluated for heterogeneity assessment for comparison. For post-treatment scans, the Mann–Whitney U-test was used to assess the differences of the investigated parameters between treatment/control groups. The support vector machine (SVM) was applied to classify treatment/control groups using the investigated parameters at each post-treatment scan day. Results: The tumor mean Ktrans and its heterogeneity measurements d1 and d2 values showed significant differences between treatment/control groups in the second post-treatment scan. In contrast, the relative values (in reference to the pretreatment value) of AUCFSD and MEFSD in both post-treatment scans showed significant differences between treatment/control groups. When using AUCFSD and MEFSD as SVM input for treatment/control classification, the achieved accuracies were 93.8% and 93.8% at first and second post-treatment scan days, respectively. In comparison, the classification accuracies using d1 and d2 of Ktrans map were 87.5% and 100% at first and second post-treatment scan days, respectively. Conclusions: As quantitative metrics of tumor contrast agent uptake heterogeneity, the selected parameters from the dynamic FSD method accurately captured the therapeutic response in the experiment. The potential application of the proposed method is promising, and its addition to the existing DCE-MRI techniques could improve DCE-MRI performance in early assessment of treatment response. PMID:26936718

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.

Molecular Imaging and Contrast Agent Database (MICAD): Evolution and Progress

PubMed Central

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

2011-01-01

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 >1000 agents in MICAD is provided in a chapter format and can be accessed through PubMed. Lists containing >4250 unique MI probes and CAs published in peer-reviewed journals and agents approved by the United States Food and Drug Administration (FDA) as well as a CSV 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, preclinical 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 PMID:21989943

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. © 2015 Wiley Periodicals, Inc.

Ultrasound Imaging Beyond the Vasculature with New Generation Contrast Agents

PubMed Central

Perera, Reshani H.; Hernandez, Christopher; Zhou, Haoyan; Kota, Pavan; Burke, Alan

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. PMID:25580914

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

PubMed

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

2015-08-19

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

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

PubMed Central

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

2015-01-01

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

Molecular Imaging of Tumors Using a Quantitative T1 Mapping Technique via Magnetic Resonance Imaging

PubMed Central

Herrmann, Kelsey; Johansen, Mette L.; Craig, Sonya E.; Vincent, Jason; Howell, Michael; Gao, Ying; Lu, Lan; Erokwu, Bernadette; Agnes, Richard S.; Lu, Zheng-Rong; Pokorski, Jonathan K.; Basilion, James; Gulani, Vikas; Griswold, Mark; Flask, Chris; Brady-Kalnay, Susann M.

2015-01-01

Magnetic resonance imaging (MRI) of glioblastoma multiforme (GBM) with molecular imaging agents would allow for the specific localization of brain tumors. Prior studies using T1-weighted MR imaging demonstrated that the SBK2-Tris-(Gd-DOTA)3 molecular imaging agent labeled heterotopic xenograft models of brain tumors more intensely than non-specific contrast agents using conventional T1-weighted imaging techniques. In this study, we used a dynamic quantitative T1 mapping strategy to more objectively compare intra-tumoral retention of the SBK2-Tris-(Gd-DOTA)3 agent over time in comparison to non-targeted control agents. Our results demonstrate that the targeted SBK2-Tris-(Gd-DOTA)3 agent, a scrambled-Tris-(Gd-DOTA)3 control agent, and the non-specific clinical contrast agent Optimark™ all enhanced flank tumors of human glioma cells with similar maximal changes on T1 mapping. However, the retention of the agents differs. The non-specific agents show significant recovery within 20 min by an increase in T1 while the specific agent SBK2-Tris-(Gd-DOTA)3 is retained in the tumors and shows little recovery over 60 min. The retention effect is demonstrated by percent change in T1 values and slope calculations as well as by calculations of gadolinium concentration in tumor compared to muscle. Quantitative T1 mapping demonstrates the superior binding and retention in tumors of the SBK2-Tris-(Gd-DOTA)3 agent over time compared to the non-specific contrast agent currently in clinical use. PMID:26435847

Carboxymethyl cellulose (CMC)-loaded Co-Cu doped manganese ferrite nanorods as a new dual-modal simultaneous contrast agent for magnetic resonance imaging and nanocarrier for drug delivery system

NASA Astrophysics Data System (ADS)

Abbasi Pour, Sajjad; Shaterian, Hamid Reza; Afradi, Mojgan; Yazdani-Elah-Abadi, Afshin

2017-09-01

We synthesized Co0.25Cu0.25Mn0.5Fe2O4@CMC (CCMFe2O4@CMC) nanorods as a new dual-modal simultaneous for magnetic resonance imaging contrast agent and nanocarrier for drug delivery system. Impact of CCMFe2O4@CMC nanorods were investigated on the longitudinal (T1), transverse (T2) and transverse (T2∗) relaxation times for in vitro MRI contrast agent in water and also for drug delivery system, L-dopa was coated on CCMFe2O4@CMC nanorods and then in vitro drug release test was carried out at three PHs values and different temperatures. In vitro MR imaging demonstrated that r2 value of CCMFe2O4@CMC nanorods is 138.33 mM-1 s-1, CCMFe2O4@CMC is useful as T2 contrast agent relative to other T2 contrast agants. In vitro drug release test shows the amount of released L-dopa from CCMFe2O4@CMC nanorods at medium with pH = 1.2 is more than pH = 5.3 and 7.4.

Contrast agent-free sonoporation: The use of an ultrasonic standing wave microfluidic system for the delivery of pharmaceutical agents

PubMed Central

Carugo, Dario; Ankrett, Dyan N.; Glynne-Jones, Peter; Capretto, Lorenzo; Boltryk, Rosemary J.; Zhang, Xunli; Townsend, Paul A.; Hill, Martyn

2011-01-01

Sonoporation is a useful biophysical mechanism for facilitating the transmembrane delivery of therapeutic agents from the extracellular to the intracellular milieu. Conventionally, sonoporation is carried out in the presence of ultrasound contrast agents, which are known to greatly enhance transient poration of biological cell membranes. However, in vivo contrast agents have been observed to induce capillary rupture and haemorrhage due to endothelial cell damage and to greatly increase the potential for cell lysis in vitro. Here, we demonstrate sonoporation of cardiac myoblasts in the absence of contrast agent (CA-free sonoporation) using a low-cost ultrasound-microfluidic device. Within this device an ultrasonic standing wave was generated, allowing control over the position of the cells and the strength of the acoustic radiation forces. Real-time single-cell analysis and retrospective post-sonication analysis of insonated cardiac myoblasts showed that CA-free sonoporation induced transmembrane transfer of fluorescent probes (CMFDA and FITC-dextran) and that different mechanisms potentially contribute to membrane poration in the presence of an ultrasonic wave. Additionally, to the best of our knowledge, we have shown for the first time that sonoporation induces increased cell cytotoxicity as a consequence of CA-free ultrasound-facilitated uptake of pharmaceutical agents (doxorubicin, luteolin, and apigenin). The US-microfluidic device designed here provides an in vitro alternative to expensive and controversial in vivo models used for early stage drug discovery, and drug delivery programs and toxicity measurements. PMID:22662060

Dual-frequency transducer with a wideband PVDF receiver for contrast-enhanced, adjustable harmonic imaging

NASA Astrophysics Data System (ADS)

Kim, Jinwook; Lindsey, Brooks D.; Li, Sibo; Dayton, Paul A.; Jiang, Xiaoning

2017-04-01

Acoustic angiography is a contrast-enhanced, superharmonic microvascular imaging method. It has shown the capability of high-resolution and high-contrast-to-tissue-ratio (CTR) imaging for vascular structure near tumor. Dual-frequency ultrasound transducers and arrays are usually used for this new imaging technique. Stacked-type dual-frequency transducers have been developed for this vascular imaging method by exciting injected microbubble contrast agent (MCA) in the vessels with low-frequency (1-5 MHz), moderate power ultrasound burst waves and receiving the superharmonic responses from MCA by a high-frequency receiver (>10 MHz). The main challenge of the conventional dual-frequency transducers is a limited penetration depth (<25 mm) due to the insufficient receiving sensitivity for highfrequency harmonic signal detection. A receiver with a high receiving sensitivity spanning a wide superharmonic frequency range (3rd to 6th) enables selectable bubble harmonic detection considering the required penetration depth. Here, we develop a new dual-frequency transducer composed of a 2 MHz 1-3 composite transmitter and a polyvinylidene fluoride (PVDF) receiver with a receiving frequency range of 4-12 MHz for adjustable harmonic imaging. The developed transducer was tested for harmonic responses from a microbubble-injected vessel-mimicking tube positioned 45 mm away. Despite the long imaging distance (45 mm), the prototype transducer detected clear harmonic response with the contrast-to-noise ratio of 6-20 dB and the -6 dB axial resolution of 200-350 μm for imaging a 200 um-diameter cellulose tube filled with microbubbles.

A preliminary evaluation of self-made nanobubble in contrast-enhanced ultrasound imaging

NASA Astrophysics Data System (ADS)

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

2014-03-01

Nanoscale bubbles (nanobubbles) have been reported to improve contrast in tumor-targeted ultrasound imaging due to the enhanced permeation and retention effects at tumor vascular leaks. In this work, a self-made nanobubble ultrasound contrast agent was preliminarily characterized and evaluated in-vitro and in-vivo. Fundamental properties such as morphology appearance, size distribution, zeta potential, bubble concentration (bubble numbers per milliliter contrast agent suspension) and the stability of nanobubbles were assessed by light microscope and particle sizing analysis. Then the concentration intensity curve and time intensity curves (TICs) were acquired by ultrasound imaging experiment in-vitro. Finally, the contrast-enhanced ultrasonography was performed on rat to investigate the procedure of liver perfusion. The results showed that the nanobubbles had good shape and uniform distribution with the average diameter of 507.9 nm, polydispersity index (PDI) of 0.527, and zeta potential of -19.17 mV. Significant contrast enhancement was observed in in-vitro ultrasound imaging, demonstrating that the self-made nanobubbles can enhance the contrast effect of ultrasound imaging efficiently in-vitro. Slightly contrast enhancement was observed in in-vivo ultrasound imaging, indicating that the nanobubbles are not stable enough in-vivo. Future work will be focused on improving the ultrasonic imaging performance, stability, and antibody binding of the nanoscale ultrasound contrast agent.

Gd-functionalised Au nanoparticles as targeted contrast agents in MRI: relaxivity enhancement by polyelectrolyte coating.

PubMed

Warsi, Muhammad Farooq; Adams, Ralph W; Duckett, Simon B; Chechik, Victor

2010-01-21

Monolayer-protected, Gd(3+)-functionalised gold nanoparticles with enhanced spin-lattice relaxivity (r(1)) were prepared; adsorption of polyelectrolytes on these materials further increased r(1) and ligand exchange with a biotin-derivatised disulfide led to a prototype avidin-targeted contrast agent.

Targeted Gold Nanoparticle Contrast Agent for Digital Breast Tomosynthesis and Computed Tomography

DTIC Science & Technology

2012-03-01

bromopropionic acid (10 millimolar) was dissolved in acetonitrile (100 mL) , after which sodium azide (50 millimolar) was added to the solution. The mixture was...Transformation of the ionic X-ray contrast agent diatrizoate and related triiodinated benzoates by Trametes versicolor. Appl Environ Microbiol

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.

Dual-frequency super harmonic imaging piezoelectric transducers for transrectal ultrasound

NASA Astrophysics Data System (ADS)

Kim, Jinwook; Li, Sibo; Kasoji, Sandeep; Dayton, Paul A.; Jiang, Xiaoning

2015-03-01

In this paper, a 2/14 MHz dual-frequency single-element transducer and a 2/22 MHz sub-array (16/48-elements linear array) transducer were developed for contrast enhanced super-harmonic ultrasound imaging of prostate cancer with the low frequency ultrasound transducer as a transmitter for contrast agent (microbubble) excitation and the high frequency transducer as a receiver for detection of nonlinear responses from microbubbles. The 1-3 piezoelectric composite was used as active materials of the single-element transducers due to its low acoustic impedance and high coupling factor. A high dielectric constant PZT ceramic was used for the sub-array transducer due to its high dielectric property induced relatively low electrical impedance. The possible resonance modes of the active elements were estimated using finite element analysis (FEA). The pulse-echo response, peak-negative pressure and bubble response were tested, followed by in vitro contrast imaging tests using a graphite-gelatin tissue-mimicking phantom. The single-element dual frequency transducer (8 × 4 × 2 mm3) showed a -6 dB fractional bandwidth of 56.5% for the transmitter, and 41.8% for the receiver. A 2 MHz-transmitter (730 μm pitch and 6.5 mm elevation aperture) and a 22 MHz-receiver (240 μm pitch and 1.5 mm aperture) of the sub-array transducer exhibited -6 dB fractional bandwidth of 51.0% and 40.2%, respectively. The peak negative pressure at the far field was about -1.3 MPa with 200 Vpp, 1-cycle 2 MHz burst, which is high enough to excite microbubbles for nonlinear responses. The 7th harmonic responses from micro bubbles were successfully detected in the phantom imaging test showing a contrast-to-tissue ratio (CTR) of 16 dB.

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.

The impact of injector-based contrast agent administration in time-resolved MRA.

PubMed

Budjan, Johannes; Attenberger, Ulrike I; Schoenberg, Stefan O; Pietsch, Hubertus; Jost, Gregor

2018-05-01

Time-resolved contrast-enhanced MR angiography (4D-MRA), which allows the simultaneous visualization of the vasculature and blood-flow dynamics, is widely used in clinical routine. In this study, the impact of two different contrast agent injection methods on 4D-MRA was examined in a controlled, standardized setting in an animal model. Six anesthetized Goettingen minipigs underwent two identical 4D-MRA examinations at 1.5 T in a single session. The contrast agent (0.1 mmol/kg body weight gadobutrol, followed by 20 ml saline) was injected using either manual injection or an automated injection system. A quantitative comparison of vascular signal enhancement and quantitative renal perfusion analyses were performed. Analysis of signal enhancement revealed higher peak enhancements and shorter time to peak intervals for the automated injection. Significantly different bolus shapes were found: automated injection resulted in a compact first-pass bolus shape clearly separated from the recirculation while manual injection resulted in a disrupted first-pass bolus with two peaks. In the quantitative perfusion analyses, statistically significant differences in plasma flow values were found between the injection methods. The results of both qualitative and quantitative 4D-MRA depend on the contrast agent injection method, with automated injection providing more defined bolus shapes and more standardized examination protocols. • Automated and manual contrast agent injection result in different bolus shapes in 4D-MRA. • Manual injection results in an undefined and interrupted bolus with two peaks. • Automated injection provides more defined bolus shapes. • Automated injection can lead to more standardized examination protocols.

Synthesis and evaluation of nanoglobular macrocyclic Mn(II) chelate conjugates as non-gadolinium(III) MRI contrast agents.

PubMed

Tan, Mingqian; Ye, Zhen; Jeong, Eun-Kee; Wu, Xueming; Parker, Dennis L; Lu, Zheng-Rong

2011-05-18

Because of the recent observation of the toxic side effects of Gd(III) based MRI contrast agents in patients with impaired renal function, there is strong interest on developing alternative contrast agents for MRI. In this study, macrocyclic Mn(II) chelates were conjugated to nanoglobular carriers, lysine dendrimers with a silsesquioxane core, to synthesize non-Gd(III) based MRI contrast agents. A generation 3 nanoglobular conjugate of Mn(II)-1,4,7-triaazacyclononane-1,4,7-triacetate-GA amide (G3-NOTA-Mn) was also synthesized and evaluated. The per ion T(1) and T(2) relaxivities of G2, G3, G4 nanoglobular Mn(II)-DOTA monoamide conjugates decreased with increasing generation of the carriers. The T(1) relaxivities of G2, G3, and G4 nanoglobular Mn(II)-DOTA conjugates were 3.3, 2.8, and 2.4 mM(-1) s(-1) per Mn(II) chelate at 3 T, respectively. The T(1) relaxivity of G3-NOTA-Mn was 3.80 mM(-1) s(-1) per Mn(II) chelate at 3 T. The nanoglobular macrocyclic Mn(II) chelate conjugates showed good in vivo stability and were readily excreted via renal filtration. The conjugates resulted in much less nonspecific liver enhancement than MnCl(2) and were effective for contrast-enhanced tumor imaging in nude mice bearing MDA-MB-231 breast tumor xenografts at a dose of 0.03 mmol Mn/kg. The nanoglobular macrocyclic Mn(II) chelate conjugates are promising nongadolinium based MRI contrast agents.

Induction of mutagenesis and transformation in BALB/c-3T3 clone A31-1 cells by diverse chemical carcinogens

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

Lubet, R.A.; Kouri, R.E.; Curren, R.A.

1990-01-01

BALB/c-3T3 cells were employed to examine the genotoxic potential of a variety of known chemical carcinogens. BALB/c-3T3 cells displayed a dose-dependent transformation response to a variety of carcinogens (polycyclic hydrocarbons, methylating agents, ethylating agents, aflatoxin B{sub 1} (AFT{sub 1}), and 4-nitroquinoline-N-oxide (4-NQO)). When the ability of these compounds to induce mutagenesis to resistance to the cardiac glycoside ouabain (OUA{sup R}) was examined, the authors found the short chain alkylating agents to be particularly effective mutagens, causing biologic effects at doses below those necessary to induce a transformation response. In contrast, the polycyclic hydrocarbons which were potent transforming agents were weaker,more » albeit significant, mutagens for the OUA{sup R} locus in this system, while AFB{sub 1} was quite weak. Further studies were performed with 5-azacytidine (5-AZA) and the nongenotoxic carcinogen cinnamyl anthranilate (CIN). 5-AZA was a potent transforming agent, but failed to cause mutagenesis. CIN similarly caused in vitro transformation. When a series of eight structurally diverse compounds were examined in both the BALB/c-3T3 and C3H10T1/2 mouse fibroblast transformation systems, the BALB/c-3T3 system was shown to be sensitive to a wide variety of potential carcinogens, whereas the C3H10T1/2 system proved routinely sensitive only to the polycyclic hydrocarbons.« less

Liquid crystal alignment in electro-responsive nanostructured thermosetting materials based on block copolymer dispersed liquid crystal.

PubMed

Tercjak, A; Garcia, I; Mondragon, I

2008-07-09

Novel well-defined nanostructured thermosetting systems were prepared by modification of a diglicydylether of bisphenol-A epoxy resin (DGEBA) with 10 or 15 wt% amphiphilic poly(styrene-b-ethylene oxide) block copolymer (PSEO) and 30 or 40 wt% low molecular weight liquid crystal 4'-(hexyl)-4-biphenyl-carbonitrile (HBC) using m-xylylenediamine (MXDA) as a curing agent. The competition between well-defined nanostructured materials and the ability for alignment of the liquid crystal phase in the materials obtained has been studied by atomic and electrostatic force microscopy, AFM and EFM, respectively. Based on our knowledge, this is the first time that addition of an adequate amount (10 wt%) of a block copolymer to 40 wt% HBC-(DGEBA/MXDA) leads to a well-organized nanostructured thermosetting system (between a hexagonal and worm-like ordered structure), which is also electro-responsive with high rate contrast. This behavior was confirmed using electrostatic force microscopy (EFM), by means of the response of the HBC liquid crystal phase to the voltage applied to the EFM tip. In contrast, though materials containing 15 wt% PSEO and 30 wt% HBC also form a well-defined nanostructured thermosetting system, they do not show such a high contrast between the uncharged and charged surface.

Ultrasound Biomicroscopy in Small Animal Research: Applications in Molecular and Preclinical Imaging

PubMed Central

Greco, A.; Mancini, M.; Gargiulo, S.; Gramanzini, M.; Claudio, P. P.; Brunetti, A.; Salvatore, M.

2012-01-01

Ultrasound biomicroscopy (UBM) is a noninvasive multimodality technique that allows high-resolution imaging in mice. It is affordable, widely available, and portable. When it is coupled to Doppler ultrasound with color and power Doppler, it can be used to quantify blood flow and to image microcirculation as well as the response of tumor blood supply to cancer therapy. Target contrast ultrasound combines ultrasound with novel molecular targeted contrast agent to assess biological processes at molecular level. UBM is useful to investigate the growth and differentiation of tumors as well as to detect early molecular expression of cancer-related biomarkers in vivo and to monitor the effects of cancer therapies. It can be also used to visualize the embryological development of mice in uterus or to examine their cardiovascular development. The availability of real-time imaging of mice anatomy allows performing aspiration procedures under ultrasound guidance as well as the microinjection of cells, viruses, or other agents into precise locations. This paper will describe some basic principles of high-resolution imaging equipment, and the most important applications in molecular and preclinical imaging in small animal research. PMID:22163379

Recent Trends in Antibody-based Oncologic Imaging

PubMed Central

Kaur, Sukhwinder; Venktaraman, Ganesh; Jain, Maneesh; Senapati, Shantibhusan; Garg, Pradeep K.; Batra, Surinder K.

2011-01-01

Antibodies, with their unmatched ability for selective binding to any target, are considered as potentially the most specific probes for imaging. Their clinical utility, however, has been limited chiefly due to their slow clearance from the circulation, longer retention in non-targeted tissues and the extensive optimization required for each antibody-tracer. The development of newer contrast agents, combined with improved conjugation strategies and novel engineered forms of antibodies (diabodies, minibodies, single chain variable fragments, and nanobodies), have triggered a new wave of antibody-based imaging approaches. Apart from their conventional use with nuclear imaging probes, antibodies and their modified forms are increasingly being employed with non-radioisotopic contrast agents (MRI and ultrasound) as well as newer imaging modalities, such as quantum dots, near infra red (NIR) probes, nanoshells and surface enhanced Raman spectroscopy (SERS). The review article provides new developments in the usage of antibodies and their modified forms in conjunction with probes of various imaging modalities such as nuclear imaging, optical imaging, ultrasound, MRI, SERS and nanoshells in preclinical and clinical studies on the diagnosis, prognosis and therapeutic responses of cancer. PMID:22104729

Current consensus and guidelines of contrast enhanced ultrasound for the characterization of focal liver lesions

PubMed Central

Jang, Jae Young; Kim, Moon Young; Jeong, Soung Won; Kim, Tae Yeob; Kim, Seung Up; Lee, Sae Hwan; Suk, Ki Tae; Park, Soo Young; Woo, Hyun Young; Kim, Sang Gyune; Heo, Jeong; Baik, Soon Koo; Kim, Hong Soo

2013-01-01

The application of ultrasound contrast agents (UCAs) is considered essential when evaluating focal liver lesions (FLLs) using ultrasonography (US). Microbubble UCAs are easy to use and robust; their use poses no risk of nephrotoxicity and requires no ionizing radiation. The unique features of contrast enhanced US (CEUS) are not only noninvasiveness but also real-time assessing of liver perfusion throughout the vascular phases. The later feature has led to dramatic improvement in the diagnostic accuracy of US for detection and characterization of FLLs as well as the guidance to therapeutic procedures and evaluation of response to treatment. This article describes the current consensus and guidelines for the use of UCAs for the FLLs that are commonly encountered in US. After a brief description of the bases of different CEUS techniques, contrast-enhancement patterns of different types of benign and malignant FLLs and other clinical applications are described and discussed on the basis of our experience and the literature data. PMID:23593604

SU-F-T-664: The Efficacy of Gold Nanoparticles as Contrast Agents in Mice

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

Yuan, Y; Zhang, Y; Sajo, E

Purpose: Micro-Computed Tomography (micro-CT) has been widely used as a non-invasive, high-resolution imaging modality in preclinical research. However, tumors cannot be well distinguished, since their density are similar to those of surrounding tissues, and the tumors’ natural contrast is very low. The benefits of using Gold Nanoparticles (AuNPs) as a promising high atomic weight contrast agent have been published in recent years. The aim of this study is to investigate the efficacy of AuNPs as contrast agents using different energy x-rays. Methods: The left flank of an immune-compromised athymic nude mouse was implanted with subcutaneous xenograft model of human lungmore » cancer line, A549 cells (from ATCC). After 14 days, this mouse was imaged with dual energy cone-beam micro-CT. The selected energies were 45 kVp and 65 kVp. 10µg AuNPs (200 µg/ml concentration) approximately 12 nm in size were injected subcutaneously into the tumor. The mouse was imaged 0, 3 and 24 hours post-injection. During scanning, this mouse was anesthetized. All projection raw data have been optimized and then images were reconstructed with the FDK Algorithm. Results: Based on images, at 0 hour, AuNPs provided obvious contrast no matter which energy selected, 45 kVp or 65 kVp; and using 45 kVp X-ray, AuNps showed greater contrast. After 3 hours or evenand longer, AuNPs distributed throughout the whole body of mouse, and they were not shown clearly shown in the images. Conclusion: In this study, we investigated the efficacy of AuNPs as image contrast agents at different energies with dual-energy micro-CT, using 200µg/mL of AuNPs. Sufficiently high concentrations of AuNPs are needed to be able to track intratumoral distribution. Images showed good contrast immediately following the administration of the agent but results were poor after 3 hours.« less

MRI and CT contrast media extravasation: A systematic review.

PubMed

Heshmatzadeh Behzadi, Ashkan; Farooq, Zerwa; Newhouse, Jeffery H; Prince, Martin R

2018-03-01

This systematic review combines data from multiple papers on contrast media extravasation to identify factors contributing to increased extravasation risk. Data were extracted from 17 papers reporting 2191 extravasations in 1,104,872 patients (0.2%) undergoing computed tomography (CT) or magnetic resonance imaging (MRI). Extravasation rates were 0.045% for gadolinium-based contrast agents (GBCA) and nearly 6-fold higher, 0.26% for iodinated contrast agents. Factors associated with increased contrast media extravasations included: older age, female gender, using an existing intravenous (IV) instead of placing a new IV in radiology, in-patient status, use of automated power injection, high injection rates, catheter location, and failing to warm up the more viscous contrast media to body temperature. Contrast media extravasation is infrequent but nearly 6 times less frequent with GBCA for MRI compared with iodinated contrast used in CT.

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 post-injection) and 461.7 +/- 78.1 ΔSI (60% decrease from the peak signal value achieved 5 minutes post-injection) in the kidney (cortex) of a New Zealand white rabbit. This multimodal contrast agent, with prolonged in vivo residence time and imaging efficacy, has the potential to bring about improvements in the fields of medical imaging and radiation therapy, particularly for image registration and guidance.

Prostate-specific membrane antigen targeted protein contrast agents for molecular imaging of prostate cancer by MRI

NASA Astrophysics Data System (ADS)

Pu, Fan; Salarian, Mani; Xue, Shenghui; Qiao, Jingjuan; Feng, Jie; Tan, Shanshan; Patel, Anvi; Li, Xin; Mamouni, Kenza; Hekmatyar, Khan; Zou, Juan; Wu, Daqing; Yang, Jenny J.

2016-06-01

Prostate-specific membrane antigen (PSMA) is one of the most specific cell surface markers for prostate cancer diagnosis and targeted treatment. However, achieving molecular imaging using non-invasive MRI with high resolution has yet to be achieved due to the lack of contrast agents with significantly improved relaxivity for sensitivity, targeting capabilities and metal selectivity. We have previously reported our creation of a novel class of protein Gd3+ contrast agents, ProCA32, which displayed significantly improved relaxivity while exhibiting strong Gd3+ binding selectivity over physiological metal ions. In this study, we report our effort in further developing biomarker-targeted protein MRI contrast agents for molecular imaging of PSMA. Among three PSMA targeted contrast agents engineered with addition of different molecular recognition sequences, ProCA32.PSMA exhibits a binding affinity of 1.1 +/- 0.1 μM for PSMA while the metal binding affinity is maintained at 0.9 +/- 0.1 × 10-22 M. In addition, ProCA32.PSMA exhibits r1 of 27.6 mM-1 s-1 and r2 of 37.9 mM-1 s-1 per Gd (55.2 and 75.8 mM-1 s-1 per molecule r1 and r2, respectively) at 1.4 T. At 7 T, ProCA32.PSMA also has r2 of 94.0 mM-1 s-1 per Gd (188.0 mM-1 s-1 per molecule) and r1 of 18.6 mM-1 s-1 per Gd (37.2 mM-1 s-1 per molecule). This contrast capability enables the first MRI enhancement dependent on PSMA expression levels in tumor bearing mice using both T1 and T2-weighted MRI at 7 T. Further development of these PSMA-targeted contrast agents are expected to be used for the precision imaging of prostate cancer at an early stage and to monitor disease progression and staging, as well as determine the effect of therapeutic treatment by non-invasive evaluation of the PSMA level using MRI.Prostate-specific membrane antigen (PSMA) is one of the most specific cell surface markers for prostate cancer diagnosis and targeted treatment. However, achieving molecular imaging using non-invasive MRI with high resolution has yet to be achieved due to the lack of contrast agents with significantly improved relaxivity for sensitivity, targeting capabilities and metal selectivity. We have previously reported our creation of a novel class of protein Gd3+ contrast agents, ProCA32, which displayed significantly improved relaxivity while exhibiting strong Gd3+ binding selectivity over physiological metal ions. In this study, we report our effort in further developing biomarker-targeted protein MRI contrast agents for molecular imaging of PSMA. Among three PSMA targeted contrast agents engineered with addition of different molecular recognition sequences, ProCA32.PSMA exhibits a binding affinity of 1.1 +/- 0.1 μM for PSMA while the metal binding affinity is maintained at 0.9 +/- 0.1 × 10-22 M. In addition, ProCA32.PSMA exhibits r1 of 27.6 mM-1 s-1 and r2 of 37.9 mM-1 s-1 per Gd (55.2 and 75.8 mM-1 s-1 per molecule r1 and r2, respectively) at 1.4 T. At 7 T, ProCA32.PSMA also has r2 of 94.0 mM-1 s-1 per Gd (188.0 mM-1 s-1 per molecule) and r1 of 18.6 mM-1 s-1 per Gd (37.2 mM-1 s-1 per molecule). This contrast capability enables the first MRI enhancement dependent on PSMA expression levels in tumor bearing mice using both T1 and T2-weighted MRI at 7 T. Further development of these PSMA-targeted contrast agents are expected to be used for the precision imaging of prostate cancer at an early stage and to monitor disease progression and staging, as well as determine the effect of therapeutic treatment by non-invasive evaluation of the PSMA level using MRI. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr09071g

Multifunctional Cu2-xTe Nanocubes Mediated Combination Therapy for Multi-Drug Resistant MDA MB 453

NASA Astrophysics Data System (ADS)

Poulose, Aby Cheruvathoor; Veeranarayanan, Srivani; Mohamed, M. Sheikh; Aburto, Rebeca Romero; Mitcham, Trevor; Bouchard, Richard R.; Ajayan, Pulickel M.; Sakamoto, Yasushi; Maekawa, Toru; Kumar, D. Sakthi

2016-10-01

Hypermethylated cancer populations are hard to treat due to their enhanced chemo-resistance, characterized by aberrant methylated DNA subunits. Herein, we report on invoking response from such a cancer lineage to chemotherapy utilizing multifunctional copper telluride (Cu2-XTe) nanocubes (NCs) as photothermal and photodynamic agents, leading to significant anticancer activity. The NCs additionally possessed photoacoustic and X-ray contrast imaging abilities that could serve in image-guided therapeutic studies.

Vaporization and recondensation dynamics of indocyanine green-loaded perfluoropentane droplets irradiated by a short pulse laser

NASA Astrophysics Data System (ADS)

Yu, Jaesok; Chen, Xucai; Villanueva, Flordeliza S.; Kim, Kang

2016-12-01

Phase-transition droplets have been proposed as promising contrast agents for ultrasound and photoacoustic imaging. Short pulse laser activated perfluorocarbon-based droplets, especially when in a medium with a temperature below their boiling point, undergo phase changes of vaporization and recondensation in response to pulsed laser irradiation. Here, we report and discuss the vaporization and recondensation dynamics of perfluoropentane droplets containing indocyanine green in response to a short pulsed laser with optical and acoustic measurements. To investigate the effect of temperature on the vaporization process, an imaging chamber was mounted on a temperature-controlled water reservoir and then the vaporization event was recorded at 5 million frames per second via a high-speed camera. The high-speed movies show that most of the droplets within the laser beam area expanded rapidly as soon as they were exposed to the laser pulse and immediately recondensed within 1-2 μs. The vaporization/recondensation process was consistently reproduced in six consecutive laser pulses to the same area. As the temperature of the media was increased above the boiling point of the perfluoropentane, the droplets were less likely to recondense and remained in a gas phase after the first vaporization. These observations will help to clarify the underlying processes and eventually guide the design of repeatable phase-transition droplets as a photoacoustic imaging contrast agent.

Synthesis of DTPA analogues derived from piperidine and azepane: potential contrast enhancement agents for magnetic resonance imaging.

PubMed

Chong, H S; Garmestani, K; Bryant, L H; Brechbiel, M W

2001-11-16

Two DTPA derivatives (PIP-DTPA and AZEP-DTPA) as potential contrast enhancement agents in MRI are synthesized. The T1 and T2 relaxivities of their corresponding Gd(III) complexes are reported. At clinically relevant field strengths, the relaxivities of the complexes are comparable to that of the contrast agent, Gd(DTPA) which is in clinical use. The serum stability of the (153)Gd-labeled complexes is assessed by measuring the release of (153)Gd from the ligands. The radiolabeled Gd chelates are found to be kinetically stable in human serum for up to at least 14 days without any measurable loss of radioactivity.

A smart T(1)-weighted MRI contrast agent for uranyl cations based on a DNAzyme-gadolinium conjugate.

PubMed

Xu, Weichen; Xing, Hang; Lu, Yi

2013-11-07

Rational design of smart MRI contrast agents with high specificity for metal ions remains a challenge. Here, we report a general strategy for the design of smart MRI contrast agents for detecting metal ions based on conjugation of a DNAzyme with a gadolinium complex. The 39E DNAzyme, which has high selectivity for UO2(2+), was conjugated to Gd(III)-DOTA and streptavidin. The binding of UO2(2+) to its 39E DNAzyme resulted in the dissociation of Gd(III)-DOTA from the large streptavidin, leading to a decrease of the T1 correlation time, and a change in the MRI signal.

Contrast-enhanced photoacoustic tomography of human joints

NASA Astrophysics Data System (ADS)

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

2016-03-01

Photoacoustic tomography (PAT) provides a unique tool to diagnose inflammatory arthritis. However, the specificity and sensitivity of PAT based on endogenous contrasts is limited. The development of contrast enhanced PAT imaging modalities in combination with small molecule contrast agents could lead to improvements in diagnosis and treatment of joint disease. Accordingly, we adapted and tested a PAT clinical imaging system for imaging the human joints, in combination with a novel PAT contrast agent derived from an FDA-approved small molecule drug. Imaging results based on a photoacoustic and ultrasound (PA/US) dual-modality system revealed that this contrast-enhanced PAT imaging system may offer additional information beyond single-modality PA or US imaging system, for the imaging, diagnosis and assessment of inflammatory arthritis.

Surface and interfacial engineering of iron oxide nanoplates for highly efficient magnetic resonance angiography.

PubMed

Zhou, Zijian; Wu, Changqiang; Liu, Hanyu; Zhu, Xianglong; Zhao, Zhenghuan; Wang, Lirong; Xu, Ye; Ai, Hua; Gao, Jinhao

2015-03-24

Magnetic resonance angiography using gadolinium-based molecular contrast agents suffers from short diagnostic window, relatively low resolution and risk of toxicity. Taking into account the chemical exchange between metal centers and surrounding protons, magnetic nanoparticles with suitable surface and interfacial features may serve as alternative T1 contrast agents. Herein, we report the engineering on surface structure of iron oxide nanoplates to boost T1 contrast ability through synergistic effects between exposed metal-rich Fe3O4(100) facets and embedded Gd2O3 clusters. The nanoplates show prominent T1 contrast in a wide range of magnetic fields with an ultrahigh r1 value up to 61.5 mM(-1) s(-1). Moreover, engineering on nanobio interface through zwitterionic molecules adjusts the in vivo behaviors of nanoplates for highly efficient magnetic resonance angiography with steady-state acquisition window, superhigh resolution in vascular details, and low toxicity. This study provides a powerful tool for sophisticated design of MRI contrast agents for diverse use in bioimaging applications.

Excess of Radiation Burden for Young Testicular Cancer Patients using Automatic Exposure Control and Contrast Agent on Whole-body Computed Tomography Imaging.

PubMed

Niiniviita, Hannele; Kulmala, Jarmo; Pölönen, Tuukka; Määttänen, Heli; Järvinen, Hannu; Salminen, Eeva

2017-06-01

The aim of the study was to assess patient dose from whole-body computed tomography (CT) in association with patient size, automatic exposure control (AEC) and intravenous (IV) contrast agent. Sixty-five testicular cancer patients (mean age 28 years) underwent altogether 279 whole-body CT scans from April 2000 to April 2011. The mean number of repeated examinations was 4.3. The GE LightSpeed 16 equipped with AEC and the Siemens Plus 4 CT scanners were used for imaging. Whole-body scans were performed with (216) and without (63) IV contrast. The ImPACT software was used to determine the effective and organ doses. Patient doses were independent (p < 0.41) of patient size when the Plus 4 device (mean 7.4 mSv, SD 1.7 mSv) was used, but with the LightSpeed 16 AEC device, the dose (mean 14 mSv, SD 4.6 mSv) increased significantly (p < 0.001) with waist cirfumference. Imaging with the IV contrast agent caused significantly higher (13% Plus 4, 35% LightSpeed 16) exposure than non-contrast imaging (p < 0.001). Great caution on the use of IV contrast agent and careful set-up of the AEC modulation parameters is recommended to avoid excessive radiation exposure on the whole-body CT imaging of young patients.

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

PubMed

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

2009-05-01

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

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

PubMed

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

2016-08-01

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

Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents

DOE PAGES

Rees, Julian A.; Deblonde, Gauthier J. -P.; An, Dahlia D.; ...

2018-03-13

Several MRI contrast agent clinical formulations are now known to leave deposits of the heavy metal gadolinium in the brain, bones, and other organs of patients. This persistent biological accumulation of gadolinium has been recently recognized as a deleterious outcome in patients administered Gd-based contrast agents (GBCAs) for MRI, prompting the European Medicines Agency to recommend discontinuing the use of over half of the GBCAs currently approved for clinical applications. Here, to address this problem, we find that the orally-available metal decorporation agent 3,4,3-LI(1,2-HOPO) demonstrates superior efficacy at chelating and removing Gd from the body compared to diethylenetriaminepentaacetic acid, amore » ligand commonly used in the United States in the GBCA Gadopentetate (Magnevist). Using the radiotracer 153Gd to obtain precise biodistribution data, the results herein, supported by speciation simulations, suggest that the prophylactic or post-hoc therapeutic use of 3,4,3-LI(1,2-HOPO) may provide a means to mitigate Gd retention in patients requiring contrast-enhanced MRI.« less

Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents

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

Rees, Julian A.; Deblonde, Gauthier J. -P.; An, Dahlia D.

Several MRI contrast agent clinical formulations are now known to leave deposits of the heavy metal gadolinium in the brain, bones, and other organs of patients. This persistent biological accumulation of gadolinium has been recently recognized as a deleterious outcome in patients administered Gd-based contrast agents (GBCAs) for MRI, prompting the European Medicines Agency to recommend discontinuing the use of over half of the GBCAs currently approved for clinical applications. Here, to address this problem, we find that the orally-available metal decorporation agent 3,4,3-LI(1,2-HOPO) demonstrates superior efficacy at chelating and removing Gd from the body compared to diethylenetriaminepentaacetic acid, amore » ligand commonly used in the United States in the GBCA Gadopentetate (Magnevist). Using the radiotracer 153Gd to obtain precise biodistribution data, the results herein, supported by speciation simulations, suggest that the prophylactic or post-hoc therapeutic use of 3,4,3-LI(1,2-HOPO) may provide a means to mitigate Gd retention in patients requiring contrast-enhanced MRI.« less

Cavitation thresholds of contrast agents in an in vitro human clot model exposed to 120-kHz ultrasound.

PubMed

Gruber, Matthew J; Bader, Kenneth B; Holland, Christy K

2014-02-01

Ultrasound contrast agents (UCAs) can be employed to nucleate cavitation to achieve desired bioeffects, such as thrombolysis, in therapeutic ultrasound applications. Effective methods of enhancing thrombolysis with ultrasound have been examined at low frequencies (<1 MHz) and low amplitudes (<0.5 MPa). The objective of this study was to determine cavitation thresholds for two UCAs exposed to 120-kHz ultrasound. A commercial ultrasound contrast agent (Definity(®)) and echogenic liposomes were investigated to determine the acoustic pressure threshold for ultraharmonic (UH) and broadband (BB) generation using an in vitro flow model perfused with human plasma. Cavitation emissions were detected using two passive receivers over a narrow frequency bandwidth (540-900 kHz) and a broad frequency bandwidth (0.54-1.74 MHz). UH and BB cavitation thresholds occurred at the same acoustic pressure (0.3 ± 0.1 MPa, peak to peak) and were found to depend on the sensitivity of the cavitation detector but not on the nucleating contrast agent or ultrasound duty cycle.

Highly stable silica-coated manganese ferrite nanoparticles as high-efficacy T2 contrast agents for magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Ahmad, Ashfaq; Bae, Hongsub; Rhee, Ilsu

2018-05-01

Highly stable silica-coated manganese ferrite nanoparticles were fabricated for application as magnetic resonance imagining (MRI) contrast agents. The manganese ferrite nanoparticles were synthesized using a hydrothermal technique and coated with silica. The particle size was investigated using transmission electron microscopy and was found to be 40-60 nm. The presence of the silica coating on the particle surface was confirmed by Fourier transform infrared spectroscopy. The crystalline structure was investigated by X-ray diffraction, and the particles were revealed to have an inverse spinel structure. Superparamagnetism was confirmed by the magnetic hysteresis curves obtained using a vibrating sample magnetometer. The efficiency of the MRI contrast agents was investigated by using aqueous solutions of the particles in a 4.7 T MRI scanner. The T1 and T2 relaxivities of the particles were 1.42 and 60.65 s-1 mM-1, respectively, in water. The ratio r2/r1 was 48.91, confirming that the silica-coated manganese ferrite nanoparticles were suitable high-efficacy T2 contrast agents.

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.

Up to 50-fold increase in urine viscosity with iso-osmolar contrast media in the rat.

PubMed

Seeliger, Erdmann; Becker, Klaus; Ladwig, Mechthild; Wronski, Thomas; Persson, Pontus B; Flemming, Bert

2010-08-01

To compare changes in urinary viscosity in the renal tubules following administration of a high-viscosity iso-osmolar contrast agent (iodixanol) to that observed following administration of a less viscous, higher osmolar contrast agent (iopromide) in anesthetized rats. A total of 43 rats were studied. Experiments were approved by the Berlin, Germany, animal protection administration. A viscometer was developed to measure viscosity in minute samples (7 microL). Urine was collected, viscosity was measured (at 37 degrees C), and glomerular filtration rate (GFR) was determined by means of creatinine clearance. Boluses of 1.5 mL of iodixanol (320 mg iodine per milliliter, iso-osmolar to plasma, high viscosity) or iopromide (370 mg iodine per milliliter, higher osmolality and lower viscosity than iodixanol) were injected into the thoracic aorta. There were five groups (seven rats per group). Groups 1 (iodixanol) and 2 (iopromide) had free access to water prior to the experiment; groups 3 (iodixanol) and 4 (iopromide) received an additional infusion of isotonic saline (4 mL/kg/h). Group 5 was treated as group 1 but received only 0.75 mL of iodixanol. The observation period was 100 minutes. Statistical comparisons were made by means of nonparametric procedures (Friedman test, Kruskal-Wallis test). Iodixanol increased urine viscosity from 0.69 to 36.7 mm(2)/sec; thus, urine became threefold more viscous than native iodixanol solution. The increase in urine viscosity after injection of iopromide was from 0.73 to 2.3 mm(2)/sec. While GFR was not significantly affected by iopromide, GFR transiently decreased by 50% after administration of iodixanol. Iopromide had a diuretic effect twofold greater than that of iodixanol. Saline infusion blunted the viscosity rise and transient decline in GFR caused by iodixanol, as did reducing the iodixanol dose by 50%. Contrast media, in particular iodixanol, increase urine viscosity (which is equal to tubular fluid viscosity in the collecting ducts); in response to iodixanol, GFR markedly decreases. Saline infusion attenuates this response, thus potentially explaining the protective effects of volume expansion in contrast medium-induced nephropathy.

Applications of optically detected MRI for enhanced contrast and penetration in metal

NASA Astrophysics Data System (ADS)

Ruangchaithaweesuk, Songtham; Yu, Dindi S.; Garcia, Nissa C.; Yao, Li; Xu, Shoujun

2012-10-01

We report quantitative measurements using optically detected magnetic resonance imaging (MRI) for enhanced pH contrast and flow inside porous metals. Using a gadolinium chelate as the pH contrast agent, we show the response is 0.6 s-1 mM-1 per pH unit at the ambient magnetic field for the pH range 6-8.5. A stopped flow scheme was used to directly measure T1 relaxation time to determine the relaxivity. Flow profiles and images were obtained for a series of porous metals with different average pore sizes. The signal amplitudes and spatial distributions were compared. A clogged region in one of the samples was revealed using optically detected MRI but not optical imaging or scanning electron microscopy. These applications will significantly broaden the impact of optically detected MRI in chemical imaging and materials research.

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.

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.

Self-assembled dual-modality contrast agents for non-invasive stem cell tracking via near-infrared fluorescence and magnetic resonance imaging.

PubMed

Liu, Hong; Tan, Yan; Xie, Lisi; Yang, Lei; Zhao, Jing; Bai, Jingxuan; Huang, Ping; Zhan, Wugen; Wan, Qian; Zou, Chao; Han, Yali; Wang, Zhiyong

2016-09-15

Stem cells hold great promise for treating various diseases. However, one of the main drawbacks of stem cell therapy is the lack of non-invasive image-tracking technologies. Although magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging have been employed to analyse cellular and subcellular events via the assistance of contrast agents, the sensitivity and temporal resolution of MRI and the spatial resolution of NIRF are still shortcomings. In this study, superparamagnetic iron oxide nanocrystals and IR-780 dyes were co-encapsulated in stearic acid-modified polyethylenimine to form a dual-modality contrast agent with nano-size and positive charge. These resulting agents efficiently labelled stem cells and did not influence the cellular viability and differentiation. Moreover, the labelled cells showed the advantages of dual-modality imaging in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

Rapid Catalyst Capture Enables Metal-Free para-Hydrogen-Based Hyperpolarized Contrast Agents.

PubMed

Barskiy, Danila A; Ke, Lucia A; Li, Xingyang; Stevenson, Vincent; Widarman, Nevin; Zhang, Hao; Truxal, Ashley; Pines, Alexander

2018-05-10

Hyperpolarization techniques based on the use of para-hydrogen provide orders of magnitude signal enhancement for magnetic resonance spectroscopy and imaging. The main drawback limiting widespread applicability of para-hydrogen-based techniques in biomedicine is the presence of organometallic compounds (the polarization transfer catalysts) in solution with hyperpolarized contrast agents. These catalysts are typically complexes of platinum-group metals, and their administration in vivo should be avoided. Herein, we show how extraction of a hyperpolarized compound from an organic phase to an aqueous phase combined with a rapid (less than 10 s) Ir-based catalyst capture by metal scavenging agents can produce pure para-hydrogen-based hyperpolarized contrast agents, as demonstrated by high-resolution nuclear magnetic resonance (NMR) spectroscopy and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The presented methodology enables fast and efficient means of producing pure hyperpolarized aqueous solutions for biomedical and other uses.

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. Copyright © 2015 John Wiley & Sons, Ltd.

Macrophages mediated diagnosis of rheumatoid arthritis using fibrin based magnetic nanoparticles as MRI contrast agents.

PubMed

Periyathambi, Prabu; Sastry, Thotapalli Parvathaleswara; Anandasadagopan, Suresh Kumar; Manickavasagam, Kanagavel

2017-01-01

A variety of bioimaging tools assists in the diagnosis and evaluation of rheumatoid arthritis (RA) and other osteoarthritis. However, detection of RA in the early stages by targeting its macrophages with suitable contrast agents will help in arresting the progression of the disease. In the present study, we investigated the effectiveness of using magnetic fibrin nanoparticles (MFNPs) conjugated with folic acid (FA-MFNPs) as a specific contrast agent to target the activated macrophages, which overexpress the folate receptors (FR) in the knee joints of rats with antigen-induced arthritis (AIA). FA-MFNPs were spherical with an average size of 18.3±1.6nm. In vitro studies have shown effective internalization of FA-MFNPs into the Raw264.7 macrophage cells. In vivo studies were carried out by injecting FA-MFNPs intravenously into the arthritic rats. The results showed enhanced MR imaging in the synovium of arthritic joints. Prussian blue histological staining confirmed uptake of FA-MFNPs by macrophages in the synovial tissue. The animal experiment results indicate that FA-MFNPs can be used as a specific MRI contrast agent in identifying phagocytic active macrophages in the synovial joints. Blood is the precursor source for synthesising the fibrin-based iron oxide (magnetic) nanoparticles (MFNPs) with diameters between 12 and 15nm. It has excellent superparamagnetic behaviour, biocompatibility, osteogenic potency, hemocompatibility, and biodegradable properties. MFNPs-based nanocomposites might be a promising contrast agent for bioimaging. Copyright © 2016 Elsevier B.V. All rights reserved.

Whole-body multicolor spectrally resolved fluorescence imaging for development of target-specific optical contrast agents using genetically engineered probes

NASA Astrophysics Data System (ADS)

Kobayashi, Hisataka; Hama, Yukihiro; Koyama, Yoshinori; Barrett, Tristan; Urano, Yasuteru; Choyke, Peter L.

2007-02-01

Target-specific contrast agents are being developed for the molecular imaging of cancer. Optically detectable target-specific agents are promising for clinical applications because of their high sensitivity and specificity. Pre clinical testing is needed, however, to validate the actual sensitivity and specificity of these agents in animal models, and involves both conventional histology and immunohistochemistry, which requires large numbers of animals and samples with costly handling. However, a superior validation tool takes advantage of genetic engineering technology whereby cell lines are transfected with genes that induce the target cell to produce fluorescent proteins with characteristic emission spectra thus, identifying them as cancer cells. Multicolor fluorescence imaging of these genetically engineered probes can provide rapid validation of newly developed exogenous probes that fluoresce at different wavelengths. For example, the plasmid containing the gene encoding red fluorescent protein (RFP) was transfected into cell lines previously developed to either express or not-express specific cell surface receptors. Various antibody-based or receptor ligand-based optical contrast agents with either green or near infrared fluorophores were developed to concurrently target and validate cancer cells and their positive and negative controls, such as β-D-galactose receptor, HER1 and HER2 in a single animal/organ. Spectrally resolved fluorescence multicolor imaging was used to detect separate fluorescent emission spectra from the exogenous agents and RFP. Therefore, using this in vivo imaging technique, we were able to demonstrate the sensitivity and specificity of the target-specific optical contrast agents, thus reducing the number of animals needed to conduct these experiments.

Contrast Media: Are There Differences in Nephrotoxicity among Contrast Media?

PubMed Central

2014-01-01

Iodinated contrast agents are usually classified based upon their osmolality—high, low, and isosmolar. Iodinated contrast agents are also nephrotoxic in some but not all patients resulting in loss of glomerular filtration rate. Over the past 30 years, nephrotoxicity has been linked to osmolality although the precise mechanism underlying such a link has been elusive. Improvements in our understanding of the pathogenesis of nephrotoxicity and prospective randomized clinical trials have attempted to further explore the relationship between osmolality and nephrotoxicity. In this review, the basis for our current understanding that there are little if any differences in nephrotoxic potential between low and isosmolar contrast media will be detailed using data from clinical studies. PMID:24587997

Risky behaviors: effects of Toxorhynchites splendens (Diptera: Culicidae) predator on the behavior of three mosquito species.

PubMed

Zuharah, Wan Fatma; Fadzly, Nik; Yusof, Nur Aishah; Dieng, Hamady

2015-01-01

Viable biocontrol agents for mosquito control are quite rare, therefore improving the efficacy of existing biological agents is an important study. We need to have a better understanding of the predation-risk behavioral responses toward prey. This research examined prey choices by Toxorhynchites splendens by monitoring the behavioral responses of Aedes aegypti, Aedes albopictus, and Anopheles sinensis larvae when exposed to the predator. The results show that Tx. splendens prefers to consume Ae. aegypti larvae. The larvae exhibited different behavioral responses when Tx. splendens was present which suggest vulnerability in the presence of predators. "Thrashing" and "browsing" activities were greater in Ae. aegypti larvae. Such active and risky movements could cause vulnerability for the Ae. aegypti larvae due to increasing of water disturbance. In contrast, Ae. albopictus and An. sinensis larvae exhibited passive, low-risk behaviors, spending most of the time on the "wall" position near the edges of the container. We postulated that Ae. aegypti has less ability to perceive cues from predation and could not successfully alter its behavior to reduce risk of predation risk compared with Ae. albopictus and An. sinensis. Our results suggest that Tx. splendens is a suitable biocontrol agent in controlling dengue hemorrhagic vector, Ae. aegypti. © The Author 2015. Published by Oxford University Press on behalf of the Entomological Society of America.

Development of Bifunctional Gadolinium-Labeled Superparamagnetic Nanoparticles (Gd-MnMEIO) for In Vivo MR Imaging of the Liver in an Animal Model.

PubMed

Kuo, Yu-Ting; Chen, Chiao-Yun; Liu, Gin-Chung; Wang, Yun-Ming

2016-01-01

Liver tumors are common and imaging methods, particularly magnetic resonance imaging (MRI), play an important role in their non-invasive diagnosis. Previous studies have shown that detection of liver tumors can be improved by injection of two different MR contrast agents. Here, we developed a new contrast agent, Gd-manganese-doped magnetism-engineered iron oxide (Gd-MnMEIO), with enhancement effects on both T1- and T2-weighted MR images of the liver. A 3.0T clinical MR scanner equipped with transmit/receiver coil for mouse was used to obtain both T1-weighted spoiled gradient-echo and T2-weighted fast spin-echo axial images of the liver before and after intravenous contrast agent injection into Balb/c mice with and without tumors. After pre-contrast scanning, six mice per group were intravenously injected with 0.1 mmol/kg Gd-MnMEIO, or the control agents, i.e., Gd-DTPA or SPIO. The scanning time points for T1-weighted images were 0.5, 5, 10, 15, 20, 25, and 30 min after contrast administration. The post-enhanced T2-weighted images were then acquired immediately after T1-weighted acquisition. We found that T1-weighted images were positively enhanced by both Gd-DTPA and Gd-MnMEIO and negatively enhanced by SPIO. The enhancement by both Gd-DTPA and Gd-MnMEIO peaked at 0.5 min and gradually declined thereafter. Gd-MnMEIO (like Gd-DTPA) enhanced T1-weighted images and (like SPIO) T2-weighted images. Marked vascular enhancement was clearly visible on dynamic T1-weighted images with Gd-MnMEIO. In addition, the T2 signal was significantly decreased at 30 min after administration of Gd-MnMEIO. Whereas the effects of Gd-MnMEIO and SPIO on T2-weighted images were similar (p = 0.5824), those of Gd-MnMEIO and Gd-DTPA differed, with Gd-MnMEIO having a significant T2 contrast effect (p = 0.0086). Our study confirms the feasibility of synthesizing an MR contrast agent with both T1 and T2 shortening effects and using such an agent in vivo. This agent enables tumor detection and characterization in single liver MRI sections.

Gd-DTPA L-cystine bisamide copolymers as novel biodegradable macromolecular contrast agents for MR blood pool imaging.

PubMed

Kaneshiro, Todd L; Ke, Tianyi; Jeong, Eun-Kee; Parker, Dennis L; Lu, Zheng-Rong

2006-06-01

The purpose of this study was to synthesize biodegradable Gd-DTPA L-cystine bisamide copolymers (GCAC) as safe and effective, macromolecular contrast agents for magnetic resonance imaging (MRI) and to evaluate their biodegradability and efficacy in MR blood pool imaging in an animal model. Three new biodegradable GCAC with different substituents at the cystine bisamide [R = H (GCAC), CH2CH2CH3 (Gd-DTPA L-cystine bispropyl amide copolymers, GCPC), and CH(CH3)2 (Gd-DTPA cystine bisisopropyl copolymers, GCIC)] were prepared by the condensation copolymerization of diethylenetriamine pentaacetic acid (DTPA) dianhydride with cystine bisamide or bisalkyl amides, followed by complexation with gadolinium triacetate. The degradability of the agents was studied in vitro by incubation in 15 microM cysteine and in vivo with Sprague-Dawley rats. The kinetics of in vivo contrast enhancement was investigated in Sprague-Dawley rats on a Siemens Trio 3 T scanner. The apparent molecular weight of the polydisulfide Gd(III) chelates ranged from 22 to 25 kDa. The longitudinal (T1) relaxivities of GCAC, GCPC, and GCIC were 4.37, 5.28, and 5.56 mM(-1) s(-1) at 3 T, respectively. The polymeric ligands and polymeric Gd(III) chelates readily degraded into smaller molecules in incubation with 15 microM cysteine via disulfide-thiol exchange reactions. The in vitro degradation rates of both the polymeric ligands and macromolecular Gd(III) chelates decreased as the steric effect around the disulfide bonds increased. The agents readily degraded in vivo, and the catabolic degradation products were detected in rat urine samples collected after intravenous injection. The agents showed strong contrast enhancement in the blood pool, major organs, and tissues at a dose of 0.1 mmol Gd/kg. The difference of their in vitro degradability did not significantly alter the kinetics of in vivo contrast enhancement of the agents. These novel GCAC are promising contrast agents for cardiovascular and tumor MRI, which are later cleaved into low molecular weight Gd(III) chelates and rapidly cleared from the body.

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

NASA Astrophysics Data System (ADS)

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

2015-02-01

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

[Development of Biliary Contrast Agents Remote Pushing Device].

PubMed

Zhu, Haoyang; Dong, Dinghui; Luo, Yu; Ren, Fenggang; Zhang, Jing; Tan, Wenjun; Shi, Aihua; Hu, Liangshuo; Wu, Rongqian; Lyu, Yi

2018-01-30

A biliary contrast agents pushing device, including a syringe pushing system and a remote controller is introduced. The syringe pushing system comprises an injector card slot, a support platform and an injection bolus fader. A 20 mL syringe can be fitted on the syringe pushing system and kept with the ground about 30 degree. This system can perform air bubble pumping back and contrast agents bolus injection as well as speed adjustment. Remote controller is an infrared remote control which can start and stop the syringe pushing system. With this device, the remote controlled cholangiography technology can be achieved, which can not only protect doctors from X-ray radiation but also improve the traditional T-tube cholangiography and the contrast effect, reduce postoperative complications in patients as well. The application of this device will improve the current diagnosis and treatment system, the device will benefit the majority of doctors and patients.

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

NASA Astrophysics Data System (ADS)

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

2016-09-01

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

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

Antibiofouling polymer coated gold nanoparticles as a dual modal contrast agent for X-ray and photoacoustic imaging

NASA Astrophysics Data System (ADS)

Huang, Guojia; Yuan, Yi; Xing, Da

2011-01-01

X-ray is one of the most useful diagnostic tools in hospitals in terms of frequency of use and cost, while photoacoustic (PA) imaging is a rapidly emerging non-invasive imaging technology that integrates the merits of high optical contrast with high ultrasound resolution. In this study, for the first time, we used gold nanoparticles (GNPs) as a dual modal contrast agent for X-ray and PA imaging. Soft gelatin phantoms with embedded tumor simulators of GNPs in various concentrations are clearly shown in both X-ray and PA imaging. With GNPs as a dual modal contrast agent, X-ray can fast detect the position of tumor and provide morphological information, whereas PA imaging has important potential applications in the image guided therapy of superficial tumors such as breast cancer, melanoma and Merkel cell carcinoma.

Reference tissue quantification of DCE-MRI data without a contrast agent calibration

NASA Astrophysics Data System (ADS)

Walker-Samuel, Simon; Leach, Martin O.; Collins, David J.

2007-02-01

The quantification of dynamic contrast-enhanced (DCE) MRI data conventionally requires a conversion from signal intensity to contrast agent concentration by measuring a change in the tissue longitudinal relaxation rate, R1. In this paper, it is shown that the use of a spoiled gradient-echo acquisition sequence (optimized so that signal intensity scales linearly with contrast agent concentration) in conjunction with a reference tissue-derived vascular input function (VIF), avoids the need for the conversion to Gd-DTPA concentration. This study evaluates how to optimize such sequences and which dynamic time-series parameters are most suitable for this type of analysis. It is shown that signal difference and relative enhancement provide useful alternatives when full contrast agent quantification cannot be achieved, but that pharmacokinetic parameters derived from both contain sources of error (such as those caused by differences between reference tissue and region of interest proton density and native T1 values). It is shown in a rectal cancer study that these sources of uncertainty are smaller when using signal difference, compared with relative enhancement (15 ± 4% compared with 33 ± 4%). Both of these uncertainties are of the order of those associated with the conversion to Gd-DTPA concentration, according to literature estimates.

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.

Self-assembled nanomaterials for photoacoustic imaging

NASA Astrophysics Data System (ADS)

Wang, Lei; Yang, Pei-Pei; Zhao, Xiao-Xiao; Wang, Hao

2016-01-01

In recent years, extensive endeavors have been paid to construct functional self-assembled nanomaterials for various applications such as catalysis, separation, energy and biomedicines. To date, different strategies have been developed for preparing nanomaterials with diversified structures and functionalities via fine tuning of self-assembled building blocks. In terms of biomedical applications, bioimaging technologies are urgently calling for high-efficient probes/contrast agents for high-performance bioimaging. Photoacoustic (PA) imaging is an emerging whole-body imaging modality offering high spatial resolution, deep penetration and high contrast in vivo. The self-assembled nanomaterials show high stability in vivo, specific tolerance to sterilization and prolonged half-life stability and desirable targeting properties, which is a kind of promising PA contrast agents for biomedical imaging. Herein, we focus on summarizing recent advances in smart self-assembled nanomaterials with NIR absorption as PA contrast agents for biomedical imaging. According to the preparation strategy of the contrast agents, the self-assembled nanomaterials are categorized into two groups, i.e., the ex situ and in situ self-assembled nanomaterials. The driving forces, assembly modes and regulation of PA properties of self-assembled nanomaterials and their applications for long-term imaging, enzyme activity detection and aggregation-induced retention (AIR) effect for diagnosis and therapy are emphasized. Finally, we conclude with an outlook towards future developments of self-assembled nanomaterials for PA imaging.

Synthesis of nanostructured barium phosphate and its application in micro-computed tomography of mouse brain vessels in ex vivo

NASA Astrophysics Data System (ADS)

Zhu, Bangshang; Yuan, Falei; Yuan, Xiaoya; Bo, Yang; Wang, Yongting; Yang, Guo-Yuan; Drummen, Gregor P. C.; Zhu, Xinyuan

2014-02-01

Micro-computed tomography (micro-CT) is a powerful tool for visualizing the vascular systems of tissues, organs, or entire small animals. Vascular contrast agents play a vital role in micro-CT imaging in order to obtain clear and high-quality images. In this study, a new kind of nanostructured barium phosphate was fabricated and used as a contrast agent for ex vivo micro-CT imaging of blood vessels in the mouse brain. Nanostructured barium phosphate was synthesized through a simple wet precipitation method using Ba(NO3)2, and (NH4)2HPO4 as starting materials. The physiochemical properties of barium phosphate were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and thermal analysis. Furthermore, the impact of the produced nanostructures on cell viability was evaluated via the MTT assay, which generally showed low to moderate cytotoxicity. Finally, the animal test images demonstrated that the use of nanostructured barium phosphate as a contrast agent in Micro-CT imaging produced sharp images with excellent contrast. Both major vessels and the microvasculature were clearly observable in the imaged mouse brain. Overall, the results indicate that nanostructured barium phosphate is a potential and useful vascular contrast agent for micro-CT imaging.

Self-assembled nanomaterials for photoacoustic imaging.

PubMed

Wang, Lei; Yang, Pei-Pei; Zhao, Xiao-Xiao; Wang, Hao

2016-02-07

In recent years, extensive endeavors have been paid to construct functional self-assembled nanomaterials for various applications such as catalysis, separation, energy and biomedicines. To date, different strategies have been developed for preparing nanomaterials with diversified structures and functionalities via fine tuning of self-assembled building blocks. In terms of biomedical applications, bioimaging technologies are urgently calling for high-efficient probes/contrast agents for high-performance bioimaging. Photoacoustic (PA) imaging is an emerging whole-body imaging modality offering high spatial resolution, deep penetration and high contrast in vivo. The self-assembled nanomaterials show high stability in vivo, specific tolerance to sterilization and prolonged half-life stability and desirable targeting properties, which is a kind of promising PA contrast agents for biomedical imaging. Herein, we focus on summarizing recent advances in smart self-assembled nanomaterials with NIR absorption as PA contrast agents for biomedical imaging. According to the preparation strategy of the contrast agents, the self-assembled nanomaterials are categorized into two groups, i.e., the ex situ and in situ self-assembled nanomaterials. The driving forces, assembly modes and regulation of PA properties of self-assembled nanomaterials and their applications for long-term imaging, enzyme activity detection and aggregation-induced retention (AIR) effect for diagnosis and therapy are emphasized. Finally, we conclude with an outlook towards future developments of self-assembled nanomaterials for PA imaging.

X-ray computed tomography imaging of a tumor with high sensitivity using gold nanoparticles conjugated to a cancer-specific antibody via polyethylene glycol chains on their surface

NASA Astrophysics Data System (ADS)

Nakagawa, Tomohiko; Gonda, Kohsuke; Kamei, Takashi; Cong, Liman; Hamada, Yoh; Kitamura, Narufumi; Tada, Hiroshi; Ishida, Takanori; Aimiya, Takuji; Furusawa, Naoko; Nakano, Yasushi; Ohuchi, Noriaki

2016-01-01

Contrast agents are often used to enhance the contrast of X-ray computed tomography (CT) imaging of tumors to improve diagnostic accuracy. However, because the iodine-based contrast agents currently used in hospitals are of low molecular weight, the agent is rapidly excreted from the kidney or moves to extravascular tissues through the capillary vessels, depending on its concentration gradient. This leads to nonspecific enhancement of contrast images for tissues. Here, we created gold (Au) nanoparticles as a new contrast agent to specifically image tumors with CT using an enhanced permeability and retention (EPR) effect. Au has a higher X-ray absorption coefficient than does iodine. Au nanoparticles were supported with polyethylene glycol (PEG) chains on their surface to increase the blood retention and were conjugated with a cancer-specific antibody via terminal PEG chains. The developed Au nanoparticles were injected into tumor-bearing mice, and the distribution of Au was examined with CT imaging, transmission electron microscopy, and elemental analysis using inductively coupled plasma optical emission spectrometry. The results show that specific localization of the developed Au nanoparticles in the tumor is affected by a slight difference in particle size and enhanced by the conjugation of a specific antibody against the tumor.

Imaging techniques for assessment of tubal status

PubMed Central

Panchal, Sonal; Nagori, Chaitanya

2014-01-01

Fallopian tubes make a vital portal for transfer of gametes and embryo. Tubal factor is responsible for infertility in 25-35% of cases. Hysterosalpingography (HSG) has been used to evaluate the uterine cavity and the tubal status since decades. It uses iodinated contrast and X-rays and is painful and inconvenient for patient. Laparoscopy is considered to be the gold standard for tubal evaluation, but is an operative procedure and needs anesthesia. Though ultrasound is a modality of choice for assessment of uterus and ovaries, it does not allow assessment of the fallopian tube unless there is any fluid surrounding it or inside the lumen. This fluid interface can be created artificially by introducing saline in the uterine cavity and fallopian tubes and scanning simultaneously. The procedure is named Saline infusion HSG. Saline infusion sonohysterosalpingography (SIS) can be done with B mode US and Doppler. SIS can demonstrate a patent tube but if blocked, the site of block cannot be demonstrated. Ultrasound contrast agents can be used for tubal assessment using contrast mode on the scanners. This procedure is known as hystero-contrast sonography (HyCoSy). This actually shows the passage of hyperechoic contrast agent through tubal lumen and delineates it and locates the site of block. Using the volume ultrasound may even make the demonstration of tubal status and fimbriae better. Results of HyCoSy have been found to correlate well with laparoscopic findings, which are a gold standard. It is recommended by National Institute for Health and Clinical Excellence as a primary investigation for tubal assessment in patients without any positive history of tubal damage and also can replace a second look laparoscopy. PMID:24829524

Methods to Enhance Laser Speckle Imaging of High-Flow and Low-Flow Vasculature

PubMed Central

Choi, Bernard; Ringold, Tyson L.; Kim, Jeehyun

2012-01-01

The objective of this paper is to present two methods to extend the response range of laser speckle imaging (LSI). We report on the use of two methods (image exposure time control and magnetomotive actuation of exogenous contrast agents) to enhance characterization of high- and low-flow vasculature, respectively. With an exposure time of 10 and 0.01 ms, the linear response range extended to 10 and 280 mm/s, respectively. With application of an AC magnetic field to a solution of stagnant SPIO particles, an apparent increase of ~3× in speckle flow index was induced. PMID:19964103

Intravenous injection of gadobutrol in an epidemiological study group did not lead to a difference in relative signal intensities of certain brain structures after 5 years.

PubMed

Kromrey, Marie-Luise; Liedtke, Kim Rouven; Ittermann, Till; Langner, Sönke; Kirsch, Michael; Weitschies, Werner; Kühn, Jens-Peter

2017-02-01

To investigate if application of macrocyclic gadolinium-based contrast agents in volunteers is associated with neuronal deposition detected by magnetic resonance imaging in a 5-year longitudinal survey. Three hundred eighty-seven volunteers who participated in a population-based study were enrolled. Subjects underwent plain T1-weighted brain MRI at baseline and 5 years later with identical sequence parameters. At baseline, 271 participants additionally received intravenous injection of the macrocyclic contrast agent gadobutrol (0.15 mmol/kg). A control group including 116 subjects received no contrast agent. Relative signal intensities of thalamus, pallidum, pons and dentate nucleus were compared at baseline and follow-up. No difference in relative signal intensities was observed between contrast group (thalamus, p = 0.865; pallidum, p = 0.263; pons, p = 0.533; dentate nucleus, p = 0.396) and control group (thalamus, p = 0.683; pallidum; p = 0.970; pons, p = 0.773; dentate nucleus, p = 0.232) at both times. Comparison between both groups revealed no significant differences in relative signal intensities (thalamus, p = 0.413; pallidum, p = 0.653; pons, p = 0.460; dentate nucleus, p = 0.751). The study showed no significant change in globus pallidus-to-thalamus or dentate nucleus-to-pons ratios. Five years after administration of a 1.5-fold dose gadobutrol to normal subjects, signal intensity of thalamus, pallidum, pons and dentate nucleus did not differ from participants who had not received gadobutrol. • Gadobutrol does not lead to neuronal signal alterations after 5 years. • Neuronal deposition of macrocyclic contrast agent could not be confirmed. • Macrocyclic contrast agents in a proven dosage are safe.

Use of trimetasphere metallofullerene MRI contrast agent for the non-invasive longitudinal tracking of stem cells in the lung

PubMed Central

Murphy, Sean V.; Hale, Austin; Reid, Tanya; Olson, John; Kidiyoor, Amritha; Tan, Josh; Zhou, Zhiguo; Jackson, John; Atala, Anthony

2016-01-01

Magnetic Resonance Imaging (MRI) is a commonly used, non-invasive imaging technique that provides visualization of soft tissues with high spatial resolution. In both a research and clinical setting, the major challenge has been identifying a non-invasive and safe method for longitudinal tracking of delivered cells in vivo. The labeling and tracking of contrast agent labeled cells using MRI has the potential to fulfill this need. Contrast agents are often used to enhance the image contrast between the tissue of interest and surrounding tissues with MRI. The most commonly used MRI contrast agents contain Gd(III) ions. However, Gd(III) ions are highly toxic in their ionic form, as they tend to accumulate in the liver, spleen, kidney and bones and block calcium channels. Endohedral metallofullerenes such as trimetallic nitride endohedral metallofullerenes (Trimetasphere®) are one unique class of fullerene molecules where a Gd3N cluster is encapsulated inside a C80 carbon cage referred to as Gd3N@C80. These endohedral metallofullerenes have several advantages over small chelated Gd(III) complexes such as increased stability of the Gd(III) ion, minimal toxic effects, high solubility in water and high proton relativity. In this study, we describe the evaluation of gadolinium-based Trimetasphere® positive contrast agent for the in vitro labeling and in vivo tracking of human amniotic fluid-derived stem cells within lung tissue. In addition, we conducted a ‘proof-of-concept’ experiment demonstrating that this methodology can be used to track the homing of stem cells to injured lung tissue and provide longitudinal analysis of cell localization over an extended time course. PMID:26546729

Coronary Computed Tomographic Angiography at Low Concentration of Contrast Agent and Low Tube Voltage in Patients with Obesity:: A Feasibility Study.

PubMed

Pan, Yu-Ning; Li, Ai-Jing; Chen, Xiao-Min; Wang, Jian; Ren, Da-Wei; Huang, Qiu-Li

2016-04-01

Using lower tube voltage can reduce the exposure to radiation and the dose of contrast agent. However, lower tube voltage is often linked to more noise and poor image quality, which create a need for more effective technology to resolve this problem. To explore the feasibility of coronary computed tomographic angiography (CCTA) in patients with obesity at low tube voltage (100 kV) and low contrast agent concentration (270 mg/mL) using iterative reconstruction. A total of 48 patients with body mass index greater than 30 kg/m(2) were included and randomly divided into two groups. Group A received a traditional protocol (iopromide 370 mg/mL + 120 kV); group B received a protocol with low tube voltage (100 kV), low contrast agent concentration (270 mg/mL), and iterative reconstruction. The effective dose (ED), average attenuation values, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), the figure of merit (FOM), image quality scores, and the total iodine intake were compared. No significant differences in average CT attenuations, SNR, CNR, and subjective scores were noticed between the two groups (P > 0.05), whereas the FOM of group B was significantly higher than that of group A. Effective radiation dose, total iodine, and iodine injection rate in group B were lower than those of group A (P <0.01). In patients with obesity, isotonic contrast agent with low iodine concentration and low-dose CCTA were feasible. Substantial reduction in radiation dose and the iodine intake could be achieved without compromising the image quality. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Use of trimetasphere metallofullerene MRI contrast agent for the non-invasive longitudinal tracking of stem cells in the lung.

PubMed

Murphy, Sean V; Hale, Austin; Reid, Tanya; Olson, John; Kidiyoor, Amritha; Tan, Josh; Zhou, Zhiguo; Jackson, John; Atala, Anthony

2016-04-15

Magnetic Resonance Imaging (MRI) is a commonly used, non-invasive imaging technique that provides visualization of soft tissues with high spatial resolution. In both a research and clinical setting, the major challenge has been identifying a non-invasive and safe method for longitudinal tracking of delivered cells in vivo. The labeling and tracking of contrast agent labeled cells using MRI has the potential to fulfill this need. Contrast agents are often used to enhance the image contrast between the tissue of interest and surrounding tissues with MRI. The most commonly used MRI contrast agents contain Gd(III) ions. However, Gd(III) ions are highly toxic in their ionic form, as they tend to accumulate in the liver, spleen, kidney and bones and block calcium channels. Endohedral metallofullerenes such as trimetallic nitride endohedral metallofullerenes (Trimetasphere®) are one unique class of fullerene molecules where a Gd3N cluster is encapsulated inside a C80 carbon cage referred to as Gd3N@C80. These endohedral metallofullerenes have several advantages over small chelated Gd(III) complexes such as increased stability of the Gd(III) ion, minimal toxic effects, high solubility in water and high proton relativity. In this study, we describe the evaluation of gadolinium-based Trimetasphere® positive contrast agent for the ​in vitro labeling and in vivo tracking of human amniotic fluid-derived stem cells within lung tissue. In addition, we conducted a 'proof-of-concept' experiment demonstrating that this methodology can be used to track the homing of stem cells to injured lung tissue and provide longitudinal analysis of cell localization over an extended time course. Copyright © 2015 Elsevier Inc. All rights reserved.

Are iso-osmolar, as compared to low-osmolar, contrast media cost-effective in patients undergoing cardiac catheterization? An economic analysis.

PubMed

Hiremath, Swapnil; Akbari, Ayub; Wells, George A; Chow, Benjamin J W

2018-04-23

Contrast-induced acute kidney injury is a prominent complication following cardiac catheterization, though the risk has progressively decreased in recent times with appropriate risk stratification and use of safer contrast agents. Despite data supporting further lowering of risk with the iso-osmolar agent, iodixanol, uptake has lagged, perhaps due to increased upfront cost of this agent. We undertook an economic analysis to estimate the cost-effectiveness of a strategy utilizing iodixanol compared to using a low-osmolar contrast agent. We created a Markov model to evaluate the two strategies, and included a differential relative risk of contrast-induced acute kidney injury, based on a systematic review of the literature. Downstream clinical events, including need for dialysis and mortality, were modeled using data from existing published literature. A third-party payer perspective was utilized for the analysis and presentation of the primary economic analysis. The strategy of using iodixanol dominated in both the low-risk and high-risk base case analyses. However, the difference was quite small in the low-risk scenario (lifetime cost: C$678,034 vs. C$678,059 and life expectancy: 19.80 vs. 19.72 years). The difference was more marked (life expectancy 15.65 vs. 14.15 years and cost C$680,989 vs. C$682,023) in the high-risk case analysis. This was robust across most of the variables tested in sensitivity analyses. The use of iodixanol, compared with low-osmolar contrast agents, for cardiac catheterization, results in a small benefit clinical outcomes, and in a savings in direct healthcare costs. Overall, our analysis supports the use of iodixanol for cardiac catheterization, especially in patients at high risk of acute kidney injury.

Recent advances in the imaging of hepatocellular carcinoma. From ultrasound to positron emission tomography scan.

PubMed

Camaggi, Valeria; Piscaglia, Fabio; Bolondi, Luigi

2007-07-01

Recent advances in imaging techniques for hepatocellular carcinoma (HCC) offer the possibility of investigating contrast perfusion of liver nodules in cirrhosis. It is now accepted that a non-invasive diagnosis of HCC can be established based on the vascular pattern obtained with pure blood pool contrast agents. The diagnostic pattern consists of contrast enhancement in the arterial phase, indicative of arterial hypervascularization, followed by contrast wash out in the portal and late phases, which leads the nodule to show the same, or, more specifically, a lower contrast signal than the surrounding parenchyma. Such patterns can be obtained by CT, MRI and, more recently, by real time Contrast Enhanced Ultrasonography with second-generation ultrasound contrast agents. A typical vascular pattern in a nodule perceptible also without contrast is highly specific for HCC, so that non-invasive diagnostic algorithms have been developed and recently updated.

MRI and CT contrast media extravasation

PubMed Central

Heshmatzadeh Behzadi, Ashkan; Farooq, Zerwa; Newhouse, Jeffery H.; Prince, Martin R.

2018-01-01

Abstract Background: This systematic review combines data from multiple papers on contrast media extravasation to identify factors contributing to increased extravasation risk. Methods: Data were extracted from 17 papers reporting 2191 extravasations in 1,104,872 patients (0.2%) undergoing computed tomography (CT) or magnetic resonance imaging (MRI). Results: Extravasation rates were 0.045% for gadolinium-based contrast agents (GBCA) and nearly 6-fold higher, 0.26% for iodinated contrast agents. Factors associated with increased contrast media extravasations included: older age, female gender, using an existing intravenous (IV) instead of placing a new IV in radiology, in-patient status, use of automated power injection, high injection rates, catheter location, and failing to warm up the more viscous contrast media to body temperature. Conclusion: Contrast media extravasation is infrequent but nearly 6 times less frequent with GBCA for MRI compared with iodinated contrast used in CT. PMID:29489663

Using T2-Exchange from Ln3+DOTA-Based Chelates for Contrast-Enhanced Molecular Imaging of Prostate Cancer with MRI

DTIC Science & Technology

2015-04-01

antigen ( PSMA ) of prostate cancer cells would then be synthesized and tested with both in vitro and in vivo experiments. Major Findings: We found that the...simplified chemistry. 15. SUBJECT TERMS MRI Contrast Agent, T2 contrast, Prostate Cancer, PSMA Targeted Agent, Early Detection and Diagnosis, Dysprosium... PSMA ), which is significantly over-expressed by prostate cancer cells, has proven to be an excellent target for imaging prostate cancer in mouse

Liver Masses: What Physicians Need to Know About Ordering and Interpreting Liver Imaging.

PubMed

Sheybani, Arman; Gaba, Ron C; Lokken, R Peter; Berggruen, Senta M; Mar, Winnie A

2017-10-18

This paper reviews diagnostic imaging techniques used to characterize liver masses and the imaging characteristics of the most common liver masses. The role of recently adopted ultrasound and magnetic resonance imaging contrast agents will be emphasized. Contrast-enhanced ultrasound is an inexpensive exam which can confirm benignity of certain liver masses without ionizing radiation. Magnetic resonance imaging using hepatocyte-specific gadolinium-based contrast agents can help confirm or narrow the differential diagnosis of liver masses.

Membrane Cholesterol Modulates Superwarfarin Toxicity

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

Marangoni, M. Natalia; Martynowycz, Michael W.; Kuzmenko, Ivan

Superwarfarins are modified analogs of warfarin with additional lipophilic aromatic rings, up to 100-fold greater potency, and longer biological half-lives. We hypothesized that increased hydrophobicity allowed interactions with amphiphilic membranes and modulation of biological responses. We find that superwarfarins brodifacoum and difenacoum increase lactate production and cell death in neuroblastoma cells. In contrast, neither causes changes in glioma cells that have higher cholesterol content. After choleterol depletion, lactate production was increased and cell viability was reduced. Drug-membrane interactions were examined by surface X-ray scattering using Langmuir monolayers of dipalmitoylphosphatidylcholine and/or cholesterol. Specular X-ray reflectivity data revealed that superwarfarins, but notmore » warfarin, intercalate between dipalmitoylphosphatidylcholine molecules, whereas grazing incidence X-ray diffraction demonstrated changes in lateral crystalline order of the film. Neither agent showed significant interactions with monolayers containing >20% cholesterol. These findings demonstrate an affinity of superwarfarins to biomembranes and suggest that cellular responses to these agents are regulated by cholesterol content.« less

Distinct gene expression profiles in peripheral blood mononuclear cells from patients infected with vaccinia virus, yellow fever 17D virus, or upper respiratory infections.

PubMed

Scherer, Christina A; Magness, Charles L; Steiger, Kathryn V; Poitinger, Nicholas D; Caputo, Christine M; Miner, Douglas G; Winokur, Patricia L; Klinzman, Donna; McKee, Janice; Pilar, Christine; Ward, Patricia A; Gillham, Martha H; Haulman, N Jean; Stapleton, Jack T; Iadonato, Shawn P

2007-08-29

Gene expression in human peripheral blood mononuclear cells was systematically evaluated following smallpox and yellow fever vaccination, and naturally occurring upper respiratory infection (URI). All three infections were characterized by the induction of many interferon stimulated genes, as well as enhanced expression of genes involved in proteolysis and antigen presentation. Vaccinia infection was also characterized by a distinct expression signature composed of up-regulation of monocyte response genes, with repression of genes expressed by B and T-cells. In contrast, the yellow fever host response was characterized by a suppression of ribosomal and translation factors, distinguishing this infection from vaccinia and URI. No significant URI-specific signature was observed, perhaps reflecting greater heterogeneity in the study population and etiological agents. Taken together, these data suggest that specific host gene expression signatures may be identified that distinguish one or a small number of virus agents.

Dual-Energy Micro-CT Functional Imaging of Primary Lung Cancer in Mice Using Gold and Iodine Nanoparticle Contrast Agents: A Validation Study

PubMed Central

Ashton, Jeffrey R.; Clark, Darin P.; Moding, Everett J.; Ghaghada, Ketan; Kirsch, David G.; West, Jennifer L.; Badea, Cristian T.

2014-01-01

Purpose To provide additional functional information for tumor characterization, we investigated the use of dual-energy computed tomography for imaging murine lung tumors. Tumor blood volume and vascular permeability were quantified using gold and iodine nanoparticles. This approach was compared with a single contrast agent/single-energy CT method. Ex vivo validation studies were performed to demonstrate the accuracy of in vivo contrast agent quantification by CT. Methods Primary lung tumors were generated in LSL-KrasG12D; p53FL/FL mice. Gold nanoparticles were injected, followed by iodine nanoparticles two days later. The gold accumulated in tumors, while the iodine provided intravascular contrast. Three dual-energy CT scans were performed–two for the single contrast agent method and one for the dual contrast agent method. Gold and iodine concentrations in each scan were calculated using a dual-energy decomposition. For each method, the tumor fractional blood volume was calculated based on iodine concentration, and tumor vascular permeability was estimated based on accumulated gold concentration. For validation, the CT-derived measurements were compared with histology and inductively-coupled plasma optical emission spectroscopy measurements of gold concentrations in tissues. Results Dual-energy CT enabled in vivo separation of gold and iodine contrast agents and showed uptake of gold nanoparticles in the spleen, liver, and tumors. The tumor fractional blood volume measurements determined from the two imaging methods were in agreement, and a high correlation (R2 = 0.81) was found between measured fractional blood volume and histology-derived microvascular density. Vascular permeability measurements obtained from the two imaging methods agreed well with ex vivo measurements. Conclusions Dual-energy CT using two types of nanoparticles is equivalent to the single nanoparticle method, but allows for measurement of fractional blood volume and permeability with a single scan. As confirmed by ex vivo methods, CT-derived nanoparticle concentrations are accurate. This method could play an important role in lung tumor characterization by CT. PMID:24520351

Prostate-specific membrane antigen targeted protein contrast agents for molecular imaging of prostate cancer by MRI†

PubMed Central

Pu, Fan; Salarian, Mani; Xue, Shenghui; Qiao, Jingjuan; Feng, Jie; Tan, Shanshan; Patel, Anvi; Li, Xin; Mamouni, Kenza; Hekmatyar, Khan; Zou, Juan; Wu, Daqing

2017-01-01

Prostate-specific membrane antigen (PSMA) is one of the most specific cell surface markers for prostate cancer diagnosis and targeted treatment. However, achieving molecular imaging using non-invasive MRI with high resolution has yet to be achieved due to the lack of contrast agents with significantly improved relaxivity for sensitivity, targeting capabilities and metal selectivity. We have previously reported our creation of a novel class of protein Gd3+ contrast agents, ProCA32, which displayed significantly improved relaxivity while exhibiting strong Gd3+ binding selectivity over physiological metal ions. In this study, we report our effort in further developing biomarker-targeted protein MRI contrast agents for molecular imaging of PSMA. Among three PSMA targeted contrast agents engineered with addition of different molecular recognition sequences, ProCA32.PSMA exhibits a binding affinity of 1.1 ± 0.1 μM for PSMA while the metal binding affinity is maintained at 0.9 ± 0.1 × 10−22 M. In addition, ProCA32.PSMA exhibits r1 of 27.6 mM−1 s−1 and r2 of 37.9 mM−1 s−1 per Gd (55.2 and 75.8 mM−1 s−1 per molecule r1 and r2, respectively) at 1.4 T. At 7 T, ProCA32.PSMA also has r2 of 94.0 mM−1 s−1 per Gd (188.0 mM−1 s−1 per molecule) and r1 of 18.6 mM−1 s−1 per Gd (37.2 mM−1 s−1 per molecule). This contrast capability enables the first MRI enhancement dependent on PSMA expression levels in tumor bearing mice using both T1 and T2-weighted MRI at 7 T. Further development of these PSMA-targeted contrast agents are expected to be used for the precision imaging of prostate cancer at an early stage and to monitor disease progression and staging, as well as determine the effect of therapeutic treatment by non-invasive evaluation of the PSMA level using MRI. PMID:26961235

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. Copyright © 2012 John Wiley & Sons, Ltd.

Cytotoxic Effects of Nonionic Iodinated Contrast Agent on Human Adipose-derived Mesenchymal Stem Cells.

PubMed

Wu, Tao; Nie, Hai; Dietz, Allan B; Salek, David R; Smith, Jay; van Wijnen, Andre J; Qu, Wenchun

2018-05-31

Transplantation of mesenchymal stem cells (MSCs) is a promising therapy for degenerative spine conditions. However, cell therapy for painful spine degeneration presently requires use of contrast agents during fluoroscopy-guided injections and the effects of these agents on MSCs represents a gap in knowledge. To investigate the biological effects of contrast media that are co-injected with MSCs. Prospective observational study. Academic medical center. Patient-derived clinical-grade culture expanded MSCs. Iohexol(Omnipaque300) was reduced to 12.5%, 25%, 50% and 100% of the stock solution and incubated with MSCs for 30 minutes, 4 hours and 48 hours. We also used complete media and 12.5%, 25%, 50%, 100% of phosphate buffered saline (PBS) as control group. We examined cytotoxicity of Iohexol at different concentrations and exposure duration, as well as the potential for recovery over time. Cell counts, mitochondrial activity, and quantitative real time reverse-transcriptase polymerase chain reaction (qRT-PCR) of related genes were analyzed immediately after exposure (day 0) and after two days of exposure (day 2). Human MSCs exhibit a time- and concentration-dependent cytotoxic response to iodinated CM. A brief 30min exposure did not affect MSCs function and viability. However, extended treatment with iohexol for 4 hours at 50% or higher concentration had a significant impact on both viability and gene expression in MSCs. CM (Omnipaque300) is cytotoxic to MSCs in a time-and concentration-dependent manner. Hence, the concentration of CM that accompanies MSC injections should be carefully considered during mesenchymal stem cell therapy for disc degenerative diseases. Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

A gene expression profile indicative of early stage HER2 targeted therapy response.

PubMed

O'Neill, Fiona; Madden, Stephen F; Clynes, Martin; Crown, John; Doolan, Padraig; Aherne, Sinéad T; O'Connor, Robert

2013-07-01

Efficacious application of HER2-targetting agents requires the identification of novel predictive biomarkers. Lapatinib, afatinib and neratinib are tyrosine kinase inhibitors (TKIs) of HER2 and EGFR growth factor receptors. A panel of breast cancer cell lines was treated with these agents, trastuzumab, gefitinib and cytotoxic therapies and the expression pattern of a specific panel of genes using RT-PCR was investigated as a potential marker of early drug response to HER2-targeting therapies. Treatment of HER2 TKI-sensitive SKBR3 and BT474 cell lines with lapatinib, afatinib and neratinib induced an increase in the expression of RB1CC1, ERBB3, FOXO3a and NR3C1. The response directly correlated with the degree of sensitivity. This expression pattern switched from up-regulated to down-regulated in the HER2 expressing, HER2-TKI insensitive cell line MDAMB453. Expression of the CCND1 gene demonstrated an inversely proportional response to drug exposure. A similar expression pattern was observed following the treatment with both neratinib and afatinib. These patterns were retained following exposure to traztuzumab and lapatinib plus capecitabine. In contrast, gefitinib, dasatinib and epirubicin treatment resulted in a completely different expression pattern change. In these HER2-expressing cell line models, lapatinib, neratinib, afatinib and trastuzumab treatment generated a characteristic and specific gene expression response, proportionate to the sensitivity of the cell lines to the HER2 inhibitor.Characterisation of the induced changes in expression levels of these genes may therefore give a valuable, very early predictor of the likely extent and specificity of tumour HER2 inhibitor response in patients, potentially guiding more specific use of these agents.

A gene expression profile indicative of early stage HER2 targeted therapy response

PubMed Central

2013-01-01

Background Efficacious application of HER2-targetting agents requires the identification of novel predictive biomarkers. Lapatinib, afatinib and neratinib are tyrosine kinase inhibitors (TKIs) of HER2 and EGFR growth factor receptors. A panel of breast cancer cell lines was treated with these agents, trastuzumab, gefitinib and cytotoxic therapies and the expression pattern of a specific panel of genes using RT-PCR was investigated as a potential marker of early drug response to HER2-targeting therapies. Results Treatment of HER2 TKI-sensitive SKBR3 and BT474 cell lines with lapatinib, afatinib and neratinib induced an increase in the expression of RB1CC1, ERBB3, FOXO3a and NR3C1. The response directly correlated with the degree of sensitivity. This expression pattern switched from up-regulated to down-regulated in the HER2 expressing, HER2-TKI insensitive cell line MDAMB453. Expression of the CCND1 gene demonstrated an inversely proportional response to drug exposure. A similar expression pattern was observed following the treatment with both neratinib and afatinib. These patterns were retained following exposure to traztuzumab and lapatinib plus capecitabine. In contrast, gefitinib, dasatinib and epirubicin treatment resulted in a completely different expression pattern change. Conclusions In these HER2-expressing cell line models, lapatinib, neratinib, afatinib and trastuzumab treatment generated a characteristic and specific gene expression response, proportionate to the sensitivity of the cell lines to the HER2 inhibitor. Characterisation of the induced changes in expression levels of these genes may therefore give a valuable, very early predictor of the likely extent and specificity of tumour HER2 inhibitor response in patients, potentially guiding more specific use of these agents. PMID:23816254

WE-H-207A-08: Characterization of a Broad-Spectrum Cancer Targeted MRI Contrast Agent

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

Brunnquell, C; Zhang, R; Pinchuk, A

Purpose: To characterize the relaxation properties and tumor targeting capabilities of a novel alkylphosphocholine (APC) analog MR contrast agent, Gd-DO3A-404. Methods: Relaxivities were measured via T1 and T2 mapping of Gd-DO3A-404 with inversion recovery and spin echo pulse sequences, respectively. Uptake was characterized in flank xenograft models of non-small cell lung cancer (A549) and glioma (U87) and compared with uptake of Dotarem. Mice (N=3 per model per agent) were delivered 2.34 moles contrast intravenously. T1-weighted MRI and T1 maps were acquired pre-contrast and at multiple time points up to seven days post-contrast. For Dotarem imaging, T1-weighted MRI was performed atmore » multiple time points from one minute to one day. Results: Relaxivities of Gd-DO3A-404 in plasma were r1=5.74 and r2=20.4 s-1/mm at 4.7T, comparing favorably to clinical contrast agent Dotarem (r1=3.3, r2=4.7). Specific, sustained uptake of Gd-DO3A-404 was observed in U87 and A549. The ratio of tumor:muscle T1-weighted signal increased from 1.24 pre-contrast to 2.12 twenty-four hours post-contrast in U87 and from 1.14 to 2.16 (same time points) in A549. Significant signal enhancement was maintained until 7 and 4 days post-contrast in U87 and A549, respectively. In comparison, uptake and washout of Dotarem in U87 occurred over the course of fifteen minutes. The ratio of tumor:muscle T1-weighted signal increased only 59% as much as Gd-DO3A-404, ranging from 1.15 pre-contrast to a maximum of 1.67 five minutes post-contrast. Significant signal enhancement from Dotarem was not sustained beyond one hour post-contrast. Conclusion: These results indicate that with favorable relaxation characteristics and sustained signal-enhancing uptake in multiple tumor models, Gd-DO3A-404 has great potential as a tumor-targeting MR contrast agent. As part of a library of APC analogs labeled with PET/optical tracers and therapeutic radionuclides, Gd-DO3A-404 further expands theranostic capabilities. Future work will investigate applications in orthotopic glioma imaging, simultaneous PET/MR, and neutron capture therapy.« less

Nonlinear ultrasound imaging of nanoscale acoustic biomolecules

NASA Astrophysics Data System (ADS)

Maresca, David; Lakshmanan, Anupama; Lee-Gosselin, Audrey; Melis, Johan M.; Ni, Yu-Li; Bourdeau, Raymond W.; Kochmann, Dennis M.; Shapiro, Mikhail G.

2017-02-01

Ultrasound imaging is widely used to probe the mechanical structure of tissues and visualize blood flow. However, the ability of ultrasound to observe specific molecular and cellular signals is limited. Recently, a unique class of gas-filled protein nanostructures called gas vesicles (GVs) was introduced as nanoscale (˜250 nm) contrast agents for ultrasound, accompanied by the possibilities of genetic engineering, imaging of targets outside the vasculature and monitoring of cellular signals such as gene expression. These possibilities would be aided by methods to discriminate GV-generated ultrasound signals from anatomical background. Here, we show that the nonlinear response of engineered GVs to acoustic pressure enables selective imaging of these nanostructures using a tailored amplitude modulation strategy. Finite element modeling predicted a strongly nonlinear mechanical deformation and acoustic response to ultrasound in engineered GVs. This response was confirmed with ultrasound measurements in the range of 10 to 25 MHz. An amplitude modulation pulse sequence based on this nonlinear response allows engineered GVs to be distinguished from linear scatterers and other GV types with a contrast ratio greater than 11.5 dB. We demonstrate the effectiveness of this nonlinear imaging strategy in vitro, in cellulo, and in vivo.

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

NASA Astrophysics Data System (ADS)

Wang, Jianxin Steven

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

Use of Radiocontrast Agents in CKD and ESRD.

PubMed

Bahrainwala, Jehan Z; Leonberg-Yoo, Amanda K; Rudnick, Michael R

2017-07-01

Contrast exposure in a population with chronic kidney disease (CKD) requires additional consideration given the risk of contrast-induced nephropathy (CIN) after exposure to iodinated contrast as well as systemic injury with exposure to gadolinium-based contrast agents (GBCA). Strategies to avoid CIN, and manage patients after exposure, including extracorporeal removal of contrast media, may differ among an advanced CKD population as compared to a general population. There is strong evidence to support the use of isotonic volume expansion and the lowest dose of low-osmolar or iso-osmolar contrast media possible to decrease CIN. The current literature on other newer prophylactic strategies such as statins, remote ischemic preconditioning, discontinuation of renin angiotensin aldosterone system (RAAS) blockade, and RenalGuard is limited thus these strategies cannot currently be recommended as routine prophylaxis for CIN. The use of extracorporeal removal of contrast agents as prophylaxis to reduce CIN has been the subject of multiple studies; however, data do not support a beneficial effect in reduction in CIN. Immediate removal of contrast by dialysis in a maintenance dialysis population is also not recommended, unless an individual's cardiopulmonary status is dependent on strict volume management. In patients with reduced renal function, GCBA exposure increases the risk of NSF. In patients with AKI, CKD stage 3 or greater (eGFR <30 ml/minute/1.73 m 2 ), or patients on dialysis, we do not recommend the use of GBCA and alternative imaging modalities should be considered. If patients absolutely need magnetic resonance imaging with GBCA, we recommend the use of the lowest dose possible of the newer macrocylic, ionic agents (gadoterate meglumine) as well as immediate postprocedural HD in patients already on HD or peritoneal dialysis or with stage 5 CKD and with a functioning dialysis access already in place. © 2017 Wiley Periodicals, Inc.

Comparison of arterial input functions measured from ultra-fast dynamic contrast enhanced MRI and dynamic contrast enhanced computed tomography in prostate cancer patients

NASA Astrophysics Data System (ADS)

Wang, Shiyang; Lu, Zhengfeng; Fan, Xiaobing; Medved, Milica; Jiang, Xia; Sammet, Steffen; Yousuf, Ambereen; Pineda, Federico; Oto, Aytekin; Karczmar, Gregory S.

2018-02-01

The purpose of this study was to evaluate the accuracy of arterial input functions (AIFs) measured from dynamic contrast enhanced (DCE) MRI following a low dose of contrast media injection. The AIFs measured from DCE computed tomography (CT) were used as ‘gold standard’. A total of twenty patients received CT and MRI scans on the same day. Patients received 120 ml Iohexol in DCE-CT and a low dose of (0.015 mM kg-1) of gadobenate dimeglumine in DCE-MRI. The AIFs were measured in the iliac artery and normalized to the CT and MRI contrast agent doses. To correct for different temporal resolution and sampling periods of CT and MRI, an empirical mathematical model (EMM) was used to fit the AIFs first. Then numerical AIFs (AIFCT and AIFMRI) were calculated based on fitting parameters. The AIFMRI was convolved with a ‘contrast agent injection’ function (AIFMRICON ) to correct for the difference between MRI and CT contrast agent injection times (~1.5 s versus 30 s). The results show that the EMMs accurately fitted AIFs measured from CT and MRI. There was no significant difference (p  >  0.05) between the maximum peak amplitude of AIFs from CT (22.1  ±  4.1 mM/dose) and MRI after convolution (22.3  ±  5.2 mM/dose). The shapes of the AIFCT and AIFMRICON were very similar. Our results demonstrated that AIFs can be accurately measured by MRI following low dose contrast agent injection.

78 FR 77471 - Prospective Grant of Exclusive License for: Convection Enhanced Delivery of a Therapeutic Agent...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-23

...-toxic macromolecular MRI contrast agents such as chelated Gd(III). These macromolecular imaging agents... Exclusive License for: Convection Enhanced Delivery of a Therapeutic Agent With a Surrogate Tracer for... Enhanced Delivery of Therapeutic Agents'', U.S. Provisional Patent Application 60/413,673 (filed September...

Evaluation of Eu(II) -based positive contrast enhancement after intravenous, intraperitoneal, and subcutaneous injections.

PubMed

Ekanger, Levi A; Polin, Lisa A; Shen, Yimin; Haacke, E Mark; Allen, Matthew J

2016-07-01

Eu(II) -based contrast agents offer physiologically relevant, metal-based redox sensing that is unachievable with Gd(III) -based contrast agents. To evaluate the in vivo contrast enhancement of Eu(II) as a function of injection type, we performed intravenous, intraperitoneal, and subcutaneous injections in mice. Our data reveal a correlation between reported oxygen content and expected rates of diffusion with the persistence of Eu(II) -based contrast enhancement. Biodistribution studies revealed europium clearance through the liver and kidneys for intravenous and intraperitoneal injections, but no contrast enhancement was observed in organs associated with clearance. These data represent a step toward understanding the behavior of Eu(II) -based complexes in vivo. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Imaging efficiency of an X-ray contrast agent-incorporated polymeric microparticle.

PubMed

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

2011-01-01

Biocompatible polymeric encapsulants have been widely used as a delivery vehicle for a variety of drugs and imaging agents. In this study, X-ray contrast agent (iopamidol) is encapsulated into a polymeric microparticle (polyvinyl alcohol) as a particulate flow tracer in synchrotron X-ray imaging system. The physical properties of the designed microparticles are investigated and correlated with enhancement in the imaging efficiency by experimental observation and theoretical interpretation. The X-ray absorption ability of the designed microparticle is assessed by Beer-Lambert-Bouguer law. Particle size, either in dried state or in solvent, primarily dominates the X-ray absorption ability under the given condition, thus affecting imaging efficiency of the designed X-ray contrast flow tracers. Copyright © 2011 John Wiley & Sons, Ltd.

Semiconducting polymer dot as a highly effective contrast agent for photoacoustic imaging

NASA Astrophysics Data System (ADS)

Yuan, Zhen; Zhang, Jian

2018-02-01

In this study, we developed a novel PIID-DTBT based semiconducting polymer dots (Pdots) that have broad and strong optical absorption in the visible-light region (500 nm - 700 nm). Gold nanoparticles (GNPs) and gold nanorods (GNRs) that have been verified as an excellent photoacoustic contrast agent were compared with Pdots based on photoacoustic imaging method. Both ex vivo and in vivo experiment demonstrated Pdots have a better photoacoustic conversion efficiency at 532 nm than GNPs and similar photoacoustic performance with GNRs at 700 nm at the same mass concentration. Our work demonstrates the great potential of Pdots as a highly effective contrast agent for precise localization of lesions relative to the blood vessels based on photoacoustic tomography imaging.

Engineering Gd-loaded nanoparticles to enhance MRI sensitivity via T1 shortening

NASA Astrophysics Data System (ADS)

Bruckman, Michael A.; Yu, Xin; Steinmetz, Nicole F.

2013-11-01

Magnetic resonance imaging (MRI) is a noninvasive imaging technique capable of obtaining high-resolution anatomical images of the body. Major drawbacks of MRI are the low contrast agent sensitivity and inability to distinguish healthy tissue from diseased tissue, making early detection challenging. To address this technological hurdle, paramagnetic contrast agents have been developed to increase the longitudinal relaxivity, leading to an increased signal-to-noise ratio. This review focuses on methods and principles that enabled the design and engineering of nanoparticles to deliver contrast agents with enhanced ionic relaxivities. Different engineering strategies and nanoparticle platforms will be compared in terms of their manufacturability, biocompatibility properties, and their overall potential to make an impact in clinical MR imaging.

The Complexities of Urban Flood Response: Hydrologic Analyses for the Charlotte, North Carolina Metropolitan Region

NASA Astrophysics Data System (ADS)

Zhou, Z.; Smith, J. A.; Yang, L.; Baeck, M. L.; Liu, S.; Ten Veldhuis, M. C.

2016-12-01

The objective of this study is to develop a broad characterization of land surface and hydrometeorological controls of urban flood frequency. We focus on a collection of "small" urban watersheds (with drainage area ranging from 7 to 200 km2) in Charlotte metropolitan region, North Carolina. These watersheds are contrasted by a variety of land surface properties, such as size, shape, land use/land cover type, impervious coverage pattern, stormwater infrastructure, etc. We carried out empirical analyses based on long-term (15 years), high-resolution (1 15 minutes) instantaneous USGS stream gaging observations as well as bias-corrected, high-resolution (1 km2, 15 min) radar rainfall fields developed through the Hydro-NEXRAD system. Extreme floods in Charlotte urban watersheds are primarily induced by a mixture of flood agents including warm season thunderstorms and tropical cyclones, which ultimately contributed to the upper-tail properties of flood frequency. Flood response in urban watersheds is dominantly dictated by space-time characteristics of rainfall, with relatively significant correlation between runoff and rainfall over more developed watersheds. The roles of antecedent soil moisture and stormwater management infrastructure in flood response are also contrasted across the urban watersheds. The largest variability of flood response, in terms of flood peak and timing, exists in the watershed at a scale of 100 km2. The scale-dependent hydrological response is closely related to the pattern and evolution of urban development across watersheds. Our analyses show the complexities of urban flood response in Charlotte metropolitan region. There are no simple metrics that could perfectly explain the contrasts in flood response across urban watersheds. Future research is directed towards sophisticated modeling studies for a predictive understanding of flood frequency in urban watersheds.

Biocompatible Nanocomplexes for Molecular Targeted MRI Contrast Agent

NASA Astrophysics Data System (ADS)

Chen, Zhijin; Yu, Dexin; Wang, Shaojie; Zhang, Na; Ma, Chunhong; Lu, Zaijun

2009-07-01

Accurate diagnosis in early stage is vital for the treatment of Hepatocellular carcinoma. The aim of this study was to investigate the potential of poly lactic acid-polyethylene glycol/gadolinium-diethylenetriamine-pentaacetic acid (PLA-PEG/Gd-DTPA) nanocomplexes using as biocompatible molecular magnetic resonance imaging (MRI) contrast agent. The PLA-PEG/Gd-DTPA nanocomplexes were obtained using self-assembly nanotechnology by incubation of PLA-PEG nanoparticles and the commercial contrast agent, Gd-DTPA. The physicochemical properties of nanocomplexes were measured by atomic force microscopy and photon correlation spectroscopy. The T1-weighted MR images of the nanocomplexes were obtained in a 3.0 T clinical MR imager. The stability study was carried out in human plasma and the distribution in vivo was investigated in rats. The mean size of the PLA-PEG/Gd-DTPA nanocomplexes was 187.9 ± 2.30 nm, and the polydispersity index was 0.108, and the zeta potential was -12.36 ± 3.58 mV. The results of MRI test confirmed that the PLA-PEG/Gd-DTPA nanocomplexes possessed the ability of MRI, and the direct correlation between the MRI imaging intensities and the nano-complex concentrations was observed ( r = 0.987). The signal intensity was still stable within 2 h after incubation of the nanocomplexes in human plasma. The nanocomplexes gave much better image contrast effects and longer stagnation time than that of commercial contrast agent in rat liver. A dose of 0.04 mmol of gadolinium per kilogram of body weight was sufficient to increase the MRI imaging intensities in rat livers by five-fold compared with the commercial Gd-DTPA. PLA-PEG/Gd-DTPA nanocomplexes could be prepared easily with small particle sizes. The nanocomplexes had high plasma stability, better image contrast effect, and liver targeting property. These results indicated that the PLA-PEG/Gd-DTPA nanocomplexes might be potential as molecular targeted imaging contrast agent.

Influence of the timing of cardiac catheterization and amount of contrast media on acute renal failure after cardiac surgery.

PubMed

Sadeghi, Mohsen Mirmohammad; Gharipour, Mojgan; Nilforoush, Peiman; Shamsolkotabi, Hamid; Sadeghi, Hamid Mirmohammad; Kiani, Amjad; Sadeghi, Pouya Mirmohammad; Farahmand, Niloufar

2011-04-01

There is limited data about the influence of timing of cardiac surgery in relation to diagnostic angiography and/or the impact of the amount of contrast media used during angiography on the occurance of acute renal failure (ARF). Therefore, in the present study the effect of the time interval between diagnostic angiography and cardiac surgery and also the amount of contrast media used during the diagnostic procedure on the incidence of ARF after cardiac surgery was investigated. Data of 1177 patients who underwent different types of cardiac surgeries after cardiac catheterization were prospectively examined. The influence of time interval between cardiac catheterization and surgery as well as the amount of contrast agent on postoperative ARF were assessed using multivariable logistic regression. The patients who progressed to ARF were more likely to have received a higher dose of contrast agent compared to the mean dose. However, the time interval between cardiac surgery and last catheterization was not significantly different between the patients with and without ARF (p = 0.05). Overall, postoperative peak creatinine was highest on day 0, then decreased and remained significantly unchanged after this period. Overall prevalence of acute renal failure during follow-up period had a changeable trend and had the highest rates in days 1 (53.57%) and 6 (52.17%) after surgery. Combined coronary bypass and valve surgery were the strongest predictor of postoperative ARF (OR: 4.976, CI = 1.613-15.355 and p = 0.002), followed by intra-aortic balloon pump insertion (OR: 6.890, CI = 1.482-32.032 and p = 0.009) and usage of higher doses of contrast media agent (OR: 1.446, CI = 1.033-2.025 and p = 0.031). Minimizing the amount of contrast agent has a potential role in reducing the incidence of postoperative ARF in patients undergoing cardiac surgery, but delaying cardiac surgery after exposure to these agents might not have this protective effect.

Towards endometriosis diagnosis by gadofosveset-trisodium enhanced magnetic resonance imaging.

PubMed

Schreinemacher, Marc H; Backes, Walter H; Slenter, Jos M; Xanthoulea, Sofia; Delvoux, Bert; van Winden, Larissa; Beets-Tan, Regina G; Evers, Johannes L H; Dunselman, Gerard A J; Romano, Andrea

2012-01-01

Endometriosis is defined as the presence of endometrial tissue outside the uterus. It affects 10-15% of women during reproductive age and has a big personal and social impact due to chronic pelvic pain, subfertility, loss of work-hours and medical costs. Such conditions are exacerbated by the fact that the correct diagnosis is made as late as 8-11 years after symptom presentation. This is due to the lack of a reliable non-invasive diagnostic test and the fact that the reference diagnostic standard is laparoscopy (invasive, expensive and not without risks). High-molecular weight gadofosveset-trisodium is used as contrast agent in Magnetic Resonance Imaging (MRI). Since it extravasates from hyperpermeable vessels more easily than from mature blood vessels, this contrast agent detects angiogenesis efficiently. Endometriosis has high angiogenic activity. Therefore, we have tested the possibility to detect endometriosis non-invasively using Dynamic Contrast-Enhanced MRI (DCE-MRI) and gadofosveset-trisodium as a contrast agent in a mouse model. Endometriotic lesions were surgically induced in nine mice by autologous transplantation. Three weeks after lesion induction, mice were scanned by DCE-MRI. Dynamic image analysis showed that the rates of uptake (inwash), persistence and outwash of the contrast agent were different between endometriosis and control tissues (large blood vessels and back muscle). Due to the extensive angiogenesis in induced lesions, the contrast agent persisted longer in endometriotic than control tissues, thus enhancing the MRI signal intensity. DCE-MRI was repeated five weeks after lesion induction, and contrast enhancement was similar to that observed three weeks after endometriosis induction. The endothelial-cell marker CD31 and the pericyte marker α-smooth-muscle-actin (mature vessels) were detected with immunohistochemistry and confirmed that endometriotic lesions had significantly higher prevalence of new vessels (CD31 only positive) than the uterus and control tissues. The diagnostic value of gadofosveset-trisodium to detect endometriosis should be tested in human settings.

MRI contrast agent for targeting glioma: interleukin-13 labeled liposome encapsulating gadolinium-DTPA.

PubMed

Liu, Xiaoli; Madhankumar, Achuthamangalam B; Miller, Patti A; Duck, Kari A; Hafenstein, Susan; Rizk, Elias; Slagle-Webb, Becky; Sheehan, Jonas M; Connor, James R; Yang, Qing X

2016-05-01

Detection of glioma with MRI contrast agent is limited to cases in which the blood-brain barrier (BBB) is compromised as contrast agents cannot cross the BBB. Thus, an early-stage infiltrating tumor is not detectable. Interleukin-13 receptor alpha 2 (IL-13Rα2), which has been shown to be overexpressed in glioma, can be used as a target moiety. We hypothesized that liposomes conjugated with IL-13 and encapsulating MRI contrast agent are capable of passing through an intact BBB and producing MRI contrast with greater sensitivity. The targeted MRI contrast agent was created by encapsulating Magnevist (Gd-DTPA) into liposomes conjugated with IL-13 and characterized by particle size distribution, cytotoxicity, and MRI relaxivity. MR image intensity was evaluated in the brain in normal mice post injection of Gd-DTPA and IL-13-liposome-Gd-DTPA one day apart. The specificity for glioma detection by IL-13-liposome-Gd-DTPA was demonstrated in an intracranial glioma mouse model and validated histologically. The average size of IL-13-liposome-Gd-DTPA was 137 ± 43 nm with relaxivity of 4.0 ± 0.4 L/mmole-s at 7 Tesla. No significant cytotoxicity was observed with MTS assay and serum chemistry in mice. The MRI signal intensity was enhanced up to 15% post injection of IL-13-liposome-Gd-DTPA in normal brain tissue following a similar time course as that for the pituitary gland outside of the BBB. MRI enhanced by IL-13-liposome-Gd-DTPA detected small tumor masses in addition to those seen with Magnevist-enhanced MRI. IL-13-liposome-Gd-DTPA is able to pass through the uncompromised BBB and detect an early stage glioma that cannot be seen with conventional contrast-enhanced MRI. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Nano-assemblies of cationic mPEG brush block copolymers with gadolinium polyoxotungstate [Gd(W5O18)2]9- form stable, high relaxivity MRI contrast agents.

PubMed

Ly, Joanne; Li, Yuhuan; Vu, Mai N; Moffat, Bradford A; Jack, Kevin S; Quinn, John F; Whittaker, Michael R; Davis, Thomas P

2018-04-19

Polyoxometalates (POMs) incorporating paramagnetic ions, such as gadolinium, show promise as contrast agents for application in magnetic resonance imaging (MRI). Specifically, [Gd(W5O18)2]9- (denoted as GdWO) has been reported to have a higher relaxivity than commercially available contrast agents, but it's clinical utility has been limited by the intrinsic instability of POMs at physiological pH (7.4). In the current report we present a stability study on neat GdWO and nano-assemblies of block copolymers with GdWO in the pH range 5.0-7.4 to assess their suitability as MRI contrast agents. Neat GdWO only maintained structural stability between pH 5.4 and 6.4, and demonstrated poor MRI contrast at pH 7.4. To address this pH instability, GdWO was self-assembled with cationic mPEG brush block copolymers containing 20 or 40 units derived from the cationic monomer, 2-dimethylaminoethyl methacrylate (DMAEMA). Nano-assemblies with different charge ratios were synthesised and characterised according to their size, stability, contrasting properties and toxicity. The longitudinal relaxivity (r1) of the nano-assemblies was found to be dependent on the charge ratio, but not on the length of the cationic polymer block. Further investigation of PDMAEMA20 nano-assemblies demonstrated that they were stable over the pH range 5.0-7.4, exhibiting a higher r1 than either neat GdWO (2.77 s-1 mM-1) or clinical MRI contrast agent Gd-DTPA (4.1 s-1 mM-1) at pH 7.4. Importantly, the nano-assembly with the lowest charge ratio (0.2), showed the highest r1 (12.1 s-1 mM-1) whilst, stabilising GdWO over the pH range studied, eliciting low toxicity with MDA-MB231 cells.

New generation of magnetic and luminescent nanoparticles for in vivo real-time imaging

PubMed Central

Lacroix, Lise-Marie; Delpech, Fabien; Nayral, Céline; Lachaize, Sébastien; Chaudret, Bruno

2013-01-01

A new generation of optimized contrast agents is emerging, based on metallic nanoparticles (NPs) and semiconductor nanocrystals for, respectively, magnetic resonance imaging (MRI) and near-infrared (NIR) fluorescent imaging techniques. Compared with established contrast agents, such as iron oxide NPs or organic dyes, these NPs benefit from several advantages: their magnetic and optical properties can be tuned through size, shape and composition engineering, their efficiency can exceed by several orders of magnitude that of contrast agents clinically used, their surface can be modified to incorporate specific targeting agents and antifolding polymers to increase blood circulation time and tumour recognition, and they can possibly be integrated in complex architecture to yield multi-modal imaging agents. In this review, we will report the materials of choice based on the understanding of the basic physics of NIR and MRI techniques and their corresponding syntheses as NPs. Surface engineering, water transfer and specific targeting will be highlighted prior to their first use for in vivo real-time imaging. Highly efficient NPs that are safer and target specific are likely to enter clinical application in a near future. PMID:24427542

Intercellular salicylic acid accumulation during compatible and incompatible Arabidopsis-Pseudomonas syringae interactions

PubMed Central

Wilson, Daniel C; Carella, Philip; Cameron, Robin K

2014-01-01

The phytohormone salicylic acid (SA) plays an important role in several disease resistance responses. During the Age-Related Resistance (ARR) response that occurs in mature Arabidopsis responding to Pseudomonas syringae pv tomato (Pst), SA accumulates in the intercellular space where it may act as an antimicrobial agent. Recently we measured intracellular and intercellular SA levels in young, ARR-incompetent plants responding to virulent and avirulent strains of Pst to determine if intercellular SA accumulation is a component of additional defense responses to Pst. In young plants virulent Pst suppressed both intra- and intercellular SA accumulation in a coronatine-dependent manner. In contrast, high levels of intra- and intercellular SA accumulated in response to avirulent Pst. Our results support the idea that SA accumulation in the intercellular space is an important component of multiple defense responses. Future research will include understanding how mature plants counteract the effects of coronatine during the ARR response. PMID:25763618

Contrast-enhanced near-infrared laser mammography with a prototype breast scanner: feasibility study with tissue phantoms and preliminary results of imaging experimental tumors.

PubMed

Boehm, T; Hochmuth, A; Malich, A; Reichenbach, J R; Fleck, M; Kaiser, W A

2001-10-01

Near-infrared (NIR) optical mammography without contrast has a low specificity. The application of optical contrast medium may improve the performance. The concentration-dependent detectability of a new NIR contrast medium was determined with a prototype optical breast scanner. In vivo imaging of experimental tumors was performed. The NIR contrast agent NIR96010 is a newly synthesized, hydrophilic contrast agent for NIR mammography. A concentration-dependent contrast resolution was determined for tissue phantoms consisting of whole milk powder and gelatin. A central part of the phantoms measuring 2 x 2 cm2 without contrast was replaced with phantom material containing 1 micromol/L to 25 nmol/L NIR96010. The composite phantoms were measured with a prototype NIR breast scanner with lasers of lambda1 = 785 nm and lambda2 = 850 nm wavelength. Intensity profiles and standard deviations of the transmission signal in areas with and without contrast were determined by linear fit procedures. Signal-to-noise ratios and spatial resolution as a function of contrast concentration were determined. Near-infrared imaging of five tumor-bearing SCID mice (MX1 breast adenocarcinoma, tumor diameter 5-10 mm) was performed before and after intravenous application of 2 micromol/kg NIR96010. Spectrometry showed an absorption maximum of the contrast agent at 755 nm. No spectral shifts occurred in protein-containing solution. Signal-to-noise ratio in the transmission intensity profiles ranged from 1.1 at 25 nmol/L contrast to 28 at 1 micromol/L. At concentrations <40 nmol/L, no differentiation from the background was possible. The transitional area between the contrast-free edge of the phantom and the central contrast-containing part appeared in the profiles as a steep increase with a width of 4.2 +/- 1.8 mm. The experimental tumors were detectable in nonenhanced images as well as contrast-enhanced images, with better delineation after contrast administration. In postcontrast absorption profiles, a 44.1% +/- 11.3% greater absorption increase was seen in tumor tissue compared with normal tissue. The laser wavelength lambda1 of the prototype laser mammography device was not situated at maximum absorption of the contrast agent NIR96010 but on the descending shoulder of the absorption spectrum. This implies a 20% signal loss for contrast detection. Despite the nonideal measurement conditions, concentrations as low as 40 nmol/L were detectable in vitro. In vivo, all tumors were detectable in color-coded nonenhanced scans as well as in contrast-enhanced scans, with better delineation after contrast administration.

Tuning the relaxation rates of dual-mode T1/T2 nanoparticle contrast agents: a study into the ideal system

NASA Astrophysics Data System (ADS)

Keasberry, Natasha A.; Bañobre-López, Manuel; Wood, Christopher; Stasiuk, Graeme. J.; Gallo, Juan; Long, Nicholas. J.

2015-09-01

Magnetic resonance imaging (MRI) is an excellent imaging modality. However the low sensitivity of the technique poses a challenge to achieving an accurate image of function at the molecular level. To overcome this, contrast agents are used; typically gadolinium based agents for T1 weighted imaging, or iron oxide based agents for T2 imaging. Traditionally, only one imaging mode is used per diagnosis although several physiological situations are known to interfere with the signal induced by the contrast agents in each individual imaging mode acquisition. Recently, the combination of both T1 and T2 imaging capabilities into a single platform has emerged as a tool to reduce uncertainties in MR image analysis. To date, contradicting reports on the effect on the contrast of the coupling of a T1 and T2 agent have hampered the application of these specialised probes. Herein, we present a systematic experimental study on a range of gadolinium-labelled magnetite nanoparticles envisioned to bring some light into the mechanism of interaction between T1 and T2 components, and advance towards the design of efficient (dual) T1 and T2 MRI probes. Unexpected behaviours observed in some of the constructs will be discussed. In this study, we demonstrate that the relaxivity of such multimodal probes can be rationally tuned to obtain unmatched potentials in MR imaging, exemplified by preparation of the magnetite-based nanoparticle with the highest T2 relaxivity described to date.Magnetic resonance imaging (MRI) is an excellent imaging modality. However the low sensitivity of the technique poses a challenge to achieving an accurate image of function at the molecular level. To overcome this, contrast agents are used; typically gadolinium based agents for T1 weighted imaging, or iron oxide based agents for T2 imaging. Traditionally, only one imaging mode is used per diagnosis although several physiological situations are known to interfere with the signal induced by the contrast agents in each individual imaging mode acquisition. Recently, the combination of both T1 and T2 imaging capabilities into a single platform has emerged as a tool to reduce uncertainties in MR image analysis. To date, contradicting reports on the effect on the contrast of the coupling of a T1 and T2 agent have hampered the application of these specialised probes. Herein, we present a systematic experimental study on a range of gadolinium-labelled magnetite nanoparticles envisioned to bring some light into the mechanism of interaction between T1 and T2 components, and advance towards the design of efficient (dual) T1 and T2 MRI probes. Unexpected behaviours observed in some of the constructs will be discussed. In this study, we demonstrate that the relaxivity of such multimodal probes can be rationally tuned to obtain unmatched potentials in MR imaging, exemplified by preparation of the magnetite-based nanoparticle with the highest T2 relaxivity described to date. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04400f

Iodinated contrast media and their adverse reactions.

PubMed

Singh, Jagdish; Daftary, Aditya

2008-06-01

Cross-use of technology between nuclear medicine and radiology technologists is expanding. The growth of PET/CT and the increasing use of intravenous contrast agents during these procedures bring the nuclear medicine technologist into direct contact with these agents and their associated complications. A basic understanding of the occurrence, risk factors, clinical features, and management of these procedures is of increasing importance to the nuclear medicine technologist. After reading this article, the technologist will be able to list the factors that increase the risk of contrast reactions; understand ways to minimize the occurrence of contrast reactions; and develop a plan to identify, treat, and manage the reactions effectively.

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

PubMed Central

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

2015-01-01

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

Contrast-enhanced ultrasound imaging and in vivo circulatory kinetics with low-boiling-point nanoscale phase-change perfluorocarbon agents.

PubMed

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

2015-03-01

Many studies have explored phase-change contrast agents (PCCAs) that can be vaporized by an ultrasonic pulse to form microbubbles for ultrasound imaging and therapy. However, few investigations have been published on the utility and characteristics of PCCAs as contrast agents in vivo. In this study, we examine the properties of low-boiling-point nanoscale PCCAs evaluated in vivo and compare data with those for conventional microbubbles with respect to contrast generation and circulation properties. To do this, we develop a custom pulse sequence to vaporize and image PCCAs using the Verasonics research platform and a clinical array transducer. Results indicate that droplets can produce contrast enhancement similar to that of microbubbles (7.29 to 18.24 dB over baseline, depending on formulation) and can be designed to circulate for as much as 3.3 times longer than microbubbles. This study also reports for the first time the ability to capture contrast washout kinetics of the target organ as a measure of vascular perfusion. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Carbon Dioxide Angiography: Scientific Principles and Practice

PubMed Central

Cho, Kyung Jae

2015-01-01

Carbon dioxide (CO2) is a colorless, odorless gas which occurs naturally in the atmosphere and human body. With the advent of digital subtraction angiography, the gas has been used as a safe and useful alternative contrast agent in both arteriography and venography. Because of its lack of renal toxicity and allergic potential, CO2 is a preferred contrast agent in patients with renal failure or contrast allergy, and particularly in patients who require large volumes of contrast medium for complex endovascular procedures. Understanding of the unique physical properties of CO2 (high solubility, low viscosity, buoyancy, and compressibility) is essential in obtaining a successful CO2 angiogram and in guiding endovascular intervention. Unlike iodinated contrast material, CO2 displaces the blood and produces a negative contrast for digital subtraction imaging. Indications for use of CO2 as a contrast agent include: aortography and runoff, detection of bleeding, renal transplant arteriography, portal vein visualization with wedged hepatic venous injection, venography, arterial and venous interventions, and endovascular aneurysm repair. CO2 should not be used in the thoracic aorta, the coronary artery, and cerebral circulation. Exploitation of CO2 properties, avoidance of air contamination and facile catheterization technique are important to the safe and effective performance of CO2 angiography and CO2-guided endovascular intervention. PMID:26509137

A strategy to measure electrophysiological changes with photoacoustic imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sepela, Rebecka J.; Sherlock, Benjamin E.; Tian, Lin; Marcu, Laura; Sack, Jon

2017-03-01

Photoacoustic imaging is an emerging technology capable of both functional and structural biological imaging. Absorption and scattering in tissue limit the penetration depth of conventional microscopy techniques to <1mm. Photoacoustic imaging however, can offer high-resolution and contrast at depths of several centimeters. Though functional imaging of endogenous contrast agents, such as hemoglobin, is widely implemented, currently photoacoustic imaging is unable to functionally report electrophysiological changes within cells. We aim to develop photoacoustic contrast agents to fulfill this need. Cells throughout the brain and body create electrical signals using ion channel proteins. These proteins undergo structural changes to regulate the flux of salt ions into the cell. We have recently developed ion channel activity tracers that dissociate from ion channels after the protein changes structure. By conjugating the tracer to dyes that are sensitive to changes in their chemical environment, we can detect tracer dissociation and therefore ion channel activity. We are exploring whether a similar mechanism can create photoacoustic signal intensity changes. To test if the environmental sensitivity of the dye is photoacoustically distinguishable, we imaged the dye in different solvent backgrounds. We report that manipulation of the chemical environment of the contrast dye results in robust changes in photoacoustic properties. We are working to capture photoacoustic signal changes that occur when ion channel proteins activate using live cell imaging. This technology could permit photoacoustic imaging of electrophysiological dynamics in deep tissue, such as the brain. Further optimization of this technology could lead to concurrent imaging of neural activity and hemodynamic responses, a crucial step towards understanding neurovascular coupling in the brain.

A modified commercial ultrasound scanner used for in vivo photoacoustic imaging of nude mice injected with non-targeted contrast agents

NASA Astrophysics Data System (ADS)

Jankovic, Ladislav; Shahzad, Khalid; Wang, Yao; Burcher, Michael; Scholle, Frank-Detlef; Hauff, Peter; Mofina, Sabine; Skobe, Mihaela

2008-02-01

Photoacoustic (PA) experiments were performed using a modified commercial ultrasound scanner equipped with an array transducer and a Nd:YAG pumped OPO laser. The contrast agent SIDAG (Bayer Schering Pharma AG, Germany), used to enhance the optical absorption, demonstrated an expected pharmacokinetic behavior of the dye in the tumor and in the bladder of the nude mice. A typical behavior in the tumor consisted of an initial linear increase in PA signal followed by an exponential decay. PA signal approached the pre-injection level after about one hour following the dye injection, which was consistent with the behavior for such contrast agents when used in other imaging modalities, such as fluorescence imaging. The in-vivo spectral PA data from the mouse bladder, conducted 1.5 hours after the dye injection, clearly demonstrated presence of the dye. The multi-spectral PA data was obtained at 760nm, 784nm and 850nm laser excitations. The PA intensities obtained at these three wavelengths accurately matched the dye absorption spectrum. In addition, in the kidney, a clearance organ for this contrast agent, both in-vivo and ex-vivo results demonstrated a significant increase (~ 40%) in the ratio of PA signal at 760nm (the peak of the dye absorption) relative to the signal at 850nm (<1% absorption), indicating significant amounts of the dye in this organ. Our initial results confirm the desired photoacoustic properties of the contrast agent, indicating its great potential to be used for imaging with a commercial array-based ultrasound scanner.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Polymeric contrast agents for medical imaging.

PubMed

Torchilin, V P

2000-09-01

Synthetic polymers and co-polymers are described, to be used as carriers of reporter groups for gamma-, magnetic resonance (MR), and computed tomography (CT) imaging. Those compounds include polychelating and amphiphilic polymers and serve as key components of various contrast agents. Single terminus-activated polychelating polymers were synthesized using poly-L-lysine (PLL) as a main chain and chelating moieties (such as diethylene triamine pentaacetic acid or DTPA) as side groups. These polymers were used for the modification of diagnostic monoclonal antibodies to increase their load with reporter metal atoms. As a result, better images within shorter time intervals were obtained in animal experiments. The application of liposomes and micelles as carriers for diagnostic imaging agents in experimental and clinical medicine is considered. The load of liposomes and micelles with contrast agents for gamma- and MR imaging (MRI) was sharply increased by using polychelating polymers additionally modified on one end with a hydrophobic phospholipid residue to give amphiphilic polymers. Such polymers easily incorporate the liposome membrane or micelle core and provide better loading of liposomes and micelles with reporter metals and, consequently, better and faster imaging of various physiological compartments, such as lymphatic and vascular systems. A block-copolymer of methoxy-poly(ethylene glycol) (MPEG) and iodine-substituted PLL was synthesized to prepare long-circulating contrast agent for CT imaging of the blood pool. In the aqueous solution, this copolymer forms stable and heavily loaded with iodine (up to 30% of iodine by weight) micelles. These micelle were successfully used for CT visualization of the vascular network in experimental animals. General trends in developing contrast polymers are discussed.

Laser ablation of basal cell carcinomas guided by confocal microscopy

NASA Astrophysics Data System (ADS)

Sierra, Heidy; Cordova, Miguel; Nehal, Kishwer; Rossi, Anthony; Chen, Chih-Shan Jason; Rajadhyaksha, Milind

2016-02-01

Laser ablation offers precise and fast removal of superficial and early nodular types of basal cell carcinomas (BCCs). Nevertheless, the lack of histological confirmation has been a limitation. Reflectance confocal microscopy (RCM) imaging combined with a contrast agent can offer cellular-level histology-like feedback to detect the presence (or absence) of residual BCC directly on the patient. We conducted an ex vivo bench-top study to provide a set of effective ablation parameters (fluence, number of passes) to remove superficial BCCs while also controlling thermal coagulation post-ablation to allow uptake of contrast agent. The results for an Er:YAG laser (2.9 um and pulse duration 250us) show that with 6 passes of 25 J/cm2, thermal coagulation can be effectively controlled, to allow both the uptake of acetic acid (contrast agent) and detection of residual (or absence) BCCs. Confirmation was provided with histological examination. An initial in vivo study on 35 patients shows that the uptake of contrast agent aluminum chloride) and imaging quality is similar to that observed in the ex vivo study. The detection of the presence of residual tumor or complete clearance was confirmed in 10 wounds with (additional) histology and in 25 lesions with follow-up imaging. Our results indicate that resolution is sufficient but further development and use of appropriate contrast agent are necessary to improve sensitivity and specificity. Advances in RCM technology for imaging of lateral and deep margins directly on the patient may provide less invasive, faster and less expensive image-guided approaches for treatment of BCCs.

Ferrimagnetic ferritin cage nanoparticles used as MRI contrast agent

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

Attenuated mutant strain of Salmonella Typhimurium lacking the ZnuABC transporter contrasts tumor growth promoting anti-cancer immune response.

PubMed

Chirullo, Barbara; Ammendola, Serena; Leonardi, Leonardo; Falcini, Roberto; Petrucci, Paola; Pistoia, Claudia; Vendetti, Silvia; Battistoni, Andrea; Pasquali, Paolo

2015-07-10

Salmonella Typhimurium has been shown to be highly effective as antitumor agent. The aim of this study was to investigate the tumor targeting efficacy and the mechanism of action of a specific attenuated mutant strain of Salmonella Typhimurium (STM) devoid of the whole operon coding for the high-affinity zinc transporter ZnuABC, which is required for bacterial growth in environments poor in zinc and for conferring full virulence to different Gram-negative pathogens.We showed that STM is able to penetrate and replicate into tumor cells in in vitro and in vivo models. The subcutaneous administration of STM in mammary adenocarcinoma mouse model led to both reduction of tumor growth and increase in life expectancy of STM treated mice. Moreover, investigating the potential mechanism behind the favorable clinical outcomes, we provide evidence that STM stimulates a potent inflammatory response and a specific immune pattern, recruiting a large number of innate and adaptive immune cells capable to contrast the immunosuppressive environment generated by tumors.

EXCI-CEST: Exploiting pharmaceutical excipients as MRI-CEST contrast agents for tumor imaging.

PubMed

Longo, Dario Livio; Moustaghfir, Fatima Zzahra; Zerbo, Alexandre; Consolino, Lorena; Anemone, Annasofia; Bracesco, Martina; Aime, Silvio

2017-06-15

Chemical Exchange Saturation Transfer (CEST) approach is a novel tool within magnetic resonance imaging (MRI) that allows visualization of molecules possessing exchangeable protons with water. Many molecules, employed as excipients for the formulation of finished drug products, are endowed with hydroxyl, amine or amide protons, thus can be exploitable as MRI-CEST contrast agents. Their high safety profiles allow them to be injected at very high doses. Here we investigated the MRI-CEST properties of several excipients (ascorbic acid, sucrose, N-acetyl-d-glucosamine, meglumine and 2-pyrrolidone) and tested them as tumor-detecting agents in two different murine tumor models (breast and melanoma cancers). All the investigated molecules showed remarkable CEST contrast upon i.v. administration in the range 1-3ppm according to the type of mobile proton groups. A marked increase of CEST contrast was observed in tumor regions up to 30min post injection. The combination of marked tumor contrast enhancement and lack of toxicity make these molecules potential candidates for the diagnosis of tumors within the MRI-CEST approach. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigation of cyano-bridged coordination nanoparticles Gd3+/[Fe(CN)6]3-/d-mannitol as T1-weighted MRI contrast agents

NASA Astrophysics Data System (ADS)

Perrier, M.; Gallud, A.; Ayadi, A.; Kennouche, S.; Porredon, C.; Gary-Bobo, M.; Larionova, J.; Goze-Bac, Ch.; Zanca, M.; Garcia, M.; Basile, I.; Long, J.; de Lapuente, J.; Borras, M.; Guari, Y.

2015-07-01

Cyano-bridged Gd3+/[Fe(CN)6]3- coordination polymer nanoparticles of 3-4 nm stabilized with d-mannitol presenting a high r1 relaxivity value of 11.4 mM-1 s-1 were investigated in vivo as contrast agents (CA) for Magnetic Resonance Imaging (MRI). They allow an increase of the MR image contrast and can act as an efficient intravascular T1 CA with a relatively long blood-circulation lifetime (60 min) without specific toxicity.Cyano-bridged Gd3+/[Fe(CN)6]3- coordination polymer nanoparticles of 3-4 nm stabilized with d-mannitol presenting a high r1 relaxivity value of 11.4 mM-1 s-1 were investigated in vivo as contrast agents (CA) for Magnetic Resonance Imaging (MRI). They allow an increase of the MR image contrast and can act as an efficient intravascular T1 CA with a relatively long blood-circulation lifetime (60 min) without specific toxicity. Electronic supplementary information (ESI) available: Experimental details and procedures, toxicological data, physical characterization. See DOI: 10.1039/c5nr01557j

Effect of contrasting agents on survival, performance, and condition of larval hybrid striped bass Morone chrysops x M. saxatilis in tanks

USDA-ARS?s Scientific Manuscript database

Contrasting agents, either algae or inert soil, cause turbidity, which is important in the tank culture of larval cannibalistic fish. Optimization of turbidity is critical to successful tank culture of new larval fish, which should include 100 mg/L of sub 5 um particle size in the assessed range. ...

Effect of contrasting agents on survival, performance, and condition of larval hybrid striped bass Morone chrysops x M. saxatilis in tanks.

USDA-ARS?s Scientific Manuscript database

Turbidity is important in the tank culture of larval cannibalistic fish. The principal goal of these studies were to characterize the utility and feasibility of select contrasting agents, either algae or inert soil, at improving sunshine bass survival and uniformity of size at time of weaning to an ...