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

NASA Astrophysics Data System (ADS)

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

2012-10-01

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

SU-E-T-407: Evaluation of the Stopping Power and Imaging Visibility for Iodine Based Contrast in Proton Therapy

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

Singh, H; Zhao, L; Rana, S

2015-06-15

Purpose: The purpose of this study was to investigate the difference between calculated and measured relative linear stopping power (RLSP) for contrast medium in proton therapy. Furthermore, the visibility for different concentrations in prostate phantom on orthogonal X-ray system was evaluated Methods and Materials: In prostate cancer patient, rectal balloon along with the contrast media was used to visualize the balloon position, thus facilitating the patient setup during each fraction of the uniform scanning proton treatment. There were no fiducial markers implanted in the prostate for this patient. A blue wax phantom with outer dimensions 10cm(H) x 14.5cm(L) x 10cm(W)more » was made in house. To hold iodine based contrast solution, a rectangular shaped hole with dimensions 7cm(H) x 8cm(L) x 4cm(W) was made inside the phantom. Organically bound 8.5% iodine based Cystografin Dilute contrast agent with molecular formula C11H9I3N2O4.C7H17NO5 was used in this study. Six solutions were prepared; each mixture of water and iodine based contrast agent at different concentrations as 0%, 5%, 10%, 20%, 30% and 50%. During computed tomographic(CT) simulation, solutions were placed together at the isocenter of CT and scanned at 120kVp using the same protocol as for prostate cancer patients. The treatment planning was done in CMS-XiO system. Multi-layer-ion-chamber (MLIC) was used to measure residual proton range. Results: The 50% concentration contrast solution was used during treatment for better visualization on orthogonal X-ray image. The measured RLSP for 5%, 10%, 20%, 30% & 50% solutions were 1.005, 1.010, 1.018, 1.023 & 1.033; and similarly calculated RLSP from XiO were 1.090, 1.135, 1.222, 1.299 & 1.448 respectively. Conclusion: The treatment planning system could overestimates the relative stopping power of contrast solution with high concentrations. It is recommended to override the contrast with measured RLSP for high atomic number based contrast solution in treatment planning for proton therapy.« less

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.

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.

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.

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.

Preclinical evaluation of a novel cyanine dye for tumor imaging with in vivo photoacoustic imaging.

PubMed

Temma, Takashi; Onoe, Satoru; Kanazaki, Kengo; Ono, Masahiro; Saji, Hideo

2014-09-01

Photoacoustic imaging (PA imaging or PAI) has shown great promise in the detection and monitoring of cancer. Although nanocarrier-based contrast agents have been studied for use in PAI, small molecule contrast agents are required due to their ease of preparation, costeffectiveness, and low toxicity. Here, we evaluated the usefulness of a novel cyanine dye IC7-1-Bu as a PAI contrast agent without conjugated targeting moieties for in vivo tumor imaging in a mice model. Basic PA characteristics of IC7-1-Bu were compared with indocyanine green (ICG), a Food and Drug Administration approved dye, in an aqueous solution. We evaluated the tumor accumulation profile of IC7-1-Bu and ICG by in vivo fluorescence imaging. In vivo PAI was then performed with a photoacoustic tomography system 24 and 48 h after intravenous injection of IC7-1-Bu into tumor bearing mice. IC7-1-Bu showed about a 2.3-fold higher PA signal in aqueous solution compared with that of ICG. Unlike ICG, IC7-1-Bu showed high tumor fluorescence after intravenous injection. In vivo PAI provided a tumor to background PA signal ratio of approximately 2.5 after intravenous injection of IC7-1-Bu. These results indicate that IC7-1-Bu is a promising PAI contrast agent for cancer imaging without conjugation of targeting moieties.

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.

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

NASA Astrophysics Data System (ADS)

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

2004-10-01

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

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

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.

Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

NASA Astrophysics Data System (ADS)

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

2010-12-01

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

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.

Physical and chemical stability of proflavine contrast agent solutions for early detection of oral cancer.

PubMed

Kawedia, Jitesh D; Zhang, Yan-Ping; Myers, Alan L; Richards-Kortum, Rebecca R; Kramer, Mark A; Gillenwater, Ann M; Culotta, Kirk S

2016-02-01

Proflavine hemisulfate solution is a fluorescence contrast agent to visualize cell nuclei using high-resolution optical imaging devices such as the high-resolution microendoscope. These devices provide real-time imaging to distinguish between normal versus neoplastic tissue. These images could be helpful for early screening of oral cancer and its precursors and to determine accurate margins of malignant tissue for ablative surgery. Extemporaneous preparation of proflavine solution for these diagnostic procedures requires preparation in batches and long-term storage to improve compounding efficiency in the pharmacy. However, there is a paucity of long-term stability data for proflavine contrast solutions. The physical and chemical stability of 0.01% (10 mg/100 ml) proflavine hemisulfate solutions prepared in sterile water was determined following storage at refrigeration (4-8℃) and room temperature (23℃). Concentrations of proflavine were measured at predetermined time points up to 12 months using a validated stability-indicating high-performance liquid chromatography method. Proflavine solutions stored under refrigeration were physically and chemically stable for at least 12 months with concentrations ranging from 95% to 105% compared to initial concentration. However, in solutions stored at room temperature increased turbidity and particulates were observed in some of the tested vials at 9 months and 12 months with peak particle count reaching 17-fold increase compared to baseline. Solutions stored at room temperature were chemically stable up to six months (94-105%). Proflavine solutions at concentration of 0.01% were chemically and physically stable for at least 12 months under refrigeration. The solution was chemically stable for six months when stored at room temperature. We recommend long-term storage of proflavine solutions under refrigeration prior to diagnostic procedure. © The Author(s) 2014.

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.

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.

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.

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.

Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

PubMed Central

2010-01-01

Biocompatible poly-[N-(2-hydroxyethyl)-d,l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C16) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Micelle size and shape were examined by dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd. PMID:21170410

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.

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

PubMed Central

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

2016-01-01

We describe the synthesis, characterization and application as contrast agents in magnetic resonance imaging of a novel type of magnetic nanoparticle based on Gd-Si oxide, which presents high Gd3+ atom density. For this purpose, we have used a Prussian Blue analogue as the sacrificial template by reacting with soluble silicate, obtaining particles with nanorod morphology and of small size (75 nm). These nanoparticles present good biocompatibility and higher longitudinal and transversal relaxivity values than commercial Gd3+ solutions, which significantly improves the sensitivity of in vivo magnetic resonance images. PMID:28335240

Non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection.

PubMed

Bagga, Puneet; Haris, Mohammad; D'Aquilla, Kevin; Wilson, Neil E; Marincola, Francesco M; Schnall, Mitchell D; Hariharan, Hari; Reddy, Ravinder

2017-05-30

Image contrast enhanced by exogenous contrast agents plays a crucial role in the early detection, characterization, and determination of the precise location of cancers. Here, we investigate the feasibility of using a non-nutritive sweetener, sucralose (commercial name, Splenda), as magnetic resonance imaging (MRI) contrast agent for cancer studies. High-resolution nuclear-magnetic-resonance spectroscopy and MR studies on sucralose solution phantom were performed to detect the chemical exchange saturation transfer (CEST) property of sucralose hydroxyl protons with bulk water (sucCEST). For the animal experiments, female Fisher rats (F344/NCR) were used to generate 9L-gliosarcoma model. MRI with CEST experiments were performed on anesthetized rats at 9.4 T MR scanner. Following the baseline CEST scans, sucralose solution was intravenously administered in control and tumor bearing rats. CEST acquisitions were continued during and following the administration of sucralose. Following the sucCEST, Gadolinium-diethylenetriamine pentaacetic acid was injected to perform Gd-enhanced imaging for visualizing the tumor. The sucCEST contrast in vitro was found to correlate positively with the sucralose concentration and negatively with the pH, indicating the potential of this technique in cancer imaging. In a control animal, the CEST contrast from the brain was found to be unaffected following the administration of sucralose, demonstrating its blood-brain barrier impermeability. In a 9L glioma model, enhanced localized sucCEST contrast in the tumor region was detected while the unaffected brain region showed unaltered CEST effect implying the specificity of sucralose toward the tumorous tissue. The CEST asymmetry plots acquired from the tumor region before and after the sucralose infusion showed elevation of asymmetry at 1 ppm, pointing towards the role of sucralose in increased contrast. We show the feasibility of using sucralose and sucCEST in study of preclinical models of cancer. This study paves the way for the potential development of sucralose and other sucrose derivatives as contrast agents for clinical MRI applications.

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.

Gd-DTPA-Dopamine-Bisphytanyl Amphiphile: Synthesis, Characterisation and Relaxation Parameters of the Nanoassemblies and Their Potential as MRI Contrast Agents.

PubMed

Gupta, Abhishek; Willis, Scott A; Waddington, Lynne J; Stait-Gardner, Tim; de Campo, Liliana; Hwang, Dennis W; Kirby, Nigel; Price, William S; Moghaddam, Minoo J

2015-09-28

Here, a new amphiphilic magnetic resonance imaging (MRI) contrast agent, a Gd(III)-chelated diethylenetriaminepentaacetic acid conjugated to two branched alkyl chains via a dopamine spacer, Gd-DTPA-dopamine-bisphytanyl (Gd-DTPA-Dop-Phy), which is readily capable of self-assembling into liposomal nanoassemblies upon dispersion in an aqueous solution, is reported. In vitro relaxivities of the dispersions were found to be much higher than Magnevist, a commercially available contrast agent, at 0.47 T but comparable at 9.40 T. Analysis of variable temperature (17)O NMR transverse relaxation measurements revealed the water exchange of the nanoassemblies to be faster than that previously reported for paramagnetic liposomes. Molecular reorientation dynamics were probed by (1)H NMRD profiles using a classical inner and outer sphere relaxation model and a Lipari-Szabo "model-free" approach. High payloads of Gd(III) ions in the liposomal nanoassemblies made solely from the Gd-DTPA-Dop-Phy amphiphiles, in combination with slow molecular reorientation and fast water exchange makes this novel amphiphile a suitable candidate to be investigated as an advanced MRI contrast agent. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design of functionalized gold nanoparticle probes for computed tomography imaging.

PubMed

Silvestri, Alessandro; Zambelli, Vanessa; Ferretti, Anna M; Salerno, Domenico; Bellani, Giacomo; Polito, Laura

2016-09-01

The development of new molecules able to efficiently act as long-circulating computed tomography (CT) contrast agents is one of the most crucial topics in the biomedical field. In the last years, the chance to manipulate materials at the nano-size level gave new boost to this research, with the specific aim to design innovative nanoprobes. Gold nanoparticles (AuNPs) have showed unique X-rays attenuation properties which, combined with their easy surface functionalization, makes them ideal candidates for the next generation of contrast agents. In this paper, we present a rational and facile approach to synthesize engineered and water-stable AuNPs, achieving concentrated colloidal solution with high Hounsfield Units (HU). An accurate control of reagents ratio allowed us to design AuNPs with different shapes, from symmetrical to anisotropic morphology, in a convenient 'one-pot' fashion. Their activity as efficient and reliable CT contrast agents has been evaluated and compared. Moreover, glucosamine-functionalized gold nanoparticles have been developed ([Au] = 31.20 mg/mL; HU = 2453), in order to obtain a CT contrast agent able to combine spatial resolution with metabolic information. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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

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.

Superparamagnetic iron oxide nanoparticles for MRI: contrast media pharmaceutical company R&D perspective.

PubMed

Corot, Claire; Warlin, David

2013-01-01

Superparamagnetic iron oxide (SPIO) nanoparticles are a relatively large class of contrast agents for magnetic resonance imaging. According to their biodistribution, distinct classes of SPIO nanoparticles have been investigated for clinical applications either as macrophage imaging agents or blood pool agents. Contrast agents which are pharmaceutics followed the same development rules as therapeutic drugs. Several drawbacks such as clinical development difficulties, organization of market access and imaging technological developments have limited the widespread use of these products. SPIO nanoparticles that are composed of thousands iron atoms providing large T2* effects are particularly suitable for theranostic. Stem cell migration and immune cell trafficking, as well as targeted SPIO nanoparticles for molecular imaging studies are mainly at the stage of proof of concept. A major economic challenge in the development of molecular imaging associated with a therapeutic treatment/procedure is to define innovative business models compatible with the needs of all players taking into account that theranostic solutions are promising to optimize resource allocation and ensure that expensive treatments are prescribed to responding patients. © 2013 Wiley Periodicals, Inc.

Metrizamide evaluation of the esophagus in infants

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

Belt, T.; Cohen, M.D.

1984-08-01

Barium and conventional hypertonic water-soluble contrast media (e.g., gastrografin) are not ideal contrast agents in the evaluation of the esophagus when leakage into the mediastinum or aspiration into the lung is possible. Metrizamide (Amipaque) is water-soluble and can be well visualized in isotonic solution. Three cases are presented where metrizamide was used successfully in the evaluation of suspected esophageal perforation or tracheoesophageal fistula.

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.

Myelography iodinated contrast media. I. Unraveling the atropisomerism properties in solution.

PubMed

Fontanive, Luca; D'Amelio, Nicola; Cesàro, Attilio; Gamini, Amelia; Tavagnacco, Letizia; Paolantoni, Marco; Brady, John W; Maiocchi, Alessandro; Uggeri, Fulvio

2015-06-01

The present work reports a thorough conformational analysis of iodinated contrast media: iomeprol, iopamidol (the world's most utilized contrast agent), and iopromide. Its main aim is the understanding of the complex structural features of these atropisomeric molecules, characterized by the presence of many conformers with hindered rotations, and of the role of atropisomerism in the physicochemical properties of their aqueous solutions. The problem was tackled by using an extensive analysis of (13)C NMR data on the solutions of whole molecules and of simple precursors in addition to FT-IR investigation and molecular simulations. This analysis demonstrated that out of the many possible atropisomers, only a few are significantly populated, and their relative population is provided. The conformational analysis also indicated that the presence of a sterically hindered amidic bond, allowing a significant population of cis forms (E in iopromide and exo in iomeprol), may be the basis for an increased thermodynamic solubility of concentrated solutions of iomeprol.

A proposed CT contrast agent using carboxybetaine zwitterionic tantalum oxide nanoparticles: Imaging, biological, and physicochemical performance

PubMed Central

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

2016-01-01

Objectives To produce and evaluate a proposed computed tomography (CT) contrast agent based on carboxybetaine zwitterionic (CZ) coated soluble tantalum oxide nanoparticles (CZ-TaO NPs). We chose tantalum to provide superior imaging performance compared to current iodine-based clinical CT contrast agents. We developed the CZ coating to provide biological and physical performance similar to that of current iodinated contrast agents. The aim of this study was to evaluate the imaging, biological, and physicochemical performance of this proposed contrast agent compared to clinically-used iodinated agents. Materials and Methods We evaluated CT imaging performance of our CZ-TaO NPs compared to an iodinated agent in live rats, imaged centrally-located within a tissue-equivalent plastic phantom that simulated a large patient. To evaluate vascular contrast enhancement, we scanned the rats’ great vessels at high temporal resolution during and following contrast agent injection. We performed several in vivo CZ-TaO NP studies in healthy rats to evaluate tolerability. These studies included injecting the agent at the anticipated clinical dose (ACD) and at 3 times and 6 times the ACD, followed by longitudinal hematology to assess impact to blood cells and organ function (from 4 hours to 1 week). Kidney histological analysis was performed 48 hours after injection at 3 times the ACD. We measured the elimination half-life of CZ-TaO NPs from blood, and we monitored acute kidney injury biomarkers with a kidney injury assay using urine collected from 4 hours to 1 week. We measured tantalum retention in individual organs and in the whole carcass 48 hours after injection at ACD. CZ-TaO NPs were synthesized and analyzed in detail. We used multi-dimensional nuclear magnetic resonance (NMR) to determine surface functionality of the nanoparticles. We measured nanoparticle size and solution properties (osmolality and viscosity) of the agent over a range of tantalum concentrations, including the high concentrations required for standard clinical CT imaging. Results CT imaging studies demonstrated image contrast improvement of approximately 40–50% using CZ-TaO NPs compared with an iodinated agent injected at the same mass concentration. Blood and organ analyses showed no adverse effects following injection in healthy naïve rats at 3 times the ACD. Retention of tantalum at 48 hours after injection was less than 2% of the injected dose in the whole carcass, which very closely matched the reported retention of existing commercial iodine-based contrast agents. Urine analysis of sensitive markers for acute kidney injury showed no responses at 1 week following injection at 3 times the ACD; however, a moderate response in the neutrophil gelatinase-associated lipocalin (NGAL) biomarker was measured at 24 and 48 hours. Compared to other tantalum oxide nanoparticles reported in the literature, CZ-TaO NPs had relatively low osmolality and viscosity at concentrations >200 mg Ta/mL, and were similar in these physical properties to dimeric iodine-based contrast agents. Conclusions We found that a CZ-TaO NP-based contrast agent is potentially viable for general-purpose clinical CT imaging. Our results suggest that such an agent can be formulated with clinically-viable physicochemical properties, can be biologically safe and cleared rapidly in urine, and can provide substantially improved image contrast at CT compared to current iodinated agents. PMID:27115702

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

PubMed

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

2016-12-01

The aim of this study was to produce and evaluate a proposed computed tomography (CT) contrast agent based on carboxybetaine zwitterionic (CZ)-coated soluble tantalum oxide (TaO) nanoparticles (NPs). We chose tantalum to provide superior imaging performance compared with current iodine-based clinical CT contrast agents. We developed the CZ coating to provide biological and physical performance similar to that of current iodinated contrast agents. In addition, the aim of this study was to evaluate the imaging, biological, and physicochemical performance of this proposed contrast agent compared with clinically used iodinated agents. We evaluated CT imaging performance of our CZ-TaO NPs compared with that of an iodinated agent in live rats, imaged centrally located within a tissue-equivalent plastic phantom that simulated a large patient. To evaluate vascular contrast enhancement, we scanned the rats' great vessels at high temporal resolution during and after contrast agent injection. We performed several in vivo CZ-TaO NP studies in healthy rats to evaluate tolerability. These studies included injecting the agent at the anticipated clinical dose (ACD) and at 3 times and 6 times the ACD, followed by longitudinal hematology to assess impact to blood cells and organ function (from 4 hours to 1 week). Kidney histological analysis was performed 48 hours after injection at 3 times the ACD. We measured the elimination half-life of CZ-TaO NPs from blood, and we monitored acute kidney injury biomarkers with a kidney injury assay using urine collected from 4 hours to 1 week. We measured tantalum retention in individual organs and in the whole carcass 48 hours after injection at ACD. Carboxybetaine zwitterionic TaO NPs were synthesized and analyzed in detail. We used multidimensional nuclear magnetic resonance to determine surface functionality of the NPs. We measured NP size and solution properties (osmolality and viscosity) of the agent over a range of tantalum concentrations, including the high concentrations required for standard clinical CT imaging. Computed tomography imaging studies demonstrated image contrast improvement of approximately 40% to 50% using CZ-TaO NPs compared with an iodinated agent injected at the same mass concentration. Blood and organ analyses showed no adverse effects after injection in healthy naive rats at 3 times the ACD. Retention of tantalum at 48 hours after injection was less than 2% of the injected dose in the whole carcass, which very closely matched the reported retention of existing commercial iodine-based contrast agents. Urine analysis of sensitive markers for acute kidney injury showed no responses at 1 week after injection at 3 times the ACD; however, a moderate response in the neutrophil gelatinase-associated lipocalin biomarker was measured at 24 and 48 hours. Compared with other TaO NPs reported in the literature, CZ-TaO NPs had relatively low osmolality and viscosity at concentrations greater than 200 mg Ta/mL and were similar in these physical properties to dimeric iodine-based contrast agents. We found that a CZ-TaO NP-based contrast agent is potentially viable for general-purpose clinical CT imaging. Our results suggest that such an agent can be formulated with clinically viable physicochemical properties, can be biologically safe and cleared rapidly in urine, and can provide substantially improved image contrast at CT compared with current iodinated agents.

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.

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

PubMed

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

2017-03-01

Three carbon samples were employed in this work, including commercial (1690 m 2  g -1 ), activated carbon prepared from guava seeds (637 m 2  g -1 ), and activated carbon prepared from avocado kernel (1068 m 2  g -1 ), to study the adsorption of the following gadolinium-based contrast agents (GBCAs): gadoterate meglumine Dotarem®, gadopentetate dimeglumine Magnevist®, and gadoxetate disodium Primovist®. The activation conditions with H 3 PO 4 were optimized using a Taguchi methodology to obtain mesoporous materials. The best removal efficiency by square meter in a batch system in aqueous solution and model urine was achieved by avocado kernel carbon, in which mesoporosity prevails over microporosity. The kinetic adsorption curves were described by a pseudo-second-order equation, and the adsorption isotherms in the concentration range 0.5-6 mM fit the Freundlich equation. The chemical characterization of the surfaces shows that materials with a greater amount of phenolic functional groups adsorb the GBCA better. Adsorption strongly depends on the pH due to the combination of the following factors: contrast agent protonated forms and carbon surface charge. The tested carbon samples were able to adsorb 70-90% of GBCA in aqueous solution and less in model urine. This research proposes a method for the elimination of GBCA from patient urine before its discharge into wastewater.

Trapping and dynamic manipulation of polystyrene beads mimicking circulating tumor cells using targeted magnetic/photoacoustic contrast agents

NASA Astrophysics Data System (ADS)

Wei, Chen-Wei; Xia, Jinjun; Pelivanov, Ivan; Hu, Xiaoge; Gao, Xiaohu; O'Donnell, Matthew

2012-10-01

Results on magnetically trapping and manipulating micro-scale beads circulating in a flow field mimicking metastatic cancer cells in human peripheral vessels are presented. Composite contrast agents combining magneto-sensitive nanospheres and highly optical absorptive gold nanorods were conjugated to micro-scale polystyrene beads. To efficiently trap the targeted objects in a fast stream, a dual magnet system consisting of two flat magnets to magnetize (polarize) the contrast agent and an array of cone magnets producing a sharp gradient field to trap the magnetized contrast agent was designed and constructed. A water-ink solution with an optical absorption coefficient of 10 cm-1 was used to mimic the optical absorption of blood. Magnetomotive photoacoustic imaging helped visualize bead trapping, dynamic manipulation of trapped beads in a flow field, and the subtraction of stationary background signals insensitive to the magnetic field. The results show that trafficking micro-scale objects can be effectively trapped in a stream with a flow rate up to 12 ml/min and the background can be significantly (greater than 15 dB) suppressed. It makes the proposed method very promising for sensitive detection of rare circulating tumor cells within high flow vessels with a highly absorptive optical background.

Preparation and Evaluation of Multiple Nanoemulsions Containing Gadolinium (III) Chelate as a Potential Magnetic Resonance Imaging (MRI) Contrast Agent.

PubMed

Sigward, Estelle; Corvis, Yohann; Doan, Bich-Thuy; Kindsiko, Kadri; Seguin, Johanne; Scherman, Daniel; Brossard, Denis; Mignet, Nathalie; Espeau, Philippe; Crauste-Manciet, Sylvie

2015-09-01

The objective was to develop, characterize and assess the potentiality of W1/O/W2 self-emulsifying multiple nanoemulsions to enhance signal/noise ratio for Magnetic Resonance Imaging (MRI). For this purpose, a new formulation, was designed for encapsulation efficiency and stability. Various methods were used to characterize encapsulation efficiency ,in particular calorimetric methods (Differential Scanning Calorimetry (DSC), thermogravimetry analysis) and ultrafiltration. MRI in vitro relaxivities were assessed on loaded DTPA-Gd multiple nanoemulsions. Characterization of the formulation, in particular of encapsulation efficiency was a challenge due to interactions found with ultrafiltration method. Thanks to the specifically developed DSC protocol, we were able to confirm the formation of multiple nanoemulsions, differentiate loaded from unloaded nanoemulsions and measure the encapsulation efficiency which was found to be quite high with a 68% of drug loaded. Relaxivity studies showed that the self-emulsifying W/O/W nanoemulsions were positive contrast agents, exhibiting higher relaxivities than those of the DTPA-Gd solution taken as a reference. New self-emulsifying multiple nanoemulsions that were able to load satisfactory amounts of contrasting agent were successfully developed as potential MRI contrasting agents. A specific DSC protocol was needed to be developed to characterize these complex systems as it would be useful to develop these self-formation formulations.

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

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.

X-ray attenuation coefficients of high-atomic-number, hexanuclear transition metal cluster compounds: a new paradigm for radiographic contrast agents.

PubMed

Mullan, B F; Madsen, M T; Messerle, L; Kolesnichenko, V; Kruger, J

2000-04-01

The purpose of this study was to examine the radiologic attenuation properties of the parent cluster compounds, particularly attenuation as a function of discrete photon energy, before investigating ligand substitutions, which are necessary to improve cluster biocompatibility and to impart desirable physicochemical properties. The linear attenuation coefficients for solutions of the cluster compounds Ta6Br14, K8Ta6O19, and (H3O)2W6Cl14 were determined at 60, 80, 103, 122, and 140 keV from gamma-ray transmission measurements with americium-241, xenon-133, gadolinium-153, cobalt-57, and technetium-99m radioactive sources. Transmission measurements were obtained for a fixed time interval that ensured a statistically accurate count distribution exceeding 20,000 counts through the sample for each trial. On a strictly mole per liter basis, a 0.075 mol/L aqueous solution of K8Ta6O19 showed 1.08 times the attenuation of 0.063 mol/L aqueous iohexol at 60 keV and 3.30 times the attenuation at 80 keV. Similarly, a 0.05 mol/L methanolic solution of (H3O)2W6Cl4 showed 0.96 times (96%) the attenuation of 0.063 mol/L aqueous iohexol at 60 keV but 3.09 times the attenuation of the iohexol solution at 80 keV. Attenuations of 0.063 mol/L aqueous iohexol and 0.0125 mol/L Ta6Br14 (ie, at approximately one-fifth the iohexol concentration) were comparable at greater than 60 keV. These results confirm the theoretic potential for use of early transition metal cluster compounds as radiographic contrast agents. At higher x-ray energies, cluster compounds demonstrate multiplied x-ray attenuation relative to iodinated contrast agents.

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

NASA Astrophysics Data System (ADS)

Siddiqui, Talha S.

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

Sono-photoacoustic imaging of gold nanoemulsions: Part II. Real time imaging

PubMed Central

Arnal, Bastien; Wei, Chen-Wei; Perez, Camilo; Nguyen, Thu-Mai; Lombardo, Michael; Pelivanov, Ivan; Pozzo, Lilo D.; O’Donnell, Matthew

2015-01-01

Photoacoustic (PA) imaging using exogenous agents can be limited by degraded specificity due to strong background signals. This paper introduces a technique called sono-photoacoustics (SPA) applied to perfluorohexane nanodroplets coated with gold nanospheres. Pulsed laser and ultrasound (US) excitations are applied simultaneously to the contrast agent to induce a phase-transition ultimately creating a transient microbubble. The US field present during the phase transition combined with the large thermal expansion of the bubble leads to 20–30 dB signal enhancement. Aqueous solutions and phantoms with very low concentrations of this agent were probed using pulsed laser radiation at diagnostic exposures and a conventional US array used both for excitation and imaging. Contrast specificity of the agent was demonstrated with a coherent differential scheme to suppress US and linear PA background signals. SPA shows great potential for molecular imaging with ultrasensitive detection of targeted gold coated nanoemulsions and cavitation-assisted theranostic approaches. PMID:25893170

The Most Effective Gold Nanorod Size for Plasmonic Photothermal Therapy: Theory and In Vitro Experiments

PubMed Central

2015-01-01

The development of new and improved photothermal contrast agents for the successful treatment of cancer (or other diseases) via plasmonic photothermal therapy (PPTT) is a crucial part of the application of nanotechnology in medicine. Gold nanorods (AuNRs) have been found to be the most effective photothermal contrast agents, both in vitro and in vivo. Therefore, determining the optimum AuNR size needed for applications in PPTT is of great interest. In the present work, we utilized theoretical calculations as well as experimental techniques in vitro to determine this optimum AuNR size by comparing plasmonic properties and the efficacy as photothermal contrast agents of three different sizes of AuNRs. Our theoretical calculations showed that the contribution of absorbance to the total extinction, the electric field, and the distance at which this field extends away from the nanoparticle surface all govern the effectiveness of the amount of heat these particles generate upon NIR laser irradiation. Comparing between three different AuNRs (38 × 11, 28 × 8, and 17 × 5 nm), we determined that the 28 × 8 nm AuNR is the most effective in plasmonic photothermal heat generation. These results encouraged us to carry out in vitro experiments to compare the PPTT efficacy of the different sized AuNRs. The 28 × 8 nm AuNR was found to be the most effective photothermal contrast agent for PPTT of human oral squamous cell carcinoma. This size AuNR has the best compromise between the total amount of light absorbed and the fraction of which is converted to heat. In addition, the distance at which the electric field extends from the particle surface is most ideal for this size AuNR, as it is sufficient to allow for coupling between the fields of adjacent particles in solution (i.e., particle aggregates), resulting in effective heating in solution. PMID:24433049

Method for nuclear magnetic resonance imaging using deuterum as a contrast agent

DOEpatents

Kehayias, Joseph J.; Joel, Darrel D.; Adams, William H.; Stein, Harry L.

1990-01-01

A method for in vivo NMR imaging of the blood vessels and organs of a patient characterized by using a dark dye-like imaging substance consisting essentially of a stable, high-purity concentration of D.sub.2 O in a solution with water.

Real-time tracking of dissociation of hyperpolarized 89Y-DTPA: a model for degradation of open-chain Gd3+ MRI contrast agents

NASA Astrophysics Data System (ADS)

Ferguson, Sarah; Niedbalski, Peter; Parish, Christopher; Kiswandhi, Andhika; Kovacs, Zoltan; Lumata, Lloyd

Gadolinium (Gd) complexes are widely used relaxation-based clinical contrast agents in magnetic resonance imaging (MRI). Gd-based MRI contrast agents with open-chain ligand such as Gd-DTPA, commercially known as magnevist, are less stable compared to Gd complexes with macrocyclic ligands such as GdDOTA (Dotarem). The dissociation of Gd-DPTA into Gd ion and DTPA ligand under certain biological conditions such as high zinc levels can potentially cause kidney damage. Since Gd is paramagnetic, direct NMR detection of the Gd-DTPA dissociation is quite challenging due to ultra-short relaxation times. In this work, we have investigated Y-DTPA as a model for Gd-DPTA dissociation under high zinc content solutions. Using dissolution dynamic nuclear polarization (DNP), the 89Y NMR signal is amplified by several thousand-fold. Due to the the relatively long T1 relaxation time of 89Y which translates to hyperpolarization lifetime of several minutes, the dissociation of Y-DTPA can be tracked in real-time by hyperpolarized 89Y NMR spectroscopy. Dissociation kinetic rates and implications on the degradation of open-chain Gd3+ MRI contrast agents will be discussed. This work was supported by the U.S. Department of Defense Award Number W81XWH-14-1-0048 and by the Robert A. Welch Foundation research Grant Number AT-1877.

MR of the small bowel with a biphasic oral contrast agent (polyethylene glycol): technical aspects and findings in patients affected by Crohn's disease.

PubMed

Laghi, Andrea; Paolantonio, Pasquale; Iafrate, Franco; Borrelli, Osvaldo; Dito, Lucia; Tomei, Ernesto; Cucchiara, Salvatore; Passariello, Roberto

2003-01-01

To report our experience using MR of the small bowel with polyethylene glycol (PEG) solution as an oral contrast agent in a population of adults and children with known Crohn's disease. 40 patients (29 males; 11 females), 15 adults (age range 24-52 years) and 25 children (age range 5-17 years), with known Crohn's disease, underwent MR of the small bowel using a supeconductive 1.5 T magnet, and polyethylene glycol solution as an oral contrast agent. The fixed amount of contrast agent was 750-1000 ml for adults and 10 ml/kg of body weight for children. The Crohn's Disease Activity Index (CDAI) was available in all patients. Our study protocol included the acquisition of T2-weighted half-Fourier single-shot turbo spin-echo (HASTE) sequences and true fast imaging in the steady-state precession (true-FISP) sequences, followed by the acquisition of "spoiled" 2D gradient echo T1-weighted sequences with fat suppression (FLASH, fast low-angle shot) or alternatively "spoiled" 3D (VIBE, volume interpolated breath-hold examination), acquired 70 seconds after intravenous administration of gadopentetate dimeglumine (Gd-DTPA) (0,1 mmol/kg). A specific MR score was created and calculated for each patient and was compared by means of the Spearman rank with CDAI. In all patients no significant side effects were observed and the MR examination was well tolerated even by paediatric patients. In all cases MR showed a small bowel wall thickening (> 4 mm) in the terminal ileum, with lumen stenosis in 26 patients. In 3 cases pathological segments proximal to the terminal ileum were observed and in another 3 cases caecal involvement was visible. The MR examination was able to show abnormalities of perivisceral fat tissue in 15 patients, mesenteric lymphadenopathy in 1 patient and abdominal abscess in 1 case. The Spearman rank showed a statistically significant correlation between CDAI and the MR score (r = 0.91, P = 0,0001). MR using PEG as an oral contrast agent could be considered a test of great interest in the evaluation of the small bowel in patients suspected of having Crohn's disease in that it is easily reproducible, well tolerated even by paediatric patients and it provides useful information about the localisation, extension and activity of inflammatory disease without the use of ionising radiation.

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

DTIC Science & Technology

2010-03-01

hearing mantle and magnetic stirrer, and the gold solution was brought to a boil (Figure 1a). Next, 0.93 g of sodium citrate dihydrate...C6H5Na3O7.2H2O ) was dissolved in 45 mL of DI-H2O and added to the boiling gold solution. Upon addition of the sodium citrate, the solution rapidly changed...diatrizoate and related triiodinated benzoates by Trametes versicolor. Appl Environ Microbiol, 1998. 64(8): p. 3114-7. 2. Baselga, J., A.D. Seidman, P.P

Fluorine-19 MRI Contrast Agents for Cell Tracking and Lung Imaging

PubMed Central

Fox, Matthew S.; Gaudet, Jeffrey M.; Foster, Paula J.

2015-01-01

Fluorine-19 (19F)-based contrast agents for magnetic resonance imaging stand to revolutionize imaging-based research and clinical trials in several fields of medical intervention. First, their use in characterizing in vivo cell behavior may help bring cellular therapy closer to clinical acceptance. Second, their use in lung imaging provides novel noninvasive interrogation of the ventilated airspaces without the need for complicated, hard-to-distribute hardware. This article reviews the current state of 19F-based cell tracking and lung imaging using magnetic resonance imaging and describes the link between the methods across these fields and how they may mutually benefit from solutions to mutual problems encountered when imaging 19F-containing compounds, as well as hardware and software advancements. PMID:27042089

Evaluation of contrast-enhanced power Doppler imaging for measuring blood flow

NASA Astrophysics Data System (ADS)

Ansaloni, Sara; Arger, Peter H.; Cary, Ted W.; Sehgal, Chandra M.

2005-04-01

Power Doppler ultrasound enhanced by microbubble contrast agent has been used to image tissue vascularity and blood flow for the assessment of antivascular therapies. We have proposed a multigating technique that measures bubble concentration as a function of ultrasound exposure for deriving tumor blood flow and vascularity.1 Techniques using ultrasound contrast agent are known to be sensitive to the choice of imaging parameters like mechanical index and tissue attenuation. In this paper, the roles of mechanical index (MI) and tissue attenuation were evaluated experimentally in a rubber tubing flow phantom connected to a mixing chamber and a variable speed pump. The contrast was injected in the mixing chamber and the flow rate was measured using power Doppler imaging. The measurements were repeated at different MIs (0.1 to 1.3), and at different levels of attenuation, obtained with solutions of glycerol-water (10-20%). True flow was measured by collecting liquid flowing out of the phantom over a fixed duration. At low MI (<0.5), the grayscale and Doppler signal were weak, making these images unsuitable for analysis. At higher MI (> 0.8), there was a well-defined enhancement by contrast agent resulting in reproducible flow measurements at variable MIs. A balance between the number of bubbles destroyed and the echo they generate must be achieved for optimal imaging. The increased attenuation of ultrasound by the overlying medium did not influence the flow measurements.

1,2-Hydroxypyridonates as Contrast Agents for Magnetic ResonanceImaging: TREN-1,2-HOPO

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

Jocher, Christoph J.; Moore, Evan G.; Xu, Jide

2007-05-08

1,2-Hydroxypyridinones (1,2-HOPO) form very stable lanthanide complexes that may be useful as contrast agents for Magnetic Resonance Imaging (MRI). X-ray diffraction of single crystals established that the solid state structures of the Eu(III) and the previously reported [Inorg. Chem. 2004, 43, 5452] Gd(III) complex are identical. The recently discovered sensitizing properties of 1,2-HOPO chelates for Eu(III) luminescence allow direct measurement of the number if water molecules in the metal complex. Fluorescence measurements of the Eu(III) complex corroborate that in solution two water molecules coordinate the lanthanide (q = 2) as proposed from the analysis of NMRD profiles. In addition, fluorescencemore » measurements have verified the anion binding interactions of lanthanide TREN-1,2-HOPO complexes in solution, studied by relaxivity, revealing only very weak oxalate binding (K{sub A} = 82.7 {+-} 6.5 M{sup -1}). Solution thermodynamic studies of the metal complex and free ligand have been carried out using potentiometry, spectrophotometry and fluorescence spectroscopy. The metal ion selectivity of TREN-1,2-HOPO supports the feasibility of using 1,2-HOPO ligands for selective lanthanide binding [pGd = 19.3 (2); pZn = 15.2 (2), pCa = 8.8 (3)].« less

Visualization and simulation of density driven convection in porous media using magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Montague, James A.; Pinder, George F.; Gonyea, Jay V.; Hipko, Scott; Watts, Richard

2018-05-01

Magnetic resonance imaging is used to observe solute transport in a 40 cm long, 26 cm diameter sand column that contained a central core of low permeability silica surrounded by higher permeability well-sorted sand. Low concentrations (2.9 g/L) of Magnevist, a gadolinium based contrast agent, produce density driven convection within the column when it starts in an unstable state. The unstable state, for this experiment, exists when higher density contrast agent is present above the lower density water. We implement a numerical model in OpenFOAM to reproduce the observed fluid flow and transport from a density difference of 0.3%. The experimental results demonstrate the usefulness of magnetic resonance imaging in observing three-dimensional gravity-driven convective-dispersive transport behaviors in medium scale experiments.

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.

SU-F-207-07: Dual-Energy Computed Tomography Detection Limit of Various Radiopaque Contrast Agents That Can Be Infused Within Absorbable Inferior Vena Cava Filters

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

Melancon, A; Jacobsen, M; Salatan, F

Purpose: Absorbable IVC filters are shown to be safe and efficacious in preventing pulmonary embolism. These absorbable filters disappear from the body after their required duration, alleviating costly removal procedures and downstream complications. Monitoring the positioning and integrity of absorbable devices using dual-energy computed tomography (DECT) would improve treatment efficacy. The purpose of this study is to determine the limit of detection and the energy dependence of DECT for various contrast agents that may be infused within the IVC filters including gold nanoparticles (AuNP) having diameters of 2 and 4 nm. Methods: All imaging studies were performed on a GEmore » Discovery CT750 system in Gemstone Spectral Imaging (GSI) mode. Plastic vials containing the contrast agent solutions of water and blood were placed in a water bath, and images were acquired with the GSI-5 preset. The images were reformatted into the coronal plane and 5mm diameter ROIs were placed within each solution on a GE Advantage Workstation. Monoenergetic reconstructions were generated from 40 – 140 keV. Results: Mass attenuation (contrast per unit density) for AuNPs was greater than iron, but less than barium and iodine. Contrast was 10.2 (± 3.6) HU for 4 nm AuNP at 0.72 mg/ml and 12.1 (± 4.2) for 2 nm AuNP at 0.31 mg/ml at 70 keV suggesting reasonable chance of visualization at these concentrations for 70 keV reconstruction. The contrast as a function of CT energy is similar in both water and blood. Iodine is most dependent, followed closely by barium and iron, and trailed by a large margin by the AuNP. This was unexpected given Au’s large atomic number and the predominance of photoelectric effect at low energy. Conclusion: Infusion of IVC filters with AuNP is feasible. Discrimination of AuNP-infused IVC filters from surrounding anatomy warrants further investigation.« less

Method and apparatus to characterize ultrasonically reflective contrast agents

NASA Technical Reports Server (NTRS)

Pretlow, Robert A., III (Inventor)

1993-01-01

A method and apparatus for characterizing the time and frequency response of an ultrasonically reflective contrast agent is disclosed. An ultrasonically reflective contrast agent is injected, under constant pressure, into a fluid flowing through a pump flow circuit. The fluid and the ultrasonically reflective contrast agent are uniformly mixed in a mixing chamber, and the uniform mixture is passed through a contrast agent chamber. The contrast agent chamber is acoustically and axially interposed between an ultrasonic transducer chamber and an acoustic isolation chamber. A pulse of ultrasonic energy is transmitted into the contrast agent chamber from the ultrasonic transducer chamber. An echo waveform is received from the ultrasonically reflective contrast agent, and it is analyzed to determine the time and frequency response of the ultrasonically reflective contrast agent.

Ultrasmall water-soluble metal-iron oxide nanoparticles as T1-weighted contrast agents for magnetic resonance imaging.

PubMed

Zeng, Leyong; Ren, Wenzhi; Zheng, Jianjun; Cui, Ping; Wu, Aiguo

2012-02-28

Using an improved hydrolysis method of inorganic salts assisted with water-bath incubation, ultrasmall water-soluble metal-iron oxide nanoparticles (including Fe(3)O(4), ZnFe(2)O(4) and NiFe(2)O(4) nanoparticles) were synthesized in aqueous solutions, which were used as T(1)-weighted contrast agents for magnetic resonance imaging (MRI). The morphology, structure, MRI relaxation properties and cytotoxicity of the as-prepared metal-iron oxide nanoparticles were characterized, respectively. The results showed that the average sizes of nanoparticles were about 4 nm, 4 nm and 5 nm for Fe(3)O(4), ZnFe(2)O(4) and NiFe(2)O(4) nanoparticles, respectively. Moreover, the nanoparticles have good water dispersibility and low cytotoxicity. The MRI test showed the strong T(1)-weighted, but the weak T(2)-weighted MRI performance of metal-iron oxide nanoparticles. The high T(1)-weighted MRI performance can be attributed to the ultrasmall size of metal-iron oxide nanoparticles. Therefore, the as-prepared metal-iron oxide nanoparticles with good water dispersibility and ultrasmall size can have potential applications as T(1)-weighted contrast agent materials for MRI.

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.

Water-Soluble Spinel Ferrites by a Modified Polyol Process as Contrast Agents in MRI

NASA Astrophysics Data System (ADS)

Basina, Georgia; Tzitzios, Vasilis; Niarchos, Dimitris; Li, Wanfeng; Khurshid, Hafsa; Mao, Hui; Hadjipanayis, Costas; Hadjipanayis, George

2010-12-01

Magnetic nanoparticles have recently been very attractive for biomedical applications. In this study, we have synthesized ferrite nanoparticles for application as contrast agents in MRI experiments. Fe3O4 and MnFe2O4 spinel ferrites with a mean size of 11-12 nm, were prepared by a modified polyol route in commercially available polyethylene glycol with molecular weight 600 (PEG-600). The reaction takes place in the presence of water soluble and non-toxic tri-block copolymer known as Pluronic® F-127 (PEO100-PPO65-PEO100). The nanoparticles have saturation magnetization values of 52 and 68 emu/g for MnFe2O4 and Fe3O4, respectively. Both the Fe3O4, and MnFe2O4 nanoparticles make stable solutions in water known as ferrofluids. Preliminary data demonstrated the capability of these nanoparticles to induce imaging contrast in T2 weighted MRI experiments, making these materials suitable for biomedical applications such as medical MRI.

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.

[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.

Visualization and simulation of density driven convection in porous media using magnetic resonance imaging.

PubMed

Montague, James A; Pinder, George F; Gonyea, Jay V; Hipko, Scott; Watts, Richard

2018-05-01

Magnetic resonance imaging is used to observe solute transport in a 40cm long, 26cm diameter sand column that contained a central core of low permeability silica surrounded by higher permeability well-sorted sand. Low concentrations (2.9g/L) of Magnevist, a gadolinium based contrast agent, produce density driven convection within the column when it starts in an unstable state. The unstable state, for this experiment, exists when higher density contrast agent is present above the lower density water. We implement a numerical model in OpenFOAM to reproduce the observed fluid flow and transport from a density difference of 0.3%. The experimental results demonstrate the usefulness of magnetic resonance imaging in observing three-dimensional gravity-driven convective-dispersive transport behaviors in medium scale experiments. Copyright © 2017 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2013-04-01

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

Ultrasound-guided photoacoustic imaging of lymph nodes with biocompatible gold nanoparticles as a novel contrast agent (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sun, In-Cheol; Dumani, Diego; Emelianov, Stanislav Y.

2017-02-01

A key step in staging cancer is the diagnosis of metastasis that spreads through lymphatic system. For this reason, researchers develop various methods of sentinel lymph node mapping that often use a radioactive tracer. This study introduces a safe, cost-effective, high-resolution, high-sensitivity, and real-time method of visualizing the sentinel lymph node: ultrasound-guided photoacoustic (US/PA) imaging augmented by a contrast agent. In this work, we use clearable gold nanoparticles covered by a biocompatible polymer (glycol chitosan) to enhance cellular uptake by macrophages abundant in lymph nodes. We incubate macrophages with glycol-chitosan-coated gold nanoparticles (0.05 mg Au/ml), and then fix them with paraformaldehyde solution for an analysis of in vitro dark-field microscopy and cell phantom. The analysis shows enhanced cellular uptake of nanoparticles by macrophages and strong photoacoustic signal from labeled cells in tissue-mimicking cell phantoms consisting gelatin solution (6 %) with silica gel (25 μm, 0.3%) and fixed macrophages (13 X 105 cells). The in-vivo US/PA imaging of cervical lymph nodes in healthy mice (nu/nu, female, 5 weeks) indicates a strong photoacoustic signal from a lymph node 10 minutes post-injection (2.5 mg Au/ml, 80 μl). The signal intensity and the nanoparticle-labeled volume of tissue within the lymph node continues to increase until 4 h post-injection. Histological analysis further confirms the accumulation of gold nanoparticles within the lymph nodes. This work suggests the feasibility of molecular/cellular US/PA imaging with biocompatible gold nanoparticles as a photoacoustic contrast agent in the diagnosis of lymph-node-related diseases.

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.

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

A morphological evaluation of botulinum neurotoxin A injections into the detrusor muscle using magnetic resonance imaging.

PubMed

Mehnert, Ulrich; Boy, Sönke; Schmid, Marius; Reitz, André; von Hessling, Alexander; Hodler, Juerg; Schurch, Brigitte

2009-06-01

Although botulinum neurotoxin type A (BoNT/A) intradetrusor injections are a recommended therapy for neurogenic detrusor overactivity (NDO), refractory to antimuscarinic drugs, a standardisation of injection technique is missing. Furthermore, some basic questions are still unanswered, as where the toxin solution exactly spreads after injection. Therefore, we investigated the distribution of the toxin solution after injection into the bladder wall, using magnet resonance imaging (MRI). Six patients with NDO were recruited. Three of six patients received 300 U of BoNT/A + contrast agent distributed over 30 injection sites (group 1). The other three patients received 300 U of BoNT/A + contrast agent distributed over 10 injection sites (group 2). Immediately after injection, MRI of the pelvis was performed. The volume of the detrusor and the total volume of contrast medium inside and outside the bladder wall were calculated. In all patients, a small volume (mean 17.6%) was found at the lateral aspects of the bladder dome in the extraperitoneal fat tissue, whereas 82.4% of the injected volume reached the target area (detrusor). In both groups there was a similar distribution of the contrast medium in the target area. A mean of 33.3 and 25.3% of the total detrusor volume was covered in group 1 and 2, respectively. Six weeks after injection, five of six patients were continent and showed no detrusor overactivity in the urodynamic follow-up. No systemic side effects were observed. Our results provide morphological arguments that the currently used injection techniques are appropriate and safe.

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

ParaCEST Agents Encapsulated in Reverse Nano-Assembled Capsules (RACs): How Slow Molecular Tumbling Can Quench CEST Contrast.

PubMed

Farashishiko, Annah; Slack, Jacqueline R; Botta, Mauro; Woods, Mark

2018-01-01

Although paraCEST is a method with immense scope for generating image contrast in MRI, it suffers from the serious drawback of high detection limits. For a typical discrete paraCEST agent the detection limit is roughly an order of magnitude higher than that of a clinically used relaxation agent. One solution to this problem may be the incorporation of a large payload of paraCEST agents into a single macromolecular agent. Here we report a new synthetic method for accomplishing this goal: incorporating a large payload of the paraCEST agent DyDOTAM 3+ into a Reverse Assembled nano-Capsule. An aggregate can be generated between this chelate and polyacrylic acid (PAA) after the addition of ethylene diamine. Subsequent addition of polyallylamine hydrochloride (PAH) followed by silica nanoparticles generated a robust encapsulating shell and afforded capsule with a mean hydrodynamic diameter of 650 ± 250 nm. Unfortunately this encapsulation did not have the effect of amplifying the CEST effect per agent, but quenched the CEST altogether. The quenching effect of encapsulation could be attributed to the effect of slowing molecular tumbling, which is inevitable when the chelate is incorporated into a nano-scale material. This increases the transverse relaxation rate of chelate protons and a theoretical examination using Solomon Bloembergen Morgan theory and the Bloch equations shows that the increase in the transverse relaxation rate constant for the amide protons, in even modestly sized nano-materials, is sufficient to significantly quench CEST.

ParaCEST Agents Encapsulated in Reverse Nano-Assembled Capsules (RACs): How Slow Molecular Tumbling Can Quench CEST Contrast

PubMed Central

Farashishiko, Annah; Slack, Jacqueline R.; Botta, Mauro; Woods, Mark

2018-01-01

Although paraCEST is a method with immense scope for generating image contrast in MRI, it suffers from the serious drawback of high detection limits. For a typical discrete paraCEST agent the detection limit is roughly an order of magnitude higher than that of a clinically used relaxation agent. One solution to this problem may be the incorporation of a large payload of paraCEST agents into a single macromolecular agent. Here we report a new synthetic method for accomplishing this goal: incorporating a large payload of the paraCEST agent DyDOTAM3+ into a Reverse Assembled nano-Capsule. An aggregate can be generated between this chelate and polyacrylic acid (PAA) after the addition of ethylene diamine. Subsequent addition of polyallylamine hydrochloride (PAH) followed by silica nanoparticles generated a robust encapsulating shell and afforded capsule with a mean hydrodynamic diameter of 650 ± 250 nm. Unfortunately this encapsulation did not have the effect of amplifying the CEST effect per agent, but quenched the CEST altogether. The quenching effect of encapsulation could be attributed to the effect of slowing molecular tumbling, which is inevitable when the chelate is incorporated into a nano-scale material. This increases the transverse relaxation rate of chelate protons and a theoretical examination using Solomon Bloembergen Morgan theory and the Bloch equations shows that the increase in the transverse relaxation rate constant for the amide protons, in even modestly sized nano-materials, is sufficient to significantly quench CEST. PMID:29682499

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

Hydrothermally synthesized PEGylated calcium phosphate nanoparticles incorporating Gd-DTPA for contrast enhanced MRI diagnosis of solid tumors.

PubMed

Mi, Peng; Kokuryo, Daisuke; Cabral, Horacio; Kumagai, Michiaki; Nomoto, Takahiro; Aoki, Ichio; Terada, Yasuko; Kishimura, Akihiro; Nishiyama, Nobuhiro; Kataoka, Kazunori

2014-01-28

Organic-inorganic hybrid nanoparticles with calcium phosphate (CaP) core and PEGylated shell were developed to incorporate magnetic resonance imaging (MRI) contrast agent diethylenetriaminepentaacetic acid gadolinium (III) (Gd-DTPA) for noninvasive diagnosis of solid tumors. A two-step preparation method was applied to elaborate hybrid nanoparticles with a z-average hydrodynamic diameter about 80nm, neutral surface ξ-potential and high colloidal stability in physiological environments by self-assembly of poly(ethylene glycol)-b-poly(aspartic acid) block copolymer, Gd-DTPA, and CaP in aqueous solution, followed with hydrothermal treatment. Incorporation into the hybrid nanoparticles allowed Gd-DTPA to show significant enhanced retention ratio in blood circulation, leading to high accumulation in tumor positions due to enhanced permeability and retention (EPR) effect. Moreover, Gd-DTPA revealed above 6 times increase of relaxivity in the nanoparticle system compared to free form, and eventually, selective and elevated contrast enhancements in the tumor positions were observed. These results indicate the high potential of Gd-DTPA-loaded PEGylated CaP nanoparticles as a novel contrast agent for noninvasive cancer diagnosis. Copyright © 2013 Elsevier B.V. All rights reserved.

Accumulation of MRI contrast agents in malignant fibrous histiocytoma for gadolinium neutron capture therapy.

PubMed

Fujimoto, T; Ichikawa, H; Akisue, T; Fujita, I; Kishimoto, K; Hara, H; Imabori, M; Kawamitsu, H; Sharma, P; Brown, S C; Moudgil, B M; Fujii, M; Yamamoto, T; Kurosaka, M; Fukumori, Y

2009-07-01

Neutron-capture therapy with gadolinium (Gd-NCT) has therapeutic potential, especially that gadolinium is generally used as a contrast medium in magnetic resonance imaging (MRI). The accumulation of gadolinium in a human sarcoma cell line, malignant fibrosis histiocytoma (MFH) Nara-H, was visualized by the MRI system. The commercially available MRI contrast medium Gd-DTPA (Magnevist, dimeglumine gadopentetate aqueous solution) and the biodegradable and highly gadopentetic acid (Gd-DTPA)-loaded chitosan nanoparticles (Gd-nanoCPs) were prepared as MRI contrast agents. The MFH cells were cultured and collected into three falcon tubes that were set into the 3-tesra MRI system to acquire signal intensities from each pellet by the spin echo method, and the longitudinal relaxation time (T1) was calculated. The amount of Gd in the sample was measured by inductively coupled plasma atomic emission spectrography (ICP-AES). The accumulation of gadolinium in cells treated with Gd-nanoCPs was larger than that in cells treated with Gd-DTPA. In contrast, and compared with the control, Gd-DTPA was more effective than Gd-nanoCPs in reducing T1, suggesting that the larger accumulation exerted the adverse effect of lowering the enhancement of MRI. Further studies are warranted to gain insight into the therapeutic potential of Gd-NCT.

Associative Interactions in Crowded Solutions of Biopolymers Counteract Depletion Effects.

PubMed

Groen, Joost; Foschepoth, David; te Brinke, Esra; Boersma, Arnold J; Imamura, Hiromi; Rivas, Germán; Heus, Hans A; Huck, Wilhelm T S

2015-10-14

The cytosol of Escherichia coli is an extremely crowded environment, containing high concentrations of biopolymers which occupy 20-30% of the available volume. Such conditions are expected to yield depletion forces, which strongly promote macromolecular complexation. However, crowded macromolecule solutions, like the cytosol, are very prone to nonspecific associative interactions that can potentially counteract depletion. It remains unclear how the cytosol balances these opposing interactions. We used a FRET-based probe to systematically study depletion in vitro in different crowded environments, including a cytosolic mimic, E. coli lysate. We also studied bundle formation of FtsZ protofilaments under identical crowded conditions as a probe for depletion interactions at much larger overlap volumes of the probe molecule. The FRET probe showed a more compact conformation in synthetic crowding agents, suggesting strong depletion interactions. However, depletion was completely negated in cell lysate and other protein crowding agents, where the FRET probe even occupied slightly more volume. In contrast, bundle formation of FtsZ protofilaments proceeded as readily in E. coli lysate and other protein solutions as in synthetic crowding agents. Our experimental results and model suggest that, in crowded biopolymer solutions, associative interactions counterbalance depletion forces for small macromolecules. Furthermore, the net effects of macromolecular crowding will be dependent on both the size of the macromolecule and its associative interactions with the crowded background.

C-field cosmological models: revisited

NASA Astrophysics Data System (ADS)

Yadav, Anil Kumar; Tawfiq Ali, Ahmad; Ray, Saibal; Rahaman, Farook; Hossain Sardar, Iftikar

2016-12-01

We investigate plane symmetric spacetime filled with perfect fluid in the C-field cosmology of Hoyle and Narlikar. A new class of exact solutions has been obtained by considering the creation field C as a function of time only. To get the deterministic solution, it has been assumed that the rate of creation of matter-energy density is proportional to the strength of the existing C-field energy density. Several physical aspects and geometrical properties of the models are discussed in detail, especially showing that some of our solutions of C-field cosmology are free from singularity in contrast to the Big Bang cosmology. A comparative study has been carried out between two models, one singular and the other nonsingular, by contrasting the behaviour of the physical parameters. We note that the model in a unique way represents both the features of the accelerating as well as decelerating universe depending on the parameters and thus seems to provide glimpses of the oscillating or cyclic model of the universe without invoking any other agent or theory in allowing cyclicity.

One-pot synthesis of magnetic nanoclusters enabling atherosclerosis-targeted magnetic resonance imaging.

PubMed

Kukreja, Aastha; Lim, Eun-Kyung; Kang, Byunghoon; Choi, Yuna; Lee, Taeksu; Suh, Jin-Suck; Huh, Yong-Min; Haam, Seungjoo

2014-01-01

In this study, dextran-encrusted magnetic nanoclusters (DMNCs) were synthesized using a one-pot solution phase method for detection of atherosclerosis by magnetic resonance imaging. Pyrenyl dextran was used as a surfactant because of its electron-stabilizing effect and its amphiphilic nature, rendering the DMNCs stable and water-dispersible. The DMNCs were 65.6±4.3 nm, had a narrow size distribution, and were superparamagnetic with a high magnetization value of 60.1 emu/g. Further, they showed biocompatibility and high cellular uptake efficiency, as indicated by a strong interaction between dextran and macrophages. In vivo magnetic resonance imaging demonstrated the ability of DMNCs to act as an efficient magnetic resonance imaging contrast agent capable of targeted detection of atherosclerosis. In view of these findings, it is concluded that DMNCs can be used as magnetic resonance imaging contrast agents to detect inflammatory disease.

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.

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

Demeclocycline as a contrast agent for detecting brain neoplasms using confocal microscopy

NASA Astrophysics Data System (ADS)

Wirth, Dennis; Smith, Thomas W.; Moser, Richard; Yaroslavsky, Anna N.

2015-04-01

Complete resection of brain tumors improves life expectancy and quality. Thus, there is a strong need for high-resolution detection and microscopically controlled removal of brain neoplasms. The goal of this study was to test demeclocycline as a contrast enhancer for the intraoperative detection of brain tumors. We have imaged benign and cancerous brain tumors using multimodal confocal microscopy. The tumors investigated included pituitary adenoma, meningiomas, glioblastomas, and metastatic brain cancers. Freshly excised brain tissues were stained in 0.75 mg ml-1 aqueous solution of demeclocyline. Reflectance images were acquired at 402 nm. Fluorescence signals were excited at 402 nm and registered between 500 and 540 nm. After imaging, histological sections were processed from the imaged specimens and compared to the optical images. Fluorescence images highlighted normal and cancerous brain cells, while reflectance images emphasized the morphology of connective tissue. The optical and histological images were in accordance with each other for all types of tumors investigated. Demeclocyline shows promise as a contrast agent for intraoperative detection of brain tumors.

Optical clearing of skin enhanced with hyaluronic acid for increased contrast of optoacoustic imaging

NASA Astrophysics Data System (ADS)

Liopo, Anton; Su, Richard; Tsyboulski, Dmitri A.; Oraevsky, Alexander A.

2016-08-01

Enhanced delivery of optical clearing agents (OCA) through skin may improve sensitivity of optical and optoacoustic (OA) methods of imaging, sensing, and monitoring. This report describes a two-step method for enhancement of light penetration through skin. Here, we demonstrate that topical application of hyaluronic acid (HA) improves skin penetration of hydrophilic and lipophilic OCA and thus enhances their performance. We examined the OC effect of 100% polyethylene and polypropylene glycols (PPGs) and their mixture after pretreatment by HA, and demonstrated significant increase in efficiency of light penetration through skin. Increased light transmission resulted in a significant increase of OA image contrast in vitro. Topical pretreatment of skin for about 30 min with 0.5% HA in aqueous solution offers effective delivery of low molecular weight OCA such as a mixture of PPG-425 and polyethylene glycol (PEG)-400. The developed approach of pretreatment by HA prior to application of clearing agents (PEG and PPG) resulted in a ˜47-fold increase in transmission of red and near-infrared light and significantly enhanced contrast of OA images.

High resolution 3D MRI of mouse mammary glands with intra-ductal injection of contrast media

PubMed Central

Markiewicz, Erica; Fan, Xiaobing; Mustafi, Devkumar; Zamora, Marta; Roman, Brian B.; Jansen, Sanaz A.; Macleod, Kay; Conzen, Suzanne D.; Karczmar, Gregory S.

2014-01-01

The purpose of this study was to use high resolution 3D MRI to study mouse mammary gland ductal architecture based on intra-ductal injection of contrast agents. Female FVB/N mice age 12–20 weeks (n = 12), were used in this study. A 34G, 45° tip Hamilton needle with a 25uL Hamilton syringe was inserted into the tip of the nipple. Approximately 20–25uL of a Gadodiamide/Trypan blue/saline solution was injected slowly over one minute into the nipple and duct. To prevent washout of contrast media from ducts due to perfusion, and maximize the conspicuity of ducts on MRI, mice were sacrificed one minute after injection. High resolution 3D T1-weighted images were acquired on a 9.4T Bruker scanner after sacrifice to eliminate motion artifacts and reduce contrast media leakage from ducts. Trypan blue staining was well distributed throughout the ductal tree. MRI showed the mammary gland ductal structure clearly. In spoiled gradient echo T1-weighted images, the signal-to-noise ratio of regions identified as enhancing mammary ducts following contrast injection was significantly higher than that of muscle (p < 0.02) and significantly higher than that of contralateral mammary ducts that were not injected with contrast media (p < 0.0001). The methods described here could be adapted for injection of specialized contrast agents to measure metabolism or target receptors in normal ducts and ducts with in situ cancers. PMID:25179139

Synthesis of Biocompatible Nanoparticulate Coordination Polymers for Diagnostic and Therapeutic Applications

NASA Astrophysics Data System (ADS)

Kandanapitiye, Murthi S.

The combination of nanotechnology with medicinal chemistry has developed into a burgeoning research area. Nanomaterials (NMs) could be seamlessly interfaced with various facets in biology, biochemistry, medicinal chemistry and environmental chemistry that may not be available to the same material in the bulk scale. This dissertation research has focused on the development of nanoparticulate coordination polymers for diagnostic and therapeutic applications. Modern imaging techniques include X-ray computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and positron emission tomography (PET). We have successfully developed several types of nanoparticulate diagnostics and therapeutics that have some potential usefulness in biomedicine. Synthesis and characterization of nanoparticulate based PET (Positron emission tomography)/SPECT (Single photon emission computed tomography) are discussed in chapter 3. In chapter 4, preparation and potential utility of non-gadolinium based MRI contrast agent are reported for T1-weighted application. As far as the solely effectiveness of relaxation is concerned, Gd-based T 1-weighted MRI contrast agents have excellent enhancement of image contrast but they have risks of biological toxicity. Consequently, the search for T 1-weighted CAs with high efficacy and low toxicity has gained attention toward the Mn(II) and Fe(III). Fe(III) is considered to be more toxic to cells because free ferric or ferrous ions can catalyze the production of reactive oxygen species via the Fenton reactions. Paramagnetic chelates of Mn(II) could be employed as T1-weighted CAs. However, it is challenging to design and synthesize highly stable Mn(II) complexes that could maintain the integrity when administered to living system. Chapter 4 describes the synthesis and utility of nanoparticulate Mn analogue of Prussian blue (K2Mn 3[FeII(CN)6]2) as an effective T1 MRI contrast agent for cellular imaging X-ray computed tomography is capable of delineating the 3-D images of soft tissues with superb quality. The variation of X-ray attenuation from one tissue to another is used to generate the well spatial resolved superb quality images. Exogenous radiopaque agents are necessary for the superb visualization of different types of soft tissues. Heavy metals with high atomic number are better suited for biomedical applications to enhance the image contrast due to their high mass attenuation coefficient. Bismuth (Z- 83) is the nonradioactive, heaviest, nontoxic element available among the other closest neighbors (Hg, Tl, Pb and Po) of the periodic table. We have set out to search for compounds that are hydrolytically stable, more efficient and more amenable in terms of biocompatibility. Moreover this new discovery can significantly reduce the average radiation dose in one CT scan. We have discovered a simple one-step aqueous solution route for preparing biocompatible and ultra-small bismuth oxyiodide BiOI nanoparticles and investigated their potential application as an efficient CT contrast agent. Our ultra-small monodisperse BiOI NPs have excellent water dispersability, thermodynamic stability, kinetic inertness, high biocompatibility and superior attenuation power, suggesting their potential as an organ-specific CT contrast agent that may fill the gap left by the other nanoparticulate and iodine-based CT contrasting agents. The chapter 6 of this dissertation discusses synthesis and characterization of novel nanoparticulate therapeutics and theranostics. D-penicillamine has the highest efficacy, and hence is currently the most widely used drug for WD across the world. We have prepared the D-PEN-conjugated Au NPs of the average size of 16 [special character omited] 2 nm with superb water dispersability, and examined the kinetics and selectivity of copper binding of such NPs in aqueous solution. We also studied the cellular uptake, cytotoxicity and intracellular copper removal of these NPs to demonstrate their potential as a novel cell-penetrable copper detoxifying agent. Our approach of tackling these problems focuses on the development of cell-permeable copper-depleting nanoparticles that can be surface-engineered to be potentially organ-specific when targeting agents are used to form new-generation drugs for WD. The latter part of chapter 6, we describe the synthesis, characterization of zinc analogue of Prussian blue (K2Zn3[Fe(CN) 6]2-ZnPB) for intracellular copper detoxification. (Abstract shortened by ProQuest.).

Dual-energy contrast-enhanced digital mammography (DE-CEDM): optimization on digital subtraction with practical x-ray low/high-energy spectra

NASA Astrophysics Data System (ADS)

Chen, Biao; Jing, Zhenxue; Smith, Andrew P.; Parikh, Samir; Parisky, Yuri

2006-03-01

Dual-energy contrast enhanced digital mammography (DE-CEDM), which is based upon the digital subtraction of low/high-energy image pairs acquired before/after the administration of contrast agents, may provide physicians physiologic and morphologic information of breast lesions and help characterize their probability of malignancy. This paper proposes to use only one pair of post-contrast low / high-energy images to obtain digitally subtracted dual-energy contrast-enhanced images with an optimal weighting factor deduced from simulated characteristics of the imaging chain. Based upon our previous CEDM framework, quantitative characteristics of the materials and imaging components in the x-ray imaging chain, including x-ray tube (tungsten) spectrum, filters, breast tissues / lesions, contrast agents (non-ionized iodine solution), and selenium detector, were systemically modeled. Using the base-material (polyethylene-PMMA) decomposition method based on entrance low / high-energy x-ray spectra and breast thickness, the optimal weighting factor was calculated to cancel the contrast between fatty and glandular tissues while enhancing the contrast of iodized lesions. By contrast, previous work determined the optimal weighting factor through either a calibration step or through acquisition of a pre-contrast low/high-energy image pair. Computer simulations were conducted to determine weighting factors, lesions' contrast signal values, and dose levels as functions of x-ray techniques and breast thicknesses. Phantom and clinical feasibility studies were performed on a modified Selenia full field digital mammography system to verify the proposed method and computer-simulated results. The resultant conclusions from the computer simulations and phantom/clinical feasibility studies will be used in the upcoming clinical study.

A Comparative Study of Probability Collectives Based Multi-agent Systems and Genetic Algorithms

NASA Technical Reports Server (NTRS)

Huang, Chien-Feng; Wolpert, David H.; Bieniawski, Stefan; Strauss, Charles E. M.

2005-01-01

We compare Genetic Algorithms (GA's) with Probability Collectives (PC), a new framework for distributed optimization and control. In contrast to GA's, PC-based methods do not update populations of solutions. Instead they update an explicitly parameterized probability distribution p over the space of solutions. That updating of p arises as the optimization of a functional of p. The functional is chosen so that any p that optimizes it should be p peaked about good solutions. The PC approach works in both continuous and discrete problems. It does not suffer from the resolution limitation of the finite bit length encoding of parameters into GA alleles. It also has deep connections with both game theory and statistical physics. We review the PC approach using its motivation as the information theoretic formulation of bounded rationality for multi-agent systems. It is then compared with GA's on a diverse set of problems. To handle high dimensional surfaces, in the PC method investigated here p is restricted to a product distribution. Each distribution in that product is controlled by a separate agent. The test functions were selected for their difficulty using either traditional gradient descent or genetic algorithms. On those functions the PC-based approach significantly outperforms traditional GA's in both rate of descent, trapping in false minima, and long term optimization.

Time-Resolved Spectroscopy and Near Infrared Imaging for Prostate Cancer Detection: Receptor-targeted and Native Biomarker

NASA Astrophysics Data System (ADS)

Pu, Yang

Optical spectroscopy and imaging using near-infrared (NIR) light provides powerful tools for non-invasive detection of cancer in tissue. Optical techniques are capable of quantitative reconstructions maps of tissue absorption and scattering properties, thus can map in vivo the differences in the content of certain marker chromophores and/or fluorophores in normal and cancerous tissues (for example: water, tryptophan, collagen and NADH contents). Potential clinical applications of optical spectroscopy and imaging include functional tumor detection and photothermal therapeutics. Optical spectroscopy and imaging apply contrasts from intrinsic tissue chromophores such as water, collagen and NADH, and extrinsic optical contrast agents such as Indocyanine Green (ICG) to distinguish disease tissue from the normal one. Fluorescence spectroscopy and imaging also gives high sensitivity and specificity for biomedical diagnosis. Recent developments on specific-targeting fluorophores such as small receptor-targeted dye-peptide conjugate contrast agent offer high contrast between normal and cancerous tissues hence provide promising future for early tumour detection. This thesis focus on a study to distinguish the cancerous prostate tissue from the normal prostate tissues with enhancement of specific receptor-targeted prostate cancer contrast agents using optical spectroscopy and imaging techniques. The scattering and absorption coefficients, and anisotropy factor of cancerous and normal prostate tissues were investigated first as the basis for the biomedical diagnostic and optical imaging. Understanding the receptors over-expressed prostate cancer cells and molecular target mechanism of ligand, two small ICG-derivative dye-peptides, namely Cypate-Bombesin Peptide Analogue Conjugate (Cybesin) and Cypate-Octreotate Peptide Conjugate (Cytate), were applied to study their clinical potential for human prostate cancer detection. In this work, the steady-state and time-resolved fluorescence spectroscopy of Cybesin (Cytate) in solution, and in cancerous and normal prostate tissues were studied. It was found that more Cybesin (Cytate) was uptaken in the cancerous prostate tissue than those in the normal tissue. The preferential uptake of Cybesin (Cytate) in cancerous tissue was used to image and distinguish cancerous areas from the normal tissue. To investigate rotational dynamics and fluorescence polarization anisotropy of the contrast agents in prostate tissues, an analytical model was used to extract the rotational times and polarization anisotropies, which were observed for higher values of Cybesin (Cytate)-stained cancerous prostate tissue in comparison with the normal tissue. These reflect changes of microstructures of cancerous and normal tissues and their different binding affinity with contrast agents. The results indicate that the use of optical spectroscopy and imaging combined with receptor-targeted contrast agents is a valuable tool to study microenvironmental changes of tissue, and detect prostate cancer in early stage.

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.

Functional Nanoparticles for Magnetic Resonance Imaging

PubMed Central

Mao, Xinpei; Xu, Jiadi; Cui, Honggang

2016-01-01

Nanoparticle-based magnetic resonance imaging (MRI) contrast agents have received much attention over the past decade. By virtue of a high payload of magnetic moieties, enhanced accumulation at disease sites, and a large surface area for additional modification with targeting ligands, nanoparticle-based contrast agents offer promising new platforms to further enhance the high resolution and sensitivity of MRI for various biomedical applications. T2* superparamagnetic iron oxide nanoparticles (SPIONs) first demonstrated superior improvement on MRI sensitivity. The prevailing SPION attracted growing interest in the development of refined nanoscale versions of MRI contrast agents. Afterwards, T1-based contrast agents were developed, and became the most studied subject in MRI due to the positive contrast they provide that avoids the susceptibility associated with MRI signal reduction. Recently, chemical exchange saturation transfer (CEST) contrast agents have emerged and rapidly gained popularity. The unique aspect of CEST contrast agents is that their contrast can be selectively turned “on” and “off” by radiofrequency (RF) saturation. Their performance can be further enhanced by incorporating a large number of exchangeable protons into well-defined nanostructure. Besides activatable CEST contrast agents, there is growing interest in developing nanoparticle-based activatable MRI contrast agents responsive to stimuli (pH, enzyme, etc.), which improves sensitivity and specificity. In this review, we summarize the recent development of various types of nanoparticle-based MRI contrast agents, and have focused our discussions on the key advantages of introducing nanoparticles in MRI. PMID:27040463

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.

Contrast Agents for Micro-Computed Tomography of Microdamage in Bone

DTIC Science & Technology

2011-01-01

solution from DI water (or PBS). For the second model, a 5 mm cube of cortical bone tissue was embedded in polymethylmethacrylate and sectioned...radiography1 and as a radiopacifer in polymethylmethacrylate bone cement.2 Current commercial products for either application use microscale BaSO4 particles... polymethylmethacrylate bone cement (Lewis, 1997). The objective of this study was to non-destructively and three-dimensionally image microdamage

Contrast Agents for Micro-Computed Tomography of Microdamage in Bone

DTIC Science & Technology

2009-01-01

carboxylate (reported in January 2009), phosphonate and bisphosphonate groups (Fig. 2). The presence of functional groups was verified by FT- IR (Fig. 3...carboxylic acid, (b) phosphonate or (c) bisphosphonate groups for calcium binding damaged tissue. (a) (b) (c) Fig. 3. FT- IR spectra for Au NPs...functional group. Quantitative measurements of the binding affinity were performed by adding hydroxyapatite (HA) crystals to functionalized Au NP solutions in

Safety of oral sulfates in rats and dogs contrasted with phosphate-induced nephropathy in rats.

PubMed

Pelham, Russell W; Russell, Robert G; Padgett, Eric L; Reno, Frederick E; Cleveland, Mark vB

2009-01-01

An oral sulfate salt solution (OSS), under development as a bowel cleansing agent for colonoscopy in humans, is studied in rats and dogs. In rats, amaximumpractical oral OSS dose (5 g/kg/d) is compared with an oral sodium phosphate (OSP) solution, both at about 7 times the clinical dose. OSS induces the intended effects of loose stools and diarrhea. In rats, higher urine sodium and potassium accompany higher clearance rates, considered adaptive to the osmotic load of OSS. OSS for 28 days is well tolerated in rats and dogs. In contrast, OSP causes increased mortality, reduced body weight and food consumption, severe kidney tubular degeneration, and calcium phosphate deposition in rats. These are accompanied by mineralization in the stomach and aorta, along with cardiac and hepatic degeneration and necrosis. The greater safety margin of OSS over OSP at similarmultiples of the clinical dose indicates its suitability for human use.

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

Facile preparation of uniform FeSe2 nanoparticles for PA/MR dual-modal imaging and photothermal cancer therapy

NASA Astrophysics Data System (ADS)

Fu, Tingting; Chen, Yuyan; Hao, Jiali; Wang, Xiaoyong; Liu, Gang; Li, Yonggang; Liu, Zhuang; Cheng, Liang

2015-12-01

Recently, magnetic photothermal nanomaterials have emerged as a new class of bio-nanomaterials for application in cancer diagnosis and therapy. Hence, we developed a new kind of magnetic nanomaterials, iron diselenide (FeSe2) nanoparticles, for multimodal imaging-guided photothermal therapy (PTT) to improve the efficacy of cancer treatment. By controlling the reaction time and temperature, FeSe2 nanoparticles were synthesized by a simple solution-phase method. After modification with polyethylene glycol (PEG), the obtained FeSe2-PEG nanoparticles showed high stability under various physiological conditions. FeSe2-PEG could serve as a T2-weighted magnetic resonance (MR) imaging contrast agent because of its strong superparamagnetic properties, with its r2 relaxivity determined to be 133.38 mM-1 S-1, a value higher than that of the clinically used Feridex. On the other hand, with high absorbance in the near-infrared (NIR) region, FeSe2-PEG also appeared to be a useful contrast agent for photoacoustic imaging (PA) as well as an effective photothermal agent for PTT cancer treatment, as demonstrated in our animal tumor model experiments. Moreover, long-term toxicity tests have proven that FeSe2-PEG nanoparticles after systematic administration rendered no appreciable toxicity to the treated animals, and could be gradually excreted from the major organs of mice. Our work indicates that FeSe2-PEG nanoparticles would be a new class of theranostic agents promising for application in bioimaging and cancer therapy.Recently, magnetic photothermal nanomaterials have emerged as a new class of bio-nanomaterials for application in cancer diagnosis and therapy. Hence, we developed a new kind of magnetic nanomaterials, iron diselenide (FeSe2) nanoparticles, for multimodal imaging-guided photothermal therapy (PTT) to improve the efficacy of cancer treatment. By controlling the reaction time and temperature, FeSe2 nanoparticles were synthesized by a simple solution-phase method. After modification with polyethylene glycol (PEG), the obtained FeSe2-PEG nanoparticles showed high stability under various physiological conditions. FeSe2-PEG could serve as a T2-weighted magnetic resonance (MR) imaging contrast agent because of its strong superparamagnetic properties, with its r2 relaxivity determined to be 133.38 mM-1 S-1, a value higher than that of the clinically used Feridex. On the other hand, with high absorbance in the near-infrared (NIR) region, FeSe2-PEG also appeared to be a useful contrast agent for photoacoustic imaging (PA) as well as an effective photothermal agent for PTT cancer treatment, as demonstrated in our animal tumor model experiments. Moreover, long-term toxicity tests have proven that FeSe2-PEG nanoparticles after systematic administration rendered no appreciable toxicity to the treated animals, and could be gradually excreted from the major organs of mice. Our work indicates that FeSe2-PEG nanoparticles would be a new class of theranostic agents promising for application in bioimaging and cancer therapy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06840a

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.

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

An evaluation of the sonoporation potential of low-boiling point phase-change ultrasound contrast agents in vitro.

PubMed

Fix, Samantha M; Novell, Anthony; Yun, Yeoheung; Dayton, Paul A; Arena, Christopher B

2017-01-01

Phase-change ultrasound contrast agents (PCCAs) offer a solution to the inherent limitations associated with using microbubbles for sonoporation; they are characterized by prolonged circulation lifetimes, and their nanometer-scale sizes may allow for passive accumulation in solid tumors. As a first step towards the goal of extravascular cell permeabilization, we aim to characterize the sonoporation potential of a low-boiling point formulation of PCCAs in vitro. Parameters to induce acoustic droplet vaporization and subsequent microbubble cavitation were optimized in vitro using high-speed optical microscopy. Sonoporation of pancreatic cancer cells in suspension was then characterized at a range of pressures (125-600 kPa) and pulse lengths (5-50 cycles) using propidium iodide as an indicator molecule. We achieved sonoporation efficiencies ranging from 8 ± 1% to 36 ± 4% (percent of viable cells), as evidenced by flow cytometry. Increasing sonoporation efficiency trended with increasing pulse length and peak negative pressure. We conclude that PCCAs can be used to induce the sonoporation of cells in vitro, and our results warrant further investigation into the use of PCCAs as extravascular sonoporation agents in vivo.

High resolution 3D MRI of mouse mammary glands with intra-ductal injection of contrast media.

PubMed

Markiewicz, Erica; Fan, Xiaobing; Mustafi, Devkumar; Zamora, Marta; Roman, Brian B; Jansen, Sanaz A; Macleod, Kay; Conzen, Suzanne D; Karczmar, Gregory S

2015-01-01

The purpose of this study was to use high resolution three-dimensional (3D) magnetic resonance imaging (MRI) to study mouse mammary gland ductal architecture based on intra-ductal injection of contrast agents. Female FVB/N mice age 12-20 weeks (n=12), were used in this study. A 34G, 45° tip Hamilton needle with a 25μL Hamilton syringe was inserted into the tip of the nipple. Approximately 20-25μL of a Gadodiamide/Trypan blue/saline solution was injected slowly over one minute into the nipple and duct. To prevent washout of contrast media from ducts due to perfusion, and maximize the conspicuity of ducts on MRI, mice were sacrificed one minute after injection. High resolution 3D T1-weighted images were acquired on a 9.4T Bruker scanner after sacrifice to eliminate motion artifacts and reduce contrast media leakage from ducts. Trypan blue staining was well distributed throughout the ductal tree. MRI showed the mammary gland ductal structure clearly. In spoiled gradient echo T1-weighted images, the signal-to-noise ratio of regions identified as enhancing mammary ducts following contrast injection was significantly higher than that of muscle (p<0.02) and significantly higher than that of contralateral mammary ducts that were not injected with contrast media (p<0.0001). The methods described here could be adapted for injection of specialized contrast agents to measure metabolism or target receptors in normal ducts and ducts with in situ cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

Basic MR relaxation mechanisms and contrast agent design.

PubMed

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

2015-09-01

The diagnostic capabilities of magnetic resonance imaging (MRI) have undergone continuous and substantial evolution by virtue of hardware and software innovations and the development and implementation of exogenous contrast media. Thirty years since the first MRI contrast agent was approved for clinical use, a reliance on MR contrast media persists, largely to improve image quality with higher contrast resolution and to provide additional functional characterization of normal and abnormal tissues. Further development of MR contrast media is an important component in the quest for continued augmentation of diagnostic capabilities. In this review we detail the many important considerations when pursuing the design and use of MR contrast media. We offer a perspective on the importance of chemical stability, particularly kinetic stability, and how this influences one's thinking about the safety of metal-ligand-based contrast agents. We discuss the mechanisms involved in MR relaxation in the context of probe design strategies. A brief description of currently available contrast agents is accompanied by an in-depth discussion that highlights promising MRI contrast agents in the development of future clinical and research applications. Our intention is to give a diverse audience an improved understanding of the factors involved in developing new types of safe and highly efficient MR contrast agents and, at the same time, provide an appreciation of the insights into physiology and disease that newer types of responsive agents can provide. © 2015 Wiley Periodicals, Inc.

"Basic MR Relaxation Mechanisms & Contrast Agent Design"

PubMed Central

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

2015-01-01

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

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

Ultrasonic Analysis of Peptide- and Antibody-Targeted Microbubble Contrast Agents for Molecular Imaging of αvβ3-Expressing Cells

PubMed Central

Dayton, Paul A.; Pearson, David; Clark, Jarrod; Simon, Scott; Schumann, Patricia A.; Zutshi, Reena; Matsunaga, Terry O.; Ferrara, Katherine W.

2008-01-01

The goal of targeted ultrasound contrast agents is to significantly and selectively enhance the detection of a targeted vascular site. In this manuscript, three distinct contrast agents targeted to the αvβ3 integrin are examined. The αvβ3 integrin has been shown to be highly expressed on metastatic tumors and endothelial cells during neovascularization, and its expression has been shown to correlate with tumor grade. Specific adhesion of these contrast agents to αvβ3-expressing cell monolayers is demonstrated in vitro, and compared with that of nontargeted agents. Acoustic studies illustrate a backscatter amplitude increase from monolayers exposed to the targeted contrast agents of up to 13-fold (22 dB) relative to enhancement due to control bubbles. A linear dependence between the echo amplitude and bubble concentration was observed for bound agents. The decorrelation of the echo from adherent targeted agents is observed over successive pulses as a function of acoustic pressure and bubble density. Frequency–domain analysis demonstrates that adherent targeted bubbles exhibit high-amplitude narrowband echo components, in contrast to the primarily wideband response from free microbubbles. Results suggest that adherent targeted contrast agents are differentiable from free-floating microbubbles, that targeted contrast agents provide higher sensitivity in the detection of angiogenesis, and that conventional ultrasound imaging techniques such as signal subtraction or decorrelation detection can be used to detect integrin-expressing vasculature with sufficient signal-to-noise. PMID:15296677

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.

Use of Yb(III) Centered Near Infra-Red (NIR) Luminescence to Determine the Hydration State of a 3,2-HOPO based MRI-Contrast Agent

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

Moore, Evan G.; Seitz, Michael; Raymond, Kenneth N.

It has been more than a decade since the first reports of [Gd(Tren-Me-3,2-HOPO)(H{sub 2}O){sub 2}] as a potential new class of magnetic resonance imaging contrast agent (MRI-CA). The defining feature of these 1-methyl-3-hydroxypyridin-2-one (Me-3,2-HOPO) based compounds has been the use of a hexadentate ligand design, and hence an increase in the number of metal bound water molecules, without sacrificing complex stability compared to the typically octadentate contrast agents used commercially. Since that time, significant advances in the properties of these chelates have been steadily reported, including improvements in relaxivity, incorporation into macromolecular architectures and, recently, the first direct verification ofmore » solution structure using the discovery of Eu(III) centered luminescence with the isomeric 1-hydroxypyridin-2-one (1,2-HOPO) chelate as a sensitizing chromophore. Nonetheless, it has remained frustrating that direct measurements of the inner sphere hydration state, q, using luminescence techniques with the parent Me-3,2-HOPO compounds have remained elusive, even when direct laser excitation of weakly absorbing f-f transitions were employed (eg. for Eu(III) complexes). This failing can likely be traced to the presence of a low lying LMCT state which efficiently quenches metal based emission. Instead, estimates of the q and hence solution structure have relied on the fitting of relaxivity data to the Solomon-Bloembergen-Morgan equations or, where sufficiently soluble in aqueous solution, studies on the temperature dependence of the paramagnetic contribution to the water {sup 17}O NMR transverse relaxation rate. Recently, Beeby et al reported on a qualitative equation to determine inner sphere hydration based on the change in lifetimes for Yb(III) in going from H{sub 2}O to D{sub 2}O solution, and we reasoned that the lower energy accepting state of Yb(III) may lie below the LMCT state which quenches Eu(III) emission, and hence may facilitate sensitized emission from Yb(III). This hypothesis was borne out experimentally, and herein we describe for the first time sensitized luminescence in the Near Infra-Red (NIR) region from a [Yb(Tren-Me-3,2-HOPO)(H{sub 2}O){sub 2}] complex, and hence the direct measurement of q for the archetypical member of this family of compounds.« less

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.

Dual-energy fluorescent x-ray computed tomography system with a pinhole design: Use of K-edge discontinuity for scatter correction

PubMed Central

Sasaya, Tenta; Sunaguchi, Naoki; Thet-Lwin, Thet-; Hyodo, Kazuyuki; Zeniya, Tsutomu; Takeda, Tohoru; Yuasa, Tetsuya

2017-01-01

We propose a pinhole-based fluorescent x-ray computed tomography (p-FXCT) system with a 2-D detector and volumetric beam that can suppress the quality deterioration caused by scatter components. In the corresponding p-FXCT technique, projections are acquired at individual incident energies just above and below the K-edge of the imaged trace element; then, reconstruction is performed based on the two sets of projections using a maximum likelihood expectation maximization algorithm that incorporates the scatter components. We constructed a p-FXCT imaging system and performed a preliminary experiment using a physical phantom and an I imaging agent. The proposed dual-energy p-FXCT improved the contrast-to-noise ratio by a factor of more than 2.5 compared to that attainable using mono-energetic p-FXCT for a 0.3 mg/ml I solution. We also imaged an excised rat’s liver infused with a Ba contrast agent to demonstrate the feasibility of imaging a biological sample. PMID:28272496

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.

The pandemonium system of reflective agents.

PubMed

Smieja, F

1996-01-01

The Pandemonium system of reflective MINOS agents solves problems by automatic dynamic modularization of the input space. The agents contain feedforward neural networks which adapt using the backpropagation algorithm. We demonstrate the performance of Pandemonium on various categories of problems. These include learning continuous functions with discontinuities, separating two spirals, learning the parity function, and optical character recognition. It is shown how strongly the advantages gained from using a modularization technique depend on the nature of the problem. The superiority of the Pandemonium method over a single net on the first two test categories is contrasted with its limited advantages for the second two categories. In the first case the system converges quicker with modularization and is seen to lead to simpler solutions. For the second case the problem is not significantly simplified through flat decomposition of the input space, although convergence is still quicker.

Fabrication of Indocyanine Green and 2H, 3H-perfluoropentane loaded microbubbles for fluorescence and ultrasound imaging

NASA Astrophysics Data System (ADS)

He, Yutong; Wu, Qiang; Ma, Rong; Chang, Shufang; Shao, Pengfei; Xu, Ronald

2016-03-01

As a near-infrared (NIR) fluorescence dye, Indocyanine Green (ICG) has not gained broader clinical applications, owing to its multiple limitations such as concentration-dependent aggregation, low fluorescence quantum yield, poor physicochemical stability and rapid elimination from the body. In the meanwhile, 2H,3H-perfluoropentane (H-PFP) has been widely studied in ultrasound imaging as a vehicle for targeted delivery of contrast agents and drugs. We synthesized a novel dual-modal fluorescence and ultrasound contrast agent by encapsulating ICG and H-PFP in lipid microbubbles using a liquid-driven coaxial flow focusing (LDCFF) process. Uniform microbubbles with the sizes ranging from 1-10um and great ICG loading efficiency was achieved by this method. Our benchtop experiments showed that ICG/H-PFP microbubbles exhibited less aggregation, increased fluorescence intensity and more stable photostability compared to free ICG aqueous solution. Our phantom experiments demonstrated that ICG/H-PFP microbubbles enhanced the imaging contrasts in fluorescence imaging and ultrasonography. Our animal experiments indicated that ICG/H-PFP microbubbles extended the ICG life time and facilitated dual mode fluorescence and ultrasound imaging in vivo.

Quantum dots as contrast agents for endoscopy: mathematical modeling and experimental validation of the optimal excitation wavelength

NASA Astrophysics Data System (ADS)

Roy, Mathieu; DaCosta, Ralph S.; Weersink, Robert; Netchev, George; Davidson, Sean R. H.; Chan, Warren; Wilson, Brian C.

2007-02-01

Our group is investigating the use of ZnS-capped CdSe quantum dot (QD) bioconjugates combined with fluorescence endoscopy for improved early cancer detection in the esophagus, colon and lung. A major challenge in using fluorescent contrast agents in vivo is to extract the relevant signal from the tissue autofluorescence (AF). Our studies are aimed at maximizing the QD signal to AF background ratio (SBR) to facilitate detection. This work quantitatively evaluates the effect of the excitation wavelength on the SBR, using both experimental measurements and mathematical modeling. Experimental SBR measurements were done by imaging QD solutions placed onto (surface) or embedded in (sub-surface) ex vivo murine tissue samples (brain, kidney, liver, lung), using a polymethylmethacrylate (PMMA) microchannel phantom. The results suggest that the maximum contrast is reached when the excitation wavelength is set at 400+/-20 μm for the surface configuration. For the sub-surface configuration, the optimal excitation wavelength varies with the tissue type and QD emission wavelengths. Our mathematical model, based on an approximation to the diffusion equation, successfully predicts the optimal excitation wavelength for the surface configuration, but needs further modifications to be accurate in the sub-surface configuration.

Self-assembly of PEGylated tetra-phenylalanine derivatives: structural insights from solution and solid state studies

PubMed Central

Diaferia, Carlo; Mercurio, Flavia Anna; Giannini, Cinzia; Sibillano, Teresa; Morelli, Giancarlo; Leone, Marilisa; Accardo, Antonella

2016-01-01

Water soluble fibers of PEGylated tetra-phenylalanine (F4), chemically modified at the N-terminus with the DOTA chelating agent, have been proposed as innovative contrast agent (CA) in Magnetic Resonance Imaging (MRI) upon complexation of the gadolinium ion. An in-depth structural characterization of PEGylated F4-fibers, in presence (DOTA-L6-F4) and in absence of DOTA (L6-F4), is reported in solution and at the solid state, by a multiplicity of techniques including CD, FTIR, NMR, DLS, WAXS and SAXS. This study aims to better understand how the aggregation process influences the performance of nanostructures as MRI CAs. Critical aggregation concentrations for L6-F4 (43 μM) and DOTA-L6-F4 (75 μM) indicate that self-aggregation process occurs in the same concentration range, independently of the presence of the CA. The driving force for the aggregation is the π-stacking between the side chains of the aromatic framework. CD, FTIR and WAXS measurements indicate an antiparallel β-sheet organization of the monomers in the resulting fibers. Moreover, WAXS and FTIR experiments point out that in solution the nanomaterials retain the same morphology and monomer organizations of the solid state, although the addition of the DOTA chelating agent affects the size and the degree of order of the fibers. PMID:27220817

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.

Torsten Almén (1931-2016): the father of non-ionic iodine contrast media.

PubMed

Nyman, Ulf; Ekberg, Olle; Aspelin, Peter

2016-09-01

The Swedish radiologist Torsten Almén is the first clinical radiologist ever to have made a fundamental contribution to intravascular contrast medium design, the development of non-ionic contrast media. He became emotionally triggered by the patients' severe pain each time he injected the ionic "high-osmolar" contrast media when performing peripheral arteriographies in the early 1960s. One day he got a flash of genius that combined the observation of pain, a pathophysiological theory and how to eliminate it with suitable contrast media chemistry. After self-studies in chemistry he developed the concept of iodine contrast media not dissociating into ions in solution to reduce their osmolality and even reach plasma isotonicity. He offered several pharmaceutical companies his concept of mono- and polymeric non-ionic agents but without response, since it was considered against the chemical laws of that time. Contrast media constructed as salts and dissociating into ions in solution was regarded an absolute necessity to achieve high enough water solubility and concentration for diagnostic purposes. Finally a small Norwegian company, Nyegaard & Co., took up his idea 1968 and together they developed the essentially painless "low-osmolar" monomeric non-ionic metrizamide (Amipaque) released in 1974 and iohexol (Omipaque) in 1982 followed by the "iso-osmolar" dimeric non-ionic iodixanol (Visipaque) released in 1993. This has implied a profound paradigm shift with regard to reduction of both hypertonic and chemotoxic side effects, which have been a prerequisite for the today's widespread use of contrast medium-enhanced CT and advanced endovascular interventional techniques even in fragile patients. © The Foundation Acta Radiologica 2016.

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.

Selective modification of NMR relaxation time in human colorectal carcinoma by using gadolinium-diethylenetriaminepentaacetic acid conjugated with monoclonal antibody 19-9.

PubMed Central

Curtet, C; Tellier, C; Bohy, J; Conti, M L; Saccavini, J C; Thedrez, P; Douillard, J Y; Chatal, J F; Koprowski, H

1986-01-01

Monoclonal antibody 19-9 (mAb 19-9) against human colon adenocarcinoma was conjugated with gadolinium X diethylenetriaminepentaacetic acid (Gd X DTPA) and used as a contrast agent in nuclear magnetic resonance (NMR) in an effort to improve tumor target selectivity in nude mice. The data indicate that Gd X DTPA-mAb 19-9 in solution decreased the T1 relaxation of water protons at 90 MHz in direct proportion to the gadolinium concentration, and this effect was greater than in Gd X DTPA solutions. T1 relaxation time at 90 MHz, measured in tumors removed from nude mice 24 hr after injection of Gd X DTPA-mAb 19-9 (Gd, 20 mumol/kg; 16 DTPA molecules per mAb molecule), was significantly decreased (by 15%) as compared with the control group. Similar results were obtained in tumors from mice injected with Gd X DTPA-mAb 19-9 solutions in which Gd was used at 2, 6, or 10 mumol/kg (16 DTPA molecules per mAb molecule). These doses are lower than those commonly used for Gd X DTPA (10-100 mumol/kg) as contrast agent. Tumor localization by the Gd X DTPA-mAb 19-9 complex containing radioactive Gd (0.3 microCi/microgram of 153Gd) to confirm scintigraphy revealed significant concentrations of the complex (5% of the injected dose per gram of tissue) in the tumor. Scan images recorded in planar scintigraphy at day 5 showed good visualization of tumors. Images PMID:3459174

In vitro and in vivo magnetic resonance imaging with chlorotoxin-conjugated superparamagnetic nanoprobes for targeting hepatocarcinoma.

PubMed

Chen, Zhu; Xiao, En-Hua; Kang, Zhen; Zeng, Wen-Bin; Tan, Hui-Long; Li, Hua-Bing; Bian, Du-Jun; Shang, Quan-Liang

2016-05-01

The present study aimed to assess the in vitro and in vivo magnetic resonance imaging (MRI) features of chlorotoxin (CTX)-conjugated superparamagnetic iron oxide (SPIO) nanoprobes. CTX-conjugated nanoprobes were composed of SPIO coated with polyethylene glycol (PEG) and conjugated with CTX. The nanoprobes were termed SPIO-PEG-CTX. MRI of the SPIO and SPIO-PEG-CTX solutions at a different concentration was performed with a 3.0-T MRI scanner (Philips Achieva 3.0T X Series; Phillips Healthcare, The Netherlands). Rabbit VX2 hepatocarcinoma was established by a traditional laparotomy method (injection of the tumor particles into the liver using a 15G syringe needle) following approval by the institutional animal care and use committee. Contrast-enhanced MRI of VX2 rabbits (n=8) was performed using the same MRI scanner with SPIO‑PEG-CTX solutions as the contrast agent. Data were analyzed with calibration curve and a paired t-test. The SPIO-PEG-CTX nanoparticles were successfully prepared. With increasing concentrations of the solutions, the MRI signal intensity was increased at T1WI, but decreased at T2WI, which were the same as that for SPIO. Rabbit VX2 carcinoma appeared as a low MRI signal at T1WI, and high at T2WI. After injection of the contrast agent, the MRI signal of carcinoma was decreased relative to that before injection at T2WI (1,161±331.5 vs. 1,346±300.5; P=0.004<0.05), while the signal of the adjacent normal hepatic tissues was unchanged (480.6±165.1 vs. 563.4±67.8; P=0.202>0.05). The SPIO-PEG-CTX nanoparticles showed MRI negative enhancement at T2WI and a targeting effect in liver cancer, which provides the theoretical basis for further study of the early diagnosis of hepatocellular carcinoma.

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

Near-infrared fluorescent aza-BODIPY dye-loaded biodegradable polymeric nanoparticles for optical cancer imaging

NASA Astrophysics Data System (ADS)

Hamon, Casey L.; Dorsey, Christopher L.; Özel, Tuğba; Barnes, Eugenia M.; Hudnall, Todd W.; Betancourt, Tania

2016-07-01

Nanoparticles are being readily investigated as carriers for the delivery of imaging and therapeutic agents for the detection, monitoring, and treatment of cancer and other diseases. In the present work, the preparation of biodegradable polymeric nanoparticles loaded with a near-infrared fluorescent aza-boron dipyrromethene (NIR-BODIPY ) derivative, and their use as contrast agents for optical imaging in cancer are described. Nanoparticles were prepared by nanoprecipitation of amphiphilic block copolymers of poly(lactic acid) and poly(ethylene glycol). The size, morphology, dye loading, spectral properties, quantum yield, cytocompatibility, and in vitro NIR imaging potential of the nanoparticles in breast and ovarian cancer cells were evaluated. Spherical nanoparticles of 30-70 nm in diameter were loaded with 0.73 w/w% BODIPY derivative. At this loading, the dye presented a fluorescence quantum yield in the same order of magnitude as in solution. Nanoparticle suspensions at concentrations up to 580 μg/mL were cytocompatible to breast (MDA-MB-231) and ovarian (SKOV-3 and Caov-3) cancer cells after a four-hour incubation period. Fluorescence microscopy images demonstrated the ability of the nanoparticles to act as imaging agents in all three cell lines in as little as 1 hour. The results shown indicate the potential of these NIR-BODIPY-loaded nanoparticles as contrast agents for near-infrared optical imaging in cancer.

Photoacoustic lifetime contrast between methylene blue monomers and self-quenched dimers as a model for dual-labeled activatable probes

NASA Astrophysics Data System (ADS)

Morgounova, Ekaterina; Shao, Qi; Hackel, Benjamin J.; Thomas, David D.; Ashkenazi, Shai

2013-05-01

Activatable photoacoustic probes efficiently combine the high spatial resolution and penetration depth of ultrasound with the high optical contrast and versatility of molecular imaging agents. Our approach is based on photoacoustic probing of the excited-state lifetime of methylene blue (MB), a fluorophore widely used in clinical therapeutic and diagnostic applications. Upon aggregation, static quenching between the bound molecules dramatically shortens their lifetime by three orders of magnitude. We present preliminary results demonstrating the ability of photoacoustic imaging to probe the lifetime contrast between monomers and dimers with high sensitivity in cylindrical phantoms. Gradual dimerization enhancement, driven by the addition of increasing concentrations of sodium sulfate to a MB solution, showed that lifetime-based photoacoustic probing decreases linearly with monomer concentration. Similarly, the addition of 4 mM sodium dodecyl sulfate, a concentration that amplifies MB aggregation and reduces the monomer concentration by more than 20-fold, led to a signal decrease of more than 20 dB compared to a solution free of surfactant. These results suggest that photoacoustic imaging can be used to selectively detect the presence of monomers. We conclude by discussing the implementation of the monomer-dimer contrast mechanism for the development of an enzyme-specific activatable probe.

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.

Immobilization of iron oxide nanoparticles within alginate nanogels for enhanced MR imaging applications.

PubMed

Sun, Wenjie; Yang, Jia; Zhu, Jianzhi; Zhou, Yiwei; Li, Jingchao; Zhu, Xiaoyue; Shen, Mingwu; Zhang, Guixiang; Shi, Xiangyang

2016-10-20

We report the design of iron oxide (Fe3O4) nanoparticle (NP)-immobilized alginate (AG) nanogels (NGs) as a novel contrast agent for enhanced magnetic resonance (MR) imaging applications. In this study, an aqueous solution of AG activated by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride was double emulsified to form NGs, followed by in situ cross-linking with polyethyleneimine (PEI)-coated Fe3O4 NPs (PEI-Fe3O4 NPs). The resultant Fe3O4 NP-immobilized AG NGs (AG/PEI-Fe3O4 NGs) were characterized via different techniques. Our results reveal that the hybrid NGs with a size of 186.1 ± 33.1 nm are water dispersible, colloidally stable, and cytocompatible in the given concentration range. Importantly, these NGs have a high r2 relaxivity (170.87 mM(-1) s(-1)) due to the high loading of Fe3O4 NPs within the NGs, and can be more significantly uptaken by cancer cells when compared with carboxylated Fe3O4 NPs. The formed AG/PEI-Fe3O4 NGs are able to be used as an effective contrast agent for the MR imaging of cancer cells in vitro and the xenografted tumor model in vivo after intravenous injection. The developed AG/PEI-Fe3O4 NGs may hold great promise for use as a novel contrast agent for the enhanced MR imaging of different biological systems.

Mass diffusion coefficient measurement for vitreous humor using FEM and MRI

NASA Astrophysics Data System (ADS)

Rattanakijsuntorn, Komsan; Penkova, Anita; Sadha, Satwindar S.

2018-01-01

In early studies, the ‘contour method’ for determining the diffusion coefficient of the vitreous humor was developed. This technique relied on careful injection of an MRI contrast agent (surrogate drug) into the vitreous humor of fresh bovine eyes, and tracking the contours of the contrast agent in time. In addition, an analytical solution was developed for the theoretical contours built on point source model for the injected surrogate drug. The match between theoretical and experimental contours as a least square fit, while floating the diffusion coefficient, led to the value of the diffusion coefficient. This method had its limitation that the initial injection of the surrogate had to be spherical or ellipsoidal because of the analytical result based on the point-source model. With a new finite element model for the analysis in this study, the technique is much less restrictive and handles irregular shapes of the initial bolus. The fresh bovine eyes were used for drug diffusion study in the vitreous and three contrast agents of different molecular masses: gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA, 938 Da), non-ionic gadoteridol (Prohance, 559 Da), and bovine albumin conjugated with gadolinium (Galbumin, 74 kDa) were used as drug surrogates to visualize the diffusion process by MRI. The 3D finite element model was developed to determine the diffusion coefficients of these surrogates with the images from MRI. This method can be used for other types of bioporous media provided the concentration profile can be visualized (by methods such as MRI or fluorescence).

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.

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

PubMed

Daryaei, Iman; Pagel, Mark D

2015-01-01

Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a "double-agent" approach to molecular imaging. Exogenous T 2 -exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T 1 and T 2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as "secret agents" in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging.

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

NASA Astrophysics Data System (ADS)

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

2013-04-01

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

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.

Platinum(II)-gadolinium(III) complexes as potential single-molecular theranostic agents for cancer treatment.

PubMed

Zhu, Zhenzhu; Wang, Xiaoyong; Li, Tuanjie; Aime, Silvio; Sadler, Peter J; Guo, Zijian

2014-11-24

Theranostic agents are emerging multifunctional molecules capable of simultaneous therapy and diagnosis of diseases. We found that platinum(II)-gadolinium(III) complexes with the formula [{Pt(NH3)2Cl}2GdL](NO3)2 possess such properties. The Gd center is stable in solution and the cytoplasm, whereas the Pt centers undergo ligand substitution in cancer cells. The Pt units interact with DNA and significantly promote the cellular uptake of Gd complexes. The cytotoxicity of the Pt-Gd complexes is comparable to that of cisplatin at high concentrations (≥0.1 mM), and their proton relaxivity is higher than that of the commercial magnetic resonance imaging (MRI) contrast agent Gd-DTPA. T1-weighted MRI on B6 mice demonstrated that these complexes can reveal the accumulation of platinum drugs in vivo. Their cytotoxicity and imaging capabilities make the Pt-Gd complexes promising theranostic agents for cancer treatment. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

In vitro comparison of intracranial stent visibility using various concentrations of gadolinium contrast agent under 1.5 T and 3 T MR angiography.

PubMed

Chiang, Chen-Hua; Tseng, Ying-Chi; Chen, Ai-Chi; Huang, Yen-Lin; Chen, David Yen-Ting; Chen, Chi-Jen; Lin, Yen-Kuang; Hsu, Hui-Ling

2017-04-01

MR angiography (MRA) is an increasingly used evaluation method following intracranial stenting. However, the various artifacts created by the stent limit this technique. The purpose of this study was to investigate the effects of various concentrations of gadolinium contrast agent on the visibility and signal characteristics of two stents using the a contrast enhanced MRA technique. Two intracranial stents (Enterprise and Helistent) were placed in polyvinyl chloride tubes as vascular phantoms. They were filled with six different doses of gadolinium contrast agent (1.0, 2.0, 4.0, 6.0, 8.0, and 10.0 mmol/L dimeglumine gadopentetate, respectively) and imaged using 3 T and 1.5 T MR systems. Relative in-stent signal (RIS) was calculated and artificial luminal narrowing (ALN) was obtained using pixel by pixel analysis. The Enterprise stent, performed in both 1.5 T and 3 T MR systems, showed mean RIS values much less than those for the Helistent for all different doses of gadolinium solution. Increased gadolinium concentration resulted in a gradual reduction in RIS values in the Enterprise group. Also, ALN in the Enterprise group showed no or little change with various gadolinium doses. The Enterprise stent demonstrated good luminal visibility regardless of gadolinium concentration. The relative in-stent signals were more predictable in the Enterprise stent with various doses of gadolinium. Therefore, the Enterprise stent has been shown to provide better in-stent visibility compared with the Helistent using various gadolinium doses. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Contrast agents in dynamic contrast-enhanced magnetic resonance imaging

PubMed Central

Yan, Yuling; Sun, Xilin; Shen, Baozhong

2017-01-01

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive method to assess angiogenesis, which is widely used in clinical applications including diagnosis, monitoring therapy response and prognosis estimation in cancer patients. Contrast agents play a crucial role in DCE-MRI and should be carefully selected in order to improve accuracy in DCE-MRI examination. Over the past decades, there was much progress in the development of optimal contrast agents in DCE-MRI. In this review, we describe the recent research advances in this field and discuss properties of contrast agents, as well as their advantages and disadvantages. Finally, we discuss the research perspectives for improving this promising imaging method. PMID:28415647

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.

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

PubMed Central

Daryaei, Iman; Pagel, Mark D

2016-01-01

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

P16.31THERANOSTIC APPLICATION OF WATER-SOLUBLE GADOLINIUM FULLERENE (GD@FUL) IN EXPERIMENTAL GLIOMA MODEL

PubMed Central

Shevtsov, M.; Nikolaev, B.; Marchenko, Y.; Yakovleva, L.; Dobrodumov, A.; Török, G.; Pitkin, E.; Lebedev, V.

2014-01-01

Glioblastoma multiforme (GMB) is a highly invasive brain tumour with poor prognosis. Alternative treatments offering a better outcome are needed. Novel approach could be based on gadofullerenes that can be used as diagnostic MR imaging contrast agent and as a therapeutic drug. Water soluble gadofullerene Gd@Ful with composition Gd@C82(OH)x x ≥20 was synthesized for theranostic study. Nanosuspensions of Gd@Ful were used for magnetic relaxation measurements in vitro and for MR imaging of a rat with intracranially implanted C6 glioma. Gd@Ful was shown to reduce proton relaxation times in vitro, and provide dual contrast of T1- and T2-weighted images in a rat brain tumour model after paramagnetic intravenous delivery. Magnetic relaxation times and relaxivity of water protons under action of Gd@Ful were strongly shortened due to cluster formation and increase of motional correlation times of protons in the vicinity of the fulleren cage. The Gd@Ful administration promoted the improvement of glioma contrast enhancement at T2-weighted images due to accumulation of paramagnetic substance at the tumour site. The contrast efficiency of Gd@Ful corresponds to the characteristics of negative contrast agent. Retention of the Gd@Ful in the C6 glioma provides not only the tumor contrast enhancement but also has a high therapeutic relevance. We observed the increased survival rates in animals that were intravenously administered with Gd@Ful. Thus, in experimental group the survival was 75% higher then in the control group, constituting 34.2 ± 9.94 and 19.5 ± 3.02 days respectively (P < 0.001). The Gd@Ful solution is shown to be a contrast enhancer with high anti-tumour therapeutic potency.

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

Thrombolytic along with anti-platelet activity of crinumin, a protein constituent of Crinum asiaticum.

PubMed

Singh, Kunwar Awaneesh; Nayak, Manasa K; Jagannadham, Medicherla V; Dash, Debabrata

2011-08-15

Several anticoagulants, anti-platelet and thrombolytic medications are used for the treatment of thrombotic disorders. Anti-coagulants and anti-platelet agents prevent the formation of blood clots but do not dissolve existing clots, whereas thrombolytic agents are able to dissolve a clot but emboli can form even after successful treatment. Thus, none of them provide a permanent and complete solution. In this regard a single molecule that could both dissolve the clot and prevent the formation of new clots would be useful in the treatment of thrombotic diseases. Crinumin, a stable and active (in many adverse conditions) serine protease, shows plasmin-like fibrinolytic activity and inhibits platelet aggregation and P-selectin exposure, as established by photography, phase contrast microscopy, whole blood optical Lumi-aggregometry and flow cytometry. Crinumin could be an efficient and inexpensive therapeutic agent for the treatment and prevention of thromboembolic diseases. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

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.

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

Fe3O4 nanoparticles modified by CD-containing star polymer for MRI and drug delivery.

PubMed

Cha, Ruitao; Li, Juanjuan; Liu, Yang; Zhang, Yifan; Xie, Qian; Zhang, Mingming

2017-10-01

Fe 3 O 4 nanoparticles with ultrasmall sizes show good T 1 or T 1 +T 2 contrast abilities, and have attracted considerable interest in the field of magnetic resonance imaging (MRI) contrast agents. For effective biomedical applications, the colloidal stability and biocompatibility of the Fe 3 O 4 nanoparticles need to be improved without reducing MRI relaxivity. In this paper, star polymers were used as coating materials to modify Fe 3 O 4 nanoparticles in view of their dense molecular architecture with moderate flexibility. The star polymer was composed of a β-cyclodextrin (β-CD) core and poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) arms. Meanwhile, reduced glutathione (GSH), as a model drug, was also associated with the star polymer. Thus, a new platform for simultaneous diagnosis and treatment was achieved. Compared to the Fe 3 O 4 nanoparticles coated with linear polymers, the Fe 3 O 4 nanoparticles coated with star polymers (Fe 3 O 4 @GCP) possessed higher GSH association capacity and better stability in serum-containing solution. GSH could be released from Fe 3 O 4 @GCP nanoparticles in response to pH value of the solution. Since the sulfhydryl group on GSH is able to combine free radicals, Fe 3 O 4 @GCP nanoparticles exhibited less cytotoxicity compared to the Fe 3 O 4 nanoparticles without including GSH. Furthermore, the nanoparticles could also serve as good T 1 MRI contrast agent, and the MRI relaxivity of Fe 3 O 4 @GCP nanoparticles did not decrease after coated with the star polymer. These results indicate that the precisely designed Fe 3 O 4 @GCP nanoparticles could be used as a versatile promising theranostic nano-platform. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Novel route synthesis of porous and solid gold nanoparticles for investigating their comparative performance as contrast agent in computed tomography scan and effect on liver and kidney function.

PubMed

Aziz, Farooq; Ihsan, Ayesha; Nazir, Aalia; Ahmad, Ishaq; Bajwa, Sadia Zafar; Rehman, Asma; Diallo, Abdoulaye; Khan, Waheed S

2017-01-01

Gold nanoparticles (GNPs) with dimension in the range of 1-100 nm have a prominent role in a number of biomedical applications like imaging, drug delivery, and cancer therapy owing to their unique optical features and biocompatibility. In this work, we report a novel technique for the synthesis of two types of GNPs namely porous gold nanoparticles (PGNPs) and solid gold nanoparticles (SGNPs). PGNPs of size 35 nm were fabricated by reduction of gold (III) solution with lecithin followed by addition of L-ascorbic acid and tri-sodium citrate, whereas SGNPs with a dimension of 28 nm were prepared by reflux method using lecithin as a single reducing agent. Comparative studies using PGNPs (λ max 560 nm) and SGNPs (λ max 548 nm) were conducted for evaluating their use as a contrast agent. These studies reveled that in direct computed tomography scan, PGNPs exhibited brighter contrast (45 HU) than SGNPs (26 HU). To investigate the effect of PGNPs and SGNPs on the liver and kidney profile, male rabbits were intravenously injected with an equal dose of 1 mg/kg weight of PGNPs and SGNPs. The effect on biochemical parameters was evaluated 72 hours after intravenous (IV) injection including liver function profile, renal (kidney) function biomarker, random blood glucose value, and cholesterol level. During one comparison of contrast in CT scan, PGNPs showed significantly enhanced contrast in whole-rabbit and organ CT scan as compared to SGNPs 6 hours after injection. Our findings suggested that the novel PGNPs enhance CT scan image with higher efficacy as compared to SGNPs. The results showed that IV administration of synthesized PGNPs increases the levels of aspartate aminotransferase (AST), alkaline phosphate (ALP), serum creatinine, and blood glucose, whereas that of SGNPs increases the levels of AST, ALP, and blood glucose.

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.

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

Gd-DTPA-loaded polymer-metal complex micelles with high relaxivity for MR cancer imaging.

PubMed

Mi, Peng; Cabral, Horacio; Kokuryo, Daisuke; Rafi, Mohammad; Terada, Yasuko; Aoki, Ichio; Saga, Tsuneo; Takehiko, Ishii; Nishiyama, Nobuhiro; Kataoka, Kazunori

2013-01-01

Nanodevices for magnetic resonance imaging of cancer were self-assembled to core-shell micellar structures by metal complex formation of K(2)PtCl(6) with diethylenetriaminepentaacetic acid gadolinium (III) dihydrogen (Gd-DTPA), a T(1)-contrast agent, and poly(ethylene glycol)-b-poly{N-[N'-(2-aminoethyl)-2-aminoethyl]aspartamide} (PEG-b-PAsp(DET)) copolymer in aqueous solution. Gd-DTPA-loaded polymeric micelles (Gd-DTPA/m) showed a hydrodynamic diameter of 45 nm and a core size of 22 nm. Confining Gd-DTPA inside the core of the micelles increased the relaxivity of Gd-DTPA more than 13 times (48 mM(-1) s(-1)). In physiological conditions Gd-DTPA/m sustainedly released Gd-DTPA, while the Pt(IV) complexes remain bound to the polymer. Gd-DTPA/m extended the circulation time in plasma and augmented the tumor accumulation of Gd-DTPA leading to successful contrast enhancement of solid tumors. μ-Synchrotron radiation-X-ray fluorescence results confirmed that Gd-DTPA was delivered to the tumor site by the micelles. Our study provides a facile strategy for incorporating contrast agents, dyes and bioactive molecules into nanodevices for developing safe and efficient drug carriers for clinical application. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

Preparation and evaluation of poly(2-hydroxyethyl aspartamide)-hexadecylamine-iron oxide for MR imaging of lymph nodes

PubMed Central

2014-01-01

The purpose of this study was to synthesize biocompatible poly(2-hydroxyethyl aspartamide)–C16-iron oxide (PHEA-C16-iron oxide) nanoparticles and to evaluate their efficacy as a contrast agent for magnetic resonance imaging of lymph nodes. The PHEA-C16-iron oxide nanoparticles were synthesized by coprecipitation method. The core size of the PHEA-C16-iron oxide nanoparticles was about 5 to 7 nm, and the overall size of the nanoparticles was around 20, 60, and 150 nm in aqueous solution. The size of the nanoparticles was controlled by the amount of C16. The 3.0-T MRI signal intensity of a rabbit lymph node was effectively reduced after intravenous administration of PHEA-C16-iron oxide with the size of 20 nm. The in vitro and in vivo toxicity tests revealed the high biocompatibility of PHEA-C16-iron oxide nanoparticles. Therefore, PHEA-C16-iron oxide nanoparticles with 20-nm size can be potentially useful as T2-weighted MR imaging contrast agents for the detection of lymph nodes. PMID:24438671

Assessing blood vessel perfusion and vital signs through retinal imaging photoplethysmography.

PubMed

Hassan, Harnani; Jaidka, Sheila; Dwyer, Vincent M; Hu, Sijung

2018-05-01

One solution to the global challenge of increasing ocular disease is a cost-effective technique for rapid screening and assessment. Current ophthalmic imaging techniques, e.g. scanning and ocular blood flow systems, are expensive, complex to operate and utilize invasive contrast agents during assessment. The work presented here demonstrates a simple retinal imaging photoplethysmography (iPPG) system with the potential to provide screening, diagnosis, monitoring and assessment that is non-invasive, painless and radiationless. Time series of individual retinal blood vessel images, captured with an eye fundus camera, are processed using standard filtering, amplitude demodulation and principle component analysis (PCA) methods to determine the values of the heart rate (HR) and respiration rate (RR), which are in compliance with simultaneously obtained measurements using commercial pulse oximetry. It also seems possible that some information on the dynamic changes in oxygen saturation levels ( SpO 2 ) in a retinal blood vessel may also be obtained. As a consequence, the retinal iPPG modality system demonstrates a potential avenue for rapid ophthalmic screening, and even early diagnosis, against ocular disease without the need for fluorescent or contrast agents.

Structural Study of the Complex Stereoselectivity of Human Butyrylcholinesterase for the Neurotoxic V-agents*

PubMed Central

Wandhammer, Marielle; Carletti, Eugénie; Van der Schans, Marcel; Gillon, Emilie; Nicolet, Yvain; Masson, Patrick; Goeldner, Maurice; Noort, Daan; Nachon, Florian

2011-01-01

Nerve agents are chiral organophosphate compounds (OPs) that exert their acute toxicity by phosphorylating the catalytic serine of acetylcholinesterase (AChE). The inhibited cholinesterases can be reactivated using oximes, but a spontaneous time-dependent process called aging alters the adduct, leading to resistance toward oxime reactivation. Human butyrylcholinesterase (BChE) functions as a bioscavenger, protecting the cholinergic system against OPs. The stereoselectivity of BChE is an important parameter for its efficiency at scavenging the most toxic OPs enantiomer for AChE. Crystals of BChE inhibited in solution or in cristallo with racemic V-agents (VX, Russian VX, and Chinese VX) systematically show the formation of the PS adduct. In this configuration, no catalysis of aging seems possible as confirmed by the three-dimensional structures of the three conjugates incubated over a period exceeding a week. Crystals of BChE soaked in optically pure VXR-(+) and VXS-(−) solutions lead to the formation of the PS and PR adduct, respectively. These structural data support an in-line phosphonylation mechanism. Additionally, they show that BChE reacts with VXR-(+) in the presence of racemic mixture of V-agents, at odds with earlier kinetic results showing a moderate higher inhibition rate for VXS-(−). These combined results suggest that the simultaneous presence of both enantiomers alters the enzyme stereoselectivity. In summary, the three-dimensional data show that BChE reacts preferentially with PR enantiomer of V-agents and does not age, in complete contrast to AChE, which is selectively inhibited by the PS enantiomer and ages. PMID:21454498

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.

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.

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

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.

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

Myocardial perfusion cardiovascular magnetic resonance: optimized dual sequence and reconstruction for quantification.

PubMed

Kellman, Peter; Hansen, Michael S; Nielles-Vallespin, Sonia; Nickander, Jannike; Themudo, Raquel; Ugander, Martin; Xue, Hui

2017-04-07

Quantification of myocardial blood flow requires knowledge of the amount of contrast agent in the myocardial tissue and the arterial input function (AIF) driving the delivery of this contrast agent. Accurate quantification is challenged by the lack of linearity between the measured signal and contrast agent concentration. This work characterizes sources of non-linearity and presents a systematic approach to accurate measurements of contrast agent concentration in both blood and myocardium. A dual sequence approach with separate pulse sequences for AIF and myocardial tissue allowed separate optimization of parameters for blood and myocardium. A systems approach to the overall design was taken to achieve linearity between signal and contrast agent concentration. Conversion of signal intensity values to contrast agent concentration was achieved through a combination of surface coil sensitivity correction, Bloch simulation based look-up table correction, and in the case of the AIF measurement, correction of T2* losses. Validation of signal correction was performed in phantoms, and values for peak AIF concentration and myocardial flow are provided for 29 normal subjects for rest and adenosine stress. For phantoms, the measured fits were within 5% for both AIF and myocardium. In healthy volunteers the peak [Gd] was 3.5 ± 1.2 for stress and 4.4 ± 1.2 mmol/L for rest. The T2* in the left ventricle blood pool at peak AIF was approximately 10 ms. The peak-to-valley ratio was 5.6 for the raw signal intensities without correction, and was 8.3 for the look-up-table (LUT) corrected AIF which represents approximately 48% correction. Without T2* correction the myocardial blood flow estimates are overestimated by approximately 10%. The signal-to-noise ratio of the myocardial signal at peak enhancement (1.5 T) was 17.7 ± 6.6 at stress and the peak [Gd] was 0.49 ± 0.15 mmol/L. The estimated perfusion flow was 3.9 ± 0.38 and 1.03 ± 0.19 ml/min/g using the BTEX model and 3.4 ± 0.39 and 0.95 ± 0.16 using a Fermi model, for stress and rest, respectively. A dual sequence for myocardial perfusion cardiovascular magnetic resonance and AIF measurement has been optimized for quantification of myocardial blood flow. A validation in phantoms was performed to confirm that the signal conversion to gadolinium concentration was linear. The proposed sequence was integrated with a fully automatic in-line solution for pixel-wise mapping of myocardial blood flow and evaluated in adenosine stress and rest studies on N = 29 normal healthy subjects. Reliable perfusion mapping was demonstrated and produced estimates with low variability.

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.

[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

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.

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

Risk factors for and the prevention of acute kidney injury after abdominal surgery.

PubMed

An, Yongbo; Shen, Kai; Ye, Yingjiang

2018-06-01

Postoperative acute kidney injury in patients undergoing abdominal surgery is not rare and often results in bad outcomes for patients. The incidence of postoperative acute kidney injury is hard to evaluate reliably due to its non-unified definitions in different studies. Risk factors for acute kidney injury specific to abdominal surgery include preoperative renal insufficiency, intraabdominal hypertension, blood transfusion, bowel preparation, perioperative dehydration, contrast agent and nephrotoxic drug use. Among these, preoperative renal insufficiency is the strongest predictor of acute kidney injury. The peri-operative management of high-risk patients should include meticulous selection of fluid solutions. Balanced crystalloid solutions and albumin are generally thought to be relatively safe, while the safety of hydroxyethyl starch solutions has been controversial. The purpose of the present review is to discuss the current knowledge regarding postoperative acute kidney injury in abdominal surgical settings to help surgeons make better decisions concerning the peri-operative management.

Optoacoustic response from graphene-based solutions embedded in optical phantoms by using 905-nm high-power diode-laser assemblies

NASA Astrophysics Data System (ADS)

Leggio, Luca; Gallego, Daniel C.; Gawali, Sandeep Babu; Dadrasnia, Ehsan; Sánchez, Miguel; Rodríguez, Sergio; González, Marta; Carpintero, Guillermo; Osiński, Marek; Lamela, Horacio

2016-03-01

During the last two decades, optoacoustic imaging has been developed as a novel biomedical imaging technique based on the generation of ultrasound waves by means of laser light. In this work, we investigate the optoacoustic response from graphene-based solutions by using a compact and cost-effective system based on an assembly of several 905-nm pulsed high-power diode lasers coupled to a bundle of 200-μm diameter- core optical fibers. The coupled light is conveyed into a lens system and focused on an absorber consisting of graphene-based nanomaterials (graphene oxide, reduced graphene oxide, and reduced graphene-oxide/gold-nanoparticle hybrid, respectively) diluted in ethanol and hosted in slightly scattering optical phantoms. The high absorption of these graphene-based solutions suggests their potential future use in optoacoustic applications as contrast agents.

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.

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.

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.

Brain-wide pathway for waste clearance captured by contrast-enhanced MRI.

PubMed

Iliff, Jeffrey J; Lee, Hedok; Yu, Mei; Feng, Tian; Logan, Jean; Nedergaard, Maiken; Benveniste, Helene

2013-03-01

The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer's disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer's disease susceptibility and progression in the live human brain.

Brain-wide pathway for waste clearance captured by contrast-enhanced MRI

PubMed Central

Iliff, Jeffrey J.; Lee, Hedok; Yu, Mei; Feng, Tian; Logan, Jean; Nedergaard, Maiken; Benveniste, Helene

2013-01-01

The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer’s disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer’s disease susceptibility and progression in the live human brain. PMID:23434588

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.

Simultaneous contrast: evidence from licking microstructure and cross-solution comparisons.

PubMed

Dwyer, Dominic M; Lydall, Emma S; Hayward, Andrew J

2011-04-01

The microstructure of rats' licking responses was analyzed to investigate both "classic" simultaneous contrast (e.g., Flaherty & Largen, 1975) and a novel discrete-trial contrast procedure where access to an 8% test solution of sucrose was preceded by a sample of either 2%, 8%, or 32% sucrose (Experiments 1 and 2, respectively). Consumption of a given concentration of sucrose was higher when consumed alongside a low rather than high concentration comparison solution (positive contrast) and consumption of a given concentration of sucrose was lower when consumed alongside a high rather than a low concentration comparison solution (negative contrast). Furthermore, positive contrast increased the size of lick clusters while negative contrast decreased the size of lick clusters. Lick cluster size has a positive monotonic relationship with the concentration of palatable solutions and so positive and negative contrasts produced changes in lick cluster size that were analogous to raising or lowering the concentration of the test solution respectively. Experiment 3 utilized the discrete-trial procedure and compared contrast between two solutions of the same type (sucrose-sucrose or maltodextrin-maltodextrin) or contrast across solutions (sucrose-maltodextrin or maltodextrin-sucrose). Contrast effects on consumption were present, but reduced in size, in the cross-solution conditions. Moreover, lick cluster sizes were not affected at all by cross-solution contrasts as they were by same-solution contrasts. These results are consistent with the idea that simultaneous contrast effects depend, at least partially, on sensory mechanisms.

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.

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

PubMed

Matsumiya, Hiroaki; Inoue, Hiroto; Hiraide, Masataka

2014-10-01

Gadolinium complexed with naturally occurring, negatively charged humic substances (humic and fulvic acids) was collected from 500 mL of sample solution onto a column packed with 150 mg of a strongly basic anion-exchanger (QAE-Sephadex A-25). A Gd-based magnetic resonance imaging contrast agent (diethylenetriamine-N,N,N',N″,N″-pentaacetato aquo gadolinium(III), Gd-DTPA(2-)) was simultaneously collected on the same column. The Gd-DTPA complex was desorbed by anion-exchange with 50mM tetramethylammonium sulfate, leaving the Gd-humic complexes on the column. The Gd-humic complexes were subsequently dissociated with 1M nitric acid to desorb the humic fraction of Gd. The two-step desorption with small volumes of the eluting agents allowed the 100-fold preconcentration for the fractionation analysis of Gd at low ng L(-1) levels by inductively coupled plasma-mass spectrometry (ICP-MS). On the other hand, Gd(III) neither complexed with humic substances nor DTPA, i.e., free species, was not sorbed on the column. The free Gd in the effluent was preconcentrated 100-fold by a conventional solid-phase extraction with an iminodiacetic acid-type chelating resin and determined by ICP-MS. The proposed analytical fractionation method was applied to river water samples. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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

Lakshminarayan, Raghuram, E-mail: raghuram.lakshminarayan@hey.nhs.u; Simpson, James O.; Ettles, Duncan F., E-mail: Duncan.Ettles@hey.nhs.u

Magnetic resonance angiography (MRA) has become an established imaging modality in the management of lower-limb arterial disease, with emerging roles in treatment planning and follow-up. Contrast-enhanced MRA is now the most widely used technique with clinically acceptable results in the majority of patients. Difficulties in imaging and image interpretation are recognised in certain subgroups, including patients with critical limb ischaemia as well as patients with stents. Although newer contrast agents and refined imaging protocols may offer some solutions to these problems, this optimism is balanced by concerns about the toxicity of certain gadolinium chelates. Further development of interventional MRA remainsmore » one of the most significant challenges in the development of magnetic resonance imaging-guided peripheral vascular intervention. The status of MRA in managing patients with lower-limb arterial disease in current clinical practice is reviewed.« less

EUV lithographic radiation grafting of thermo-responsive hydrogel nanostructures

NASA Astrophysics Data System (ADS)

Farquet, Patrick; Padeste, Celestino; Solak, Harun H.; Gürsel, Selmiye Alkan; Scherer, Günther G.; Wokaun, Alexander

2007-12-01

Nanostructures of the thermoresponsive poly( N-isopropyl acrylamide) (PNIPAAm) and of PNIPAAm-block-poly(acrylic acid) copolymers were produced on poly(tetrafluoroethylene-co-ethyelene) (ETFE) films using extreme ultraviolet (EUV) lithographic exposure with subsequent graft-polymerization. The phase transition of PNIPAAm nanostructures at the low critical solution temperature (LCST) at 32 °C was imaged by atomic force microscopy (AFM) phase contrast measurements in pure water. Results show a higher phase contrast for samples measured below the LCST temperature than for samples above the LCST, proving that the soft PNIPAAm hydrogel transforms into a much more compact conformation above the LCST. EUV lithographic exposures were combined with the reversible addition-fragment chain transfer (RAFT)-mediated polymerization using cyanoisopropyl dithiobenzoate (CPDB) as chain transfer agent to synthesize PNIPAAm block-copolymer nanostructures.

Single-walled carbon nanotube-loaded doxorubicin and Gd-DTPA for targeted drug delivery and magnetic resonance imaging.

PubMed

Yan, Chenyu; Chen, Chengqun; Hou, Lin; Zhang, Huijuan; Che, Yingyu; Qi, Yuedong; Zhang, Xiaojian; Cheng, Jingliang; Zhang, Zhenzhong

2017-02-01

An aspargine-glycine-arginine (NGR) peptide modified single-walled carbon nanotubes (SWCNTs) system, developed by a simple non-covalent approach, could be loaded with the anticancer drug doxorubicin (DOX) and magnetic resonance imaging (MRI) contrast agent gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). This DOX- and Gd-DTPA-loaded NGR functionalized SWCNTs (DOX/NGR-SWCNTs/Gd-DPTA) retained both cytotoxicity of DOX and MRI contrast effect of Gd-DPTA. This drug delivery system showed excellent stability in physiological solutions. This DOX/NGR-SWCNTs/Gd-DPTA system could accumulate in tumors and enter into tumor cells, which facilitated combination chemotherapy with diagnosis of tumor in one system. An excellent in vitro anti-tumor effect was shown in MCF-7 cells treated by DOX/NGR-SWCNTs/Gd-DPTA, compared with DOX solution, DOX/SWCNTs and DOX/SWCNTs/Gd-DPTA. In vivo data of DOX/NGR-SWCNTs/Gd-DPTA group in tumor-bearing mice further confirmed that this system performed much higher tumor targeting capacity and anti-tumor efficacy than other control groups.

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.

Paramagnet induced signal quenching in MAS-DNP experiments in frozen homogeneous solutions

NASA Astrophysics Data System (ADS)

Corzilius, Björn; Andreas, Loren B.; Smith, Albert A.; Ni, Qing Zhe; Griffin, Robert G.

2014-03-01

The effects of nuclear signal quenching induced by the presence of a paramagnetic polarizing agent are documented for conditions used in magic angle spinning (MAS)-dynamic nuclear polarization (DNP) experiments on homogeneous solutions. In particular, we present a detailed analysis of three time constants: (1) the longitudinal build-up time constant TB for 1H; (2) the rotating frame relaxation time constant T1ρ for 1H and 13C and (3) T2 of 13C, the transverse relaxation time constant in the laboratory frame. These relaxation times were measured during microwave irradiation at a magnetic field of 5 T (140 GHz) as a function of the concentration of four polarizing agents: TOTAPOL, 4-amino-TEMPO, trityl (OX063), and Gd-DOTA and are compared to those obtained for a sample lacking paramagnetic doping. We also report the EPR relaxation time constants T1S and T2S, the DNP enhancements, ε, and the parameter E, defined below, which measures the sensitivity enhancement for the four polarizing agents as a function of the electron concentration. We observe substantial intensity losses (paramagnetic quenching) with all of the polarizing agents due to broadening mechanisms and cross relaxation during MAS. In particular, the monoradical trityl and biradical TOTAPOL induce ∼40% and 50% loss of signal intensity. In contrast there is little suppression of signal intensity in static samples containing these paramagnetic species. Despite the losses due to quenching, we find that all of the polarizing agents provide substantial gains in signal intensity with DNP, and in particular that the net enhancement is optimal for biradicals that operate with the cross effect. We discuss the possibility that much of this polarization loss can be regained with the development of instrumentation and methods to perform electron decoupling.

Minimally Invasive Monitoring of Chronic Central Venous Catheter Patency in Mice Using Digital Subtraction Angiography (DSA)

PubMed Central

Figueiredo, Giovanna; Fiebig, Teresa; Kirschner, Stefanie; Nikoubashman, Omid; Kabelitz, Lisa; Othman, Ahmed; Nonn, Andrea; Kramer, Martin; Brockmann, Marc A.

2015-01-01

Background Repetitive administration of medication or contrast agents is frequently performed in mice. The introduction of vascular access mini-ports (VAMP) for mice allows long-term vascular catheterization, hereby eliminating the need for repeated vessel puncture. With catheter occlusion being the most commonly reported complication of chronic jugular vein catheterization, we tested whether digital subtraction angiography (DSA) can be utilized to evaluate VAMP patency in mice. Methods Twenty-three mice underwent catheterization of the jugular vein and subcutaneous implantation of a VAMP. The VAMP was flushed every second day with 50 μL of heparinized saline solution (25 IU/ml). DSA was performed during injection of 100 μL of an iodine based contrast agent using an industrial X-ray inspection system intraoperatively, as well as 7±2 and 14±2 days post implantation. Results DSA allowed localization of catheter tip position, to rule out dislocation, kinking or occlusion of a microcatheter, and to evaluate parent vessel patency. In addition, we observed different ante- and retrograde collateral flow patterns in case of jugular vein occlusion. More exactly, 30% of animals showed parent vessel occlusion after 7±2 days in our setting. At this time point, nevertheless, all VAMPs verified intravascular contrast administration. After 14±2 days, intravascular contrast injection was verified in 70% of the implanted VAMPs, whereas at this point of time 5 animals had died or were sacrificed and in 2 mice parent vessel occlusion hampered intravascular contrast injection. Notably, no occlusion of the catheter itself was observed. Conclusion From our observations we conclude DSA to be a fast and valuable minimally invasive tool for investigation of catheter and parent vessel patency and for anatomical studies of collateral blood flow in animals as small as mice. PMID:26098622

Preliminary study of copper oxide nanoparticles acoustic and magnetic properties for medical imaging

NASA Astrophysics Data System (ADS)

Perlman, Or; Weitz, Iris S.; Azhari, Haim

2015-03-01

The implementation of multimodal imaging in medicine is highly beneficial as different physical properties may provide complementary information, augmented detection ability, and diagnosis verification. Nanoparticles have been recently used as contrast agents for various imaging modalities. Their significant advantage over conventional large-scale contrast agents is the ability of detection at early stages of the disease, being less prone to obstacles on their path to the target region, and possible conjunction to therapeutics. Copper ions play essential role in human health. They are used as a cofactor for multiple key enzymes involved in various fundamental biochemistry processes. Extremely small size copper oxide nanoparticles (CuO-NPs) are readily soluble in water with high colloidal stability yielding high bioavailability. The goal of this study was to examine the magnetic and acoustic characteristics of CuO-NPs in order to evaluate their potential to serve as contrast imaging agent for both MRI and ultrasound. CuO-NPs 7nm in diameter were synthesized by hot solution method. The particles were scanned using a 9.4T MRI and demonstrated a concentration dependent T1 relaxation time shortening phenomenon. In addition, it was revealed that CuO-NPs can be detected using the ultrasonic B-scan imaging. Finally, speed of sound based ultrasonic computed tomography was applied and showed that CuO-NPs can be clearly imaged. In conclusion, the preliminary results obtained, positively indicate that CuO-NPs may be imaged by both MRI and ultrasound. The results motivate additional in-vivo studies, in which the clinical utility of fused images derived from both modalities for diagnosis improvement will be studied.

An open source, 3D printed preclinical MRI phantom for repeated measures of contrast agents and reference standards.

PubMed

Cox, B L; Ludwig, K D; Adamson, E B; Eliceiri, K W; Fain, S B

2018-03-01

In medical imaging, clinicians, researchers and technicians have begun to use 3D printing to create specialized phantoms to replace commercial ones due to their customizable and iterative nature. Presented here is the design of a 3D printed open source, reusable magnetic resonance imaging (MRI) phantom, capable of flood-filling, with removable samples for measurements of contrast agent solutions and reference standards, and for use in evaluating acquisition techniques and image reconstruction performance. The phantom was designed using SolidWorks, a computer-aided design software package. The phantom consists of custom and off-the-shelf parts and incorporates an air hole and Luer Lock system to aid in flood filling, a marker for orientation of samples in the filled mode and bolt and tube holes for assembly. The cost of construction for all materials is under $90. All design files are open-source and available for download. To demonstrate utility, B 0 field mapping was performed using a series of gadolinium concentrations in both the unfilled and flood-filled mode. An excellent linear agreement (R 2 >0.998) was observed between measured relaxation rates (R 1 /R 2 ) and gadolinium concentration. The phantom provides a reliable setup to test data acquisition and reconstruction methods and verify physical alignment in alternative nuclei MRI techniques (e.g. carbon-13 and fluorine-19 MRI). A cost-effective, open-source MRI phantom design for repeated quantitative measurement of contrast agents and reference standards in preclinical research is presented. Specifically, the work is an example of how the emerging technology of 3D printing improves flexibility and access for custom phantom design.

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.

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.

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.

A review of responsive MRI contrast agents: 2005–2014

PubMed Central

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

2014-01-01

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

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.

Effects of Electronic-State-Dependent Solute Polarizability: Application to Solute-Pump/Solvent-Probe Spectra.

PubMed

Sun, Xiang; Ladanyi, Branka M; Stratt, Richard M

2015-07-23

Experimental studies of solvation dynamics in liquids invariably ask how changing a solute from its electronic ground state to an electronically excited state affects a solution's dynamics. With traditional time-dependent-fluorescence experiments, that means looking for the dynamical consequences of the concomitant change in solute-solvent potential energy. But if one follows the shift in the dynamics through its effects on the macroscopic polarizability, as recent solute-pump/solvent-probe spectra do, there is another effect of the electronic excitation that should be considered: the jump in the solute's own polarizability. We examine the spectroscopic consequences of this solute polarizability change in the classic example of the solvation dye coumarin 153 dissolved in acetonitrile. After demonstrating that standard quantum chemical methods can be used to construct accurate multisite models for the polarizabilities of ground- and excited-state solvation dyes, we show via simulation that this polarizability change acts as a contrast agent, significantly enhancing the observable differences in optical-Kerr spectra between ground- and excited-state solutions. A comparison of our results with experimental solute-pump/solvent-probe spectra supports our interpretation and modeling of this spectroscopy. We predict, in particular, that solute-pump/solvent-probe spectra should be sensitive to changes in both the solvent dynamics near the solute and the electronic-state-dependence of the solute's own rotational dynamics.

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.

Use of Magnetic Nanoparticles to Monitor Alginate-Encapsulated βTC-tet Cells

PubMed Central

Constantinidis, Ioannis; Grant, Samuel C.; Simpson, Nicholas E.; Oca-Cossio, Jose A.; Sweeney, Carol A.; Mao, Hui; Blackband, Stephen J.; Sambanis, Athanassios

2008-01-01

Non-invasive monitoring of tissue-engineered constructs is an important component in optimizing construct design and assessing therapeutic efficacy. In recent years, cellular and molecular imaging initiatives have spurred the use of iron oxide based contrast agents in the field of NMR imaging. Although their use in medical research has been widespread, their application in tissue engineering has been limited. In this study, the utility of Monocrystalline Iron Oxide Nanoparticles (MION) as an NMR contrast agent was evaluated for βTC-tet cells encapsulated within alginate/poly-L-lysine/alginate (APA) microbeads. The constructs were labeled with MION in two different ways: (a) MION-labeled βTC-tet cells were encapsulated in APA beads (i.e., intracellular compartment); and (b) MION particles were suspended in the alginate solution prior to encapsulation so that the alginate matrix was labeled with MION instead of the cells (i.e., extracellular compartment). The data show that although the location of cells can be identified within APA beads, cell growth or rearrangement within these constructs cannot be effectively monitored, regardless of the location of MION compartmentalization. The advantages and disadvantages of these techniques and their potential use in tissue engineering are discussed. PMID:19165877

18F-positron-emitting/fluorescent labeled erythrocytes allow imaging of internal hemorrhage in a murine intracranial hemorrhage model

PubMed Central

Wang, Ye; An, Fei-Fei; Chan, Mark; Friedman, Beth; Rodriguez, Erik A; Tsien, Roger Y; Aras, Omer

2017-01-01

An agent for visualizing cells by positron emission tomography is described and used to label red blood cells. The labeled red blood cells are injected systemically so that intracranial hemorrhage can be visualized by positron emission tomography (PET). Red blood cells are labeled with 0.3 µg of a positron-emitting, fluorescent multimodal imaging probe, and used to non-invasively image cryolesion induced intracranial hemorrhage in a murine model (BALB/c, 2.36 × 108 cells, 100 µCi, <4 mm hemorrhage). Intracranial hemorrhage is confirmed by histology, fluorescence, bright-field, and PET ex vivo imaging. The low required activity, minimal mass, and high resolution of this technique make this strategy an attractive alternative for imaging intracranial hemorrhage. PET is one solution to a spectrum of issues that complicate single photon emission computed tomography (SPECT). For this reason, this application serves as a PET alternative to [99mTc]-agents, and SPECT technology that is used in 2 million annual medical procedures. PET contrast is also superior to gadolinium and iodide contrast angiography for its lack of clinical contraindications. PMID:28054494

Solid-water detoxifying reagents for chemical and biological agents

DOEpatents

Hoffman, Dennis M [Livermore, CA; Chiu, Ing Lap [Castro Valley, CA

2006-04-18

Formation of solid-water detoxifying reagents for chemical and biological agents. Solutions of detoxifying reagent for chemical and biological agents are coated using small quantities of hydrophobic nanoparticles by vigorous agitation or by aerosolization of the solution in the presence of the hydrophobic nanoparticles to form a solid powder. For example, when hydrophobic fumed silica particles are shaken in the presence of IN oxone solution in approximately a 95:5-weight ratio, a dry powder results. The hydrophobic silica forms a porous coating of insoluble fine particles around the solution. Since the chemical or biological agent tends to be hydrophobic on contact with the weakly encapsulated detoxifying solution, the porous coating breaks down and the detoxifying reagent is delivered directly to the chemical or biological agent for maximum concentration at the point of need. The solid-water (coated) detoxifying solutions can be blown into contaminated ventilation ducting or other difficult to reach sites for detoxification of pools of chemical or biological agent. Once the agent has been detoxified, it can be removed by flushing the area with air or other techniques.

Multimodal imaging of lymph nodes and tumors using glycol-chitosan-coated gold nanoparticles (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sun, In-Cheol; Dumani, Diego S.; Emelianov, Stanislav Y.

2017-03-01

A key step in staging cancer is the diagnosis of metastasis that spreads through lymphatic system. For this reason, researchers develop various methods of sentinel lymph node mapping that often use a radioactive tracer. This study introduces a safe, cost-effective, high-resolution, high-sensitivity, and real-time method of visualizing the sentinel lymph node: ultrasound-guided photoacoustic (US/PA) imaging augmented by a contrast agent. In this work, we use clearable gold nanoparticles covered by a biocompatible polymer (glycol chitosan) to enhance cellular uptake by macrophages abundant in lymph nodes. We incubate macrophages with glycol-chitosan-coated gold nanoparticles (0.05 mg Au/ml), and then fix them with paraformaldehyde solution for an analysis of in vitro dark-field microscopy and cell phantom. The analysis shows enhanced cellular uptake of nanoparticles by macrophages and strong photoacoustic signal from labeled cells in tissue-mimicking cell phantoms consisting gelatin solution (6 %) with silica gel (25 μm, 0.3%) and fixed macrophages. The in-vivo US/PA imaging of cervical lymph nodes in healthy mice (nu/nu, female, 5 weeks) indicates a strong photoacoustic signal from a lymph node 10 minutes post-injection (2.5 mg Au/ml, 80 μl). The signal intensity and the nanoparticle-labeled volume of tissue within the lymph node continues to increase until 4 h post-injection. Histological analysis further confirms the accumulation of gold nanoparticles within the lymph nodes. This work suggests the feasibility of molecular/cellular US/PA imaging with biocompatible gold nanoparticles as a photoacoustic contrast agent in the diagnosis of lymph-node-related diseases.

Using an Electron Scanning Microscope to Assess the Penetrating Abilities of an Experimental Preparation with Features of a Dental Infiltrant: Preliminary Study.

PubMed

Skucha-Nowak, Małgorzata; Mertas, Anna; Tanasiewicz, Marta

2016-01-01

The resin infiltration technique is one of the micro-invasive methods whose aim is the penetration of demineralized enamel with a low viscosity resin. This technique allows the dentist to avoid the application of mechanical means of treatment. The objective of this preliminary study was to attempt to determine the possibilities of using an electron microscope to assess the penetrating abilities of an experimental preparation with features of a dental infiltrant and to compare the depth of infiltration of the designed experimental preparation with an infiltrant available on the market. A bioactive methacrylate monomer based on PMMAn with built-in metronidazole was synthesized. The commercially available Icon solution (with contrast agent YbF3) and the experimental solution were applied to the relevant parts of teeth. The dissected sections along the long tooth axis and polished surfaces were then examined with use of an electron scanning microscope. The backscattered electron technique gives much better results than the secondary electron method as it makes it possible to localize even very small YbF3 particles. The authors concluded that the backscattered electron technique gives much better results than the secondary electron method as it makes it possible to localize even very small particles of the contrast agent. In order to prevent blockage of decalcified enamel tissue by ytterbium trifluoride (YbF3) grains, a nanoparticle form of that compound should be used (that is, particles with sizes in the range of 10-9 m).

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.

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.

Subharmonic emissions from microbubbles: effect of the driving pulse shape.

PubMed

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

2006-11-01

The aims of this work are to investigate the response of the ultrasonic contrast agents (UCA) insonified by different arbitrary-shaped pulses at different acoustic pressures and concentration of the contrast agent focusing on subharmonic emission. A transmission setup was developed in order to insonify the contrast agent contained in a measurement chamber. The transmitted ultrasonic signals were generated by an arbitrary wave generator connected to a linear power amplifier able to drive a single-element transducer. The transmitted ultrasonic pulses that passed through the contrast agent-filled chamber were received by a second transducer or a hydrophone aligned with the first one. The radio frequency (RF) signals were acquired by fast echographic multiparameters multi-image novel apparatus (FEMMINA), which is an echographic platform able to acquire ultrasonic signals in a real-time modality. Three sets of ultrasonic signals were devised in order to evaluate subharmonic response of the contrast agent respect with sinusoidal burst signals used as reference pulses. A decreasing up to 30 dB in subharmonic response was detected for a Gaussian-shaped pulse; differences in subharmonic emission up to 21 dB were detected for a composite pulse (two-tone burst) for different acoustic pressures and concentrations. Results from this experimentation demonstrated that the transmitted pulse shape strongly affects subharmonic emission in spite of a second harmonic one. In particular, the smoothness of the initial portion of the shaped pulses can inhibit subharmonic generation from the contrast agents respect with a reference sinusoidal burst signal. It also was shown that subharmonic generation is influenced by the amplitude and the concentration of the contrast agent for each set of the shaped pulses. Subharmonic emissions that derive from a nonlinear mechanism involving nonlinear coupling among different oscillation modes are strongly affected by the shape of the ultrasonic driving pulse.

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.

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.

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.

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.

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

Influence of Anti-inflammatory Drugs on the Rheological Properties of Synovial Fluid and Its Components

NASA Astrophysics Data System (ADS)

Krause, Wendy E.; Klossner, Rebecca R.; Liang, Jing; Colby, Ralph H.

2006-03-01

The polyelectrolyte hyaluronic acid (HA, hyaluronan), its interactions with anti-inflammatory drugs and other biopolymers, and its role in synovial fluid are being studied. We are investigating the rheological properties of sodium hyaluronate (NaHA) solutions and an experimental model of synovial fluid (comprised of NaHA, and the plasma proteins albumin and γ-globulins). Steady shear measurements on bovine synovial fluid, the synovial fluid model, and plasma protein solutions indicate that the fluids are rheopectic (stress increases with time under steady shear). In addition, the influence of anti-inflammatory agents on these solutions is being explored. Initial results indicate that D-penicillamine and hydroxychloroquine (HCQ) affect the rheology of the synovial fluid model and its components. While HCQ has no effect on the viscosity of NaHA solutions, it inhibits/suppresses the observed rheopexy of the synovial fluid model and plasma protein solutions. In contrast, D-penicillamine has a complex, time dependent effect on the viscosity of NaHA solutions,---reducing the zero shear rate viscosity of a 3 mg/mL NaHA (in phosphate buffered saline) by ca. 40% after 44 days. The potential implications of these results will be discussed.

Synthesis of a colloid solution of silica-coated gold nanoparticles for X-ray imaging applications

NASA Astrophysics Data System (ADS)

Kobayashi, Yoshio; Nagasu, Ryoko; Shibuya, Kyosuke; Nakagawa, Tomohiko; Kubota, Yohsuke; Gonda, Kohsuke; Ohuchi, Noriaki

2014-08-01

This work proposes a method for fabricating silica-coated gold (Au) nanoparticles, surface modified with poly(ethylene glycol) (PEG) (Au/SiO2/PEG), with a particle size of 54.8 nm. X-ray imaging of a mouse is performed with the colloid solution. A colloid solution of 17.9 nm Au nanoparticles was prepared by reducing Au ions (III) with sodium citrate in water at 80 °C. The method used for silica-coating the Au nanoparticles was composed of surface-modification of the Au nanoparticles with (3-aminopropyl)-trimethoxysilane (APMS) and a sol-gel process. The sol-gel process was performed in the presence of the surface-modified Au nanoparticles using tetraethylorthosilicate, APMS, water, and sodium hydroxide, in which the formation of silica shells and the introduction of amino groups to the silica-coated particles took place simultaneously (Au/SiO2-NH2). Surface modification of the Au/SiO2-NH2 particles with PEG, or PEGylation of the particle surface, was performed by adding PEG with a functional group that reacted with an amino group in the Au/SiO2-NH2 particle colloid solution. A computed tomography (CT) value of the aqueous colloid solution of Au/SiO2/PEG particles with an actual Au concentration of 0.112 M was as high as 922 ± 12 Hounsfield units, which was higher than that of a commercial X-ray contrast agent with the same iodine concentration. Injecting the aqueous colloid solution of Au/SiO2/PEG particles into a mouse increased the light contrast of tissues. A CT value of the heart rose immediately after the injection, and this rise was confirmed for up to 6 h.

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 ...

High-resolution contrast-enhanced optical coherence tomography in mice retinae

NASA Astrophysics Data System (ADS)

Sen, Debasish; SoRelle, Elliott D.; Liba, Orly; Dalal, Roopa; Paulus, Yannis M.; Kim, Tae-Wan; Moshfeghi, Darius M.; de la Zerda, Adam

2016-06-01

Optical coherence tomography (OCT) is a noninvasive interferometric imaging modality providing anatomical information at depths of millimeters and a resolution of micrometers. Conventional OCT images limit our knowledge to anatomical structures alone, without any contrast enhancement. Therefore, here we have, for the first time, optimized an OCT-based contrast-enhanced imaging system for imaging single cells and blood vessels in vivo inside the living mouse retina at subnanomolar sensitivity. We used bioconjugated gold nanorods (GNRs) as exogenous OCT contrast agents. Specifically, we used anti-mouse CD45 coated GNRs to label mouse leukocytes and mPEG-coated GNRs to determine sensitivity of GNR detection in vivo inside mice retinae. We corroborated OCT observations with hyperspectral dark-field microscopy of formalin-fixed histological sections. Our results show that mouse leukocytes that otherwise do not produce OCT contrast can be labeled with GNRs leading to significant OCT intensity equivalent to a 0.5 nM GNR solution. Furthermore, GNRs injected intravenously can be detected inside retinal blood vessels at a sensitivity of ˜0.5 nM, and GNR-labeled cells injected intravenously can be detected inside retinal capillaries by enhanced OCT contrast. We envision the unprecedented resolution and sensitivity of functionalized GNRs coupled with OCT to be adopted for longitudinal studies of retinal disorders.

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.

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.

Protein interactions in concentrated ribonuclease solutions

NASA Astrophysics Data System (ADS)

Boyer, Mireille; Roy, Marie-Odile; Jullien, Magali; Bonneté, Françoise; Tardieu, Annette

1999-01-01

To investigate the protein interactions involved in the crystallization process of ribonuclease A, dynamic light scattering (DLS) and small angle X-ray scattering experiments (SAXS) were performed on concentrated solutions. Whereas the translational diffusion coefficient obtained from DLS is sensitive to thermodynamic and hydrodynamic interactions and permits to calculate an interaction parameter, the shape of the SAXS curves is related to the type of interaction (attractive or repulsive). We compared the effect of pH on protein interactions in the case of two types of crystallizing agents: a mixture of salts (3 M sodium chloride plus 0.2 M ammonium sulfate) and an organic solvent (ethanol). The results show that in the presence of ethanol, as in low salt, protein interactions become more attractive as the pH increases from 4 to 8 and approaches the isoelectric point. In contrast, a reverse effect is observed in high salt conditions: the strength of attractive interactions decreases as the pH increases. The range of the pH effect can be related to ionization of histidine residues, particularly those located in the active site of the protein. The present observations point out the important role played by localized charges in crystallization conditions, whatever the precipitating agent.

Calixarene cleansing formulation for uranium skin contamination.

PubMed

Phan, Guillaume; Semili, Naïma; Bouvier-Capely, Céline; Landon, Géraldine; Mekhloufi, Ghozlene; Huang, Nicolas; Rebière, François; Agarande, Michelle; Fattal, Elias

2013-10-01

An oil-in-water cleansing emulsion containing calixarene molecule, an actinide specific chelating agent, was formulated in order to improve the decontamination of uranium from the skin. Commonly commercialized cosmetic ingredients such as surfactants, mineral oil, or viscosifying agents were used in preparing the calixarene emulsion. The formulation was characterized in terms of size and apparent viscosity measurements and then was tested for its ability to limit uranyl ion permeation through excoriated pig-ear skin explants in 24-h penetration studies. Calixarene emulsion effectiveness was compared with two other reference treatments consisting of DTPA and EHBP solutions. Application of calixarene emulsion induced the highest decontamination effect with an 87% decrease in uranium diffusion flux. By contrast, EHBP and DTPA solutions only allowed a 50% and 55% reduction of uranium permeation, respectively, and had the same effect as a simple dilution of the contamination by pure water. Uranium diffusion decrease was attributed to uranyl ion-specific chelation by calixarene within the formulation, since no significant effect was obtained after application of the same emulsion without calixarene. Thus, calixarene cleansing emulsion could be considered as a promising treatment in case of accidental contamination of the skin by highly diffusible uranium compounds.

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 ...

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.

Patents – Melvin Calvin

Science.gov Websites

plutonium from uranium and fission products in an aqueous acidic solution by use of a chelating agent. The concentration is adjusted to about 1 N bar. The aqueous solution is then contacted with a water-immiscible organic solvent solution and the chelating agent. The chelating agents covered by this invention comprise

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

Normal saline as a natural intravascular contrast agent for dynamic perfusion-weighted MRI of the brain: Proof of concept at 1.5T.

PubMed

Jara, Hernán; Mian, Asim; Sakai, Osamu; Anderson, Stephan W; Horn, Mitchel J; Norbash, Alexander M; Soto, Jorge A

2016-12-01

Gadolinium-based contrast agents have associated risks. Normal saline (NS) is a nontoxic sodium chloride water solution that can significantly increase the magnetic resonance imaging (MRI) relaxation times of blood via transient hemodilution (THD). The purpose of this pilot study was to test in vivo in the head the potential of normal saline as a safer, exogenous perfusion contrast agent. This Health Insurance Portability and Accountability Act (HIPAA)-compliant prospective study was approved by the local Institutional Review Board (IRB): 12 patients were scanned with T 1 -weighted inversion recovery turbo spin echo pulse sequence at 1.5T. The dynamic inversion recovery pulse sequence was run before, during, and after the NS injection for up to 5 minutes: 100 ml of NS was power-injected via antecubital veins at 3-4 ml/s. Images were processed to map maximum enhancement area-under-the-curve, time-to-peak, and mean-transit-time. These maps were used to identify the areas showing significant NS injection-related signal and to generate enhancement time curves. Hardware and pulse sequence stability were studied via phantom experimentation. Main features of the time curves were tested against theoretical modeling of THD signal effects using inversion recovery pulse sequences. Pearson correlation coefficient (R) mapping was used to differentiate genuine THD effects from motion confounders and noise. The scans of 8 out of 12 patients showed NS injection-related effects that correlate in magnitude with tissue type (gray matter ∼15% and white matter ∼3%). Motion artifacts prevented ascertaining NS signal effects in the remaining four patients. Positive and negative time curves were observed in vivo and this dual THD signal polarity was also observed in the theoretical simulations. R-histograms that were approximately constant in the range 0.1 < |R| < 0.8 and leading to correlation fractions of F corr (|R| > 0.5) = 0.45 and 0.59 were found to represent scans with genuine THD signal effects. A measurable perfusion effect in brain tissue was demonstrated in vivo using NS as an injectable intravascular contrast agent. J. Magn. Reson. Imaging 2016;44:1580-1591. © 2016 International Society for Magnetic Resonance in Medicine.

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.

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

Simple 1H NMR spectroscopic method for assay of salts of the contrast agent diatrizoate in commercial solutions.

PubMed

Hanna, G M; Lau-Cam, C A

1996-01-01

A simple, accurate, and specific 1H NMR spectroscopic method was developed for the assay of diatrizoate meglumine or the combination diatrizoate meglumine and diatrizoate sodium in commercial solutions for injection. A mixture of injectable solution and sodium acetate, the internal standard, was diluted with D2O and the 1H NMR spectrum of the solution was obtained. Two approaches were used to calculate the drug content, based on the integral values for the -N-CO-CH3 protons of diatrizoic acid at 2.23 ppm, and -N-CH3 protons of meglumine at 2.73 ppm, and the CH3-CO-protons of sodium acetate at 1.9 ppm. Recoveries (mean +/- standard deviation) of diatrizoic acid and meglumine from 10 synthetic mixtures of various amounts of these compounds with a fixed amount of internal standard were 100.3 +/- 0.55% and 100.1 +/- 0.98%, respectively. In addition to providing a direct means of simultaneously assaying diatrizoic acid and meglumine, the proposed NMR method can also be used to identify diatrizoate meglumine and each of its molecular components.

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

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

Quantitative segmentation of fluorescence microscopy images of heterogeneous tissue: Approach for tuning algorithm parameters

NASA Astrophysics Data System (ADS)

Mueller, Jenna L.; Harmany, Zachary T.; Mito, Jeffrey K.; Kennedy, Stephanie A.; Kim, Yongbaek; Dodd, Leslie; Geradts, Joseph; Kirsch, David G.; Willett, Rebecca M.; Brown, J. Quincy; Ramanujam, Nimmi

2013-02-01

The combination of fluorescent contrast agents with microscopy is a powerful technique to obtain real time images of tissue histology without the need for fixing, sectioning, and staining. The potential of this technology lies in the identification of robust methods for image segmentation and quantitation, particularly in heterogeneous tissues. Our solution is to apply sparse decomposition (SD) to monochrome images of fluorescently-stained microanatomy to segment and quantify distinct tissue types. The clinical utility of our approach is demonstrated by imaging excised margins in a cohort of mice after surgical resection of a sarcoma. Representative images of excised margins were used to optimize the formulation of SD and tune parameters associated with the algorithm. Our results demonstrate that SD is a robust solution that can advance vital fluorescence microscopy as a clinically significant technology.

Targeted in-vivo computed tomography (CT) imaging of tissue ACE using concentrated lisinopril-capped gold nanoparticle solutions

NASA Astrophysics Data System (ADS)

Daniel, Marie-Christine; Aras, Omer; Smith, Mark F.; Nan, Anjan; Fleiter, Thorsten

2010-04-01

The development of cardiac and pulmonary fibrosis have been associated with overexpression of angiotensin-converting enzyme (ACE). Moreover, ACE inhibitors, such as lisinopril, have shown a benificial effect for patients diagnosed with heart failure or systemic hypertension. Thus targeted imaging of the ACE is of crucial importance for monitoring of the tissue ACE activity as well as the treatment efficacy in heart failure. In this respect, lisinopril-capped gold nanoparticles were prepared to provide a new type of probe for targeted molecular imaging of ACE by tuned K-edge computed tomography (CT) imaging. Concentrated solutions of these modified gold nanoparticles, with a diameter around 16 nm, showed high contrast in CT imaging. These new targeted imaging agents were thus used for in vivo imaging on rat models.

Interaction Between Cyanine Dye IR-783 and Polystyrene Nanoparticles in Solution.

PubMed

Zhang, Yunzhi; Xu, Hui; Casabianca, Leah B

2018-05-17

The interactions between small molecule drugs or dyes and nanoparticles are important to the use of nanoparticles in medicine. Noncovalent adsorption of dyes on nanoparticle surfaces is also important to the development of nanoparticle dual-use imaging contrast agents. In the present work, solution-state NMR is used to examine the noncovalent interaction between a near-infrared cyanine dye and the surface of polystyrene nanoparticles in solution. Using 1D proton NMR, we can approximate the number of dye molecules that associate with each nanoparticle for different sized nanoparticles. Saturation-Transfer Difference (STD)-NMR was also used to show that protons near the positively-charged nitrogen in the dye are more strongly associated with the negatively-charged nanoparticle surface than protons near the negatively-charged sulfate groups of the dye. The methods described here can be used to study similar drug or dye molecules interacting with the surface of organic nanoparticles. This article is protected by copyright. All rights reserved.

Irradiation treatment of pharmaceutical and personal care products (PPCPs) in water and wastewater: An overview

NASA Astrophysics Data System (ADS)

Wang, Jianlong; Chu, Libing

2016-08-01

Pharmaceutical and personal care products (PPCPs), especially the pharmaceutically active compounds (PhACs) such as antibiotics and hormones have attracted great concerns worldwide for their persistence and potential threat to ecosystem and public health. This paper presents an overview on the ionizing irradiation-induced degradation of PPCPs in aqueous solution. Parameters that affect PPCPs degradation, such as the absorbed dose, solution pH, dose rate, water matrices and the presence of some inorganic ions and humic acid are evaluated. The mechanism and pathways of radiolytic degradation of PPCPs are reviewed. In many cases, PPCPs such as antibiotics and X-ray contrast agent could be removed completely by radiation, but a higher absorbed dose was needed for their mineralization and toxicity reduction. The combination of ionizing irradiation with other methods such as H2O2, ozonation and TiO2 nanoparticles could improve the degradation efficacy and reduce the cost. Ionizing irradiation is a promising alternative for degradation of PPCPs in aqueous solution.

Magnetic Resonance Imaging (MRI) (For Parents)

MedlinePlus

... problems, your child may be given a contrast solution through an IV. The solution, which is painless as it goes into the ... to any medications or food before the contrast solution is given. The contrast solution used in MRI ...

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

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.

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

NASA Astrophysics Data System (ADS)

Laoui, Samir

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

Quantitative Gd-DOTA uptake from cerebrospinal fluid into rat brain using 3D VFA-SPGR at 9.4T.

PubMed

Lee, Hedok; Mortensen, Kristian; Sanggaard, Simon; Koch, Palle; Brunner, Hans; Quistorff, Bjørn; Nedergaard, Maiken; Benveniste, Helene

2018-03-01

We propose a quantitative technique to assess solute uptake into the brain parenchyma based on dynamic contrast-enhanced MRI (DCE-MRI). With this approach, a small molecular weight paramagnetic contrast agent (Gd-DOTA) is infused in the cerebral spinal fluid (CSF) and whole brain gadolinium concentration maps are derived. We implemented a 3D variable flip angle spoiled gradient echo (VFA-SPGR) longitudinal relaxation time (T1) technique, the accuracy of which was cross-validated by way of inversion recovery rapid acquisition with relaxation enhancement (IR-RARE) using phantoms. Normal Wistar rats underwent Gd-DOTA infusion into CSF via the cisterna magna and continuous MRI for approximately 130 min using T1-weighted imaging. Dynamic Gd-DOTA concentration maps were calculated and parenchymal uptake was estimated. In the phantom study, T1 discrepancies between the VFA-SPGR and IR-RARE sequences were approximately 6% with a transmit coil inhomogeneity correction. In the in vivo study, contrast transport profiles indicated maximal parenchymal retention of approximately 19% relative to the total amount delivered into the cisterna magna. Imaging strategies for accurate 3D contrast concentration mapping at 9.4T were developed and whole brain dynamic concentration maps were derived to study solute transport via the glymphatic system. The newly developed approach will enable future quantitative studies of the glymphatic system in health and disease states. Magn Reson Med 79:1568-1578, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

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

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.

Magnetic Resonance Imaging (MRI): Brain (For Parents)

MedlinePlus

... problems, your child may be given a contrast solution through an IV. The solution is painless as it goes into the vein. ... to any medications or food before the contrast solution is given. The contrast solution used in MRI ...

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.

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.

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

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.

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.

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.

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"

Amphiphilic complexes of Ho(iii), Dy(iii), Tb(iii) and Eu(iii) for optical and high field magnetic resonance imaging.

PubMed

Harris, Michael; Henoumont, Céline; Peeters, Wannes; Toyouchi, Shuichi; Vander Elst, Luce; Parac-Vogt, Tatjana N

2018-05-29

Lanthanides, holmium(iii), dysprosium(iii), and terbium(iii), were coordinated to an amphiphilic DOTA bis-coumarin derivative and then further assembled with an amphiphilic europium(iii) DTPA bis-coumarin derivative into mono-disperse micelles. The self-assembled micelles were characterized and assessed for their potential as bimodal contrast agents for high field magnetic resonance and optical imaging applications. All micelles showed a high transverse relaxation (r2) of 46, 34, and 30 s-1 mM-1 at 500 MHz and 37 °C for Dy(iii), Ho(iii) and Tb(iii), respectively, which is a result of the high magnetic moment of these lanthanides and the long rotational correlation time of the micelles. The quantum yield in aqueous solution ranged from 1.8% for Tb/Eu to 1.4% for Dy/Eu and 1.0% for the Ho/Eu micelles. Multi-photon excited emission spectroscopy has shown that due to the two-photon absorption of the coumarin chromophore the characteristic Eu(iii) emission could be observed upon excitation at 800 nm, demonstrating the usefulness of the system for in vivo fluorescence imaging applications. To the best of our knowledge, this is the first example reporting the potential of a holmium(iii) chelate as a negative MRI contrast agent.

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.

Stability analysis of ultrasound thick-shell contrast agents

PubMed Central

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

2012-01-01

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

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.

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.

Paramagnetic perfluorocarbon-filled albumin-(Gd-DTPA) microbubbles for the induction of focused-ultrasound-induced blood-brain barrier opening and concurrent MR and ultrasound imaging

NASA Astrophysics Data System (ADS)

Liao, Ai-Ho; Liu, Hao-Li; Su, Chia-Hao; Hua, Mu-Yi; Yang, Hung-Wei; Weng, Yu-Ting; Hsu, Po-Hung; Huang, Sheng-Min; Wu, Shih-Yen; Wang, Hsin-Ell; Yen, Tzu-Chen; Li, Pai-Chi

2012-05-01

This paper presents new albumin-shelled Gd-DTPA microbubbles (MBs) that can concurrently serve as a dual-modality contrast agent for ultrasound (US) imaging and magnetic resonance (MR) imaging to assist blood-brain barrier (BBB) opening and detect intracerebral hemorrhage (ICH) during focused ultrasound brain drug delivery. Perfluorocarbon-filled albumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm and concentration of 2.903×109 MBs ml-1 using albumin-(Gd-DTPA) and by sonication with perfluorocarbon (C3F8) gas. The albumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated until the free Gd3+ ions were eliminated (which were detected by the xylenol orange sodium salt solution). The albumin-(Gd-DTPA) MBs were also characterized and evaluated both in vitro and in vivo by US and MR imaging. Focused US was used with the albumin-(Gd-DTPA) MBs to induce disruption of the BBB in 18 rats. BBB disruption was confirmed with contrast-enhanced T1-weighted turbo-spin-echo sequence MR imaging. Heavy T2*-weighted 3D fast low-angle shot sequence MR imaging was used to detect ICH. In vitro US imaging experiments showed that albumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T1-, T2- and T2*-weighted MR images. The r1 and r2 relaxivities for Gd-DTPA were 7.69 and 21.35 s-1mM-1, respectively, indicating that the MBs represent a positive contrast agent in T1-weighted images. In vivo MR imaging experiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA) MBs can be used to both induce disruption of the BBB and detect ICH. To compare the signal intensity change between pure BBB opening and BBB opening accompanying ICH, albumin-(Gd-DTPA) MB imaging can provide a ratio of 5.14 with significant difference (p = 0.026), whereas Gd-DTPA imaging only provides a ratio of 2.13 and without significant difference (p = 0.108). The results indicate that albumin-(Gd-DTPA) MBs have potential as a US/MR dual-modality contrast agent for BBB opening and differentiating focused-US-induced BBB opening from ICH, and can monitor the focused ultrasound brain drug delivery process.

Paramagnetic perfluorocarbon-filled albumin-(Gd-DTPA) microbubbles for the induction of focused-ultrasound-induced blood-brain barrier opening and concurrent MR and ultrasound imaging.

PubMed

Liao, Ai-Ho; Liu, Hao-Li; Su, Chia-Hao; Hua, Mu-Yi; Yang, Hung-Wei; Weng, Yu-Ting; Hsu, Po-Hung; Huang, Sheng-Min; Wu, Shih-Yen; Wang, Hsin-Ell; Yen, Tzu-Chen; Li, Pai-Chi

2012-05-07

This paper presents new albumin-shelled Gd-DTPA microbubbles (MBs) that can concurrently serve as a dual-modality contrast agent for ultrasound (US) imaging and magnetic resonance (MR) imaging to assist blood-brain barrier (BBB) opening and detect intracerebral hemorrhage (ICH) during focused ultrasound brain drug delivery. Perfluorocarbon-filled albumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm and concentration of 2.903×10(9) MBs ml(-1) using albumin-(Gd-DTPA) and by sonication with perfluorocarbon (C(3)F(8)) gas. The albumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated until the free Gd(3+) ions were eliminated (which were detected by the xylenol orange sodium salt solution). The albumin-(Gd-DTPA) MBs were also characterized and evaluated both in vitro and in vivo by US and MR imaging. Focused US was used with the albumin-(Gd-DTPA) MBs to induce disruption of the BBB in 18 rats. BBB disruption was confirmed with contrast-enhanced T(1)-weighted turbo-spin-echo sequence MR imaging. Heavy T(2)*-weighted 3D fast low-angle shot sequence MR imaging was used to detect ICH. In vitro US imaging experiments showed that albumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T(1)-, T(2)- and T(2)*-weighted MR images. The r(1) and r(2) relaxivities for Gd-DTPA were 7.69 and 21.35 s(-1)mM(-1), respectively, indicating that the MBs represent a positive contrast agent in T(1)-weighted images. In vivo MR imaging experiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA) MBs can be used to both induce disruption of the BBB and detect ICH. To compare the signal intensity change between pure BBB opening and BBB opening accompanying ICH, albumin-(Gd-DTPA) MB imaging can provide a ratio of 5.14 with significant difference (p = 0.026), whereas Gd-DTPA imaging only provides a ratio of 2.13 and without significant difference (p = 0.108). The results indicate that albumin-(Gd-DTPA) MBs have potential as a US/MR dual-modality contrast agent for BBB opening and differentiating focused-US-induced BBB opening from ICH, and can monitor the focused ultrasound brain drug delivery process.

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.

Comparative evaluation of methylene blue and demeclocycline for enhancing optical contrast of brain neoplasms

NASA Astrophysics Data System (ADS)

Wirth, Dennis J.

Brain tumors cause significant morbidity and mortality even when benign. Completeness of resection of brain tumors has been associated with better quality of life. However, that is often difficult to accomplish. The goal of this study was to evaluate the feasibility of using contrast enhanced multimodal confocal imaging for intraoperative detection of brain neoplasms. Different types of benign and malignant, primary and metastatic brain tumors, stained with Methylene Blue (MB) as a contrast agent, were imaged. MB is a traditional histopathologic stain that absorbs light in the red spectral range and fluoresces in the near infrared. It is FDA-approved for in vivo staining of human skin and breast tissue. Optical images showed good correlation with histopathology, demonstrating the potential of contrast enhanced multimodal confocal imaging for intraoperative detection of brain neoplasms ex vivo. However, the safety of MB for staining human brain in vivo is questionable. Demeclocycline (DMN), an antibiotic of the tetracycline family, has shown to be effective in differentiating normal from cancerous tissue in various organs. DMN is a fluorophore, which absorbs light in the violet spectral range and has a broad emission band covering green and yellow wavelengths. It is commonly used to treat infection and inflammatory disorders, and could provide a safer alternative to MB. To test this hypothesis, fresh excess human brain tissues were bisected and stained with aqueous solutions of either MB or DMN and then imaged. Reflectance and fluorescence images acquired from tissues stained with the two dyes were compared, and correlated with processed H&E histopathology. Comparison showed similar staining patterns and contrast of diagnostic features in glioblastomas, stained using either MB or DMN. The results show potential of both MB and DMN for the intraoperative detection of microscopic nests of brain neoplasms. Further studies will establish safety and efficacy of these agents in vivo.

COORDINATION COMPOUND-SOLVENT EXTRACTION PROCESS FOR URANIUM RECOVERY

DOEpatents

Reas, W.H.

1959-03-10

A method is presented for the separation of uranium from aqueous solutions containing a uranyl salt and thorium. Thc separation is effected by adding to such solutions an organic complexing agent, and then contacting the solution with an organic solvent in which the organic complexing agent is soluble. By use of the proper complexing agent in the proper concentrations uranium will be complexed and subsequently removed in the organic solvent phase, while the thorium remains in the aqueous phase. Mentioned as suitable organic complexing agents are antipyrine, bromoantipyrine, and pyramidon.

Postprocedural pain in shoulder arthrography: differences between using preservative-free normal saline and normal saline with benzyl alcohol as an intraarticular contrast diluent.

PubMed

Storey, Troy F; Gilbride, George; Clifford, Kelly

2014-11-01

The purpose of this study was to prospectively evaluate the effect of benzyl alcohol, a common preservative in normal saline, on postprocedural pain after intraarticular injection for direct shoulder MR arthrography. From April 2011 through January 2013, 138 patients underwent direct shoulder MR arthrography. Using the Wong-Baker Faces Pain Scale, patients were asked to report their shoulder pain level immediately before and immediately after the procedure and then were contacted by telephone 6, 24, and 48 hours after the procedure. Fourteen patients did not receive the prescribed amount of contrast agent for diagnostic reasons or did not complete follow-up. Sixty-two patients received an intraarticular solution including preservative-free normal saline (control group) and 62 patients received an intraarticular solution including normal saline with 0.9% benzyl alcohol as a contrast diluent (test group). Patients were randomized as to which intraarticular diluent they received. Fluoroscopic and MR images were reviewed for extracapsular contrast agent administration or extravasation, full-thickness rotator cuff tears, and adhesive capsulitis. The effect of preservative versus control on pain level was estimated with multiple regression, which included time after procedure as the covariate and accounted for repeated measures over patients. Pain scale scores were significantly (p = 0.0382) higher (0.79 units; 95% CI, 0.034-1.154) with benzyl alcohol preservative compared with control (saline). In both study arms, the pain scale scores decreased slightly after the procedure, increased by roughly 1 unit over baseline for the test group and 0.3 unit over baseline for the control group by 6 hours after the procedure, were 0.50 unit over baseline for the test group and 0.12 unit over baseline for the control group at 24 hours, then fell to be slightly greater than baseline at 48 hours with benzyl alcohol and slightly less than baseline without benzyl alcohol. These trends over time were highly significant (p < 0.0001). Shoulder arthrography is often associated with postprocedural discomfort that begins immediately after the procedure and resolves by 48 hours. There is significantly increased patient discomfort at 6 and 48 hours when using normal saline preserved with benzyl alcohol as a diluent compared with using normal saline without preservative as a diluent.

Emergence of a snake-like structure in mobile distributed agents: an exploratory agent-based modeling approach.

PubMed

Niazi, Muaz A

2014-01-01

The body structure of snakes is composed of numerous natural components thereby making it resilient, flexible, adaptive, and dynamic. In contrast, current computer animations as well as physical implementations of snake-like autonomous structures are typically designed to use either a single or a relatively smaller number of components. As a result, not only these artificial structures are constrained by the dimensions of the constituent components but often also require relatively more computationally intensive algorithms to model and animate. Still, these animations often lack life-like resilience and adaptation. This paper presents a solution to the problem of modeling snake-like structures by proposing an agent-based, self-organizing algorithm resulting in an emergent and surprisingly resilient dynamic structure involving a minimal of interagent communication. Extensive simulation experiments demonstrate the effectiveness as well as resilience of the proposed approach. The ideas originating from the proposed algorithm can not only be used for developing self-organizing animations but can also have practical applications such as in the form of complex, autonomous, evolvable robots with self-organizing, mobile components with minimal individual computational capabilities. The work also demonstrates the utility of exploratory agent-based modeling (EABM) in the engineering of artificial life-like complex adaptive systems.

Emergence of a Snake-Like Structure in Mobile Distributed Agents: An Exploratory Agent-Based Modeling Approach

PubMed Central

Niazi, Muaz A.

2014-01-01

The body structure of snakes is composed of numerous natural components thereby making it resilient, flexible, adaptive, and dynamic. In contrast, current computer animations as well as physical implementations of snake-like autonomous structures are typically designed to use either a single or a relatively smaller number of components. As a result, not only these artificial structures are constrained by the dimensions of the constituent components but often also require relatively more computationally intensive algorithms to model and animate. Still, these animations often lack life-like resilience and adaptation. This paper presents a solution to the problem of modeling snake-like structures by proposing an agent-based, self-organizing algorithm resulting in an emergent and surprisingly resilient dynamic structure involving a minimal of interagent communication. Extensive simulation experiments demonstrate the effectiveness as well as resilience of the proposed approach. The ideas originating from the proposed algorithm can not only be used for developing self-organizing animations but can also have practical applications such as in the form of complex, autonomous, evolvable robots with self-organizing, mobile components with minimal individual computational capabilities. The work also demonstrates the utility of exploratory agent-based modeling (EABM) in the engineering of artificial life-like complex adaptive systems. PMID:24701135

Mutual and asynchronous anticipation and action in sports as globally competitive and locally coordinative dynamics

PubMed Central

Fujii, Keisuke; Isaka, Tadao; Kouzaki, Motoki; Yamamoto, Yuji

2015-01-01

Humans interact by changing their actions, perceiving other’s actions and executing solutions in conflicting situations. Using oscillator models, nonlinear dynamics have been considered for describing these complex human movements as an emergence of self-organisation. However, these frameworks cannot explain the hierarchical structures of complex behaviours between conflicting inter-agent and adapting intra-agent systems, especially in sport competitions wherein mutually quick decision making and execution are required. Here we adopt a hybrid multiscale approach to model an attack-and-defend game during which both players predict the opponent’s movement and move with a delay. From both simulated and measured data, one synchronous outcome between two-agent (i.e. successful defence) can be described as one attractor. In contrast, the other coordination-breaking outcome (i.e. successful attack) cannot be explained using gradient dynamics because the asymmetric interaction cannot always assume a conserved physical quantity. Instead, we provide the asymmetric and asynchronous hierarchical dynamical models to discuss two-agent competition. Our framework suggests that possessing information about an opponent and oneself in local-coordinative and global-competitive scale enables us to gain a deeper understanding of sports competitions. We anticipate developments in the scientific fields of complex movement adapting to such uncontrolled environments. PMID:26538452

Mutual and asynchronous anticipation and action in sports as globally competitive and locally coordinative dynamics

NASA Astrophysics Data System (ADS)

Fujii, Keisuke; Isaka, Tadao; Kouzaki, Motoki; Yamamoto, Yuji

2015-11-01

Humans interact by changing their actions, perceiving other’s actions and executing solutions in conflicting situations. Using oscillator models, nonlinear dynamics have been considered for describing these complex human movements as an emergence of self-organisation. However, these frameworks cannot explain the hierarchical structures of complex behaviours between conflicting inter-agent and adapting intra-agent systems, especially in sport competitions wherein mutually quick decision making and execution are required. Here we adopt a hybrid multiscale approach to model an attack-and-defend game during which both players predict the opponent’s movement and move with a delay. From both simulated and measured data, one synchronous outcome between two-agent (i.e. successful defence) can be described as one attractor. In contrast, the other coordination-breaking outcome (i.e. successful attack) cannot be explained using gradient dynamics because the asymmetric interaction cannot always assume a conserved physical quantity. Instead, we provide the asymmetric and asynchronous hierarchical dynamical models to discuss two-agent competition. Our framework suggests that possessing information about an opponent and oneself in local-coordinative and global-competitive scale enables us to gain a deeper understanding of sports competitions. We anticipate developments in the scientific fields of complex movement adapting to such uncontrolled environments.

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

Hybrid Multilayered Plasmonic Nanostars for Coherent Random Lasing.

PubMed

Munkhbat, Battulga; Ziegler, Johannes; Pöhl, Hannes; Wörister, Christian; Sivun, Dmitry; Scharber, Markus C; Klar, Thomas A; Hrelescu, Calin

2016-10-20

Here, we report that hybrid multilayered plasmonic nanostars can be universally used as feedback agents for coherent random lasing in polar or nonpolar solutions containing gain material. We show that silver-enhancement of gold nanostars reduces the pumping threshold for coherent random lasing substantially for both a typical dye (R6G) and a typical fluorescent polymer (MEH-PPV). Further, we reveal that the lasing intensity and pumping threshold of random lasers based on silver-enhanced gold nanostars are not influenced by the silica coating, in contrast to gold nanostar-based random lasers, where silica-coated gold nanostars support only amplified spontaneous emission but no coherent random lasing.

Crowding Shifts the FMN Recognition Mechanism of Riboswitch Aptamer from Conformational Selection to Induced Fit.

PubMed

Rode, Ambadas B; Endoh, Tamaki; Sugimoto, Naoki

2018-06-04

In bacteria, the binding between the riboswitch aptamer domain and ligand is regulated by environmental cues, such as low Mg 2+ in macrophages during pathogenesis to ensure spatiotemporal expression of virulence genes. Binding was investigated between the flavin mononucleotide (FMN) riboswitch aptamer and its anionic ligand in the presence of molecular crowding agent without Mg 2+ ion, which mimics pathogenic conditions. Structural, kinetic, and thermodynamic analyses under the crowding revealed more dynamic conformational rearrangements of the FMN riboswitch aptamer compared to dilute Mg 2+ -containing solution. It is hypothesized that under crowding conditions FMN binds through an induced fit mechanism in contrast to the conformational selection mechanism previously demonstrated in dilute Mg 2+ solution. Since these two mechanisms involve different conformational intermediates and rate constants, these findings have practical significance in areas such as drug design and RNA engineering. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fabrication of monodisperse magnetic nanoparticles released in solution using a block copolymer template

NASA Astrophysics Data System (ADS)

Morcrette, Mélissa; Ortiz, Guillermo; Tallegas, Salomé; Joisten, Hélène; Tiron, Raluca; Baron, Thierry; Hou, Yanxia; Lequien, Stéphane; Bsiesy, Ahmad; Dieny, Bernard

2017-07-01

This paper describes a fabrication process of monodisperse magnetic nanoparticles released in solution, based on combined ‘top-down’ and ‘bottom-up’ approaches. The process involves the use of a self-assembled PS-PMMA block copolymer formed on a sacrificial layer. Such an approach was so far mostly explored for the preparation of patterned magnetic media for ultrahigh density magnetic storage. It is here extended to the preparation of released monodisperse nanoparticles for biomedical applications. A special sacrificial layer had to be developed compatible with the copolymer self-organization. The resulting nanoparticles exhibit very narrow size dispersion (≈7%) and can be good candidates as contrast agents for medical imaging i.e. magnetic resonance imaging or magnetic particle imaging. The approach provides a great freedom in the choice of the particles shapes and compositions. In particular, they can be made of biocompatible magnetic material.

ParaCEST agents encapsulated in Reverse nano-Assembled Capsules (RACs): How slow molecular tumbling can quench CEST

NASA Astrophysics Data System (ADS)

Farashishiko, Annah; Slack, Jacqueline R.; Botta, Mauro; Woods, Mark

2018-04-01

Although paraCEST is a method with immense scope for generating image contrast in MRI, it suffers from the series the serious drawback of high detection limits. For a typical discrete paraCEST agent the detection limit is roughly an order of magnitude higher than that of a clinically used relaxation agent. One solution to this problem may be the incorporation of a large payload of paraCEST agents into a single macromolecular agent. Here we report a new synthetic method for accomplishing this goal: incorporating a large payload of the paraCEST agent DyDOTAM3+ into a Reverse Assembled nano-Capsule. An aggregate can be generated between this chelate and polyacrylic acid after the addition of ethylene diamine. Subsequent addition of polyallylamine hydrochloride followed by silica nanoparticles generated a robust encapsulating shell and afforded capsule with a mean hydrodynamic diameter of 650 ± 250 nm. Unfortunately this encapsulation did not have the effect of amplifying the CEST effect per agent, but quenched the CEST altogether. A significant proportion of the quenching effect of encapsulation could be attributed to the effect of slowing molecular tumbling, which is inevitable when the chelate is incorporated into a nano-scale material. This increases the transverse relaxation rate of chelate protons and a theoretical examination using Solomon Bloembergen Morgan theory and the Bloch equations shows that the increase in the transverse relaxation rate constant for the amide protons, in even modestly sized nano-materials, is sufficient to significantly quench CEST.

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.

Simultaneous magnetic resonance imaging and pharmacokinetic analysis of intramuscular depots.

PubMed

Probst, Mareike; Kühn, Jens-Peter; Scheuch, Eberhard; Seidlitz, Anne; Hadlich, Stefan; Evert, Katja; Oswald, Stefan; Siegmund, Werner; Weitschies, Werner

2016-04-10

The present pilot study introduces a method that might give novel insights in drug absorption processes from intramuscularly administered depots. An oily suspension or an aqueous solution of paracetamol (6 mg/kg body mass), prednisolone or its hemisuccinate sodium salt for the aqueous solutions (10mg/kg body mass) or diclofenac (10mg/kg body mass) was injected into the muscle tissue of the hind leg of female Lewis-rats (n=47). For the oily suspensions the micronized particles were suspended in medium-chain triglycerides. The aqueous solutions were buffered to a pH of 7.4 ± 0.5. Polyethylene glycol was added as a cosolvent in the formulations containing paracetamol (acetaminophen) and diclofenac and sodium chloride was added to the aqueous solutions of prednisolone hemisuccinate sodium to achieve nearly isotonic formulations. The formed depot was visualized by magnetic resonance imaging (MRI) and characterized with regard to volume and surface area. A 7 T-small animal scanner was used and T1-weighted and T2-weighted sequences including a fat saturation were performed. Simultaneously blood samples were taken and the drugs were quantitatively analyzed. The water based solvent and the oily dispersion agent were visible in the MRI images without the use of contrast agents. Since a free hand injection mostly led to an application directly into the fascia, resulting in a fast removal of the depot, MRI-guided injection was conducted. Comparing pharmacokinetic data with MRI data it was observed that maximal blood levels occurred before the solvent and the dispersion agent were removed from the muscle tissue. Thus, the drug is not absorbed together with the depot. Furthermore, no correlation was found between the shape of the depot and the rate of absorption. Consequently, a higher surface area or volume of the depot did not result in a faster release or absorption of the drugs from the tested formulations. In contrast to the paracetamol and prednisolone formulations the formulations containing diclofenac led to a massive accumulation of interstitial fluid around the injection area being a sign for an acute local reaction. Histological analysis of the muscle tissue revealed a clear correspondence between the amount of interstitial fluid and the extent of infiltrating lymphocytes and granulocytes indicating a tissue response. In conclusion combining MRI with pharmacokinetic data is a suitable method to gain deeper insights into drug absorption processes from intramuscular depots. Furthermore, MRI offers a great possibility detecting local side effects caused by an intramuscularly applied dosage form. This might be very useful in preclinical phases during the development of new intramuscular formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Distributed Coordination of Heterogeneous Agents Using a Semantic Overlay Network and a Goal-Directed Graphplan Planner

PubMed Central

Lopes, António Luís; Botelho, Luís Miguel

2013-01-01

In this paper, we describe a distributed coordination system that allows agents to seamlessly cooperate in problem solving by partially contributing to a problem solution and delegating the subproblems for which they do not have the required skills or knowledge to appropriate agents. The coordination mechanism relies on a dynamically built semantic overlay network that allows the agents to efficiently locate, even in very large unstructured networks, the necessary skills for a specific problem. Each agent performs partial contributions to the problem solution using a new distributed goal-directed version of the Graphplan algorithm. This new goal-directed version of the original Graphplan algorithm provides an efficient solution to the problem of "distraction", which most forward-chaining algorithms suffer from. We also discuss a set of heuristics to be used in the backward-search process of the planning algorithm in order to distribute this process amongst idle agents in an attempt to find a solution in less time. The evaluation results show that our approach is effective in building a scalable and efficient agent society capable of solving complex distributable problems. PMID:23704885

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.

Application of a novel 3-fluid nozzle spray drying process for the microencapsulation of therapeutic agents using incompatible drug-polymer solutions.

PubMed

Sunderland, Tara; Kelly, John G; Ramtoola, Zebunnissa

2015-04-01

The aim of this study was to evaluate a novel 3-fluid concentric nozzle (3-N) spray drying process for the microencapsulation of omeprazole sodium (OME) using Eudragit L100 (EL100). Feed solutions containing OME and/or EL100 in ethanol were assessed visually for OME stability. Addition of OME solution to EL100 solution resulted in precipitation of OME followed by degradation of OME reflected by a colour change from colourless to purple and brown. This was related to the low pH of 2.8 of the EL100 solution at which OME is unstable. Precipitation and progressive discoloration of the 2-fluid nozzle (2-N) feed solution was observed over the spray drying time course. In contrast, 3-N solutions of EL100 or OME in ethanol were stable over the spray drying period. Microparticles prepared using either nozzle showed similar characteristics and outer morphology however the internal morphology was different. DSC showed a homogenous matrix of drug and polymer for 2-N microparticles while 3-N microparticles had defined drug and polymer regions distributed as core and coat. The results of this study demonstrate that the novel 3-N spray drying process can allow the microencapsulation of a drug using an incompatible polymer and maintain the drug and polymer in separate regions of the microparticles.

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.

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.

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.

TU-F-CAMPUS-I-05: Investigation of An EMCCD Detector with Variable Gain in a Micro-CT System

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

Krishnakumar, S Bysani; Ionita, C; Rudin, S

Purpose: To investigate the performance of a newly built Electron Multiplying Charged Coupled Device (EMCCD) based Micro-CT system, with variable detector gain, using a phantom containing contrast agent of different concentrations. Methods: We built a micro- CT system with an EMCCD having 8 microns pixels and on-chip variable gain. We tested the system using a phantom containing five tubes filled with different iodine contrast solutions (30% to 70%). First, we scanned the phantom using various x-ray exposures values at 40 kVp and constant detector gain. Next, for the same tube currents, the detector gain was increased to maintain the airmore » value of the projection image constant. A standard FDK algorithm was used to reconstruct the data. Performance was analyzed by comparing the signal-to-noise ratio (SNR) measurements for increased gain with those for the low constant gain at each exposure. Results: The high detector gain reconstructed data SNR was always greater than the low gain data SNR for all x-ray settings and for all iodine features. The largest increases were observed for low contrast features, 30% iodine concentration, where the SNR improvement approached 2. Conclusion: One of the first implementations of an EMCCD based micro- CT system was presented and used to image a phantom with various iodine solution concentrations. The analysis of the reconstructed volumes showed a significant improvement of the SNR especially for low contrast features. The unique on-chip gain feature is a substantial benefit allowing the use of the system at very low x-ray exposures per frame.Partial support: NIH grant R01EB002873 and Toshiba Medical Systems Corp. Partial support: NIH grant R01EB002873 and Toshiba Medical Systems Corp.« less

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

Effects of ultrasound and ultrasound contrast agent on vascular tissue

PubMed Central

2012-01-01

Background Ultrasound (US) imaging can be enhanced using gas-filled microbubble contrast agents. Strong echo signals are induced at the tissue-gas interface following microbubble collapse. Applications include assessment of ventricular function and virtual histology. Aim While ultrasound and US contrast agents are widely used, their impact on the physiological response of vascular tissue to vasoactive agents has not been investigated in detail. Methods and results In the present study, rat dorsal aortas were treated with US via a clinical imaging transducer in the presence or absence of the US contrast agent, Optison. Aortas treated with both US and Optison were unable to contract in response to phenylephrine or to relax in the presence of acetylcholine. Histology of the arteries was unremarkable. When the treated aortas were stained for endothelial markers, a distinct loss of endothelium was observed. Importantly, terminal deoxynucleotidyl transferase mediated dUTP nick-end-labeling (TUNEL) staining of treated aortas demonstrated incipient apoptosis in the endothelium. Conclusions Taken together, these ex vivo results suggest that the combination of US and Optison may alter arterial integrity and promote vascular injury; however, the in vivo interaction of Optison and ultrasound remains an open question. PMID:22805356

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

In situ preparation of high relaxivity iron oxide nanoparticles by coating with chitosan: A potential MRI contrast agent useful for cell tracking

NASA Astrophysics Data System (ADS)

Tsai, Zei-Tsan; Wang, Jen-Fei; Kuo, Hsiao-Yun; Shen, Chia-Rui; Wang, Jiun-Jie; Yen, Tzu-Chen

2010-01-01

Iron oxide nanocrystals are of considerable interest in nanoscience and nanotechnology because of their nanoscale dimensions, nontoxic nature, and superior magnetic properties. Colloidal solutions of magnetic nanoparticles (ferrofluids) with a high magnetite content are highly desirable for most molecular imaging applications. In this paper, we present a method for in situ coating of superparamagnetic iron oxide (SPIO) with chitosan in order to increase the content of magnetite. Iron chloride salts (Fe 3+ and Fe 2+) were directly coprecipitated inside a porous matrix of chitosan by Co-60 γ-ray irradiation in an aqueous solution of acetic acid. Following sonication, iron oxide nanoparticles were formed inside the chitosan matrix at a pH value of 9.5 and a temperature of 50 °C. The [Fe 3+]:[Fe 2+]:[NH 4OH] molar ratio was 1.6:1:15.8. The final ferrofluid was formed with a pH adjustment to approximately 2.0/3.0, alongside with the addition of mannitol and lactic acid. We subsequently characterized the particle size, the zeta potential, the iron concentration, the magnetic contrast, and the cellular uptake of our ferrofluid. Results showed a z-average diameter of 87.2 nm, a polydispersity index (PDI) of 0.251, a zeta potential of 47.9 mV, and an iron concentration of 10.4 mg Fe/mL. The MRI parameters included an R1 value of 22.0 mM -1 s -1, an R2 value of 202.6 mM -1 s -1, and a R2/R1 ratio of 9.2. An uptake of the ferrofluid by mouse macrophages was observed. Altogether, our data show that Co-60 γ-ray radiation on solid chitosan may improve chitosan coating of iron oxide nanoparticles and tackle its aqueous solubility at pH 7. Additionally, our methodology allowed to obtain a ferrofluid with a higher content of magnetite and a fairly unimodal distribution of monodisperse clusters. Finally, MRI and cell experiments demonstrated the potential usefulness of this product as a potential MRI contrast agent that might be used for cell tracking.

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

Electromarking solution

DOEpatents

Bullock, Jonathan S.; Harper, William L.; Peck, Charles G.

1976-06-22

This invention is directed to an aqueous halogen-free electromarking solution which possesses the capacity for marking a broad spectrum of metals and alloys selected from different classes. The aqueous solution comprises basically the nitrate salt of an amphoteric metal, a chelating agent, and a corrosion-inhibiting agent.

Magnetic Resonance Imaging (MRI) (For Teens)

MedlinePlus

... a few minutes. Some people get a contrast solution as part of an MRI exam. Contrast solution is a liquid that goes inside the body ... not show up otherwise. If you need contrast solution, the tech will probably use an IV to ...

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

A biomarker-responsive T2ex MRI contrast agent.

PubMed

Daryaei, Iman; Randtke, Edward A; Pagel, Mark D

2017-04-01

This study investigated a fundamentally new type of responsive MRI contrast agent for molecular imaging that alters T 2 exchange (T 2ex ) properties after interacting with a molecular biomarker. The contrast agent Tm-DO3A-oAA was treated with nitric oxide (NO) and O 2 . The R 1 and R 2 relaxation rates of the reactant and product were measured with respect to concentration, temperature, and pH. Chemical exchange saturation transfer (CEST) spectra of the reactant and product were acquired using a 7 Tesla (T) MRI scanner and analyzed to estimate the chemical exchange rates and r 2ex relaxivities. The reaction of Tm-DO3A-oAA with NO and O 2 caused a 6.4-fold increase in the r 2 relaxivity of the agent, whereas r 1 relaxivity remained unchanged, which demonstrated that Tm-DO3A-oAA is a responsive T 2ex agent. The effects of pH and temperature on the r 2 relaxivities of the reactant and product supported the conclusion that the product's benzimidazole ligand caused the agent to have a fast chemical exchange rate relative to the slow exchange rate of the reactant's ortho-aminoanilide ligand. T 2ex MRI contrast agents are a new type of responsive agent that have good detection sensitivity and specificity for detecting a biomarker, which can serve as a new tool for molecular imaging. Magn Reson Med 77:1665-1670, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

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.

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

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.

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

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.

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.

Solving optimization problems by the public goods game

NASA Astrophysics Data System (ADS)

Javarone, Marco Alberto

2017-09-01

We introduce a method based on the Public Goods Game for solving optimization tasks. In particular, we focus on the Traveling Salesman Problem, i.e. a NP-hard problem whose search space exponentially grows increasing the number of cities. The proposed method considers a population whose agents are provided with a random solution to the given problem. In doing so, agents interact by playing the Public Goods Game using the fitness of their solution as currency of the game. Notably, agents with better solutions provide higher contributions, while those with lower ones tend to imitate the solution of richer agents for increasing their fitness. Numerical simulations show that the proposed method allows to compute exact solutions, and suboptimal ones, in the considered search spaces. As result, beyond to propose a new heuristic for combinatorial optimization problems, our work aims to highlight the potentiality of evolutionary game theory beyond its current horizons.

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.

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

PubMed

O' Doherty, Jim; Schleyer, Paul

2017-12-01

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

Residual antimicrobial effect of chlorhexidine digluconate and octenidine dihydrochloride on reconstructed human epidermis.

PubMed

Müller, G; Langer, J; Siebert, J; Kramer, A

2014-01-01

The objective of the present investigation was to examine the residual antimicrobial activity after a topical exposure of reconstructed human epidermis (RHE) to equimolar solutions of either chlorhexidine digluconate (CHG, 0.144% w/v) or octenidine dihydrochloride (OCT, 0.1% w/v) for 15 min. RHE-associated antiseptic agents were more effective on Staphylococcus aureus than on Pseudomonas aeruginosa. S. aureus was not detected after 24 h of contact, which demonstrated a microbicidal efficacy of greater than 5-log10 reduction. In contrast, P. aeruginosa was reduced by approximately 2 log10 at the same incubation time, which parallels the growth of the initial inoculum. This result could be interpreted either as a microbiostatic effect or as an adherence of P. aeruginosa to a low positively charged surface. Small amounts of CHG and OCT can penetrate the stratum corneum. Using these antiseptic agents, the viability of keratinocytes was reduced to 65-75% of that of the untreated RHE control following 24 h incubation in the presence of test microorganisms. With consideration of antimicrobial activity and cytotoxic effect, OCT corresponds better to a biocompatible antiseptic agent than CHG. Copyright © 2013 S. Karger AG, Basel.

Method and apparatus for back-extracting metal chelates

DOEpatents

Wai, Chien M.; Smart, Neil G.; Lin, Yuehe

1998-01-01

A method of extracting metal and metalloid species from a solid or liquid substrate using a supercritical fluid solvent containing one or more chelating agents followed by back-extracting the metal and metalloid species from the metal and metalloid chelates formed thereby. The back-extraction acidic solution is performed utilizing an acidic solution. Upon sufficient exposure of the metal and metalloid chelates to the acidic solution, the metal and metalloid species are released from the chelates into the acid solution, while the chelating agent remains in the supercritical fluid solvent. The chelating agent is thereby regenerated and the metal and metalloid species recovered.

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

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.

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.

Investigation of optimal parameters for penalized maximum-likelihood reconstruction applied to iodinated contrast-enhanced breast CT

NASA Astrophysics Data System (ADS)

Makeev, Andrey; Ikejimba, Lynda; Lo, Joseph Y.; Glick, Stephen J.

2016-03-01

Although digital mammography has reduced breast cancer mortality by approximately 30%, sensitivity and specificity are still far from perfect. In particular, the performance of mammography is especially limited for women with dense breast tissue. Two out of every three biopsies performed in the U.S. are unnecessary, thereby resulting in increased patient anxiety, pain, and possible complications. One promising tomographic breast imaging method that has recently been approved by the FDA is dedicated breast computed tomography (BCT). However, visualizing lesions with BCT can still be challenging for women with dense breast tissue due to the minimal contrast for lesions surrounded by fibroglandular tissue. In recent years there has been renewed interest in improving lesion conspicuity in x-ray breast imaging by administration of an iodinated contrast agent. Due to the fully 3-D imaging nature of BCT, as well as sub-optimal contrast enhancement while the breast is under compression with mammography and breast tomosynthesis, dedicated BCT of the uncompressed breast is likely to offer the best solution for injected contrast-enhanced x-ray breast imaging. It is well known that use of statistically-based iterative reconstruction in CT results in improved image quality at lower radiation dose. Here we investigate possible improvements in image reconstruction for BCT, by optimizing free regularization parameter in method of maximum likelihood and comparing its performance with clinical cone-beam filtered backprojection (FBP) algorithm.

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

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.

Inhibition of heterologously expressed cystic fibrosis transmembrane conductance regulator Cl− channels by non-sulphonylurea hypoglycaemic agents

PubMed Central

Cai, Z; Lansdell, K A; Sheppard, D N

1999-01-01

Hypoglycaemia-inducing sulphonylureas, such as glibenclamide, inhibit cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channels. In search of modulators of CFTR, we investigated the effects of the non-sulphonylurea hypoglycaemic agents meglitinide, repaglinide, and mitiglinide (KAD-1229) on CFTR Cl− channels in excised inside-out membrane patches from C127 cells expressing wild-type human CFTR. When added to the intracellular solution, meglitinide and mitiglinide inhibited CFTR Cl− currents with half-maximal concentrations of 164±19 μM and 148±36 μM, respectively. However, repaglinide only weakly inhibited CFTR Cl− currents. To understand better how non-sulphonylurea hypoglycaemic agents inhibit CFTR, we studied single channels. Channel blockade by both meglitinide and mitiglinide was characterized by flickery closures and a significant decrease in open probability (Po). In contrast, repaglinide was without effect on either channel gating or Po, but caused a small decrease in single-channel current amplitude. Analysis of the dwell time distributions of single channels indicated that both meglitinide and mitiglinide greatly decreased the open time of CFTR. Mitiglinide-induced channel closures were about 3-fold longer than those of meglitinide. Inhibition of CFTR by meglitinide and mitiglinide was voltage-dependent: at positive voltages channel blockade was relieved. The data demonstrate that non-sulphonylurea hypoglycaemic agents inhibit CFTR. This indicates that these agents have a wider specificity of action than previously recognized. Like glibenclamide, non-sulphonylurea hypoglycaemic agents may inhibit CFTR by occluding the channel pore and preventing Cl− permeation. PMID:10498841

SEPARATION PROCESS FOR TRANSURANIC ELEMENT AND COMPOUNDS THEREOF

DOEpatents

Calvin, M.

1958-10-14

S> A process is presented for the separation of pluto nium from uranium and fission products in an aqueous acidic solution by use of a chelating agent. The plutonium is maintained in the tetravalent state and the uranium in the hexavalent state, and the acidic concentration is adjusted to about 1 N bar. The aqueous solution is then contacted with a water-immiscible organic solvent solution and the chelating agent. The chelating agents covered by this invention comprise a group of compounds characterized as fluorinated beta-diketones.

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

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

NASA Astrophysics Data System (ADS)

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

2016-12-01

Superparamagnetic iron oxide nanoparticles (SPIONs) as T2 contrast agents have great potential to sense calcium ion (Ca2+) using magnetic resonance imaging (MRI). Here we prepared calcium-responsive SPIONs for MRI, formed by combining poly(ethylene glycol) (PEG) and polyethylenimine (PEI) coated iron oxide nanoparticle (PEI/PEG-SPIONs) contrast agents with the straightforward calcium-sensing compound EGTA (ethylene glycol tetraacetic acid). EGTA was conjugated onto PEI/PEG-SPIONs using EDC/sulfo-NHS method. EGTA-SPIONs were characterized using TEM, XPS, DSL, TGA and SQUIID. DSL results show that the SPIONs aggregate in the presence of Ca2+. MRI analyses indicate that the water proton T2 relaxation rates in HEPES suspensions of the EGTA-SPIONs significantly increase with the calcium concentration because the SPIONs aggregate in the presence of Ca2+. The T2 values decreased 25% when Ca2+ concentration decreased from 1.2 to 0.8 mM. The aggregation of EGTA-SPIONs could be reversed by EDTA. EGTA-SPIONs have potential as smart contrast agents for Ca2+-sensitive MRI.

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.

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.

Status of the effectiveness of contact lens disinfectants in Malaysia against keratitis-causing pathogens.

PubMed

Abjani, Farhat; Khan, Naveed Ahmed; Jung, Suk Yul; Siddiqui, Ruqaiyyah

2017-12-01

The aim of this study was (i) to assess the antimicrobial effects of contact lens disinfecting solutions marketed in Malaysia against common bacterial eye pathogens and as well as eye parasite, Acanthamoeba castellanii, and (ii) to determine whether targeting cyst wall would improve the efficacy of contact lens disinfectants. Using ISO 14729 Stand-Alone Test for disinfecting solutions, bactericidal and amoebicidal assays of six different contact lens solutions including Oxysept ® , AO SEPT PLUS, OPTI-FREE ® pure moist ® , Renu ® fresh™, FreshKon ® CLEAR and COMPLETE RevitaLens™ were performed using Manufacturers Minimum recommended disinfection time (MRDT). The efficacy of contact lens solutions was determined against keratitis-causing microbes, namely: Pseudomonas aeruginosa, Methicillin-resistant Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, and Acanthamoeba castellanii. In addition, using chlorhexidine as an antiamoebic compound and cellulase enzyme to disrupt cyst wall structure, we determined whether combination of both agents can enhance efficacy of marketed contact lens disinfectants against A. castellanii trophozoites and cysts, in vitro. The results revealed that all contact lens disinfectants tested showed potent bactericidal effects exhibiting 100% kill against all bacterial species tested. In contrast, none of the contact lens disinfectants had potent effects against Acanthamoeba cysts viability. When tested against trophozoites, two disinfectants, Oxysept Multipurpose and AO-sept Multipurpose showed partial amoebicidal effects. Using chlorhexidine as an antiamoebic compound and cellulase enzyme to disrupt cyst wall structure, the findings revealed that combination of both agents in contact lens disinfectants abolished viability of A. castellanii cysts and trophozoites. Given the inefficacy of contact lens disinfectants tested in this study, these findings present a significant concern to public health. These findings revealed that targeting cyst wall by using cyst wall degrading molecules in contact lens disinfecting solutions will enhance their efficacy against this devastating eye infection. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Extravasation of Noncytotoxic Drugs: A Review of the Literature.

PubMed

Le, Ann; Patel, Samit

2014-07-01

Extravasation is a potential complication associated with intravenous therapy administration. Inadvertent leakage of medications with vesicant properties can cause severe tissue necrosis, which can lead to devastating long-term consequences. Recognizing potential agents is an essential step in mitigating the risk of extravasation. A literature search was carried out using PubMed with the following key words: extravasation, soft tissue injury, phlebitis, and infiltration, from January 1961 through January 2014. The publications were screened manually and reviewed to identify reports for medications that included synonyms of the International Nonproprietary Name, while excluding antineoplastic agents, radiographic contrast material, investigational or nonmarketed drugs, and animal data, to yield 70 articles. Furthermore, reference citations from publications were also reviewed for relevance and yielded 4 articles. We discovered 232 cases of extravasation involving 37 agents (in order of frequency): phenytoin, parenteral nutrition, calcium gluconate, potassium chloride, calcium chloride, dopamine, dextrose solutions, epinephrine, sodium bicarbonate, nafcillin, propofol, norepinephrine, mannitol, arginine, promethazine, vancomycin, tetracycline, dobutamine, vasopressin, sodium thiopental, acyclovir, amphotericin, ampicillin, cloxacillin, gentamicin, metronidazole, oxacillin, penicillin, amiodarone, albumin, furosemide, lipids, lorazepam, immunoglobulin, morphine, and sodium valproate. Potential properties contributing to extravasation include the following: pH, osmolarity, diluent, vasoactive properties, and inactive ingredients. Antidotes and supportive care agents used in the management of these cases of extravasation include hyaluronidase, phentolamine, terbutaline, topical anesthetics (such as lidocaine and prilocaine cream), topical antimicrobials (such as silver sulfadiazine and chlorhexidine), topical debridement agents (collagenase ointment), topical steroids, and topical vasodilators (nitroglycerin). Data on the management of noncytotoxic extravasations is sparse, consisting primarily of case reports and anecdotal evidence. Fortunately, this adverse outcome is preventable and identification of vesicant agents plays a pivotal role. The intent of this review is to provide a reference identifying noncytotoxic vesicants and the management of extravasations associated with specific agents. © The Author(s) 2014.

Learning Sequences of Actions in Collectives of Autonomous Agents

NASA Technical Reports Server (NTRS)

Turner, Kagan; Agogino, Adrian K.; Wolpert, David H.; Clancy, Daniel (Technical Monitor)

2001-01-01

In this paper we focus on the problem of designing a collective of autonomous agents that individually learn sequences of actions such that the resultant sequence of joint actions achieves a predetermined global objective. We are particularly interested in instances of this problem where centralized control is either impossible or impractical. For single agent systems in similar domains, machine learning methods (e.g., reinforcement learners) have been successfully used. However, applying such solutions directly to multi-agent systems often proves problematic, as agents may work at cross-purposes, or have difficulty in evaluating their contribution to achievement of the global objective, or both. Accordingly, the crucial design step in multiagent systems centers on determining the private objectives of each agent so that as the agents strive for those objectives, the system reaches a good global solution. In this work we consider a version of this problem involving multiple autonomous agents in a grid world. We use concepts from collective intelligence to design goals for the agents that are 'aligned' with the global goal, and are 'learnable' in that agents can readily see how their behavior affects their utility. We show that reinforcement learning agents using those goals outperform both 'natural' extensions of single agent algorithms and global reinforcement, learning solutions based on 'team games'.

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.

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.

Redefining the properties of an osmotic agent in an intestinal-specific preservation solution

PubMed Central

Schlachter, Kimberly; Kokotilo, Matthew S; Carter, Jodi; Thiesen, Aducio; Ochs, Angela; Khadaroo, Rachel G; Churchill, Thomas A

2010-01-01

AIM: To investigate the effects of dextrans of various molecular weights (Mw) during a 12 h cold storage time-course on energetics, histology and mucosal infiltration of fluorescein isothiocyanate (FITC)-dextran. METHODS: Rodent intestines were isolated and received a standard University of Wisconsin vascular flush followed by intraluminal administration of a nutrient-rich preservation solution containing dextrans of varying Mw: Group D1, 73 kdal; Group D2, 276 kdal; Group D3, 534 kdal; Group D4, 1185 kdal; Group D5, 2400 kdal. RESULTS: Using FITC-labeled dextrans, fluorescent micrographs demonstrated varying degrees of mucosal infiltration; lower Mw (groups D1-D3: 73-534 kdal) dextrans penetrated the mucosa as early as 2 h, whereas the largest dextran (D5: 2400 kdal) remained captive within the lumen and exhibited no permeability even after 12 h. After 12 h, median injury grades ranged from 6.5 to 7.5 in groups D1-D4 (73-1185 kdal) representing injury of the regenerative cryptal regions and submucosa; this was in contrast to group D5 (2400 kdal) which exhibited villus denudation (with intact crypts) corresponding to a median injury grade of 4 (P < 0.05). Analysis of tissue energetics reflected a strong positive correlation between Mw and adenosine triphosphate (r2 = 0.809), total adenylates (r2 = 0.865) and energy charge (r2 = 0.667). CONCLUSION: Our data indicate that dextrans of Mw > 2400 kdal act as true impermeant agents during 12 h ischemic storage when incorporated into an intraluminal preservation solution. PMID:21128319

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

Semipermeable Hollow Fiber Phantoms for Development and Validation of Perfusion-Sensitive MR Methods and Signal Models

PubMed Central

Anderson, J.R.; Ackerman, J.J.H.; Garbow, J.R.

2015-01-01

Two semipermeable, hollow fiber phantoms for the validation of perfusion-sensitive magnetic resonance methods and signal models are described. Semipermeable hollow fibers harvested from a standard commercial hemodialysis cartridge serve to mimic tissue capillary function. Flow of aqueous media through the fiber lumen is achieved with a laboratory-grade peristaltic pump. Diffusion of water and solute species (e.g., Gd-based contrast agent) occurs across the fiber wall, allowing exchange between the lumen and the extralumenal space. Phantom design attributes include: i) small physical size, ii) easy and low-cost construction, iii) definable compartment volumes, and iv) experimental control over media content and flow rate. PMID:26167136

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.

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.

Method and apparatus for back-extracting metal chelates

DOEpatents

Wai, C.M.; Smart, N.G.; Lin, Y.

1998-08-11

A method is described for extracting metal and metalloid species from a solid or liquid substrate using a supercritical fluid solvent containing one or more chelating agents followed by back-extracting the metal and metalloid species from the metal and metalloid chelates formed thereby. The back-extraction acidic solution is performed utilizing an acidic solution. Upon sufficient exposure of the metal and metalloid chelates to the acidic solution, the metal and metalloid species are released from the chelates into the acid solution, while the chelating agent remains in the supercritical fluid solvent. The chelating agent is thereby regenerated and the metal and metalloid species recovered. 3 figs.

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

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

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.

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

Gossip-based solutions for discrete rendezvous in populations of communicating agents.

PubMed

Hollander, Christopher D; Wu, Annie S

2014-01-01

The objective of the rendezvous problem is to construct a method that enables a population of agents to agree on a spatial (and possibly temporal) meeting location. We introduce the buffered gossip algorithm as a general solution to the rendezvous problem in a discrete domain with direct communication between decentralized agents. We compare the performance of the buffered gossip algorithm against the well known uniform gossip algorithm. We believe that a buffered solution is preferable to an unbuffered solution, such as the uniform gossip algorithm, because the use of a buffer allows an agent to use multiple information sources when determining its desired rendezvous point, and that access to multiple information sources may improve agent decision making by reinforcing or contradicting an initial choice. To show that the buffered gossip algorithm is an actual solution for the rendezvous problem, we construct a theoretical proof of convergence and derive the conditions under which the buffered gossip algorithm is guaranteed to produce a consensus on rendezvous location. We use these results to verify that the uniform gossip algorithm also solves the rendezvous problem. We then use a multi-agent simulation to conduct a series of simulation experiments to compare the performance between the buffered and uniform gossip algorithms. Our results suggest that the buffered gossip algorithm can solve the rendezvous problem faster than the uniform gossip algorithm; however, the relative performance between these two solutions depends on the specific constraints of the problem and the parameters of the buffered gossip algorithm.

Gossip-Based Solutions for Discrete Rendezvous in Populations of Communicating Agents

PubMed Central

Hollander, Christopher D.; Wu, Annie S.

2014-01-01

The objective of the rendezvous problem is to construct a method that enables a population of agents to agree on a spatial (and possibly temporal) meeting location. We introduce the buffered gossip algorithm as a general solution to the rendezvous problem in a discrete domain with direct communication between decentralized agents. We compare the performance of the buffered gossip algorithm against the well known uniform gossip algorithm. We believe that a buffered solution is preferable to an unbuffered solution, such as the uniform gossip algorithm, because the use of a buffer allows an agent to use multiple information sources when determining its desired rendezvous point, and that access to multiple information sources may improve agent decision making by reinforcing or contradicting an initial choice. To show that the buffered gossip algorithm is an actual solution for the rendezvous problem, we construct a theoretical proof of convergence and derive the conditions under which the buffered gossip algorithm is guaranteed to produce a consensus on rendezvous location. We use these results to verify that the uniform gossip algorithm also solves the rendezvous problem. We then use a multi-agent simulation to conduct a series of simulation experiments to compare the performance between the buffered and uniform gossip algorithms. Our results suggest that the buffered gossip algorithm can solve the rendezvous problem faster than the uniform gossip algorithm; however, the relative performance between these two solutions depends on the specific constraints of the problem and the parameters of the buffered gossip algorithm. PMID:25397882

A water market simulator considering pair-wise trades between agents

NASA Astrophysics Data System (ADS)

Huskova, I.; Erfani, T.; Harou, J. J.

2012-04-01

In many basins in England no further water abstraction licences are available. Trading water between water rights holders has been recognized as a potentially effective and economically efficient strategy to mitigate increasing scarcity. A screening tool that could assess the potential for trade through realistic simulation of individual water rights holders would help assess the solution's potential contribution to local water management. We propose an optimisation-driven water market simulator that predicts pair-wise trade in a catchment and represents its interaction with natural hydrology and engineered infrastructure. A model is used to emulate licence-holders' willingness to engage in short-term trade transactions. In their simplest form agents are represented using an economic benefit function. The working hypothesis is that trading behaviour can be partially predicted based on differences in marginal values of water over space and time and estimates of transaction costs on pair-wise trades. We discuss the further possibility of embedding rules, norms and preferences of the different water user sectors to more realistically represent the behaviours, motives and constraints of individual licence holders. The potential benefits and limitations of such a social simulation (agent-based) approach is contrasted with our simulator where agents are driven by economic optimization. A case study based on the Dove River Basin (UK) demonstrates model inputs and outputs. The ability of the model to suggest impacts of water rights policy reforms on trading is discussed.

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

Recent progress in tissue optical clearing for spectroscopic application

NASA Astrophysics Data System (ADS)

Sdobnov, A. Yu.; Darvin, M. E.; Genina, E. A.; Bashkatov, A. N.; Lademann, J.; Tuchin, V. V.

2018-05-01

This paper aims to review recent progress in optical clearing of the skin and over naturally turbid biological tissues and blood using this technique in vivo and in vitro with multiphoton microscopy, confocal Raman microscopy, confocal microscopy, NIR spectroscopy, optical coherence tomography, and laser speckle contrast imaging. Basic principles of the technique, its safety, advantages and limitations are discussed. The application of optical clearing agent on a tissue allows for controlling the optical properties of tissue. Optical clearing-induced reduction of tissue scattering significantly facilitates the observation of deep-located tissue regions, at the same time improving the resolution and image contrast for a variety of optical imaging methods suitable for clinical applications, such as diagnostics and laser treatment of skin diseases, mucosal tumor imaging, laser disruption of pathological abnormalities, etc. Structural images of different skin layers obtained ex vivo for porcine ear skin samples at application of Omnipaque™ and glycerol solutions during 60 min. Red color corresponds to TPEAF signal channel. Green color corresponds to SHG signal channel.

Drug-eluting stents. Insights from invasive imaging technologies.

PubMed

Honda, Yasuhiro

2009-08-01

Drug-eluting stents (DES) represent a revolutionary technology in their unique ability to provide both mechanical and biological solutions simultaneously to the target lesion. As a result of biological effects from the pharmacological agents and interaction of DES components with the arterial wall, considerable differences exist between DES and conventional bare metal stents (BMS), yet some of the old lessons learned in the BMS era remain clinically significant. In this context, contrast angiography provides very little information about in vivo device properties and their biomechanical effects on the arterial wall. In contrast, current catheter-based imaging tools, such as intravascular ultrasound, optical coherence tomography, and intracoronary angioscopy can offer unique insights into DES through direct assessment of the device and treated vessel in the clinical setting. This article reviews these insights from current DES with particular focus on performance and safety characteristics as well as discussing an optimal deployment technique, based upon findings obtained through the use of the invasive imaging technologies.

Cell tracking with caged xenon: using cryptophanes as MRI reporters upon cellular internalization.

PubMed

Klippel, Stefan; Döpfert, Jörg; Jayapaul, Jabadurai; Kunth, Martin; Rossella, Federica; Schnurr, Matthias; Witte, Christopher; Freund, Christian; Schröder, Leif

2014-01-07

Caged xenon has great potential in overcoming sensitivity limitations for solution-state NMR detection of dilute molecules. However, no application of such a system as a magnetic resonance imaging (MRI) contrast agent has yet been performed with live cells. We demonstrate MRI localization of cells labeled with caged xenon in a packed-bed bioreactor working under perfusion with hyperpolarized-xenon-saturated medium. Xenon hosts enable NMR/MRI experiments with switchable contrast and selectivity for cell-associated versus unbound cages. We present MR images with 10(3) -fold sensitivity enhancement for cell-internalized, dual-mode (fluorescence/MRI) xenon hosts at low micromolar concentrations. Our results illustrate the capability of functionalized xenon to act as a highly sensitive cell tracer for MRI detection even without signal averaging. The method will bridge the challenging gap for translation to in vivo studies for the optimization of targeted biosensors and their multiplexing applications. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Temperature affects transport of polysaccharides and proteins in articular cartilage explants.

PubMed

Moeini, Mohammad; Lee, Kwan-Bong; Quinn, Thomas M

2012-07-26

Solute transport phenomena mediate many aspects of the physiology and contrast agent-based clinical imaging of articular cartilage. Temperatures up to 10°C below standard body temperature (37°C) are common in articulating joints during normal activities and clinically (e.g. cold treatment of injuries). Therefore it is of interest to characterize the effects of temperature changes on solute transport parameters in cartilage. A range of fluorescent solutes including fluorescein isothiocyanate, 4 and 40kDa dextrans, myoglobin, insulin and chondroitin sulfate were prepared and used in assays of solute effective partition coefficient and effective diffusivity in bovine intermediate zone articular cartilage explants maintained at 10, 22 or 37°C. Trends for increasing partition coefficient with increasing temperature were evident for all solutes except chondroitin sulfate, with significant changes between 22 and 37°C for 4kDa dextran, insulin and myoglobin. Diffusivities of most solutes tested also tended to increase with increasing temperature, with significant changes between 10 and 22°C for FITC, 40kDa dextran and myoglobin. Oddly, insulin diffusivity decreased significantly as temperature increased from 22 to 37°C while chondroitin sulfate diffusivity exhibited no clear temperature dependence. These results highlight solute-specific temperature dependences of transport phenomena which may depend upon molecular weight, chemical structure, molecular conformation, and solute-matrix and solute-solute interactions. The articular cartilage explants themselves exhibited small but significant changes in water and glycosaminoglycan contents during experiments, underscoring the importance of solute-matrix interactions. Solute transport parameters in cartilage and their temperature dependences are therefore not easily predicted, and case-by-case experimental determination may be essential. Copyright © 2012 Elsevier Ltd. All rights reserved.

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...