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

Science.gov (United States)

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

2017-04-01

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

The optimal use of contrast agents at high field MRI

International Nuclear Information System (INIS)

Trattnig, Siegfried; Pinker, Kathia; Ba-Ssalamah, Ahmed; Noebauer-Huhmann, Iris-Melanie

2006-01-01

The intravenous administration of a standard dose of conventional gadolinium-based contrast agents produces higher contrast between the tumor and normal brain at 3.0 Tesla (T) than at 1.5 T, which allows reducing the dose to half of the standard one to produce similar contrast at 3.0 T compared to 1.5 T. The assessment of cumulative triple-dose 3.0 T images obtained the best results in the detection of brain metastases compared to other sequences. The contrast agent dose for dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging at 3.0 T can be reduced to 0.1 mmol compared to 0.2 mmol at 1.5 T due to the increased susceptibility effects at higher magnetic field strengths. Contrast agent application makes susceptibility-weighted imaging (SWI) at 3.0 T clinically attractive, with an increase in spatial resolution within the same scan time. Whereas a double dose of conventional gadolinium-based contrast agents was optimal in SWI with respect to sensitivity and image quality, a standard dose of gadobenate dimeglumine, which has a two-fold higher T1-relaxivity in blood, produced the same effect. For MR-arthrography, optimized concentrations of gadolinium-based contrast agents are similar at 3.0 and 1.5 T. In summary, high field MRI requires the optimization of the contrast agent dose in different clinical applications. (orig.)

Analytical interference by contrast agents in biochemical assays

DEFF Research Database (Denmark)

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

2017-01-01

Objective. To provide a clinically relevant overview of the analytical interference by contrast agents (CA) in laboratory blood test measurements. Materials and Methods. The effects of five CAs, gadobutrol, gadoterate meglumine, gadoxetate disodium, iodixanol, and iomeprol, were studied on the 29...... most frequently performed biochemical assays. One-day-old plasma, serum, and whole blood were spiked with doses of each agent such that the gadolinium agents and the iodine agents reached concentrations of 0.5mMand 12mg iodine/mL, respectively. Subsequently, 12 assays were reexamined using 1/2 and 1...

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

Science.gov (United States)

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 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 contrast agent volume to bladder filling was the

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

2015-12-01

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

Gadolinium-porphyrins: new potential magnetic resonance imaging contrast agents for melanoma detection

Directory of Open Access Journals (Sweden)

Daryoush Shahbazi-Gahrouei

2006-11-01

Full Text Available BACKGROUND: Two new porphyrin-based magnetic resonance imaging (MRI contrast agents, Gd-hematoporphyrin (Gd-H and Gd-tetra-carboranylmethoxyphenyl-porphyrin (Gd-TCP were synthesized and tested in nude mice with human melanoma (MM-138 xenografts as new melanoma contrast agents. METHODS: Subcutaneous xenografts of human melanoma cells (MM-138 were studied in 30 (five groups of six nude mice. The effect of different contrast agents (Gd-TCP, Gd-H, GdCl3 and Gd-DTPA on proton relaxation times was measured in tumors and other organs. T1 values, signal enhancement and the Gd concentration for different contrast agent solutions were also investigated. RESULTS: The porphyrin agents showed higher relaxivity compared to the clincal agent, Gd-DTPA. A significant 16% and 21% modification in T1 relaxation time of the water in human melanoma tumors grafted in the nude mice was revealed 24 hours after injection of Gd-TCP and Gd-H, respectively. The percentage of injected Gd localized to the tumor measured by inductively coupled plasma atomic emission spectrometry (ICP-AES was approximately 21% for Gd-TCP and 28% for Gd-H which were higher than that of Gd-DTPA (10%. CONCLUSIONS: The high concentration of Gd in the tumor is indicative of a selective retention of the compounds and indicates that Gd-TCP and Gd-H are promising MR imaging contrast agents for melanoma detection. Gd-porphyrins have considerable promise for further diagnostic applications in magnetic resonance imaging. KEY WORDS: MRI, porphyrin-based contrast agent, hematoporphyrin, melanoma.

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

Science.gov (United States)

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.

Oral gadopentetate dimeglumine administration as a negative gastrointestinal contrast agent to improve image quality of MR cholangiopancreatography

International Nuclear Information System (INIS)

Chen Yi; Xu Yikai; Zhao Yuhui; Wang Guisheng

2008-01-01

Objective: To choose optimal concentration and volume of Gd-DTPA solution as a oral gastrointestinal negative contrast agent for MRCP. To evaluate the role of Gd-DTPA solution in improving image quality of MRCP. Methods: In vitro experiment: Gd-DTPA solution was made with different concentrations. T 1 WI, T 2 WI, two-dimensional single slice fast spin echo sequence and three-dimensional half-fourier acquisition single-shot fast spin echo sequence were performed to measure the signal intensity of these contrast agents respectively, so Gd-DTPA solution with the optimal concentration can be decided as oral negative gastrointestinal contrast agent on MRCP. Clinical study: The Gd-DTPA solution with optimal concentration and volume was regarded as an oral negative gastrointestinal contrast agent of MRCP. Twenty- four' patients were performed with MRCP before and after (5-10 minutes and 10-15 minutes) administration of oral negative gastrointestinal contrast agent and image quality was analyzed. Statistical analysis was performed using analysis of variance with SPSS 10.0. Results: When the concentration of Gd-DTPA solution was ≤0.01 mol/L, the contrast agent was hyperintense on T 1 WI. On T 2 WI, when the concentration was ≥0.015 mol/L, it was as hypointense as basic ground; On 2D FSE MRCP images, controls were hyperintense and the contrast agent with concentration ranging from 0.0025 mol/L to 0.03 mol/L was hypointense. On 3D HEAST MRCP image, controls were hyperintense and when the concentration of Gd-DTPA was ≥0.01 mol, the contrast agent was hypointense. The Gd-DTPA solution with the concentration of 0.01 mol/L and the volume of 100 ml was chosen as MRCP oral negative gastrointestinal contrast agent. On MRCP images after oral administration of the contrast agent, in 10-15 minutes, the average grade scores within 24 patients of the intrahepatic bile duct, the common hepatic bile duct, the gall bladder, the common bile duct and pancreatic duct (the average grade

Viscosity of iodinated contrast agents during renal excretion

International Nuclear Information System (INIS)

Jost, Gregor; Lengsfeld, Philipp; Lenhard, Diana C.; Pietsch, Hubertus; Huetter, Joachim; Sieber, Martin A.

2011-01-01

Objective: Modern iodinated non-ionic contrast agents (CAs) can be classified based on their molecular structure into monomeric and dimeric CAs and have at comparable iodine concentrations a different viscosity and osmolality. During their renal excretion, CAs are concentrated in the renal tubuli which might enhance the viscosity difference between monomeric and dimeric CAs. The viscosity of a CA might have an underestimated importance for renal safety, as suggested by recent publications. In this study, we investigated the viscosities of CAs at the concentrations expected to be present in renal tubules. This concentration process was simulated in vitro using dialysis. Furthermore, we investigated urine viscosity and urine flow in rodents after administration of several non-ionic monomeric and dimeric CAs. Materials and methods: To estimate the viscosity of the CAs in vivo, we performed an in vitro dialysis of monomeric and dimeric CAs at various physiological osmolalities of the renal tubulus (290, 400, 500, 700 and 1000 mOsm/kg H 2 O). Following the dialysis, the iodine concentrations and the viscosities of the CAs were determined. Furthermore, to investigate the concentration process in vivo, we measured the urine viscosity and the urine flow in Han Wister rats after the administration of Iopromide, Iohexol, Ioversol, Iomeprol, Iodixanol, and Iosimenol at comparable iodine concentrations. As a control, saline was injected at the same volume. Results: In vitro dialysis of the dimeric CA increased the iodine concentration and strongly increased the viscosity at all tested osmolalities. In contrast, for the monomeric agents an increase in concentration and viscosity was observed only at 700 as well 1000 mOsm/kg H 2 O but to a lesser extent. In summary, dialysis strongly enhanced the viscosity differences between the non-ionic monomeric and dimeric CAs. The administration of dimeric CAs leads to a strong increase in urine viscosity; this was not observed for the

Viscosity of iodinated contrast agents during renal excretion

Energy Technology Data Exchange (ETDEWEB)

Jost, Gregor, E-mail: Gregor.Jost@bayer.com [TRG Diagnostic Imaging, Bayer Schering Pharma AG, Berlin (Germany); Lengsfeld, Philipp, E-mail: Philipp.Lengsfeld@bayer.com [Global Medical Affairs Diagnostic Imaging, Bayer Schering Pharma AG, Berlin (Germany); Lenhard, Diana C., E-mail: Diana.Lenhard@bayer.com [TRG Diagnostic Imaging, Bayer Schering Pharma AG, Berlin (Germany); Pietsch, Hubertus, E-mail: Hubertus.Pietsch@bayer.com [TRG Diagnostic Imaging, Bayer Schering Pharma AG, Berlin (Germany); Huetter, Joachim, E-mail: Joachim.Huetter@bayer.com [TRG Diagnostic Imaging, Bayer Schering Pharma AG, Berlin (Germany); Sieber, Martin A., E-mail: Martin.Sieber@bayer.com [TRG Diagnostic Imaging, Bayer Schering Pharma AG, Berlin (Germany)

2011-11-15

Objective: Modern iodinated non-ionic contrast agents (CAs) can be classified based on their molecular structure into monomeric and dimeric CAs and have at comparable iodine concentrations a different viscosity and osmolality. During their renal excretion, CAs are concentrated in the renal tubuli which might enhance the viscosity difference between monomeric and dimeric CAs. The viscosity of a CA might have an underestimated importance for renal safety, as suggested by recent publications. In this study, we investigated the viscosities of CAs at the concentrations expected to be present in renal tubules. This concentration process was simulated in vitro using dialysis. Furthermore, we investigated urine viscosity and urine flow in rodents after administration of several non-ionic monomeric and dimeric CAs. Materials and methods: To estimate the viscosity of the CAs in vivo, we performed an in vitro dialysis of monomeric and dimeric CAs at various physiological osmolalities of the renal tubulus (290, 400, 500, 700 and 1000 mOsm/kg H{sub 2}O). Following the dialysis, the iodine concentrations and the viscosities of the CAs were determined. Furthermore, to investigate the concentration process in vivo, we measured the urine viscosity and the urine flow in Han Wister rats after the administration of Iopromide, Iohexol, Ioversol, Iomeprol, Iodixanol, and Iosimenol at comparable iodine concentrations. As a control, saline was injected at the same volume. Results: In vitro dialysis of the dimeric CA increased the iodine concentration and strongly increased the viscosity at all tested osmolalities. In contrast, for the monomeric agents an increase in concentration and viscosity was observed only at 700 as well 1000 mOsm/kg H{sub 2}O but to a lesser extent. In summary, dialysis strongly enhanced the viscosity differences between the non-ionic monomeric and dimeric CAs. The administration of dimeric CAs leads to a strong increase in urine viscosity; this was not observed for

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

Directory of Open Access Journals (Sweden)

Daniel J. Korchinski

2015-01-01

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

Contrast Agent in Magnetic Resonance Imaging

DEFF Research Database (Denmark)

Vu-Quang, Hieu

2015-01-01

Nanoparticles have been employed as contrast agent in magnetic resonance imaging (MRI) in order to improve sensitivity and accuracy in diagnosis. In addition, these contrast agents are potentially combined with other therapeutic compounds or near infrared bio-imaging (NIR) fluorophores to obtain...... theranostic or dual imaging purposes, respectively. There were two main types of MRI contrast agent that were synthesized during this PhD project including fluorine containing nanoparticles and magnetic nanoparticles. In regard of fluorine containing nanoparticles, there were two types contrast agent...... cancer cells for cancer diagnosis in MRI. F127-Folate coated SPION were stable in various types of suspension medium for over six months. They could specifically target folate receptor of cancer cells in vitro and in vivo thus enhancing the contrast in MRI T2/T2* weighted images. These are preliminary...

Polymer Assembly Encapsulation of Lanthanide Nanoparticles as Contrast Agents for In Vivo Micro-CT.

Science.gov (United States)

Cruje, Charmainne; Dunmore-Buyze, Joy; MacDonald, Jarret P; Holdsworth, David W; Drangova, Maria; Gillies, Elizabeth R

2018-03-12

Despite recent technological advancements in microcomputed tomography (micro-CT) and contrast agent development, preclinical contrast agents are still predominantly iodine-based. Higher contrast can be achieved when using elements with higher atomic numbers, such as lanthanides; lanthanides also have X-ray attenuation properties that are ideal for spectral CT. However, the formulation of lanthanide-based contrast agents at the high concentrations required for vascular imaging presents a significant challenge. In this work, we developed an erbium-based contrast agent that meets micro-CT imaging requirements, which include colloidal stability upon redispersion at high concentrations, evasion of rapid renal clearance, and circulation times of tens of minutes in small animals. Through systematic studies with poly(ethylene glycol) (PEG)-poly(propylene glycol), PEG-polycaprolactone, and PEG-poly(l-lactide) (PLA) block copolymers, the amphiphilic block copolymer PEG 114 -PLA 53 was identified to be ideal for encapsulating oleate-coated lanthanide-based nanoparticles for in vivo intravenous administration. We were able to synthesize a contrast agent containing 100 mg/mL of erbium that could be redispersed into colloidally stable particles in saline after lyophilization. Contrast enhancement of over 250 HU was achieved in the blood pool for up to an hour, thereby meeting the requirements of live animal micro-CT.

Evaluation of clot formation in blood-contrast agent mixture: experimental study on ionic/nonionic contrast agents and plastic/ glass syringes

International Nuclear Information System (INIS)

Shim, Hyung Jin; Lee, Jong Beum; Lee, Yong Chul; Lee, Kwan Seh; Kim, Kun Sang

1991-01-01

Recent introduction of low-osmolar nonionic contrast agents has allowed the performance of angiography with certain advantages such as reduced pain, reduced osmotic load and other potential advantages, over high osmolar ionic contrast agents. But the potential thrombogenic risk of nonionic contrast agent has been debate because of their weak anticoagulation effect. Several reports have recently documented the formation of thrombi in catheters and syringes containing nonionic contrast agent, and thromboembolic episodes have been noted during angiographic procedures. We have also been experienced blood clotting within blood mixed contrast agent syringe during angiography. Thus, we have studied with blood mixed ionic (Diatrizoate, Ioglicate) agents and nonionic (Iopamidol, Iopromide) agents, that used usually in our hospital, and saline in plastic and glass syringes. Each syringes were checked the clot formation on 10,30,60,90 minutes. Total 340 samples were obtained from 8 adults before angiography. Our data showed that nonionic contrast agents had significantly lesser anticoagulation effect than ionic contrast agents (ρ < 0.0001) on Chi-square test), both in plastic and glass syringes. And formation of clotting in glass syringes were significantly greater than that in plastic syringes (ρ < 0.0001). Thus meticulous technique is required to prevent thrombosis during angiographic procedure using nonionic contrast agents

Interactions of ionic and nonionic contrast agents with thrombolytic agents

International Nuclear Information System (INIS)

Fareed, J.; Moncada, R.; Scanlon, P.; Hoppensteadt, D.; Huan, X.; Walenga, J.M.

1987-01-01

Both the ionic and nonionic intravascular contrast media have been used before and after the administration of thrombolytic agents to evaluate clot lysis during angioplasty and the treatment of myocardial infarction. In experimental animal models, the authors found that the clot lytic efficacy of streptokinase, streptokinase-plasminogen complex, and tissue plasminogen activator (t-PA) is markedly augmented if these agents are administered within 1 hour after the angiographic producers. Furthermore, contrast agents injected after the administration of t-Pa exhibit a synergistic action. In stimulated models administration of one ionic contrast medium (Angiovist, Berlex, Wayne, NJ) and two nonionic contrast agents (Isovue-370, Squibb Diagnostics, New Brunswick, NJ; Omnipaque-350, Winthrop, NY) 15 minutes before the administration of t-PA resulted in marked enhancement of the lytic activity. Although the mechanism of this interaction is unknown at this time, it should be taken into consideration in the treatment of patients with myocardial infarction, in whom contrast agents are continually used to evaluate the therapeutic lysis. Furthermore, this interaction may be partly related to the therapeutic efficacy and/or hemorrhagic actions observed

Novel MR imaging contrast agents for cancer detection

Directory of Open Access Journals (Sweden)

Daryoush Shahbazi-Gahrouei

2009-05-01

Full Text Available

• BACKGROUND: Novel potential MR imaging contrast agents Gd-tetra-carboranylmethoxyphenyl-porphyrin (Gd-TCP, Gd-hematoporphyrin (Gd-H, Gd-DTPA-9.2.27 against melanoma, Gd-DTPA-WM53 against leukemia and Gd-DTPAC595 against breast cancer cells were synthesized and applied to mice with different human cancer cells (melanoma MM-138, leukemia HL-60, breast MCF-7. The relaxivity, the biodistribution, T1 relaxation times, and signal enhancement of the contrast agents are presented and the results are compared.
• METHODS: After preparation of contrast agents, the animal studies were performed. The cells (2×106 cells were injected subcutaneously in the both flanks of mice. Two to three weeks after tumor plantation, when the tumor diameter was 2-4 mm, mice were injected with the different contrast agents. The animals were sacrificed at 24 hr post IP injection followed by removal of critical organs. The T1 relaxation times and signal intensities of samples were measured using 11.4 T magnetic field and Gd concentration were measured using UV-spectrophotometer.
• RESULTS: For Gd-H, the percent of Gd localized to the tumors measured by UV-spect was 28, 23 and 21 in leukemia, melanoma and breast cells, respectively. For Gd-TCP this amount was 21%, 18% and 15%, respectively. For Gd-DTPA-9.2.27, Gd-DTPA-WM53 and Gd-DTPA-C595 approximately 35%, 32% and 27% of gadolinium localized to their specific tumor, respectively.
• CONCLUSION: The specific studied conjugates showed good tumor uptake in the relevant cell lines and low levels of Gd in the liver, kidney and spleen. The studied agents have considerable promise for further diagnosis applications of MR imaging.
• KEYWORDS: Magnetic Resonance, Imaging, Monoclonal Antibody, Contrast Agents, Gadolinium, Early Detection of Cancer.

Fundamental studies of oral contrast agents for MR. Comparison of manganese agent and iron agent

International Nuclear Information System (INIS)

Fujita, Osamu; Hiraishi, Kumiko; Suginobu, Yoshito; Takeuchi, Masayasu; Narabayashi, Isamu

1996-01-01

We investigated and compared signal intensity and the effect of imaging the upper abdomen with blueberry juice (B.J.), a Mn agent utilizing the properties of paramagnetic metals, and FerriSeltz (F.S.), an iron agent. Since the relaxation effect was much stronger with B.J. than with F.S., the signal intensity required of a peroral contrast agent was able to be obtained at a much lower concentration of B.J. In imaging the upper abdomen, B.J. had a positive effect on imaging in T1-weighted images, and a negative effect in T2-weighted images. F.S. had a positive imaging effect in both, and because it showed extremely high signals in T2-weighted images, motion artifact arose. (author)

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

Science.gov (United States)

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.

Non-radiological contrast agents (MRI)

International Nuclear Information System (INIS)

Bonnemain, B.; Lautrou, J.; Meyer, D.; Doucet, D.

1987-01-01

Over the past few years, extensive research has been carried out in an attempt to develop contrast agents that could help improve both the performance (acquisition times) and the diagnostic efficacy of Magnetic Resonance Imaging (MRI) techniques. On the basis of physicochemical and pharmacological criteria discussed in this presentation, a few efficacious, well-tolerated compounds could be developed. Two of them, the gadolinium complexes Gd-DOTA and Gd-DTPA, are currently being tried in man. This first generation of contrast agents, which are aspecific markers of the intravascular space, has been shown to have good diagnostic potential in conventional MRI procedures. The diagnostic contribution of these contrast agents will probably be a most essential factor in new MRI techniques using low field strengh or fast imaging sequences [fr

Microbubbles as contrast agent for in-line x-ray phase-contrast imaging

International Nuclear Information System (INIS)

Xi Yan; Zhao Jun; Tang Rongbiao; Wang Yujie

2011-01-01

In the present study, we investigated the potential of gas-filled microbubbles as contrast agents for in-line x-ray phase-contrast imaging (PCI) in biomedical applications. When imaging parameters are optimized, the microbubbles function as microlenses that focus the incoming x-rays to form bright spots, which can significantly enhance the image contrast. Since microbubbles have been shown to be safe contrast agents in clinical ultrasonography, this contrast-enhancement procedure for PCI may have promising utility in biomedical applications, especially when the dose of radiation is a serious concern. In this study, we performed both numerical simulations and ex vivo experiments to investigate the formation of the contrast and the effectiveness of microbubbles as contrast agents in PCI.

Method and apparatus to characterize ultrasonically reflective contrast agents

Science.gov (United States)

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.

Beat frequency ultrasonic microsphere contrast agent detection system

Science.gov (United States)

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

1997-01-01

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

Trends and developments in MRI contrast agent research

International Nuclear Information System (INIS)

Cavagna, F.M.; Dapra, M.; Castelli, P.M.; Maggioni, F.; Kirchin, M.A.

1997-01-01

The currently prevailing trends in industrial contrast agent research for MRI are discussed. Specific mention is made of contrast agents for liver imaging using both static and delayed procedures, of the potential for blood pool agents and the form such agents may take, and of the ultimate challenge for contrast agent R and D: tissue-targeting in a wider sense to both normal and pathologic tissues. (orig.)

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

Science.gov (United States)

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.

A biomarker-responsive T2ex MRI contrast agent.

Science.gov (United States)

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.

Red blood cell labeling with technetium-99m. Effect of radiopaque contrast agents

International Nuclear Information System (INIS)

Finkel, J.; Chervu, L.R.; Bernstein, R.G.; Srivastava, S.C.

1988-01-01

Radiographic contrast agents have been reported in the literature to interfere significantly with red blood cell (RBC) labeling in vivo by Tc-99m. Moreover, in the presence of contrast agents, red cells have been known to undergo significant morphologic changes. These observations led to the current RBC labeling study in patients (N = 25) undergoing procedures with the administration of contrast media. Before and after contrast administration, blood samples were drawn from each patient into vacutainer tubes containing heparin and RBC labeling was performed using 1-ml aliquots of these samples following the Brookhaven National Laboratory protocol. The differences in average percentage labeling yield with and without contrast media were not significant. In vivo labeling in hypertensive rats with administration of contrast media up to 600 mg likewise consistently gave high labeling yields at all concentrations. Purported alterations in cell labeling attributed to contrast agents are not reflected in these studies, and other pathophysiologic factors need to be identified to substantiate the previous reports. In vitro study offers a potentially useful and simple method to delineate effects of various agents on cell labeling

Characterization of colloidal manganese hydroxylapatite: A potential magnetic resonance contrast agent

Science.gov (United States)

Dorshow, Richard B.; Kofi Adzamli, I.; Nosco, Dennis L.; Joslin, Frederick L.

1996-03-01

Particulate contrast agents for blood pool imaging need to be constructed with the appropriate particle size distribution (PSD), and need to be resistant to opsonization. Hence, the PSD of an aqueous colloidal suspension of polyethylene glycol (PEG)-stabilized manganese hydroxylapatite (potentially useful as a magnetic resonance contrast agent for blood pool imaging) has been investigated as a function of PEG concentration and molecular weight. At low PEG concentrations, dynamic light scattering (DLS) and sedimentation field flow fractionation measurements yield a broad PSD, with the largest particle diameters near 100nm. Flow field flow fractionation (FlFFF) measurements, however, yield a distinct population near 10nm, which is not readily detectable by the other two techniques. As the PEG concentration is increased, the PSD shifts toward the lower size population. At the highest PEG concentration employed, only particles of diameter 10nm remain, verified by both FlFFF and DLS. Thus, the search for an optimum PSD for blood pool imaging is facilitated by choice of PEG molecular weight and concentration, and by employing complementary use of light scattering and field flow fractionation techniques.

Hepatobiliary contrast agents for contrast-enhanced MRI of the liver: properties, clinical development and applications

International Nuclear Information System (INIS)

Reimer, Peter; Schneider, Guenter; Schima, Wolfgang

2004-01-01

Hepatobiliary contrast agents with uptake into hepatocytes followed by variable biliary excretion represent a unique class of cell-specific MR contrast agents. Two hepatobiliary contrast agents, mangafodipir trisodium and gadobenate dimeglumine, are already clinically approved. A third hepatobiliary contrast agent, Gd-EOB-DTPA, is under consideration. The purpose of this review is to provide an overview on the properties, clinical development and application of these three hepatobiliary contrast agents. Bolus injectable paramagnetic hepatobiliary contrast agents combine established features of extracellular agents with the advantages of hepatocyte specificity. The detection and characterisation of focal liver disease appears to be improved compared to unenhanced MRI, MRI with unspecific contrast agents and contrast-enhanced CT. To decrease the total time spent by a patient in the MR scanner, it is advisable to administer the agent immediately after acquisition of unenhanced T1-w MRI. After infusion or bolus injection (with dynamic FS-T1-w 2D or 3D GRE) of the contrast agent, moderately and heavily T2w images are acquired. Post-contrast T1-w MRI is started upon completion of T2-w MRI for mangafodipir trisodium and Gd-EOB-DTPA as early as 20 min following injection, while gadobenate dimeglumine scans are obtained >60 min following injection. Post-contrast acquisition techniques with near isotropic 3D pulse sequences with fat saturation parallel the technical progress made by MSCT combined with an unparalleled improvement in tumour-liver contrast. The individual decision that hepatobiliary contrast agent one uses is partly based on personal preferences. No comparative studies have been conducted comparing the advantages or disadvantages of all three agents directly against each other. (orig.)

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

DEFF Research Database (Denmark)

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

1998-01-01

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

Biocompatible Nanocomplexes for Molecular Targeted MRI Contrast Agent

Science.gov (United States)

Chen, Zhijin; Yu, Dexin; Wang, Shaojie; Zhang, Na; Ma, Chunhong; Lu, Zaijun

2009-07-01

Accurate diagnosis in early stage is vital for the treatment of Hepatocellular carcinoma. The aim of this study was to investigate the potential of poly lactic acid-polyethylene glycol/gadolinium-diethylenetriamine-pentaacetic acid (PLA-PEG/Gd-DTPA) nanocomplexes using as biocompatible molecular magnetic resonance imaging (MRI) contrast agent. The PLA-PEG/Gd-DTPA nanocomplexes were obtained using self-assembly nanotechnology by incubation of PLA-PEG nanoparticles and the commercial contrast agent, Gd-DTPA. The physicochemical properties of nanocomplexes were measured by atomic force microscopy and photon correlation spectroscopy. The T1-weighted MR images of the nanocomplexes were obtained in a 3.0 T clinical MR imager. The stability study was carried out in human plasma and the distribution in vivo was investigated in rats. The mean size of the PLA-PEG/Gd-DTPA nanocomplexes was 187.9 ± 2.30 nm, and the polydispersity index was 0.108, and the zeta potential was -12.36 ± 3.58 mV. The results of MRI test confirmed that the PLA-PEG/Gd-DTPA nanocomplexes possessed the ability of MRI, and the direct correlation between the MRI imaging intensities and the nano-complex concentrations was observed ( r = 0.987). The signal intensity was still stable within 2 h after incubation of the nanocomplexes in human plasma. The nanocomplexes gave much better image contrast effects and longer stagnation time than that of commercial contrast agent in rat liver. A dose of 0.04 mmol of gadolinium per kilogram of body weight was sufficient to increase the MRI imaging intensities in rat livers by five-fold compared with the commercial Gd-DTPA. PLA-PEG/Gd-DTPA nanocomplexes could be prepared easily with small particle sizes. The nanocomplexes had high plasma stability, better image contrast effect, and liver targeting property. These results indicated that the PLA-PEG/Gd-DTPA nanocomplexes might be potential as molecular targeted imaging contrast agent.

Biocompatible Nanocomplexes for Molecular Targeted MRI Contrast Agent

Directory of Open Access Journals (Sweden)

Yu Dexin

2009-01-01

Full Text Available Abstract Accurate diagnosis in early stage is vital for the treatment of Hepatocellular carcinoma. The aim of this study was to investigate the potential of poly lactic acid–polyethylene glycol/gadolinium–diethylenetriamine-pentaacetic acid (PLA–PEG/Gd–DTPA nanocomplexes using as biocompatible molecular magnetic resonance imaging (MRI contrast agent. The PLA–PEG/Gd–DTPA nanocomplexes were obtained using self-assembly nanotechnology by incubation of PLA–PEG nanoparticles and the commercial contrast agent, Gd–DTPA. The physicochemical properties of nanocomplexes were measured by atomic force microscopy and photon correlation spectroscopy. The T1-weighted MR images of the nanocomplexes were obtained in a 3.0 T clinical MR imager. The stability study was carried out in human plasma and the distribution in vivo was investigated in rats. The mean size of the PLA–PEG/Gd–DTPA nanocomplexes was 187.9 ± 2.30 nm, and the polydispersity index was 0.108, and the zeta potential was −12.36 ± 3.58 mV. The results of MRI test confirmed that the PLA–PEG/Gd–DTPA nanocomplexes possessed the ability of MRI, and the direct correlation between the MRI imaging intensities and the nano-complex concentrations was observed (r = 0.987. The signal intensity was still stable within 2 h after incubation of the nanocomplexes in human plasma. The nanocomplexes gave much better image contrast effects and longer stagnation time than that of commercial contrast agent in rat liver. A dose of 0.04 mmol of gadolinium per kilogram of body weight was sufficient to increase the MRI imaging intensities in rat livers by five-fold compared with the commercial Gd–DTPA. PLA–PEG/Gd–DTPA nanocomplexes could be prepared easily with small particle sizes. The nanocomplexes had high plasma stability, better image contrast effect, and liver targeting property. These results indicated that the PLA–PEG/Gd–DTPA nanocomplexes might be potential as molecular

Magnetic resonance imaging contrast agents: Overview and perspectives

International Nuclear Information System (INIS)

Yan Guoping; Robinson, Leslie; Hogg, Peter

2007-01-01

Magnetic resonance imaging (MRI) is a non-invasive clinical imaging modality, which has become widely used in the diagnosis and/or staging of human diseases around the world. Some MRI examinations include the use of contrast agents. The categorizations of currently available contrast agents have been described according to their effect on the image, magnetic behavior and biodistribution in the body, respectively. In this field, superparamagnetic iron oxide particles and soluble paramagnetic metal chelates are two main classes of contrast agents for MRI. This review outlines the research and development of MRI contrast agents. In future, the ideal MRI contrast agent will be focused on the neutral tissue- or organ-targeting materials with high relaxivity and specificity, low toxicity and side effects, suitable long intravascular duration and excretion time, high contrast enhancement with low dose in vivo, and with minimal cost

A prospective evaluation of contrast and radiation dose and image quality in cardiac CT in children with complex congenital heart disease using low-concentration iodinated contrast agent and low tube voltage and current.

Science.gov (United States)

Hou, Qiao-Ru; Gao, Wei; Sun, Ai-Min; Wang, Qian; Qiu, Hai-Sheng; Wang, Fang; Hu, Li-Wei; Li, Jian-Ying; Zhong, Yu-Min

2017-02-01

To the assess image quality, contrast dose and radiation dose in cardiac CT in children with congenital heart disease (CHD) using low-concentration iodinated contrast agent and low tube voltage and current in comparison with standard dose protocol. 110 patients with CHD were randomized to 1 of the 2 scan protocols: Group A (n = 45) with 120 mA tube current and contrast agent of 270 mgI/ml in concentration (Visipaque ™ ; GE Healthcare Ireland, Co., Cork, UK); and Group B (n = 65) with the conventional 160 mA and 370 mgI/ml concentration contrast (Iopamiro ® ; Shanghai Bracco Sine Pharmaceutical Corp Ltd, Shanghai, China). Both groups used 80 kVp tube voltage and were reconstructed with 70% adaptive statistical iterative reconstruction algorithm. The CT value and noise in aortic arch were measured and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. A five-point scale was used to subjectively evaluate image quality. Contrast and radiation dose were recorded. There was no difference in age and weight between the two groups (all p > 0.05). The iodine load and radiation dose in Group A were statistically lower (3976 ± 747 mgI vs 5763 ± 1018 mgI in iodine load and 0.60 ± 0.08 mSv vs 0.77 ± 0.10 mSv in effective dose; p  0.05), and with good agreement between the two observers. Comparing the surgery results, the diagnostic accuracy for extracardiac and intracardiac defects for Group A was 96% and 92%, respectively, while the corresponding numbers for Group B were 95% and 93%. Compared with the standard dose protocol, the use of low tube voltage (80 kVp), low tube current (120 mA) and low-concentration iodinated contrast agent (270 mgI/ml) enables a reduction of 30% in iodine load and 22% in radiation dose while maintaining compatible image quality and diagnostic accuracy. Advances in knowledge: The new cardiac CT scanning protocol can largely reduce the adverse effects of

Use of contrast agents for liver MRI

International Nuclear Information System (INIS)

Ward, Janice

2007-01-01

Contrast-enhanced MRI is recognised as one of the most accurate imaging methods for investigating diseases of the liver. Uniquely several different types of contrast agents are available for liver MRI. They can be divided into non-specific extracellular fluid space (ECF), hepatocyte specific and reticulo-endothelial system (RES) specific agents. They are used to improve the detection of focal liver lesions by increasing normal-abnormal tissue contrast and to assist in lesion characterisation by demonstrating tissue perfusion and cellular function. ECF-gadolinium (Gd) chelates have been widely used in abdominal MRI for many years. They provide valuable information regarding the vascularisation and perfusion characteristics of lesions and assist in lesion detection, particularly of hypervascular lesions. The hepatocyte and RES-specific agents further improve lesion detection, provide important functional information and allow the distinction between hepatocellular and non-hepatocellular tumours. This article describes the different MR contrast agents and discusses their current status for diagnosing focal liver lesions. The importance of optimised technique and appropriate selection of contrast agent is emphasised

Fundamental study of DSA images using gadolinium contrast agent

International Nuclear Information System (INIS)

Nagashima, Hiroyuki; Shiraishi, Akihisa; Igarashi, Hitoshi; Sakamoto, Hajime; Sano, Yoshitomo

2002-01-01

Most contrast agents used in digital subtraction angiography (DSA) are non-ionic iodinated contrast agents, which can cause severe side effects in patients with contraindications for iodine or allergic reactions to iodine. Therefore, DSA examinations using carbon dioxide gas or examinations done by magnetic resonance imaging (MRI) and ultrasound (US) were carried out in these patients. However, none of these examinations provided mages as clear as those of DSA with an iodinated contrast agent. We experienced DSA examination using a gadolinium contrast agent in a patient contraindicated for iodine. The patient had undergone MRI examination with a gadolinium contrast agent previously without side effects. The characteristics of gadolinium and the iodinated contrast agent were compared, and the DSA images obtained clinically using these media were also evaluated. The signal-to-noise (SN) ratio of the gadolinium contrast agent was the highest at tube voltages of 70 to 80 kilovolts and improved slightly when the image intensifier (I.I.) entrance dose was greater than 300 μR (77.4 nC/kg). The dilution ratios of five iodinated contrast agents showed the same S/N value as the undiluted gadolinium contrast agent. Clinically, the images obtained showed a slight decrease in contrast but provided the data necessary to make a diagnosis and made it possible to obtain interventional radiology (IVR) without any side effects. DSA examinations using a gadolinium contrast agent have some benefit with low risk and are thought to be useful for patients contraindicated for iodine. (author)

Basic MR relaxation mechanisms and contrast agent design.

Science.gov (United States)

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

2015-09-01

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

Methylene blue microbubbles as a model dual-modality contrast agent for ultrasound and activatable photoacoustic imaging

Science.gov (United States)

Jeon, Mansik; Song, Wentao; Huynh, Elizabeth; Kim, Jungho; Kim, Jeesu; Helfield, Brandon L.; Leung, Ben Y. C.; Goertz, David E.; Zheng, Gang; Oh, Jungtaek; Lovell, Jonathan F.; Kim, Chulhong

2014-01-01

Ultrasound and photoacoustic imaging are highly complementary modalities since both use ultrasonic detection for operation. Increasingly, photoacoustic and ultrasound have been integrated in terms of hardware instrumentation. To generate a broadly accessible dual-modality contrast agent, we generated microbubbles (a standard ultrasound contrast agent) in a solution of methylene blue (a standard photoacoustic dye). This MB2 solution was formed effectively and was optimized as a dual-modality contrast solution. As microbubble concentration increased (with methylene blue concentration constant), photoacoustic signal was attenuated in the MB2 solution. When methylene blue concentration increased (with microbubble concentration held constant), no ultrasonic interference was observed. Using an MB2 solution that strongly attenuated all photoacoustic signal, high powered ultrasound could be used to burst the microbubbles and dramatically enhance photoacoustic contrast (>800-fold increase), providing a new method for spatiotemporal control of photoacoustic signal generation.

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

International Nuclear Information System (INIS)

Silvast, T. S.; Jurvelin, J.S.; Aula, A.S.; Lammi, M.J.; Toeyraes, J.

2009-01-01

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

The feasibility of a targeted ultrasound contrast agent carrying genes and cell-penetrating peptides to hypoxic HUVEC

International Nuclear Information System (INIS)

Tian Ju; Wang Zhigang; Ren Jianli; Zhang Qingfeng; Liu Li

2012-01-01

Objective: To prepare an anti-P-selectin targeted ultrasound contrast agent carrying genes and cell-penetrating peptides (CPP) and to investigate its feasibility of delivery to hypoxic human umbilical vein endothelial cells (HUVEC). Methods: Anti-P-selectin targeted ultrasound contrast agent carrying a green fluorescent protein gene (pEGFP-N1) and CPP was prepared by mechanical vibration and carbodiimide techniques. The appearance, distribution, concentration and diameter of the ultrasound contrast agent were measured. The gene and CPP distribution on the agent was investigated using confocal laser scanning microscopy (CLSM). The efficiency of the ultrasound contrast agent to carry the gene and CPP was investigated by fluorospectrophotometry. HUVEC were cultured in vitro and hypoxic HUVEC were prepared using hydrogen peroxide (H 2 O 2 ). Hypoxic HUVEC were randomly assigned targeted ultrasound contrast agents and non-targeted ultrasound contrast agents for transfection. The transfection effect of green fluorescent protein in the two groups was observed using fluorescence microscopy and flow cytometry. T-test and linear correlation analysis were used for statistical analysis. Results: The average diameter of anti-P-selectin targeted ultrasound contrast agents carrying gene and CPP was (2.15 ±0.36) μm and the concentration was (1.58 ± 0.23) × 10 7 /ml.The results of CLSM showed that gene and CPP were distributed on the shell of the agent. The gene encapsulation efficiency was 28% (y=0.932x-0.09, r=0.993, P<0.05), and the CPP encapsulation efficiency was 25% (y=5.875x-0.81, r=0.987, P<0.05). EGFP expression was observed using fluorescence microscopy in targeted ultrasound contrast agents and non-targeted ultrasound contrast agents. The average transfection efficiencies of targeted ultrasound contrast agents and non-targeted ultrasound contrast agents were (18.74 ± 0.47) % and (15.34 ± 0.22) % after 24 h (t=10.923, P<0.001). Conclusions: The in vitro studies

The interaction of MRI contrast agents with phospholipids

International Nuclear Information System (INIS)

Jendrasiak, Gordon L.; Smith, Ralph L.; Ribeiro, Anthony A.

2000-01-01

The molecular interactions of three clinically used MRI contrast agents with lipid vesicles, consisting of egg phosphatidylcholine (EPC), have been studied using high-field NMR techniques. At a molar ratio of one contrast agent molecule to five phospholipid molecules, a significant increase in the proton resonance line width occurred for certain lipid head group moieties. A large decrease in the T 1 relaxation times for the head group moieties was also observed. These two effects occurred regardless of the ionic status and the chelate structure of the three contrast agents. The structure of the contrast agents did, however, affect the magnitude of the two NMR parameter changes. These NMR effects also differed in magnitude amongst the various head group entities. The NMR effects were greatest for the head group moieties at or near the vesicle-water interface. The results are discussed in terms of the structure of the phospholipid-water interface. Since the use of contrast agents has become routine in clinical MRI, our results are of importance in terms of the interaction of the agents with physiological surfaces, many of which contain phospholipids. The understanding of such interactions should be of value not only for improved diagnostics, but also in the development of new contrast agents. (author)

Contrast agent incompatibility with intravascular medications

International Nuclear Information System (INIS)

Irving, H.D.; Burbridge, B.E.

1988-01-01

In vitro and in vivo precipitation of iodinated contrast agents with commonly used medications have been reported. The intent of this in vitro study is to verify these reports and investigate other medications not previously tested. Contrast agents and medications were analyzed with a light spectrometer and observed for visible precipitates for up to 120 minutes. Previously reported incompatibilities were verified, and several new incompatibilities were discovered

Hexabrix (ioxaglate), a new low osmolality contrast agent for lumbar epidural double-catheter venography

International Nuclear Information System (INIS)

Meijenhorst, G.C.H.; Bruin, J.N.T. de

1980-01-01

Hexabrix (ioxaglate), a new low osmolality contrast agent, has been compared with Telebrix (ioxitalamate) in a series of 50 lumbar epidural venograms. The intensity of the pain and heat sensation experienced by the patient was significantly lower following the injection of Hexabrix. For this reason Hexabrix may be considered the contrast medium of choice for epidural venography. In 15 additional cases Hexabrix was compared with Amipaque (metrizamide) in the same iodine concentration (320 mg/ml). In these patients hardly any difference in pain and heat sensation was observed after the injection of both contrast agents. Frequently only a slight feeling of warmth was noticed. A minimal sensation of pain was occasionally observed to the same degree with both contrast agents. (orig.)

Multiwalled carbon nanotube hybrids as MRI contrast agents

Directory of Open Access Journals (Sweden)

Nikodem Kuźnik

2016-07-01

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

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

International Nuclear Information System (INIS)

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

1984-01-01

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

Large abnormal peak on capillary zone electrophoresis due to contrast agent.

Science.gov (United States)

Wheeler, Rachel D; Zhang, Liqun; Sheldon, Joanna

2017-01-01

Background Some iodinated radio-contrast media absorb ultraviolet light and can therefore be detected by capillary zone electrophoresis. If seen, these peaks are typically small with 'quantifications' of below 5 g/L. Here, we describe the detection of a large peak on capillary zone electrophoresis that was due to the radio-contrast agent, Omnipaque™. Methods Serum from a patient was analysed by capillary zone electrophoresis, and the IgG, IgA, IgM and total protein concentrations were measured. The serum sample was further analysed by gel electrophoresis and immunofixation. Results Capillary zone electrophoresis results for the serum sample showed a large peak with a concentration high enough to warrant urgent investigation. However, careful interpretation alongside the serum immunoglobulin concentrations and total protein concentration showed that the abnormal peak was a pseudoparaprotein rather than a monoclonal immunoglobulin. This was confirmed by analysis with gel electrophoresis and also serum immunofixation. The patient had had a CT angiogram with the radio-contrast agent Omnipaque™; addition of Omnipaque™ to a normal serum sample gave a peak with comparable mobility to the pseudoparaprotein in the patient's serum. Conclusions Pseudoparaproteins can appear as a large band on capillary zone electrophoresis. This case highlights the importance of a laboratory process that detects significant electrophoretic abnormalities promptly and interprets them in the context of the immunoglobulin concentrations. This should avoid incorrect reporting of pseudoparaproteins which could result in the patient having unnecessary investigations.

Contrast-enhanced voiding urosonography phantom study: intravenous iodinated and gadolinium-based contrast agents may cause false-negative results in assessment of vesicoureteral reflux in children

International Nuclear Information System (INIS)

Veldhoen, Simon; Sauer, Alexander; Gassenmaier, Tobias; Petritsch, Bernhard; Herz, Stefan; Blanke, Philipp; Bley, Thorsten A.; Wirth, Clemens; Derlin, Thorsten

2015-01-01

Contrast-enhanced voiding urosonography (ce-VUS) is commonly requested simultaneously to other diagnostic imaging necessitating intravenous contrast agents. To date there is limited knowldedge about intravesical interactions between different types of contrast agents. To assess the effect of excreted intravenous iodinated and gadolinium-based contrast agents on the intravesical distribution of ultrasound contrast within contrast-enhanced voiding urosonography. Iodinated (iomeprol, iopamidol) and gadolinium-based (gadoterate meglumine) contrast agents were diluted to bladder concentration and injected into balloons filled with saline solution. CT scans were performed to assess the contrast distribution in these phantoms. Regions of interest were placed at the top and bottom side of each balloon and Hounsfield units (HU) were measured. Three other balloons were filled with saline solution and contrast media likewise. The ultrasound contrast agent sulphur hexafluoride was added and its distribution was assessed using sonography. MDCT scans showed a separation of two liquid layers in all bladder phantoms with the contrast layers located at the bottom and the saline solution at the top. Significant differences of the HU measurements at the top and bottom side were observed (P < 0.001-0.007). Following injection of ultrasound contrast agent, US showed its distribution exclusively among the saline solution. False-negative results of contrast-enhanced voiding urosonography may occur if it is performed shortly after imaging procedures requiring intravenous contrast. (orig.)

An albumin-based gold nanocomposites as potential dual mode CT/MRI contrast agent

Science.gov (United States)

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.

Superparamagnetic nanoparticle-inclusion microbubbles for ultrasound contrast agents

International Nuclear Information System (INIS)

Yang Fang; Li Yixin; Chen Zhongping; Gu Ning; Li Ling; Wu Junru

2008-01-01

We have developed a new type of ultrasound (US) contrast agent, consisting of a gas core, a layer of superparamagnetic iron oxide Fe 3 O 4 nanoparticles (SPIO) and an oil in water outermost layer. The newly developed US contrast agent microbubbles have a mean diameter of 760 nm with a polydisperity index (PI) of 0.699. Our in vitro and in vivo experiments have shown that they have the following advantages compared to gas-encapsulated microbbubbles without SPIO inclusion: (1) they provide better contrast for US images; (2) the SPIO-inclusion microbubbles generate a higher backscattering signal; the mean grey scale is 97.9, which is 38.6 higher than that of microbubbles without SPIO; and (3) since SPIO can also serve as a contrast agent of magnetic resonance images (MRI) in vitro, they can be potentially used as contrast agents for double-modality (MRI and US) clinical studies.

Contrast agent choice for intravenous coronary angiography

International Nuclear Information System (INIS)

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

1990-01-01

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. (orig./HSI)

Nanoparticle Contrast Agents for Computed Tomography: A Focus on Micelles

Science.gov (United States)

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

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

Science.gov (United States)

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

2016-12-01

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

The primary applications of Gd-DTPA as an oral negative gastrointestinal contrast agent for MRCP

International Nuclear Information System (INIS)

Chen Yanping; Zhang Xuelin; Cheng Guanxun; Chang Renmin; Zhang Yuzhong; Cang Peng; Xia Qiong

2003-01-01

Objective: Using oral Gd-DTPA as a negative contrast agent to null the bowel signal during MR cholangiopancreatography (MRCP) to improve the quality of MRCP. Methods: A phantom study was performed to select the optimal concentration of Gd-DTPA to be used as an oral negative contrast agent in MRCP. 15 patients suspected of biliary tract and pancreatic disease were performed with MRCP before and after using 250 ml oral contrast agents (1:5 diluted Gd-DTPA, 1.488 g/L). All MR images were acquired using a 1.5 T whole body MR scanner (Vision Plus, Siemens). MRCP was acquired using two-dimensional single slice fast spin-echo sequence and HASTE (half-fourier acquisition single-shot fast spin echo) sequence. Results: The phantom study showed that the dilution ratio 1:5 of Gd-DTPA oral contrast agent was best in decreasing the signal intensity both in T 2 WI (59.3%) and in HASTE sequence (82.45%). All the dilution ratio of Gd-DTPA oral contrast agent decreased the signal intensity up to 90% on single slice MRCP. In all the patients the high signal intensity from the stomach and intestinal fluid was completely suppressed. The depictions of common bile duct and pancreatic duct were markedly improved by the oral contrast agent (P<0.05). Conclusion: 1:5 diluted (1.488 g/L) oral MR contrast agent Gd-DTPA can be an effective and safe negative contrast agent in eliminating signal intensity of the gastrointestinal tract, thus improving the depiction of the biliary system in MRCP

Contrast agent choice for intravenous coronary angiography

International Nuclear Information System (INIS)

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

1989-01-01

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 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 contains a 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

Evaluation of oral abdominal contrast agent containing ferric ammonium citrate

International Nuclear Information System (INIS)

Shiga, Toshiko; Kawamura, Yasutaka; Iwasaki, Toshiko

1991-01-01

We evaluated the effectiveness of oral MRI contrast agent containing ferric ammonium citrate. Twenty patients were arbitrarily divided into 2 groups according to the given dose of 100 and 200 mg Fe of oral MRI contrast agent. MRI was performed before and immediately after ingesting 300 ml solution of oral MRI contrast agent using a 1.5 T superconducting system (GE: Signa). Each dose of 100 and 200 mg Fe of oral MRI contrast agent produced sufficient enhancement of gastrointestinal tract, enough to make clear the pancreatic contour and porta hepatis. There was no significant change in blood and urine analysis observed after taking oral MRI contrast agent. The use of ferric ammonium citrate as an oral MRI contrast agent seems to add valuable information in performing upper abdominal MRI imaging. (author)

Micro-radiography of biological samples with medical contrast agents

International Nuclear Information System (INIS)

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

2013-01-01

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

Micro-radiography of biological samples with medical contrast agents

Energy Technology Data Exchange (ETDEWEB)

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

2013-12-01

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

Gadolinium-based contrast agents in pediatric magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

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

2017-05-15

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

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

Science.gov (United States)

Takeshita, Keizo; Kinoshita, Shota; Okazaki, Shoko

2012-01-01

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

Neuroimaging: do we really need new contrast agents for MRI?

International Nuclear Information System (INIS)

Roberts, T.P.L.; Chuang, N.; Roberts, H.C.

2000-01-01

The use of exogenous contrast media in magnetic resonance imaging of the brain has brought dramatic improvement in the sensitivity of detection and delineation of pathological structures, such as primary and metastatic brain tumors, inflammation and ischemia. Disruption of the blood brain barrier leads to accumulation of the intravenously injected contrast material in the extravascular space, leading to signal enhancement. Magnetic resonance angiography benefits from T 1 -shortening effects of contrast agent, improving small vessel depiction and providing vascular visualization even in situations of slow flow. High speed dynamic MRI after bolus injection of contrast media allows tracer kinetic modeling of cerebral perfusion. Progressive enhancement over serial post-contrast imaging allows modeling of vascular permeability and thus quantitative estimation of the severity of blood brain barrier disruption. With such an array of capabilities and ever improving technical abilities, it seems that the role of contrast agents in MR neuroimaging is established and the development of new agents may be superfluous. However, new agents are being developed with prolonged intravascular residence times, and with in-vivo binding of ever-increasing specificity. Intravascular, or blood pool, agents are likely to benefit magnetic resonance angiography of the carotid and cerebral vessels; future agents may allow the visualization of therapeutic drug delivery, the monitoring of, for example, gene expression, and the imaging evaluation of treatment efficacy. So while there is a substantial body of work that can be performed with currently available contrast agents, especially in conjunction with optimized image acquisition strategies, post processing, and mathematical analysis, there are still unrealized opportunities for novel contrast agent introduction, particularly those exploiting biological specificity. This article reviews the current use of contrast media in magnetic resonance

Gd-HOPO Based High Relaxivity MRI Contrast Agents

Energy Technology Data Exchange (ETDEWEB)

Datta, Ankona; Raymond, Kenneth

2008-11-06

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

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

Science.gov (United States)

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

2010-09-01

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

Magnetic Resonance Imaging Contrast Agents: A Review of Literature

Directory of Open Access Journals (Sweden)

Zahra Sahraei

2015-10-01

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

Semiconducting polymer dot as a highly effective contrast agent for photoacoustic imaging

Science.gov (United States)

Yuan, Zhen; Zhang, Jian

2018-02-01

In this study, we developed a novel PIID-DTBT based semiconducting polymer dots (Pdots) that have broad and strong optical absorption in the visible-light region (500 nm - 700 nm). Gold nanoparticles (GNPs) and gold nanorods (GNRs) that have been verified as an excellent photoacoustic contrast agent were compared with Pdots based on photoacoustic imaging method. Both ex vivo and in vivo experiment demonstrated Pdots have a better photoacoustic conversion efficiency at 532 nm than GNPs and similar photoacoustic performance with GNRs at 700 nm at the same mass concentration. Our work demonstrates the great potential of Pdots as a highly effective contrast agent for precise localization of lesions relative to the blood vessels based on photoacoustic tomography imaging.

Effects of contrast agents on the fallopian tube in a rabbit model

International Nuclear Information System (INIS)

Moore, D.E.

1989-01-01

Selection of the optimal contrast agent for hysterosalpingography was the focus of this study. The authors have evaluated the effect of different iodinated contrast agents on the fallopian tube of a rabbit. Ethiodol (oil-soluble contrast agent), methylglucamine iothalomate (water-soluble ionic agent) 30% and 60%, and Ioxilan (water-soluble monionic contrast agent) were compared. The agents were introduced by fallopian tube catheterization. Findings suggested that nonionic water-soluble contrast agents were the least detrimental to the fallopian tube and surrounding tissue. Iothalomate 60% resulted in mild inflammatory changes. Oil-soluble contrast agents caused granulomatous reaction and fibrinous adhesions

Apparition of iodinated contrast agents in twin neonatal gastrointestinal tracts after maternal contrast-enhanced computed tomography

International Nuclear Information System (INIS)

Kato, Hiroki; Kanematsu, Masayuki; Kato, Zenichiro; Kondo, Naomi; Orii, Kenji E.; Morimoto, Masahiro

2011-01-01

We describe a case of the appearance of iodinated contrast agents in the same locations of twins' neonatal gastrointestinal tracts 1 day after maternal contrast-enhanced computed tomography (CT). The CT examination had been performed on the expectant mother for suspected deep venous thrombosis on the day previous to the twin delivery. At 23 h after the CT examination and after cesarean section, iodinated contrast agents appeared in the same place in the twins' neonatal gastrointestinal tracts, mainly in the ascending colon, on plain abdominal radiographs. Radiologists, obstetricians, and pediatricians should understand the mechanism of appearance of iodinated contrast agents in fetal gastrointestinal tracts when the expectant mother had been given iodinated contrast agents intravenously shortly before delivery. (author)

Influence of radiographic contrast agents on quantitative coronary angiography

International Nuclear Information System (INIS)

Jost, Stefan; Hausmann, Dirk; Lippolt, Peter; Gerhardt, Uwe; Lichtlen, Paul R.

1997-01-01

Purpose. Quantitative angiographic studies on the vasomotility of epicardial coronary arteries are gaining increasing relevance. We investigated whether radiographic contrast agents might influence coronary vasomotor tone and thereby the results of such studies. Methods. Coronary angiograms were taken in 12 patients with coronary artery disease at intervals of 5, 3, 2, and 1 min with the low-osmolar, nonionic contrast agent iopamidol 300, and were repeated at identical intervals with the high-osmolar, ionic agent diatrizoate 76%. Results. Quantitative cine film analysis demonstrated no significant diameter changes in angiographically normal and stenotic coronary arteries with iopamidol. With diatrizoate, however, normal segments were dilated 2%±2% (p<0.01) after 2 min and 10%±3% after the 1 min interval (p<0.001). Stenoses showed no uniform responses to diatrizoate. Conclusion. Low-osmolar, nonionic contrast agents should be preferred for quantitative angiographic studies on epicardial coronary vasomotility. When using ionic contrast agents, injection intervals of at least 3 min are required

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

Science.gov (United States)

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.

Cationic Contrast Agent Diffusion Differs Between Cartilage and Meniscus.

Science.gov (United States)

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.

Contrasts agents in magnetic resonance imaging

International Nuclear Information System (INIS)

Bonnet, P.A.; Fernandez, J.P.; Milhavet, J.C.; Chapat, J.P.; Almes, C.; Bruel, J.M.; Rouanet, J.P.; Lamarque, J.L.

1984-01-01

Changing different parameters involved in imaging procedures, paramagnetic substances provide contrast enhancement in MRI. Contrast agents presently studied in animals and clinical trials, are either salts or complexes of mineral ions either nitroxide stable free radicals. Their development should extend the possibilities of tissular characterization and fonctional or metabolic evaluation of the MRI [fr

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

Science.gov (United States)

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

2006-01-01

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

The use of contrast agents in cardiac MRI

International Nuclear Information System (INIS)

Maurer, A.H.; Osbakken, M.

1988-01-01

Inherent NMR phenomena such as T/sub 1/ and T/sub 2/, and proton density can be used to provide tissue contrast on MR images. However, there are times when this contrast is not sufficient or does not provide tissue characterization data sufficient for use in definition of a pathophysiological insult. In this later case, paramagnetic agents might be of use in enhancement of relaxation time differences in one tissue or one portion of a tissue compared to another. Although several agents have been evaluated in this regard, most have been found inadequate because of their tissue toxicity. At present, gadolinium diethylenetriamine pentaacetric acid (Gd-DTPA) (which is an agent used in nuclear medicine studies) appears to be a good agent to use to distinguish normal from ischemic tissue. This agent has been used by a number of investigators to evaluate myocardial ischemia and provides images with better sensitivity and specificity for ischemia than imaging techniques using natural tissue contrast based on T/sub 1/ and T/sub 2/ differences

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

DEFF Research Database (Denmark)

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

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

Correlation of contrast agent kinetics between iodinated contrast-enhanced spectral tomosynthesis and gadolinium-enhanced MRI of breast lesions

International Nuclear Information System (INIS)

Froeling, Vera; Diekmann, Felix; Renz, Diane M.; Fallenberg, Eva M.; Steffen, Ingo G.; Diekmann, Susanne; Schmitzberger, Florian F.; Lawaczeck, Ruediger

2013-01-01

Assessment of contrast agent kinetics in contrast-enhanced MRI (CE-MRI) with gadolinium-containing contrast agents offers the opportunity to predict breast lesion malignancy. The goal of our study was to determine if similar patterns exist for spectral contrast-enhanced digital breast tomosynthesis (CE-DBT) using an iodinated contrast agent. The protocol of our prospective study was approved by the relevant institutional review board and the German Federal Office for Radiation Protection. All patients provided written informed consent. We included 21 women with a mean age of 62.4 years. All underwent ultrasound-guided biopsy of a suspect breast lesion, spectral CE-DBT and CE-MRI. For every breast lesion, contrast agent kinetics was assessed by signal intensity-time curves for spectral CE-DBT and CE-MRI. Statistical comparison used Cohen's kappa and Spearman's rho test. Spearman's rho of 0.49 showed significant (P = 0.036) correlation regarding the contrast agent kinetics in signal intensity-time curves for spectral CE-DBT and CE-MRI. Cohen's kappa indicated moderate agreement (kappa = 0.438). There is a statistically significant correlation between contrast agent kinetics in the signal intensity-time curves for spectral CE-DBT and CE-MRI. Observing intralesional contrast agent kinetics in spectral CE-DBT may aid evaluation of malignant breast lesions. (orig.)

CEST and PARACEST MR contrast agents

International Nuclear Information System (INIS)

Hancu, Ileana; Dixon, W. Thomas; Woods, Mark; Sherry, A. Dean; Vinogradov, Elena; Lenkinski, Robert E.

2010-01-01

In this review we describe the status of development for a new class of magnetic resonance (MR) contrast agents, based on chemical exchange saturation transfer (CEST). The mathematics and physics relevant to the description of the CEST effect in MR are presented in an appendix published in the online version only. We discuss the issues arising when translating in vitro results obtained with CEST agents to using these MR agents in in vivo model studies and in humans. Examples are given on how these agents are imaged in vivo. We summarize the status of development of these CEST agents, and speculate about the next steps that may be taken towards the demonstration of CEST MR imaging in clinical applications

SU-F-T-664: The Efficacy of Gold Nanoparticles as Contrast Agents in Mice

Energy Technology Data Exchange (ETDEWEB)

Yuan, Y; Zhang, Y; Sajo, E [University of Massachusetts Lowell, Lowell, MA (United States); Yasmin-Karim, S; Karve, A [Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (United States); Ngwa, W [University of Massachusetts Lowell, Lowell, MA (United States); Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA (United States)

2016-06-15

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 lung 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.

Ultrasound Contrast Agent Microbubble Dynamics

NARCIS (Netherlands)

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

2010-01-01

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

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

Directory of Open Access Journals (Sweden)

Justin J. Tse

2017-01-01

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

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

International Nuclear Information System (INIS)

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

2012-01-01

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

The effects of water soluble contrast agents on the respiratory tract

International Nuclear Information System (INIS)

Lovett, I.; Donchey, S.; Doust, B.; Branson, J.; Munro, V.

1989-01-01

The water soluble contrast agents Gastrografin R (Sodium diatrizoate and meglumine diatrizoate, Schering, Berlin), Iopamiro 300 R (Iopamidol, Schering, Berlin), and Dionosil Aqueous R (propyliodone BP, Glaxo, England) were instilled into the tracheobronchial tree of rats in doses of either 0.1 ml and 0.25 ml. Rats being used as controls, underwent sham operations with the instillation of air instead of contrast agent. In all, 85 rats were used. All rats that had not already died from the effects of contrast agent were sacrificed 30 minutes after instillation. The relative effects of the contrast agents were measured by comparing: survival time; radiographic effects of the contrast agents on the lungs; and pathological changes as estimated by post mortem lung section and microscopy. The least toxic agent was the one with the lowest osmotic activity, namely Aqueous Dionosil. It is therefore recommended that Aqueous Dionosil be used in preference to Gastrografin or Iopamidol for studies of the oesophagus whenever there is a danger of aspiration of contrast agent into the tracheobronchial tree. 11 refs., 3 figs., 5 tabs

Development of microbubble contrast agents for high frequency ultrasound microscopy

Energy Technology Data Exchange (ETDEWEB)

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

2007-05-15

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

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

Science.gov (United States)

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

2013-01-01

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

Modeling of ultrasound propagation through contrast agents

NARCIS (Netherlands)

Grootens, J.J.F.A.H.; Mischi, M.; Böhmer, M.; Korsten, H.; Aarts, R.M.; Vander Sloten, Jos; Verdonck, Pascal; Nyssen, Marc

2008-01-01

In the past years many advances have been made in the detection of ultrasound contrast agents (UCA) by exploiting their nonlinear behavior. However, little attention has been paid to the nonlinear distortion of ultrasound (US) waves propagating through contrast media. The aim of this study is to

Spectral triangulation molecular contrast optical coherence tomography with indocyanine green as the contrast agent

OpenAIRE

Yang, Changhuei; McGuckin, Laura E. L.; Simon, John D.; Choma, Michael A.; Applegate, Brian E.; Izatt, Joseph A.

2004-01-01

We report a new molecular contrast optical coherence tomography (MCOCT) implementation that profiles the contrast agent distribution in a sample by measuring the agent's spectral differential absorption. The method, spectra triangulation MCOCT, can effectively suppress contributions from spectrally dependent scatterings from the sample without a priori knowledge of the scattering properties. We demonstrate molecular imaging with this new MCOCT modality by mapping the distribution of indocyani...

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

Science.gov (United States)

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.

Targeting cancer chemotherapeutic agents by use of lipiodol contrast medium

International Nuclear Information System (INIS)

Konno, T.

1990-01-01

Arterially administered Lipiodol Ultrafluid contrast medium selectively remained in various malignant solid tumors because of the difference in time required for the removal of Lipiodol contrast medium from normal capillaries and tumor neovasculature. Although blood flow was maintained in the tumor, even immediately after injection Lipiodol contrast medium remained in the neovasculature of the tumor. To target anti-cancer agents to tumors by using Lipiodol contrast medium as a carrier, the characteristics of the agents were examined. Anti-cancer agents had to be soluble in Lipiodol, be stable in it, and separate gradually from it so that the anti-cancer agents would selectively remain in the tumor. These conditions were found to be necessary on the basis of the measurement of radioactivity in VX2 tumors implanted in the liver of 16 rabbits that received arterial injections of 14C-labeled doxorubicin. Antitumor activities and side effects of arterial injections of two types of anti-cancer agents were compared in 76 rabbits with VX2 tumors. Oily anti-cancer agents that had characteristics essential for targeting were compared with simple mixtures of anti-cancer agents with Lipiodol contrast medium that did not have these essential characteristics. Groups of rabbits that received oily anti-cancer agents responded significantly better than groups that received simple mixtures, and side effects were observed more frequently in the groups that received the simple mixtures. These results suggest that targeting of the anti-cancer agent to the tumor is important for treatment of solid malignant tumors

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

Science.gov (United States)

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

2005-10-01

To detect specific cardiomyocyte injury induced by myocardial contrast material-enhanced echocardiography (ie, myocardial contrast echocardiography) in rats and to ascertain the influences of contrast material dose and ultrasound exposure on this injury. All animal procedures were approved by the university committee for the use and care of animals. Myocardial contrast echocardiography with 1:4 electrocardiographic (ECG) triggering was performed at 1.5 MHz in 61 anesthetized rats. Evans blue (EB) dye was injected as the vital stain for cardiomyocyte injury. At the start of myocardial contrast echocardiography, which lasted 10 minutes, perflutren lipid microsphere-based contrast material was infused through the tail vein for 5 minutes. Premature heartbeats were counted from the ECG record. The numbers of EB-stained cells counted on sections of heart specimens obtained 24 hours after myocardial contrast echocardiography and then either fresh frozen or embedded in paraffin were determined by using fluorescence microscopy. Results were compared statistically by using t tests and Mann-Whitney rank sum tests. EB-stained cells were concentrated in the anterior region of the myocardium. In the paraffin-embedded specimens, EB-stained cells were often accompanied by but largely separate from areas of inflammatory cell infiltration. At end-systolic triggering with a 50 microL/kg dose of microsphere contrast material, the EB-stained cell count increased with increasing peak rarefactional pressure amplitude, with significantly increased cell counts at 1.6 MPa (P .1). EB-stained cell counts increased with increasing contrast material dose, from 10 to 50 microL/kg, at 2.0 MPa. Cardiomyocyte injury was induced by the interaction of ultrasound pulses with contrast agent microbubbles during myocardial contrast echocardiography in rats, and the numbers of injured cells increased with increasing contrast agent dose and ultrasound exposure. RSNA, 2005

The clinical use of contrast agents in magnetic resonance imaging

International Nuclear Information System (INIS)

Bydder, G.M.

1987-01-01

Interest in the use of external agents to increase tissue contrasts has come from many sources dating back to the earliest work in NMR, to animal studies and to the widespread use of contrast agents in conventional radiological practice. The first clinical magnetic resonance images were published in 1980 and in the following year a brief account of the use of the paramagnetic agents in human volunteers was established. It was apparent relatively early in the development of magnetic resonance imaging (MRI) that a high level of soft tissue contrast was available de novo and the need for externally administered agents might therefore be small. This observation was tempered by the fact that separation of tumour from oedema was frequently better with contrast enhanced CT X-ray than with unenhanced MRI and that of a contrast agent might therefore be needed for MRI. At the end of 1983 the first parenteral agent gadoliminum diethylene triamine pentaacetic acid (Gd-DTPA) was used in volunteers and clinical studies began in 1984. At the present time only molecular O/sub 2/, oral iron compounds and Gd-DTPA are in clinical use although there are a number of other agents which have been used in animals and some of these may become available for clinical use in the foreseeable future

A prospective evaluation of the contrast, radiation dose and image quality of contrast-enhanced CT scans of paediatric abdomens using a low-concentration iodinated contrast agent and low tube voltage combined with 70% ASIR algorithm.

Science.gov (United States)

Wang, Xiaoxia; Zhong, Yumin; Hu, Liwei; Xue, Lianyan; Shi, Meihua; Qiu, Haisheng; Li, Jianying

2016-09-01

To quantitatively and subjectively assess the image quality of and radiation dose for an abdominal enhanced computed tomography (CT) scan with a low tube voltage and a low concentration of iodinated contrast agent in children. Forty-eight patients were randomised to one of the two following protocols: Group A (n=24, mean age 46.96±44.65 months, mean weight 15.71±9.11 kg, BMI 16.48±2.40 kg/m(2) ) and Group B (n=24, mean age 41.33±44.59 months, mean weight 18.15±17.67 kg, BMI 17.50±3.73 kg/m(2) ). Group A: 80 kVp tube voltage, 270 mg iodine (I)/mL contrast agent (Visipaque, GE Healthcare) and images were reconstructed using 70% adaptive statistical iterative reconstruction (ASIR). Group B: 100 kVp tube voltage, 370 mg I/mL contrast agent (Iopamiro, Bracco) and images were reconstructed using 50% ASIR. The volume of the contrast agent was 1.30 mL/kg in both Groups A and B. The degree of enhancement and noise in the abdominal aorta (AO) in the arterial phase (AP) and the portal vein (PV) in the portal venous phase (PVP) was measured; while the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for the AO and PV were calculated. A 5-point scale was used to subjectively evaluate the image quality and image noise by two radiologists with more than 10 years of experience. Dose-length product (DLP) (mGy-cm) and CTDIvol (mGy) were calculated. Objective measurements and subjective quality scores for the two groups were compared using paired t-tests and Mann-Whitney U tests, respectively. There was no significant difference in age, weight or body mass index (BMI) between the two groups (all P>.5). The iodine load in Group A (5517.3±3197.2 mg I) was 37% lower than that in Group B (8772.1±8474.6 mg I), although there was no significant difference between them (P=.111). The DLP and the CT dose index (CTDIvol ) for Group A were also lower than for Group B, but were not statistically significantly different (DLP, 104 mGy-cm±45.81 vs 224.5�

Severe reactions to iodinated contrast agents: is anaphylaxis responsible?

International Nuclear Information System (INIS)

Dewachter, P.; Mouton-Faivre, C.

2001-01-01

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

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

International Nuclear Information System (INIS)

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

2016-01-01

Highlights: • SPIONs were conjugated with EGTA by EDC/sulfo-NHS method. • The presence of Ca"2"+ induced the aggregation of EGTA-SPIONs. • The aggregation of EGTA-SPIONs increased the T2 relaxation time. • EGTA-SPIONs can be used for the calcium imaging with MRI. - Abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) as T2 contrast agents have great potential to sense calcium ion (Ca"2"+) using magnetic resonance imaging (MRI). Here we prepared calcium-responsive SPIONs for MRI, formed by combining poly(ethylene glycol) (PEG) and polyethylenimine (PEI) coated iron oxide nanoparticle (PEI/PEG-SPIONs) contrast agents with the straightforward calcium-sensing compound EGTA (ethylene glycol tetraacetic acid). EGTA was conjugated onto PEI/PEG-SPIONs using EDC/sulfo-NHS method. EGTA-SPIONs were characterized using TEM, XPS, DSL, TGA and SQUIID. DSL results show that the SPIONs aggregate in the presence of Ca"2"+. MRI analyses indicate that the water proton T2 relaxation rates in HEPES suspensions of the EGTA-SPIONs significantly increase with the calcium concentration because the SPIONs aggregate in the presence of Ca"2"+. The T2 values decreased 25% when Ca"2"+ concentration decreased from 1.2 to 0.8 mM. The aggregation of EGTA-SPIONs could be reversed by EDTA. EGTA-SPIONs have potential as smart contrast agents for Ca"2"+-sensitive MRI.

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-12-15

Highlights: • SPIONs were conjugated with EGTA by EDC/sulfo-NHS method. • The presence of Ca{sup 2+} induced the aggregation of EGTA-SPIONs. • The aggregation of EGTA-SPIONs increased the T2 relaxation time. • EGTA-SPIONs can be used for the calcium imaging with MRI. - Abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) as T2 contrast agents have great potential to sense calcium ion (Ca{sup 2+}) using magnetic resonance imaging (MRI). Here we prepared calcium-responsive SPIONs for MRI, formed by combining poly(ethylene glycol) (PEG) and polyethylenimine (PEI) coated iron oxide nanoparticle (PEI/PEG-SPIONs) contrast agents with the straightforward calcium-sensing compound EGTA (ethylene glycol tetraacetic acid). EGTA was conjugated onto PEI/PEG-SPIONs using EDC/sulfo-NHS method. EGTA-SPIONs were characterized using TEM, XPS, DSL, TGA and SQUIID. DSL results show that the SPIONs aggregate in the presence of Ca{sup 2+}. MRI analyses indicate that the water proton T2 relaxation rates in HEPES suspensions of the EGTA-SPIONs significantly increase with the calcium concentration because the SPIONs aggregate in the presence of Ca{sup 2+}. The T2 values decreased 25% when Ca{sup 2+} concentration decreased from 1.2 to 0.8 mM. The aggregation of EGTA-SPIONs could be reversed by EDTA. EGTA-SPIONs have potential as smart contrast agents for Ca{sup 2+}-sensitive MRI.

Macromolecular and dendrimer-based magnetic resonance contrast agents

Energy Technology Data Exchange (ETDEWEB)

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

2010-09-15

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

In vivo Photoacoustic Imaging of Prostate Cancer Using Targeted Contrast Agent

Science.gov (United States)

2016-11-01

AD______________ AWARD NUMBER: W81XWH-14-1-0242 TITLE: In Vivo Photoacoustic Imaging of Prostate Cancer Using Targeted Contrast Agent PRINCIPAL...TITLE AND SUBTITLE In vivo Photoacoustic Imaging of Prostate Cancer Using T argeted Contrast Agent 5a. CONTRACT NUMBER W81XWH-14-1-0242 5b. GRANT...diagnose prostate cancer based on the near-infrared optical absorption of either endogenous tissue constituents or exogenous contrast agents . Although

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

Science.gov (United States)

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

2017-06-06

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

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

Directory of Open Access Journals (Sweden)

Antonella Antonelli

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-10-15

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

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

International Nuclear Information System (INIS)

Lee, Hak Jong; Yoon, Tae Jong; Yoon, Young Il

2017-01-01

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

Use of carbon dioxide as an intravascular contrast agent: A review of current literature

OpenAIRE

Ali, Fahad; Mangi, Muhammad Asif; Rehman, Hiba; Kaluski, Edo

2017-01-01

Use of X-ray contrast allows us to differentiate between two or more adjacent structures on radiographic studies. The X-ray contrast agent can be the one with increase X-ray absorption, like iodine and a barium X-ray contrast agent or the one with decrease X-ray absorption like air and carbon dioxide contrast agent. Each contrast agent possesses different risks and benefits in various ways. Carbon dioxide as an intravascular contrast agent can be used as an alternative intravascular contrast ...

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

DEFF Research Database (Denmark)

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

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

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

Energy Technology Data Exchange (ETDEWEB)

Lemelle, A; Veksler, B; Piletsky, S A; Meglinski, I [Cranfield Health, Cranfield University, Cranfield, MK43 0AL (United Kingdom); Kozhevnikov, I S; Akchurin, G G, E-mail: a.lemelle.s06@cranfield.ac.uk [Physics Faculty, Saratov State University, Saratov 410012 (Russian Federation)

2009-01-15

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.

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

International Nuclear Information System (INIS)

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

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

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

Paul A. Dayton

2004-04-01

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

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

International Nuclear Information System (INIS)

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

2015-01-01

We report evidence for the possible application of chitosan-coated nickel-ferrite (NiFe 2 O 4 ) nanoparticles as both T 1 and T 2 contrast agents in magnetic resonance imaging (MRI). The coating of nickel-ferrite nanoparticles with chitosan was performed simultaneously with the synthesis of the nickel-ferrite nanoparticles by a chemical co-precipitation method. The coated nanoparticles were cylindrical in shape with an average length of 17 nm and an average width of 4.4 nm. The bonding of chitosan onto the ferrite nanoparticles was confirmed by Fourier transform infrared spectroscopy. The T 1 and T 2 relaxivities were 0.858±0.04 and 1.71±0.03 mM −1 s −1 , respectively. In animal experimentation, both a 25% signal enhancement in the T 1 -weighted mage and a 71% signal loss in the T 2 -weighted image were observed. This demonstrated that chitosan-coated nickel-ferrite nanoparticles are suitable as both T 1 and T 2 contrast agents in MRI. We note that the applicability of our nanoparticles as both T 1 and T 2 contrast agents is due to their cylindrical shape, which gives rise to both inner and outer sphere processes of nanoparticles. - Highlights: • Chitosan-coated nickel-ferrite (Ni-Fe 2 O 4 ) nanoparticles were synthesized in an aqueous system by chemical co-precipitation. • The characterization of bare and chitosan-coated nanoparticles were performed using various analytical tools, such as TEM, FTIR, XRD, and VMS. • We evaluated the coated particles as potential T 1 and T 2 contrast agents for MRI by measuring T 1 and T 2 relaxation times as a function of iron concentration. • Both T 1 and T 2 effects were also observed in animal experimentation

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

Science.gov (United States)

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

Investigation of contrast agent dosage for perfusion-weighted MRI

International Nuclear Information System (INIS)

Erb, G.; Benner, T.; Heiland, S.; Reith, W.; Sartor, K.; Forsting, M.

1997-01-01

Purpose: In this study we investigated, whether increasing the dosage of a paramagnetic contrast agent results in a stronger signal decrease in T 2 *-weighted perfusion sequences and therefore more meaningful parameter maps. Material and methods: In a prospective study bolus injection of gadolinium-DTPA was performed at dosages of 0.1, 0.2, and 0.3 mmol/kg body weight (BW) in 10 patients each. Before, during and after bolus injection 40 T 2 *-weighted images of a reference brain slice were acquired within 65.6 seconds on a 1.0 T clinical scanner and perfusion parameters were calculated. Results: Due to the limited signal decrease during bolus passage and the resulting low signal-difference-to-noise ratio (ΔS/N) no reliable differentiation of gray and white matter was possible at a contrast agent dosage of 0.1 mmol/kg BW. Only at higher dosages, both, signal decrease and ΔS/N were strong enough to allow differentiation of gray and white matter and to yield reliable parameter maps. Conclusion: For meaningful MR perfusion imaging at 1.0 T and with the given sequence a contrast agent dosage of at least 0.2 mmol/kg BW is necessary, if a 0.5-molar contrast agent is used. (orig.) [de

Ultrasound contrast-agent improves imaging of lower limb occlusive disease

DEFF Research Database (Denmark)

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

2003-01-01

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

Cellulose nanoparticles: photoacoustic contrast agents that biodegrade to simple sugars

Science.gov (United States)

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

2014-03-01

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

Quinone-fused porphyrins as contrast agents for photoacoustic imaging

KAUST Repository

Banala, Srinivas

2017-06-27

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

Safety of ultrasound contrast agents in stress echocardiography.

Science.gov (United States)

Gabriel, Ruvin S; Smyth, Yvonne M; Menon, Venu; Klein, Allan L; Grimm, Richard A; Thomas, James D; Sabik, Ellen Mayer

2008-11-01

Definity and Optison are perflutren-based ultrasound contrast agents used in echocardiography. United States Food and Drug Administration warnings regarding serious cardiopulmonary reactions and death after Definity administration highlighted the limited safety data in patients who undergo contrast stress echocardiography. From 1998 and 2007, 2,022 patients underwent dobutamine stress echocardiography and 2,764 underwent exercise stress echocardiography with contrast at the Cleveland Clinic. The echocardiographic database, patient records, and the Social Security Death Index were reviewed for the timing and cause of death, severe adverse events, arrhythmias, and symptoms. Complication rates for contrast dobutamine stress echocardiography and exercise stress echocardiography were compared with those in a control group of 5,012 patients matched for test year and type who did not receive contrast. Ninety-five percent of studies were performed in outpatients. There were no differences in the rates of severe adverse events (0.19% vs 0.17%, p = 0.7), death within 24 hours (0% vs 0.04%, p = 0.1), cardiac arrest (0.04% vs 0.04%, p = 0.96), and sustained ventricular tachycardia (0.2% vs 0.1%, p = 0.32) between patients receiving and not receiving intravenous contrast, respectively. In conclusion, severe adverse reactions to intravenous contrast agents during stress echocardiography are uncommon. Contrast use does not add to the baseline risk for severe adverse events in patients who undergo stress echocardiography.

Ultrasound-induced Gas Release from Contrast Agent Microbubbles

NARCIS (Netherlands)

Postema, M.A.B.; Postema, Michiel; Bouakaz, Ayache; Versluis, Michel; de Jong, N.

2005-01-01

We investigated gas release from two hard-shelled ultrasound contrast agents by subjecting them to high-mechanical index (MI) ultrasound and simultaneously capturing high-speed photographs. At an insonifying frequency of 1.7 MHz, a larger percentage of contrast bubbles is seen to crack than at 0.5

Process for preparation of MR contrast agents

DEFF Research Database (Denmark)

2002-01-01

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

State and development of new clinical contrast agents for MR diagnosis of liver diseases

International Nuclear Information System (INIS)

Rummeny, E.J.; Peters, P.E.

1992-01-01

MR contrast agents are developed for pharmaceutical manipulation of tissue signal intensities. Today it is widely recognized that MR contrast agents will play an increasingly important role in MR imaging of the liver. Contrast-enhanced MR-imaging allows to obtain simultaneously dynamic physiologic information and high anatomci detail. Up to now three major classes of MR contrast agents are available for clinical MR-imaging of the liver. These include paramagnetic perfusion agents, hepatobiliary agents, and superparamagnetic RES-specific iron oxide particles. A fourth class of contrast agents now in use for animal experiments includes ultrasmall superparamagnetic particles which can be targeted to extrareticuloendothelial structures such as asialoglycoprotein receptors of hepatocytes. In this article, we review recent advances in the development of MR contrast media and the clinical of contrast-enhanced MR imaging of the liver. (orig.) [de

Evaluation of date syrup as an oral negative contrast agent for MRCP.

Science.gov (United States)

Govindarajan, Arunkumar; Lakshmanan, Prakash Manikka; Sarawagi, Radha; Prabhakaran, Velu

2014-11-01

The purpose of this study was to compare the in vitro effects of date syrup with those of other contrast agents by qualitative and quantitative analysis and in vivo evaluation of the use of date syrup to improve the quality of MRCP images. Phantoms containing date syrup, ferumoxsil, pineapple juice, and water were imaged by 1.5-T MRI with T2-weighted and MRCP sequences, and signal-to-noise ratios were calculated. Biochemical analysis of date syrup was performed to find the nature of iron in it, and the iron content was quantified by energy-dispersive x-ray spectroscopy. Sixty patients underwent MRCP before and 30 minutes after ingestion of 100 mL of date syrup. Unenhanced and contrast-enhanced images were scored for gastrointestinal tract signal suppression and visualization of various pancreaticobiliary structures. In vitro evaluation showed that images obtained with date syrup had a signal-to-noise ratio comparable to that of images obtained with ferumoxsil in T2-weighted and MRCP sequences. The iron concentration in date syrup was 2.6 mg/dL, and it was in ferric form. Images obtained after oral contrast administration had statistically significant improvement in gastrointestinal tract signal suppression (p Date syrup can be used as a negative oral contrast agent for gastrointestinal tract signal suppression during MRCP and for improving visualization of various pancreaticobiliary structures.

The advantage of high relaxivity contrast agents in brain perfusion

International Nuclear Information System (INIS)

Cotton, F.; Hermier, M.

2006-01-01

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

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

Directory of Open Access Journals (Sweden)

Estelrich J

2015-03-01

Full Text Available Joan Estelrich,1,2 María Jesús Sánchez-Martín,1 Maria Antònia Busquets1,2 1Departament de Fisicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Catalonia, Spain; 2Institut de Nanociència I Nanotecnologia (IN2UB, Barcelona, Catalonia, SpainAbstract: Magnetic resonance imaging (MRI has become one of the most widely used and powerful tools for noninvasive clinical diagnosis owing to its high degree of soft tissue contrast, spatial resolution, and depth of penetration. MRI signal intensity is related to the relaxation times (T1, spin–lattice relaxation and T2, spin–spin relaxation of in vivo water protons. To increase contrast, various inorganic nanoparticles and complexes (the so-called contrast agents are administered prior to the scanning. Shortening T1 and T2 increases the corresponding relaxation rates, 1/T1 and 1/T2, producing hyperintense and hypointense signals respectively in shorter times. Moreover, the signal-to-noise ratio can be improved with the acquisition of a large number of measurements. The contrast agents used are generally based on either iron oxide nanoparticles or ferrites, providing negative contrast in T2-weighted images; or complexes of lanthanide metals (mostly containing gadolinium ions, providing positive contrast in T1-weighted images. Recently, lanthanide complexes have been immobilized in nanostructured materials in order to develop a new class of contrast agents with functions including blood-pool and organ (or tumor targeting. Meanwhile, to overcome the limitations of individual imaging modalities, multimodal imaging techniques have been developed. An important challenge is to design all-in-one contrast agents that can be detected by multimodal techniques. Magnetoliposomes are efficient multimodal contrast agents. They can simultaneously bear both kinds of contrast and can, furthermore, incorporate targeting ligands and chains of polyethylene glycol to enhance the accumulation of

Dynamic contrast-enhanced MRI using a macromolecular MR contrast agent (P792): Evaluation of antivascular drug effect in a rabbit VX2 liver tumor model

Energy Technology Data Exchange (ETDEWEB)

Park, Hee Sun [Dept. of Radiology, Konkuk University School of Medicine, Seoul (Korea, Republic of); Han, Joon Koo; Lee, Jeong Min; Woo, Sung Min; Choi, Byung Ihn [Seoul National University Hospital, Seoul (Korea, Republic of); Kim, Young Il [Dept. of Radiology, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah (United Arab Emirates); Choi, Jin Young [Dept. of Radiology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

2015-10-15

To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (Ktrans) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. P792 group showed a more prominent decrease in Ktrans and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent.

Dynamic contrast-enhanced MRI using a macromolecular MR contrast agent (P792): Evaluation of antivascular drug effect in a rabbit VX2 liver tumor model

International Nuclear Information System (INIS)

Park, Hee Sun; Han, Joon Koo; Lee, Jeong Min; Woo, Sung Min; Choi, Byung Ihn; Kim, Young Il; Choi, Jin Young

2015-01-01

To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (Ktrans) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. P792 group showed a more prominent decrease in Ktrans and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent

10% low density corn-oil emulsion oral contrast agent for abdominal computed tomography

International Nuclear Information System (INIS)

Choi, Sun Kyou; Chon, Dong Kwon; Han, Young Min; Kim, Chong Soo; Sohn, Myung Hee; Song, Ho Young; Choi, Ki Chul

1990-01-01

CT of the gastrointestinal tract is commonly performed after administration of a high-density diluted iodinated oral contrast material. However, because if inadequate mixing of the contrast material with the gastrointestinal contents, pseudotumor and poor mucosal visualization are frequently shown on abdominal CT. To overcome these problem, 10% corn oil emulsion (COE) is tested as an alternative oral contrast agent in 40 patients. We analyse patients tolerance, gastric mucosal visualization and discrimination of pancreas from the duodenal C-loop to 10% COE in 40 patients compared with those obtained from 35 patients, who was received high-density diluted iodinated oral contrast agent (gastrografin). The results are as follows : 1. Patients' tolerance to 10% COE is similar to that to conventional oral contrast agent. 2. Image of the gastric mucosa from patients receiving 10% COE is superior to that receiving oral contrast agent. 3. The discrimination between pancreatic head from duodenal C-loop is better in patients receiving 10% COE than in patients receiving conventional oral contrast agent. 4. In patients receiving 10% COE, differentiation of cystic masses from intestinal loops is sometimes difficult. The results of this study indicate that 10% COE may be useful oral contrast agent for optimal visualization of gastric mucosa and pancreatico-duodenal discrimination on abdominal CT

Ex Vivo Perfusion-Simulation Measurements of Microbubbles as a Scattering Contrast Agent for Grating-Based X-Ray Dark-Field Imaging.

Directory of Open Access Journals (Sweden)

Astrid Velroyen

Full Text Available The investigation of dedicated contrast agents for x-ray dark-field imaging, which exploits small-angle scattering at microstructures for contrast generation, is of strong interest in analogy to the common clinical use of high-atomic number contrast media in conventional attenuation-based imaging, since dark-field imaging has proven to provide complementary information. Therefore, agents consisting of gas bubbles, as used in ultrasound imaging for example, are of particular interest. In this work, we investigate an experimental contrast agent based on microbubbles consisting of a polyvinyl-alcohol shell with an iron oxide coating, which was originally developed for multimodal imaging and drug delivery. Its performance as a possible contrast medium for small-animal angiography was examined using a mouse carcass to realistically consider attenuating and scattering background signal. Subtraction images of dark field, phase contrast and attenuation were acquired for a concentration series of 100%, 10% and 1.3% to mimic different stages of dilution in the contrast agent in the blood vessel system. The images were compared to the gold-standard iodine-based contrast agent Solutrast, showing a good contrast improvement by microbubbles in dark-field imaging. This study proves the feasibility of microbubble-based dark-field contrast-enhancement in presence of scattering and attenuating mouse body structures like bone and fur. Therefore, it suggests a strong potential of the use of polymer-based microbubbles for small-animal dark-field angiography.

Development of organic MRI contrast agents

International Nuclear Information System (INIS)

Hayashi, Hiroyuki; Sato, Yuichiro; Karasawa, Satoru; Koga, Noboru

2008-01-01

Described are trends of the development in the title since those agents with target properties are awaited for specific organ and regional MRI. The contrast agents alter the relaxation time of water proton to yield the enhanced contrast between organs and tissues with different water volumes. Nowadays Gd-complexes and nano-particle of superparamagnetic iron oxide (Fe(III)) are widely used for enhancing in clinic. Among organic compounds with paramagnetic spin, those possessing nitroxide radical like TEMPO- and PROXYL-radicals have been subject to development by their derivatization. High spin molecules conceivably affect the relaxivity, which, however, is found smaller per spin of synthesized triplet complexes than doublet ones. This has lead to basic approach for molecules restricting water movement due to their hydrogen bond like DNA as a model, for introducing many radicals in high molecular weight compounds, and their polymer, as one of which authors have developed a derivative of hyperbranched polymer (HPS)-TEMPO having the similar relaxivity to gadolinium-diethylenetiamine pentaacetid acid (Gd-DTPA) (R.T.)

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

Science.gov (United States)

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

2018-09-01

We sought to investigate the potential of D-maltose, D-sorbitol, and D-mannitol as T 2 exchange magnetic resonance imaging (MRI) contrast agents. We also sought to compare the in vivo pharmacokinetics of D-maltose with D-glucose with dynamic contrast enhancement (DCE) MRI. T 1 and T 2 relaxation time constants of the saccharides were measured using eight pH values and nine concentrations. The effect of echo spacing in a multiecho acquisition sequence used for the T 2 measurement was evaluated for all samples. Finally, performances of D-maltose and D-glucose during T 2 -weighted DCE-MRI were compared in vivo. Estimated T 2 relaxivities (r 2 ) of D-glucose and D-maltose were highly and nonlinearly dependent on pH and echo spacing, reaching their maximum at pH = 7.0 (∼0.08 mM -1 s -1 ). The r 2 values of D-sorbitol and D-mannitol were estimated to be ∼0.02 mM -1 s -1 and were invariant to pH and echo spacing for pH ≤7.0. The change in T 2 in tumor and muscle tissues remained constant after administration of D-maltose, whereas the change in T 2 decreased in tumor and muscle after administration of D-glucose. Therefore, D-maltose has a longer time window for T 2 -weighted DCE-MRI in tumors. We have demonstrated that D-maltose can be used as a T 2 exchange MRI contrast agent. The larger, sustained T 2 -weighted contrast from D-maltose relative to D-glucose has practical advantages for tumor diagnoses during T 2 -weighted DCE-MRI. Magn Reson Med 80:1158-1164, 2018. © 2018 International Society for Magnetic Resonance in Medicine. © 2018 International Society for Magnetic Resonance in Medicine.

Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin-avidin-specific binding.

Science.gov (United States)

Liu, Yongjun; Wu, Xiaoyun; Sun, Xiaohe; Wang, Dan; Zhong, Ying; Jiang, Dandan; Wang, Tianqi; Yu, Dexin; Zhang, Na

2017-01-01

Developing magnetic resonance imaging (MRI) contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR)-targeted poly (l-lysine) (PLL)-diethylene triamine pentacetate acid (DTPA)-gadolinium (Gd) (VEGFR-targeted PLL-DTPA-Gd, VPDG), was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin-avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22%) in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG) (25.16%±4.71%, P contrast agent and held great potential for molecular diagnosis of tumor.

Evaluation of potential gastrointestinal contrast agents for echoplanar MR imaging

International Nuclear Information System (INIS)

Reimer, P.; Schmitt, F.; Ladebeck, R.; Graessner, J.; Schaffer, B.

1993-01-01

The purpose of this study was to investigate approved aqueous gastrointestinal contrast agents for use in abdominal EPI. Conventional and echoplanar MR imaging experiments were performed with 1.0 Tesla whole body systems. Phantom measurements of Gastrografin, barium sulfate suspension, oral gadopentetate dimeglumine, water, and saline were performed. Signal intensity (SI) of aqueous oral barium sulfate and iodine based CT contrast agents was lower on conventional spin-echo (SE), Flash, and Turbo-Flush images than on EP images. The contrast agents exhibited higher SI on T2-weighted SE PE images and TI-time dependence on inversion recovery EP-images. The barium sulfate suspension was administered in volunteers to obtain information about bowel lumen enhancement and susceptibility artifacts. Oral administration of the aqueous barium sulfate suspension increased bowel lumen signal and reduced susceptibility artifacts. (orig.)

Acoustically active lipospheres containing paclitaxel: a new therapeutic ultrasound contrast agent.

Science.gov (United States)

Unger, E C; McCreery, T P; Sweitzer, R H; Caldwell, V E; Wu, Y

1998-12-01

Paclitaxel-carrying lipospheres (MRX-552) were developed and evaluated as a new ultrasound contrast agent for chemotherapeutic drug delivery. Paclitaxel was suspended in soybean oil and added to an aqueous suspension of phospholipids in vials. The headspace of the vials was replaced with perfluorobutane gas; the vials were sealed, and they were agitated at 4200 rpm on a shaking device. The resulting lipospheres containing paclitaxel were studied for concentration, size, acute toxicity in mice, and acoustic activity and drug release with ultrasound. Lipospheres containing sudan black dye were produced to demonstrate the acoustically active liposphere (AAL)-ultrasound release concept. Acoustically active lipospheres containing paclitaxel had a mean particle count of approximately 1 x 10(9) particles per mL and a mean size of 2.9 microns. Acute toxicity studies in mice showed a 10-fold reduction in toxicity for paclitaxel in AALs compared with free paclitaxel. The AALs reflected ultrasound as a contrast agent. Increasing amounts of ultrasound energy selectively ruptured the AALs and released the paclitaxel. Acoustically active lipospheres represent a new class of acoustically active drug delivery vehicles. Future studies will assess efficacy of AALs for ultrasound-mediated drug delivery.

Contrast enhanced MRA: do contrast agents with a higher T1 relaxitivity improve the visualization of carotid artery stenoses?

International Nuclear Information System (INIS)

Friese, S.; Krapf, H.; Skalej, M.; Kueker, W.; Fetter, M.; Vonthein, R.

2001-01-01

CE-MRA is a powerful tool for the non-invasive evaluation of carotid artery occlusive disease. However, due to certain drawbacks, it has not completely replaced DSA. The purpose of this study was to evaluate if Gd-BOPTA, a contrast agent with high T 1 relaxivity, can increase the diagnostic accuracy of CE-MRA. Material and Methods: The CE-MRA examinations of 54 consecutive patients were evaluated by two experienced radiologists, independently. The examinations of 27 patients were contrasted either with 20 ml Gd-BOPTA or with 20 ml Gd-DTPA. The reviewers were blinded to the contrast agent chosen and to the ultrasound results. They rated the overall image quality and the degree of the ICA stenoses. Results: For the estimation of the degree of the ICA stenoses there was a high interrater validity. In comparison to the ultrasound findings, 6 of 50 high-degree stenoses were underestimated as moderate stenoses. In one of seven sonographically occluded vessels, MRA revealed residual patency in the vessel lumen. It was not possible to identify the contrast agent that was taken for a study. Subjective estimation of the image quality (arterial contrast of the ICA, contrast of the other vessels, and general impression) did not significantly change with the contrast agent employed. Conclusion: The diagnostic accuracy of CE-MRA for the evaluation of internal carotid artery stenoses is not improved by Gd-BOPTA if identical volumina of contrast media are applied. The potential of this contrast agent can be the reduction of the amount of contrast without loss of diagnostic information. Further studies are necessary. (orig.) [de

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

Energy Technology Data Exchange (ETDEWEB)

Ahmad, Tanveer [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Department of Physics, Abdul Wali Khan University, Mardan (Pakistan); Bae, Hongsub; Iqbal, Yousaf [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Rhee, Ilsu, E-mail: ilrhee@knu.ac.kr [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Hong, Sungwook [Division of Science Education, Daegu University, Gyeongsan 712-714 (Korea, Republic of); Chang, Yongmin; Lee, Jaejun [Department of Diagnostic Radiology, College of Medicine, Kyungpook National University and Hospital, Daegu 700-721 (Korea, Republic of); Sohn, Derac [Department of Physics, Hannam University, Daejon (Korea, Republic of)

2015-05-01

We report evidence for the possible application of chitosan-coated nickel-ferrite (NiFe{sub 2}O{sub 4}) nanoparticles as both T{sub 1} and T{sub 2} contrast agents in magnetic resonance imaging (MRI). The coating of nickel-ferrite nanoparticles with chitosan was performed simultaneously with the synthesis of the nickel-ferrite nanoparticles by a chemical co-precipitation method. The coated nanoparticles were cylindrical in shape with an average length of 17 nm and an average width of 4.4 nm. The bonding of chitosan onto the ferrite nanoparticles was confirmed by Fourier transform infrared spectroscopy. The T{sub 1} and T{sub 2} relaxivities were 0.858±0.04 and 1.71±0.03 mM{sup −1} s{sup −1}, respectively. In animal experimentation, both a 25% signal enhancement in the T{sub 1}-weighted mage and a 71% signal loss in the T{sub 2}-weighted image were observed. This demonstrated that chitosan-coated nickel-ferrite nanoparticles are suitable as both T{sub 1} and T{sub 2} contrast agents in MRI. We note that the applicability of our nanoparticles as both T{sub 1} and T{sub 2} contrast agents is due to their cylindrical shape, which gives rise to both inner and outer sphere processes of nanoparticles. - Highlights: • Chitosan-coated nickel-ferrite (Ni-Fe{sub 2}O{sub 4}) nanoparticles were synthesized in an aqueous system by chemical co-precipitation. • The characterization of bare and chitosan-coated nanoparticles were performed using various analytical tools, such as TEM, FTIR, XRD, and VMS. • We evaluated the coated particles as potential T{sub 1} and T{sub 2} contrast agents for MRI by measuring T{sub 1} and T{sub 2} relaxation times as a function of iron concentration. • Both T{sub 1} and T{sub 2} effects were also observed in animal experimentation.

Cardiac image segmentation for contrast agent videodensitometry

NARCIS (Netherlands)

Mischi, M.; Kalker, A.A.C.M.; Korsten, H.H.M.

2005-01-01

Indicator dilution techniques are widely used in the intensive care unit and operating room for cardiac parameter measurements. However, the invasiveness of current techniques represents a limitation for their clinical use. The development of stable ultrasound contrast agents allows new applications

Advanced detection strategies for ultrasound contrast agents

NARCIS (Netherlands)

J.M.G. Borsboom (Jerome)

2005-01-01

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

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

International Nuclear Information System (INIS)

Lim, Hyo Soon; Kim, Jae Kyu; Shen, Yu Lan; Oh, Jeong Won; Chang, Nam Kyu; Shin, Sang Soo; Park, Jin Gyoon; Kang, Heoung Keun

2006-01-01

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

Characteristics of gadolinium-DTPA complex: a potential NMR contrast agent

International Nuclear Information System (INIS)

Weinmann, H.J.; Brasch, R.C.; Press, W.R.; Wesbey, G.E.

1984-01-01

Chelation of the rare-earth element gadolinium (Gd) with diethylenetriaminepentaacetic acid (DTPA) results in a strongly paramagnetic, stable complex that is well tolerated in animals. The strongly paramagnetic gadolinium complex reduces hydrogen-proton relaxation times even in low concentrations (less than 0.01 mmol/L). The pharmacokinetic behavior of intravenously delivered Gd-DTPA is similar to the well known iodinated contrast agents used in urography and angiography; excretion is predominately through the kidneys with greater than 90% recovery in 24 hr. The intravenous LD 50 of the meglumine salt of Gd-DTPA is 10 mmol/kg for the rat; in vivo there is no evidence of dissociation of the gadolinium ion from the DTPA ligand. The combination of strong proton relaxation, in-vivo stability, rapid urinary excretion, and high tolerance favors the further development and the potential clinical application of gadolinium-DTPA as a contrast enhancer in magnetic resonance imaging

Sequential gadolinium-enhanced magnetic resonance angiography of the aortoiliac and the femoropopliteal arteries with repetitive administration of low-dose contrast agent

International Nuclear Information System (INIS)

Ito, Koichiro; Kumazaki, Tatsuo

2000-01-01

To obtain a wide-range contrast MR angiography in a single examination, we performed two sequential administrations of low-dose (0.08 mmol/kg) gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) with three dimensional inversion recovery prepared fast spoiled gradient recalled acquisition in the steady-state (3D IR-fast SPGR) sequence. Signal characteristics of the sequence were estimated by computed simulations and an in vitro study. A clinical study of 19 examinations was done with sequential MR angiography of the aortoiliac and femoropopliteal arteries. Great signal differences were observed between the high and low Gd concentrations. Higher Gd concentrations generated significantly stronger signals. Greater signals were produced at TIs of longer than 150 msec than at shorter than 100 msec. In the clinical study, the arteries were visualized with sufficient signals even with a small amount of contrast agent. Contrast-to-noise ratios between the arteries and surrounding skeletal muscles or fat tissues ranged from 10.5±9.6 to 4.7±2.2 and 6.6±2.8 to -3.1±11.2, respectively. No venous enhancement was found with diluted contrast agent on the second MR angiography. Two consecutive contrast MR angiographies can be obtained with repetitive administration of low-dose contrast agent. (author)

Sequential gadolinium-enhanced magnetic resonance angiography of the aortoiliac and the femoropopliteal arteries with repetitive administration of low-dose contrast agent

Energy Technology Data Exchange (ETDEWEB)

Ito, Koichiro [Nippon Medical School, Inba, Chiba (Japan). Chiba Hokusoh Hospital; Kumazaki, Tatsuo

2000-12-01

To obtain a wide-range contrast MR angiography in a single examination, we performed two sequential administrations of low-dose (0.08 mmol/kg) gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) with three dimensional inversion recovery prepared fast spoiled gradient recalled acquisition in the steady-state (3D IR-fast SPGR) sequence. Signal characteristics of the sequence were estimated by computed simulations and an in vitro study. A clinical study of 19 examinations was done with sequential MR angiography of the aortoiliac and femoropopliteal arteries. Great signal differences were observed between the high and low Gd concentrations. Higher Gd concentrations generated significantly stronger signals. Greater signals were produced at TIs of longer than 150 msec than at shorter than 100 msec. In the clinical study, the arteries were visualized with sufficient signals even with a small amount of contrast agent. Contrast-to-noise ratios between the arteries and surrounding skeletal muscles or fat tissues ranged from 10.5{+-}9.6 to 4.7{+-}2.2 and 6.6{+-}2.8 to -3.1{+-}11.2, respectively. No venous enhancement was found with diluted contrast agent on the second MR angiography. Two consecutive contrast MR angiographies can be obtained with repetitive administration of low-dose contrast agent. (author)

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

International Nuclear Information System (INIS)

Pereira, G.A.; Geraldes, C.F.G.C.; University of Coimbra

2007-01-01

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

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

Science.gov (United States)

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 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.

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-07-01

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

Enhanced conjugation stability and blood circulation time of macromolecular gadolinium-DTPA contrast agent

Energy Technology Data Exchange (ETDEWEB)

Jenjob, Ratchapol [Department of New Drug Development, School of Medicine, Inha University, 2F A-dong, Jeongseok Bldg., Sinheung-dong 3-ga, Jung-gu, Incheon 400-712 (Korea, Republic of); Kun, Na [Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743 (Korea, Republic of); Ghee, Jung Yeon [Utah-Inha DDS and Advanced Therapeutics, B-403 Meet-You-All Tower, SongdoTechnopark, 7–50, Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Shen, Zheyu; Wu, Xiaoxia [Division of Functional Materials and Nano-Devices, Ningbo Institute of Materials Technology & Engineering (NIMTE), Chinese Academy of Sciences, 519 Zhuangshi Street, Zhenhai District, Ningbo, Zhejiang 315201 (China); Cho, Steve K., E-mail: scho@gist.ac.kr [Division of Liberal Arts and Science, GIST College, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of); Lee, Don Haeng [Utah-Inha DDS and Advanced Therapeutics, B-403 Meet-You-All Tower, SongdoTechnopark, 7–50, Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Department of Internal Medicine, School of Medicine, Inha University Hospital, Incheon 420-751 (Korea, Republic of); Yang, Su-Geun, E-mail: Sugeun.Yang@Inha.ac.kr [Department of New Drug Development, School of Medicine, Inha University, 2F A-dong, Jeongseok Bldg., Sinheung-dong 3-ga, Jung-gu, Incheon 400-712 (Korea, Republic of)

2016-04-01

In this study, we prepared macromolecular MR T1 contrast agent: pullulan-conjugated Gd diethylene triamine pentaacetate (Gd-DTPA-Pullulan) and estimated residual free Gd{sup 3+}, chelation stability in competition with metal ions, plasma and tissue pharmacokinetics, and abdominal MR contrast on rats. Residual free Gd{sup 3+} in Gd-DTPA-Pullulan was measured using colorimetric spectroscopy. The transmetalation of Gd{sup 3+} incubated with Ca{sup 2+} was performed by using a dialysis membrane (MWCO 100–500 Da) and investigated by ICP-OES. The plasma concentration profiles of Gd-DTPA-Pullulan were estimated after intravenous injection at a dose 0.1 mmol/kg of Gd. The coronal-plane abdominal images of normal rats were observed by MR imaging. The content of free Gd{sup 3+}, the toxic residual form, was less than 0.01%. Chelation stability of Gd-DTPA-Pullulan was estimated, and only 0.2% and 0.00045% of Gd{sup 3+} were released from Gd-DTPA-Pullulan after 2 h incubation with Ca{sup 2+} and Fe{sup 2+}, respectively. Gd-DTPA-Pullulan displayed the extended plasma half-life (t{sub 1/2,α} = 0.43 h, t{sub 1/2,β} = 2.32 h), much longer than 0.11 h and 0.79 h of Gd-EOB-DTPA. Abdominal MR imaging showed Gd-DTPA-Pullulan maintained initial MR contrast for 30 min. The extended plasma half-life of Gd-DTPA-Pullulan probably allows the prolonged MR acquisition time in clinic with enhanced MR contrast. - Highlights: • Macromolecule (pullulan) conjugated Gd contrast agent (Gd-DTPA-Pullulan) showed the extended plasma half-life (t{sub 1/2,α} = 0.43 h, t{sub 1/2,β} = 2.32 h) in comparison with Gd-EOB-DTPA • Gd-DTPA-pullulan T1 contrast agent exhibited strong chelation stability against Gd. • The extended blood circulation attributed the enhanced and prolonged MR contrast on abdominal region of rats. • The extended blood circulation may provide prolonged MR acquisition time window in clinics.

A smart magnetic resonance contrast agent for selective copper sensing.

Science.gov (United States)

Que, Emily L; Chang, Christopher J

2006-12-20

We describe the synthesis and properties of Copper-Gad-1 (CG1), a new type of smart magnetic resonance (MR) sensor for selective detection of copper. CG1 is composed of a gadolinium contrast agent core tethered to copper-selective recognition motif. Cu2+-induced modulation of inner-sphere water access to the Gd3+ center provides a sensing mechanism for reporting Cu2+ levels by reading out changes in longitudinal proton relaxivity values. CG1 features good selectivity for Cu2+ over abundant biological cations and a 41% increase in relaxivity upon Cu2+ binding and is capable of detecting micromolar changes in Cu2+ concentrations in aqueous media.

Modified natural nanoparticles as contrast agents for medical imaging

NARCIS (Netherlands)

Cormode, David P.; Jarzyna, Peter A.; Mulder, Willem J. M.; Fayad, Zahi A.

2010-01-01

The development of novel and effective contrast agents is one of the drivers of the ongoing improvement in medical imaging. Many of the new agents reported are nanoparticle-based. There are a variety of natural nanoparticles known, e.g. lipoproteins, viruses or ferritin. Natural nanoparticles have

[Development of Biliary Contrast Agents Remote Pushing Device].

Science.gov (United States)

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.

Antibiofouling polymer coated gold nanoparticles as a dual modal contrast agent for X-ray and photoacoustic imaging

International Nuclear Information System (INIS)

Guojia Huang; Yi Yuan; 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.

Contrast agents in magnetic resonance imaging

International Nuclear Information System (INIS)

Karadjian, V.

1987-01-01

The origine of nuclear magnetic resonance signal is reminded and different ways for contrast enhancement in magnetic resonance imaging are presented, especially, modifications of tissus relaxation times. Investigations have focused on development of agents incorporating either paramagnetic ions or stable free radicals. Pharmacological and toxicological aspects are developed. The diagnostic potential of these substances is illustrated by the example of gadolinium complexes [fr

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

NARCIS (Netherlands)

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

2013-01-01

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

Nonspherical oscilllations of ultrasound contrast agent microbubbles

NARCIS (Netherlands)

Dollet, B.; van der Meer, S.M.; Garbin, V.; Garbin, Valeria; de Jong, N.; Lohse, Detlef; Versluis, Michel

2008-01-01

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

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

OpenAIRE

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

2013-01-01

The high affinity of a cationic iodinated contrast agent for cartilage provides better tissue visualization, easier segmentation, higher contrast-to-noise ratios, and longer usable imaging windows and requires a lower dose of injected contrast agent compared with an anionic contrast agent.

Ferrimagnetic ferritin cage nanoparticles used as MRI contrast agent

Science.gov (United States)

Cai, Y.; Cao, C.; Zhang, T.; Xu, H.; Pan, Y.

2017-12-01

The nano-sized ferrimagnetic ferritin cage nanoparticles are ideal materials for understanding of superparamagnetism, biomimetic synthesis of ultrafine magnetic particles and their application in biomedicine. Ferrimagnetic M-HFn nanoparticles with size of magnetite cores in a mean size ranges from 2.7 nm to 5.3 nm were synthesized through loading different amount of iron into recombinant human H chain ferritin (HFn) shells. Both the saturation magnetization (Ms) and blocking temperature (Tb) were increased with the size of ferrimagnetic cores. In essence, magnetic resonance imaging (MRI) analysis showed that the synthesized M-HFn nanoparticles (5.3 nm magnetite core) has extremely high transverse relaxivity (r2) values up to 320.9 mM-1S-1, which indicate that M-HFn nanoparticles are promising negative contrast agent in early detection of tumors. In addition, the longitudinal relaxivity (r1) (10.4 mM-1S-1) and r2/r1 ratio ( 2.2) of M-HFn nanoparticles ( 2.7 nm magnetite core in diameter) will make it a considerable potential as a positive contrast agent in MRI. This means the M-HFn nanoparticles can be used as dual functional MR contrast agent. Acute toxicity study of M-HFn in rats showed that a dosage of 20 mg Fe/kg makes no abnormalities by serum biochemical and hematological analysis as well as histopathological examination. Compared with a similar commercial contrast agent, combidex (with a clinical dosage of 2.7 mg Fe/kg), it indicates that M-HFn nanoparticle is of a relative safe ferrimagnetic nanoparticle when used in vivo.

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

International Nuclear Information System (INIS)

Ma, J; Chen, K

2016-01-01

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 Ni 3 S 2 @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 Ni 3 S 2 @Ni, respectively) will shed some light on the development of new-type MRI contrast agents. (paper)

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

Science.gov (United States)

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

2016-01-01

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

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

Science.gov (United States)

Daryaei, Iman; Pagel, Mark D

2015-01-01

Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a "double-agent" approach to molecular imaging. Exogenous 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.

Ultrasmall cationic superparamagnetic iron oxide nanoparticles as nontoxic and efficient MRI contrast agent and magnetic-targeting tool

Science.gov (United States)

Uchiyama, Mayara Klimuk; Toma, Sergio Hiroshi; Rodrigues, Stephen Fernandes; Shimada, Ana Lucia Borges; Loiola, Rodrigo Azevedo; Cervantes Rodríguez, Hernán Joel; Oliveira, Pedro Vitoriano; Luz, Maciel Santos; Rabbani, Said Rahnamaye; Toma, Henrique Eisi; Poliselli Farsky, Sandra Helena; Araki, Koiti

2015-01-01

Fully dispersible, cationic ultrasmall (7 nm diameter) superparamagnetic iron oxide nanoparticles, exhibiting high relaxivity (178 mM−1s−1 in 0.47 T) and no acute or subchronic toxicity in Wistar rats, were studied and their suitability as contrast agents for magnetic resonance imaging and material for development of new diagnostic and treatment tools demonstrated. After intravenous injection (10 mg/kg body weight), they circulated throughout the vascular system causing no microhemorrhage or thrombus, neither inflammatory processes at the mesentery vascular bed and hepatic sinusoids (leukocyte rolling, adhesion, or migration as evaluated by intravital microscopy), but having been spontaneously concentrated in the liver, spleen, and kidneys, they caused strong negative contrast. The nanoparticles are cleared from kidneys and bladder in few days, whereas the complete elimination from liver and spleen occurred only after 4 weeks. Ex vivo studies demonstrated that cationic ultrasmall superparamagnetic iron oxide nanoparticles caused no effects on hepatic and renal enzymes dosage as well as on leukocyte count. In addition, they were readily concentrated in rat thigh by a magnet showing its potential as magnetically targeted carriers of therapeutic and diagnostic agents. Summarizing, cationic ultrasmall superparamagnetic iron oxide nanoparticles are nontoxic and efficient magnetic resonance imaging contrast agents useful as platform for the development of new materials for application in theranostics. PMID:26251595

Experimental considerations on the removal of alimentary tract signal in T2 multi shot inversion recovery echo planar imaging using ferric ammonium citrate as contrast agent

International Nuclear Information System (INIS)

Kato, Joji; Saito, Haruyoshi; Tomisato, Kenichi; Maruyama, Tomoyuki; Watanabe, Tsuneo; Kawamura, Yoshihiko

1997-01-01

We investigated the removal of alimentary tract signal in T 2 echo planar imaging using an oral positive contrast agent for the alimentary tract mainly consisting of ferric ammonium citrate (FerriSeltz: Otsuka Pharmaceutical Co., Ltd.). It has been reported that the FerriSeltz preparation is useful as negative contrast agent because of its enhancing effect of reducing T 2 at high concentrations. However, it was shown to enhance susceptibility artifact in echo planar imaging (EPI). Thus, it is considered difficult to use FerriSeltz at high concentrations in EPI. In contrast, in IR EPI (TI 150 and 200 ms) high concentrations of FerriSeltz are not required, and it is possible to achieve excellent signal suppression at an ordinary concentration of 5.97 mmol/l. This might be due to the fact that the bounce point of FerriSeltz aqueous solution reached about 150 to 200 ms. At present, no effective negative contrast agent for alimentary tract MRI is available. Therefore, it is thought that IR EPI combined with FerriSeltz is a useful technique, since it can eliminate the signal of the alimentary tract at an ordinary concentration. (author)

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-07-01

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

Can aquatic macrophytes be biofilters for gadolinium based contrasting agents?

Science.gov (United States)

Braun, Mihály; Zavanyi, Györgyi; Laczovics, Attila; Berényi, Ervin; Szabó, Sándor

2018-05-15

The use of gadolinium-based contrasting agents (GBCA) is increasing because of the intensive usage of these agents in magnetic resonance imaging (MRI). Waste-water treatment does not reduce anthropogenic Gd-concentration significantly. Anomalous Gd-concentration in surface waters have been reported worldwide. However, removal of GBCA-s by aquatic macrophytes has still hardly been investigated. Four aquatic plant species (Lemna gibba, Ceratophyllum demersum, Elodea nuttallii, E. canadensis) were investigated as potential biological filters for removal of commonly used but structurally different GBCA-s (Omniscan, Dotarem) from water. These plant species are known to accumulate heavy metals and are used for removing pollutants in constructed wetlands. The Gd uptake and release of the plants was examined under laboratory conditions. Concentration-dependent infiltration of Gd into the body of the macrophytes was measured, however significant bioaccumulation was not observed. The tissue concentration of Gd reached its maximum value between day one and four in L. gibba and C. demersum, respectively, and its volume was significantly higher in C. demersum than in L. gibba. In C. demersum, the open-chain ligand Omniscan causes two-times higher tissue Gd concentration than the macrocyclic ligand Dotarem. Gadolinium was released from Gd-treated duckweeds into the water as they were grown further in Gd-free nutrient solution. Tissue Gd concentration dropped by 50% in duckweed treated by Omniscan and by Dotarem within 1.9 and 2.9 days respectively. None of the macrophytes had a significant impact on the Gd concentration of water in low and medium concentration levels (1-256 μg L -1 ). Biofiltration of GBCA-s by common macrophytes could not be detected in our experiments. Therefore it seems that in constructed wetlands, aquatic plants are not able to reduce the concentration of GBCA-s in the water. Furthermore there is a low risk that these plants cause the

New MR contrast agent

International Nuclear Information System (INIS)

Grossman, C.D.; Subramanian, G.; Schneider, R.; Szeverenyi, N.E.; Rosenbaum, A.M.; Gagne, G.; Tillapaugh-Fay, G.; Berlin, R.; Ritter-Hrncirik, C.; Yu, S.

1990-01-01

This paper evaluates an MR contrast agent-meglumine tris-(2,6-dicarboxypyridine) gadolinium (III) or gadolinium dipicolinate (Gd-DPC)-produced in-house. Rats were anesthetized with pentobarbital. For renal imaging, bowel motion artifact was minimized with glucagon (0.014 mg/kg, intravenous (IV)). Enhanced images were generated on a 2-T chemical shift imaging system with a 31-cm horizontal bore magnet after IV injection of Gd-DPC (100 μM/kg). Coronal sections of the kidneys and sagittal sections of the brain, 2 mm thick, were made. Six to eight excitations and 128 or 356 phase-encoding steps were used for each image. Control animals were injected with equivalent doses of gadopentetate dimeglumine

Gd-DTPA: a bowel contrast agent for magnetic resonance imaging of the abdomen

International Nuclear Information System (INIS)

Vlahos, L.; Gouliamos, A.; Clauss, W.; Kalovidouris, A.; Hadjiioannou, A.; Athanasopoulou, A.; Trakadas, S.; Papavasiliou, C.

1992-01-01

Forty patients with suspected pathology in the abdomen and pelvis have been investigated with MRI before and after administration of Gd-DTPA as an oral or rectal solution. The findings are analysed with respect to: (a) filling of the GI tract; (b) contrast in the region of interest, surrounding fat and vessels; (c) diagnostic yield in comparison to non-enhanced MRI and contrast CT. At a concentration of 1 mmol/l Gd-DTPA provided consistent positive contrast in the stomach and bowel in all cases. In 57.5% of cases we achieved complete filling of the GI tract. The opacification in the region of interest was good or satisfactory in 90% of cases. The diagnostic value of contrast MRI was better in 93% of cases than the non-enhanced MRI of the abdomen. In comparison with contrast CT, the contrast MRI was better or of the same value in 92% of cases. Despite the disadvantage of poor fat-to-bowel contrast (35% of cases were classified as poor), it is concluded that Gd-DTPA-enhanced MRI provides good delineation of organs adjacent to the bowel so this contrast agent has potential for a future role in abdominal MRI. (orig.)

Gd-DTPA: a bowel contrast agent for magnetic resonance imaging of the abdomen

Energy Technology Data Exchange (ETDEWEB)

Vlahos, L. [Dept. of Radiology, Univ. of Athens, Areteion Hospital (Greece); Gouliamos, A. [Dept. of Radiology, Univ. of Athens, Areteion Hospital (Greece); Clauss, W. [Schering A. G., Berlin (Germany); Kalovidouris, A. [Dept. of Radiology, Univ. of Athens, Areteion Hospital (Greece); Hadjiioannou, A. [Dept. of Radiology, Univ. of Athens, Areteion Hospital (Greece); Athanasopoulou, A. [Dept. of Radiology, Univ. of Athens, Areteion Hospital (Greece); Trakadas, S. [Dept. of Radiology, Univ. of Athens, Areteion Hospital (Greece); Papavasiliou, C. [Dept. of Radiology, Univ. of Athens, Areteion Hospital (Greece)

1992-08-01

Forty patients with suspected pathology in the abdomen and pelvis have been investigated with MRI before and after administration of Gd-DTPA as an oral or rectal solution. The findings are analysed with respect to: (a) filling of the GI tract; (b) contrast in the region of interest, surrounding fat and vessels; (c) diagnostic yield in comparison to non-enhanced MRI and contrast CT. At a concentration of 1 mmol/l Gd-DTPA provided consistent positive contrast in the stomach and bowel in all cases. In 57.5% of cases we achieved complete filling of the GI tract. The opacification in the region of interest was good or satisfactory in 90% of cases. The diagnostic value of contrast MRI was better in 93% of cases than the non-enhanced MRI of the abdomen. In comparison with contrast CT, the contrast MRI was better or of the same value in 92% of cases. Despite the disadvantage of poor fat-to-bowel contrast (35% of cases were classified as poor), it is concluded that Gd-DTPA-enhanced MRI provides good delineation of organs adjacent to the bowel so this contrast agent has potential for a future role in abdominal MRI. (orig.)

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

Directory of Open Access Journals (Sweden)

Vera ePaefgen

2015-09-01

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

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

OpenAIRE

Ai-Ho Liao

2016-01-01

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

Contrast agents provide a faster learning curve in dipyridamole stress echocardiography.

Science.gov (United States)

Zamorano, Jose; Sánchez, Violeta; Moreno, Raúl; Almería, Carlos; Rodrigo, Jose; Serra, Viviana; Azcona, Luis; Aubele, Adalia; Mataix, Luis; Sánchez-Harguindey, Luis

2002-12-01

Interobserver variability is an important limitation of the stress echocardiography and depends on the echocardiographer training. Our aim was to evaluate if the use of contrast agents during dipyridamole stress echocardiography would improve the agreement between an experienced and a non-experienced observer in stress echo and therefore if contrast would affect the learning period of dypyridamole stress echo. Two independent observers without knowledge of any patient data interpreted all stress studies. One observer was an experienced one and the other had experience in echocardiography but not in stress echo. Two observers analysed 87 non-selected and consecutive studies. Out of the 87 studies, 46 were performed without contrast administration, whereas i.v. contrast (2.5 g Levovist by two bolus at rest and at peak stress) was administered in 41. In all cases, second harmonic imaging and stress digitalisation pack was used. The agreement between observers showed a kappa index of 0.58 and 0.83 without and with contrast administration, respectively. The use of contrast agents provides a better agreement in the evaluation of stress echo between an experienced and a non-experienced observer in stress echo. Adding routinely contrast agents could probably reduce the number of exams required for the necessary learning curve in stress echocardiography.

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

Science.gov (United States)

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

2009-01-01

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

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

Directory of Open Access Journals (Sweden)

Rongzuo Xu

2010-09-01

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

Longitudinal study of iodine in toenails following IV administration of an iodine-containing contrast agent

International Nuclear Information System (INIS)

Spate, V.L.; Morris, J.S.; Nichols, T.A.; Baskett, C.K.; Mason, M.M.; Horsman, T.L.; McDougall, I.R.

1998-01-01

The literature on the relationship between diet and thyroid cancer (TC) risk and the higher incidence of TC among Asian immigrants to the US compared to second and third generation subgroups has prompted epidemiologists to hypothesize that increased levels of iodine consumption may be associated with TC risk, particularly among persons with a history of clinical or subclinical thyroid dysfunction. At the University of Missouri Research Reactor (MURR), we have applied epiboron neutron activation analysis to investigate human nails as a dietary monitor for iodine. Preliminary studies have indicated a positive correlation between dietary iodine intake and the concentration of iodine in toenails. However, these studies are confounded by high iodine levels (up to 30 ppm) in approximately 5% of the nails studied. We hypothesize that, in the subjects we have studied, the high iodine levels may be due to iodine-containing medications, in particular contrast-agents containing iopamidol. This paper will report on longitudinal studies using contrast agent subjects who where followed-up for almost two years compared to a longitudinal control and a population mean. Based on this study, we suggest that iodine-containing contrast agents contaminate nail samples via non-specific binding in the short term followed by incorporation in the nail as a result of absorption. (author)

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

Directory of Open Access Journals (Sweden)

Wenjun Le

2016-04-01

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

Photoacoustic imaging at 1064nm wavelength with exogenous contrast agents

Science.gov (United States)

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.

Comparison of differently viscous iodinated and bariumcontaining contrast agents in the detection of pharyngeal perforation

International Nuclear Information System (INIS)

Keberle, M.; Wittenberg, G.; Trusen, A.; Hahn, D.; Baumgartner, W.

2001-01-01

Purpose: In contrast to esophageal perforations, the more radiopaque barium-suspensions are not as important as iodinated aqueous contrast agents for the detection of pharyngeal perforations. This study was performed to find out whether the highly different viscosities (of iodinated and barium-containing contrast agents with comparable radiopacities) are a reason for this. Methods: Viscosity, subjective difference in contrast, and CT-density of an iodinated aqueous (Telebrix) and a 50 wt/vol% barium-containing contrast agent (Micropaque) were determined. Moreover, to exclude postoperative perforation, 104 patients were prospectively examined by pharyngography using both contrast media. Pharyngographies of patients with perforation were later compared by two independent readers. All patients with perforation were followed up clinically to exclude complications due to barium administration. Results: In-vitro comparison showed comparable radiopacity but the 50 wt/vol% barium-suspension was much more viscous that the iodinated contrast agent. During pharyngography, totally, 14 perforations were clearly delineated with the iodinated aqueous contrast agent. However, two of them were not detected with the barium-suspension. All the other perforations presented equally. Conclusions: Given a sufficient radiopacity, a low viscosity appears to be essential for a contrast agent to detect especially pharyngeal perforations. Thus, we recommend the sole use of an iodinated contrast agent (at suspicion of aspiration as isoosmolar variant) for this purpose. (orig.) [de

Iron oxide nanoparticles for use in contrast agents in magnetic resonance imaging

International Nuclear Information System (INIS)

Oliveira, Elisa M.N. de; Rocha, Maximiliano S. da; Caimi, Priscila de A.; Basso, Nara R. de S.; Zanini, Mara L.; Papaleo, Ricardo M.

2015-01-01

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

A functionalized superparamagnetic iron oxide colloid as a receptor directed MR contrast agent

International Nuclear Information System (INIS)

Josephson, L.; Groman, E.V.; Menz, E.; Lewis, J.M.; Bengele, H.

1990-01-01

We have synthesized a surface functionalized superparamagnetic iron oxide colloid whose clearance from the vascular compartment was inhibited by asialofetuin but not fetuin. Unlike other particulate or colloidal magnetic resonance (MR) contrast agents, the agent of the current communication is not withdrawn from the vascular compartment by cells of the macrophage-monocyte phagocytic system, as indicated by its selective increase in hepatic relaxation rates. Because of this we refer to this colloid as a hepatic selective (HS) MR contrast agent. At 20 mumol Fe/kg the HS MR agent darkened MR images of liver. The HS MR agent exhibited no acute toxicity when injected into rats at 1800 mumol Fe/kg. Based on these observations, surface functionalized superparamagnetic iron oxide colloids may be the basis of MR contrast agents internalized by receptor mediated endocytosis generally, and by the asialoglycoprotein receptor in particular

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

Science.gov (United States)

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

2017-09-01

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

Comparison of positive and negative enteral contrast agents for MR imaging of the abdomen

International Nuclear Information System (INIS)

Kaminsky, S.; Langer, M.

1994-01-01

Following oral administration of a buffered gadopentetate-dimeglumine solution (Magnevist enteral R , 1 mmol/l, 6-17 ml/kg) T 1 -, proton-density- and T 2 -weighted spin-echo images of abdominal and retroperitoneal lesions were acquired (0.5 T). Gadopentetate is a signal-enhancing, positive MR contrast agent, intraluminar air served as a model of a signal-free, negative agent. In 21 patients contrast/noise ratios of gadopentetate and air versus lesions and fat were compared quantitatively (t-test). In T 1 - and T 2 -weighted images contrast/noise ratios of gadopentetate versus lesions were significantly higher than those of air. In proton-density images there was no significant difference. In T 1 - and proton-density images contrast/noise ratios of air versus abdominal fat were significantly higher than those of gadopentetate, in T 2 -weighted images gadopentetate had a significantly higher contrast/noise ratio than air. Signal-enhancing positive contrast agents seem advantageous over signal-free negative enteral MR contrast agents. (orig.) [de

An experimental study on tissue reaction of various contrast agents on endometrium, tuber mucosa, and peritoneum

International Nuclear Information System (INIS)

Kim, Jae Seung; Kim, Seung Hyup; Park, In Ae; Park, Jae Hyung; Yoon, Dae Young; Yeon, Kyung Mo

1994-01-01

To compare the tissue reactions of various water-soluble and oil-based contrast agents on the endometrium, salpingeal mumosa, and peritoneum. Thirty-three rabbits were used for evaluating the histologic reactions of uterine endometrium, salpinx, and peritoneum. Hysterosalpingography(HSG) was underwent in these rabbits by used Lipiodol, Hexabrix, Rayvist. Ultravist-300, Ultravist-370, and normal saline. Pathologic results were obtained in each of the six groups from the uterine endometrium, salpingeal mucosa, and peritoneum without knowledge of the contrast agent used and time interval from HSG. Mild inflammations were observed in the endometrium, salpingeal mucosa, and peritoneum during the first week of HSG in all rabbits in which water-soluble contrast agents were used. Although there was no significant difference in the degree of inflammation among the groups using various contrast agents, the group with oil-based contrast agent(Lipiodol) showed delayed absorption of contrast agent in the peritoneum, frequent intravasation, fat granuloma, peritoneal adhesion, or uterine infarction. Our results suggest that water-soluble contrast agents can be used safely for HSG, but the use of oil-based contrast agent is questional in safety and should be avoid in patients with tubal obstruction, salpingitis, or endometritis

In vitro evaluation of alternative oral contrast agents for MRI of the gastrointestinal tract

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Babos, Magor [University of Szeged, Faculty of Science (Hungary); Euromedic Diagnostics Szeged, 6720 Szeged, Semmelweiss u. 6 (Hungary)], E-mail: babosmagor@yahoo.com; Schwarcz, Attila [University of Pecs, Department of Neurosurgery, Pecs Diagnostic Institute, 7624 Pecs, Retu. 2 (Hungary)], E-mail: attila.schwarcz@aok.pte.hu; Randhawa, Manjit Singh [University of Szeged, Faculty of Medicine, Department of Radiology, 6720 Szeged, Semmelweiss u. 6 (Hungary)], E-mail: majyaal@hotmail.com; Marton, Balazs [University of Szeged, Faculty of Medicine, Department of Radiology, 6720 Szeged, Semmelweiss u. 6 (Hungary)], E-mail: balazsmarton@freemail.hu; Kardos, Lilla [Euromedic Diagnostics Szeged, 6720 Szeged, Semmelweiss u. 6 (Hungary)], E-mail: medlis@tiszanet.hu; Palko, Andras [Euromedic Diagnostics Szeged, 6720 Szeged, Semmelweiss u. 6 (Hungary); University of Szeged, Faculty of Medicine, Department of Radiology, 6720 Szeged, Semmelweiss u. 6 (Hungary)], E-mail: palko@radio.szote.u-szeged.hu

2008-01-15

Purpose: In vitro evaluation of different materials as potential alternative oral contrast agents for small bowel MRI. Materials and methods: The T1 and T2 relaxation times of rose hip syrup, black currant extract, cocoa, iron-deferoxamine solution and a commonly used oral contrast material (1 mM Gd-DTPA) were determined in vitro at different concentrations on a 1.0 T clinical MR scanner. T1 values were obtained with an inversion prepared spoiled gradient echo sequence. T2 values were obtained using multiple echo sequences. Finally the materials were visualized on T1-, T2- and T2*-weighted MR images. Results: The relaxation times of the undiluted rose hip syrup (T1 = 110 {+-} 5 ms, T2 = 86 {+-} 3 ms), black currant extract (T1 = 55 {+-} 3 ms, T2 = 39 {+-} 2 ms) and 5 mM iron-deferoxamine solution (T1 = 104 {+-} 4 ms, T2 = 87 {+-} 2 ms) were much shorter than for a 1 mM Gd-DTPA solution (T1 = 180 {+-} 8 ms, T2 = 168 {+-} 5 ms). Dilution of black currant extract to 30% or a 3 mM iron-deferoxamine solution conducted to T1 relaxation times which are quite comparable to a 1 mM Gd-DTPA solution. Despite its much lower metal content an aqueous cocoa suspension (100 g/L) produced T2 relaxation times (T1 = 360 {+-} 21 ms, T2 = 81 {+-} 3 ms) more or less in the same range like the 5 mM iron-deferoxamine solution. Imaging of our in vitro model using clinical sequences allowed to anticipate the T1-, T2- and T2*-depiction of all used substances. Cocoa differed from all other materials with its low to moderate signal intensity on T1- and T2-weighted sequences. While all substances presented a linear 1/T1 and 1/T2 relationship towards concentration, rose hip syrup broke ranks with a disproportionately high increase of relaxation at higher concentrations. Conclusions: Rose hip syrup, black currant extract and iron-deferoxamine solution due to their positive T1 enhancement characteristics and drinkability appear to be valuable oral contrast agents for T1-weighted small bowel MRI

In vitro evaluation of alternative oral contrast agents for MRI of the gastrointestinal tract

International Nuclear Information System (INIS)

Babos, Magor; Schwarcz, Attila; Randhawa, Manjit Singh; Marton, Balazs; Kardos, Lilla; Palko, Andras

2008-01-01

Purpose: In vitro evaluation of different materials as potential alternative oral contrast agents for small bowel MRI. Materials and methods: The T1 and T2 relaxation times of rose hip syrup, black currant extract, cocoa, iron-deferoxamine solution and a commonly used oral contrast material (1 mM Gd-DTPA) were determined in vitro at different concentrations on a 1.0 T clinical MR scanner. T1 values were obtained with an inversion prepared spoiled gradient echo sequence. T2 values were obtained using multiple echo sequences. Finally the materials were visualized on T1-, T2- and T2*-weighted MR images. Results: The relaxation times of the undiluted rose hip syrup (T1 = 110 ± 5 ms, T2 = 86 ± 3 ms), black currant extract (T1 = 55 ± 3 ms, T2 = 39 ± 2 ms) and 5 mM iron-deferoxamine solution (T1 = 104 ± 4 ms, T2 = 87 ± 2 ms) were much shorter than for a 1 mM Gd-DTPA solution (T1 = 180 ± 8 ms, T2 = 168 ± 5 ms). Dilution of black currant extract to 30% or a 3 mM iron-deferoxamine solution conducted to T1 relaxation times which are quite comparable to a 1 mM Gd-DTPA solution. Despite its much lower metal content an aqueous cocoa suspension (100 g/L) produced T2 relaxation times (T1 = 360 ± 21 ms, T2 = 81 ± 3 ms) more or less in the same range like the 5 mM iron-deferoxamine solution. Imaging of our in vitro model using clinical sequences allowed to anticipate the T1-, T2- and T2*-depiction of all used substances. Cocoa differed from all other materials with its low to moderate signal intensity on T1- and T2-weighted sequences. While all substances presented a linear 1/T1 and 1/T2 relationship towards concentration, rose hip syrup broke ranks with a disproportionately high increase of relaxation at higher concentrations. Conclusions: Rose hip syrup, black currant extract and iron-deferoxamine solution due to their positive T1 enhancement characteristics and drinkability appear to be valuable oral contrast agents for T1-weighted small bowel MRI. Cocoa with its

Novel contrast agent for liver and spleen

International Nuclear Information System (INIS)

Seltzer, S.E.; Blau, M.; Adams, D.F.; Janoff, A.; Minchey, S.

1991-01-01

This paper determines whether the biodistribution and imaging characteristics of a liposome-encapsulated contrast agent, iotrolan-carrying interdigitation fusion (IF) vesicles, were acceptable for a liver-spleen CT contrast agent. IF vesicles with iotrolan in their aqueous phase were prepared by fusing small unilamellar liposomes into larger vesicles. The iodine-to-lipid ratio was 4.7. Biodistribution was measured with I-125 iotrolan-labeled IF vesicles in rats. CT imaging (Somatom Plus, Siemens Medical Systems) was performed in dogs. At the lowest dose (10 mg of iodine and 2.1 mg of lipid per kilogram) 72% of the ID was in the liver, 5% in spleen, and 1% in lungs at 1 hour. At the highest dose, (1,000 mg of iodine and 212 mg of lipid per kilogram), liver values were 68% ID, while spleen rose to 18%, lung 5%. Liver and spleen values stayed at peak for 24 hours then fell; the half-life was 6 days. In dogs, liver and spleen enhancement at 1 hour averaged 652 and 256 HU above baseline per gram of iodine per kilogram, respectively

Utility decay rates of T1-weighted magnetic resonance imaging contrast based on redox-sensitive paramagnetic nitroxyl contrast agents

International Nuclear Information System (INIS)

Matsumoto, Ken-ichiro

2009-01-01

The availability and applicability of the combination of paramagnetic nitroxyl contrast agent and T 1 -weighted gradient echo (GE)-based dynamic magnetic resonance imaging (MRI) measurement for redox imaging are described. The time courses of T 1 -weighted GE MRI signal intensities according to first-order paramagnetic loss of a nitroxyl contrast agent were simulated for several experimental conditions. The apparent decay rate calculated based on decreasing T 1 -weighted MRI contrast (k MRI ) can show an approximate value of the original decay rate (k true ) discretionarily given for simulation with suitable experimental parameters. The difference between k MRI and k true can be sufficiently small under T 1 -weighted spoiled gradient echo (SPGR) scan conditions (repetition time=75 ms, echo time=3 ms, and flip angle=45deg), with a conventional redox-sensitive nitroxyl contrast agent, such as 4-hydroxy-2,2,6,6,-tetramethylpiperidine-N-oxyl (TEMPOL) and/or 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (carbamoyl-PROXYL), and with intravenous (i.v.) doses of below 1.5 γmol/g body weight (b.w.) for mice. The results of this simulation suggest that the k MRI of nitroxyl contrast agents can be the primary index of redox status under biological conditions. (author)

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Non-toxic lead sulfide nanodots as efficient contrast agents for visualizing gastrointestinal tract.

Science.gov (United States)

Liu, Zhen; Ran, Xiang; Liu, Jianhua; Du, Yingda; Ren, Jinsong; Qu, Xiaogang

2016-09-01

Non-invasive imaging of gastrointestinal (GI) tract using novel but efficient contrast agents is of the most important issues in the diagnosis and prognosis of GI diseases. Here, for the first time, we reported the design and synthesis of biothiol-decorated lead sulfide nanodots, as well as their usages in functional dual-modality imaging of GI tract in vivo. Due to the presence of glutathione on the surface of the nanodots, these well-prepared contrast agents could decrease the unwanted ion leakage, withstand the harsh conditions in GI tract, and avoid the systemic absorption after oral administration. Compared with clinical barium meal and iodine-based contrast agents, these nanodots exhibited much more significant enhancement in contrast efficiency during both 2D X-ray imaging and 3D CT imaging. Different from some conventional invasive imaging modalities, such as gastroscope and enteroscope, non-invasive imaging strategy by using glutathione modified PbS nanodots as contrast agents could reduce the painfulness towards patients, facilitate the imaging procedure, and economize the manipulation period. Moreover, long-term toxicity and bio-distribution of these nanodots after oral administration were evaluated in detail, which indicated their overall safety. Based on our present study, these nanodots could act as admirable contrast agents to integrate X-ray imaging and CT imaging for the direct visualization of GI tract. Copyright © 2016 Elsevier Ltd. All rights reserved.

Smart Contrast Agents for Magnetic Resonance Imaging.

Science.gov (United States)

Bonnet, Célia S; Tóth, Éva

2016-01-01

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

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

Science.gov (United States)

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.

Gadolinium as a CT contrast agent: an experimental study for the effects of injection parameters in the rabbit brain model

International Nuclear Information System (INIS)

Kim, Hyun Jin; Choi, Hye Young; Lee, Sun Wha; Hwang, Ji Young

2005-01-01

We wanted to investigate the use of gadolinium based contrast agent (Gd-DTPA) for computed tomography (CT), and we also wanted to assess the effects of valuable injection parameters on enhancement in an experimental rabbit brain model. In vitro, attenuation measurements of serial dilutions of Gd-DTPA and iopromide were compared. In five rabbits, single level dynamic gadolinium-enhanced brain CT studies were obtained using different injection parameters. A comparision CT scan after iopromide administration was performed. The time-attenuation curves of the brain vessel and parenchyma were obtained and the magnitude of enhancement (Hmax) and the time to peak enhancement (Tmax) were analyzed. In vitro, the attenuation coefficient of undiluted Gd-DTPA (2,578 HU) was higher than that of iopromide (1,761 HU) at equimolar concentrations. In 5 rabbits, the time-attenuation curve demonstrated a distinct pattern with peak enhancement only in the brain vessel, but not in the brain parenchyma. There was increasing linear relationship between the injection rate of Gd-DTPA and Hmax, and a declining linear relationship with Tmax. The higher the concentration of Gd-DTPA, the higher Hmax was, but no significant difference was found for the Tmax. Higher volumes of Gd-DTPA revealed a higher Hmax and a delayed Tmax. Enhancement of the brain parenchyma on gadolinium-enhanced CT is minimal, while enhancement of the brain vessels is distinctive. The most important factor affecting Hmax of the vessel is the concentration of the contrast medium and the most important factor affecting Tmax of the vessel is volume of the contrast medium. The gadolinium-based contrast agent may be an reasonable alternative contrast agent for brain CT, and especially in cerebral vessels, and it may also be advantageous for brain parenchyma of those patients with BBB dysfunction

Research on a new oral contrast agent for abdominal MRI using free manganese ion

International Nuclear Information System (INIS)

Hasegawa, Hideo; Fujita, Osamu; Hiraishi, Kumiko; Narabayashi, Isamu; Komba, Toshinori; Hamamura, Yoshinori.

1996-01-01

Manganese chloride (Mn: 3 mg/100 g) aqueous solution with hydragenated oligosaccharide and xanthan gum (T 1 : 0.1 sec, T 2 : 0.03 sec at 0.5T) functions in gut as a positive contrast agent on MR T 1 -weighted images and a low signal component on MR T 2 -weighted images. The manganese in the solution functions as a contrast agent under free manganese ion (Mn 2+ ). Further, the solution has special characteristics in terms of MRI signal intensity and relaxation time that are equal to those of blueberry juice, which performs as an effective contrast agent on T 1 -and T 2 -weighted images, and functions as a contrast agent in vitro and in vivo. (author)

Pulsed focused ultrasound combined with micro-bubble contrast agent can open the blood-brain barrier of gliblastoma patients and improve the efficacy of Temozolomide treatment

Directory of Open Access Journals (Sweden)

Qian DONG

2017-06-01

Full Text Available Objective This research examined the effect of microbubble contrast agent plus ultrasound on the permeability of blood-brain barrier, and explored whether it affects the efficacy of chemotherapeutic drugs on cerebral glioblastoma. Methods Wistar rats were divided into three groups to find the optimal concentration of ultrasonic contrast agent. To identify the best ultrasound mode that affected the permeability of blood brain barrier, we employed transmission electron microscopy for study of brain ultrastructure. Western blotting was used to detect the tight junction protein claudin-5. Evans blue staining of brain tissues was utilized to identify the best ultrasonic contrast agent concentration and mode. Rat glioma cells (line 9L were injected into Wistar rats. After temozolomide chemotherapy, the tumor size was measured and the tumor marker GFAP in serum was detected by ELISA. Results The best contrast agent concentration which increases permeability of BBB in rats was found to be 1ml/kg and the best ultrasound mode was intermittently- triggered pulses lasting for 10min (with interval was set at 400ms. More Evans blue passed the blood-brain barrier in ultrasonic cavitation effect group than in control group (P<0.05. After temozolomide chemotherapy, more tumor marker GFAP was detected in ultrasonic cavitation effect group than in control group (P<0.05. Conclusion The permeability of BBB was increased and more temozolomide went through BBB when the rats were subjected to intermittently triggered ultrasonic pulses and were injected at contrast agent at 1ml/kg, which could help to achieve better therapeutic efficacy for glioblastoma. DOI: 10.11855/j.issn.0577-7402.2017.05.06

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

Science.gov (United States)

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.

In vitro chondrocyte toxicity following long-term, high-dose exposure to Gd-DTPA and a novel cartilage-targeted MR contrast agent

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Midura, Sharon; Midura, Ronald J. [Cleveland Clinic, Biomedical Engineering, Lerner Research Institute, Cleveland, OH (United States); Schneider, Erika [Cleveland Clinic, Imaging Institute, A21, Cleveland, OH (United States); NitroSci Pharmaceuticals, New Berlin, WI (United States); Rosen, Gerald M. [University of Maryland School of Pharmacy, Department of Pharmaceutical Sciences, Baltimore, MD (United States); NitroSci Pharmaceuticals, New Berlin, WI (United States); Winalski, Carl S. [Cleveland Clinic, Biomedical Engineering, Lerner Research Institute, Cleveland, OH (United States); Cleveland Clinic, Imaging Institute, A21, Cleveland, OH (United States)

2017-01-15

To determine the concentrations exhibiting toxicity of a cartilage-targeted magnetic resonance imaging contrast agent compared with gadopentetate dimeglumine (Gd-DT-PA) in chondrocyte cultures. A long-term Swarm rat chondrosarcoma chondrocyte-like cell line was exposed for 48 h to 1.0-20 mM concentrations of diaminobutyl-linked nitroxide (DAB4-DLN) citrate, 1.0-20 mM Gd-DTPA, 1.0 μM staurosporine (positive control), or left untreated. Cell appearance, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays of metabolic activity, quantitative PicoGreen assays of DNA content, and calcein-AM viability assays were compared. At 1.0-7.5 mM, minimal decrease in cell proliferation was found for both agents. At all doses of both agents, cell culture appearances were similar after 24 h of treatment. At the higher doses, differences in cell culture appearance were found after 48 h of treatment, with dose-dependent declines in chondrocyte populations for both agents. Concentration-dependent declines in DNA content and calcein fluorescence were found after 48 h of treatment, but beginning at a lower dose of DAB4-DLN citrate than Gd-DTPA. Dose-dependent decreases in MTT staining (cell metabolism) were apparent for both agents, but larger effects were evident at a lower dose for DAB-DLN citrate. Poor MTT staining of cells exposed for 48 h to 20 mM DAB4-DLN citrate probably indicates dead or dying cells. The minimal effect of the long-term exposure of model chondrocyte cell cultures to DAB4-DLN citrate and Gd-DTPA concentrations up to 7.5 mM (3x typical arthrographic administration) is supporting evidence that these doses are acceptable for MR arthrography. The findings are reassuring given that the experimental exposure to the contrast agents at sustained concentrations was much longer than when used clinically. (orig.)

In vitro chondrocyte toxicity following long-term, high-dose exposure to Gd-DTPA and a novel cartilage-targeted MR contrast agent

International Nuclear Information System (INIS)

Midura, Sharon; Midura, Ronald J.; Schneider, Erika; Rosen, Gerald M.; Winalski, Carl S.

2017-01-01

To determine the concentrations exhibiting toxicity of a cartilage-targeted magnetic resonance imaging contrast agent compared with gadopentetate dimeglumine (Gd-DT-PA) in chondrocyte cultures. A long-term Swarm rat chondrosarcoma chondrocyte-like cell line was exposed for 48 h to 1.0-20 mM concentrations of diaminobutyl-linked nitroxide (DAB4-DLN) citrate, 1.0-20 mM Gd-DTPA, 1.0 μM staurosporine (positive control), or left untreated. Cell appearance, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays of metabolic activity, quantitative PicoGreen assays of DNA content, and calcein-AM viability assays were compared. At 1.0-7.5 mM, minimal decrease in cell proliferation was found for both agents. At all doses of both agents, cell culture appearances were similar after 24 h of treatment. At the higher doses, differences in cell culture appearance were found after 48 h of treatment, with dose-dependent declines in chondrocyte populations for both agents. Concentration-dependent declines in DNA content and calcein fluorescence were found after 48 h of treatment, but beginning at a lower dose of DAB4-DLN citrate than Gd-DTPA. Dose-dependent decreases in MTT staining (cell metabolism) were apparent for both agents, but larger effects were evident at a lower dose for DAB-DLN citrate. Poor MTT staining of cells exposed for 48 h to 20 mM DAB4-DLN citrate probably indicates dead or dying cells. The minimal effect of the long-term exposure of model chondrocyte cell cultures to DAB4-DLN citrate and Gd-DTPA concentrations up to 7.5 mM (3x typical arthrographic administration) is supporting evidence that these doses are acceptable for MR arthrography. The findings are reassuring given that the experimental exposure to the contrast agents at sustained concentrations was much longer than when used clinically. (orig.)

Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine

DEFF Research Database (Denmark)

Tepel, Martin; van der Giet, M; Schwarzfeld, C

2000-01-01

Radiographic contrast agents can cause a reduction in renal function that may be due to reactive oxygen species. Whether the reduction can be prevented by the administration of antioxidants is unknown.......Radiographic contrast agents can cause a reduction in renal function that may be due to reactive oxygen species. Whether the reduction can be prevented by the administration of antioxidants is unknown....

Acoustic bubble sorting for ultrasound contrast agent enrichment

NARCIS (Netherlands)

Segers, T.J.; Versluis, Michel

2014-01-01

An ultrasound contrast agent (UCA) suspension contains encapsulated microbubbles with a wide size distribution, with radii ranging from 1 to 10 μm. Medical transducers typically operate at a single frequency, therefore only a small selection of bubbles will resonate to the driving ultrasound pulse.

Ultrasonographic detection of focal liver lesions: increased sensitivity and specificity with microbubble contrast agents

International Nuclear Information System (INIS)

Hohmann, J.; Albrecht, T.; Hoffmann, C.W.; Wolf, K.-J.

2003-01-01

Ultrasonography (US) is the first choice for screening patients with suspected liver lesions. However, due to a lack of contrast agents, US used to be less sensitive and specific compared with computed tomography (CT) and magnet resonance imaging (MRI). The advent of microbubble contrast agents increased both sensitivity and specificity dramatically. Rapid developments of the contrast agents as well as of special imaging techniques were made in recent years. Today numerous different US imaging methods exist which based either on Doppler or on harmonic imaging. They are using the particular behaviour of microbubbles in a sound field which varies depending on the energy of insonation (low/high mechanical index, MI) as well as on the properties of the agent themselves. Apart from just blood pool enhancement some agents have a hepatosplenic specific late phase. US imaging during this late phase using relatively high MI in phase inversion mode (harmonic imaging) or stimulated acoustic emission (SAE; Doppler method) markedly improves the detection of focal liver lesions and is also very helpful for lesion characterisation. With regards to detection, contrast enhanced US performs similarly to CT as shown by recent studies. Early results of studies using low MI imaging and the newer perfluor agents are also showing promising results for lesion detection. Low MI imaging with these agents has the advantage of real time imaging and is particularly helpful for characterisation of focal lesions based on their dynamic contrast behaviour. Apart from the techniques which based on the morphology of liver lesions there were some attempts for the detection of occult metastases or micrometastases by means of liver blood flow changes. Also in this field the use of US contrast agents appears to have advantages over formerly used non contrast-enhanced methods although no conclusive results are available yet

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

International Nuclear Information System (INIS)

Fink, C.; Goyen, M.; Lotz, J.

2007-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2007-03-15

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

Gd-DTPA as a paramagnetic contrast agent in MR imaging of focal liver lesions

International Nuclear Information System (INIS)

Hamm, B.; Roemer, T.; Wolf, K.J.; Felix, R.; Weinmann, H.J.

1986-01-01

Gd-DTPA enhances signal intensity in healthy liver and in intrahepatic tumors. However, after contrast agent administration, tumor enhances significantly more than liver parenchyma (2α≤ 0.05). Doubling the dose of Gd-DTPA from 0.1 to 0.2 mmol/kg of body weight increases the enhancement of intrahepatic tumors (2α≤ 0.05) and optimizes the contrast between tumor and liver in T1-weighted spin-echo sequences. However, the contrast between tumor and liver on inversion-recovery and T2-weighted images obtained before contrast agent administration is much greater than the difference on T1-weighted images obtained after contrast agent administration (2α≤ 0.05). In fast images the contrast between liver and tumor can be markedly improved by administering Gd-DTPA

Contrast enhancement by differently sized paramagnetic MRI contrast agents in mice with two phenotypes of atherosclerotic plaque

NARCIS (Netherlands)

van Bochove, Glenda S.; Paulis, Leonie E. M.; Segers, Dolf; Mulder, Willem J. M.; Krams, Rob; Nicolay, Klaas; Strijkers, Gustav J.

2011-01-01

Interest in the use of contrast-enhanced MRI to enable in vivo specific characterization of atherosclerotic plaques is increasing. In this study the intrinsic ability of three differently sized gadolinium-based contrast agents to permeate different mouse plaque phenotypes was evaluated with MRI. A

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

Energy Technology Data Exchange (ETDEWEB)

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

2011-06-15

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

Towards MRI T2 contrast agents of increased efficiency

Energy Technology Data Exchange (ETDEWEB)

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

2015-03-01

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

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

Science.gov (United States)

Balint, Richard; Lowe, Tristan; Shearer, Tom

2016-01-01

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

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

Science.gov (United States)

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

2018-02-01

Purpose To synthesize two low-molecular-weight iron chelates and compare their T1 contrast effects with those of a commercial gadolinium-based contrast agent for their applicability in dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging. Materials and Methods The animal experiments were approved by the local ethics committee. Two previously described iron (Fe) chelates of pentetic acid (Fe-DTPA) and of trans-cyclohexane diamine tetraacetic acid (Fe-tCDTA) were synthesized with stability constants several orders of magnitude higher than those of gadolinium-based contrast agents. The T1 contrast effects of the two chelates were compared with those of gadopentetate dimeglumine in blood serum phantoms at 1.5 T, 3 T, and 7 T. For in vivo studies, a human breast cancer cell line (MDA-231) was implanted in five mice per group. The dynamic contrast effects of the chelates were compared by performing DCE MR imaging with intravenous application of Fe-DTPA or Fe-tCDTA on day 1 and DCE MR imaging in the same tumors with gadopentetate dimeglumine on day 2. Quantitative DCE maps were generated with software and were compared by means of a one-tailed Pearson correlation test. Results Relaxivities in serum (0.94 T at room temperature) of Fe-tCDTA (r1 = 2.2 mmol -1 · sec -1 , r2 = 2.5 mmol -1 · sec -1 ) and Fe-DTPA (r1 = 0.9 mmol -1 · sec -1 , r2 = 0.9 mmol -1 · sec -1 ) were approximately twofold and fivefold lower, respectively, compared with those of gadopentetate dimeglumine (r1 = 4.1 mmol -1 · sec -1 , r2 = 4.8 mmol -1 · sec -1 ). Used at moderately higher concentrations, however, iron chelates generated similar contrast effects at T1-weighted MR imaging in vitro in serum, in vivo in blood, and for DCE MR imaging of breast cancer xenografts. The volume transfer constant values for Fe-DTPA and Fe-tCDTA in the same tumors correlated well with those observed for gadopentetate dimeglumine (Fe-tCDTA Pearson R, 0.99; P = .0003; Fe-DTPA Pearson R, 0.97; P

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

Science.gov (United States)

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.

Quinone-fused porphyrins as contrast agents for photoacoustic imaging

KAUST Repository

Banala, Srinivas; Fokong, Stanley; Brand, Christian; Andreou, Chrysafis; Krä utler, Bernhard; Rueping, Magnus; Kiessling, Fabian

2017-01-01

Photoacoustic (PA) imaging is an emerging non-invasive diagnostic modality with many potential clinical applications in oncology, rheumatology and the cardiovascular field. For this purpose, there is a high demand for exogenous contrast agents

Measuring SPIO and Gd contrast agent magnetization using 3 T MRI

Science.gov (United States)

Cantillon-Murphy, Pádraig; Wald, Lawrence L.; Zahn, Markus; Adalsteinsson, Elfar

2011-01-01

Traditional methods of measuring magnetization in magnetic fluid samples, such as vibrating sample magnetometry (VSM), are typically limited to maximum field strengths of about 1 T. This work demonstrates the ability of MRI to measure the magnetization associated with two commercial MRI contrast agents at 3 T by comparing analytical solutions to experimental imaging results for the field pattern associated with agents in cylindrical vials. The results of the VSM and fitted MRI data match closely. The method represents an improvement over VSM measurements since results are attainable at imaging field strengths. The agents investigated are Feridex, a superparamagnetic iron oxide suspension used primarily for liver imaging, and Magnevist, a paramagnetic, gadolinium-based compound used for tumors, inflammation and vascular lesions. MR imaging of the agents took place in sealed cylindrical vials in the presence of a surrounding volume of deionized water where the effects of the contrast agents had a measurable effect on the water's magnetization in the vicinity of the compartment of contrast agent. A pair of phase images were used to reconstruct a B0 fieldmap. The resultant B0 maps in the water region, corrected for shimming and container edge effects, were used to predict the agent's magnetization at 3 T. The results were compared with the results from VSM measurements up to 1.2 T and close correlation was observed. The technique should be of interest to those seeking quantification of the magnetization associated with magnetic suspensions beyond the traditional scope of VSM. The magnetization needs to be sufficiently strong (Ms≳50 Am2/kg Fe for Feridex and χm≳5 × 10−5 m3/kg Gd for Magnevist) for a measurable dipole field in the surrounding water. For this reason, the technique is mostly suitable for undiluted agents. PMID:19588450

Multiphase contrast-enhanced CT with highly concentrated contrast agent can be used for PET attenuation correction in integrated PET/CT imaging

International Nuclear Information System (INIS)

Aschoff, Philip; Plathow, Christian; Lichy, Matthias P.; Claussen, Claus D.; Pfannenberg, Christina; Beyer, Thomas; Erb, Gunter; Oeksuez, Mehmet Oe.

2012-01-01

State-of-the-art positron emission tomography/computed tomography (PET/CT) systems incorporate multislice CT technology, thus facilitating the acquisition of multiphase, contrast-enhanced CT data as part of integrated PET/CT imaging protocols. We assess the influence of a highly concentrated iodinated contrast medium (CM) on quantification and image quality following CT-based attenuation correction (CT-AC) in PET/CT. Twenty-eight patients with suspected malignant liver lesions were enrolled prospectively. PET/CT was performed 60 min after injection of 400 MBq of 18 F-fluorodeoxyglucose (FDG) and following the biphasic administration of an intravenous CM (400 mg iodine/ml, Iomeron 400). PET images were reconstructed with CT-AC using any of four acquired CT image sets: non-enhanced, pre-contrast (n-PET), arterial phase (art-PET), portal venous phase (pv-PET) and late phase (late-PET). Normal tissue activity and liver lesions were assessed visually and quantitatively on each PET/CT image set. Visual assessment of PET following CT-AC revealed no noticeable difference in image appearance or quality when using any of the four CT data sets for CT-AC. A total of 44 PET-positive liver lesions was identified in 21 of 28 patients. There were no false-negative or false-positive lesions on PET. Mean standardized uptake values (SUV) in 36 evaluable lesions were: 5.5 (n-PET), 5.8 (art-PET), 5.8 (pv-PET) and 5.8 (late-PET), with the highest mean increase in mean SUV of 6%. Mean SUV changes in liver background increased by up to 10% from n-PET to pv-PET. Multiphase CT data acquired with the use of highly concentrated CM can be used for qualitative assessment of liver lesions in torso FDG PET/CT. The influence on quantification of FDG uptake is small and negligible for most clinical applications. (orig.)

Tumor Vessel Compression Hinders Perfusion of Ultrasonographic Contrast Agents

Directory of Open Access Journals (Sweden)

Mirco Galiè

2005-05-01

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

Advanced Contrast Agents for Multimodal Biomedical Imaging Based on Nanotechnology.

Science.gov (United States)

Calle, Daniel; Ballesteros, Paloma; Cerdán, Sebastián

2018-01-01

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

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

Science.gov (United States)

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

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

Science.gov (United States)

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

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-12-15

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

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

International Nuclear Information System (INIS)

Johnson, Joyce T.; Robinson, Joshua D.; Deng, Jie; Rigsby, Cynthia K.

2016-01-01

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

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

2008-09-01

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

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

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

2012-06-15

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

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

Directory of Open Access Journals (Sweden)

Egemen Altan

2013-01-01

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

Extracellular gadolinium contrast agents: Differences in stability

International Nuclear Information System (INIS)

Morcos, S.K.

2008-01-01

Extracellular gadolinium contrast agents (Gd-CA) are either linear or macrocyclic chelates available as ionic or non-ionic preparations. The molecular structure whether cyclic or linear and ionicity determines the stability of Gd-CA. Linear chelates are flexible open chains which do not offer a strong binding to Gd 3+ . In contrast, the macrocyclic chelates offer a strong binding to Gd 3+ by the virtue of being preorganized rigid rings of almost optimal size to cage the gadolinium atom. Non-ionic preparations are also less stable in comparison to the ionic ones as the binding between Gd 3+ with the negatively charged carboxyl groups is stronger in comparison to that with amides or alcohol in the non-ionic preparations. According to stability constants and kinetic measurements, the most stable Gd-CM is the ionic-macrocyclic chelate Gd-DOTA and the least stable agents are the non-ionic linear chelates gadodiamide and gadoversetamide. In vivo data confirmed the low stability of non-ionic linear chelates but no significant difference was observed amongst the macrocyclic agents whether ionic (Gd-DOTA) or non-ionic such as Gd-HP-DO3A and Gd-BT-DO3A. The stability of Gd-CA seems to be an important factor in the pathogenesis of the serious complication of nephrogenic systemic fibrosis. Gd-CA of low stability are likely to undergo transmetallation and release free Gd ions that deposit in tissue and attract circulating fibrocytes to initiate the process of fibrosis. No cases of NSF have been observed so far after the exclusive use of the stable macrocyclic Gd-CA

Clinical application of a triombrin in urology, a new Soviet radiographic contrast agent

International Nuclear Information System (INIS)

Perel'man, V.M.

1980-01-01

A water-soluble radiographic contrast agent triombrin which is a methylglucosamine sodium salt mixture of diatrizoate was studied. The analysis is based on the observation of 175 patients subjected to 186 tests, mainly excretory urography with the double dose of the contrast agent. The correlation between the quality of the picture obtained and the individual features of the patients has been established. Assessment of urograms obtained with the use of hypaque, urografin, verografin, urotrast and triombrin has revealed results similar to those with triombrin. Allergic reactions and complications have been noted in 23 (14%) of 164 patients after excretory and infusion urography. Satisfactory contrast and a good tolerance of the agent allowed recommending triombrin for wide use in medical practice

Preclinical Studies of a Kidney Safe Iodinated Contrast Agent.

Science.gov (United States)

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

2016-09-01

Contrast-induced acute kidney injury (CI-AKI) is a serious complication of the use of iodinated contrast agents. This problem is particularly acute in interventional neurology and interventional cardiology, probably due to the intra-arterial route of injection, high contrast volumes, and preexisting risk factors of these patients. In an attempt to develop a contrast agent that is less damaging to the kidneys, we have studied the effects of adding a small amount of the substituted cyclodextrin, sulfobutyl-ether-β-cyclodextrin (SBECD), to iohexol in rodent models of renal toxicity. Renally compromised mice and rats were injected with iohexol and iohexol-SBECD via the tail vein. The renal pathology, creatinine clearance, and survival benefits of iohexol-SBECD were studied. The safety of direct intra-arterial injection of the iohexol-SBECD formulation was studied in a dog heart model system. Mechanism of action studies in cell culture model using a human kidney cell line was performed using flow cytometry. Nephrotoxicity was significantly reduced using iohexol-SBECD compared to iohexol alone, at mole ratios of iohexol:SBECD of 1:0.025. SBECD increased survival from 50% to 88% in a rat survival study. In the dog heart model, iohexol-SBECD was safe. Cell culture studies suggest that SBECD interferes with the early stages of contrast-induced apoptosis in a human renal cell line. We have shown that the addition of a small amount of SBECD (one molecule of SBECD per 40 iohexol molecules) significantly protects rodent kidneys from CI-AKI. Further development of this new formulation of iodinated contrast is warranted. © 2016 The Authors. Journal of Neuroimaging published by Wiley Periodicals, Inc. on behalf of American Society of Neuroimaging.

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

Science.gov (United States)

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

Biological in situ characterization of polymeric microbubble contrast agents

NARCIS (Netherlands)

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

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

Phase change events of volatile liquid perfluorocarbon contrast agents produce unique acoustic signatures

International Nuclear Information System (INIS)

Sheeran, Paul S; Dayton, Paul A; Matsunaga, Terry O

2014-01-01

Phase-change contrast agents (PCCAs) provide a dynamic platform to approach problems in medical ultrasound (US). Upon US-mediated activation, the liquid core vaporizes and expands to produce a gas bubble ideal for US imaging and therapy. In this study, we demonstrate through high-speed video microscopy and US interrogation that PCCAs composed of highly volatile perfluorocarbons (PFCs) exhibit unique acoustic behavior that can be detected and differentiated from standard microbubble contrast agents. Experimental results show that when activated with short pulses PCCAs will over-expand and undergo unforced radial oscillation while settling to a final bubble diameter. The size-dependent oscillation phenomenon generates a unique acoustic signal that can be passively detected in both time and frequency domain using confocal piston transducers with an ‘activate high’ (8 MHz, 2 cycles), ‘listen low’ (1 MHz) scheme. Results show that the magnitude of the acoustic ‘signature’ increases as PFC boiling point decreases. By using a band-limited spectral processing technique, the droplet signals can be isolated from controls and used to build experimental relationships between concentration and vaporization pressure. The techniques shown here may be useful for physical studies as well as development of droplet-specific imaging techniques. (paper)

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

Science.gov (United States)

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

2015-09-01

The stochastic behavior of cavitation can lead to major problems of initiation and maintenance of cavitation during sonication, responsible of poor reproducibility of US-induced bioeffects in the context of sonoporation for instance. To overcome these disadvantages, the injection of ultrasound contrast agents as cavitation nuclei ensures fast initiation and lower acoustic intensities required for cavitation activity. More recently, regulated-cavitation devices based on the real-time modulation of the applied acoustic intensity have shown their potential to maintain a stable cavitation state during an ultrasonic shot, in continuous or pulsed wave conditions. In this paper is investigated the interest, in terms of cavitation activity, of using such regulated-cavitation device or injecting ultrasound contrast agents in the sonicated medium. When using fixed applied acoustic intensity, results showed that introducing ultrasound contrast agents increases reproducibility of cavitation activity (coefficient of variation 62% and 22% without and with UCA, respectively). Moreover, the use of the regulated-cavitation device ensures a given cavitation activity (coefficient of variation less 0.4% in presence of UCAs or not). This highlights the interest of controlling cavitation over time to free cavitation-based application from the use of UCAs. Interestingly, during a one minute sonication, while ultrasound contrast agents progressively disappear, the regulated-cavitation device counterbalance their destruction to sustain a stable inertial cavitation activity. Copyright © 2015 Elsevier B.V. All rights reserved.

Ultrasmall cationic superparamagnetic iron oxide nanoparticles as nontoxic and efficient MRI contrast agent and magnetic-targeting tool

Directory of Open Access Journals (Sweden)

Uchiyama MK

2015-07-01

Full Text Available Mayara Klimuk Uchiyama,1 Sergio Hiroshi Toma,1 Stephen Fernandes de Paula Rodrigues,2 Ana Lucia Borges Shimada,2 Rodrigo Azevedo Loiola,2 Hernán Joel Cervantes Rodríguez,3 Pedro Vitoriano Oliveira,4 Maciel Santos Luz,4 Said Rahnamaye Rabbani,3 Henrique Eisi Toma,1 Sandra Helena Poliselli Farsky,2 Koiti Araki11Laboratory of Supramolecular Chemistry and Nanotechnology, Department of Fundamental Chemistry, Institute of Chemistry, 2Laboratory of Experimental Toxicology, Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, 3Magnetic Resonance Laboratory, Department of General Physics, Institute of Physics, 4Analysis and Research Group in Spectrometry, Department of Fundamental Chemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, SP, BrazilAbstract: Fully dispersible, cationic ultrasmall (7 nm diameter superparamagnetic iron oxide nanoparticles, exhibiting high relaxivity (178 mM-1s-1 in 0.47 T and no acute or subchronic toxicity in Wistar rats, were studied and their suitability as contrast agents for magnetic resonance imaging and material for development of new diagnostic and treatment tools demonstrated. After intravenous injection (10 mg/kg body weight, they circulated throughout the vascular system causing no microhemorrhage or thrombus, neither inflammatory processes at the mesentery vascular bed and hepatic sinusoids (leukocyte rolling, adhesion, or migration as evaluated by intravital microscopy, but having been spontaneously concentrated in the liver, spleen, and kidneys, they caused strong negative contrast. The nanoparticles are cleared from kidneys and bladder in few days, whereas the complete elimination from liver and spleen occurred only after 4 weeks. Ex vivo studies demonstrated that cationic ultrasmall superparamagnetic iron oxide nanoparticles caused no effects on hepatic and renal enzymes dosage as well as on leukocyte count. In addition, they were readily concentrated in rat

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

International Nuclear Information System (INIS)

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

2016-01-01

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. (paper)

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

Science.gov (United States)

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

2014-04-18

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

The impact of injector-based contrast agent administration in time-resolved MRA.

Science.gov (United States)

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.

The influence of upper limb position on the effect of a contrast agent in chest CT enhancement

International Nuclear Information System (INIS)

Feng, Shi-Ting; Wang, Meng; Gao, Zhenhua; Tan, Guosheng; Cai, Huasong; Hu, Xiaoshu; Yang, Jianyong; Li, Zi-Ping

2013-01-01

Purpose: To compare the influence of two different upper limb positions on contrast agent effects in chest CT enhancement. Materials and methods: In 142 patients undergoing contrast-enhanced CT chest scanning, an indwelling venous catheter was placed in the right hand and iodinated contrast agent was injected through a high-pressure single syringe pump. The patients were divided into three age groups (<40 years; 40–60 years; and >60 years) and randomly assigned to one of two upper limb position groups: (1) supine position, both upper limbs extended and raised above head in the same horizontal plane as the body; and (2) supine position, both upper limbs raised and crossed on the forehead, with the right arm on top. Differences in mean CT values on the two sides of the thoracic inlet along the right subclavian vein were used to evaluate the effects of the contrast agent. Results: Although contrast agent effects were not significantly different among the three age groups with either limb position, there was a significant difference between patients adopting the second limb positions (Chi-square value was 5.936, P < 0.05). An excellent or good contrast agent effect was observed in 63.08% of patients assuming the first limb position, as compared with 81.69% assuming the second position. Conclusion: For contrast-enhanced CT chest scans, use of the second limb position can reduce retention of the contrast agent in the right axillary vein and the right subclavian vein outside the thorax, increase contrast agent utilization, and decrease artifacts caused by high-density, local retention of the contrast agent

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

Science.gov (United States)

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

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

Directory of Open Access Journals (Sweden)

Sabine Franckenberg, MD

2018-02-01

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

Chemistry of paramagnetic and diamagnetic contrast agents for Magnetic Resonance Imaging and Spectroscopy

International Nuclear Information System (INIS)

Perez-Mayoral, Elena; Negri, Viviana; Soler-Padros, Jordi; Cerdan, Sebastian; Ballesteros, Paloma

2008-01-01

We provide a brief overview of the chemistry and most relevant properties of paramagnetic and diamagnetic contrast agents (CAs) for Magnetic Resonance Imaging and Magnetic Resonance Spectroscopic Imaging. Paramagnetic CAs for MRI consist mainly of Gd(III) complexes from linear or macrocyclic polyaminopolycarboxylates. These agents reduce, the relaxation times T 1 and T 2 of the water protons in a concentration dependent manner, increasing selectively MRI contrast in those regions in which they accumulate. In most instances they provide anatomical information on the localization of lesions and in some specific cases they may allow to estimate some physiological properties of tissues including mainly vascular performance. Because of its ability to discriminate easily between normal and diseased tissue, extracellular pH (pH e ) has been added recently, to the battery of variables amenable to MRI investigation. A variety of Gd(III) containing macrocycles sensitive to pH, endogenous or exogenous polypeptides or even liposomes have been investigated for this purpose, using the pH dependence of their relaxivity or magnetization transfer rate constant (chemical exchange saturation transfer, CEST). Many environmental circumstances in addition to pH affect, however, relaxivity or magnetization transfer rate constants of these agents, making the results of pH measurements by MRI difficult to interpret. To overcome these limitations, our laboratory synthesized and developed a novel series of diamagnetic CAs for Magnetic Resonance Spectroscopic Imaging, a new family of monomeric and dimeric imidazolic derivatives able to provide unambiguous measurements of pH e , independent of water relaxivity, diffusion or exchange

Chemistry of paramagnetic and diamagnetic contrast agents for Magnetic Resonance Imaging and Spectroscopy

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Perez-Mayoral, Elena [Laboratorio de Sintesis Organica e Imagen Molecular por Resonancia Magnetica, Facultad de Ciencias, UNED, Paseo Senda del Rey 9, E-28040 Madrid (Spain); Departamento de Quimica Inorganica y Quimica Tecnica, Facultad de Ciencias, UNED, Paseo Senda del Rey 9, E-28040 Madrid (Spain); Negri, Viviana; Soler-Padros, Jordi [Laboratorio de Sintesis Organica e Imagen Molecular por Resonancia Magnetica, Facultad de Ciencias, UNED, Paseo Senda del Rey 9, E-28040 Madrid (Spain); Cerdan, Sebastian [Laboratorio de Imagen Espectroscopica por Resonancia Magnetica (LIERM), Instituto de Investigaciones Biomedicas ' Alberto Sols' , CSIC/UAM, c/Arturo Duperier 4, E-28029 Madrid (Spain); Ballesteros, Paloma [Laboratorio de Sintesis Organica e Imagen Molecular por Resonancia Magnetica, Facultad de Ciencias, UNED, Paseo Senda del Rey 9, E-28040 Madrid (Spain)], E-mail: pballesteros@ccia.uned.es

2008-09-15

We provide a brief overview of the chemistry and most relevant properties of paramagnetic and diamagnetic contrast agents (CAs) for Magnetic Resonance Imaging and Magnetic Resonance Spectroscopic Imaging. Paramagnetic CAs for MRI consist mainly of Gd(III) complexes from linear or macrocyclic polyaminopolycarboxylates. These agents reduce, the relaxation times T{sub 1} and T{sub 2} of the water protons in a concentration dependent manner, increasing selectively MRI contrast in those regions in which they accumulate. In most instances they provide anatomical information on the localization of lesions and in some specific cases they may allow to estimate some physiological properties of tissues including mainly vascular performance. Because of its ability to discriminate easily between normal and diseased tissue, extracellular pH (pH{sub e}) has been added recently, to the battery of variables amenable to MRI investigation. A variety of Gd(III) containing macrocycles sensitive to pH, endogenous or exogenous polypeptides or even liposomes have been investigated for this purpose, using the pH dependence of their relaxivity or magnetization transfer rate constant (chemical exchange saturation transfer, CEST). Many environmental circumstances in addition to pH affect, however, relaxivity or magnetization transfer rate constants of these agents, making the results of pH measurements by MRI difficult to interpret. To overcome these limitations, our laboratory synthesized and developed a novel series of diamagnetic CAs for Magnetic Resonance Spectroscopic Imaging, a new family of monomeric and dimeric imidazolic derivatives able to provide unambiguous measurements of pH{sub e}, independent of water relaxivity, diffusion or exchange.

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

International Nuclear Information System (INIS)

Joergensen, Jan Troest; Rief, Matthias; Wagner, Moritz; Brismar, Torkel B.; Albiin, Nils

2012-01-01

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

Assessment of local changes of cerebral perfusion and blood concentration by ultrasound harmonic B-mode contrast measurement in piglet.

NARCIS (Netherlands)

Wijk, M.C. van; Klaessens, J.H.G.M.; Hopman, J.C.W.; Liem, K.D.; Thijssen, J.M.

2003-01-01

This study tested the hypothesis that changes in the blood concentration, and possibly in the perfusion, of different areas in the brain can be assessed by the use of ultrasound contrast agent (CA) and (linear) echo densitometry. The experiments were performed with piglets (n=3) under general

Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin–avidin-specific binding

Science.gov (United States)

Liu, Yongjun; Wu, Xiaoyun; Sun, Xiaohe; Wang, Dan; Zhong, Ying; Jiang, Dandan; Wang, Tianqi; Yu, Dexin; Zhang, Na

2017-01-01

Developing magnetic resonance imaging (MRI) contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR)-targeted poly (l-lysine) (PLL)-diethylene triamine pentacetate acid (DTPA)-gadolinium (Gd) (VEGFR-targeted PLL-DTPA-Gd, VPDG), was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin–avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22%) in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG) (25.16%±4.71%, P<0.05). In MRI studies in vitro, significantly higher T1 relaxivity (14.184 mM−1 s−1) was observed compared to Magnevist® (4.9 mM−1 s−1; P<0.01). Furthermore, in vivo MRI study results showed that VPDG could significantly enhance the tumor signal intensity and prolong the diagnostic time (from <1 h to 2.5 h). These results indicated that macromolecular VPDG was a promising MRI contrast agent and held great potential for molecular diagnosis of tumor. PMID:28765707

High spatial resolution and high contrast visualization of brain arteries and veins. Impact of blood pool contrast agent and water-selective excitation imaging at 3T

International Nuclear Information System (INIS)

Spuentrup, E.; Jacobs, J.E.; Kleimann, J.F.

2010-01-01

Purpose: To investigate a blood pool contrast agent and water-selective excitation imaging at 3 T for high spatial and high contrast imaging of brain vessels including the veins. Methods and Results: 48 clinical patients (47 ± 18 years old) were included. Based on clinical findings, twenty-four patients received a single dose of standard extracellular Gadoterate-meglumine (Dotarem registered ) and 24 received the blood pool contrast agent Gadofosveset (Vasovist registered ). After finishing routine MR protocols, all patients were investigated with two high spatial resolution (0.15 mm 3 voxel size) gradient echo sequences in random order in the equilibrium phase (steady-state) as approved by the review board: A standard RF-spoiled gradient-echo sequence (HR-SS, TR/TE 5.1 / 2.3 msec, FA 30 ) and a fat-suppressed gradient-echo sequence with water-selective excitation (HR-FS, 1331 binominal-pulse, TR/TE 8.8 / 3.8 msec, FA 30 ). The images were subjectively assessed (image quality with vessel contrast, artifacts, depiction of lesions) by two investigators and contrast-to-noise ratios (CNR) were compared using the Student's t-test. The image quality and CNR in the HR-FS were significantly superior compared to the HR-SS for both contrast agents (p < 0.05). The CNR was also improved when using the blood pool agent but only to a minor extent while the subjective image quality was similar for both contrast agents. Conclusion: The utilized sequence with water-selective excitation improved image quality and CNR properties in high spatial resolution imaging of brain arteries and veins. The used blood pool contrast agent improved the CNR only to a minor extent over the extracellular contrast agent. (orig.)

An experimental study on tissue reaction of various contrast agents on mediastinum

International Nuclear Information System (INIS)

Chung, Jin Wook; Kim, Hyung Jin; Kim, Seung Hyup; Park, Jae Hyung; Chang, Kee Hyun

1989-01-01

Till now, there is no consensus about appropriate contrast agents for use in clinical investigation in suspected perforation of the esophagus. Gastrografin, most widely used water soluble contrast agent, is less sensitive in detection of fistulous tract and can induce pulmonary edema, leading to death occasionally, if aspirated. Barium sulphate has been contraindicated without actual evaluation of its effect on mediastinum by experimental and clinical study. The purpose of this experimental study is to evaluate the type of tissue reaction and its severity in mediastinum and, as a result, to propose appropriate contrast agents in various clinical situations of suspected esophageal leakage. Barium sulphate, Hytrat, Gastrografin, Telebrix, Hexabrix, Amipaque, Niopam, and Ultravist were injected into mediastinum of 20 rats in each. The tissue reaction of injection sites were examined microscopically and graded according severity of inflammatory reaction with serial follow up from 1 day to 8 weeks after injection. The results are as follows, 1. Barium sulphate and Hytrast produced highly significant (p<0.01) tissue reaction compared to saline group and early inflammatory reaction was more severe in Hytrast. 2. Water soluble agents produced no significant reaction in mediastinum compared to saline control group and proved to be safe in the situation of leakage into mediastinum. 3. Injected barium caused no death during 8 week follow up in spite of large injected amount and histologically produced localized indolent granuloma after 4 weeks which is expected not to cause any delayed complications. In consideration of above results, superior physical characteristics of barium sulphate and drawbacks of Gastrografin, we concluded as follows. 1. For postoperative assessment of esophageal anastomosis, Barium sulphate is the contrast agent of choice

Design, synthesis, and evaluation of VEGFR-targeted macromolecular MRI contrast agent based on biotin–avidin-specific binding

Directory of Open Access Journals (Sweden)

Liu YJ

2017-07-01

Full Text Available Yongjun Liu,1 Xiaoyun Wu,1 Xiaohe Sun,1 Dan Wang,1 Ying Zhong,1 Dandan Jiang,1 Tianqi Wang,1 Dexin Yu,2 Na Zhang1 1School of Pharmaceutical Science, Shandong University, 2Department of Radiology Medicine, Qilu Hospital, Jinan, People’s Republic of China Abstract: Developing magnetic resonance imaging (MRI contrast agents with high relaxivity and specificity was essential to increase MRI diagnostic sensitivity and accuracy. In this study, the MRI contrast agent, vascular endothelial growth factor receptor (VEGFR-targeted poly (l-lysine (PLL-diethylene triamine pentacetate acid (DTPA-gadolinium (Gd (VEGFR-targeted PLL-DTPA-Gd, VPDG, was designed and prepared to enhance the MRI diagnosis capacity of tumor. Biotin-PLL-DTPA-Gd was synthesized first, then, VEGFR antibody was linked to biotin-PLL-DTPA-Gd using biotin–avidin reaction. In vitro cytotoxicity study results showed that VPDG had low toxicity to MCF-7 cells and HepG2 cells at experimental concentrations. In cell uptake experiments, VPDG could significantly increase the internalization rates (61.75%±5.22% in VEGFR-positive HepG2 cells compared to PLL-DTPA-Gd (PDG (25.16%±4.71%, P<0.05. In MRI studies in vitro, significantly higher T1 relaxivity (14.184 mM-1 s-1 was observed compared to Magnevist® (4.9 mM-1 s-1; P<0.01. Furthermore, in vivo MRI study results showed that VPDG could significantly enhance the tumor signal intensity and prolong the diagnostic time (from <1 h to 2.5 h. These results indicated that macromolecular VPDG was a promising MRI contrast agent and held great potential for molecular diagnosis of tumor. Keywords: MRI, contrast agent, VEGFR, biotin–avidin reaction, relaxivity

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

Science.gov (United States)

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

2017-08-01

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

Self-Assembled Nanomicelles as MRI Blood-Pool Contrast Agent.

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Babič, Andrej; Vorobiev, Vassily; Xayaphoummine, Céline; Lapicorey, Gaëlle; Chauvin, Anne-Sophie; Helm, Lothar; Allémann, Eric

2018-01-26

Gadolinium-loaded nanomicelles show promise as future magnetic resonance imaging (MRI) contrast agents (CAs). Their increased size and high gadolinium (Gd) loading gives them an edge in proton relaxivity over smaller molecular Gd-complexes. Their size and stealth properties are fundamental for their long blood residence time, opening the possibility for use as blood-pool contrast agents. Using l-tyrosine as a three-functional scaffold we synthesized a nanostructure building block 8. The double C18 aliphatic chain on one side, Gd-1,4,7,10-tetraazacyclododecane-1-4-7-triacetic acid (Gd-DO3A) with access to bulk water in the center and 2 kDa PEG on the hydrophilic side gave the amphiphilic properties required for the core-shell nanomicellar architecture. The self-assembly into Gd-loaded monodispersed 10-20 nm nanomicelles occurred spontaneously in water. These nanomicelles (Tyr-MRI) display very high relaxivity at 29 mm -1  s -1 at low field strength and low cytotoxicity. Good contrast enhancement of the blood vessels and the heart together with prolonged circulation time in vivo, makes Tyr-MRI an excellent candidate for a new supramolecular blood-pool MRI CA. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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

2017-05-15

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

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

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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

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

Energy Technology Data Exchange (ETDEWEB)

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

2008-01-15

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

Arterial double-contrast dual-energy MDCT: in-vivo rabbit atherosclerosis with iodinated nanoparticles and gadolinium agents

Science.gov (United States)

Carmi, Raz; Kafri, Galit; Altman, Ami; Goshen, Liran; Planer, David; Sosna, Jacob

2010-03-01

An in-vivo feasibility study of potentially improved atherosclerosis CT imaging is presented. By administration of two different contrast agents to rabbits with induced atherosclerotic plaques we aim at identifying both soft plaque and vessel lumen simultaneously. Initial injection of iodinated nanoparticle (INP) contrast agent (N1177 - Nanoscan Imaging), two to four hours before scan, leads to its later accumulation in macrophage-rich soft plaque, while a second gadolinium contrast agent (Magnevist) injected immediately prior to the scan blends with the aortic blood. The distinction between the two agents in a single scan is achieved with a double-layer dual-energy MDCT (Philips Healthcare) following material separation analysis using the reconstructed images of the different x-ray spectra. A single contrast agent injection scan, where only INP was injected two hours prior to the scan, was compared to a double-contrast scan taken four hours after INP injection and immediately after gadolinium injection. On the single contrast agent scan we observed along the aorta walls, localized iodine accumulation which can point on INP uptake by atherosclerotic plaque. In the double-contrast scan the gadolinium contributes a clearer depiction of the vessel lumen in addition to the lasting INP presence. The material separation shows a good correlation to the pathologies inferred from the conventional CT images of the two different scans while performing only a single scan prevents miss-registration problems and reduces radiation dose. These results suggest that a double-contrast dual-energy CT may be used for advanced clinical diagnostic applications.

Contrast visibility for indirect MR arthrography with different protein contents and agent relaxivities at different field strengths: An in vitro model

International Nuclear Information System (INIS)

Nouh, M.R.; Schweitzer, M.E.; Ragatte, Ravinder R.

2011-01-01

Objectives: Protein binding and relaxivity are major determinants of the relative effectiveness of an MR arthrographic contrast agent. We sought to evaluate the optimal concentrations of high and usual relaxivity agents in two different proteinous environments at variable field strength for two MR contrast agents of different relaxivities. Materials and methods: At 1.5, 3.0 and 7.0 T, gadobenate dimeglumine (Multihance) with high-relaxivity in proteinous environment and gadoteridol (Prohance) with more typical behavior were studied at 1.25, 2.5, 5, and 10 mmol in 1.7 g/dL and 3 g/dL albumin (mimicking protein content of normal and inflammatory synovial fluids, respectively) vs. pure normal saline, as a control. Analysis of image signal intensity (SI) and relaxivity values was done. Results: In our study a change in concentration had no significant effect on T1 SI. In contrast, nearly every change in concentration led to a significant change in T2 SI. In 1.25 mmol concentration, there was no effect on T1 SI of either protein concentrations while higher concentrations showed significant decreased SI in either protein carrier compared to saline. The SI of Gadoteridol was significantly higher (p < 0.0001) than that of gadobenate at each of 3 T and 7 T, but was significantly lower (p < 0.001) at 1.5 T in saline solution while this was not significant for either protein carrier. Both protein carriers had significant effect on T1 (p = 0.0124) and T2 (p = 0.0118) relaxivities. Also solution concentration significantly (p < 0.01) affected both T1 and T2 relaxivities. Field strength did not affect T1 relaxivity (p = 0.02511) while it significantly affected T2 relaxivity (p < 0.001). This was significant (p = 0.035) in case of gadoteridol at 3 T. Conclusion: 1.25 mmol concentration of both gadoteridol and gadobenate solutions yields the best diagnostic T1 SI specially in higher fields (3 T and 7 T) and avoid the deleterious effect of increasing concentration on T2 SI

Tumor Vessel Compression Hinders Perfusion of Ultrasonographic Contrast Agents1

Science.gov (United States)

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

2005-01-01

Abstract Contrast-enhanced ultrasound (CEUS) is an advanced approach to in vivo assessment of tumor vascularity and is being increasingly adopted in clinical oncology. It is based on 1- to 10 µm-sized gas microbubbles, which can cross the capillary beds of the lungs and are effective echo enhancers. It is known that high cell density, high transendothelial fluid exchange, and poorly functioning lymphatic circulation all provoke solid stress, which compresses vessels and drastically reduces tumor blood flow. Given their size, we supposed that the perfusion of microbubbles is affected by anatomic features of tumor vessels more than are contrast agents traditionally used in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Here, we compared dynamic information obtained from CEUS and DCE-MRI on two experimental tumor models exhibiting notable differences in vessel anatomy. We found that tumors with small, flattened vessels show a much higher resistance to microbubble perfusion than to MRI contrast agents, and appear scarcely vascularized at CEUS examination, despite vessel volume adequate for normal function. Thus, whereas CEUS alone could induce incorrect diagnosis when tumors have small or collapsed vessels, integrated analysis using CEUS and DCE-MRI allows in vivo identification of tumors with a vascular profile frequently associated with malignant phenotypes. PMID:15967105

Ultrasound contrast agents: An overview

International Nuclear Information System (INIS)

Cosgrove, David

2006-01-01

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

Intravenous digital subtraction angiography contrast media time-concentration curves

International Nuclear Information System (INIS)

Burbank, F.H.; Brody, W.R.

1985-01-01

At any specified radiation dose and system signal-to-noise ratio, temporal (masked-mode) intravenous digital subtraction angiography (IV-DSA) image quality is dependent upon the shape of the arterial time-concentration curve produced by the intravenous injection of iodinated contrast media. If contrast media appears in the arterial circulation as a compact bolus and reaches a high peak, images containing low or no iodine (the mask image or images) and high iodine concentration (the enhanced image or images) can be obtained close together in time, maximizing contrast media enhancement and minimizing the potential for spatial movement (misregistration). However, if the contrast media bolus is broad, rising slowly to a low concentration peak, sufficient time may pass for movement to occur and the opacification difference between the mask image and the enhanced image may be too small to visualize vessels of interest. Consequently, knowledge of the rules which govern the formation of time-concentration curves is central to IV-DSA

Biochemical Stability Analysis of Nano Scaled Contrast Agents Used in Biomolecular Imaging Detection of Tumor Cells

Science.gov (United States)

Kim, Jennifer; Kyung, Richard

Imaging contrast agents are materials used to improve the visibility of internal body structures in the imaging process. Many agents that are used for contrast enhancement are now studied empirically and computationally by researchers. Among various imaging techniques, magnetic resonance imaging (MRI) has become a major diagnostic tool in many clinical specialties due to its non-invasive characteristic and its safeness in regards to ionizing radiation exposure. Recently, researchers have prepared aqueous fullerene nanoparticles using electrochemical methods. In this paper, computational simulations of thermodynamic stabilities of nano scaled contrast agents that can be used in biomolecular imaging detection of tumor cells are presented using nanomaterials such as fluorescent functionalized fullerenes. In addition, the stability and safety of different types of contrast agents composed of metal oxide a, b, and c are tested in the imaging process. Through analysis of the computational simulations, the stabilities of the contrast agents, determined by optimized energies of the conformations, are presented. The resulting numerical data are compared. In addition, Density Functional Theory (DFT) is used in order to model the electron properties of the compound.

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

Directory of Open Access Journals (Sweden)

Y. Lalatonne

2010-01-01

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

Tissue-specific MR contrast agents. Impact on imaging diagnosis and future prospects

International Nuclear Information System (INIS)

Yoshimitsu, Kengo; Nakayama, Tomohiro; Kakihara, Daisuke; Irie, Hiroyuki; Tajima, Tsuyoshi; Asayama, Yoshiki; Hirakawa, Masakazu; Ishigami, Kousei; Honda, Hiroshi

2005-01-01

Superparamagnetic iron oxide (SPIO) is the only tissue-specific MR agent currently available in Japan. It is quickly taken up by Kupffer cells at the first pass (either arterial or portal) and becomes clustered in the lysosome, providing characteristic T2 * and T2 shortening effects that suppresses the signal of normal or non-tumorous liver tissue. SPIO has dramatically changed the diagnostic algorithm of liver metastasis in clinical practice, now serving as the gold standard instead of CT during arterial portography (CTAP). Its role in the diagnosis of hepatocellular carcinoma (HCC), however, is somewhat complicated, owing to its heterogeneous uptake by the background cirrhotic liver, as well as by some of the HCCs themselves. It has been shown to be useful in the diagnosis of pseudolesions (arterioportal shunts) and some benign hepatocellular lesions (focal nodular hyperplasia or adenoma) by their complete or partial uptake of SPIO, in contrast to an absence of uptake by true liver lesions. It has also been suggested that the histological grade of HCC affects the degree of SPIO uptake. Thus, SPIO serves as a complementary tool to the primary modalities of vascular survey, namely, dynamic CT/MR and CT during hepatic arteriography (CTHA)/CTAP, in the diagnosis of HCC. Gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) is a novel hepatobiliary contrast agent that is not yet available but is supposed to be approved by the Ministry of Health, Labour, and Welfare of Japan in the near future. It is taken up by hepatocytes and excreted into the bile, providing a T1-shortening effect that enhances the normal or non-tumorous liver tissue. It has also been shown to have the effect of positive enhancement of hypervascular liver tumors on the arterial phase, just like the usual extracellular contrast agent (gadopentetate dimeglumine: Gd-DTPA). Thus, Gd-EOB-DTPA was once thought to be an ideal contrast agent for liver tumors, providing information on both

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

International Nuclear Information System (INIS)

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

2005-01-01

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

Ultrasound contrast agents: an overview.

Science.gov (United States)

Cosgrove, David

2006-12-01

With the introduction of microbubble contrast agents, diagnostic ultrasound has entered a new era that allows the dynamic detection of tissue flow of both the macro and microvasculature. Underpinning this development is the fact that gases are compressible, and thus the microbubbles expand and contract in the alternating pressure waves of the ultrasound beam, while tissue is almost incompressible. Special software using multiple pulse sequences separates these signals from those of tissue and displays them as an overlay or on a split screen. This can be done at low acoustic pressures (MIdeveloped for myocardial perfusion. In radiology, the most important application is the liver, especially for focal disease. The approach parallels that of dynamic CT or MRI but ultrasound has the advantages of high spatial and temporal resolution. Thus, small lesions that can be indeterminate on CT can often be studied with ultrasound, and situations where the flow is very rapid (e.g., focal nodular hyperplasia where the first few seconds of arterial perfusion may be critical to making the diagnosis) are readily studied. Microbubbles linger in the extensive sinusoidal space of normal liver for several minutes whereas they wash out rapidly from metastases, which have a low vascular volume and thus appear as filling defects. The method has been shown to be as sensitive as three-phase CT. Microbubbles have clinical uses in many other applications where knowledge of the microcirculation is important (the macrocirculation can usually be assessed adequately using conventional Doppler though there are a few important situations where the signal boost given by microbubbles is useful, e.g., transcranial Doppler for evaluating vasospasm after subarachnoid haemorrhage). An important situation where demonstrating tissue devitalisation is important is in interstitial ablation of focal liver lesions: using microbubble contrast agents at the end of a procedure allows immediate evaluation of the

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.

Science.gov (United States)

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.

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

Science.gov (United States)

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

2015-06-01

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

A model for ultrasound contrast agent in a phantom vessel

KAUST Repository

Qamar, Adnan; Samtaney, Ravi

2014-01-01

A theoretical framework to model the dynamics of Ultrasound Contrast Agent (UCA) inside a phantom vessel is presented. The model is derived from the reduced Navier-Stokes equation and is coupled with the evolving flow field solution inside

Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

Directory of Open Access Journals (Sweden)

Kim Hyo Jeong

2010-01-01

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

Glucose-installed, SPIO-loaded PEG- b-PCL micelles as MR contrast agents to target prostate cancer cells

Science.gov (United States)

Theerasilp, Man; Sunintaboon, Panya; Sungkarat, Witaya; Nasongkla, Norased

2017-11-01

Polymeric micelles of poly(ethylene glycol)- block-poly(ɛ-caprolactone) bearing glucose analog encapsulated with superparamagnetic iron oxide nanoparticles (Glu-SPIO micelles) were synthesized as an MRI contrast agent to target cancer cells based on high-glucose metabolism. Compared to SPIO micelles (non-targeting SPIO micelles), Glu-SPIO micelles demonstrated higher toxicity to human prostate cancer cell lines (PC-3) at high concentration. Atomic absorption spectroscopy was used to determine the amount of iron in cells. It was found that the iron in cancer cells treated by Glu-SPIO micelles were 27-fold higher than cancer cells treated by SPIO micelles at the iron concentration of 25 ppm and fivefold at the iron concentration of 100 ppm. To implement Glu-SPIO micelles as a MR contrast agent, the 3-T clinical MRI was applied to determine transverse relaxivities ( r 2*) and relaxation rate (1/ T 2*) values. In vitro MRI showed different MRI signal from cancer cells after cellular uptake of SPIO micelles and Glu-SPIO micelles. Glu-SPIO micelles was highly sensitive with the r 2* in agarose gel at 155 mM-1 s-1. Moreover, the higher 1/ T 2* value was found for cancer cells treated with Glu-SPIO micelles. These results supported that glucose ligand increased the cellular uptake of micelles by PC-3 cells with over-expressing glucose transporter on the cell membrane. Thus, glucose can be used as a small molecule ligand for targeting prostate cancer cells overexpressing glucose transporter.

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

Science.gov (United States)

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.

Risk Stratification of iodine-induced thyrotoxicosis before contrast agent application

International Nuclear Information System (INIS)

Fricke, E.

2004-01-01

Today, examinations using iodine containing contrast media are rather frequent. Even though in modern contrast agents the content of free iodine is low, in vivo deiodination results in a non physiologic high iodine load of the thyroid gland. Whilst in normal thyroid tissue iodine metabolism and hormone production are self-regulating in spite of the variable iodine load, those mechanisms are disturbed in autonomous thyroid tissue. Clinical studies displayed low risk of iodine induced thyrotoxicosis after application of contrast agent. Nonetheless the clinician has to assess the risk of thyrotoxicosis for each individual patient and he has to decide how to cope with this risk. Thyroid scintigraphy using Tc-99m-pertechnetate with quantitative measurement of the thyroidal uptake (TcTU) has been shown to be a useful tool in this question, especially when performed under suppression of the non-autonomous tissue (TcTUs). In particular patients with pre-existing suppression of the TSH secretion should be selected for this investigation. Also at risk are elderly persons and those with diffuse or nodular goitres. In spite of the high frequency of contrast agent applications, data on scintigraphy for risk evaluation of thyrotoxicosis and on efficacy of prophylactic medication are scarce. Based on own results and on a review of literature, the risk of thyrotoxicosis seems to be negligible in patients with a TcTUs of less than 1% even in case of preexistent latent hyperthyroidism. If a suppressed TSH level is known and TcTUs is higher than 1%, prophylactic medication should be given. There is evidence for a combination therapy inhibiting both iodine uptake and metabolism, i.e. with perchlorate and thiamazole, being more efficient than monotherapy, particularly in patients with high risk of thyrotoxicosis. (orig.)

Studies on polyaspartamide gadolinium complexes as potential magnetic resonance imaging contrast agents

International Nuclear Information System (INIS)

Yan Guoping; Liu Maili; Li Liyun

2005-01-01

Purpose: A series of polyaspartamide gadolinium complexes containing pyridoxamine groups were studied as the potential magnetic resonance imaging (MRI) contrast agents for liver enhancement. Methods: These polyaspartamide gadolinium complexes were prepared and evaluated by relaxivity, acute toxicity studies and magnetic resonance imaging of the liver in rats. Results: These polyaspartamide gadolinium complexes have higher relaxation effectiveness than that of the clinically used gadolinium diethylenetriaminepentaacetic acid and possess the low intravenous acute toxicities to Institute for Cancer Research (ICR) mice. Magnetic resonance imaging of the liver in rats indicated that they greatly enhance the contrast of magnetic resonance images and provide prolonged intravascular duration in the liver. Conclusion: These results indicated that the polyaspartamide gadolinium complexes containing pyridoxamine groups could be considered as the appropriate MRI contrast agents for liver enhancement

Study on the uptake and distribution of gadolinium based contrast agents in biological samples using laser ablation with inductively coupled plasma mass spectroscopy

International Nuclear Information System (INIS)

Lingott, Jana

2016-01-01

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

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

Science.gov (United States)

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

2006-10-03

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

Effect of contrast media iodine concentration on bolus tracking

International Nuclear Information System (INIS)

Ishihara, Toshihiro; Hayashi, Takayuki; Nakaya, Yoshihiro; Naoi, Kuniji; Ikeno, Naoya; Kobayashi, Tatsushi; Satake, Mitsuo

2006-01-01

Computer-assisted bolus tracking has been confirmed to be a useful technique in computed tomography (CT) imaging and allows images to be captured with automated timing. The inflow of the contrast medium is monitored, and when the contrast medium reaches a predetermined level, CT image capture starts automatically. However, it has been shown that the preset threshold value of contrast medium is affected by its iodine concentration, which causes variations in image capture times. Greater speed in current multislice CT imaging requires that medical technicians pay more attention to setting the timing of image capture during venous examinations by taking into account the iodine concentration in contrast media. (author)

An MR Contrast Agent for Intra-Prostatic Imaging of Prostatic Cancer

National Research Council Canada - National Science Library

Josephson, Lee

2004-01-01

The goal of the current research is the development of a magnetic nanoparticle based MR contrast agent that binds the gastrin releasing peptide receptor, a molecular marker associated with neoplasia...

Contrast Agents for Micro-Computed Tomography of Microdamage in Bone

National Research Council Canada - National Science Library

Roeder, Ryan K

2008-01-01

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

Imaging efficiency of an X-ray contrast agent-incorporated polymeric microparticle.

Science.gov (United States)

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

2011-01-01

Biocompatible polymeric encapsulants have been widely used as a delivery vehicle for a variety of drugs and imaging agents. In this study, X-ray contrast agent (iopamidol) is encapsulated into a polymeric microparticle (polyvinyl alcohol) as a particulate flow tracer in synchrotron X-ray imaging system. The physical properties of the designed microparticles are investigated and correlated with enhancement in the imaging efficiency by experimental observation and theoretical interpretation. The X-ray absorption ability of the designed microparticle is assessed by Beer-Lambert-Bouguer law. Particle size, either in dried state or in solvent, primarily dominates the X-ray absorption ability under the given condition, thus affecting imaging efficiency of the designed X-ray contrast flow tracers. Copyright © 2011 John Wiley & Sons, Ltd.

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

Science.gov (United States)

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

2017-04-01

The introduction of spectral CT imaging in the form of fast clinical dual-energy CT enabled contrast material to be differentiated from other radiodense materials, improved lesion detection in contrast-enhanced scans, and changed the way that existing iodine and barium contrast materials are used in clinical practice. More profoundly, spectral CT can differentiate between individual contrast materials that have different reporter elements such that high-resolution CT imaging of multiple contrast agents can be obtained in a single pass of the CT scanner. These spectral CT capabilities would be even more impactful with the development of contrast materials designed to complement the existing clinical iodine- and barium-based agents. New biocompatible high-atomic number contrast materials with different biodistribution and X-ray attenuation properties than existing agents will expand the diagnostic power of spectral CT imaging without penalties in radiation dose or scan time. Copyright © 2016 Elsevier B.V. All rights reserved.

Adverse events caused by MRI contrast agents: Implications for radiographers who inject

International Nuclear Information System (INIS)

Marshall, Gill; Kasap, Chris

2012-01-01

This article provides a comprehensive literature review regarding side effects both minor and major associated with contrast agent injection. This includes a discussion of nephrogenic systemic fibrosis (NSF), which remains highly topical. Radiographers now commonly are responsible for injection of contrast agent in patients, in keeping with their extended role. Therefore it is incumbent on them to understand the agents they inject, the contra-indications for injection and any potential associated risks, so that they can act and react accordingly in a timely manner. The need for this knowledge was made very evident after the recent death of a patient from anaphylactic shock when there was a delay in mounting the appropriate procedure. This paper represents a synthesis of relevant articles and reflects on the results, before drawing appropriate conclusions particularly those of special relevance to radiographers.

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

Science.gov (United States)

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

An MR Contrast Agent for Intra-Prostatic Imaging of Prostatic Cancer

National Research Council Canada - National Science Library

Josephson, Lee

2005-01-01

An MR contrast agent targeted to the GRP receptor will be a novel pharmaceutical capable of non-invasively, and at high spatial resolution, characterizing healthy and patholological regions within the prostate...

Contrast agent based on nano-emulsion for targeted biomedical imaging

International Nuclear Information System (INIS)

Attia, Mohamed

2016-01-01

X-ray imaging agents are essential in combination with X-ray computed tomography to improve contrast enhancement aiming at providing complete visualization of blood vessels and giving structural and functional information on lesions allowing the detection of a tumor. As well as it is fundamental tool to discriminate between healthy cells and pathogens. We successfully limit the problems presented in commercial X-ray contrast agents like poor contrasting in Fenestra VC associated with short blood circulation time and to avoid rapid renal elimination from the body as found in Xenetix (Iobitriol). We developed nontoxic and blood pool iodine-containing nano-emulsion contrast agents serving in preclinical X-ray μ-CT imaging such as, a- Tocopherol (vitamin E), Cholecalciferol (vitamin D3), Castor oil, Capmul MCMC8 oil and oleic acid. Those formulated nano emulsions were prepared by low energy spontaneous emulsification technic with slight modification for each platform. They showed new specific features rendering them promising agents in in vivo experiments as improving the balance between the efficacy and the toxicity of targeted therapeutic interventions. We investigate the effect of size and the chemical composition of the nanoparticles on their biodistribution, pharmacokinetics and toxicity. They demonstrated that the chemical structures of the droplet's cores have significant role in targeting for example vitamin E was mainly accumulated in liver and castor oil formulation was passively accumulated in spleen explaining the proof-of-concept of EPR effect. On the other hand, two different platform sizes of Cholecalciferol molecule revealing that no real impact on the pharmacokinetics and biodistribution but presented remarkable effect on the toxicity. Of particular interest is studying the effect of the surface charge of nanoparticles on their biodistribution, this is why oleic acid nano-emulsion was selected to proceed this study by presence of amphiphilic polymer

Synthesis of Laboratory Ultrasound Contrast Agents

Directory of Open Access Journals (Sweden)

Jaemin Oh

2013-10-01

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

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

Science.gov (United States)

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

2013-04-01

Despite the wide application of gadolinium as a contrast agent for magnetic resonance imaging (MRI), there is a serious lack of information on its toxicity. Gadolinium and gadolinium oxide (Gd-oxide) are used as contrast agents for magnetic resonance imaging (MRI). There are methods for reducing toxicity of these materials, such as core nanoparticles coating or conjugating. Therefore, for toxicity evaluation, we compared the viability of commercial contrast agents in MRI (Gd-DTPA) and three nanoparticles with the same core Gd2O3 and small particulate gadolinium oxide or SPGO (DTPA. The MTT and LDH assay results showed that Gd2O3-DEG nanoparticles were more toxic than Gd-DTPA and other nanoparticles. Also, SPGO-mPEG-silane2000 was more biocompatible than other nanoparticles. The obtained results did not show any significant increase in cytotoxicity of the nanoparticles and Gd-DTPA, neither dose-dependent nor time-dependent. Therefore, DEG and PEG, due to their considerable properties and irregular sizes (different molecular weights), were selected as the useful surface covering materials of nanomagnetic particles that could reveal noticeable relaxivity and biocompatibility characteristics.

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

International Nuclear Information System (INIS)

D'Ippolito, Giuseppe; Braga, Fernanda Angeli; Resende, Marcelo Cardoso; Bretas, Elisa Almeida Sathler; Nunes, Thiago Franchi; Rosas, George de Queiroz; Tiferes, Dario Arie

2012-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-05-15

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

Novel Synthesis of Ultra-Small Dextran Coated Maghemite Nanoparticles for MRI and CT Contrast Agents via a Low Temperature Co-Precipitation Reaction.

Science.gov (United States)

Rabias, Ioannis; Fardis, Michael; Kehagias, Thomas; Kletsas, Dimitris; Pratsinis, Harris; Tsitrouli, Danai; Maris, Thomas G; Papavassiliou, George

2015-01-01

Ultra-small dextran coated maghemite nanoparticles are synthesized via a low temperature modified co-precipitation method. A monoethylene glycol/water solution of 1:1 molar ratios and a fixed apparatus is used at a constant temperature of 5-10 degrees C. The growth of nanoparticles is prohibited due to low temperature synthesis and differs from usual thermal decomposition methods via Ostwald ripening. Strict temperature control and reaction timing of less than 20 minutes are essential to maintain narrow distribution in particle size. These nanoparticles are water-dispersible and biocompatible by capping with polyethylene glycol ligands. The aqueous suspensions are tested for cytotoxic activity on normal human skin fibroblasts. There is no reduction of the cells' viability at any concentration tested, the highest being 1% v/v of the suspension in culture medium, corresponding to the highest concentrations to be administered in vivo. Initial comparison with a T1 MRI contrast agent in sale shows that maghemite nanoparticles exhibit high r1 and r2 relaxivities in MRI tomography and strong contrast in computed tomography, demonstrating that these nanoparticles can be efficient T1, T2 and CT contrast agents.

Optical-based molecular imaging: contrast agents and potential medical applications

International Nuclear Information System (INIS)

Bremer, Christoph; Ntziachristos, Vasilis; Weissleder, Ralph

2003-01-01

Laser- and sensitive charge-coupled device technology together with advanced mathematical modelling of photon propagation in tissue has prompted the development of novel optical imaging technologies. Fast surface-weighted imaging modalities, such as fluorescence reflectance imaging (FRI) and 3D quantitative fluorescence-mediated tomography have now become available [1, 2]. These technical advances are paralleled by a rapid development of a whole range of new optical contrasting strategies, which are designed to generate molecular contrast within a living organism. The combination of both, technical advances of light detection and the refinement of optical contrast media, finally yields a new spectrum of tools for in vivo molecular diagnostics. Whereas the technical aspects of optical imaging are covered in more detail in a previous review article in ''European Radiology'' [3], this article focuses on new developments in optical contrasting strategies and design of optical contrast agents for in vivo diagnostics. (orig.)

Effervescent agents in the double contrast examination of the stomach

International Nuclear Information System (INIS)

Virkkunen, P.; Kreula, J.

1981-01-01

The buffer capacities of the BaSO 4 contrast media are poor. Yet the pH changes caused by effervescent agents or gastric contents are insignificant for mucosal adsorption. The increase of the viscosity and decrease of the density impair the results of the examination. (Auth.)

Non-invasive estimation of blood pressure using ultrasound contrast agents

DEFF Research Database (Denmark)

Andersen, Klaus Scheldrup; Jensen, Jørgen Arendt

2009-01-01

Local blood pressure measurements provide important information on the state of health of organs in the body and can be used to diagnose diseases in the heart, lungs, and kidneys. This paper presents an experimental setup for investigating the ambient pressure sensitivity of a contrast agent using...

Acoustic bubble sorting for ultrasound contrast agent enrichment.

Science.gov (United States)

Segers, Tim; Versluis, Michel

2014-05-21

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

Contrast agents for tumor diagnosis in magnetic resonance imaging

Energy Technology Data Exchange (ETDEWEB)

Goto, Rensuke; Doi, Hisayoshi; Okada, Shoji [University of Shizuoka (Japan). School of Pharmaceutical Science; Yano, Masayuki; Katano, Susumu; Nakajima, Nobuaki

1992-01-01

In order to develop contrast agents for tumor diagnosis in magnetic resonance imaging (MRI), we investigated the effects of several gadolinium complexes on T{sub 1} relaxation time of proton in some tissues of Ehrlich solid tumor-bearing mice. L-Aspartic acid, L-glutamic acid, DL-homocysteine, L-glutamyl-glutamic acid, glutathione, sperimidine and ethylenediaminetetrakis (methylenephosphate) (EDTMP) were used as ligands for Gd{sup 3+}. Since each Gd-complex could not be purified except Gd-EDTMP, the mixture of GdCl{sub 3} and a ligand was administered intravenously. Among the compounds tested, the mixture of aspartic acid, glutathione or spermidine with GdCl{sub 3} showed almost the same or above reduction of T{sub 1} relaxation times in the tumor tissue compared with Gd-diethylenetriamine pentaacetic acid (Gd-DTPA) which is used clinically. Furthermore, the contrast-enhancing effect of the three mixtures in the tumor was observed by in vivo T{sub 1}-weighted magnetic resonance imaging. The in vivo tissue distribution using radioactive {sup 153}Gd{sup 3+} showed that these mixtures mentioned above were also taken up more highly in the tumor than {sup 153}GdCl{sub 3} itself and {sup 153}Gd-DTPA, suggesting the formation of Gd-complexes. However, the overall tissue distribution of the mixtures was similar to that of {sup 153}GdCl{sub 3} because the Gd-complexes were not purified. Gd-EDTMP exhibited the almost same effects with Gd-DTPA as a contrast agent. (author).

Synthesis Of Gd-dtpa-folat For Magnetic Resonance Imaging Contrast Agent And Characterization By Using 153gd-dtpa-folate Radioactive

OpenAIRE

G., Adang H; S., Yono; Maskur

2012-01-01

Contrast agent was used to clarify the image of the organ that is difficult to distinguish by MRI (Magnetic Resonance Imaging) techniques, particularly in soft tissues of the central nervous system, liver, digestive system, lymphatic system, breast, cardiovascular and pulmonary systems. One of the commonly used contrast agents in hospitals is Gadolinium-DieThylenetriamine Pentaacetic Acid (Gd-DTPA). Gd-DTPA is non specific contrast agent, therefore it has led to develop a contrast agent that ...

Renal perfusion image using harmonic ultrasound with microbble contrast agent: preliminary study

International Nuclear Information System (INIS)

Kim, Jung Hoon; Choi, Jae Ho; Han, Dong Chul; Lee, Hi Bahl; Choi, Deuk Lin; Eun, Hyo Won; Lee, Hun Jae

2003-01-01

To compare, in terms of their feasibility and normal range, 99m Tc-DTPA renal perfusion imaging and renal perfusion imaging using harmonic ultrasound (US) with a microbubble contrast agent for the evaluation of renal perfusion after renal transplantation. During a six-month period, thirty patients who had received a renal transplant underwent both 99m Tc-DTPA renal perfusion imaging and renal perfusion imaging using harmonic US with a microbubble contrast agent. Sonographic renal perfusion images were obtained before and after a bolus injection of the microbubble contrast agent Levovist TM (SH U 5084; Schering AG, Berlin, Germany) every 3 seconds for 3 minutes. Sonographic renal perfusion images were converted into a renal perfusion curve by a computer program and T peak of the curve thus obtained was compared with that of the 99m Tc-DTPA curve. Average T peak of the 99m Tc-DTPA renal perfusion curve was 16.2 seconds in the normal group and 39.6 seconds in the delayed perfusion group, while average T peak of the sonographic renal perfusion curve was 23.7 seconds and 46.2 seconds, respectively. T peak of the sonographic renal perfusion curve showed a good correlation with that of the 99m Tc-DTPA curve (correlation coefficient=0.8209; p=0.0001). The cut-off value of T peak of the sonographic renal perfusion curve was 35 seconds (sensitivity=90%, specificity=95%). In patients who have received a renal transplant, the findings of renal perfusion imaging using harmonic US with a microbubble contrast agent show close correlation with those of 99m Tc-DTPA renal perfusion imaging. The optimal cut-off value of T peak of the sonographic renal perfusion curve was 35 seconds

Fluorine cardiovascular magnetic resonance angiography in vivo at 1.5 T with perfluorocarbon nanoparticle contrast agents.

Science.gov (United States)

Neubauer, Anne M; Caruthers, Shelton D; Hockett, Franklin D; Cyrus, Tillman; Robertson, J David; Allen, J Stacy; Williams, Todd D; Fuhrhop, Ralph W; Lanza, Gregory M; Wickline, Samuel A

2007-01-01

While the current gold standard for coronary imaging is X-ray angiography, evidence is accumulating that it may not be the most sensitive technique for detecting unstable plaque. Other imaging modalities, such as cardiovascular magnetic resonance (CMR), can be used for plaque characterization, but suffer from long scan and reconstruction times for determining regions of stenosis. We have developed an intravascular fluorinated contrast agent that can be used for angiography with cardiovascular magnetic resosnace at clinical field strengths (1.5 T). This liquid perfluorocarbon nanoparticle contains a high concentration of fluorine atoms that can be used to generate contrast on 19F MR images without any competing background signal from surrounding tissues. By using a perfluorocarbon with 20 equivalent fluorine molecules, custom-built RF coils, a modified clinical scanner, and an efficient steady-state free procession sequence, we demonstrate the use of this agent for angiography of small vessels in vitro, ex vivo, and in vivo. The surprisingly high signal generated with very short scan times and low doses of perfluorocarbon indicates that this technique may be useful in clinical settings when coupled with advanced imaging strategies.

Evaluation of chirp reversal power modulation sequence for contrast agent imaging

International Nuclear Information System (INIS)

Novell, A; Sennoga, CA; Escoffre, JM; Chaline, J; Bouakaz, A

2014-01-01

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

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

International Nuclear Information System (INIS)

Yazdani, Farshad; Fattahi, Bahare; Azizi, Najmodin

2016-01-01

The aim of this research was the preparation of functionalized magnetite nanoparticles to use as a liver targeting contrast agent in magnetic resonance imaging (MRI). For this purpose, Fe_3O_4 nanoparticles were synthesized via the co-precipitation method. The synthesized nanoparticles were coated with silica via the Stober method and finally the coated nanoparticles were functionalized with mebrofenin. Formation of crystalline magnetite particles was confirmed by X-ray diffraction (XRD) analysis. The Fourier transform infrared spectroscopy (FTIR) and energy dispersive X-ray analyzer (EDX) of the final product showed that silica had been effectively bonded onto the surface of the magnetite nanoparticles and the coated nanoparticles functionalized with mebrofenin. The magnetic resonance imaging of the functional nanoparticles showed that the Fe_3O_4–SiO_2-mebrofenin composite is an effective MRI contrast agent for liver targeting. - Highlights: • Superparamagnetic magnetite nanoparticles have been synthesized by simple and economical method. • Preperation of functional MNPs as a MRI contrast agent for liver targeting. • Gaining a good r_2 relaxivity of the coated functional nanoparticles.

PEGylated chitosan grafted with polyamidoaminedendron as tumor-targeted magnetic resonance imaging contrast agent

International Nuclear Information System (INIS)

Guangyue Zu; Xiaoyan Tong; Yi Cao; Ye Kuang; Yajie Zhang; Min Liu; Renjun Pei

2017-01-01

Macromolecular contrast agents labeled with targeting ligands are now receiving growing interest in tumor-targeted magnetic resonance imaging. In this study, a macromolecular contrast agent based on PEGylated chitosan was synthesized and characterized, and its application as an MRI contrast agent was then demonstrated both in vitro and in vivo. First, the chitosan backbone was partially grafted with poly(ethylene glycol), which was used to improve the in vivo stability, followed by modifying with azide groups. Second, alkynyl-terminated PAMAM dendron modified with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) was synthesized and conjugated onto the chitosan backbone through click chemistry. Finally, the obtained mCA was further functionalized with folic acid to improve the target specificity. The obtained FA labeled mCA exhibited higher relaxivity (9.53 mM"-"1.s"-"1) relative to Gd-DTPA (4.25 mM"-"1.s"-"1) and showed negligible toxicity as determined by the WST assay. In vivo MRI results suggested that a relatively high signal enhancement was observed in the tumor region, which made it a promising candidate for tumor-targeted MRI CA. (authors)

The usefulness of US with contrast agent on breast tumors

International Nuclear Information System (INIS)

Jung, Hye An; Jung, Jung Im; Kim, Hak Hee; Son, Sang Bum; Byun, Jae Young; Lee, Jae Mun; Hahn, Sung Tae; Kim, Choon Yul

2000-01-01

To evaluate the usefulness of US with contrast agent breast tumors. Fifteen breast tumors in fourteen patients underwent color Doppler US before and after intravenous injection of a microbubble contrast agent (Levovist, Schering AG, Berlin, Germany). Benign lesions were 8 and malignant lesions were 7 among these. Real-time power Doppler ultrasonographic images were recorded on a videotape and representative images were color-printed. Tumor vascularity was analyzed on real-time images in regard to its presence or absence, and changes in diameter and number of vessels, presence or absence of blush around the vessels. Two observers reached a consensus. Results of malignant tumors were compared with those of benign tumors. Color Doppler signal intensity increased in 12 of 15 cases (80%). Number of vessel increased in 9 of 15 cases (60%) and diameter of vessel increased in 12 of 15 cases (80%). Vascular blush around the enhanced vessel was present in 5 of 15 patients (53%). Color Doppler signal increased in 5 of 8 benign lesions (63%) and 7 of 7 malignant lesions (100%). Number of vessel increased in 4 of 8 benign lesion (50%) and 5 of 7 malignant lesions (71%). Diameter of vessel increased in 5 of 8 benign lesions (63%) and 7 of 7 malignant lesions (100%). Blush around the enhanced vessel was present in one of 8 benign lesions (13%) and 4 of 7 malignant lesions (57%). The time to peak enhancement was shorter in malignant cases (mean=45 sec) than benign cases (mean=82 sec). US with contrast agent on breast tumors is effective to detect blood flow within the mass and may be helpful to differentiate malignant from benign lesions.

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

Science.gov (United States)

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

2015-07-01

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

Photoacoustic tomography of joints aided by an Etanercept-conjugated gold nanoparticle contrast agent-an ex vivo preliminary rat study

International Nuclear Information System (INIS)

Chamberland, David L; Agarwal, Ashish; Kotov, Nicholas; Fowlkes, J Brian; Carson, Paul L; Wang Xueding

2008-01-01

Monitoring of anti-rheumatic drug delivery in experimental models and in human diseases would undoubtedly be very helpful for both basic research and clinical management of inflammatory diseases. In this study, we have investigated the potential of an emerging hybrid imaging technology-photoacoustic tomography-in noninvasive monitoring of anti-TNF drug delivery. After the contrast agent composed of gold nanorods conjugated with Etanercept molecules was produced, ELISA experiments were performed to prove the conjugation and to show that the conjugated anti-TNF-α drug was biologically active. PAT of ex vivo rat tail joints with the joint connective tissue enhanced by intra-articularly injected contrast agent was conducted to examine the performance of PAT in visualizing the distribution of the gold-nanorod-conjugated drug in articular tissues. By using the described system, gold nanorods with a concentration down to 1 pM in phantoms or 10 pM in biological tissues can be imaged with good signal-to-noise ratio and high spatial resolution. This study demonstrates the feasibility of conjugating TNF antagonist pharmaceutical preparations with gold nanorods, preservation of the mechanism of action of TNF antagonist along with preliminary evaluation of novel PAT technology in imaging optical contrast agents conjugated with anti-rheumatic drugs. Further in vivo studies on animals are warranted to test the specific binding between such conjugates and targeted antigen in joint tissues affected by inflammation

The effects of X-ray energy and an iodine-based contrast agent on chromosome aberrations

International Nuclear Information System (INIS)

Matsubara, Sho; Kubota, Nobuo; Katoh, Tsuguhisa; Yoshino, Norio; Sasaki, Takehito; Sasaki, Masao S.

1994-01-01

A study was undertaken to evaluate the effect of combining irradiation with X rays of various energies and an iodine-based contrast agent on the induction of chromosome aberrations in the peripheral lymphocytes of blood samples taken from healthy young donors. Although no enhancement of the effect of radiation was induced when blood samples with the iodine-based contrast agent were given 35 kV X irradiation, an 80 kV X-ray exposure induced an enhanced level of chromosome aberrations, and a 250 kV X irradiation, an enhancement of the frequencies of chromosome aberrations was seen in blood samples with the iodine-based contrast agent, especially when a Lucite phantom was employed in studies to increase the scattered rays. It was thus shown by microdosimetric analysis that X irradiation combined with an iodine-based contrast agent causes an enhancement of the absorbed radiation dose, which is dependent on the X-ray energies employed. This phenomenon may have clinical use in the radiotherapeutic management of tumors, although further extensive studies of tumor vascularity must be pursued before this can be applied clinically. 21 refs., 8 figs., 3 tabs

Interaction of a high-order Bessel beam with a submerged spherical ultrasound contrast agent shell - Scattering theory.

Science.gov (United States)

Mitri, F G

2010-03-01

Acoustic scattering properties of ultrasound contrast agents are useful in extending existing or developing new techniques for biomedical imaging applications. A useful first step in this direction is to investigate the acoustic scattering of a new class of acoustic beams, known as helicoidal high-order Bessel beams, to improve the understanding of their scattering characteristics by an ultrasound contrast agent, which at present is very limited. The transverse acoustic scattering of a commercially available albuminoidal ultrasound contrast agent shell filled with air or a denser gas such as perfluoropropane and placed in a helicoidal Bessel beam of any order is examined numerically. The shell is assumed to possess an outer radius a=3.5 microns and a thickness of approximately 105 nm. Moduli of the total and resonance transverse acoustic scattering form functions are numerically evaluated in the bandwidth 0scattering of a helicoidal Bessel beam of order m1 so that the dynamics of contrast agents would be significantly altered. The main finding of the present theory is the suppression or enhancement for a particular resonance that may be used to advantage in imaging with ultrasound contrast agents for clinical applications. 2009 Elsevier B.V. All rights reserved.

MRI contrast agent for targeting glioma: interleukin-13 labeled liposome encapsulating gadolinium-DTPA.

Science.gov (United States)

Liu, Xiaoli; Madhankumar, Achuthamangalam B; Miller, Patti A; Duck, Kari A; Hafenstein, Susan; Rizk, Elias; Slagle-Webb, Becky; Sheehan, Jonas M; Connor, James R; Yang, Qing X

2016-05-01

Detection of glioma with MRI contrast agent is limited to cases in which the blood-brain barrier (BBB) is compromised as contrast agents cannot cross the BBB. Thus, an early-stage infiltrating tumor is not detectable. Interleukin-13 receptor alpha 2 (IL-13Rα2), which has been shown to be overexpressed in glioma, can be used as a target moiety. We hypothesized that liposomes conjugated with IL-13 and encapsulating MRI contrast agent are capable of passing through an intact BBB and producing MRI contrast with greater sensitivity. The targeted MRI contrast agent was created by encapsulating Magnevist (Gd-DTPA) into liposomes conjugated with IL-13 and characterized by particle size distribution, cytotoxicity, and MRI relaxivity. MR image intensity was evaluated in the brain in normal mice post injection of Gd-DTPA and IL-13-liposome-Gd-DTPA one day apart. The specificity for glioma detection by IL-13-liposome-Gd-DTPA was demonstrated in an intracranial glioma mouse model and validated histologically. The average size of IL-13-liposome-Gd-DTPA was 137 ± 43 nm with relaxivity of 4.0 ± 0.4 L/mmole-s at 7 Tesla. No significant cytotoxicity was observed with MTS assay and serum chemistry in mice. The MRI signal intensity was enhanced up to 15% post injection of IL-13-liposome-Gd-DTPA in normal brain tissue following a similar time course as that for the pituitary gland outside of the BBB. MRI enhanced by IL-13-liposome-Gd-DTPA detected small tumor masses in addition to those seen with Magnevist-enhanced MRI. IL-13-liposome-Gd-DTPA is able to pass through the uncompromised BBB and detect an early stage glioma that cannot be seen with conventional contrast-enhanced MRI. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

Energy Technology Data Exchange (ETDEWEB)

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

2010-04-09

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

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

International Nuclear Information System (INIS)

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

2010-01-01

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

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

Science.gov (United States)

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

2010-04-01

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

Efficacy of high iodine concentration contrast medium with saline pushing in hepatic CT in patients with chronic liver disease. Comparison of high doses-standard contrast medium concentration

International Nuclear Information System (INIS)

Matoba, Munetaka; Kondo, Tamaki; Nishikawa, Takahiro; Kuginuki, Yasuaki; Yokota, Hajime; Higashi, Kotaro; Tonami, Hisao

2006-01-01

The aim of this study was to compare the enhancement of liver parenchyama with high iodine concentration contrast medium with saline pushing to that with high doses standard iodine concentration in hepatic CT in patients with chronic liver disease. There was no statistically significant difference regarding to the enhancement of liver parenchyama between the 370 mgI/ml of contrast medium with saline pushing and high doses standard iodine concentration contrast medium. (author)

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

NARCIS (Netherlands)

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

2006-01-01

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

Contrast agents and cardiac MR imaging of myocardial ischemia: from bench to bedside

International Nuclear Information System (INIS)

Croisille, Pierre; Revel, Didier; Saeed, Maythem

2006-01-01

This review paper presents, in the first part, the different classes of contrast media that are already used or are in development for cardiac magnetic resonance imaging. A classification of the different types of contrast media is proposed based on the distribution of the compounds in the body, their type of relaxivity and their potential affinity to particular molecules. In the second part, the different uses of the extracellular type of T1-enhancing contrast agent for myocardial imaging is covered from the detection of stable coronary artery disease to the detection and characterization of chronic infarction. A particular emphasis is placed on the clinical use of gadolinium-chelates, which are the universally used type of MRI contrast agent in the clinical routine. Both approaches, first-pass magnetic resonance imaging (FP-MRI) as well as delayed-enhanced magnetic resonance imaging (DE-MRI), are covered in the different situations of acute and chronic myocardial infarction. (orig.)

Microbubble embedded with upconversion nanoparticles as a bimodal contrast agent for fluorescence and ultrasound imaging

International Nuclear Information System (INIS)

Jin, Birui; Lin, Min; You, Minli; Xu, Feng; Lu, Tianjian; Zong, Yujin; Wan, Mingxi; Duan, Zhenfeng

2015-01-01

Bimodal imaging offers additional imaging signal thus finds wide spread application in clinical diagnostic imaging. Fluorescence/ultrasound bimodal imaging contrast agent using fluorescent dyes or quantum dots for fluorescence signal has emerged as a promising method, which however requires visible light or UV irradiation resulting in photobleaching, photoblinking, auto-fluorescence and limited tissue penetration depth. To surmount these problems, we developed a novel bimodal contrast agent using layer-by-layer assembly of upconversion nanoparticles onto the surface of microbubbles. The resulting microbubbles with average size of 2 μm provide enhanced ultrasound echo for ultrasound imaging and upconversion emission upon near infrared irradiation for fluorescence imaging. The developed bimodal contrast agent holds great potential to be applied in ultrasound target technique for targeted diseases diagnostics and therapy. (paper)

Silicon nanoparticles as contrast agents in the methods of optical biomedical diagnostics

Science.gov (United States)

Zabotnov, S. V.; Kashaev, F. V.; Shuleiko, D. V.; Gongalsky, M. B.; Golovan, L. A.; Kashkarov, P. K.; Loginova, D. A.; Agrba, P. D.; Sergeeva, E. A.; Kirillin, M. Yu

2017-07-01

The efficiency of light scattering by nanoparticles formed using the method of picosecond laser ablation of silicon in water and by nanoparticles of mechanically grinded mesoporous silicon is compared. The ensembles of particles of both types possess the scattering coefficients sufficient to use them as contrast agents in optical coherence tomography (OCT), particularly in the range of wavelengths 700-1000 nm, where the absorption of both silicon and most biological and mimicking tissues is small. According to the Mie theory the main contribution to the scattering in this case is made by the particles having a relatively large size (150-300 nm). In the experiments on visualising the agar phantom surface by means of OCT, the contrast of the medium boundary, provided by nanoparticles amounted to 14 dB and 30 dB for the ablated particles and the porous silicon powder, respectively. The numerical simulation of OCT images of skin in the presence of nanoparticles, confirmed the efficiency of using them as a contrast agent.

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

Science.gov (United States)

Wiener, Edzard; Settles, Marcus; Diederichs, Gerd

2010-01-01

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

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

Science.gov (United States)

Pablico, Michele Huelar

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

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

Science.gov (United States)

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

2018-01-01

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

MRI observation of the light-induced release of a contrast agent from photo-controllable polymer micelles

International Nuclear Information System (INIS)

Lepage, Martin; Jiang Jinqiang; Babin, Jerome; Qi, Bo; Tremblay, Luc; Zhao Yue

2007-01-01

The encapsulation of molecules into nanocarriers is studied for its potential in delivering a high dose of anticancer drugs to a tumor, while minimizing side effects. Most systems either release their content in a non-specific manner or under specific environmental conditions such as temperature or pH. We have synthesized a novel class of photo-controllable polymer micelles that can stably encapsulate a hydrophilic compound and subsequently release it upon absorption of UV light. Here, we describe an in vitro magnetic resonance imaging assay that can evaluate the state of incorporation of a small Gd-based contrast agent. Our results indicate that the contrast agent alone can diffuse through a filter, but that the same agent incorporated into micelles cannot. After exposure to UV light, the micelles released the contrast agent, which could then diffuse through the filter. (note)

[Preparation and preliminary evaluation of KGDS-targeted ultrasound contrast agent].

Science.gov (United States)

Gao, Feng; Ding, Yanfei; Sheng, Xiaoxi; Wang, Wei; Liang, Qi; Luo, Zhuoqiong; Zhou, Ping; Li, Hui

2009-12-01

To prepare a thrombus-targeted ultrasonic contrast agent and to investigate its targeted ability to fresh blood clots. We first synthesized FITC-KGDS-Palm compound, and then prepared thrombus-targeted microbubbles using "ultrasound & high speed shearing method". Fluorescence labeling thrombus-specific peptides and KGDS, directed at the activated glycoprotein(GP)IIb/IIIa receptor of platelets were attached to the surface of lipid microbubbles. The concentration and size of TUCA were measured by Malvern Zeta Sizer Nano-ZS590 and Coulter counter. Immunofluorescence was applied to confirm the conjugation. The conjunct ratio was assessed by flow cytometer (FCM). The KGDS-TUCA was straw yellow turbid liquor, and the concentration was 1.5 x 10(9)/mL, and the average size was 1.5 microm. The targeted microbubbles conjugated with the thrombus-specific peptides showed bright green rings by fluorescence microscope. FCM demonstrated that the wavelength of shell of KGDS-TUCA changed greatly, and the conjunct ratio was 90.04%. In vitro study showed KGDS-TUCA remained stable for 48 h at 4 degree C and target-attached to blood clots and showed good stability. The ultrasound & high speed shearing method to prepare TUCA is easy and in favor of purification. KGDS-TUCA has high specific biological activity. The conjunct ratio and stability of KGDS-TUCA are excellent.

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

Energy Technology Data Exchange (ETDEWEB)

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

2008-07-15

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

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

Science.gov (United States)

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.

Ferric ammonium citrate as a positive bowel contrast agent for MR imaging of the upper abdomen

Energy Technology Data Exchange (ETDEWEB)

Kivelitz, D.; Taupitz, M.; Hamm, B. [Universitaetsklinikum Charite, Berlin (Germany). Inst. fuer Radiologie; Gehl, H.B. [Medizinische Univ. Luebeck (Germany). Inst. fuer Radiologie; Heuck, A. [Muenchen Univ. (Germany). Radiologische Klinik; Krahe, T. [Koeln Univ. (Germany). Inst. fuer Radiologische Diagnostik; Lodemann, K.P. [Bracco-Byk Gulden GmbH, Konstanz (Germany)

1999-07-01

Purpose: To evaluate the safety and diagnostic efficacy of two different doses of ferric ammonium citrate as a paramagnetic oral contrast agent for MR imaging of the upper abdomen. Material and methods: Ninety-nine adult patients referred for MR imaging for a known or suspected upper abdominal pathology were included in this randomized multicenter double-blind clinical trial. Imaging was performed with spin-echo (T1- and T2-weighted) and gradient-echo (T1-weighted) techniques before and after administration of either 1200 mg or 2400 mg of ferric ammonium citrate dissolved in 600 ml of water. Safety analysis included monitoring of vital signs, assessment of adverse events, and laboratory testing. Efficacy with regard to organ distension, contrast distribution, bowel enhancement and delineation of adjacent structures was graded qualitatively. Results: No serious adverse events were reported for either of the two concentrations. A total of 31 minor side effects were noted, of which significantly more occurred in the higher dose group (p<0.01). The diagnostic confidence in defining or excluding disease was graded as better after contrast administration for 48% of all images. Marked or moderate enhancement of the upper gastrointestinal tract was achieved at both doses in 69.5% of cases with no evident difference between the two doses. The higher dose tended to show better results in terms of the contrast assessment parameters. Conclusion: Ferric ammonium citrate is a safe and effective oral contrast agent for MR imaging of the upper abdomen at two different dose levels. The higher dose showed a tendency toward better imaging results while the lower dose caused significantly fewer side effects. Therefore, the 1200 mg dose can be recommended in view of the risk-to-benefit ratio. (orig.)

Nephrogenic systemic fibrosis after application of gadolinium-based contrast agents - a status paper

International Nuclear Information System (INIS)

Heinrich, M.; Uder, M.

2007-01-01

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

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

Science.gov (United States)

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.

Optimization of the Contrast Mixture Ratio for Simultaneous Direct MR and CT Arthrography: an in Vitro Study

International Nuclear Information System (INIS)

Choi, Ja Young; Hong, Sung Hwan; Kim, Na Ra; Jun, Woo Sun; Moon, Sung Gyu; Kang, Heung Sik; Lee, Joon Woo; Choi, Jung Ah

2008-01-01

This study was designed to determine the optimal mixture ratio of gadolinium and iodinated contrast agent for simultaneous direct MR arthrography and CT arthrography. An in vitro study was performed utilizing mixtures of gadolinium at six different concentrations (0.625, 1.25, 2.5, 5.0, 10 and 20 mmol/L) and iodinated contrast agent at seven different concentrations (0, 12.5, 25, 37.5, 50, 75 and 92-99.9%). These mixtures were placed in tissue culture plates, and were then imaged with CT and MR (with T1-weighted sequences, proton-density sequences and T2-weighted sequences). CT numbers and signal intensities were measured. Pearson's correlation coefficients were used to assess the correlations between the gadolinium/iodinated contrast agent mixtures and the CT numbers/MR signal intensities. Scatter diagrams were plotted for all gadolinium/iodinated contrast agent combinations and two radiologists in consensus identified the mixtures that yielded the optimal CT numbers and MR signal intensities. The CT numbers showed significant correlation with iodinated contrast concentrations (r = 0.976, p < 0.001), whereas the signal intensities as measured on MR images showed a significant correlation with both gadolinium and iodinated contrast agent concentrations (r = -484 to -0.719, p < 0.001). A review of the CT and MR images, graphs, and scatter diagram of 42 combinations of the contrast agent showed that a concentration of 1.25 mmol/L gadolinium and 25% iodinated contrast agent was the best combination for simultaneous CT and MR imaging. A mixture of 1.25 mmol/L gadolinium and 25% iodinated contrast agent was found to be optimal for simultaneous direct MR arthrography and CT arthrography

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

Directory of Open Access Journals (Sweden)

Arthur Taylor

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

Effects of gadolinium-based MRI contrast agents on liver tissue.

Science.gov (United States)

Mercantepe, Tolga; Tümkaya, Levent; Çeliker, Fatma Beyazal; Topal Suzan, Zehra; Çinar, Seda; Akyildiz, Kerimali; Mercantepe, Filiz; Yilmaz, Adnan

2018-04-01

MRI with contrast is often used clinically. However, recent studies have reported a high accumulation of gadolinium-based contrast agents (GBCAs) in kidney, liver, and spleen tissues in several mouse models. To compare the effects on liver tissue of gadolinium-based MRI contrast agents in the light of biochemical and histopathological evaluation. Institutional Review Board (IRB)-approved controlled longitudinal study. In all, 32 male Sprague-Dawley rats were divided into a healthy control group subjected to no procedure (Group 1), a sham group (Group 2), a gadodiamide group (Group 3), and a gadoteric acid group (Group 4). Not applicable. Liver tissues removed at the end of the fifth week and evaluated pathologically (scored Knodell's histological activity index [HAI] method by two histopathologists) immunohistochemical (caspase-3 and biochemical tests (AST, ALT, TAS, TOS, and OSI method by Erel et al) were obtained. Differences between groups were analyzed using the nonparametric Kruskal-Wallis test followed by the Tamhane test, and one-way analysis of variance (ANOVA) followed by Turkey's HSD test. An increase was observed in histological activity scores in sections from rats administered gadodiamide and gadoteric acid, and in caspase-3, AST and ALT values (P total antioxidant and antioxidant capacity. 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Three-dimensional contrast-enhanced MRI using an intravascular contrast agent for detection of traumatic intra-abdominal hemorrhage and abdominal parenchymal injuries: an experimental study

International Nuclear Information System (INIS)

Weishaupt, D.; Ruehm, S.G.; Patak, M.A.; Schmidt, M.; Debatin, J.F.; Hetzer, F.H.

2000-01-01

The aim of this study was to compare the performance of 3D MRI in conjunction with an intravascular contrast agent to spiral contrast-enhanced CT, regarding the detection of abdominal parenchymal injuries as well as peritoneal hemorrhage in an animal model. Liver and kidney injuries were created surgically in six female pigs under general anesthesia. All pigs underwent contrast-enhanced spiral CT and 3D MR imaging following administration of an intravascular contrast agent (NC100150 Injection). Two readers rated their confidence independently on MR and CT data sets using a five-point scale for the presence of organ injury and hemoperitoneum. Autopsy findings served as standard of reference. Sensitivity and specificity for MR in detecting hepatic and renal injuries as well as hemoperitoneum was 100 %. Computed tomography was less accurate with sensitivity and specificity values of 90 and 94 %, respectively. Receiver operating characteristics (ROC) analysis revealed a higher confidence when interpretation was based on MR images. In an animal model 3D MR imaging in conjunction with an intravascular contrast agent proved highly accurate in detecting and localizing parenchymal injuries to the upper abdomen as well as in detecting intraperitoneal blood collections. (orig.)

Ultrasonically induced dynamics of a contrast agent microbubble between two parallel elastic walls

International Nuclear Information System (INIS)

Doinikov, Alexander A; Bouakaz, Ayache

2013-01-01

This work presents the derivation of a Rayleigh–Plesset-like equation that describes the radial oscillation of a contrast agent microbubble between two elastic walls, assuming that the bubble is attached to one of them. The obtained equation is then used in numerical simulations in order to establish how the presence of the second wall affects the resonance properties and the scattered echo of the contrast microbubble. The effect of encapsulation on the dynamics of the microbubble is simulated by the Marmottant shell model which is commonly used for the modeling of the dynamics of lipid-shelled contrast agents. Two cases are examined. In the first, the mechanical properties of the walls are set to correspond to OptiCell chambers which are widely used in experiments on microbubble contrast agents. In the second, the properties of the walls correspond to walls of blood vessels. It is shown that the presence of the second wall increases the resonance frequency of the contrast microbubble and decreases the amplitudes of the radial oscillation and the scattered echo of the microbubble as compared to the case that the second wall is absent. It is also shown that the presence of the second wall can change noticeably the intensity of the second harmonic in the spectrum of the scattered pressure. It is demonstrated that, depending on the value of the driving frequency, the presence of the second wall can either increase or decrease the intensity of the second harmonic as compared to its intensity in the case that the second wall is absent. (paper)

In vitro and in vivo evaluation of poly(L-lactide-co glycolide)( PLGA) micro bubbles as a contrast agent

International Nuclear Information System (INIS)

Cui, W.; Bei, J.; Wang, S.; Zhao, Y.; Zhi, G.

2005-01-01

To achieve reliable and reproducible myocardial opacification after intravenous administration of echocardiographic contrast agents, this study was performed to fabricate a kind of poly(L-lactide-co-glycolide) (PLGA) micro bubbles-based contrast agent with a modified double emulsion method which incorporates and later sublimes po rogen, leaving voids capable of being filled with gas in their places. The morphology and size distribution of the micro bubbles were investigated. The porous inner structure formed in the micro bubble contrast agents were further proved by con focal laser scanning microscope (CLSM). All the results satisfied the requirements of ideal contrast agents. Acoustic measurement set-up detected the excellent scatter ability of the PLGA (70/30) micro bubbles. It demonstrated this kind of polymer-shell contrast agents could achieve efficient left ventricular opacification and the improved delineation of left ventricular endocardial borders. Especially the safe and successful myocardial opacification in close-chest dogs were observed

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

DEFF Research Database (Denmark)

Andersen, Klaus Scheldrup

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

Modified Gadonanotubes as a Promising Novel MRI Contrasting Agent

OpenAIRE

Rouzbeh Jahanbakhsh; Fatemeh Atyabi; Saeed Shanehsazzadeh; Zahra Sobhani; Mohsen Adeli; Rassoul Dinarvand

2013-01-01

Background and purpose of the study Carbon nanotubes (CNTs) are emerging drug and imaging carrier systems which show significant versatility. One of the extraordinary characteristics of CNTs as Magnetic Resonance Imaging (MRI) contrasting agent is the extremely large proton relaxivities when loaded with gadolinium ion (Gdn 3+) clusters. Methods In this study equated Gdn 3+ clusters were loaded in the sidewall defects of oxidized multiwalled (MW) CNTs. The amount of loaded gadolinium ion into ...

EXCI-CEST: Exploiting pharmaceutical excipients as MRI-CEST contrast agents for tumor imaging.

Science.gov (United States)

Longo, Dario Livio; Moustaghfir, Fatima Zzahra; Zerbo, Alexandre; Consolino, Lorena; Anemone, Annasofia; Bracesco, Martina; Aime, Silvio

2017-06-15

Chemical Exchange Saturation Transfer (CEST) approach is a novel tool within magnetic resonance imaging (MRI) that allows visualization of molecules possessing exchangeable protons with water. Many molecules, employed as excipients for the formulation of finished drug products, are endowed with hydroxyl, amine or amide protons, thus can be exploitable as MRI-CEST contrast agents. Their high safety profiles allow them to be injected at very high doses. Here we investigated the MRI-CEST properties of several excipients (ascorbic acid, sucrose, N-acetyl-d-glucosamine, meglumine and 2-pyrrolidone) and tested them as tumor-detecting agents in two different murine tumor models (breast and melanoma cancers). All the investigated molecules showed remarkable CEST contrast upon i.v. administration in the range 1-3ppm according to the type of mobile proton groups. A marked increase of CEST contrast was observed in tumor regions up to 30min post injection. The combination of marked tumor contrast enhancement and lack of toxicity make these molecules potential candidates for the diagnosis of tumors within the MRI-CEST approach. Copyright © 2017 Elsevier B.V. All rights reserved.

Nonlinear Dynamics of a Bubble Contrast Agent Oscillating near an Elastic Wall

Science.gov (United States)

Garashchuk, Ivan R.; Sinelshchikov, Dmitry I.; Kudryashov, Nikolay A.

2018-05-01

Contrast agent microbubbles, which are encapsulated gas bubbles, are widely used to enhance ultrasound imaging. There are also several new promising applications of the contrast agents such as targeted drug delivery and noninvasive therapy. Here we study three models of the microbubble dynamics: a nonencapsulated bubble oscillating close to an elastic wall, a simple coated bubble and a coated bubble near an elastic wall.We demonstrate that complex dynamics can occur in these models. We are particularly interested in the multistability phenomenon of bubble dynamics. We show that coexisting attractors appear in all of these models, but for higher acoustic pressures for the models of an encapsulated bubble.We demonstrate how several tools can be used to localize the coexisting attractors. We provide some considerations why the multistability can be undesirable for applications.

Myocardial Contrast Agents – Safety Considerations and Clinical Efficacy in Stress Echocardiography

Directory of Open Access Journals (Sweden)

Maier Anca

2016-11-01

Full Text Available Transthoracic echocardiographic examination is known to be a safe, non-invasive and reproducible method, used in every day clinical practice to obtain important information about cardiac structure and function. Unfortunately, a significant proportion of studies have highlighted the considerable technically difficultly in producing diagnostic images due to a poor acoustic window and more than 33% of patients undergoing stress echocardiography have suboptimal echocardiographic images. All these limitations have led to the use of contrast agents to improve the quality of standard ultrasound examination to provide a better delineation of left ventricle endocardial borders or to obtain information that cannot be achieved by using standard echocardiography, such as assessing myocardial microcirculation and therefore perfusion. This paper sought to review the clinical efficacy and safety of ultrasound contrast agents focusing on stress echocardiography.

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

International Nuclear Information System (INIS)

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

1988-01-01

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

Contrast venography of the leg: diagnostic efficacy, tolerance, and complication rates with ionic and nonionic contrast media

International Nuclear Information System (INIS)

Bettmann, M.A.; Robbins, A.; Braun, S.D.; Wetzner, S.; Dunnick, N.R.; Finkelstein, J.

1987-01-01

A prospective, three-center study of two contrast agents for leg venography was performed to evaluate both the relative frequency of adverse effects and whether low-osmolality agents provided significant advantages for this procedure. Fifty-four patients were studied with the standard preparation (iothalamate meglumine) and 57 with a nonionic agent (iopamidol). Both were used at an iodine concentration of 200 mg/mL, and there were no differences in volume of contrast material, duration of infusion, percentage of positive studies, or overall diagnostic adequacy. Patient discomfort was less with iopamidol than with iothalamate (18% vs. 44%), although discomfort was generally mild in both groups. By objective follow-up studies, the frequency of postvenographic thrombosis was not significantly different in the two groups (8% vs. 9%). Contrast venography, then, had a low frequency of complications when either a dilute conventional or a low-osmolality agent was employed. Although the frequency of postvenographic thrombosis was low with both agents, patient discomfort was less with the low-osmolality formulation

Targeted nanodiamonds as phenotype-specific photoacoustic contrast agents for breast cancer.

Science.gov (United States)

Zhang, Ti; Cui, Huizhong; Fang, Chia-Yi; Cheng, Kun; Yang, Xinmai; Chang, Huan-Cheng; Forrest, M Laird

2015-03-01

The aim is to develop irradiated nanodiamonds (INDs) as a molecularly targeted contrast agent for high-resolution and phenotype-specific detection of breast cancer with photoacoustic (PA) imaging. The surface of acid treated radiation-damaged nanodiamonds was grafted with PEG to improve its stability and circulation time in blood, followed by conjugation to an anti-HER2 peptide with a final nanoparticle size of approximately 92 nm. Immunocompetent mice bearing orthotopic HER2-positive or negative tumors were administered INDs and PA imaged using an 820-nm near-infrared laser. PA images demonstrated that INDs accumulate in tumors and completely delineated the entire tumor within 10 h. HER2 targeting significantly enhanced imaging of HER2-positive tumors. Pathological examination demonstrated INDs are nontoxic. PA technology is adaptable to low-cost bedside medicine, and with new contrast agents described herein, PA can achieve high-resolution (sub-mm) and phenotype-specific monitoring of cancer growth.

Influence of hyperosmotic agent (glycerol) in contrast enhancement

International Nuclear Information System (INIS)

Moriyama, Takashi; Suzuki, Shigeharu; Nakaoka, Tsutomu

1981-01-01

For getting a better contrast enhancement (CE) of computed tomography (CT) in brain tumors, we tried to increase the extravascular iodine concentration. A vailing ourselves of the period of returning water following intravenously administered glycerol, a drip injection of the contrast medium gave a better CE effect than the usual CE. In two benign gliomas, CE with glycerol was much better than CE without glycerol, and in two malignant gliomas and two metastatic tumors, CE with glycerol was better, but not so much better as with the benign tumors. In general, the CE effect in primary brain tumors showed a decreasing pattern, whereas in metastatic brain tumors the best time was 60 minutes after the injection of the contrast material (increasing and decreasing pattern), suggesting an increase in the extravascular iodine and a severe failure of the blood brain barrier. Two cystic malignant gliomas allowed the intravenously injected contrast medium to enter the cysts. It appears that the contrast medium passes through and/or is secreted from the wall of the cyst. (author)

Liver imaging with MDCT and high concentration contrast media

International Nuclear Information System (INIS)

Spielmann, Audrey L.

2003-01-01

Liver imaging has advanced greatly over the last 10 years with helical CT capability and more recently the addition of multidetector-row CT (MDCT). Multidetector CT technology facilitates imaging at faster speeds with improved image quality and less breathing artifact [Abdom. Imaging 25 (2000) 643]. Exquisite three-dimensional data sets can be obtained with thin collimation providing improved lesion detection, multiplanar imaging, and the ability to perform CT angiography of the liver and mesenteric vessels. New challenges arise with this advance in technology including safety considerations. The radiation dose to the patient has increased with MDCT and this is compounded by the ability to perform multi-phase liver imaging. Furthermore, issues of contrast media administration require reconsideration including optimal timing and rate of administration, the total volume of contrast needed and the ideal iodine concentration of the contrast media. Recently, the use of high concentration contrast media (HCCM) has been explored and study results to date will be reviewed

Dynamic magnetic resonance angiography of the arteries of the hand. A comparison between an extracellular and an intravascular contrast agent

International Nuclear Information System (INIS)

Reisinger, Clemens; Gluecker, Thomas; Jacob, Augustinus Ludwig; Bongartz, Georg; Bilecen, Deniz

2009-01-01

The purpose of this study was to compare the image quality of the intravascular contrast agent gadofosveset with the extracellular contrast agent gadoterate meglumine in time-resolved three-dimensional magnetic resonance (MR) angiography of the human arteries of the hand. The value of cuff compression technique for suppression of venous enhancement for both contrast agents was also investigated. Three-dimensional MR angiograms of both hands of 11 healthy volunteers were acquired for each contrast agent at 1.5-T, while subsystolic cuff compression was applied at one side. Quantitative and qualitative evaluation were performed and analyzed with Student's t-test. Visualization of vessels was superior in the images acquired with gadofosveset, especially in the late phases. Quantitative and qualitative evaluation showed significantly higher values for gadofosveset. The cuff compression at the lower arm proved to be an effective method to enhance arterial vessels. In conclusion the blood pool agent gadofosveset is superior for the dynamic imaging of the vessels of the hand when compared with the extracellular contrast agent gadoterate meglumine. To fully utilize the advantages of intravascular contrast agents, venous overlay has to be delayed or reduced, which can be achieved effectively by subsystolic lower arm cuff compression. (orig.)

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

Science.gov (United States)

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 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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-06-15

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

Enhanced conjugation stability and blood circulation time of macromolecular gadolinium-DTPA contrast agent.

Science.gov (United States)

Jenjob, Ratchapol; Kun, Na; Ghee, Jung Yeon; Shen, Zheyu; Wu, Xiaoxia; Cho, Steve K; Lee, Don Haeng; Yang, Su-Geun

2016-04-01

In this study, we prepared macromolecular MR T1 contrast agent: pullulan-conjugated Gd diethylene triamine pentaacetate (Gd-DTPA-Pullulan) and estimated residual free Gd(3+), chelation stability in competition with metal ions, plasma and tissue pharmacokinetics, and abdominal MR contrast on rats. Residual free Gd(3+) in Gd-DTPA-Pullulan was measured using colorimetric spectroscopy. The transmetalation of Gd(3+) incubated with Ca(2+) was performed by using a dialysis membrane (MWCO 100-500 Da) and investigated by ICP-OES. The plasma concentration profiles of Gd-DTPA-Pullulan were estimated after intravenous injection at a dose 0.1 mmol/kg of Gd. The coronal-plane abdominal images of normal rats were observed by MR imaging. The content of free Gd(3+), the toxic residual form, was less than 0.01%. Chelation stability of Gd-DTPA-Pullulan was estimated, and only 0.2% and 0.00045% of Gd(3+) were released from Gd-DTPA-Pullulan after 2h incubation with Ca(2+) and Fe(2+), respectively. Gd-DTPA-Pullulan displayed the extended plasma half-life (t1/2,α=0.43 h, t1/2,β=2.32 h), much longer than 0.11h and 0.79 h of Gd-EOB-DTPA. Abdominal MR imaging showed Gd-DTPA-Pullulan maintained initial MR contrast for 30 min. The extended plasma half-life of Gd-DTPA-Pullulan probably allows the prolonged MR acquisition time in clinic with enhanced MR contrast. Copyright © 2016 Elsevier B.V. All rights reserved.

Impact of contrast agent viscosity on coronary balloon deflation times: bench testing results.

Science.gov (United States)

Mogabgab, Owen; Patel, Vishal G; Michael, Tesfaldet T; Kotsia, Anna; Christopoulos, George; Banerjee, Subhash; Brilakis, Emmanouil S

2014-04-01

To assess the impact of viscosity on angioplasty balloon deflation times. Lower contrast viscosity could result in more rapid coronary balloon deflation times. We performed a bench comparison of coronary balloon deflation times using 2 contrast agents with different viscosity (ioxaglate and iodixanol), 3 contrast dilutions, and 2 inflation syringe filling volumes. Ten identical pairs of coronary angioplasty balloons were used to conduct each comparison after balloon inflation to 12 atmospheres. Simultaneous deflations were performed under cineangiography. The time to full contrast extraction and the area of contrast remaining after 5 seconds of deflation (quantified by opaque pixel count) were compared between groups. The mean time to full contrast extraction during balloon deflation was 8.3 ± 2.5 seconds for ioxaglate (lower viscosity) versus 10.1 ± 2.9 seconds for iodixanol (higher viscosity) (17.4% decrease, P = 0.005), with a 35.6% (P = 0.004) reduction in contrast area at 5 seconds. Compared to 1:1 ioxaglate-saline mixture, 1:2 and 1:3 ioxaglate/saline mixes resulted in 26.7% (P deflation time, respectively, but at the expense of decreased balloon opacity. Filling the inflation syringe with 5 versus 15 ml of contrast/saline solution was associated with 7.5% decrease in balloon deflation time (P = 0.005), but no difference in contrast area at 5 seconds (P = 0.749). Use of a lower viscosity contrast agent and higher contrast dilution significantly reduced coronary balloon deflation times, whereas use of lower syringe filling volume had a modest effect. Rapid coronary balloon deflation could improve the safety of interventional procedures. © 2014 Wiley Periodicals, Inc.

Direct synthesis of magnetite nanoparticles from iron(II) carboxymethylcellulose and their performance as NMR contrast agents

Energy Technology Data Exchange (ETDEWEB)

Gomes da Silva, Delmarcio; Hiroshi Toma, Sergio; Menegatti de Melo, Fernando [Instituto de Química, Universidade de São Paulo, São Paulo, SP (Brazil); Carvalho, Larissa Vieira C.; Magalhães, Alvicler; Sabadini, Edvaldo [Instituto de Química, Universidade Estadual de Campinas – UNICAMP, Campinas, SP (Brazil); Domingues dos Santos, Antônio [Instituto de Física, Universidade de São Paulo, São Paulo, SP (Brazil); Araki, Koiti [Instituto de Química, Universidade de São Paulo, São Paulo, SP (Brazil); Toma, Henrique E., E-mail: henetoma@iq.usp.br [Instituto de Química, Universidade de São Paulo, São Paulo, SP (Brazil)

2016-01-01

Iron(II) carboxymethylcellulose (CMC) has been successfully employed in the synthesis of hydrophylic magnetite nanoparticles stabilized with a biopolymer coating, aiming applications in NMR imaging. The new method encompasses a convenient one-step synthetic procedure, allowing a good size control and yielding particles of about 10 nm (core size). In addition to the biocompatibility, the nanoparticles have promoted a drastic reduction in the transverse relaxation time (T{sub 2}) of the water protons. The relaxivity rates have been investigated as a function of the nanoparticles concentration, showing a better performance in relation to the common NMR contrast agents available in the market. - Highlights: • Stable, hydrophylic magnetic nanoparticles have been obtained. • Direct use of iron(II) carboxymethylcellulose improves the synthesis. • The magnetic nanoparticles exhibit high spin–spin relaxivity. • The particles promote dark contrast by decreasing the T{sub 2} relaxation time.

Radiochromic film dosimetry of contrast-enhanced radiotherapy (CERT)

International Nuclear Information System (INIS)

Morris, Kevin N; Weil, Michael D; Malzbender, Rainer

2006-01-01

Contrast-enhanced radiotherapy (CERT) employs elevated concentrations of high-Z contrast media in targets to dramatically increase the absorbed dose of radiation relative to the surrounding tissues. However, it is difficult to measure the dose enhancement with routine clinical instruments because the photoelectrons and Auger electrons produced by the interaction of kilovoltage x-rays with the contrast agent travel extremely short distances. We have developed a technique utilizing unlaminated radiochromic film to measure the maximum dose enhancement factor attainable in solutions of contrast agent with iodine concentrations ranging from 0% to 37% (w/v). The films were also used to simultaneously measure the dose enhancement and beam attenuation through solutions containing 0%, 5% and 10% iodine (w/v). These depth-dose measurements were made in phantoms representing 3 cm targets located 0 and 4.8 cm deep in acrylic. Higher concentrations of contrast yielded greater dose enhancement and target-to-surface dose ratios, but caused more rapid attenuation of the beam as it traversed the target. The dose distribution across the entire target could be improved by employing multiple beams. These results, using concentrations of contrast that are clinically achievable by intratumoural injection, illustrate the potential of CERT for the specific delivery of high doses of radiation to targets at depth

Gadolinium-conjugated PLA-PEG nanoparticles as liver targeted molecular MRI contrast agent.

Science.gov (United States)

Chen, Zhijin; Yu, Dexin; Liu, Chunxi; Yang, Xiaoyan; Zhang, Na; Ma, Chunhong; Song, Jibin; Lu, Zaijun

2011-09-01