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.)

Characterization of Focal Liver Lesions using CEUS and MRI with Liver-Specific Contrast Media: Experience of a Single Radiologic Center.

Science.gov (United States)

Beyer, Lukas Philipp; Wassermann, Florian; Pregler, Benedikt; Michalik, Katharina; Rennert, Janine; Wiesinger, Isabel; Stroszczynski, Christian; Wiggermann, Philipp; Jung, Ernst Michael

2017-12-01

 The purpose of this study was to compare contrast-enhanced ultrasound (CEUS), magnetic resonance imaging (MRI) using liver-specific contrast agent and a combination of both for the characterization of focal liver lesions (FLL).  83 patients with both benign and malignant liver lesions were examined using CEUS and MRI after the intravenous administration of liver-specific contrast media. All patients had inconclusive results from prior imaging examinations. Histopathological specimens could be obtained in 53 patients. Ultrasound was performed using a multi-frequency curved probe (1 - 6 MHz) after the injection of 1 - 2.4 ml ultrasound contrast media. The sensitivity, specificity, positive predictive value and negative predictive value of CEUS, MRI and a combination of both (CEUS + MRI) were compared.  The sensitivity, specificity, positive and negative predictive values regarding lesion classification were 90.9 %, 70.6 %, 92.3 % and 66.6 %, respectively, for CEUS; 90.9 %, 82.4 %, 95.2 % and 70.0 %, respectively, for MRI; and 96.9 %, 70.6 %, 92.7 % and 85.7 % respectively, for CEUS + MRI. There were no statistically significant differences. 6 malignant lesions were missed using CEUS or MRI alone (false negatives). The use of both modalities combined reduced the false-negative results to 2.  CEUS and MRI with liver-specific contrast media are very reliable and of equal informative value in the characterization of focal liver lesions. The number of false-negative results can be decreased using a combination of the two methods. © Georg Thieme Verlag KG Stuttgart · New York.

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

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.

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.

Contrast enhanced ultrasound in liver imaging

International Nuclear Information System (INIS)

Nielsen, Michael Bachmann; Bang, Nanna

2004-01-01

Ultrasound contrast agents were originally introduced to enhance the Doppler signals when detecting vessels with low velocity flow or when imaging conditions were sub-optimal. Contrast agents showed additional properties, it was discovered that a parenchymal enhancement phase in the liver followed the enhancement of the blood pool. Contrast agents have made ultrasound scanning more accurate in detection and characterization of focal hepatic lesions and the sensitivity is now comparable with CT and MRI scanning. Further, analysis of the transit time of contrast agent through the liver seems to give information on possible hepatic involvement, not only from focal lesions but also from diffuse benign parenchymal disease. The first ultrasound contrast agents were easily destroyed by the energy from the sound waves but newer agents have proved to last for longer time and hereby enable real-time scanning and make contrast enhancement suitable for interventional procedures such as biopsies and tissue ablation. Also, in monitoring the effect of tumour treatment contrast agents have been useful. A brief overview is given on some possible applications and on different techniques using ultrasound contrast agents in liver imaging. At present, the use of an ultrasound contrast agent that allows real-time scanning with low mechanical index is to be preferred

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

DEFF Research Database (Denmark)

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

2002-01-01

The purpose of this study was to assess the ability of pulse-inversion ultrasound (US) scanning (PIUS), combined with an IV contrast agent, to detect malignant liver lesions and its impact on patient management (resectability). Additionally, to determine the feasibility of US-guided biopsy of new...... PIUS-findings at the same session. A total of 30 patients with known or clinically suspected cancer underwent conventional B-mode scanning and PIUS with IV-administered contrast agent. The number of liver metastases in the right and the left liver lobe, respectively, was recorded. All patients...... findings were performed in 17 of 18 patients. All biopsies of additional findings confirmed malignancy. PIUS with an IV contrast agent increased the ability to detect liver metastases compared to conventional US scanning. The technique had a high impact on patient management. The results showed that PIUS...

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

A nanoparticle magnetic resonance imaging (MRI) contrast agent targeted to liver was developed by conjugation of gadolinium (Gd) chelate groups onto the biocompatible poly(l-lactide)-block-poly (ethylene glycol) (PLA-PEG) nanoparticles. PLA-PEG conjugated with diethylenetriaminopentaacetic acid (DTPA) was used to formulate PLA-PEG-DTPA nanoparticles by solvent diffusion method, and then Gd was loaded onto the nanoparticles by chelated with the unfolding DTPA on the surface of the PLA-PEG-DTPA nanoparticles. The mean size of the nanoparticles was 265.9 ± 6.7 nm. The relaxivity of the Gd-labeled nanoparticles was measured, and the distribution in vivo was evaluated in rats. Compared with conventional contrast agent (Magnevist), the Gd-labeled PLA-PEG nanoparticles showed significant enhancement both on liver targeting ability and imaging signal intensity. The T(1) and T(2) relaxivities per [Gd] of the Gd-labeled nanoparticles was 18.865 mM(-1) s(-1) and 24.863 mM(-1) s(-1) at 3 T, respectively. In addition, the signal intensity in vivo was stronger comparing with the Gd-DTPA and the T(1) weight time was lasting for 4.5 h. The liver targeting efficiency of the Gd-labeled PLA-PEG nanoparticles in rats was 14.57 comparing with Magnevist injection. Therefore, the Gd-labeled nanoparticles showed the potential as targeting molecular MRI contrast agent for further clinical utilization.

Manganese and Gd-DTPA stearyl liposomes as reticuloendothelial-system-specific MR imaging contrast agents

International Nuclear Information System (INIS)

Wuthrich, R.; Schwendener, R.; Duewell, S.; VonSchulthess, G.K.; Fuchs, W.A.

1988-01-01

Liposomes can be used to target metal ions as MR contrast agents to liver and spleen. It was the aim of this work to examine unilamellar liposomes containing manganese and gadolinium ions with respect to their targetting ability, contrast enhancement, and in vivo kinetics in rats and dogs. Unilamellar liposomes containing DTPA stearate were complexed with Mn/sup 2+/ and Gd/sup 3+/ resulting in vesicles of 30-40 nm. Injected into rats, approximately 35% of manganese liposomes were present in the liver after 30-60 minutes, and after 24 hours more than 80% had been eliminated. The pharmacokinetics of gadolinium were more protracted. In MR imaging, a reduction in the T1 of the liver parenchyma from 450 to 170 and 280 msec was observed for manganese and gadolinium liposomes (0.03 mmol/kg body weight), respectively, with the liver appearing as bright as fat. Manganese (and Gd-DTPA) stearyl liposomes are potential organ-selective contrast agents for liver and spleen and are eliminated through a hepatobiliary route

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

Effect of microbubble contrast agent during high intensity focused ultrasound ablation on rabbit liver in vivo

International Nuclear Information System (INIS)

Chung, Dong Jin; Cho, Se Hyun; Lee, Jae Mun; Hahn, Seong-Tae

2012-01-01

Objective: To evaluate the effect of a microbubble contrast agent (SonoVue) during HIFU ablation of a rabbit liver. Materials and methods: HIFU ablations (intensity of 400 W/cm 2 for 4 s, six times, with a 5 s interval between exposures) were performed upon 16 in vivo rabbit livers before and after intravenous injection of a microbubble contrast agent (0.8 ml). A Wilcoxon signed rank test was used to compare mean ablation volume and time required to tissue ablation on real-time US. Shape of ablation and pattern of coagulative necrosis were analyzed by Fisher's exact test. Results: The volume of coagulative necrosis was significantly larger in the combination microbubble and HIFU group than in the HIFU alone group (P < 0.05). Also, time to reach ablation was shorter in the combination microbubble and HIFU group than in the HIFU alone group (P < 0.05). When analyzing the shape of tissue ablation, a pyramidal shape was more prevalently in the HIFU alone group compared to the combination microbubble and HIFU group (P < 0.05). Following an analysis of the pattern of coagulative necrosis, non-cavitary necrosis was found in ten and cavitary necrosis in six of the samples in the combination microbubble and HIFU group. Conversely, non-cavitary necrosis occurred in all 16 samples in the HIFU alone group (P < 0.05). Conclusion: HIFU of in vivo rabbit livers with a microbubble contrast agent produced larger zones of ablation and more cavitary tissue necrosis than without the use of a microbubble contrast agent. Microbubble contrast agents may be useful in tissue ablation by enhancing the treatment effect of HIFU.

Dendrimer-based Macromolecular MRI Contrast Agents: Characteristics and Application

Directory of Open Access Journals (Sweden)

Hisataka Kobayashi

2003-01-01

Full Text Available Numerous macromolecular MRI contrast agents prepared employing relatively simple chemistry may be readily available that can provide sufficient enhancement for multiple applications. These agents operate using a ~100-fold lower concentration of gadolinium ions in comparison to the necessary concentration of iodine employed in CT imaging. Herein, we describe some of the general potential directions of macromolecular MRI contrast agents using our recently reported families of dendrimer-based agents as examples. Changes in molecular size altered the route of excretion. Smaller-sized contrast agents less than 60 kDa molecular weight were excreted through the kidney resulting in these agents being potentially suitable as functional renal contrast agents. Hydrophilic and larger-sized contrast agents were found better suited for use as blood pool contrast agents. Hydrophobic variants formed with polypropylenimine diaminobutane dendrimer cores created liver contrast agents. Larger hydrophilic agents are useful for lymphatic imaging. Finally, contrast agents conjugated with either monoclonal antibodies or with avidin are able to function as tumor-specific contrast agents, which also might be employed as therapeutic drugs for either gadolinium neutron capture therapy or in conjunction with radioimmunotherapy.

Characterisation of focal liver lesions with contrast enhanced ultrasonography

International Nuclear Information System (INIS)

Dietrich, Christoph F.

2004-01-01

Ultrasound contrast agents (USCA) have improved the detection rate of liver tumours in recent years. Conventional ultrasound has been reported to be relatively unreliable in the characterisation of liver tumours. SonoVue [reg] (Bracco Imaging Spa) has been shown to be particularly advantageous in the differentiation of benign and malignant liver tumours and, therefore, possibly represents a new cost-effective competitive alternative to other liver imaging modalities (e.g. computed tomography and magnetic resonance imaging), thus allowing these important technologies to be available for other indications (e.g. brain, thorax). More detailed and specific liver tumour characterisation is possible in about 80% of liver tumours due to typical vascularity and perfusion patterns. The role of USCA for better characterisation, which is possible through the analysis of flow characteristics in real time, places a particular emphasis on agent use. Contrast enhanced real-time imaging techniques with SonoVue [reg] allow real-time analysis of tumour perfusion in patients with liver lesions. Liver tumours known to be hyperperfused in the arterial phase (e.g. focal nodular hyperplasia, hepatocellular adenoma and carcinoma, and hyperperfused metastases) can be better detected and characterised. Hypoperfused tumours (e.g. liver metastases of the gastrointestinal tract) can be recognised in the portal venous phase as less perfused 'black spots'. In this article we discuss liver tumour characterisation by contrast enhanced ultrasonography

Contrast agents for MRI

International Nuclear Information System (INIS)

Bonnemain, B.

1994-01-01

Contrast agents MRI (Magnetic Resonance Imaging) have been developed to improve the diagnostic information obtained by this technic. They mainly interact on T1 and T2 parameters and increase consequently normal to abnormal tissues contrast. The paramagnetic agents which mainly act on longitudinal relaxation rate (T1) are gadolinium complexes for which stability is the main parameter to avoid any release of free gadolinium. The superparamagnetic agents that decrease signal intensity by an effect on transversal relaxation rate (T2) are developed for liver, digestive and lymph node imaging. Many area of research are now opened for optimal use of present and future contrast agents in MRI. (author). 28 refs., 4 tabs

MR tomography of focal liver lesions using the superparamagnetic contrast agent AMI-25 at 1.5 tesla

International Nuclear Information System (INIS)

Duda, S.H.; Laniado, M.; Kopp, A.F.; Groenewaeller, E.; Aicher, K.P.; Pavone, P.; Jehle, E.; Claussen, C.D.

1994-01-01

Superparamagnetic iron oxide particles (AMI-25) were evaluated as a liver contrast agent in high-field MR imaging (1.5 T). 16 patients with up to 5 presumed focal liver lesions (liver metastases n=8, HCC n=5, Klatskin tumours n=2, FNH n=1) received 15 μmol Fe/kg BW intravenously and were examined via standard T 1 - and T 2 -weighted spin-echo sequences. Quantitative image analysis showed a post-contrast increase of the contrast-to-noise ratio (C/N) from 1.6 to 7.4 on SE 2,500/15 images (p [de

Guidelines and good clinical practice recommendations for Contrast Enhanced Ultrasound (CEUS) in the liver - update 2012

DEFF Research Database (Denmark)

Claudon, Michel; Dietrich, Christoph F; Choi, Byung Ihn

2013-01-01

Initially, a set of guidelines for the use of ultrasound contrast agents was published in 2004 dealing only with liver applications. A second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some...... Medizin/European Journal of Ultrasound for EFSUMB). These guidelines and recommendations provide general advice on the use of all currently clinically available ultrasound contrast agents (UCA). They are intended to create standard protocols for the use and administration of UCA in liver applications...... non-liver applications. Time has moved on, and the need for international guidelines on the use of CEUS in the liver has become apparent. The present document describes the third iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS) using contrast specific imaging...

Optimized detection and characterization of liver metastases. The role of current MRI contrast agents; Optimierte Detektion und Charakterisierung von Lebermetastasen. Leistungsvermoegen aktueller MRT-Kontrastmittel

Energy Technology Data Exchange (ETDEWEB)

Weinrich, J.M.; Well, L.; Bannas, P. [Universitaetsklinikum Hamburg-Eppendorf, Zentrum fuer Radiologie und Endoskopie, Klinik und Poliklinik fuer diagnostische und interventionelle Radiologie und Nuklearmedizin, Hamburg (Germany)

2017-05-15

Metastases are the most common malignant lesions of the liver. The presence of liver metastases is an important prognostic factor and is decisive for the further management, especially in patients with colorectal cancer. Detection and characterization of liver metastases as well as differentiation from benign lesions are of high importance and a daily challenge in clinical radiology. Contrast-enhanced magnetic resonance imaging (MRI) has the highest sensitivity in detecting liver metastases. The sensitivity of MRI has been further increased due to the development of liver-specific contrast agents. This article describes the role of extracellular and hepatobiliary contrast agents for the detection and characterization of liver metastases. Moreover, the current knowledge on safety, sequence optimization, transient severe dyspnea and the combination of hepatobiliary with intravascular contrast agents for liver imaging is discussed. (orig.) [German] Metastasen sind die haeufigsten malignen Leberlaesionen. Das Vorhandensein von Lebermetastasen ist entscheidend fuer die Prognose und weitere Therapieplanung von Tumorpatienten, insbesondere von Patienten mit kolorektalen Karzinomen. Die Detektion von Lebermetastasen sowie deren Unterscheidung von anderen Leberlaesionen sind daher von hoechster Bedeutung und stellen eine alltaegliche Herausforderung fuer den Radiologen dar. Die Bildgebung mit der hoechsten Sensitivitaet fuer die Detektion von Lebermetastasen stellt die dynamische kontrastmittelgestuetzte Magnetresonanztomographie (MRT) dar. Die bereits hohe Sensitivitaet der MRT wird durch den Einsatz leberspezifischer Kontrastmittel noch weiter gesteigert. Dieser Artikel beleuchtet die Rolle der aktuellen unspezifischen und leberspezifischen MRT-Kontrastmittel fuer die Detektion und Charakterisierung von Lebermetastasen. Weiterhin werden Erkenntnisse zur Sicherheit, Sequenzoptimierung, zu transienten Atemartefakten und zur Kombination von MRT-Kontrastmitteln fuer die

Detection of hepatic VX2 tumors in rabbits: comparison of conventional US and phase- inversion harmonic US during the liver- specific late phase of contrast enhancement

International Nuclear Information System (INIS)

Lee, Jeong Min; Youk, Ji Hyun; Lee, Young Hwan; Kim, Young Kon; Kim, Chong Soo; Li, Chun Ai

2003-01-01

To compare phase-inversion sonography during the liver-specific phase of contrast enhancement using a microbubble contrast agent with conventional B-mode sonography for the detection of VX2 liver tumors. Twenty-three rabbits, 18 of which had VX2 liver tumor implants, received a bolus injection of 0.6 g of Levovist (200 mg/ml). During the liver-specific phase of this agent, they were evaluated using both conventional sonography and contrast-enhanced phase-inversion harmonic imaging (CEPIHI). Following sacrifice of the animals, pathologic analysis was performed and the reference standard thus obtained. The conspicuity, size and number of the tumors before and after contrast administration, as determined by a sonographer, were compared between the two modes and with the pathologic findings. CE-PIHI demonstrated marked hepatic parenchymal enhancement in all rabbits. For VX2 tumors detected at both conventional US and CE- PIHI, conspicuity was improved by contrast-enhanced PIHI. On examination of gross specimens, 52 VX2 tumors were identified. Conventional US correctly detected 18 of the 52 (34.6%), while PIHI detected 35 (67.3%) (p < 0.05). In particular, conventional US detected only three (8.3%) of the 36 tumors less than 10 mm in diameter, but CE-PIHI detected 19 such tumors (52.8%) (p < 0.05). Compared to conventional sonography, PIHI performed during the liver-specific phase after intravenous injection of Levovist is markedly better at detecting VX2 liver tumors

Contrast amplification of the liver parenchyma in the computer tomogram by using intravenous and peroral biliary contrast media

International Nuclear Information System (INIS)

Justich, E.; Sager, W.D.; Dietrich, G.; Fotter, R.; Nedden, D. zur; Innsbruck Univ.

1980-01-01

If intravenous, biliary contrast media are used, a slight albeit specific enhancement of contrast of the liver parenchyma occurs with the applied dosage, which can be utilised in individual cases, for example for identifying isodense lesions. Contrast amplification by the peroral cholegraphic agent under examination, is insufficient for use in computer tomography of the liver. The use of biliary contrast media usually enables very good visualisation of the extrahepatic bile ducts. Attention is drawn to the possibility of pharmakokinetic studies by means of computer tomography. (orig.) [de

Differentiation of focal liver lesions by contrast-enhanced MRI

International Nuclear Information System (INIS)

Heintz, P.; Ehrenheim, C.

1989-01-01

47 patients with liver tumours (haemangioma, focal nodular hyperplasia, hepatocellular carcinoma) underwent MRI of the liver before and after i.v. injection of 0.2 ml./kg. gadolinium-DTPA in addition to other imaging methods. The demarcation of focal nodular hyperplasia is not influenced by use of the contrast agent as it almost behaves like surrounding normal liver tissue, thus only indirectly facilitating its identification. With regard to liver haemangiomas that show the most intensive uptake of gadolinium-DTPA, the contrast enhanced image does not reach to contrast and sensitivity of a native T 2 -weighted SE image, especially in cases of small haemangiomas. The contrast agent is helpful, however, in the recognition of large cavernous haemangiomas that are partially fibrotic or thrombotic. Emphasis is given to the contrast agent in hepatomas: gadolinium-DTPA presents a pattern of uptake and distribution frequently found in hepatocellular carcinoma providing additional information on the delineation of internal tumour details. (orig.) [de

Current status of superparamagnetic iron oxide contrast agents for liver magnetic resonance imaging.

Science.gov (United States)

Wang, Yi-Xiang J

2015-12-21

Five types of superparamagnetic iron oxide (SPIO), i.e. Ferumoxides (Feridex(®) IV, Berlex Laboratories), Ferucarbotran (Resovist(®), Bayer Healthcare), Ferumoxtran-10 (AMI-227 or Code-7227, Combidex(®), AMAG Pharma; Sinerem(®), Guerbet), NC100150 (Clariscan(®), Nycomed,) and (VSOP C184, Ferropharm) have been designed and clinically tested as magnetic resonance contrast agents. However, until now Resovist(®) is current available in only a few countries. The other four agents have been stopped for further development or withdrawn from the market. Another SPIO agent Ferumoxytol (Feraheme(®)) is approved for the treatment of iron deficiency in adult chronic kidney disease patients. Ferumoxytol is comprised of iron oxide particles surrounded by a carbohydrate coat, and it is being explored as a potential imaging approach for evaluating lymph nodes and certain liver tumors.

Dynamic-contrast-enhanced magnetic resonance imaging of cirrhotic liver parenchyma: A comparison between gadolinium–diethylenetriamine pentaacetic acid and gadolinium–ethoxybenzyl–diethylenetriamine pentaacetic acid

OpenAIRE

Lin, Chun-Yi; Chang, Wei-Chou; Chou, Chen-Te; Chen, Ran-Chou

2015-01-01

Background: The newly developed magnetic-resonance-imaging (MRI) hepatocyte-specific contrast agent, gadolinium–ethoxybenzyl–diethylenetriamine pentaacetic acid (Gd–EOB–DTPA), has different excretion pathways from the conventional MRI contrast agent, gadolinium–diethylenetriamine pentaacetic acid (Gd–DTPA). In this study, we compare the enhancement effect of the liver and renal parenchyma between these two contrast agents for patients with liver cirrhosis. Methods: We retrospectively inclu...

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.

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

Rare earth contrast agents in hepatic computed tomography

International Nuclear Information System (INIS)

Seltzer, S.E.

1981-01-01

Materials with atomic numbers ranging from the upper 50's to the lower 70's proved to have the highest computed tomography (CT) numbers when scanned at 120 kVp. Therefore, to produce particulate contrast agents possessing maximum radiopacity, suspensions of cerium oxide, gadolinium, and dysprosium oxides as well as silver iodide colloid were prepared. All 4 agents were selectively concentrated in the reticulo-endothelial system. The agents produced greater and longer opacification of the normal liver and larger liver-to-tumor differences in rabbits with hepatic tumors than did equivalent amounts of standard intravenous iodinated agents. Lesions as small as 5 mm were visible with CT. These materials have favorable characteristics as hepatic contrast agents, but their toxicity (LD 50 in mice = 5.4 g/kg for Ce) and long-term retention may limit clinical use. (Auth.)

Contrast-enhanced Ultrasound for Non-tumor Liver Diseases

Directory of Open Access Journals (Sweden)

H Maruyama

2012-03-01

Full Text Available Contrast-enhanced ultrasound (CEUS is a simple, safe and reliable technique for the clinical management of patients with various liver diseases. Although the major target of the technique may be focal hepatic lesions, it is also effective for the diagnosis of non-tumor liver diseases, such as grading hepatic fibrosis, characterization of chronic liver diseases and diagnosis of portal vein thrombosis. This review article aimed to overview the recent application of CEUS in the assessment of non-tumor liver diseases. Keywords: Cirrhosis, contrast agent, fibrosis, idiopathic portal hypertension, microbubble, portal vein thrombosis, ultrasound.

Experimental approbation of a new ultrosound contrast agent based on sulfur geksafluoride in diagnostics of focal liver lesions of inflammatory genesis

Directory of Open Access Journals (Sweden)

S. V. Fomina

2017-01-01

Full Text Available Purpose of the study. Experimental approbation of a new domestic ultrasound contrast agent (UCA based on sulfur hexafluoride in the diagnosis of focal liver lesions of inflammatory genesis.Materials and methods. The investigated ultrasound contrast agent (UCA was a heterogeneous gas-liquid system consisting of micro bubbles of a sparingly soluble gas of sulfur hexafluoride (SF6 surrounded by a flexible mobile membrane of surfactants. Experimental work was carried out on rabbits. The study group included rabbits of males and females with focal liver lesion of inflammatory genesis (n = 12 weighing 1500- 1700 g. UCA was administered to animals in the ear vein. Focal lesions of the liver in animals were created in the experimental laboratory conditions. 14 days after the operation, all animals were subjected to ultrasound examination of the surgical intervention zones by using the Toshiba Aplio 400 scanners (Japan with a 3,5–8 MHz convection sensor. In a natural study, the size, structure and echogenicity of the focus were assessed, the degree of vascularization, the evenness and clarity of the contours were determined. When performing post contrast ultrasound, the time of the onset of contrast enhancement, the total duration of contrast, the changes in the contrast enhancement of the focus in different phases of the study were measured, the dimensions of the focus were measured, and the evenness and acuity of contours were measured. For histological examination, liver fragments and lungs were used. 

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 ...

Iron-EHPG as an hepatobiliary MR contrast agent: initial imaging and biodistribution studies

International Nuclear Information System (INIS)

Lauffer, R.B.; Greif, W.L.; Stark, D.D.; Vincent, A.C.; Saini, S.; Wedeen, V.J.; Brady, T.J.

1988-01-01

A paramagnetic relaxation agent targeted to functioning hepatocytes of the liver and excreted into the bile would be useful in the enhancement of normal liver and biliary anatomy in MR imaging. We sought to demonstrate the feasibility of this approach using the prototype hepatobiliary MR contrast agent, iron(III) ethylenebis-(2-hydroxyphenylglycine) (Fe(EHPG) - ). The biodistribution, relaxation enhancement, and imaging characteristics of Fe(EHPG) - were compared to those of the non-specific iron chelate iron(III) diethylenetriaminepentaacetic acid (Fe(DTPA) 2- ), which has a comparable effect on water proton relaxation times. (author)

Magnetic resonance cholangiopancreatography (MRCP) using new negative per-oral contrast agent based on superparamagnetic iron oxide nanoparticles for extrahepatic biliary duct visualization in liver cirrhosis.

Science.gov (United States)

Polakova, Katerina; Mocikova, Ingrid; Purova, Dana; Tucek, Pavel; Novak, Pavel; Novotna, Katerina; Izak, Niko; Bielik, Radoslav; Zboril, Radek; Miroslav, Herman

2016-12-01

Magnetic resonance cholangiopancreatography (MRCP) is often used for imaging of the biliary tree and is required by surgeons before liver transplantation. Advanced liver cirrhosis and ascites in patients however present diagnostic problems for MRCP. The aim of this study was to find out if the use of our negative per-oral contrast agent containing superparamagnetic iron oxide nanoparticles (SPIO) in MRCP is helpful for imaging of hepatobiliary tree in patients with liver cirrhosis. Forty patients with liver cirrhosis were examined on a 1.5 T MR unit using standard MRCP protocol. Twenty patients (group A) underwent MRCP after administration of per-oral SPIO contrast agent 30 min before examination. In group B, twenty patients were examined without per-oral bowel preparation. Ascites was present in eleven patients from group A and in thirteen patients in group B. Four radiologists analyzed MR images for visibility and delineation of the biliary tree. χ 2 tests were used for comparison of the visibility of intrahepatic and extrahepatic biliary ducts in patients with and without ascites. Better extrahepatic biliary duct visualization and visibility of extraluminal pathologies in patients with ascites was proved after administration of SPIO contrast agent. No statistically significant difference between group A and B was found for visualization of extrahepatic biliary ducts in patients without ascites. Delineation of intrahepatic biliary ducts was independent on bowel preparation. Application of our negative per-oral SPIO contrast agent before MRCP improves the visualization of extrahepatic biliary ducts in patients with ascites which is helpful during the liver surgery, mainly in liver transplantation.

An intravenously injectable emulsified iodinated oil contrast agent for liver CT. Experimental study of lipiodol emulsion emulsified by lecithin (LEL38) in rabbits

International Nuclear Information System (INIS)

Kamei, Tsuyoshi

1994-01-01

LEL38 (lipiodol emulsion emulsified by lecithin 38 mgI/ml, mean diameter 200 nm) is a new intravenously injectable oil contrast agent for liver CT. The aim of this report was to evaluate its ability to enhance contrast in the liver of 46 rabbits with regard to the correlation of density with time at an injected dose of 76 mgI/kg (before to 120 minutes after), the correlation of density with dose (0-760 mgI/kg) and the detectability of liver mass. The time-density correlation of LEL38 in the liver, that is, peak density, was achieved after 30 minutes, and it was elevated to 20.9 H. U. Thereafter, it decreased slowly. In the blood vessels, it reached a sharp peak after immediately being elevated to 14. 7 H. U. Thereafter detectability decreased quickly. The maximum difference in density between liver and blood vessels was 34 H. U. after 60 minutes. The dose-density correlation in the liver and blood vessels was linear. Tumors were detected as clear areas of low density. The minimal detectability was about 3 mm. LEL38 may be an effective contrast agent for screening CT studies of liver disease. (author)

MRT of experimental liver abscesses - comparison of a new blood pool contrast agent with gadolinium-DTPA

International Nuclear Information System (INIS)

Dick, A.; Adam, G.; Spuentrup, E.; Prescher, A.; Muehler, A.; Guenther, R.W.

1996-01-01

Purpose: In an experimental pyogenic liver abscess model, the signal intensities were compared intraindividually and interindividually after the application of a new blood pool contrast agent, 24-gadolinium-DTPA (diethylenetriamine-pentaacetic acid) cascade polymer, and after the application of gadopentetate dimeglumine. Methods: In 20 rabbits with experimentally induced liver abscesses, the relative signal intensities of the liver, abscess centre, abscess wall and portal vein were assessed before and between 30 seconds and 60 minutes after injection of a 25 μmol/kg dose of gadolinium polymer and of 100 μmol/kg of gadolinium-DTPA, respectively. Measurements were performed at 1.5 Tesla, using a head coil and a Flash-2-D sequence. Results: The interindividual comparison (unpaired T-test, p [de

Part 1: MRI features of focal nodular hyperplasia with an emphasis on hepatobiliary contrast agents

International Nuclear Information System (INIS)

Sutherland, Tom; Seale, Melanie; Yap, Yap

2014-01-01

Focal nodular hyperplasia (FNH) is the second most common benign liver tumour and typically do not require any treatment. An accurate non-invasive diagnosis is therefore vital to avoid unnecessary intervention and to reassure patients. This article discusses the demographics and pathology of FNH and reviews the appearance of FNH at MRI using liver-specific contrast agents.

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

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.

Magnetic resonance imaging after radiofrequency ablation in a rodent model of liver tumor: tissue characterization using a novel necrosis-avid contrast agent

International Nuclear Information System (INIS)

Ni, Yicheng; Yu, Jie; Marchal, Guy; Chen, Feng; Mulier, Stefaan; Sun, Xihe; Landuyt, Willy; Verbruggen, Alfons

2006-01-01

We exploited a necrosis-avid contrast agent ECIV-7 for magnetic resonance imaging (MRI) in rodent liver tumors after radiofrequency ablation (RFA). Rats bearing liver rhabdomyosarcoma (R1) were randomly allocated to three groups: group I, complete RFA, group II, incomplete RFA, and group III, sham ablation. Within 24 h after RFA, T1-weighted (T1-w) MRI was performed before and after injection of ECIV-7 at 0.05 mmol/kg and followed up from 6-24 h. Signal intensities (SIs) were measured with relative enhancement (RE) and contrast ratio (CR) calculated. The MRI findings were verified histomorphologically. On plain T1-w MRI the contrasts between normal liver, RFA lesion, residual and/or intact tumor were vague. Early after administration of ECIV-7, the liver SI was strongly enhanced (RE=40-50%), leaving the RFA lesion as a hypointense region in groups I and II. At delayed phase, two striking peri-ablational enhancement patterns appeared (RE=90% and CR=1.89%), i.e., ''O'' type of hyperintense rim in group I and ''C'' type of incomplete rim in group II. These MRI manifestations could be proven histologically. In this study, tissue components after RFA could be characterized with discernable contrasts by necrosis-avid contrast agent (NACA)-enhanced MRI, especially at delayed phase. This approach may prove useful for defining the ablated area and identifying residual tumor after RFA. (orig.)

Gadolinium Complex of 1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-1,4,7-trisacetic Acid (DO3A) Conjugate of Tranexamates: A Quest for a Liver-specific Magnetic Resonance Imaging Contrast Agent

International Nuclear Information System (INIS)

Nam, Kisoo; Jeong, Hyunjeong; Kim, Heekyung; Choi, Garam; Chang, Yongmin; Kim, Taejeong; Suh, Kyungjin

2014-01-01

The work is directed toward the synthesis of a series of DO3A conjugates of tranexamates (1c-e) and their Gd complexes (2c-e) for use as a liver-specific MRI CA. All these complexes show thermodynamic and kinetic stabilities comparable to those of structurally related clinical agents such as Dotarem. Their R 1 relaxivities also compare well with those of commercial agent, ranging 3.68-4.84 mM -1 s -1 . In vivo MR images of mice with 2a-e reveal that only 2a exhibits liver-specificity. Although 2b and 2c show strong enhancement in liver, yet no bile-excretion is observed to be termed as a liver-specific agent. The rest behaves much like ordinary ECF CAs like Dotarem. The new series possess no toxicity to be employed in vivo

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.

Detection of an occult hepatocellular carcinoma using ultrasound with liver-specific microbubbles

International Nuclear Information System (INIS)

Harvey, Christopher J.; Lim, Adrian K.P.; Blomley, Martin J.K.; Cosgrove, David O.; Taylor-Robinson, Simon D.; Gedroyc, Wladyslaw M.W.

2002-01-01

The radiological surveillance of cirrhosis to detect the development of hepatocellular carcinoma (HCC) is problematic because no highly sensitive and specific imaging investigation is available. Ultrasound is typically the first modality used but is less accurate than other imaging modalities. We report the first case of a patient with cirrhosis in whom US imaging with liver-specific microbubbles detected an HCC prior to its detection by MR. The use of liver-specific microbubble US contrast agents is an exciting development in the detection of HCC in chronic liver disease and may help to rectify some of the shortcomings of US. (orig.)

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

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

2015-01-01

Aim The aim is to develop irradiated nanodiamonds (INDs) as a molecularly-targeted contrast agent for high resolution and phenotype-specific detection of breast cancer with photoacoustic (PA) imaging. Materials & Methods The surface of acid treated radiation-damaged nanodiamonds was grafted with polyethylene glycol (PEG) to improve its stability and circulation time in blood, followed by conjugation to an anti-Human epidermal growth factor receptor-2 (HER2) peptide (KCCYSL) with a final nanoparticle size of ca. 92 nm. Immunocompetent mice bearing orthotopic HER2 positive or negative tumors were administered INDs and PA imaged using an 820-nm near infrared laser. Results PA images demonstrated that INDs accumulate in tumors and completely delineated the entire tumor within 10 hours. HER2 targeting significantly enhanced imaging of HER2-positive tumors. Pathological examination demonstrated INDs are non-toxic. Conclusions PA technology is adaptable to low-cost bedside medicine, and with new contrast agents described herein, PA can achieve high resolution (sub-mm) and phenotype specific monitoring of cancer growth. PMID:25723091

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.

Hepatic Vein Arrival Time for Diagnosis of Liver Cirrhosis: A 10-Year Single-Center Experience With Contrast-Enhanced Sonography.

Science.gov (United States)

Abbattista, Teresa; Ridolfi, Francesco; Consalvo, Giovanni Traina; Brunelli, Eugenio

2016-10-01

To evaluate the performance of contrast-enhanced sonography with a second-generation contrast agent in assessing the severity of chronic diffuse liver disease and differentiating cirrhotic from noncirrhotic liver disease. Contrast-enhanced sonography was performed after intravenous bolus injection of a second-generation contrast agent in 14 healthy control participants and 160 consecutive patients with cirrhotic and noncirrhotic liver disease (n = 78 and 82, respectively) enrolled between March 2004 and April 2014. The intensity of enhancement in a main hepatic vein was used to determine hepatic vein arrival time, time to peak intensity, and peak contrast enhancement. The hepatic vein arrival time was lower in cirrhotic patients compared with both noncirrhotic patients and controls (mean ± SD, 15.0 ± 2.8, 21.5 ± 3.4, and 25.6 ± 4.7 seconds, respectively; P < .05). The hepatic vein arrival time in noncirrhotic patients was also significantly lower than that in controls (P < .05). The time to peak intensity was significantly lower in cirrhotic patients compared with noncirrhotic patients and controls (40.7 ± 13.7, 49.4 ± 12.8, and 51.2 ± 13.7 seconds; P < .05). A receiver operating characteristic curve analysis revealed that the hepatic vein arrival time more accurately excluded a diagnosis of liver cirrhosis than the time to peak intensity (area under the receiver operating characteristic curve, 0.953 versus 0.694). Specifically, a hepatic vein arrival time cutoff value of 17 seconds excluded liver cirrhosis with 91.1% sensitivity and 93.6% specificity. Contrast-enhanced sonography is a valid alternative method for noninvasive staging of liver diseases. The hepatic vein arrival time could be used to exclude liver cirrhosis in a clinical setting.

Preclinical evaluation of severely defective manganese-based nanocrystal as a liver-specific contrast media for MR imaging: comparison with Gd-EOB-DTPA and MnDPDP

Science.gov (United States)

Zhang, Yu; Xiao, Xiao-ping; Shu, Ting; Cai, Jing; Xiao, Xin-lan; Li, Yan-shu; Zhang, Zhong-wei; Tang, Qun

2018-06-01

Manganese-based (chemically formulated of KMnF3) nanocrystal was evaluated as a liver-specific contrast agent for MR imaging and its imaging performance was also compared with those of two commercial hepatobiliary contrast media (Gd-EOB-DTPA and MnDPDP). KMnF3 nanocrystal was post-treated using a plasma technique to cause severe defects, leading to appropriate water dispersibility and high relaxivity. Severely defective KMnF3 nanocrystal (SD-KMnF3) has characteristic high tolerance, as evidenced by cytotoxicity on the macrophage cell, and acute and subchronic toxicity on the healthy mouse. SD-KMnF3 showed better hepatic MR imaging as the T 1 relaxation time of the liver decreased to only 17% of the control group, compared to 22% of the control group for Gd-EOB-DTPA (P hepatocarcinoma or metastatic lesions.

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.)

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...

Malignant focal hepatic lesions complicating underlying liver disease: dual-phase contrast-enhanced spiral CT sensitivity and specificity in orthotopic liver transplant patients

International Nuclear Information System (INIS)

Mortele, K.J.; De Keukeleire, K.; Praet, M.; Van Vlierberghe, H.; Hemptinne, B. de; Ros, P.R.

2001-01-01

The aim of this study was to determine the accuracy of contrast-enhanced biphasic spiral CT as a screening tool in the preoperative evaluation of orthotopic liver transplant (OLT) patients. Spiral-CT examinations were performed before liver transplantation in 53 patients. Scans were retrospectively reviewed and compared with pathologic findings in fresh-sectioned livers. When findings between spiral CT and pathology were discordant, formalized livers were reexamined with lesion-by lesion evaluation. Fresh pathologic evaluation revealed 23 liver lesions (16 HCC, 7 macro-regenerative nodules). Malignancy was identified in 13 of 53 patients (24.5%). Pre-transplantation spiral CT depicted 27 liver lesions (23 HCC, 4 macro-regenerative nodules). Malignancy was suspected in 14 patients (26.4%). In 10 of 53 (18.9%), spiral CT and pathologic evaluation were discordant. Subsequent retrospective pathologic evaluation showed malignancy in 4 additional patients. Spiral CT compared with the retrospective pathologic findings revealed 36 real-negative, 14 real-positive, 0 false-positive, and 3 false-negative patients with malignancy. Sensitivity and specificity of spiral CT in detection of malignancy was 82 and 100%, respectively. Contrast-enhanced biphasic spiral CT is an accurate technique in the evaluation of patients preceding OLT. Routine fresh-sectioned liver pathologic findings are not as sensitive as previously estimated. (orig.)

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

Comparison of gadolinium Cy2DOTA, a new hepatobiliary agent, and gadolinium HP-DO3A, an extracellular agent, in healthy liver and metastatic disease

International Nuclear Information System (INIS)

Runge, V.M.; Wells, J.W.; Williams, N.M.

1995-01-01

A new gadolinium (Gd) chelate with preferential hepatobiliary uptake, Gd Cy 2 DOTA, was compared in two animal species with Gd HP-DO3A (gadoteridol), a clinically approved contrast agent with extracellular distribution. Liver enhancement was evaluated for these two contrast agents using magnetic resonance imaging, whereas an experimental model of metastatic disease was used to evaluate the agents' efficacy for liver-lesion delineation. The two agents were compared in four healthy Rhesus monkeys (eight studies) and five New Zealand White rabbits with implanted VX-2 liver tumors (ten studies). The contrast dose was 0.1 mmol/kg, with the agents given in random order and at least 72 hours between contrast injections. Breathhold T1-weighted spin echo scans were obtained at 1.5 tesla (T) before and after contrast was administered. Postcontrast scans were obtained 1 to 90 minutes after injection in the monkeys and 1 to 240 minutes after injection in the rabbits. Prolonged hepatic enhancement, superior in degree to that with Gd HP-DO3A, was noted to both monkeys and rabbits after injection of Gd Cy 2 DOTA. Two minutes after contrast, liver SI was 1.94 ± 0.05 with Gd Cy 2 DOTA compared with 1.5 ± 0.05 with Gd HP-DO3A in monkeys. Sixty minutes after contrast, liver SI was 1.60 ± 0.09 compared with 1.20 ± 0.02. The difference between agents was significant at all times from 2 to 60 minutes after contrast injection (P 2 DOTA but not with Gd HP-DO3A. The maximum improvement in lesion conspicuity (rabbit) occurred 45 minutes after injection of Gd Cy 2 DOTA and 5 minutes after injection of Gd HP-DO3A. 22 refs., 12 figs

Liver nodules. MR imaging using extracellular gadolinium agent

International Nuclear Information System (INIS)

Yoshimitsu, Kengo; Honda, Hiroshi

2009-01-01

Extracellular gadolinium (Gd)-containing contrast medium, including gadopentetate dimeglumine (Gd-DTPA), has been playing a main role in the diagnostic MR imaging of the liver. Its significance is two-fold: assessment of the degree of neovascularity or angiogenesis in its early dynamic phase, and that of bulk of interstitium in its equilibrium phase. With the advent of gadolinium ethoxybenzyl diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA), which can be used as a dynamic study agent by bolus injection in addition to its original use as a tissue-specific agent, some possibility has been suggested that extracellular Gd agent would be no longer available in the near future in the field of liver MR imaging. Neovascularity or arterial supply of a lesion may well be assessed by Gd-EOB-DTPA, when carefully selected pulse sequence and well designed injection protocol are used, as well as by Gd-DTPA. However, the pertinent assessment of interstitium or stroma can never be achieved by Gd-EOB-DTPA or any other contrast medium present. The interstitium of neoplasm, typically called as stromal fibrosis, is generated through the interaction between the neoplasm per se and its host, and its clinicopathological significance related to disease prognosis has well been established in some disease entities. Extracellular Gd agent is the only contrast medium that can provide information regarding the tumor stroma in a simple, easy, safe and non-invasive fashion, when properly used. This review article discusses, dynamic MR imaging features of representative liver diseases, including several recent topics. From technical point of view, 3D gradient-echo sequence with fat suppression should be used for dynamic studies along with tailored injection protocol using autoinjector and saline flush. Vascularity of hepatocellular carcinoma (HCC) can now be properly assessed by dynamic MR with approximately 90% concordance with CT during hepatic arteriography. Portal phase images can be used to

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

Computed Tomography Imaging of Solid Tumors Using a Liposomal-Iodine Contrast Agent in Companion Dogs with Naturally Occurring Cancer.

Science.gov (United States)

Ghaghada, Ketan B; Sato, Amy F; Starosolski, Zbigniew A; Berg, John; Vail, David M

2016-01-01

Companion dogs with naturally occurring cancer serve as an important large animal model in translational research because they share strong similarities with human cancers. In this study, we investigated a long circulating liposomal-iodine contrast agent (Liposomal-I) for computed tomography (CT) imaging of solid tumors in companion dogs with naturally occurring cancer. The institutional animal ethics committees approved the study and written informed consent was obtained from all owners. Thirteen dogs (mean age 10.1 years) with a variety of masses including primary and metastatic liver tumors, sarcomas, mammary carcinoma and lung tumors, were enrolled in the study. CT imaging was performed pre-contrast and at 15 minutes and 24 hours after intravenous administration of Liposomal-I (275 mg/kg iodine dose). Conventional contrast-enhanced CT imaging was performed in a subset of dogs, 90 minutes prior to administration of Liposomal-I. Histologic or cytologic diagnosis was obtained for each dog prior to admission into the study. Liposomal-I resulted in significant (p contrast agent was demonstrated. Liposomal-I enabled visualization of primary and metastatic liver tumors. Sub-cm sized liver lesions grossly appeared as hypo-enhanced compared to the surrounding normal parenchyma with improved lesion conspicuity in the post-24 hour scan. Large liver tumors (> 1 cm) demonstrated a heterogeneous pattern of intra-tumoral signal with visibly higher signal enhancement at the post-24 hour time point. Extra-hepatic, extra-splenic tumors, including histiocytic sarcoma, anaplastic sarcoma, mammary carcinoma and lung tumors, were visualized with a heterogeneous enhancement pattern in the post-24 hour scan. The long circulating liposomal-iodine contrast agent enabled prolonged visualization of small and large tumors in companion dogs with naturally occurring cancer. The study warrants future work to assess the sensitivity and specificity of the Liposomal-I agent in various types of

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)

Confluent focal nodular hyperplasia mimicking liver cancer: Value of liver-specific contrast-enhanced MRI for diagnosis

Directory of Open Access Journals (Sweden)

Yu-Chi Cheng

2012-07-01

Full Text Available Focal nodular hyperplasia is the second most common benign hepatic tumor. Unlike adenoma as well as the malignant neoplasms, focal nodular hyperplasia can often be managed successfully without surgery. Use of liver-specific contrast-enhanced magnetic resonance imaging allows clinicians to confirm the diagnosis noninvasively in some patients, allowing select patients to avoid surgery. We report a case of a patient who presented with the rare profile of multiple, confluent lesions that were diagnosed, using magnetic resonance imaging with gadolinium-dimeglumine, as focal nodular hyperplasia. This complicated case was managed successfully and noninvasively based on algorithm found in the recent literature that allows patients to avoid unnecessary surgery.

Prostate-specific membrane antigen targeted protein contrast agents for molecular imaging of prostate cancer by MRI

Science.gov (United States)

Pu, Fan; Salarian, Mani; Xue, Shenghui; Qiao, Jingjuan; Feng, Jie; Tan, Shanshan; Patel, Anvi; Li, Xin; Mamouni, Kenza; Hekmatyar, Khan; Zou, Juan; Wu, Daqing; Yang, Jenny J.

2016-06-01

Prostate-specific membrane antigen (PSMA) is one of the most specific cell surface markers for prostate cancer diagnosis and targeted treatment. However, achieving molecular imaging using non-invasive MRI with high resolution has yet to be achieved due to the lack of contrast agents with significantly improved relaxivity for sensitivity, targeting capabilities and metal selectivity. We have previously reported our creation of a novel class of protein Gd3+ contrast agents, ProCA32, which displayed significantly improved relaxivity while exhibiting strong Gd3+ binding selectivity over physiological metal ions. In this study, we report our effort in further developing biomarker-targeted protein MRI contrast agents for molecular imaging of PSMA. Among three PSMA targeted contrast agents engineered with addition of different molecular recognition sequences, ProCA32.PSMA exhibits a binding affinity of 1.1 +/- 0.1 μM for PSMA while the metal binding affinity is maintained at 0.9 +/- 0.1 × 10-22 M. In addition, ProCA32.PSMA exhibits r1 of 27.6 mM-1 s-1 and r2 of 37.9 mM-1 s-1 per Gd (55.2 and 75.8 mM-1 s-1 per molecule r1 and r2, respectively) at 1.4 T. At 7 T, ProCA32.PSMA also has r2 of 94.0 mM-1 s-1 per Gd (188.0 mM-1 s-1 per molecule) and r1 of 18.6 mM-1 s-1 per Gd (37.2 mM-1 s-1 per molecule). This contrast capability enables the first MRI enhancement dependent on PSMA expression levels in tumor bearing mice using both T1 and T2-weighted MRI at 7 T. Further development of these PSMA-targeted contrast agents are expected to be used for the precision imaging of prostate cancer at an early stage and to monitor disease progression and staging, as well as determine the effect of therapeutic treatment by non-invasive evaluation of the PSMA level using MRI.Prostate-specific membrane antigen (PSMA) is one of the most specific cell surface markers for prostate cancer diagnosis and targeted treatment. However, achieving molecular imaging using non-invasive MRI with high

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

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

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

OpenAIRE

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

2017-01-01

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 endotheli...

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

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

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

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.

Contrast-enhanced peripheral MRA. Technique and contrast agents

International Nuclear Information System (INIS)

Nielsen, Yousef W.; Thomsen, Henrik S.

2012-01-01

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

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

Science.gov (United States)

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

2017-08-16

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

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.

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

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.

Abdominal MR: liver and pancreas

International Nuclear Information System (INIS)

Bartolozzi, C.; Lencioni, R.; Donati, F.; Cioni, D.

1999-01-01

Following the introduction of rapid, high-quality scan techniques and the development of new, tissue-specific contrast agents, the applications of MRI for abdominal imaging are experiencing unprecedented growth. This article examines the current status of liver and pancreatic MRI, highlighting technical and methodological approach, use of contrast agents, and main clinical applications. The MRI technique appears to be the ideal diagnostic tool for detection and characterization of benign and malignant liver neoplasms, and for evaluating tumor response after nonsurgical treatments. Dynamic imaging after bolus injection of a gadolinium chelate is currently a fundamental component of an MRI examination of the liver in many instances. Optimal dynamic scanning depends on the use of a multisection spoiled gradient-echo technique that allows one to image the entire region of interest during a single suspended respiration. Images are obtained during four phases relative to the injection of the contrast agent: precontrast, arterial (pre-sinusoidal), portal (sinusoidal), and delayed (extracellular) phase. Liver-specific contrast agents, including hepatobiliary agents and reticuloendothelial system-targeted iron oxide particles, however, may offer advantages over gadolinium chelates in some clinical settings. Computed tomography is still preferred to MRI for imaging the pancreas. However, state-of-the-art MRI may currently be at least as accurate as spiral CT for depiction of inflammatory and neoplastic pancreatic diseases. Moreover, MRI has the advantage of allowing simultaneous investigation of the biliary tree, owing to cholangiopancreatography techniques. Hence, a comprehensive assessment of most pancreatic diseases can be achieved with a single examination. (orig.)

Evaluation of living liver transplant donors: method for precise anatomic definition by using a dedicated contrast-enhanced MR imaging protocol.

Science.gov (United States)

Sahani, Dushyant; D'souza, Roy; Kadavigere, Rajagopal; Hertl, Martin; McGowan, Jennifer; Saini, Sanjay; Mueller, Peter R

2004-01-01

Liver transplantation from a living donor involves removal of part of the donor liver in a fashion that does not endanger its vascular supply or metabolic function. The radiologist plays an important role in evaluation of the living donor to define the conditions under which graft donation is contraindicated and to identify anatomic variations that may alter the surgical approach. In the past, diagnostic work-up of the donor involved costly and invasive tests. Currently, dynamic contrast material-enhanced computed tomography and magnetic resonance (MR) imaging are the imaging tests performed, each of which has advantages and limitations. MR imaging performed with liver-specific and extravascular contrast agents may be used as a single imaging test for comprehensive noninvasive evaluation of living liver transplant donors. MR imaging provides valuable information about variations in the vascular and biliary anatomy and allows evaluation of the hepatic parenchyma for diffuse or focal abnormalities. Copyright RSNA, 2004

Low density contrast agents for x-ray phase contrast imaging: the use of ambient air for x-ray angiography of excised murine liver tissue

International Nuclear Information System (INIS)

Laperle, Christopher M; Wintermeyer, Philip; Derdak, Zoltan; Wands, Jack R; Hamilton, Theron J; Walker, Evan J; Diebold, Gerald; Rose-Petruck, Christoph; Shi, Daxin; Anastasio, Mark A

2008-01-01

We report a new preparative method for providing contrast through reduction in electron density that is uniquely suited for propagation-based differential x-ray phase contrast imaging. The method, which results in an air or fluid filled vasculature, makes possible visualization of the smallest microvessels, roughly down to 15 μm, in an excised murine liver, while preserving the tissue for subsequent histological workup. We show the utility of spatial frequency filtering for increasing the visibility of minute features characteristic of phase contrast imaging, and the capability of tomographic reconstruction to reveal microvessel structure and three-dimensional visualization of the sample. The effect of water evaporation from livers during x-ray imaging on the visibility of blood vessels is delineated. The deformed vascular tree in a cancerous murine liver is imaged.

Contrast agent enhanced pQCT of articular cartilage

Energy Technology Data Exchange (ETDEWEB)

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

2007-02-21

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

Contrast agent enhanced pQCT of articular cartilage

Science.gov (United States)

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

2007-02-01

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

Contrast agent enhanced pQCT of articular cartilage

International Nuclear Information System (INIS)

Kallioniemi, A S; Jurvelin, J S; Nieminen, M T; Lammi, M J; Toeyraes, J

2007-01-01

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

Field strength and dose dependence of contrast enhancement by gadolinium-based MR contrast agents

International Nuclear Information System (INIS)

Rinck, P.A.; Muller, R.N.

1999-01-01

The relaxivities r 1 and r 2 of magnetic resonance contrast agents and the T 1 relaxation time values of tissues are strongly field dependent. We present quantitative data and simulations of different gadolinium-based extracellular fluid contrast agents and the modulation of their contrast enhancement by the magnetic field to be able to answer the following questions: How are the dose and field dependences of their contrast enhancement? Is there an interrelationship between dose and field dependence? Should one increase or decrease doses at specific fields? Nuclear magnetic relaxation dispersion data were acquired for the following contrast agents: gadopentetate dimeglumine, gadoterate meglumine, gadodiamide injection, and gadoteridol injection, as well as for several normal and pathological human tissue samples. The magnetic field range stretched from 0.0002 to 4.7 T, including the entire clinical imaging range. The data acquired were then fitted with the appropriate theoretical models. The combination of the diamagnetic relaxation rates (R 1 = 1/T 1 and R 2 = 1/T 2 ) of tissues with the respective paramagnetic contributions of the contrast agents allowed the prediction of image contrast at any magnetic field. The results revealed a nearly identical field and dose-dependent increase of contrast enhancement induced by these contrast agents within a certain dose range. The target tissue concentration (TTC) was an important though nonlinear factor for enhancement. The currently recommended dose of 0.1 mmol/kg body weight seems to be a compromise close to the lower limits of diagnostically sufficient contrast enhancement for clinical imaging at all field strengths. At low field contrast enhancement might be insufficient. Adjustment of dose or concentration, or a new class of contrast agents with optimized relaxivity, would be a valuable contribution to a better diagnostic yield of contrast enhancement at all fields. (orig.)

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

Science.gov (United States)

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

2004-10-01

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

Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

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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.

Casein-Coated Fe5C2 Nanoparticles with Superior r2 Relaxivity for Liver-Specific Magnetic Resonance Imaging.

Science.gov (United States)

Cowger, Taku A; Tang, Wei; Zhen, Zipeng; Hu, Kai; Rink, David E; Todd, Trever J; Wang, Geoffrey D; Zhang, Weizhong; Chen, Hongmin; Xie, Jin

2015-01-01

Iron oxide nanoparticles have been extensively used as T2 contrast agents for liver-specific magnetic resonance imaging (MRI). The applications, however, have been limited by their mediocre magnetism and r2 relaxivity. Recent studies show that Fe5C2 nanoparticles can be prepared by high temperature thermal decomposition. The resulting nanoparticles possess strong and air stable magnetism, suggesting their potential as a novel type of T2 contrast agent. To this end, we improve the synthetic and surface modification methods of Fe5C2 nanoparticles, and investigated the impact of size and coating on their performances for liver MRI. Specifically, we prepared 5, 14, and 22 nm Fe5C2 nanoparticles and engineered their surface by: 1) ligand addition with phospholipids, 2) ligand exchange with zwitterion-dopamine-sulfonate (ZDS), and 3) protein adsorption with casein. It was found that the size and surface coating have varied levels of impact on the particles' hydrodynamic size, viability, uptake by macrophages, and r2 relaxivity. Interestingly, while phospholipid- and ZDS-coated Fe5C2 nanoparticles showed comparable r2, the casein coating led to an r2 enhancement by more than 2 fold. In particular, casein coated 22 nm Fe5C2 nanoparticle show a striking r2 of 973 mM(-1)s(-1), which is one of the highest among all of the T2 contrast agents reported to date. Small animal studies confirmed the advantage of Fe5C2 nanoparticles over iron oxide nanoparticles in inducing hypointensities on T2-weighted MR images, and the particles caused little toxicity to the host. The improvements are important for transforming Fe5C2 nanoparticles into a new class of MRI contrast agents. The observations also shed light on protein-based surface modification as a means to modulate contrast ability of magnetic nanoparticles.

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

In-line X-ray phase-contrast imaging of murine liver microvasculature ex vivo

International Nuclear Information System (INIS)

Li Beilei; Xu Min; Shi Hongcheng; Chen Shaoliang; Wu Weizhong; Peng Guanyun; Zhang Xi; Peng Yifeng

2012-01-01

Imaging blood vessels is of importance for determining the vascular distribution of organs and tumors. Phase-contrast X-ray imaging can reveal the vessels in much more detail than conventional X-ray absorption method. Visualizing murine liver microvasculature ex vivo with phase-contrast X-ray imaging was performed at Shanghai Synchrotron Radiation Facility. Barium sulfate and physiological saline were used as contrast agents for the blood vessels. Blood vessels of <Φ20 μm could be detected by replacing resident blood with physiological saline or barium sulfate. An entire branch of the portal vein (from the main axial portal vein to the ninth generation of branching) could be captured in a single phase-contrast image. It is demonstrated that selective angiography based on phase contrast X-ray imaging, with a physiological material of low Z elements (such as saline) being the contrast agent, is a viable imaging strategy. Further efforts will be focused on using the technique to image tumor angiogenesis. (authors)

Magnetic Resonance Imaging Contrast Agents: A Review of Literature

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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.

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.

Three-dimensional visualization of the microvasculature of bile duct ligation-induced liver fibrosis in rats by x-ray phase-contrast imaging computed tomography

Science.gov (United States)

Xuan, Ruijiao; Zhao, Xinyan; Hu, Doudou; Jian, Jianbo; Wang, Tailing; Hu, Chunhong

2015-07-01

X-ray phase-contrast imaging (PCI) can substantially enhance contrast, and is particularly useful in differentiating biological soft tissues with small density differences. Combined with computed tomography (CT), PCI-CT enables the acquisition of accurate microstructures inside biological samples. In this study, liver microvasculature was visualized without contrast agents in vitro with PCI-CT using liver fibrosis samples induced by bile duct ligation (BDL) in rats. The histological section examination confirmed the correspondence of CT images with the microvascular morphology of the samples. By means of the PCI-CT and three-dimensional (3D) visualization technique, 3D microvascular structures in samples from different stages of liver fibrosis were clearly revealed. Different types of blood vessels, including portal veins and hepatic veins, in addition to ductular proliferation and bile ducts, could be distinguished with good sensitivity, excellent specificity and excellent accuracy. The study showed that PCI-CT could assess the morphological changes in liver microvasculature that result from fibrosis and allow characterization of the anatomical and pathological features of the microvasculature. With further development of PCI-CT technique, it may become a novel noninvasive imaging technique for the auxiliary analysis of liver fibrosis.

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.

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

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

Parametric imaging for characterizing focal liver lesions in contrast-enhanced ultrasound.

Science.gov (United States)

Rognin, Nicolas G; Arditi, Marcel; Mercier, Laurent; Frinking, Peter J A; Schneider, Michel; Perrenoud, Geneviève; Anaye, Anass; Meuwly, Jean-Yves; Tranquart, François

2010-11-01

The differentiation between benign and malignant focal liver lesions plays an important role in diagnosis of liver disease and therapeutic planning of local or general disease. This differentiation, based on characterization, relies on the observation of the dynamic vascular patterns (DVP) of lesions with respect to adjacent parenchyma, and may be assessed during contrast-enhanced ultrasound imaging after a bolus injection. For instance, hemangiomas (i.e., benign lesions) exhibit hyper-enhanced signatures over time, whereas metastases (i.e., malignant lesions) frequently present hyperenhanced foci during the arterial phase and always become hypo-enhanced afterwards. The objective of this work was to develop a new parametric imaging technique, aimed at mapping the DVP signatures into a single image called a DVP parametric image, conceived as a diagnostic aid tool for characterizing lesion types. The methodology consisted in processing a time sequence of images (DICOM video data) using four consecutive steps: (1) pre-processing combining image motion correction and linearization to derive an echo-power signal, in each pixel, proportional to local contrast agent concentration over time; (2) signal modeling, by means of a curve-fitting optimization, to compute a difference signal in each pixel, as the subtraction of adjacent parenchyma kinetic from the echopower signal; (3) classification of difference signals; and (4) parametric image rendering to represent classified pixels as a support for diagnosis. DVP parametric imaging was the object of a clinical assessment on a total of 146 lesions, imaged using different medical ultrasound systems. The resulting sensitivity and specificity were 97% and 91%, respectively, which compare favorably with scores of 81 to 95% and 80 to 95% reported in medical literature for sensitivity and specificity, respectively.

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)

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.

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

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

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

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

Contrast-enhanced ultrasound in the diagnosis of nodules in liver cirrhosis.

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Kim, Tae Kyoung; Jang, Hyun-Jung

2014-04-07

Contrast-enhanced ultrasound (CEUS) using microbubble contrast agents are useful for the diagnosis of the nodules in liver cirrhosis. CEUS can be used as a problem-solving method for indeterminate nodules on computed tomography (CT) or magnetic resonance imaging (MRI) or as an initial diagnostic test for small newly detected liver nodules. CEUS has unique advantages over CT and MRI including no renal excretion of contrast, real-time imaging capability, and purely intravascular contrast. Hepatocellular carcinoma (HCC) is characterized by arterial-phase hypervascularity and later washout (negative enhancement). Benign nodules such as regenerative nodules or dysplastic nodules are usually isoechoic or slightly hypoechoic in the arterial phase and isoechoic in the late phase. However, there are occasional HCC lesions with atypical enhancement including hypovascular HCC and hypervascular HCC without washout. Cholangiocarcinomas are infrequently detected during HCC surveillance and mostly show rim-like or diffuse hypervascularity followed by rapid washout. Hemangiomas are often found at HCC surveillance and are easily diagnosed by CEUS. CEUS can be effectively used in the diagnostic work-up of small nodules detected at HCC surveillance. CEUS is also useful to differentiate malignant and benign venous thrombosis and to guide and monitor the local ablation therapy for HCC.

Measuring SPIO and Gd contrast agent magnetization using 3 T MRI

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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

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.

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

Directory of Open Access Journals (Sweden)

Aziz F

2017-02-01

Full Text Available Farooq Aziz,1,2 Ayesha Ihsan,1 Aalia Nazir,2 Ishaq Ahmad,3 Sadia Zafar Bajwa,1 Asma Rehman,1 Abdoulaye Diallo,4 Waheed S Khan1 1Nanobiotechnology Group, National Institute for Biotechnology and Genetic Engineering (NIBGE, Faisalabad, 2Department of Physics, Islamia University of Bahawalpur, Bahawalpur, 3National Center for Physics, Quaid-I-Azam University, Islamabad, Pakistan; 4Laboratory of Photonics and Nano-Fabrication, Faculty of Science and Technology, Cheikh Anta Diop University of Dakar (UCAD, Dakar-Fann Dakar, Senegal Abstract: Gold nanoparticles (GNPs with dimension in the range of 1–100 nm have a prominent role in a number of biomedical applications like imaging, drug delivery, and cancer therapy owing to their unique optical features and biocompatibility. In this work, we report a novel technique for the synthesis of two types of GNPs namely porous gold nanoparticles (PGNPs and solid gold nanoparticles (SGNPs. PGNPs of size 35 nm were fabricated by reduction of gold (III solution with lecithin followed by addition of L-ascorbic acid and tri-sodium citrate, whereas SGNPs with a dimension of 28 nm were prepared by reflux method using lecithin as a single reducing agent. Comparative studies using PGNPs (λmax 560 nm and SGNPs (λmax 548 nm were conducted for evaluating their use as a contrast agent. These studies reveled that in direct computed tomography scan, PGNPs exhibited brighter contrast (45 HU than SGNPs (26 HU. To investigate the effect of PGNPs and SGNPs on the liver and kidney profile, male rabbits were intravenously injected with an equal dose of 1 mg/kg weight of PGNPs and SGNPs. The effect on biochemical parameters was evaluated 72 hours after intravenous (IV injection including liver function profile, renal (kidney function biomarker, random blood glucose value, and cholesterol level. During one comparison of contrast in CT scan, PGNPs showed significantly enhanced contrast in whole-rabbit and organ CT scan as

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.

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.

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.

Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: a biocompatible, size-tunable contrast agent for magnetic resonance imaging.

Science.gov (United States)

Unterweger, Harald; Janko, Christina; Schwarz, Marc; Dézsi, László; Urbanics, Rudolf; Matuszak, Jasmin; Őrfi, Erik; Fülöp, Tamás; Bäuerle, Tobias; Szebeni, János; Journé, Clément; Boccaccini, Aldo R; Alexiou, Christoph; Lyer, Stefan; Cicha, Iwona

2017-01-01

Iron oxide-based contrast agents have been in clinical use for magnetic resonance imaging (MRI) of lymph nodes, liver, intestines, and the cardiovascular system. Superparamagnetic iron oxide nanoparticles (SPIONs) have high potential as a contrast agent for MRI, but no intravenous iron oxide-containing agents are currently approved for clinical imaging. The aim of our work was to analyze the hemocompatibility and immuno-safety of a new type of dextran-coated SPIONs (SPIONdex) and to characterize these nanoparticles with ultra-high-field MRI. Key parameters related to nanoparticle hemocompatibility and immuno-safety were investigated in vitro and ex vivo. To address concerns associated with hypersensitivity reactions to injectable nanoparticulate agents, we analyzed complement activation-related pseudoallergy (CARPA) upon intravenous administration of SPIONdex in a pig model. Furthermore, the size-tunability of SPIONdex and the effects of size reduction on their biocompatibility were investigated. In vitro, SPIONdex did not induce hemolysis, complement or platelet activation, plasma coagulation, or leukocyte procoagulant activity, and had no relevant effect on endothelial cell viability or endothelial-monocytic cell interactions. Furthermore, SPIONdex did not induce CARPA even upon intravenous administration of 5 mg Fe/kg in pigs. Upon SPIONdex administration in mice, decreased liver signal intensity was observed after 15 minutes and was still detectable 24 h later. In addition, by changing synthesis parameters, a reduction in particle size contrast agent.

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.

Evaluation of liver parenchyma and perfusion using dynamic contrast-enhanced computed tomography and contrast-enhanced ultrasonography in captive green iguanas (Iguana iguana) under general anesthesia.

Science.gov (United States)

Nardini, Giordano; Di Girolamo, Nicola; Leopardi, Stefania; Paganelli, Irene; Zaghini, Anna; Origgi, Francesco C; Vignoli, Massimo

2014-05-13

Contrast-enhanced diagnostic imaging techniques are considered useful in veterinary and human medicine to evaluate liver perfusion and focal hepatic lesions. Although hepatic diseases are a common occurrence in reptile medicine, there is no reference to the use of contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT) to evaluate the liver in lizards. Therefore, the aim of this study was to evaluate the pattern of change in echogenicity and attenuation of the liver in green iguanas (Iguana iguana) after administration of specific contrast media. An increase in liver echogenicity and density was evident during CEUS and CECT, respectively. In CEUS, the mean ± SD (median; range) peak enhancement was 19.9% ± 7.5 (18.3; 11.7-34.6). Time to peak enhancement was 134.0 ± 125.1 (68.4; 59.6-364.5) seconds. During CECT, first visualization of the contrast medium was at 3.6 ± 0.5 (4; 3-4) seconds in the aorta, 10.7 ± 2.2 (10.5; 7-14) seconds in the hepatic arteries, and 15 ± 4.5 (14.5; 10-24) seconds in the liver parenchyma. Time to peak was 14.1 ± 3.4 (13; 11-21) and 31 ± 9.6 (29; 23-45) seconds in the aorta and the liver parenchyma, respectively. CEUS and dynamic CECT are practical means to determine liver hemodynamics in green iguanas. Distribution of contrast medium in iguana differed from mammals. Specific reference ranges of hepatic perfusion for diagnostic evaluation of the liver in iguanas are necessary since the use of mammalian references may lead the clinician to formulate incorrect diagnostic suspicions.

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

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)

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.)

Investigation of a potential macromolecular MRI contrast agent prepared from PPI (G = 2, polypropyleneimine, generation 2) dendrimer bifunctional chelates

Science.gov (United States)

Wang, Jianxin Steven

The long-term objective is to develop magnetic resonance (MR) contrast agents that actively and passively target tumors for diagnosis and therapy. Many diagnostic imaging techniques for cancer lack specificity. A dendrimer based magnetic resonance imaging contrast agent has been developed with large proton relaxation enhancements and high molecular relaxivities. A new type of linear dendrimer based MRI contrast agent that is built from the polypropyleneimine and polyamidoamine dendrimers in which free amines have been conjugated to the chelate DTPA, which further formed the complex with Gadolinium (Gd) was studied. The specific research goals were to test the hypothesis that a linear chelate with macromolecular agents can be used in vitro and in vivo. This work successfully examined the adequacy and viability of the application for this agent in vitro and in vivo. A small animal whole body counter was designed and constructed to allow us to monitor biodistribution and kinetic mechanisms using a radioisotope labeled complex. The procedures of metal labeling, separation and purification have been established from this work. A biodistribution study has been performed using radioisotope induced organ/tissue counting and gamma camera imaging. The ratio of percentage of injected dose per gram organ/tissue for kidney and liver is 3.71 from whole body counter and 3.77 from the gamma camera. The results suggested that retention of Gd (III) is too high and a more kinetically stable chelate should be developed. The pharmacokinetic was evaluated in the whole animal model with the whole body clearance, and a kinetics model was developed. The pharmacokinetic results showed a bi-exponential decay in the animal model with two component excretion constants 1.43e(-5) and 0.0038511, which give half-lives of 3 hours and 33.6 days, respectively. Magnetic resonance imaging of this complex resulted in a 52% contrast enhancement in the rat kidney following the agents' administration in

Three-dimensional imaging of the aortic vessel wall using an elastin-specific magnetic resonance contrast agent.

Science.gov (United States)

Makowski, Marcus R; Preissel, Anne; von Bary, Christian; Warley, Alice; Schachoff, Sylvia; Keithan, Alexandra; Cesati, Richard R; Onthank, David C; Schwaiger, Markus; Robinson, Simon P; Botnar, René M

2012-07-01

The aim of this study was to demonstrate the feasibility of high-resolution 3-dimensional aortic vessel wall imaging using a novel elastin-specific magnetic resonance contrast agent (ESMA) in a large animal model. The thoracic aortic vessel wall of 6 Landrace pigs was imaged using a novel ESMA and a nonspecific control agent. On day 1, imaging was performed before and after the administration of a nonspecific control agent, gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA; Bayer Schering AG, Berlin, Germany). On day 3, identical scans were repeated before and after the administration of a novel ESMA (Lantheus Medical Imaging, North Billerica, Massachusetts). Three-dimensional inversion recovery gradient echo delayed-enhancement imaging and magnetic resonance (MR) angiography of the thoracic aortic vessel wall were performed on a 1.5-T MR scanner (Achieva; Philips Medical Systems, the Netherlands). The signal-to-noise ratio and the contrast-to-noise ratio of arterial wall enhancement, including the time course of enhancement, were assessed for ESMA and Gd-DTPA. After the completion of imaging sessions, histology, electron microscopy, and inductively coupled plasma mass spectroscopy were performed to localize and quantify the gadolinium bound to the arterial vessel wall. Administration of ESMA resulted in a strong enhancement of the aortic vessel wall on delayed-enhancement imaging, whereas no significant enhancement could be measured with Gd-DTPA. Ninety to 100 minutes after the administration of ESMA, significantly higher signal-to-noise ratio and contrast-to-noise ratio could be measured compared with the administration of Gd-DTPA (45.7 ± 9.6 vs 13.2 ± 3.5, P wall imaging using a novel ESMA in a large animal model under conditions resembling a clinical setting. Such an approach could be useful for the fast 3-dimensional assessment of the arterial vessel wall in the context of atherosclerosis, aortic aneurysms, and hypertension.

Synthesis and evaluation of novel polysaccharide-Gd-DTPA compounds as contrast agent for MRI

Science.gov (United States)

Sun, Guoying; Feng, Jianghua; Jing, Fengying; Pei, Fengkui; Liu, Maili

2003-09-01

Macromolecular conjugates of two kinds of natural polysaccharides, that from Panax quinquefolium linn (PQPS) and Ganoderma applanatum pat (GAPS), with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) have been synthesized and characterized by means of FTIR, elementary analysis and ICP-AES. Their stability was investigated by competition study with Ca 2+, EDTA (ethylenediaminetetraacetic acid) and DTPA. Polysaccharide-bound complexes exhibit T1 relaxivities of 1.5-1.7 times that of Gd-DTPA in D 2O at 25°C and 9.4 T. MR imaging of Sprague-Dawley (SD) rats showed remarkable enhancement in rat liver and kidney after i.v. injection of these two complexes: liver parenchyma 60.9±5.6%, 57.8±7.4% at 65-85 min; kidney 144.9±14.5%, 199.9±25.4% at 10-30 min for PQPS-Gd-DTPA, GAPS-Gd-DTPA at gadolinium dose of 0.083 and 0.082 mmol/kg, respectively. Our preliminary in vivo and in vitro study indicates that the two kinds of polysaccharide-bound complexes are potential tissue-specific contrast agents for MRI.

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

International Nuclear Information System (INIS)

Lazaro, Francisco Jose; Gutierrez, Lucia; Rosa Abadia, Ana; Soledad Romero, Maria; Lopez, Antonio; Jesus Munoz, Maria

2007-01-01

A magnetic AC susceptibility characterisation of rat tissues after intravenous administration of superparamagnetic iron oxide (Endorem ( R)), at the same dose as established for Magnetic Resonance Imaging (MRI) contrast enhancement in humans, has been carried out. The measurements reveal the presence of the contrast agent as well as that of physiological ferritin in liver and spleen while no traces have been magnetically detected in heart and kidney. This preliminary work opens suggestive possibilities for future biodistribution studies of any type of magnetic carriers

Single-energy non-contrast hepatic steatosis criteria applied to virtual non-contrast images: is it still highly specific and positively predictive?

Science.gov (United States)

Haji-Momenian, S; Parkinson, W; Khati, N; Brindle, K; Earls, J; Zeman, R K

2018-06-01

To determine the sensitivity, specificity, and predictive values of single-energy non-contrast hepatic steatosis criteria on dual-energy virtual non-contrast (VNC) images. Forty-eight computed tomography (CT) examinations, which included single-energy non-contrast (TNC) and contrast-enhanced dual-energy CT angiography (CTA) of the abdomen, were enrolled. VNC images were reconstructed from the CTA. Region of interest (ROI) attenuations were measured in the right and left hepatic lobes, spleen, and aorta on TNC and VNC images. The right and left hepatic lobes were treated as separate samples. Steatosis was diagnosed based on TNC liver attenuation of ≤40 HU or liver attenuation index (LAI) of ≤-10 HU, which are extremely specific and predictive for moderate to severe steatosis. The sensitivity, specificity, and predictive values of VNC images for steatosis were calculated. VNC-TNC deviations were correlated with aortic enhancement and patient water equivalent diameter (PWED). Thirty-two liver ROIs met steatosis criteria based on TNC attenuation; VNC attenuation had sensitivity, specificity, and a positive predictive value of 66.7%, 100%, and 100%, respectively. Twenty-one liver ROIs met steatosis criteria based on TNC LAI. VNC LAI had sensitivity, specificity, and positive predictive values of 61.9%, 90.7%, and 65%, respectively. Hepatic and splenic VNC-TNC deviations did not correlate with one another (R 2 =0.08), aortic enhancement (R 2 predictive for moderate to severe steatosis on VNC reconstructions from the arterial phase. Hepatic attenuation performs better than LAI criteria. VNC deviations are independent of aortic enhancement and PWED. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

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

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)

Intra-individual comparison of image contrast in SPIO-enhanced liver MRI at 1.5T and 3.0T

International Nuclear Information System (INIS)

Falkenhausen, Marcus von; Meyer, Carsten; Lutterbey, Goetz; Morakkabati, Nuschin; Bloemer, Renate; Willinek, Winfried A.; Kuhl, Christiane K.; Schild, Hans H.; Walter, Oliver; Gieseke, Juergen

2007-01-01

The purpose of the study was to examine if the higher susceptibility at 3.0 Tesla (T) compared to 1.5 T will affect the contrast in MR imaging of the liver after application of superparamagnetic iron oxide particles (SPIO). The study was approved by our institutional review board and informed consent was obtained. Seventeen healthy volunteers were examined in a prospective, intra-individual comparative study within one day on a 1.5 T and a 3.0 T MRI system. T2 weighted TSE sequences were acquired after bolus injection of a SPIO contrast agent. Image contrast and signal to noise ratio (SNR) were compared between the field strengths. Image contrast was calculated between the liver tissue and the kidneys / spleen / muscles and fluids. The students'T-test was used for statistical analysis. No influence of the higher field strength could be observed on image contrast except for the liver / muscle contrast. This was due to a distinct SNR increase of the muscle tissue at 3.0 T as a result of their relaxation properties. The higher susceptibility at 3.0 T compared to 1.5 T does not translate into a stronger signal attenuation of the SPIO enhanced liver parenchyma. (orig.)

Intra-individual comparison of image contrast in SPIO-enhanced liver MRI at 1.5T and 3.0T

Energy Technology Data Exchange (ETDEWEB)

Falkenhausen, Marcus von; Meyer, Carsten; Lutterbey, Goetz; Morakkabati, Nuschin; Bloemer, Renate; Willinek, Winfried A.; Kuhl, Christiane K.; Schild, Hans H. [University of Bonn, Department of Radiology, Bonn (Germany); Walter, Oliver [Leibniz-Institute for Science Education, Kiel (Germany); Gieseke, Juergen [University of Bonn, Department of Radiology, Bonn (Germany); Philips Medical Systems, Hamburg (Germany)

2007-05-15

The purpose of the study was to examine if the higher susceptibility at 3.0 Tesla (T) compared to 1.5 T will affect the contrast in MR imaging of the liver after application of superparamagnetic iron oxide particles (SPIO). The study was approved by our institutional review board and informed consent was obtained. Seventeen healthy volunteers were examined in a prospective, intra-individual comparative study within one day on a 1.5 T and a 3.0 T MRI system. T2 weighted TSE sequences were acquired after bolus injection of a SPIO contrast agent. Image contrast and signal to noise ratio (SNR) were compared between the field strengths. Image contrast was calculated between the liver tissue and the kidneys / spleen / muscles and fluids. The students'T-test was used for statistical analysis. No influence of the higher field strength could be observed on image contrast except for the liver / muscle contrast. This was due to a distinct SNR increase of the muscle tissue at 3.0 T as a result of their relaxation properties. The higher susceptibility at 3.0 T compared to 1.5 T does not translate into a stronger signal attenuation of the SPIO enhanced liver parenchyma. (orig.)

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.

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

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.

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)

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

Science.gov (United States)

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

2017-01-01

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

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

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

Dynamic-contrast-enhanced magnetic resonance imaging of cirrhotic liver parenchyma: A comparison between gadolinium–diethylenetriamine pentaacetic acid and gadolinium–ethoxybenzyl–diethylenetriamine pentaacetic acid

Directory of Open Access Journals (Sweden)

Chun-Yi Lin

2015-11-01

Conclusion: The enhancement effect of the liver parenchyma using both MRI contrast agents was not affected by the degree of liver cirrhosis or abnormal liver function. However, it was affected by the serum-bilirubin levels in the Gd–EOB–DTPA-enhanced MRIs. Furthermore, enhancement of the liver was higher when using Gd–EOB–DTPA in the VP, DP, and HP. This knowledge is helpful when performing dynamic MRIs to diagnose focal hepatic lesions in the heterogeneous liver parenchyma.

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

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.

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

Science.gov (United States)

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

2011-01-01

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

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)

Polymeric nanoparticles as OCT contrast agents

Energy Technology Data Exchange (ETDEWEB)

Al Rawashdeh, Wa' el [RWTH Aachen University, Experimental Molecular Imaging (Germany); Kray, Stefan [RWTH Aachen University, Institute for Semiconductor Electronics (Germany); Pich, Andrij; Pargen, Sascha; Balaceanu, Andreea [RWTH Aachen University, Interactive Material Research (DWI) (Germany); Lenz, Markus; Spoeler, Felix [RWTH Aachen University, Institute for Semiconductor Electronics (Germany); Kiessling, Fabian, E-mail: fkiessling@ukaachen.de; Lederle, Wiltrud [RWTH Aachen University, Experimental Molecular Imaging (Germany)

2012-12-15

In this study, the optical properties of two nano-sized polymer colloids in optical coherence tomography (OCT) were compared in vitro with respect to their potential use as contrast agents. We used two types of particles: compact hydrophobic spherical polystyrene (PS) particles and soft water-swollen nanogel (NG) particles both with grafted hydrophilic shell, both prepared at two different sizes (PS at 300 and 150 nm, NG at 300 and 200 nm). The OCT backscattering signals of the particles in a vessel-mimicking highly scattering agar/TiO{sub 2} phantom were compared on either number of particles or weight percent. Larger particles and higher concentrations produced higher OCT contrast. At each concentration tested, a markedly higher contrast was achieved by PS particles than NG particles. PS particles generated a markedly higher OCT contrast than the phantom at concentrations of at least 1 Multiplication-Sign 10{sup 10} or 0.1 % for PS 300 nm and at least 3 Multiplication-Sign 10{sup 11} particles/mL or 0.4 % for PS 150 nm. The contrast generated by NG 300 nm was above the phantom contrast at concentrations of at least 3 Multiplication-Sign 10{sup 11} particles/mL or 1 %, whereas NG 200 nm only at 4 %. At any given weight percent, the differences in OCT contrast between differently sized particles were much less evident than in the comparison based on particle number. PS 300 nm generated also a good contrast ex vivo on chicken muscle tissue. These results strongly suggest that PS spheres have strong potential as intravascular OCT contrast agent, while NG particles need further contrast enhancer for being used as OCT contrast agent.

Contrast enhanced cartilage imaging: Comparison of ionic and non-ionic contrast agents

International Nuclear Information System (INIS)

Wiener, Edzard; Woertler, Klaus; Weirich, Gregor; Rummeny, Ernst J.; Settles, Marcus

2007-01-01

Our objective was to compare relaxation effects, dynamics and spatial distributions of ionic and non-ionic contrast agents in articular cartilage at concentrations typically used for direct MR arthrography at 1.5 T. Dynamic MR-studies over 11 h were performed in 15 bovine patella specimens. For each of the contrast agents gadopentetate dimeglumine, gadobenate dimeglumine, gadoteridol and mangafodipir trinatrium three patellae were placed in 2.5 mmol/L contrast solution. Simultaneous measurements of T 1 and T 2 were performed every 30 min using a high-spatial-resolution 'MIX'-sequence. T 1 , T 2 and ΔR 1 , ΔR 2 profile plots across cartilage thickness were calculated to demonstrate the spatial and temporal distributions. The charge is one of the main factors which controls the amount of the contrast media diffusing into intact cartilage, but independent of the charge, the spatial distribution across cartilage thickness remains highly inhomogeneous even after 11 h of diffusion. The absolute ΔR 2 -effect in cartilage is at least as large as the ΔR 1 -effect for all contrast agents. Maximum changes were 5-12 s -1 for ΔR 1 and 8-15 s -1 for ΔR 2 . This study indicates that for morphologically intact cartilage only the amount of contrast agents within cartilage is determined by the charge but not the spatial distribution across cartilage thickness. In addition, ΔR 2 can be considered for quantification of contrast agent concentrations, since it is of the same magnitude and less time consuming to measure than ΔR 1

Contrast-enhanced ultra-high-field liver MRI: A feasibility trial

Energy Technology Data Exchange (ETDEWEB)

Umutlu, Lale, E-mail: Lale.Umutlu@uk-essen.de [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (Germany); Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Bitz, Andreas K.; Maderwald, Stefan; Orzada, Stephan; Kinner, Sonja; Kraff, Oliver; Brote, Irina; Ladd, Susanne C.; Schroeder, Tobias; Forsting, Michael; Antoch, Gerald; Ladd, Mark E. [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (Germany); Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Quick, Harald H. [Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Institute of Medical Physics, University Nuernberg-Erlangen (Germany); Lauenstein, Thomas C. [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (Germany); Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany)

2013-05-15

The aim of this study was to investigate the feasibility of dynamic contrast-enhanced 7 T MRI of the liver using an eight-channel radiofrequency (RF) transmit/receive body-coil. 16 healthy subjects were examined on a 7 T MR system utilizing a custom-built eight-channel RF body-coil suitable for RF-shimming. The following data were acquired: (1) steady state free precession imaging, (2) T2w turbo spin echo imaging, (3) T1w in and opposed-phase imaging, (4) T1w 3D FLASH images pre-contrast and in arterial, portal-venous and venous phase and (5) a fat-saturated pre- and post-contrast 2D FLASH sequence. Visual evaluation of (1) the delineation of liver vasculature, (2) the overall image quality, and (3) artifact presence and consequent image impairment was performed. SNR of the liver parenchyma was measured for the contrast-enhanced 2D and 3D FLASH sequences. For statistical analysis, a Wilcoxon-Rank Test was used. Best delineation of non-enhanced liver vasculature and overall image quality was found for 2D FLASH MRI, with only slight improvement in vessel conspicuity after the application of contrast media. T2-weighted TSE imaging remained strongly impaired, falling short of diagnostic relevance and precluding a clinical application. Our results demonstrate the feasibility and diagnostic potential of dedicated contrast-enhanced 7 T liver MRI as well as the potential for non-contrast-enhanced angiographic application.

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.

Contrast-enhanced ultrasound vs multidetector-computed tomography for detecting liver metastases in colorectal cancer: a prospective, blinded, patient-by-patient analysis

DEFF Research Database (Denmark)

Rafaelsen, S R; Jakobsen, A

2011-01-01

This study compared the sensitivity and specificity of contrast-enhanced ultrasound (CEUS) and multidetector-computed tomography (MDCT) in the detection of liver metastases in patients with colorectal cancer.......This study compared the sensitivity and specificity of contrast-enhanced ultrasound (CEUS) and multidetector-computed tomography (MDCT) in the detection of liver metastases in patients with colorectal cancer....

Contrast between hypervascularized liver lesions and hepatic parenchyma. Early dynamic PET versus contrast-enhanced CT

International Nuclear Information System (INIS)

Freesmeyer, M.; Winkens, T.; Schierz, J.-H.

2014-01-01

To detect hypervascularized liver lesions, early dynamic (ED) 18 F-FDG PET may be an alternative when contrast-enhanced (CE) imaging is infeasible. This retrospective pilot analysis compared contrast between such lesions and liver parenchyma, an important objective image quality variable, in ED PET versus CE CT. Twenty-eight hypervascularized liver lesions detected by CE CT [21 (75%) hepatocellular carcinomas; mean (range) diameter 4.9 ± 3.5 (1-14) cm] in 20 patients were scanned with ED PET. Using regions of interest, maximum and mean lesional and parenchymal signals at baseline, arterial and venous phases were calculated for ED PET and CE CT. Lesional/parenchymal signal ratio was significantly higher (P < 0.005) with ED PET versus CE CT at the arterial phase and similar between the methods at the venous phase. In liver imaging, ED PET generates greater lesional-parenchymal contrast during the arterial phase than does CE CT; these observations should be formally, prospectively evaluated. (author)

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

International Nuclear Information System (INIS)

Ogunlade, Olumide; Beard, Paul

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-01-15

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

Novel DiR and SPIO nanoparticles embedded PEG-PLGA nanobubbles as a multimodalimaging contrast agent.

Science.gov (United States)

Luo, Binhua; Zhang, Huajie; Liu, Xuhan; Rao, Rong; Wu, Yun; Liu, Wei

2015-01-01

Fluorescence dye DiR and superparamagnetic iron oxide nanoparticles (SPIONs) embedded in PEG-PLGA nanobubbles (DiR-SPIO-NBs) were produced using double emulsion method on a membrane of Shirasu porous glass (SPG). The nanobubbles encapsulated with DiR and SPIONs had a liquid core (perfluoropentane) and a PEG-PLGA shell. DiR-SPIO-NBs showed biocompatibility based on MTT cytotoxicity and hemolysis studies. The PFP encapsulated in the nanobubbles experienced phase transition under ultrasonic irradation. Nanobubbles dispersed well in saline over 3 months, and the relaxivity was 127.9 mM(-1)s(-1), suggesting that it could be used as a contrast agent in MRI. The MR and fluorescence images in vivo demonstrated that the signal intensity in the spleen and liver was significantly enhanced with the treatment of nanobubbles. In addition, results of ultrasound images suggested that the nanobubbles had persistent contrast ability. In conclusion, nanobubbles could be utilized as an US/MRI/fluorescence contrast agent.

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.

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

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)

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.

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

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)

Synchrotron Based Phase Contrast Tomography of Hyper cholesteromic Rat Liver

Directory of Open Access Journals (Sweden)

Fatima A

2017-05-01

Full Text Available X-ray phase contrast imaging technique has been applied for the study of morphological variations in soft tissues. The effect of an antioxidant, α-lipoic acid in reducing hypercholesterolemia in rats is investigated. The experiment was conducted to measure serum lipid profile and diameter of vessels in rat liver, as liver is the most vital organ in hypolipidemic activity studies. Methods: Four groups of male Wistar rats, control (Group I, hyperlipidemic (Group II, positive control (Group III and treated Group IV were studied for serum lipid profile and liver vessels with synchrotron X-ray phase tomography. The Group I rats received chow diet, in Group II rats, administration of 20% butter rich diet induced hyperlipidemia. Group III, treated rats received hypolipidemic drug Atorvastatin and Group IV animals received a potent antioxidant DL-α-Lipoic acid. The excised liver tissue immersed in 10% formalin. X-ray phase contrast tomography was performed for comparison of diameter of liver vessels. Results: Among the four group of animals, the diameter of liver vessels was much larger in hypercholesterolemic rat (Group II. The liver vessel diameter comparison with X-ray phase contrast tomography and the lipid profile shows reduction in serum lipids and lipoproteins by ALA treatment.

Mn-DPDP, the first contrast agent for the pancreas

International Nuclear Information System (INIS)

Gehl, H.B.; Vorwerk, D.; Klose, K.C.; Raber, H.; Guenther, R.W.

1990-01-01

Mn-DPDP, known as a contrast agent for the hepatobiliary system, shows signal intensity increase of the pancreas as well. This paper describes the extent of signal intensity increase in the pancreas as a function of time. Six healthy volunteers were imaged with a 1.5-T MR unit using a T1-weighted gradient-echo sequence. Acquisitions were taken in 3-minute intervals for the first 45 minutes, followed by intervals of 30 minutes for 7 hours after infusion of Mn-DPDP. As a special formulation, 10 μmol per kg Mn-DPDP were infused. The enhancement of the head and the tail of the pancreas were measured and plotted as a function of time; the percentage increase in pancreas signal intensity was calculated and compared with the increase in liver signal intensity

The potentials of spiral CT for detection of focal liver lesions

International Nuclear Information System (INIS)

Helmberger, H.; Kersting-Sommerhoff, B.; Lenz, M.; Kirsten, R.; Bautz, W.

1996-01-01

Spiral CT currently is the modality of choice for all aspects of diagnostic evaluation of the liver. Optimal selection of treatment should be based inter alia on the findings obtained by spiral CT with arterial application of contrast medium, as for example S-CTA (primary liver tumors), or S-CTAP (secondary liver tumors). Ultrasonography is the major supplementing modality. In the near future, MR imaging applying liver-specific contrast-enhancing agents is expected to become an important competing technique, and further developments of interest in diagnostic imaging of the liver are in the offing: it is not yet known which technique will be the modality of choice at the onset of the 21st century. (orig.) [de

Microwave ablation of liver metastases guided by contrast-enhanced ultrasound

DEFF Research Database (Denmark)

Lorentzen, T; Skjoldbye, B O; Nolsoe, C P

2011-01-01

The aim of our study was to evaluate the efficacy of microwave (MW) ablation of liver metastases guided by B-mode ultrasound (US) and contrast-enhanced US (CEUS).......The aim of our study was to evaluate the efficacy of microwave (MW) ablation of liver metastases guided by B-mode ultrasound (US) and contrast-enhanced US (CEUS)....

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.

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.)

Enhancing contrast of magnetic resonance imaging in patients with ...

African Journals Online (AJOL)

DTPA), a recent magnetic resonance imaging (MRI) contrast agent, in hepatobiliary system of patients with liver cirrhosis. Methods: Liver cirrhosis patients that underwent contrast MRI examination at Renai Hospital, Taipei City, Taiwan were ...

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.

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)

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)

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.)

Visual assessment of biliary excretion of Gd-EOB-DTPA in patients with suspected diffuse liver disease – A biopsy-verified prospective study

International Nuclear Information System (INIS)

Norén, Bengt; Dahlström, Nils; Forsgren, Mikael Fredrik; Dahlqvist Leinhard, Olof; Kechagias, Stergios; Almer, Sven; Wirell, Staffan; Smedby, Örjan; Lundberg, Peter

2015-01-01

•MR using hepatocyte specific contrast may potentially assess liver function.•Covariance between contrast uptake and histo-pathological scoring of liver fibrosis.•No relationship between visually assessed biliary contrast excretion and fibrosis scoring.•No relationship between visually assessed biliary excretion and contrast uptake parameters. MR using hepatocyte specific contrast may potentially assess liver function. Covariance between contrast uptake and histo-pathological scoring of liver fibrosis. No relationship between visually assessed biliary contrast excretion and fibrosis scoring. No relationship between visually assessed biliary excretion and contrast uptake parameters. To qualitatively evaluate late dynamic contrast phases, 10, 20 and 30 min, after administration of Gd-EOB-DTPA with regard to biliary excretion in patients presenting with elevated liver enzymes without clinical signs of cirrhosis or hepatic decompensation and to compare the visual assessment of contrast agent excretion with histo-pathological fibrosis stage, contrast uptake parameters and blood tests. 29 patients were prospectively examined using 1.5 T MRI. The visually assessed presence or absence of contrast agent for each of five anatomical regions in randomly reviewed time-series was summarized on a four grade scale for each patient. The scores, including a total visual score, were related to the histo-pathological findings, the quantitative contrast agent uptake parameters, expressed as K Hep or LSC-N, and blood tests. No relationship between the fibrosis grade or contrast uptake parameters could be established. A negative correlation between the visual assessment and alkaline phosphatase (ALP) was found. Comparing a sub-group of cholestatic patients with fibrosis score and Gd-EOB-DTPA dynamic parameters did not add any additional significant correlation. No correlation between visually assessed biliary excretion of Gd-EOB-DTPA and histo-pathological or contrast uptake

Diagnosis of portal vein thrombosis discontinued with liver tumors in patients with liver cirrhosis and tumors by contrast-enhanced US: A pilot study

Energy Technology Data Exchange (ETDEWEB)

Song Zezhou; Huang Min [Department of Ultrasound, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province (China); Jiang Tianan, E-mail: tiananjiang@hzcnc.co [Department of Ultrasound, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province (China); Zhao Qiyu [Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou (China); Yao Lei; Mou Yun; Zhao Junkang; Ao Jianyang [Department of Ultrasound, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province (China); Chen Fen [Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou (China); Chen Yan [Department of Ultrasound, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province (China)

2010-08-15

Aims: We assessed the role of contrast-enhanced ultrasound (CEUS) in the differential diagnosis between benign and malignant portal vein thrombosis (PVT) in patients who had liver tumors. Methods: Seventeen consecutive patients who had cirrhosis, liver tumors, and PVT were prospectively studied with CEUS. CEUS was performed at low mechanical index after intravenous administration of a second-generation contrast agent (SonoVue, Bracco, Milan, Italy). Presence or absence of thrombus enhancement on CEUS were considered diagnostic for malignant or benign PVT. Five patients also underwent percutaneous portal vein fine-needle biopsy under US guidance. All patients were followed-up. Shrinkage of the thrombus and/or recanalization of the vessels on CDUS during follow-up were considered definitive evidence of the benign nature of the thrombosis, whereas the enlargement of the thrombus, disruption of the vessel wall, and parenchymal infiltration over follow-up were considered consistent with malignancy. Results: Follow-up showed signs of malignant thrombosis in 14 of 17 patients. CEUS showed early arterial enhancement of the PVT in 14 patients of 14 malignant PVT, 1 patient of 3 benign PVT and the absence of thrombus enhancement in 2 patients of 3 benign PVT. FNB confirmed the results for malignant PVT in four of five patients, for benign granulomatous inflammation PVT in one of five patients in which CEUS showed early arterial enhancement of the PVT. The sensitivity, specificity and accuracy is 100%, 66.7% and 93.3% at diagnosis of malignant PVT using CEUS. In one patient with intrahepatic bile duct stone, CEUS were positive for malignant PVT, whereas FNB was negative (benign granulomatous inflammation PVT); follow-up examination confirmed benign PVT. Conclusion: CEUS seems to be the pretty sensitive and specific test for diagnosing malignant portal vein thrombosis in patients with cirrhosis and tumors.

Hydrogel based tissue mimicking phantom for in-vitro ultrasound contrast agents studies.

Science.gov (United States)

Demitri, Christian; Sannino, Alessandro; Conversano, Francesco; Casciaro, Sergio; Distante, Alessandro; Maffezzoli, Alfonso

2008-11-01

Ultrasound medical imaging (UMI) is the most widely used image analysis technique, and often requires advanced in-vitro set up to perform morphological and functional investigations. These studies are based on contrast properties both related to tissue structure and injectable contrast agents (CA). In this work, we present a three-dimensional structure composed of two different hydrogels reassembly the microvascular network of a human tissue. This phantom was particularly suitable for the echocontrastographic measurements in human microvascular system. This phantom has been characterized to present the acoustic properties of an animal liver, that is, acoustic impedance (Z) and attenuation coefficient (AC), in UMI signal analysis in particular; the two different hydrogels have been selected to simulate the target organ and the acoustic properties of the vascular system. The two hydrogels were prepared starting from cellulose derivatives to simulating the target organ parenchyma and using a PEG-diacrylate to reproduce the vascular system. Moreover, harmonic analysis was performed on the hydrogel mimicking the liver parenchyma hydrogel to evaluate the ultrasound (US) distortion during echographic measurement. The phantom was employed in the characterization of an experimental US CA. Perfect agreement was found when comparing the hydrogel acoustical properties materials with the corresponding living reference tissues (i.e., vascular and parenchimal tissue).

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

The behavior after intravenous injection in mice of multiwalled carbon nanotube / Fe3O4 hybrid MRI contrast agents.

Science.gov (United States)

Wu, Huixia; Liu, Gang; Zhuang, Yeming; Wu, Dongmei; Zhang, Haoqiang; Yang, Hong; Hu, He; Yang, Shiping

2011-07-01

Fe(3)O(4) nanoparticles were in situ loaded on the surface of multiwalled carbon nanotubes (MWCNTs) by a solvothermal method using diethylene glycol and diethanolamine as solvents and complexing agents. The as-prepared MWCNT/Fe(3)O(4) hybrids exhibited excellent hydrophilicity, superparamagnetic property at room temperature, and a high T(2) relaxivity of 175.5 mM(-1) s(-1) in aqueous solutions. In vitro experiments revealed that MWCNT/Fe(3)O(4) had an excellent magnetic resonance imaging (MRI) enhancement effect on cancer cells, and importantly, they displayed low cytotoxicity and neglectable hemolytic activity. After intravenous administration, the T(2)-weighted MRI signal in the liver and spleen of mice decreased significantly, suggesting the potential application of the hybrids as MRI contrast agents. The organ biodistribution studies, histological analyses and elimination investigations showed that the hybrids were uptaken by the liver, lung and spleen after intravenous injection, and could be excreted from the liver and kidney. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

Colloidal dispersions of maghemite nanoparticles produced by laser pyrolysis with application as NMR contrast agents

Energy Technology Data Exchange (ETDEWEB)

Veintemillas-Verdaguer, Sabino [Instituto de Ciencia de Materiales de Madrid, CSIC, Cantoblanco, 28049 Madrid (Spain); Morales, Maria del Puerto [Instituto de Ciencia de Materiales de Madrid, CSIC, Cantoblanco, 28049 Madrid (Spain); Bomati-Miguel, Oscar [Instituto de Ciencia de Materiales de Madrid, CSIC, Cantoblanco, 28049 Madrid (Spain); Bautista, Carmen [Instituto de Ciencia de Materiales de Madrid, CSIC, Cantoblanco, 28049 Madrid (Spain); Zhao, Xinqing [Instituto de Ciencia de Materiales de Madrid, CSIC, Cantoblanco, 28049 Madrid (Spain); Bonville, Pierre [CEA, CE Saclay, DSM/DRECAM/SPEC, 91191 Gif-Sur-Yvette (France); Alejo, Rigoberto Perez de [Universidad Complutense de Madrid, Unidad de RMN, Paseo Juan XXIII, 1, 28040 Madrid (Spain); Ruiz-Cabello, Jesus [Universidad Complutense de Madrid, Unidad de RMN, Paseo Juan XXIII, 1, 28040 Madrid (Spain); Santos, Martin [Hospital Universitario Puerta de Hierro, Servicio de Cirugia Experimental. C/San Martin de Porres 4, 28035 Madrid (Spain); Tendillo-Cortijo, Francisco J [Hospital Universitario Puerta de Hierro, Servicio de Cirugia Experimental. C/San Martin de Porres 4, 28035 Madrid (Spain); Ferreiros, Joaquin [Hospital Clinico de Madrid ' San Carlos' , Ciudad Universitaria, 28040 Madrid (Spain)

2004-08-07

Biocompatible magnetic dispersions have been prepared from {gamma}-Fe{sub 2}O{sub 3} nanoparticles (5 nm) synthesized by continuous laser pyrolysis of Fe(CO){sub 5} vapours. The feasibility of using these dispersions as magnetic resonance imaging (MRI) contrast agents has been analysed in terms of chemical structure, magnetic properties, {sup 1}H NMR relaxation times and biokinetics. The magnetic nanoparticles were dispersed in a strong alkaline solution in the presence of dextran, yielding stable colloids in a single step. The dispersions consist of particle-aggregates 25 nm in diameter measured using transmission electron microscope and a hydrodynamic diameter of 42 nm measured using photon correlation spectroscopy. The magnetic and relaxometric properties of the dispersions were of the same order of magnitude as those of commercial contrast agents produced using coprecipitation. However, these dispersions, when injected intravenously in rats at standard doses showed a mono-exponential blood clearance instead of a biexponential one, with a blood half-life of 7 {+-} 1 min. Furthermore, an important enhancement of the image contrast was observed after the injection, mainly located at the liver and the spleen of the rat. In conclusion, the laser pyrolysis technique seems to be a good alternative to the coprecipitation method for producing MRI contrast agents, with the advantage of being a continuous synthesis method that leads to very uniform particles capable of being dispersed and therefore transformed in a biocompatible magnetic liquid.

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.

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.)

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.

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

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

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

Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

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Donghee Park

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

Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

Science.gov (United States)

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

2016-01-01

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

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.

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

Science.gov (United States)

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

2013-01-01

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

3D map of theranostic nanoparticles distribution in mice brain and liver by means of X-ray Phase Contrast Tomography

Science.gov (United States)

Longo, E.; Bravin, A.; Brun, F.; Bukreeva, I.; Cedola, A.; Fratini, M.; Le Guevel, X.; Massimi, L.; Sancey, L.; Tillement, O.; Zeitoun, P.; de La Rochefoucauld, O.

2018-01-01

The word "theranostic" derives from the fusion of two terms: therapeutic and diagnostic. It is a promising research field that aims to develop innovative therapies with high target specificity by exploiting the therapeutic and diagnostic properties, in particular for metal-based nanoparticles (NPs) developed to erase cancer. In the framework of a combined research program on low dose X-ray imaging and theranostic nanoparticles (NPs), high resolution Phase-Contrast Tomography images of mice organs injected with gadolinium and gold-NPs were acquired at the European Synchrotron Radiation Facility (ESRF). Both compounds are good X-ray contrast agents due to their high attenuation coefficient with respect to biological tissues, especially immediately above K-edge energy. X-ray tomography is a powerful non-invasive technique to image the 3D vasculature network in order to detect abnormalities. Phase contrast methods provide more detailed anatomical information with higher discrimination among soft tissues. We present the images of mice liver and brain injected with gold and gadolinium NPs, respectively. We discuss different image processing methods used aiming at enhancing the accuracy on localizing nanoparticles.

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.

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 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

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.

MRI contrast agent concentration and tumor interstitial fluid pressure.

Science.gov (United States)

Liu, L J; Schlesinger, M

2016-10-07

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

MRI contrast agents from molecules to particles

CERN Document Server

Laurent, Sophie; Stanicki, Dimitri; Boutry, Sébastien; Lipani, Estelle; Belaid, Sarah; Muller, Robert N; Vander Elst, Luce

2017-01-01

This book describes the multiple aspects of (i) preparation of the magnetic core, (ii) the stabilization with different coatings, (iii) the physico-chemical characterization and (iv) the vectorization to obtain specific nanosystems. Several bio-applications are also presented in this book. In the early days of Magnetic Resonance Imaging (MRI), paramagnetic ions were proposed as contrast agents to enhance the diagnostic quality of MR images. Since then, academic and industrial efforts have been devoted to the development of new and more efficient molecular, supramolecular and nanoparticular systems. Old concepts and theories, like paramagnetic relaxation, were revisited and exploited, leading to new scientific tracks. With their high relaxivity payload, the superparamagnetic nanoparticles are very appealing in the context of molecular imaging but challenges are still numerous: absence of toxicity, specificity, ability to cross the biological barriers, etc. .

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

The synthesis of a D-glucosamine contrast agent, Gd-DTPA-DG, and its application in cancer molecular imaging with MRI

International Nuclear Information System (INIS)

Zhang Wei; Chen Yue; Guo Dajing; Huang Zhanwen; Cai Liang; He Ling

2011-01-01

Objective: The purpose of this study is to describe the synthesis of Gadolinium-diethylenetriamine pentaacetic acid-deoxyglucosamine (Gd-DTPA-DG) which is a D-glucosamine metabolic MR imaging contrast agent. We will also discuss its use in a pilot MRI study using a xenograft mouse model of human adenocarcinoma. Methods: This novel contrast agent was specifically studied because of its ability to 'target' metabolically active tumor tissues. In this study Gd-DTPA-DG is used to investigate how tumor tissues would react to a dose of 0.2 mmol Gd/kg over a 120 min exposure in a xenograft mouse model. These experiments used athymic mice implanted with human pulmonary adenocarcinoma (A549) as demonstrated by dynamic MRI. Alternately, another contrast agent that is not specific for targeting, Gd-DTPA, was used as the control at a similar dose of gadolinium. Efficacy of the targeted contrast agent was assessed by measuring relaxation rate in vitro and signal intensity (SI) in vivo. Statistical differences were calculated using one-way analysis of variance. Results: The synthesized Gd-DTPA-DG was shown to improve the contrast of tumor tissue in this model. Gd-DTPA-DG was also shown to have a similar pharmacokinetic rate but generated a higher relaxation rate in tumor tissues relative to the control contrast Gd-DTPA. In comparison to the pre-contrast imaging, the SI of tumor tissue in the experimental group was shown to be significantly increased at 15 min after injection of Gd-DTPA-DG (p < 0.001). The enhanced signal intensity spread from the edge of the tumor to the center and seemed to strengthen the idea that MRI performance would be useful in different tumor tissues. Conclusion: This preliminary study shows that this new chelated contrast agent, Gd-DTPA-DG, can be specifically targeted to accumulation in tumor tissue as compared to normal tissues. This targeted paramagnetic contrast agent has potential for specific cancer molecular imaging with MRI.

Recombinant high-density lipoprotein nanoparticles containing gadolinium-labeled cholesterol for morphologic and functional magnetic resonance imaging of the liver

Directory of Open Access Journals (Sweden)

Rui M

2012-07-01

Full Text Available Mengjie Rui,1 Wei Guo,2 Qian Ding,2 Xiaohui Wei,2 Jianrong Xu,3 Yuhong Xu21School of Life Science and Biotechnology, 2School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China; 3Department of Radiology, Renji Hospital Affiliation with Medical School of Shanghai Jiao Tong University, Shanghai, People's Republic of ChinaBackground: Natural high-density lipoproteins (HDL possess important physiological functions to the transport of cholesterol from the peripheral tissues to the liver for metabolic degradation and excretion in the bile.Methods and results: In this work, we took advantage of this pathway and prepared two different gadolinium (Gd-DTPA-labeled cholesterol-containing recombinant HDL nanoparticles (Gd-chol-HDL and Gd-(chol2-HDL as liver-specific magnetic resonance imaging (MRI contrast agents. The reconstituted HDL nanoparticles had structural similarity to native HDL, and could be taken up by HepG2 cells via interaction with HDL receptors in vitro. In vivo MRI studies in rats after intravenous injections of 10 µmol gadolinium per kg of recombinant HDL nanoparticles indicated that both nanoparticles could provide signal enhancement in the liver and related organs. However, different T1-weighted image details suggested that they participated in different cholesterol metabolism and excretion pathways in the liver.Conclusion: Such information could be highly useful to differentiate functional changes as well as anatomic differences in the liver. These cholesterol-derived contrast agents and their recombinant HDL preparations may warrant further development as a new class of contrast agents for MRI of the liver and related organs.Keywords: magnetic resonance imaging, apolipoprotein, high-density lipoprotein, contrast agent, gadolinium, liver

Preoperative evaluation of colorectal liver metastases: comparison between gadoxetic acid-enhanced 3.0-T MRI and contrast-enhanced MDCT with histopathological correlation

Energy Technology Data Exchange (ETDEWEB)

Scharitzer, M.; Ba-Ssalamah, A.; Ringl, H.; Koelblinger, C.; Weber, M. [Medical University of Vienna, Department of Radiology, Vienna (Austria); Gruenberger, T. [Medical University of Vienna, Department of Surgery, Vienna (Austria); Schima, W. [Department of Radiology, KH Goettlicher Heiland, KH der Barmherzigen Schwestern and St Josef-Krankenhaus, Vienna (Austria)

2013-08-15

The aim of this prospective study was to compare the diagnostic performance of 64-row MDCT and gadoxetic-acid-enhanced MRI at 3.0 T in patients with colorectal liver metastases in correlation with histopathological findings. Lesions detected at MDCT and MRI were interpreted by three blinded readers and compared with histopathological workup as the term of reference. Two subgroups of lesions were additionally evaluated: (1) metastases smaller than 10 mm and (2) lesions in patients with and without steatosis of the liver, assessed histopathologically. Surgery and histopathological workup revealed 81 colorectal liver metastases in 35 patients and diffuse metastatic involvement in 3 patients. In a lesion-by-lesion analysis, significant sensitivity differences could only be found for reader 1 (P = 0.035) and reader 3 (P = 0.003). For segment-based evaluation, MRI was more sensitive only for reader 3 (P = 0.012). The number of false-positive results ranged from 3 to 12 for MDCT and 8 to 11 for MRI evaluation. In the group of small lesions, the sensitivity differed significantly between both methods (P = 0.003). In patients with hepatic steatosis, MRI showed a trend toward better performance than MDCT, but without statistical performance. The 3.0-T MRI with liver-specific contrast agents is the preferred investigation in the preoperative setting, especially for the assessment of small colorectal liver metastases. (orig.)

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

A Multiscale Agent-Based in silico Model of Liver Fibrosis Progression

International Nuclear Information System (INIS)

Dutta-Moscato, Joyeeta; Solovyev, Alexey; Mi, Qi; Nishikawa, Taichiro; Soto-Gutierrez, Alejandro; Fox, Ira J.; Vodovotz, Yoram

2014-01-01

Chronic hepatic inflammation involves a complex interplay of inflammatory and mechanical influences, ultimately manifesting in a characteristic histopathology of liver fibrosis. We created an agent-based model (ABM) of liver tissue in order to computationally examine the consequence of liver inflammation. Our liver fibrosis ABM (LFABM) is comprised of literature-derived rules describing molecular and histopathological aspects of inflammation and fibrosis in a section of chemically injured liver. Hepatocytes are modeled as agents within hexagonal lobules. Injury triggers an inflammatory reaction, which leads to activation of local Kupffer cells and recruitment of monocytes from circulation. Portal fibroblasts and hepatic stellate cells are activated locally by the products of inflammation. The various agents in the simulation are regulated by above-threshold concentrations of pro- and anti-inflammatory cytokines and damage-associated molecular pattern molecules. The simulation progresses from chronic inflammation to collagen deposition, exhibiting periportal fibrosis followed by bridging fibrosis, and culminating in disruption of the regular lobular structure. The ABM exhibited key histopathological features observed in liver sections from rats treated with carbon tetrachloride (CCl 4 ). An in silico “tension test” for the hepatic lobules predicted an overall increase in tissue stiffness, in line with clinical elastography literature and published studies in CCl 4 -treated rats. Therapy simulations suggested differential anti-fibrotic effects of neutralizing tumor necrosis factor alpha vs. enhancing M2 Kupffer cells. We conclude that a computational model of liver inflammation on a structural skeleton of physical forces can recapitulate key histopathological and macroscopic properties of CCl 4 -injured liver. This multiscale approach linking molecular and chemomechanical stimuli enables a model that could be used to gain translationally relevant insights into

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

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

2017-09-15

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

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

International Nuclear Information System (INIS)

Didier, Ryne A.; Hopkins, Katharine L.; Coakley, Fergus V.; Foster, Bryan R.; Krishnaswami, Sanjay; Spiro, David M.

2017-01-01

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

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

Contrast-enhanced ultrasound in diagnosis and characterization of focal hepatic lesions.

Science.gov (United States)

Molins, Inés Gómez; Font, Juan Manuel Fernández; Alvaro, Juan Carrero; Navarro, Jose Luís Lledó; Gil, Marta Fernández; Rodríguez, Conrado M Fernández

2010-12-28

The extensive use of imaging techniques in differential diagnosis of abdominal conditions and screening of hepatocellular carcinoma in patients with chronic hepatic diseases, has led to an important increase in identification of focal liver lesions. The development of contrast-enhanced ultrasound (CEUS) opens a new window in the diagnosis and follow-up of these lesions. This technique offers obvious advantages over the computed tomography and magnetic resonance, without a decrease in its sensitivity and specificity. The new second generation contrast agents, due to their intravascular distribution, allow a continuous evaluation of the enhancement pattern, which is crucial in characterization of liver lesions. The dual blood supply in the liver shows three different phases, namely arterial, portal and late phases. The enhancement during portal and late phases can give important information about the lesion's behavior. Each liver lesion has a different enhancement pattern that makes possible an accurate approach to their diagnosis. The role of emerging techniques as a contrast-enhanced three-dimensional US is also discussed. In this article, the advantages, indications and technique employed during CEUS and the different enhancement patterns of most benign and malignant focal liver lesions are discussed.

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 ...

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)

Troubleshooting arterial-phase MR images of gadoxetate disodium-enhanced liver

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Huh, Ji Mi; Kim, So Yeon; Lee, Seung Soo; Kim, Kyoung Won [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Yeh, Benjamin M.; Wang, Z. Jane [Dept. of Radiologyand Biomedical Imaging, University of California San Francisco, San Francisco (United States); Wu, En Haw [Dept. of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou and Chang Gung University College of Medicine, Taoyuan (China); Zhao, Li Qin [Beijing Friendship Hospital, Capital Medical University, Beijing (China); Chang, Wei Chou [Tri-Service General Hospital and National Defense Medical Center, Taipei (China)

2015-12-15

Gadoxetate disodium is a widely used magnetic resonance (MR) contrast agent for liver MR imaging, and it provides both dynamic and hepatobiliary phase images. However, acquiring optimal arterial phase images at liver MR using gadoxetate disodium is more challenging than using conventional extracellular MR contrast agent because of the small volume administered, the gadolinium content of the agent, and the common occurrence of transient severe motion. In this article, we identify the challenges in obtaining high-quality arterial-phase images of gadoxetate disodium-enhanced liver MR imaging and present strategies for optimizing arterial-phase imaging based on the thorough review of recent research in this field.

Troubleshooting arterial-phase MR images of gadoxetate disodium-enhanced liver

International Nuclear Information System (INIS)

Huh, Ji Mi; Kim, So Yeon; Lee, Seung Soo; Kim, Kyoung Won; Yeh, Benjamin M.; Wang, Z. Jane; Wu, En Haw; Zhao, Li Qin; Chang, Wei Chou

2015-01-01

Gadoxetate disodium is a widely used magnetic resonance (MR) contrast agent for liver MR imaging, and it provides both dynamic and hepatobiliary phase images. However, acquiring optimal arterial phase images at liver MR using gadoxetate disodium is more challenging than using conventional extracellular MR contrast agent because of the small volume administered, the gadolinium content of the agent, and the common occurrence of transient severe motion. In this article, we identify the challenges in obtaining high-quality arterial-phase images of gadoxetate disodium-enhanced liver MR imaging and present strategies for optimizing arterial-phase imaging based on the thorough review of recent research in this field

Iron Oxide as an MRI Contrast Agent for Cell Tracking

Science.gov (United States)

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

2015-01-01

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

Dual contrast enhanced magnetic resonance imaging of the liver with superparamagnetic iron oxide followed by gadolinium for lesion detection and characterization

International Nuclear Information System (INIS)

Kubaska, Samantha; Sahani, Dushyant V.; Saini, Sanjay; Hahn, Peter F.; Halpern, Elkan

2001-01-01

AIM: Iron oxide contrast agents are useful for lesion detection, and extracellular gadolinium chelates are advocated for lesion characterization. We undertook a study to determine if dual contrast enhanced liver imaging with sequential use of ferumoxides particles and gadolinium (Gd)-DTPA can be performed in the same imaging protocol. MATERIALS AND METHODS: Sixteen patients underwent dual contrast magnetic resonance imaging (MRI) of the liver for evaluation of known/suspected focal lesions which included, metastases (n = 5), hepatocellular carcinoma (HCC;n = 3), cholangiocharcinoma(n = 1) and focal nodular hyperplasia (FNH;n = 3). Pre- and post-iron oxide T1-weighted gradient recalled echo (GRE) and T2-weighted fast spin echo (FSE) sequences were obtained, followed by post-Gd-DTPA (0.1 mmol/kg) multi-phase dynamic T1-weighted out-of-phase GRE imaging. Images were analysed in a blinded fashion by three experts using a three-point scoring system for lesion conspicuity on pre- and post-iron oxide T1 images as well as for reader's confidence in characterizing liver lesions on post Gd-DTPA T1 images. RESULTS: No statistically significant difference in lesion conspicuity was observed on pre- and post-iron oxide T1-GRE images in this small study cohort. The presence of iron oxide did not appreciably diminish image quality of post-gadolinium sequences and did not prevent characterization of liver lesions. CONCLUSION: Our results suggest that characterization of focal liver lesion with Gd-enhanced liver MRI is still possible following iron oxide enhanced imaging. Kubaska, S. et al. (2001)

Multicenter analysis of tolerance and clinical safety of the extracellular MR contrast agent gadobenate dimeglumine (MultiHance registered)

International Nuclear Information System (INIS)

Herborn, Christoph U.; Jaeger-Booth, I.; Goyen, M.; Lodemann, K.P.; Spinazzi, A.

2009-01-01

Purpose: Retrospective analysis of the occurrence of adverse events and the diagnostic efficacy of a paramagnetic contrast agent with weak intermittent protein binding and high relaxivity. Materials end methods: Postmarketing surveillance studies for gadobenate dimeglumine (MultiHance, BRACCO Altana Pharma, Constance) were conducted in Germany between 1998 and 2006 and then retrospectively analyzed. Demographic data, relevant comorbidities, and allergies were recorded. The safety and tolerability of MultiHance were logged on a standardized data sheet. Results: A total of 38568 patients were included in the study. 829 patients (2.1%) had a known intolerance against contrast media. The examined regions included the central nervous system, the liver, and the vascular bed. The injection rate with automated injectors (n = 10456) varied between 1.0 und 3.0 ml/sec in 86.5% of patients. Adverse events totaled 1.2%. 11 patients (0.03%) experienced serious adverse events. The most frequent findings were nausea, vomiting and a feeling of warmth. Conclusion: MultiHance is a safe and very well tolerated contrast agent for magnetic resonance imaging (MRI) with a profile and frequency of adverse events similar to other extracellular MR contrast materials. (orig.)

Molecular design of sequence specific DNA alkylating agents.

Science.gov (United States)

Minoshima, Masafumi; Bando, Toshikazu; Shinohara, Ken-ichi; Sugiyama, Hiroshi

2009-01-01

Sequence-specific DNA alkylating agents have great interest for novel approach to cancer chemotherapy. We designed the conjugates between pyrrole (Py)-imidazole (Im) polyamides and DNA alkylating chlorambucil moiety possessing at different positions. The sequence-specific DNA alkylation by conjugates was investigated by using high-resolution denaturing polyacrylamide gel electrophoresis (PAGE). The results showed that polyamide chlorambucil conjugates alkylate DNA at flanking adenines in recognition sequences of Py-Im polyamides, however, the reactivities and alkylation sites were influenced by the positions of conjugation. In addition, we synthesized conjugate between Py-Im polyamide and another alkylating agent, 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI). DNA alkylation reactivies by both alkylating polyamides were almost comparable. In contrast, cytotoxicities against cell lines differed greatly. These comparative studies would promote development of appropriate sequence-specific DNA alkylating polyamides against specific cancer cells.

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

A Multiscale Agent-Based in silico Model of Liver Fibrosis Progression

Energy Technology Data Exchange (ETDEWEB)

Dutta-Moscato, Joyeeta [Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA (United States); Department of Surgery, University of Pittsburgh, Pittsburgh, PA (United States); Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Solovyev, Alexey [Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Department of Mathematics, University of Pittsburgh, Pittsburgh, PA (United States); Mi, Qi [Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Department of Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, PA (United States); Nishikawa, Taichiro [McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Department of Surgery, Children’s Hospital of Pittsburgh, Pittsburgh, PA (United States); Soto-Gutierrez, Alejandro [McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Department of Pathology, University of Pittsburgh, Pittsburgh, PA (United States); Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA (United States); Fox, Ira J. [McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Department of Surgery, Children’s Hospital of Pittsburgh, Pittsburgh, PA (United States); Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA (United States); Vodovotz, Yoram, E-mail: vodovotzy@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, PA (United States); Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA (United States)

2014-05-30

Chronic hepatic inflammation involves a complex interplay of inflammatory and mechanical influences, ultimately manifesting in a characteristic histopathology of liver fibrosis. We created an agent-based model (ABM) of liver tissue in order to computationally examine the consequence of liver inflammation. Our liver fibrosis ABM (LFABM) is comprised of literature-derived rules describing molecular and histopathological aspects of inflammation and fibrosis in a section of chemically injured liver. Hepatocytes are modeled as agents within hexagonal lobules. Injury triggers an inflammatory reaction, which leads to activation of local Kupffer cells and recruitment of monocytes from circulation. Portal fibroblasts and hepatic stellate cells are activated locally by the products of inflammation. The various agents in the simulation are regulated by above-threshold concentrations of pro- and anti-inflammatory cytokines and damage-associated molecular pattern molecules. The simulation progresses from chronic inflammation to collagen deposition, exhibiting periportal fibrosis followed by bridging fibrosis, and culminating in disruption of the regular lobular structure. The ABM exhibited key histopathological features observed in liver sections from rats treated with carbon tetrachloride (CCl{sub 4}). An in silico “tension test” for the hepatic lobules predicted an overall increase in tissue stiffness, in line with clinical elastography literature and published studies in CCl{sub 4}-treated rats. Therapy simulations suggested differential anti-fibrotic effects of neutralizing tumor necrosis factor alpha vs. enhancing M2 Kupffer cells. We conclude that a computational model of liver inflammation on a structural skeleton of physical forces can recapitulate key histopathological and macroscopic properties of CCl{sub 4}-injured liver. This multiscale approach linking molecular and chemomechanical stimuli enables a model that could be used to gain translationally relevant

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

Science.gov (United States)

Runge, Val M

2017-06-01

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

Detection of liver metastases in cancer patients with geographic fatty infiltration of the liver: the added value of contrast-enhanced sonography

International Nuclear Information System (INIS)

Bartolotta, Tommaso Vincenzo; Taibbi, Adele; Picone, Dario; Anastasi, Andrea; Midiri, Massimo; Lagalla, Roberto

2017-01-01

The aim of this study is to assess the role of contrast-enhanced ultrasonography (CEUS) in the detection of liver metastases in cancer patients with geographic liver fatty deposition on greyscale ultrasonography (US). Thirty-seven consecutive cancer patients (24 women and 13 men; age, 33 to 80 years; mean, 58.1 years) with geographic liver fatty deposition, but without any detectable focal liver lesion on greyscale US, underwent sulphur hexafluoride-enhanced US. Two readers reported by consensus the presence, size, and location of any detected lesion. All patients underwent magnetic resonance imaging (MRI) as a confirmatory study. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and accuracy were calculated. Seven focal liver lesions (size, 4 to 10 mm; mean, 6.1 mm) were detected in 4/37 patients (10.8%): four metastases (size, 5 to 10 mm; mean, 6.7 mm) were detected both by CEUS and MRI, with one hemangioma and two cysts (size range, 4 to 6 mm; mean, 5.3 mm) detected by MRI only. In 1/37 patients (2.7%), CEUS misdiagnosed geographic fatty change as three metastases. In 32/37 patients (86.5%), no lesions were detected. Sensitivity, specificity, PPV, NPV, and accuracy of CEUS were 100% (95% confidence Interval [CI], 1.000 to 1.000), 97.1% (95% CI, 0.914 to 1.027), 75%, 100%, and 97.3%, respectively. No statistically significant differences were found between CEUS and MRI in the detection of focal liver lesions (P=0.480), whereas both of them performed better than baseline US (P<0.001). CEUS improves the detection of liver metastases in cancer patients with geographic liver fatty deposition on greyscale US

Detection of liver metastases in cancer patients with geographic fatty infiltration of the liver: the added value of contrast-enhanced sonography

Energy Technology Data Exchange (ETDEWEB)

Bartolotta, Tommaso Vincenzo; Taibbi, Adele; Picone, Dario; Anastasi, Andrea; Midiri, Massimo; Lagalla, Roberto [Dept. of Radiology-Di.Bi.Med., University of Palermo, Palermo (Italy)

2017-04-15

The aim of this study is to assess the role of contrast-enhanced ultrasonography (CEUS) in the detection of liver metastases in cancer patients with geographic liver fatty deposition on greyscale ultrasonography (US). Thirty-seven consecutive cancer patients (24 women and 13 men; age, 33 to 80 years; mean, 58.1 years) with geographic liver fatty deposition, but without any detectable focal liver lesion on greyscale US, underwent sulphur hexafluoride-enhanced US. Two readers reported by consensus the presence, size, and location of any detected lesion. All patients underwent magnetic resonance imaging (MRI) as a confirmatory study. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and accuracy were calculated. Seven focal liver lesions (size, 4 to 10 mm; mean, 6.1 mm) were detected in 4/37 patients (10.8%): four metastases (size, 5 to 10 mm; mean, 6.7 mm) were detected both by CEUS and MRI, with one hemangioma and two cysts (size range, 4 to 6 mm; mean, 5.3 mm) detected by MRI only. In 1/37 patients (2.7%), CEUS misdiagnosed geographic fatty change as three metastases. In 32/37 patients (86.5%), no lesions were detected. Sensitivity, specificity, PPV, NPV, and accuracy of CEUS were 100% (95% confidence Interval [CI], 1.000 to 1.000), 97.1% (95% CI, 0.914 to 1.027), 75%, 100%, and 97.3%, respectively. No statistically significant differences were found between CEUS and MRI in the detection of focal liver lesions (P=0.480), whereas both of them performed better than baseline US (P<0.001). CEUS improves the detection of liver metastases in cancer patients with geographic liver fatty deposition on greyscale US.

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

PEGylated superparamagnetic iron oxide nanoparticles labeled with 68Ga as a PET/MRI contrast agent. A biodistribution study

International Nuclear Information System (INIS)

Afsaneh Lahooti; Gruttner, Cordula; Parham Geramifar; Hassan Yousefnia

2017-01-01

The purpose of this study is to evaluate the biodistribution of polyethylene glycol (PEG) coated superparamagnetic iron oxide nanoparticles radiolabeled with 68 Ga in normal mice after intravenous administration of this probe. Three mice were sacrificed at specific time intervals. The biodistribution data revealed high uptake by liver and spleen (60.62 and 12.65 %ID/g at 120 min post injection for liver and spleen, respectively). The clearance of other organs was fast. These results suggest that 68 Ga-PEG-SPIONs has magnificent capabilities for applying in (PET-MRI) as a theranostic agent for detection of liver and spleen malignancies. (author)

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)....

A new procedure for imaging liver and spleen with water soluble contrast media in liposomes

International Nuclear Information System (INIS)

Zherbin, E.A.; Davidenkova, E.F.; Khanson, K.P.; Gubareva, A.V.; Zhdanova, N.V.; Aliyakparov, M.T.; Loshakova, L.V.; Fomina, Eh.V.; Rozenberg, O.A.

1983-01-01

The problems of long-term, reversible, and safe contrast investigation of liver and spleen and reduction of the irritating action of water-soluble contrast media on the wall of blood vessels are unresolved. The production and experimental application of contrast media encapsulated in liposomes are described. It is possible to produce a liposome preparation with 10-20 % Verografin content. After intravenous injection it leads to a quick (after 16-30 min), persisting (10-12 h) and reversible (24-30 h) contrast imaging of liver and spleen in rodents. The contrast medium has no pathological effects on heart, blood and circulatory system and on the morphology of liver, spleen, heart, lungs, kidneys and urinary bladder. The perspectives of clinical application of such contrast media are discussed. (author)

Specific sequestering agents for the actinides: Pt. 10

International Nuclear Information System (INIS)

Ren Hongyu; Wang Huicai

1991-01-01

In this article, ten new and four known polyaminocarboxy-licphenolic sequestering agents have been synthesized. The result of animal screening of ten of these sequestering agents indicates: six of all, at a dose of 50 μmol/kg can excrete liver Am·Va (N, N'-di(2-hydroxybenzyl)-diethylenetriamine-N 1 , N 4 , N 7 -triacetic acid) is the most effective, it can excrete liver Am, skeleten Am and kidney Am. But all are less effective than DTPA. The structure-activity relationship has been discussed, ligand with more aminocarboxylic acid groups showed a better result than the ligand with more phenolic groups

Virtual non-contrast of liver from dual energy CT: a clinical application

International Nuclear Information System (INIS)

Qian Yu'e; Hu Hongjie; Zhang Qiaowei; Hu Peng; Shen Guohui

2011-01-01

Objective: To assess the virtual non-contrast liver CT from dual-energy CT for the clinical application. Methods: In total, 51 patients were included in the study, and all patients underwent multi-phase liver CT on a dual-source CT. The True non-contrast liver CT (TNCT) was performed in a single-energy acquisition mode, but the arterial and portovenous liver CT (VNCT) were performed in a dual- energy mode of 110 kV and 140 kV respectively. The virtual non-contrast CT images were derived from the arterial data using liver virtual non-contrast software. Between the true non-contrast CT and the virtual non- contrast CT, the image quality, mean CT HU values in the liver and muscle, signal to noise (SNR), the radiation dose of volume CT dose index (CTDIvol) and dose length product (DLP) in a single phase and total examination were compared with t test. Results: There was no significant difference in the detection of' liver lesions between TNCT and VNCT. The CT Hu values of muscle on both TNCT and VNCT images were almost equal. The CT HU values of liver on VNCT images were higher than that on TNCT images and the difference was significant [61.32±6.04 vs. (56.85±4.80) HU, t=-3.927, P<0.01]. There was also significant difference of SNR between TNCT (11.28±2.78) and VNCT (8.65±1.56) images (t=-5.590, P<0.01). The CTDIvol and DLP of single phase were (7.07±0.85) mGy and (155.11± 22.52) mGy · cm respectively in TNCT, and (7.05±0.87) mGy and (154.48±23.12) mGy · cm in VNCT. The total CTDIvol and DLP in VNCT were (14.35±1.66) mGy and (313.91±45.08) mGy · cm respectively, but in TNCT the total CTDIvol and DLP reached (21.43±2.46) mGy and (469.02± 66.22) mGy · cm. The difference of CTDIvol and DLP in single phase between TNCT and VNCT showed no significance, but the total CTDIvol and DLP were significantly different (t=16.168 and 13.132, P< 0.01). Conclusion: With the consequent reduction in radiation dose, the VNCT can replace TNCT as an imaging protocol in multi

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

Contrast Enhanced US in the Abdomen

International Nuclear Information System (INIS)

Chung, Yong Eun; Kim, Ki Whang

2012-01-01

Contrast enhanced ultrasound, which was introduced in 1996, has been widely used in Europe and Eastern Asia. Ultrasound contrast agent can be classified as first generation and second generation, depending on the gas within the microbubble. With the first generation contrast agent, the high MI technique was used, and only intermittent scanning was possible due to destruction of the microbubble during scanning. Use of the second generation contrast agent with the low MI technique makes continuous scanning possible. Contrast enhanced US can be used in detection and differentiation of focal liver lesions. It is also helpful for monitoring of radiofrequency ablation and for targeting of US guided biopsy. Currently, because morphologic criteria alone may not reflect the response of the tumor to treatment, new criteria are needed for treatment evaluation after administration of anti-angiogenic agents. Contrast enhanced US could provide quantitative markers for evaluation of the response to treatment via use of dynamic contrast enhanced US. Due to cost-effectiveness, contrast enhanced US is not yet widely used in Korea; however, considering recent issues regarding contrast agent related adverse reaction, such as contrast induced nephropathy and nephrogenic systemic fibrosis, and radiation exposure, contrast enhanced US might be more widely used in Korea, as an alternative imaging modality in the future.

Use of trimetasphere metallofullerene MRI contrast agent for the non-invasive longitudinal tracking of stem cells in the lung.

Science.gov (United States)

Murphy, Sean V; Hale, Austin; Reid, Tanya; Olson, John; Kidiyoor, Amritha; Tan, Josh; Zhou, Zhiguo; Jackson, John; Atala, Anthony

2016-04-15

Magnetic Resonance Imaging (MRI) is a commonly used, non-invasive imaging technique that provides visualization of soft tissues with high spatial resolution. In both a research and clinical setting, the major challenge has been identifying a non-invasive and safe method for longitudinal tracking of delivered cells in vivo. The labeling and tracking of contrast agent labeled cells using MRI has the potential to fulfill this need. Contrast agents are often used to enhance the image contrast between the tissue of interest and surrounding tissues with MRI. The most commonly used MRI contrast agents contain Gd(III) ions. However, Gd(III) ions are highly toxic in their ionic form, as they tend to accumulate in the liver, spleen, kidney and bones and block calcium channels. Endohedral metallofullerenes such as trimetallic nitride endohedral metallofullerenes (Trimetasphere®) are one unique class of fullerene molecules where a Gd3N cluster is encapsulated inside a C80 carbon cage referred to as Gd3N@C80. These endohedral metallofullerenes have several advantages over small chelated Gd(III) complexes such as increased stability of the Gd(III) ion, minimal toxic effects, high solubility in water and high proton relativity. In this study, we describe the evaluation of gadolinium-based Trimetasphere® positive contrast agent for the ​in vitro labeling and in vivo tracking of human amniotic fluid-derived stem cells within lung tissue. In addition, we conducted a 'proof-of-concept' experiment demonstrating that this methodology can be used to track the homing of stem cells to injured lung tissue and provide longitudinal analysis of cell localization over an extended time course. Copyright © 2015 Elsevier Inc. All rights reserved.

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...

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...

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)

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)

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

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.

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

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

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.

Vascularization of liver tumors - preliminary results with Coded Harmonic Angio (CHA), phase inversion imaging, 3D power Doppler and contrast medium-enhanced B-flow with second generation contrast agent (Optison).

Science.gov (United States)

Jung, E M; Kubale, R; Jungius, K-P; Jung, W; Lenhart, M; Clevert, D-A

2006-01-01

To investigate the dynamic value of contrast medium-enhanced ultrasonography with Optison for appraisal of the vascularization of hepatic tumors using harmonic imaging, 3D-/power Doppler and B-flow. 60 patients with a mean age of 56 years (range 35-76 years) with 93 liver tumors, including histopathologically proven hepatocellular carcinoma (HCC) [15 cases with 20 lesions], liver metastases of colorectal tumors [17 cases with 33 lesions], metastases of breast cancer [10 cases with 21 lesions] and hemangiomas [10 cases with 19 lesions] were prospectively investigated by means of multislice CT as well as native and contrast medium-enhanced ultrasound using a multifrequency transducer (2.5-4 MHz, Logig 9, GE). B scan was performed with additional color and power Doppler, followed by a bolus injection of 0.5 ml Optison. Tumor vascularization was evaluated with coded harmonic angio (CHA), pulse inversion imaging with power Doppler, 3D power Doppler and in the late phase (>5 min) with B-flow. In 15 cases with HCC, i.a. DSA was performed in addition. The results were also correlated with MRT and histological findings. Compared to spiral-CT/MRT, only 72/93 (77%) of the lesions could be detected in the B scan, 75/93 (81%) with CHA and 93/93 (100%) in the pulse inversion mode. Tumor vascularization was detectable in 43/93 (46%) of lesions with native power Doppler, in 75/93 (81%) of lesions after administering contrast medium in the CHA mode, in 81/93 (87%) of lesions in the pulse inversion mode with power Doppler and in 77/93 (83%) of lesions with contrast-enhanced B-flow. Early arterial and capillary perfusion was best detected with CHA, particularly in 20/20 (100%) of the HCC lesions, allowing a 3D reconstruction. 3D power Doppler was especially useful in investigating the tumor margins. Up to 20 min after contrast medium injection, B-flow was capable of detecting increased metastatic tumor vascularization in 42/54 (78%) of cases and intratumoral perfusion in 17/20 (85

Synergistic enhancement of iron oxide nanoparticle and gadolinium for dual-contrast MRI

International Nuclear Information System (INIS)

Zhang, Fan; Huang, Xinglu; Qian, Chunqi; Zhu, Lei; Hida, Naoki; Niu, Gang; Chen, Xiaoyuan

2012-01-01

Highlights: ► MR contrast agents exert influence on T 1 or T 2 relaxation time of the surrounding tissue. ► Combined use of iron oxide and Gd-DTPA can improve the sensitivity/specificity of lesion detection. ► Dual contrast MRI enhances the delineation of tumor borders and small lesions. ► The effect of DC-MRI can come from the high paramagnetic susceptibility of Gd 3+ . ► The effect of DC-MRI can also come from the distinct pharmacokinetic distribution of SPIO and Gd-DTPA. -- Abstract: Purpose: The use of MR contrast agents allows accurate diagnosis by exerting an influence on the longitudinal (T 1 ) or transverse (T 2 ) relaxation time of the surrounding tissue. In this study, we combined the use of iron oxide (IO) particles and nonspecific extracellular gadolinium chelate (Gd) in order to further improve the sensitivity and specificity of lesion detection. Procedures: With a 7-Tesla scanner, pre-contrasted, IO-enhanced and dual contrast agent enhanced MRIs were performed in phantom, normal animals, and animal models of lymph node tumor metastases and orthotopic brain tumor. For the dual-contrast (DC) MRI, we focused on the evaluation of T 2 weighted DC MRI with IO administered first, then followed by the injection of a bolus of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). Results: Based on the C/N ratios and MRI relaxometry, the synergistic effect of coordinated administration of Gd-DTPA and IO was observed and confirmed in phantom, normal liver and tumor models. At 30 min after administration of Feridex, Gd-DTPA further decreased T 2 relaxation in liver immediately after the injection. Additional administration of Gd-DTPA also immediately increased the signal contrast between tumor and brain parenchyma and maximized the C/N ratio to −4.12 ± 0.71. Dual contrast MRI also enhanced the delineation of tumor borders and small lesions. Conclusions: DC-MRI will be helpful to improve diagnostic accuracy and decrease the threshold size for

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.)

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

Drug-induced liver injury due to antimicrobials, central nervous system agents, and nonsteroidal anti-inflammatory drugs.

Science.gov (United States)

Devarbhavi, Harshad; Andrade, Raúl J

2014-05-01

Antimicrobial agents including antituberculosis (anti-TB) agents are the most common cause of idiosyncratic drug-induced liver injury (DILI) and drug-induced liver failure across the world. Better molecular and genetic biomarkers are acutely needed to help identify those at risk of liver injury particularly for those needing antituberculosis therapy. Some antibiotics such as amoxicillin-clavulanate and isoniazid consistently top the lists of agents in retrospective and prospective DILI databases. Central nervous system agents, particularly antiepileptics, account for the second most common class of agents implicated in DILI registries. Hepatotoxicity from older antiepileptics such as carbamazepine, phenytoin, and phenobarbital are often associated with hypersensitivity features, whereas newer antiepileptic drugs have a more favorable safety profile. Antidepressants and nonsteroidal anti-inflammatory drugs carry very low risk of significant liver injury, but their prolific use make them important causes of DILI. Early diagnosis and withdrawal of the offending agent remain the mainstays of minimizing hepatotoxicity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

Pharmacokinetic and in vivo evaluation of a self-assembled gadolinium(III)-iron(II) contrast agent with high relaxivity.

Science.gov (United States)

Parac-Vogt, Tatjana N; Vander Elst, Luce; Kimpe, Kristof; Laurent, Sophie; Burtéa, Carmen; Chen, Feng; Van Deun, Rik; Ni, Yicheng; Muller, Robert N; Binnemans, Koen

2006-01-01

A high-molecular weight tetrametallic supramolecular complex [(Ln-DTPA-phen)3Fe]- (Ln = Gd, Eu, La) has been obtained upon self-assembly around one iron(II) ion of three 1,10-phenantroline-based molecules substituted in 5'-position with the polyaminocarboxylate diethylenetriamine-N,N,N',N',N'-pentaacetate, DTPA-phen(4-). The ICP-MS measurements indicated that the lanthanide:iron ratio is 3:1. Photoluminescence spectra of [Eu-DTPA-phen](-) and of [(Eu-DTPA-phen)3Fe]- are nearly identical, implying that the first coordination sphere of the lanthanide(III) ion has not been changed upon coordination of phenantroline unit to iron(II) ion. NMRD measurements revealed that at 20 MHz and 310 K the relaxivity of the [(Gd-DTPA-phen)3Fe]- is equal to 9.5 +/- 0.3 s(-1) mM(-1) of Gd (28.5 s(-1) per millimole per liter of complex) which is significantly higher than that for Gd-DTPA (3.9 s(-1) mM(-1)). The pharmacokinetic parameters of [(Gd-DTPA-phen)3Fe]- in rats indicate that the elimination of [(Gd-DTPA-phen)3Fe]- is significantly slower than that of Gd-DTPA and is correlated with a reduced volume of distribution. The low volume of distribution and the longer elimination time (T(e1/2)) suggest that the agent is confined to the blood compartment, so it could have an important potential as a blood pool contrast agent. The biodistribution profile of [(Gd-DTPA-phen)3Fe]- 2 h after injection indicates significantly higher concentrations of [(Gd-DTPA-phen)3Fe]- as compared with Gd-DTPA in kidney, liver, lungs, heart and spleen. The images obtained on rats by MR angiography show the enhancement of the abdominal blood vessels. The signal intensity reaches a maximum of 55% at 7 min post-contrast and remains around 25% after 90 min. MRI-histomorphological correlation studies of [Gd-DTPA-phen]- and [(Gd-DTPA-phen)3Fe]- showed that both agents displayed potent contrast enhancement in organs including the liver. The necrosis avidity tests indicated that, in contrast to the [Gd

Deep Learning with Convolutional Neural Network for Differentiation of Liver Masses at Dynamic Contrast-enhanced CT: A Preliminary Study.

Science.gov (United States)

Yasaka, Koichiro; Akai, Hiroyuki; Abe, Osamu; Kiryu, Shigeru

2018-03-01

Purpose To investigate diagnostic performance by using a deep learning method with a convolutional neural network (CNN) for the differentiation of liver masses at dynamic contrast agent-enhanced computed tomography (CT). Materials and Methods This clinical retrospective study used CT image sets of liver masses over three phases (noncontrast-agent enhanced, arterial, and delayed). Masses were diagnosed according to five categories (category A, classic hepatocellular carcinomas [HCCs]; category B, malignant liver tumors other than classic and early HCCs; category C, indeterminate masses or mass-like lesions [including early HCCs and dysplastic nodules] and rare benign liver masses other than hemangiomas and cysts; category D, hemangiomas; and category E, cysts). Supervised training was performed by using 55 536 image sets obtained in 2013 (from 460 patients, 1068 sets were obtained and they were augmented by a factor of 52 [rotated, parallel-shifted, strongly enlarged, and noise-added images were generated from the original images]). The CNN was composed of six convolutional, three maximum pooling, and three fully connected layers. The CNN was tested with 100 liver mass image sets obtained in 2016 (74 men and 26 women; mean age, 66.4 years ± 10.6 [standard deviation]; mean mass size, 26.9 mm ± 25.9; 21, nine, 35, 20, and 15 liver masses for categories A, B, C, D, and E, respectively). Training and testing were performed five times. Accuracy for categorizing liver masses with CNN model and the area under receiver operating characteristic curve for differentiating categories A-B versus categories C-E were calculated. Results Median accuracy of differential diagnosis of liver masses for test data were 0.84. Median area under the receiver operating characteristic curve for differentiating categories A-B from C-E was 0.92. Conclusion Deep learning with CNN showed high diagnostic performance in differentiation of liver masses at dynamic CT. © RSNA, 2017 Online

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.

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.

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

Science.gov (United States)

Didier, Ryne A; Hopkins, Katharine L; Coakley, Fergus V; Krishnaswami, Sanjay; Spiro, David M; Foster, Bryan R

2017-09-01

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

Multislice CT of the liver. Effects of contrast material pushed with saline solution on hepatic enhancement

International Nuclear Information System (INIS)

Sekiguchi, Ryuzo; Hayashi, Takayuki; Tsukamoto, Tatsuaki; Kuroki, Yoshinori; Nasu, Katsuhiro; Murakami, Koji; Nawano, Shigeru

2004-01-01

The purpose of this study was to evaluate the usefulness of a method of power injection of contrast material pushed with saline solution for hepatic multislice CT using a dual-head power injector. One hundred twenty-one patients who underwent multislice CT to detect liver metastases were divided into two groups, depending on the protocol of contrast material administration: 100 mL of non-ionic contrast material (370 mgI/mL) or 100 mL of the same contrast material pushed with 30 mL of saline solution. Both contrast material and saline solution were administered at a rate of 2.5 mL/sec using a dual-head power injector. Attenuation values for the two protocols were obtained from the liver, portal vein, and descending aorta. Hepatic enhancement above 50 Hounsfield unit (HU), which is needed for the diagnosis of liver metastases, was achieved in 76.5% of patients given 100 mL of contrast material and 92.5% of those given 100 mL of contrast material pushed with a 30 mL saline solution. In contingency-table analysis, the CT attenuation value of liver categorized as less than 50 HU or more than 50 HU, showed a good relation between the categorized group and the protocol (p=0.0437). In patients with a body weight of 50 kg or more, 100 mL of contrast material pushed with saline solution provided significantly better CT attenuation values in the liver (p=0.0113), portal vein (p=0.0094), and descending aorta (p=0.0394) than those provided by the injection of 100 mL of contrast material alone. When contrast material pushed with saline solution was used, CT attenuation values in the liver were significantly increased, especially in patients with a body weight of 50 kg or more. This technique will provide a decrease in the volume of contrast material administered and a potential decrease in the side effects of contrast material. (author)

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.

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

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.

A new automated quantification algorithm for the detection and evaluation of focal liver lesions with contrast-enhanced ultrasound.

Science.gov (United States)

Gatos, Ilias; Tsantis, Stavros; Spiliopoulos, Stavros; Skouroliakou, Aikaterini; Theotokas, Ioannis; Zoumpoulis, Pavlos; Hazle, John D; Kagadis, George C

2015-07-01

Detect and classify focal liver lesions (FLLs) from contrast-enhanced ultrasound (CEUS) imaging by means of an automated quantification algorithm. The proposed algorithm employs a sophisticated segmentation method to detect and contour focal lesions from 52 CEUS video sequences (30 benign and 22 malignant). Lesion detection involves wavelet transform zero crossings utilization as an initialization step to the Markov random field model toward the lesion contour extraction. After FLL detection across frames, time intensity curve (TIC) is computed which provides the contrast agents' behavior at all vascular phases with respect to adjacent parenchyma for each patient. From each TIC, eight features were automatically calculated and employed into the support vector machines (SVMs) classification algorithm in the design of the image analysis model. With regard to FLLs detection accuracy, all lesions detected had an average overlap value of 0.89 ± 0.16 with manual segmentations for all CEUS frame-subsets included in the study. Highest classification accuracy from the SVM model was 90.3%, misdiagnosing three benign and two malignant FLLs with sensitivity and specificity values of 93.1% and 86.9%, respectively. The proposed quantification system that employs FLLs detection and classification algorithms may be of value to physicians as a second opinion tool for avoiding unnecessary invasive procedures.

Metabolomic Analysis of N-acetylcysteine Protection of Injury from Gadolinium-DTPA Contrast Agent in Rats with Chronic Renal Failure.

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Wan, Chuanling; Xue, Rong; Zhan, Youyang; Wu, Yijie; Li, Xiaojing; Pei, Fengkui

2017-09-01

Gadolinium-based contrast agents (GBCAs) are frequently used to enhance the diagnostic efficacy of magnetic resonance imaging. On the other hand, the association between GBCA administration in patients with advanced renal disease and nephrogenic systemic fibrosis (NSF) was also noted. NSF is a systemic disorder characterized by widespread tissue fibrosis that may lead to death. N-acetylcysteine (NAC) protects rats from injury induced by gadolinium-based contrast agents, but the underlying mechanisms remain unclear. In this study, a nuclear magnetic resonance-based metabolomic approach was used to systematically investigate the protective effects of NAC on Gd-DTPA-induced injury. Thirty-two male Sprague-Dawley rats were given adenine (200 mg·kg -1 body weight) by oral gavage once a day for 3 weeks to induce chronic renal failure (CRF). NAC (600 mg/L in drinking water for 9 days) pretreatment was initiated 2 days before Gd-DTPA injection (a single tail vein injection, 2 mmol/kg body weight). Serum and liver samples were collected on day 7 after Gd-DTPA injection. By study design, the serum and hepatic metabolic changes of rats were measured in four groups of eight each: CRF, CRF-Gd, CRF-Gd-NAC, and CRF-NAC. Gd-DTPA administration to rats with CRF resulted in disturbances of several metabolic pathways, including glucose, lipid, glutamate, choline, gut microbiota, one-carbon, and purine metabolism. NAC pretreatment reversed the abundance changes of high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, glutamate, glutamine, oxidized glutathione, choline, phosphocholine, glycerophosphocholine, trimethylamine, and trimethylamine-N-oxide induced by Gd-DTPA. It is noteworthy, however, that the ameliorating effects of NAC on the disturbance of glutamate, choline, and gut microbiota metabolism may be specific to Gd-DTPA. In all, these findings could be potentially useful to decipher the underlying mechanisms of NAC protective effects from the

Synthesis and application of strawberry-like Fe3O4-Au nanoparticles as CT-MR dual-modality contrast agents in accurate detection of the progressive liver disease.

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Zhao, Hui Y; Liu, Sen; He, Jian; Pan, Chao C; Li, Hui; Zhou, Zheng Y; Ding, Yin; Huo, Da; Hu, Yong

2015-05-01

Development of non-invasive assay for the accurate diagnosis of progressive liver diseases (e.g., fatty liver and hepatocellular carcinoma (HCC)) is of great clinical significance and remains to be a big challenge. Herein, we reported the synthesis of strawberry-like Fe3O4-Au hybrid nanoparticles at room temperature that simultaneously exhibited fluorescence, enhanced X-ray attenuation, and magnetic properties. The results of in vitro fluorescence assay showed that the nanoparticles had significant photo-stability and could avoid the endosome degradation in cells. The in vivo imaging of normal mice demonstrated that the Fe3O4-Au nanoparticles provided 34.61-fold contrast enhancement under magnetic resonance (MR) guidance 15 min post the administration. Computed tomography (CT) measurements showed that the highest Hounsfield Unit (HU) was 174 at 30 min post the injection of Fe3O4-Au nanoparticles. In vivo performance of the Fe3O4-Au nanoparticles was further evaluated in rat models bearing three different liver diseases. For the fatty liver model, nearly homogeneous contrast enhancement was observed under both MR (highest contrast ratio 47.33) and CT (from 19 HU to 72 HU) guidances without the occurrences of focal nodules or dysfunction. For the cirrhotic liver and HCC, pronounced enhancement under MR and CT guidance could be seen in liver parenchyma with highlighted lesions after Fe3O4-Au injection. Furthermore, pathological, hematological and biochemical analysis revealed the absence of acute and chronic toxicity, confirming the biocompatibility of our platform for in vivo applications. Collectively, These Fe3O4-Au nanoparticles showed great promise as a candidate for multi-modality bio-imaging. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular Imaging Agents Specific for the Annulus Fibrosus of the Intervertebral Disk

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Summer L. Gibbs-Strauss

2010-05-01

Full Text Available Low back pain is a prevalent medical condition that is difficult to diagnose and treat. Current imaging methods are unable to correlate pain reliably with spinal structures, and surgical removal of painful damaged or degenerating disks is technically challenging. A contrast agent specific for the intervertebral disk could assist in the detection, diagnosis, and surgical treatment of low back pain. The styryl pyridinium (FM fluorophores were characterized and structure-activity relationships between chemical structure and in vivo uptake were established. Two novel FM fluorophores with improved optical properties for imaging the intervertebral disks were synthesized and evaluated in mice, rats, and pigs. After a single systemic injection, eight of eight FM fluorophores provided high-contrast imaging of the trigeminal ganglia, whereas six of eight provided high-contrast imaging of the dorsal root ganglia. Unexpectedly, three of eight FM fluorophores provided high-contrast imaging of annulus fibrosus tissue of the intervertebral disks, confirmed histologically. We present the first known contrast agent specific for the intervertebral disks and identify the chemical structural motif that mediates uptake. FM fluorophores could be used for image-guided surgery to assist in the removal of intervertebral disk and lay the foundation for derivatives for magnetic resonance imaging and positron emission tomography.

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)

CT manifestations of liver abscess

International Nuclear Information System (INIS)

Yan Jianfeng; Peng Yongjun

2006-01-01

Objective: To study CT findings of hepatic abscess. Methods: CT findings and clinical materials of 38 patients with liver abscess verified by aspiration were retrospectively viewed. All patients were examined by non-enhanced and contrast enhanced CT. Results: In 25 cases, inhomogeneous hypodense lesions with unclear demarcation were found on non-enhanced CT. On contrast enhanced CT scan, target or cluster enhancement was found Additionally, air was found within some lesions. In the rest 13 cases with early stage liver abscess, no typical sign was found on non-enhanced CT, while rosette sign and continued enhancement sign were demonstrated after the contrast agent was given. Conclusion: Various CT findings are found in different stages of liver abscess. The diagnosis and differential diagnosis should be based on CT manifestations and clinical history as well. (authors)

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

Usefulness of liposomes carrying losefamate for CT opacification of liver and spleen

International Nuclear Information System (INIS)

Seltzer, S.E.; Shulkin, P.M.; Adams, D.F.; Davis, M.A.; Hoey, G.B.; Hopkins, R.M.; Bosworth, M.E.

1984-01-01

Iosefamate, a hepatobiliary contrast agent, was encapsulated into liposomes to increase its ability to opacify the liver and spleen on computed tomographic (CT) images. Multilamellar lipid vesicles containing iosefamate in their aqueous phase were prepared. Seven dogs received intravenous injections of 100-300 mg l/kg in one of three forms; encapsulated, unencapsulated, or a mixture of the two in equal parts. Animals that received the opaque vesicles had marked opacification of their livers, bile ducts, gallbladders, spleens and gastrointestinal tracts. At the high-dose level, liver upake of the encapsulated materials was also greater. Liposome-encapsulated hepatobiliary contrast agents are effective liver and spleen opacifiers for CT imaging in the dog

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

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

2013-02-01

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

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

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

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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 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...

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

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)

Suppression of Oncolytic Adenovirus-Mediated Hepatotoxicity by Liver-Specific Inhibition of NF-κB

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Mitsuhiro Machitani

2017-12-01

Full Text Available Telomerase-specific replication-competent adenoviruses (Ads, i.e., TRADs, which possess an E1 gene expression cassette driven by the human telomerase reverse transcriptase promoter, are promising agents for cancer treatment. However, even though oncolytic Ads, including TRAD, are intratumorally administered, they are disseminated from the tumor to systemic circulation, causing concern about oncolytic Ad-mediated hepatotoxicity (due mainly to leaky expression of Ad genes in liver. We reported that inhibition of nuclear factor-κB (NF-κB leads to the suppression of replication-incompetent Ad vector-mediated hepatotoxicity via reduction of the leaky expression of Ad genes in liver. Here, to develop a TRAD with an improved safety profile, we designed a TRAD that carries a liver-specific promoter-driven dominant-negative IκBα (DNIκBα expression cassette (TRAD-DNIκBα. Compared with a conventional TRAD, TRAD-DNIκBα showed hepatocyte-specific inhibition of NF-κB signaling and significantly reduced Ad gene expression and replication in the normal human hepatocyte cell line. TRAD-induced hepatotoxicity was largely suppressed in mice following intravenous administration of TRAD-DNIκBα. However, the replication profiles and oncolytic activities of TRAD-DNIκBα were comparable with those of the conventional TRAD in human non-hepatic tumor cells. These results indicate that oncolytic Ads containing the liver-specific DNIκBα expression cassette have improved safety profiles without inhibiting oncolytic activities.

A novel nitroreductase-enhanced MRI contrast agent and its potential application in bacterial imaging

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Yun Liu

2018-05-01

Full Text Available Nitroreductases (NTRs are known to be able to metabolize nitro-substituted compounds in the presence of reduced nicotinamide adenine dinucleotide (NADH as an electron donor. NTRs are present in a wide range of bacterial genera and, to a lesser extent, in eukaryotes hypoxic tumour cells and tumorous tissues, which makes it an appropriate biomarker for an imaging target to detect the hypoxic status of cancer cells and potential bacterial infections. To evaluate the specific activation level of NTR, great efforts have been devoted to the development of fluorescent probes to detect NTR activities using fluorogenic methods to probe its behaviour in a cellular context; however, NTR-responsive MRI contrast agents are still by far underexplored. In this study, para-nitrobenzyl substituted T1-weighted magnetic resonance imaging (MRI contrast agent Gd-DOTA-PNB (probe 1 has been designed and explored for the possible detection of NTR. Our experimental results show that probe 1 could serve as an MRI-enhanced contrast agent for monitoring NTR activity. The in vitro response and mechanism of the NTR catalysed reduction of probe 1 have been investigated through LC–MS and MRI. Para-nitrobenzyl substituted probe 1 was catalytically reduced by NTR to the intermediate para-aminobenzyl substituted probe which then underwent a rearrangement elimination reaction to Gd-DOTA, generating the enhanced T1-weighted MR imaging. Further, LC–MS and MRI studies of living Escherichia coli have confirmed the NTR activity detection ability of probe 1 at a cellular level. This method may potentially be used for the diagnosis of bacterial infections. KEY WORDS: Nitroreductase, MRI contrast agent, Smart imaging probes, Bacterial imaging, Bacterial infection

Magnetic resonance tomography for focal lesions in the liver using the para-magnetic contrast medium gadolinium DTPA

International Nuclear Information System (INIS)

Hamm, B.; Roemer, T.; Felix, R.; Wolf, K.J.; Klinikum Charlottenburg, Berlin

1986-01-01

The use of the para-magnetic contrast medium gadolinium DTPA for magnetic resonance tomography of focal lesions in the liver was investigated in 31 patients. Two dosage schedules of the contrast medium (0.1 and 0.2 mmol/kg body weight) were used with field strengths of 0.35 and 0.5 Tesla. Using T 1 sequences, gadolinium DTPA showed increased signal intensity in the liver and in tumours, but this was significantly more marked in the tumour. On T 1 spin-echo sequences, previously iso-intense lesions became visible after administration of contrast. On the other hand, contrast-enhanced lesions were less well seen on inversion recovery sequences because of a reduction in the contrast between tumour and liver tissue. The contrast between tumour and liver tissue was not improved by gadolinium DTPA in comparison with precontrast inversion recovery sequences and T 2 spin-echo sequences. The perfusion of intra-hepatic tumours could be elucidated by magnetic resonance tomography after the administration of gadolinium DTPA. (orig.) [de

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

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)

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.)

Multivariable analysis of clinical influence factors on liver enhancement of Gd-EOB-DTPA-enhanced 3T MRI

International Nuclear Information System (INIS)

Verloh, N.; Haimerl, M.; Stroszczynski, C.; Fellner, C.; Wiggermann, P.; Zeman, F.; Teufel, A.; Lang, S.

2015-01-01

The purpose of this study was to identify clinical factors influencing Gd-EOB-DTPA liver uptake in patients with healthy liver parenchyma. A total of 124 patients underwent contrast-enhanced MRI with a hepatocyte-specific contrast agent at 3T. T1-weighted volume interpolated breath-hold examination (VIBE) sequences with fat suppression were acquired before and 20 minutes after contrast injection. The relative enhancement (RE) between plain and contrast-enhanced signal intensity was calculated. Simple and multiple linear regression analyses were performed to evaluate clinical factors influencing the relative enhancement. Patients were subdivided into three groups according to their relative liver enhancement (HRE, RE ≥ 100 %; MRE, 100 % > RE > 50 %; NRE, RE ≤ 50 %) and were analyzed according to the relevant risk factors. Simple regression analyses revealed patient age, transaminases (AST, ALT, GGT), liver, spleen and delta-liver volume (the difference between the volumetrically measured liver volume and the estimated liver volume based on body weight) as significant factors influencing relative enhancement. In the multiple analysis the transaminase AST, spleen and delta liver volume remained significant factors influencing relative enhancement. Delta liver volume showed a significant difference between all analyzed groups. Liver enhancement in the hepatobiliary phase depends on a variety of factors. Body weight-adapted administration of Gd-EOB-DTPA may lead to inadequate liver enhancement after 20 minutes especially when the actual liver volume differs from the expected volume.

[Preoperative imaging/operation planning for liver surgery].

Science.gov (United States)

Schoening, W N; Denecke, T; Neumann, U P

2015-12-01

The currently established standard for planning liver surgery is multistage contrast media-enhanced multidetector computed tomography (CM-CT), which as a rule enables an appropriate resection planning, e.g. a precise identification and localization of primary and secondary liver tumors as well as the anatomical relation to extrahepatic and/or intrahepatic vascular and biliary structures. Furthermore, CM-CT enables the measurement of tumor volume, total liver volume and residual liver volume after resection. Under the condition of normal liver function a residual liver volume of 25 % is nowadays considered sufficient and safe. Recent studies in patients with liver metastases of colorectal cancer showed a clear staging advantage of contrast media-enhanced magnetic resonance imaging (CM-MRI) versus CM-CT. In addition, most recent data showed that the use of liver-specific MRI contrast media further increases the sensitivity and specificity of detection of liver metastases. This imaging technology seems to lead closer to the ideal "one stop shopping" diagnostic tool in preoperative planning of liver resection.

Focal hepatic lesions: contrast-enhancement patterns at pulse-inversion harmonic US using a microbubble contrast agent

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Kim, Eun-A; Yoon, Kwon-Ha; Lee, Young-Hwan; Kim, Hye-Won; Juhng, Seon-Kwan; Won, Jong-Jin [Wonkwang University, Iksan (Korea, Republic of)

2003-12-15

To analyze the contrast-enhancement patterns obtained at pulse-inversion harmonic imaging (PIHI) of focal hepatic lesions, and to thus determine tumor vascularity and the acoustic emission effect. We reviewed pulse-inversion images in 90 consecutive patients with focal hepatic lesions, namely hepatocellular carcinoma (HHC) (n=43), metastases (n=30), and hemangioma (n=17). Vascular and delayed phase images were obtained immediately and five minutes following the injection of a microbubble contrast agent. Tumoral vascularity at vascular phase imaging and the acoustic emission effect at delayed phase imaging were each classified as one of four patterns. Vascular phase images depicted internal vessels in 93% of HCCs, marginal vessels in 83% of metastases, and peripheral enhancement in 71% of hemangiomas. Delayed phase images showed inhomogeneous enhancement in 86% of HCCs; hypoechoic, decreased enhancement in 93% of metastases; and hypoechoic and reversed echogenicity in 65% of hemangiomas. Vascular and delayed phase enhancement patterns were associated with a specificity of 91% or greater, and 92% or greater, respectively, and with positive predictive values of 71% or greater, and 85% or greater, respectively. Contrast-enhancement patterns depicting tumoral vascularity and the acoustic emission effect at PIHI can help differentiate focal hepatic lesions.

Cyanine 5.5 conjugated nanobubbles as a tumor selective contrast agent for dual ultrasound-fluorescence imaging in a mouse model.

Directory of Open Access Journals (Sweden)

Liyi Mai

Full Text Available Nanobubbles and microbubbles are non-invasive ultrasound imaging contrast agents that may potentially enhance diagnosis of tumors. However, to date, both nanobubbles and microbubbles display poor in vivo tumor-selectivity over non-targeted organs such as liver. We report here cyanine 5.5 conjugated nanobubbles (cy5.5-nanobubbles of a biocompatible chitosan-vitamin C lipid system as a dual ultrasound-fluorescence contrast agent that achieved tumor-selective imaging in a mouse tumor model. Cy5.5-nanobubble suspension contained single bubble spheres and clusters of bubble spheres with the size ranging between 400-800 nm. In the in vivo mouse study, enhancement of ultrasound signals at tumor site was found to persist over 2 h while tumor-selective fluorescence emission was persistently observed over 24 h with intravenous injection of cy5.5-nanobubbles. In vitro cell study indicated that cy5.5-flurescence dye was able to accumulate in cancer cells due to the unique conjugated nanobubble structure. Further in vivo fluorescence study suggested that cy5.5-nanobubbles were mainly located at tumor site and in the bladder of mice. Subsequent analysis confirmed that accumulation of high fluorescence was present at the intact subcutaneous tumor site and in isolated tumor tissue but not in liver tissue post intravenous injection of cy5.5-nanobubbles. All these results led to the conclusion that cy5.5-nanobubbles with unique crosslinked chitosan-vitamin C lipid system have achieved tumor-selective imaging in vivo.

A smart T(1)-weighted MRI contrast agent for uranyl cations based on a DNAzyme-gadolinium conjugate.

Science.gov (United States)

Xu, Weichen; Xing, Hang; Lu, Yi

2013-11-07

Rational design of smart MRI contrast agents with high specificity for metal ions remains a challenge. Here, we report a general strategy for the design of smart MRI contrast agents for detecting metal ions based on conjugation of a DNAzyme with a gadolinium complex. The 39E DNAzyme, which has high selectivity for UO2(2+), was conjugated to Gd(III)-DOTA and streptavidin. The binding of UO2(2+) to its 39E DNAzyme resulted in the dissociation of Gd(III)-DOTA from the large streptavidin, leading to a decrease of the T1 correlation time, and a change in the MRI signal.

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

[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.

Depiction of blood vessels by x-ray phase contrast

Energy Technology Data Exchange (ETDEWEB)

Momose, Atsushi [School of Engineering, University of Tokyo, Tokyo (Japan); Takeda, Tohoru; Itai, Yuji [Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki (Japan)

2001-04-01

Blood vessels in livers of a mouse and a rat were depicted by phase-contrast x-ray imaging with an x-ray interferometer without using contrast agents. X-ray interference patterns were converted to image mapping x-ray phase shift caused by the livers using the technique of phase-shifting x-ray interferometry. The arteries and veins to and from the livers were tied before excision in order to prevent blood from flowing out of the liver. The x-ray phase shift caused by blood was substantially different from that caused by other soft sues, and consequently trees of blood vessels were revealed in the images. Vessels of diameter smaller than 0.1 mm were detected. This result suggests new possibilities for investigating vascular systems. (author)

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.

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

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.

Extended diagnosis of liver tumor with gadolinium DTPA supplementary to routine procedure in nuclear medicine

International Nuclear Information System (INIS)

Ehrenheim, C.; Heintz, P.; Schwarzrock, R.; Schober, O.; Hundeshagen, H.

1988-01-01

Several imaging methods and especially their combined application are proven to be useful in the diagnosis and differentiation of liver tumors: Ultrasound, roentgen computed tomography, sequential hepatobiliary scintigraphy (HBSS), blood pool scintigraphy and magnetic resonance imaging. 38 patients with liver tumors (hemangioma, hepatocellular carcinoma, focal nodular hyperplasia) underwent MRI of the liver before and after i.v. injection of 0.2 mmol/kg Gadolinium-DTPA in addition to other imaging methods. Written informed consent we achieved in all cases. The normal and pathological findings in MRI were documented in T1- and T2-weighted images, proton density image, calculated T1- and T2-images and a T1-weighted image after application of the contrast agent. The application of Gadolinium-DTPA as contrast agent improves the delimitation of the most intrahepatic lesions. Concerning the hemangiomas of the liver the improved contrast behaviour induced by Gadolinium-DTPA does not reach the contrast and sensitivity of a native T2-weighted SE image. The demarcation of focal nodular hyperplasia is not improved by use of the contrast agent. This finding supports the assumption that the FNH is not basically different from normal liver tissue. Gadolinium-DTPA provides additional information concerning the delineation of internal tumor details in hepatocellular carcinoma (hyperperfused areas, necroses, fibrous capsular structures). (orig.)

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)

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.

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.

Characterisation of focal liver lesions with unenhanced and contrast enhanced low MI real time ultrasound: On-site unblinded versus off-site blinded reading

International Nuclear Information System (INIS)

Hohmann, Joachim; Skrok, Jan; Basilico, Raffaella; Jennett, Manfred; Müller, Anja; Wolf, Karl-Jürgen; Albrecht, Thomas

2012-01-01

Objective: To compare on-site and blinded off-site reading of baseline ultrasound (US) and contrast enhanced ultrasound (CEUS) for classification and characterisation of focal liver lesions. Materials and methods: 99 patients (57 women and 42 men, age range 18–89 years, mean age: 59 years) with 53 malignant and 46 benign liver lesions were studied with unenhanced US followed by contrast enhanced US after injection of 2.4 ml SonoVue ® (Bracco, Milano, Italy). Image interpretation was performed on-site with clinical information available by consensus of two readers and off-site by two independent blinded readers at two different centers. Comparison of pre and post contrast scans and of the different readers was performed. Reference examinations were histology, intraoperative US, MRI or CT. Results: Sensitivity for malignancy improved from 81/89/66% (on-site/off-site reader 1/2) before to 100/96/96% post contrast administration (p < 0.05, except for reader 1). Specificity improved from 48/48/54% on baseline US to 89/80/76% on CEUS (p < 0.05). Accuracy for specific lesion diagnosis was 62/59/50% pre and 90/77/72% post contrast (p < 0.05). Classification and characterisation post contrast were mildly inferior for off-site reading. Agreement between on-site and off-site readers of unenhanced scans was fair (κ = 0.29–0.39) while it was good for CEUS (κ = 0.63–0.79). Conclusions: CEUS improves classification and characterisation of focal liver lesions and interobserver agreement compared to conventional US. Classification and characterisation post contrast were mildly but statistically significantly better for on-site than for off-site reading.

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.)

Early quantification of the therapeutic efficacy of the vascular disrupting agent, CKD-516, using dynamic contrast-enhanced ultrasonography in rabbit VX2 liver tumors

Energy Technology Data Exchange (ETDEWEB)

Joo, Ijin; Kim, Jung Hoon; Lee, Jeong Min; Choi, Jin Woo; Han, Joon Koo; Choi, Byung Ihn [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

2014-03-15

To evaluate the usefulness of dynamic contrast-enhanced ultrasonography (DCE-US) in the early quantification of hemodynamic change following administration of the vascular disrupting agent (VDA) CKD-516 using a rabbit VX2 liver tumor model. This study was approved by our institutional animal care and use committee. Eight VX2 liver-tumor-bearing rabbits were treated with intravenous CKD-516, and all underwent DCE-US using SonoVue before and again 2, 4, 6, and 24 hours following their treatment. The tumor perfusion parameters were obtained from the time-intensity curve of the DCE-US data. Repeated measures analysis of variance was performed to assess any significant change in tumor perfusion over time. Relative changes in the DCE-US parameters between the baseline and follow-up assessments were correlated with the relative changes in tumor size over the course of seven days using Pearson correlation. CKD-516 treatment resulted in significant changes in the DCE-US parameters, including the peak intensity, total area under the time-intensity curve (AUCtotal), and AUC during wash-out (AUCout) over time (P<0.05). Pairwise comparison tests revealed that the AUCtotal and AUC during wash-in (AUCin) seen on the two-hour follow-up were significantly lower than the baseline values (P<0.05). However, none of early changes in the DCE-US parameters until 24-hour follow-up showed a significant correlation with the relative changes in tumor size during seven days after CKD-516 treatment. Our results suggest that a novel VDA (CKD-516) can cause disruption of tumor perfusion as early as two hours after treatment and that the therapeutic effect of CKD-516 treatment can be effectively quantified using DCE-US.

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)

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.

Automated extraction of metastatic liver cancer regions from abdominal contrast CT images

International Nuclear Information System (INIS)

Yamakawa, Junki; Matsubara, Hiroaki; Kimura, Shouta; Hasegawa, Junichi; Shinozaki, Kenji; Nawano, Shigeru

2010-01-01

In this paper, automated extraction of metastatic liver cancer regions from abdominal contrast X-ray CT images is investigated. Because even in Japan, cases of metastatic liver cancers are increased due to recent Europeanization and/or Americanization of Japanese eating habits, development of a system for computer aided diagnosis of them is strongly expected. Our automated extraction procedure consists of following four steps; liver region extraction, density transformation for enhancement of cancer regions, segmentation for obtaining candidate cancer regions, and reduction of false positives by shape feature. Parameter values used in each step of the procedure are decided based on density and shape features of typical metastatic liver cancers. In experiments using practical 20 cases of metastatic liver tumors, it is shown that 56% of true cancers can be detected successfully from CT images by the proposed procedure. (author)

Gadolinium-ethoxybenzyl-DTPA as a hepatobiliary contrast agent for use in MR cholangiography: results of an in vivo phase-I clinical evaluation

International Nuclear Information System (INIS)

Bollow, M.; Taupitz, M.; Hamm, B.; Staks, T.; Wolf, K.J.; Weinmann, H.J.

1997-01-01

The purpose of this study was to investigate the time course of contrast enhancement in bile ducts and the gallbladder (GB) after injection of gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA). In a clinical phase-I study, MR imaging at 1.5T was performed in 16 healthy volunteers with four different doses of Gd-EOB-DTPA (10, 25, 50, and 100 μmol/kg b. w., four volunteers per dosage). The study protocol comprised a heavily T1-weighted fast multiplanar gradient-echo (GE) sequence before and at increasing intervals for up to 360 min after injection of Gd-EOB-DTPA. The signal enhancement was evaluated in extra-and intrahepatic bile ducts as well as in the GB. In all 16 volunteers the common bile duct showed intense signal enhancement beginning 5-16 min after injection (mean 10 min) and persisting for at least 120 min in 4 subjects and for 360 min in 12 subjects. The duration of signal enhancement was significantly (p < 0.05) longer for higher doses (50, 100 μmol/kg) than for lower doses (10, 25 μmol/kg). Intrahepatic bile ducts were hyperintense as compared with liver parenchyma in all subjects receiving 10 μmol/kg from approximately 50-120 min after contrast agent application. Intrahepatic bile ducts were not displayed using the higher doses, probably because of the strong enhancement of the liver parenchyma. Gallbladder contrasting was achieved in all cases beginning 7-33 min after injection (mean 19 min) and remained visible for up to 360 min in 94 %. Hyperintense visualization of normal extrahepatic bile ducts as well as the GB is regularly achieved with the hepatobiliary contrast agent Gd-EOB-DTPA. The dosage for hyperintense visualization of intrahepatic bile ducts is 10 μmol/kg. (orig.). With 8 figs., 2 tabs

Accumulation of Bile in the Gallbladder: Evaluation by means of Serial Dynamic Contrast-Enhanced Magnetic Resonance Cholangiography with Gadolinium Ethoxybenzyl Diethylenetriaminepentaacetic Acid

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Tsutomu Tamada

2014-01-01

Full Text Available The aim of this study was to evaluate the process of biliary excretion of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA into the biliary tract and to assess the accumulation patterns in the gallbladder using MR cholangiography obtained with Gd-EOB-DTPA which is a liver-specific hepatobiliary contrast agent. Seventy-five patients underwent Gd-EOB-DTPA enhanced MR imaging. Serial multiphasic hepatobiliary phase imaging was qualitatively reviewed to evaluate the process of the biliary excretion of contrast agent into the bile duct and the gallbladder. The accumulation pattern of contrast agent into gallbladder was classified into two groups (group 1 = orthodromic type and group 2 = delayed type. Furthermore, the results in differences of the presence of T1 hyperintense bile or sludge of gallbladder, gall stones, wall thickening of gallbladder, chronic liver disease, and liver cirrhosis between two groups were compared. Forty-eight of 75 patients (64% were included in group 1, and remaining 27 (36% were in group 2. The frequency of the presence of T1 hyperintense bile or sludge of gallbladder was significantly higher in patients with group 2 than that in patients with group 1 (P=0.041. MR cholangiography obtained with Gd-EOB-DTPA showed that there may be an association between the biliary accumulation pattern in the gallbladder and the pathological condition.

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

Targeted gadolinium-loaded dendrimer nanoparticles for tumor-specific magnetic resonance contrast enhancement

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Scott D Swanson

2008-06-01

Full Text Available Scott D Swanson1, Jolanta F Kukowska-Latallo2, Anil K Patri5, Chunyan Chen6, Song Ge4, Zhengyi Cao3, Alina Kotlyar3, Andrea T East7, James R Baker31Department of Radiology, The University of Michigan Medical School, 2Department of Internal Medicine, The University of Michigan Medical School, 3Michigan Nanotechnology Institute for Medicine and Biological Sciences, The University of Michigan, 4Applied Physics, The University of Michigan, MD, USA; 5Present address: National Cancer Institute at Frederick (Contractor, MD, USA; 6Present address: Intel Corporation, Chandler, AZ, USA; 7Present address: Stritch School of Medicine, Chicago, ILL, USAAbstract: A target-specific MRI contrast agent for tumor cells expressing high affinity folate receptor was synthesized using generation five (G5 of polyamidoamine (PAMAM dendrimer. Surface modified dendrimer was functionalized for targeting with folic acid (FA and the remaining terminal primary amines of the dendrimer were conjugated with the bifunctional NCS-DOTA chelator that forms stable complexes with gadolinium (Gd III. Dendrimer-DOTA conjugates were then complexed with GdCl3, followed by ICP-OES as well as MRI measurement of their longitudinal relaxivity (T1 s−1 mM−1 of water. In xenograft tumors established in immunodeficient (SCID mice with KB human epithelial cancer cells expressing folate receptor (FAR, the 3D MRI results showed specific and statistically significant signal enhancement in tumors generated with targeted Gd(III-DOTA-G5-FA compared with signal generated by non-targeted Gd(III-DOTA-G5 contrast nanoparticle. The targeted dendrimer contrast nanoparticles infiltrated tumor and were retained in tumor cells up to 48 hours post-injection of targeted contrast nanoparticle. The presence of folic acid on the dendrimer resulted in specific delivery of the nanoparticle to tissues and xenograft tumor cells expressing folate receptor in vivo. We present the specificity of the dendrimer

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

Quantitative evaluation of contrast-enhanced ultrasound after intravenous administration of a microbubble contrast agent for differentiation of benign and malignant thyroid nodules: assessment of diagnostic accuracy.

Science.gov (United States)

Nemec, Ursula; Nemec, Stefan F; Novotny, Clemens; Weber, Michael; Czerny, Christian; Krestan, Christian R

2012-06-01

To investigate the diagnostic accuracy, through quantitative analysis, of contrast-enhanced ultrasound (CEUS), using a microbubble contrast agent, in the differentiation of thyroid nodules. This prospective study enrolled 46 patients with solitary, scintigraphically non-functional thyroid nodules. These patients were scheduled for surgery and underwent preoperative CEUS with pulse-inversion harmonic imaging after intravenous microbubble contrast medium administration. Using histology as a standard of reference, time-intensity curves of benign and malignant nodules were compared by means of peak enhancement and wash-out enhancement relative to the baseline intensity using a mixed model ANOVA. ROC analysis was performed to assess the diagnostic accuracy in the differentiation of benign and malignant nodules on CEUS. The complete CEUS data of 42 patients (31/42 [73.8%] benign and 11/42 [26.2%] malignant nodules) revealed a significant difference (P benign and malignant nodules. Furthermore, based on ROC analysis, CEUS demonstrated sensitivity of 76.9%, specificity of 84.8% and accuracy of 82.6%. Quantitative analysis of CEUS using a microbubble contrast agent allows the differentiation of benign and malignant thyroid nodules and may potentially serve, in addition to grey-scale and Doppler ultrasound, as an adjunctive tool in the assessment of patients with thyroid nodules. • Contrast-enhanced ultrasound (CEUS) helps differentiate between benign and malignant thyroid nodules. • Quantitative CEUS analysis yields sensitivity of 76.9% and specificity of 84.8%. • CEUS may be a potentially useful adjunct in assessing thyroid nodules.

Tumor Vessel Compression Hinders Perfusion of Ultrasonographic Contrast Agents

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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.

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

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Rand, Danielle; Derdak, Zoltan; Carlson, Rolf; Wands, Jack R.; Rose-Petruck, Christoph

2015-10-01

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is almost uniformly fatal. Current methods of detection include ultrasound examination and imaging by CT scan or MRI; however, these techniques are problematic in terms of sensitivity and specificity, and the detection of early tumors (<1 cm diameter) has proven elusive. Better, more specific, and more sensitive detection methods are therefore urgently needed. Here we discuss the application of a newly developed x-ray imaging technique called Spatial Frequency Heterodyne Imaging (SFHI) for the early detection of HCC. SFHI uses x-rays scattered by an object to form an image and is more sensitive than conventional absorption-based x-radiography. We show that tissues labeled in vivo with gold nanoparticle contrast agents can be detected using SFHI. We also demonstrate that directed targeting and SFHI of HCC tumors in a mouse model is possible through the use of HCC-specific antibodies. The enhanced sensitivity of SFHI relative to currently available techniques enables the x-ray imaging of tumors that are just a few millimeters in diameter and substantially reduces the amount of nanoparticle contrast agent required for intravenous injection relative to absorption-based x-ray imaging.

Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: a biocompatible, size-tunable contrast agent for magnetic resonance imaging

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Unterweger H

2017-07-01

Full Text Available Harald Unterweger,1,* Christina Janko,1,* Marc Schwarz,2 László Dézsi,3 Rudolf Urbanics,4 Jasmin Matuszak,1 Erik Őrfi,3 Tamás Fülöp,3 Tobias Bäuerle,2 János Szebeni,3,4 Clément Journé,5 Aldo R Boccaccini,6 Christoph Alexiou,1 Stefan Lyer,1 Iwona Cicha1 1Cardiovascular Nanomedicine Unit, Section of Experimental Oncology und Nanomedicine (SEON, Else Kröner-Fresenius-Stiftung-Professorship, ENT Department, University Hospital Erlangen, Friedrich-Alexander-Universitaet Erlangen-Nuernberg, 2Preclinical Imaging Platform Erlangen (PIPE, Institute of Radiology, University Hospital Erlangen, Erlangen, Germany; 3Nanomedicine Research and Education Center, Semmelweis University, 4SeroScience Ltd., Budapest, Hungary; 5Inserm U1148, Fédération de Recherche en Imagerie Multimodalités (FRIM, X Bichat Hospital, Paris Diderot University, Paris, France; 6Institute of Biomaterials, Department of Materials Science and Engineering, University Erlangen-Nuremberg, Erlangen, Germany *These authors contributed equally to this work Abstract: Iron oxide-based contrast agents have been in clinical use for magnetic resonance imaging (MRI of lymph nodes, liver, intestines, and the cardiovascular system. Superparamagnetic iron oxide nanoparticles (SPIONs have high potential as a contrast agent for MRI, but no intravenous iron oxide-containing agents are currently approved for clinical imaging. The aim of our work was to analyze the hemocompatibility and immuno-safety of a new type of dextran-coated SPIONs (SPIONdex and to characterize these nanoparticles with ultra-high-field MRI. Key parameters related to nanoparticle hemocompatibility and immuno-safety were investigated in vitro and ex vivo. To address concerns associated with hypersensitivity reactions to injectable nanoparticulate agents, we analyzed complement activation-related pseudoallergy (CARPA upon intravenous administration of SPIONdex in a pig model. Furthermore, the size-tunability of SPIONdex and

Diffusion weighted imaging of liver lesions suspect for metastases: Apparent diffusion coefficient (ADC) values and lesion contrast are independent from Gd-EOB-DTPA administration

International Nuclear Information System (INIS)

Benndorf, Matthias; Schelhorn, Juliane; Dietzel, Matthias; Kaiser, Werner A.; Baltzer, Pascal A.T.

2012-01-01

Purpose: Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced liver MRI is widely used for detection and differentiation of focal liver lesions. Diffusion weighted imaging (DWI) including apparent diffusion coefficient (ADC) measurements is increasingly utilised as a fast and, with limitations, quantitative method for liver lesion detection and characterisation. Herein we investigate whether the administration of Gd-EOB-DTPA affects DWI. Materials and methods: 31 consecutive patients referred to standardised liver MRI (1.5 T, Gd-EOB-DTPA, 0.025 mmol/kg) were retrospectively reviewed. All underwent a breathhold DWI sequence before and after contrast agent administration (EPI-DWI, TR/TE (effective): 2100/62 ms, b-values: 0 and 800 s/mm 2 ). Patients with previously treated liver lesions were excluded. Signal intensity of lesion, parenchyma and noise on DWI images as well as the ADC value were measured after identification by two observers in consensus using manually placed regions of interest. The reference standard was imaging follow-up determined separately by two radiologists. Data analysis included signal-to-noise (SNR) ratio and contrast-to-noise ratio (CNR) calculations, comparisons were drawn by employing multiple Bonferroni corrected Wilcoxon signed-rank tests. Results: 50 malignant and 39 benign lesions were identified. Neither SNR, CNR nor ADC values showed significant differences between pre- and postcontrast DWI. Both pre- and postcontrast ADC values differed significantly between benign and malignant lesions (P < 0.001). Conclusion: We did not identify a significant influence of Gd-EOB-DTPA on DWI of liver lesions. This allows for individual tailoring of imaging protocols according to clinical needs.

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

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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.

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

International Nuclear Information System (INIS)

Park, Ji-Ae; Lee, Yong Jin; Ko, In Ok; Kim, Tae-Jeong; Chang, Yongmin; Lim, Sang Moo; Kim, Kyeong Min; Kim, Jung Young

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-12-12

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-06-15

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

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

Science.gov (United States)

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

2015-09-01

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

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.