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Sample records for contrast agents targeted

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. Gd-functionalised Au nanoparticles as targeted contrast agents in MRI: relaxivity enhancement by polyelectrolyte coating.

    Science.gov (United States)

    Warsi, Muhammad Farooq; Adams, Ralph W; Duckett, Simon B; Chechik, Victor

    2010-01-21

    Monolayer-protected, Gd(3+)-functionalised gold nanoparticles with enhanced spin-lattice relaxivity (r(1)) were prepared; adsorption of polyelectrolytes on these materials further increased r(1) and ligand exchange with a biotin-derivatised disulfide led to a prototype avidin-targeted contrast agent.

  7. 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)

  8. 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.

  9. 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.

  10. Magnetic resonance imaging of osteosarcoma using a bis(alendronate)-based bone-targeted contrast agent.

    Science.gov (United States)

    Ge, Pingju; Sheng, Fugeng; Jin, Yiguang; Tong, Li; Du, Lina; Zhang, Lei; Tian, Ning; Li, Gongjie

    2016-12-01

    Magnetic resonance (MR) is currently used for diagnosis of osteosarcoma but not well even though contrast agents are administered. Here, we report a novel bone-targeted MR imaging contrast agent, Gd 2 -diethylenetriaminepentaacetate-bis(alendronate) (Gd 2 -DTPA-BA) for the diagnosis of osteosarcoma. It is the conjugate of a bone cell-seeking molecule (i.e., alendronate) and an MR imaging contrast agent (i.e., Gd-DTPA). Its physicochemical parameters were measured, including pK a , complex constant, and T 1 relaxivity. Its bone cell-seeking ability was evaluated by measuring its adsorption on hydroxyapatite. Hemolysis was investigated. MR imaging and biodistribution of Gd 2 -DTPA-BA and Gd-DTPA were studied on healthy and osteosarcoma-bearing nude mice. Gd 2 -DTPA-BA showed high adsorption on hydroxyapatite, the high MR relaxivity (r 1 ) of 7.613mM -1 s -1 (2.6 folds of Gd-DTPA), and no hemolysis. The MR contrast effect of Gd 2 -DTPA-BA was much higher than that of Gd-DTPA after intravenous injection to the mice. More importantly, the MR imaging of osteosarcoma was significantly improved by Gd 2 -DTPA-BA. The signal intensity of Gd 2 -DTPA-BA reached 120.3% at 50min, equal to three folds of Gd-DTPA. The bone targeting index (bone/blood) of Gd 2 -DTPA-BA in the osteosarcoma-bearing mice was very high to 130 at 180min. Furthermore, the contrast enhancement could also be found in the lung due to metastasis of osteosarcoma. Gd 2 -DTPA-BA plays a promising role in the diagnoses of osteosacomas, including the primary bone tumors and metastases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. 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.

  12. 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.

  13. 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

  14. Hyaluronic acid-functionalized single-walled carbon nanotubes as tumor-targeting MRI contrast agent

    Directory of Open Access Journals (Sweden)

    Hou L

    2015-07-01

    Full Text Available Lin Hou,* Huijuan Zhang,* Yating Wang, Lili Wang, Xiaomin Yang, Zhenzhong ZhangSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China*These authors contributed equally to this workAbstract: A tumor-targeting carrier, hyaluronic acid (HA-functionalized single-walled carbon nanotubes (SWCNTs, was explored to deliver magnetic resonance imaging (MRI contrast agents (CAs targeting to the tumor cells specifically. In this system, HA surface modification for SWCNTs was simply accomplished by amidation process and could make this nanomaterial highly hydrophilic. Cellular uptake was performed to evaluate the intracellular transport capabilities of HA-SWCNTs for tumor cells and the uptake rank was HA-SWCNTs> SWCNTs owing to the presence of HA, which was also evidenced by flow cytometry. The safety evaluation of this MRI CAs was investigated in vitro and in vivo. It revealed that HA-SWCNTs could stand as a biocompatible nanocarrier and gadolinium (Gd/HA-SWCNTs demonstrated almost no toxicity compared with free GdCl3. Moreover, GdCl3 bearing HA-SWCNTs could significantly increase the circulation time for MRI. Finally, to investigate the MRI contrast enhancing capabilities of Gd/HA-SWCNTs, T1-weighted MR images of tumor-bearing mice were acquired. The results suggested Gd/HA-SWCNTs had the highest tumor-targeting efficiency and T1-relaxivity enhancement, indicating HA-SWCNTs could be developed as a tumor-targeting carrier to deliver the CAs, GdCl3, for the identifiable diagnosis of tumor.Keywords: gadolinium, magnetic resonance, SWCNTs, hyaluronic acid, contrast agent

  15. 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

  16. 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

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

    Science.gov (United States)

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

    2009-12-01

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

  18. 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.

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

    Science.gov (United States)

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

    2013-03-01

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

  20. 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

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

    Science.gov (United States)

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

    2009-05-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-06-15

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

  3. Orotracheal administration of contrast agents: a new protocol for brain tumor targeting.

    Science.gov (United States)

    Bianchi, Andrea; Moncelet, Damien; Lux, François; Plissonneau, Marie; Rizzitelli, Silvia; Ribot, Emeline Julie; Tassali, Nawal; Bouchaud, Véronique; Tillement, Olivier; Voisin, Pierre; Crémillieux, Yannick

    2015-06-01

    The development of new non-invasive diagnostic and therapeutic approaches is of paramount importance in order to improve the outcome of patients with glioblastoma (GBM). In this work we investigated a completely non-invasive pre-clinical protocol to effectively target and detect brain tumors through the orotracheal route, using ultra-small nanoparticles (USRPs) and MRI. A mouse model of GBM was developed. In vivo MRI acquisitions were performed before and after intravenous or orotracheal administration of the nanoparticles to identify and segment the tumor. The accumulation of the nanoparticles in neoplastic lesions was assessed ex vivo through fluorescence microscopy. Before the administration of contrast agents, MR images allowed the identification of the presence of abnormal brain tissue in 73% of animals. After orotracheal or intravenous administration of USRPs, in all the mice an excellent co-localization of the position of the tumor with MRI and histology was observed. The elimination time of the USRPs from the tumor after the orotracheal administration was approximately 70% longer compared with intravenous injection. MRI and USRPs were shown to be powerful imaging tools able to detect, quantify and longitudinally monitor the development of GBMs. The absence of ionizing radiation and high resolution of MRI, along with the complete non-invasiveness and good reproducibility of the proposed protocol, make this technique potentially translatable to humans. To our knowledge, this is the first time that the advantages of a needle-free orotracheal administration route have been demonstrated for the investigation of the pathomorphological changes due to GBMs. Copyright © 2015 John Wiley & Sons, Ltd.

  4. Early Detection of Prostate Cancer with New Nanoparticle Based UltrasoundContrast Agents Targeted to PSMA

    Science.gov (United States)

    2017-08-01

    in learning and careers in science, technology, and the humanities. What do you plan to do during the next reporting period to accomplish...Report.” Describe how results from the project made an impact, or are likely to make an impact, beyond the bounds of science, engineering , and the...Lipid Acyl Chain Length Improves Stability of Nano-sized Ultrasound Contrast Agents In Vitro. Biomedical Engineering Society 2017 meeting. Under review

  5. A Functional Iron Oxide Nanoparticles Modified with PLA-PEG-DG as Tumor-Targeted MRI Contrast Agent.

    Science.gov (United States)

    Xiong, Fei; Hu, Ke; Yu, Haoli; Zhou, Lijun; Song, Lina; Zhang, Yu; Shan, Xiuhong; Liu, Jianping; Gu, Ning

    2017-08-01

    Tumor targeting could greatly promote the performance of magnetic nanomaterials as MRI (Magnetic Resonance Imaging) agent for tumor diagnosis. Herein, we reported a novel magnetic nanoparticle modified with PLA (poly lactic acid)-PEG (polyethylene glycol)-DG (D-glucosamine) as Tumor-targeted MRI Contrast Agent. In this work, we took use of the D-glucose passive targeting on tumor cells, combining it on PLA-PEG through amide reaction, and then wrapped the PLA-PEG-DG up to the Fe 3 O 4 @OA NPs. The stability and anti phagocytosis of Fe 3 O 4 @OA@PLA-PEG-DG was tested in vitro; the MRI efficiency and toxicity was also detected in vivo. These functional magnetic nanoparticles demonstrated good biocompatibility and stability both in vitro and in vivo. Cell experiments showed that Fe 3 O 4 @OA@PLA-PEG-DG nanoparticles exist good anti phagocytosis and high targetability. In vivo MRI images showed that the contrast effect of Fe 3 O 4 @OA@PLA-PEG-DG nanoparticles prevailed over the commercial non tumor-targeting magnetic nanomaterials MRI agent at a relatively low dose. The DG can validly enhance the tumor-targetting effect of Fe 3 O 4 @OA@PLA-PEG nanoparticle. Maybe MRI agents with DG can hold promise as tumor-targetting development in the future.

  6. 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

  7. 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.

  8. 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.

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

    Science.gov (United States)

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

    2015-07-01

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

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

    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.Keywords: cationic USPIOs, MRI, contrast agent, magnetic targeting, in vivo toxicity, intravital microscopy

  18. Early Detection of Prostate Cancer with New Nanoparticle-Based Ultrasound Contrast Agents Targeted to PSMA

    Science.gov (United States)

    2017-08-01

    protein therapy making use of a filamentous nanotechnology. The targeted delivery of doxorubicin and tumor necrosis factor-related apoptosis...3/31/2012 Vascular modulation with or without chemotherapy for enhancement of RF ablation; Role: Co- Investigator 2010 SIR Foundation Grant (PI...Characterization of Slow Precipitating Implants for Vascular Occlusion. IEEE International Ultrasonics Symposium 2017 Annual meeting. In preparation

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

    Science.gov (United States)

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

    2017-11-01

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

  20. Gold Nanorods Targeted to Delta Opioid Receptor: Plasmon-Resonant Contrast and Photothermal Agents

    Directory of Open Access Journals (Sweden)

    Kvar C. Black

    2008-01-01

    Full Text Available Molecularly targeted gold nanorods were investigated for applications in both diagnostic imaging and disease treatment with cellular resolution. The nanorods were tested in two genetically engineered cell lines derived from the human colon carcinoma HCT-116, a model for studying ligand-receptor interactions. One of these lines was modified to express delta opioid receptor (δOR and green fluorescent protein, whereas the other was receptor free and expressed a red fluorescent protein, to serve as the control. Deltorphin, a high-affinity ligand for δOR, was stably attached to the gold nanorods through a thiol-terminated linker. In a mixed population of cells, we demonstrated selective imaging and destruction of receptor-expressing cells while sparing those cells that did not express the receptor. The molecularly targeted nanorods can be used as an in vitro ligand-binding and cytotoxic treatment assay platform and could potentially be applied in vivo for diagnostic and therapeutic purposes with endoscopic technology.

  1. Biocompatible PEGylated gold nanorods as colored contrast agents for targeted in vivo cancer applications

    Science.gov (United States)

    Kopwitthaya, Atcha; Yong, Ken-Tye; Hu, Rui; Roy, Indrajit; Ding, Hong; Vathy, Lisa A.; Bergey, Earl J.; Prasad, Paras N.

    2010-08-01

    In this contribution, we report the use of a PEGylated gold nanorods formulation as a colored dye for tumor labeling in vivo. We have demonstrated that the nanorod-targeted tumor site can be easily differentiated from the background tissues by the 'naked eye' without the need of sophisticated imaging instruments. In addition to tumor labeling, we have also performed in vivo toxicity and biodistribution studies of PEGylated gold nanorods in vivo by using BALB/c mice as the model. In vivo toxicity studies indicated no mortality or adverse effects or weight changes in BALB/c mice treated with PEGylated gold nanorods. This finding will provide useful guidelines in the future development of diagnostic probes for cancer diagnosis, optically guided tumor surgery, and lymph node mapping applications.

  2. Biocompatible PEGylated gold nanorods as colored contrast agents for targeted in vivo cancer applications

    Energy Technology Data Exchange (ETDEWEB)

    Kopwitthaya, Atcha; Hu Rui; Roy, Indrajit; Ding Hong; Vathy, Lisa A; Bergey, Earl J; Prasad, Paras N [Institute for Lasers, Photonics and Biophotonics, University at Buffalo, State University of New York, Buffalo, NY 14260-4200 (United States); Yong, Ken-Tye, E-mail: ktyong@ntu.edu.sg, E-mail: pnprasad@buffalo.edu [School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798 (Singapore)

    2010-08-06

    In this contribution, we report the use of a PEGylated gold nanorods formulation as a colored dye for tumor labeling in vivo. We have demonstrated that the nanorod-targeted tumor site can be easily differentiated from the background tissues by the 'naked eye' without the need of sophisticated imaging instruments. In addition to tumor labeling, we have also performed in vivo toxicity and biodistribution studies of PEGylated gold nanorods in vivo by using BALB/c mice as the model. In vivo toxicity studies indicated no mortality or adverse effects or weight changes in BALB/c mice treated with PEGylated gold nanorods. This finding will provide useful guidelines in the future development of diagnostic probes for cancer diagnosis, optically guided tumor surgery, and lymph node mapping applications.

  3. Highly biocompatible TiO2:Gd3+ nano-contrast agent with enhanced longitudinal relaxivity for targeted cancer imaging

    Science.gov (United States)

    Chandran, Parwathy; Sasidharan, Abhilash; Ashokan, Anusha; Menon, Deepthy; Nair, Shantikumar; Koyakutty, Manzoor

    2011-10-01

    We report the development of a novel magnetic nano-contrast agent (nano-CA) based on Gd3+ doped amorphous TiO2 of size ~25 nm, exhibiting enhanced longitudinal relaxivity (r1) and magnetic resonance (MR) contrasting together with excellent biocompatibility. Quantitative T1 mapping of phantom samples using a 1.5 T clinical MR imaging system revealed that the amorphous phase of doped titania has the highest r1 relaxivity which is ~2.5 fold higher than the commercially used CA Magnevist™. The crystalline (anatase) samples formed by air annealing at 250 °C and 500 °C showed significant reduction in r1 values and MR contrast, which is attributed to the loss of proton-exchange contribution from the adsorbed water and atomic re-arrangement of Gd3+ ions in the crystalline host lattice. Nanotoxicity studies including cell viability, plasma membrane integrity, reactive oxygen stress and expression of pro-inflammatory cytokines, performed on human primary endothelial cells (HUVEC), human blood derived peripheral blood mononuclear cells (PBMC) and nasopharyngeal epidermoid carcinoma (KB) cell line showed excellent biocompatibility up to relatively higher doses of 200 μg ml-1. The potential of this nano-CA to cause hemolysis, platelet aggregation and plasma coagulation were studied using human peripheral blood samples and found no adverse effects, illustrating the possibility of the safe intravenous administration of these agents for human applications. Furthermore, the ability of these agents to specifically detect cancer cells by targeting molecular receptors on the cell membrane was demonstrated on folate receptor (FR) positive oral carcinoma (KB) cells, where the folic acid conjugated nano-CA showed receptor specific accumulation on cell membrane while leaving the normal fibroblast cells (L929) unstained. This study reveals that the Gd3+ doped amorphous TiO2 nanoparticles having enhanced magnetic resonance contrast and high biocompatibility is a promising candidate for

  4. 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...

  5. Targeting property and toxicity of a novel ultrasound contrast agent microbubble carrying the targeting and drug-loaded complex FA-CNTs-PTX on MCF7 cells.

    Science.gov (United States)

    Zhang, Jie; Zhang, Yu; Liu, Junxi; Li, Guozhong; Wen, Zhaohui; Zhao, Yue; Zhang, Xiangyu; Liu, Fenghua

    2017-10-01

    The application of ultrasound contrast agents not only is confined to the enhancement of ultrasound imaging but also has started to be used as a drug system for diagnosis and treatment. In this paper, Span60 and PEG1500 were used as membrane materials, and a new targeting and drug-loading multifunctional ultrasound contrast agent microbubble enveloping the FA-CNTs-PTX complex was successfully prepared by acoustic cavitation. With the breast cancer cell line MCF7 as the research target, the effects of the microbubble with FA-CNTs-PTX on the proliferation and toxicity of MCF7 cells were studied using a CCK-8 and AO/EB double-staining method. The influences of the microbubbles with FA-CNTs-PTX on the cellular morphology and apoptosis period of the MCF7 cells were detected using an inverted fluorescence microscope. The apoptosis of MCF7 cells induced by the microbubbles with FA-CNTs-PTX was investigated with flow cytometry and an annexin and PI double staining fluorescence quantitative analysis. The results indicated that the ultrasound contrast agent microbubble with FA-CNTs-PTX remarkably inhibited the proliferation of MCF7 cells, which was mainly controlled by the drug loading rate and the nanometer size of the microbubbles. Moreover, the proliferative inhibition rate of the microbubbles with FA-CNTs-PTX was related to the cell apoptosis period of MCF7 cells. Its inhibition degree on the proliferation of MCF7 cells was higher than that of the hepatoma HepG2 cells. The apoptosis rate of MCF7 cells induced by the microbubbles with FA-CNTs-PTX was higher than that of normal human umbilical vein endothelial cells (HUVECs), and the microbubbles with FA-CNTs-PTX could target the MCF7 cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. 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...

  7. Synthesis and characterization of Bombesin-superparamagnetic iron oxide nanoparticles as a targeted contrast agent for imaging of breast cancer using MRI

    International Nuclear Information System (INIS)

    Jafari, Atefeh; Shayesteh, Saber Farjami; Salouti, Mojtaba; Heidari, Zahra; Rajabi, Ahmad Bitarafan; Boustani, Komail; Nahardani, Ali

    2015-01-01

    The targeted delivery of superparamagnetic iron oxide nanoparticles (SPIONs) as a contrast agent may facilitate their accumulation in cancer cells and enhance the sensitivity of MR imaging. In this study, SPIONs coated with dextran (DSPIONs) were conjugated with bombesin (BBN) to produce a targeting contrast agent for detection of breast cancer using MRI. X-ray diffraction, transmission electron microscopy, and vibrating sample magnetometer analyses indicated the formation of dextran-coated superparamagnetic iron oxide nanoparticles with an average size of 6.0 ± 0.5 nm. Fourier transform infrared spectroscopy confirmed the conjugation of the BBN with the DSPIONs. A stability study proved the high optical stability of DSPION–BBN in human blood serum. DSPION–BBN biocompatibility was confirmed by cytotoxicity evaluation. A binding study showed the targeting ability of DSPION–BBN to bind to T47D breast cancer cells overexpressing gastrin-releasing peptide (GRP) receptors. T 2 -weighted and T 2 *-weighted color map MR images were acquired. The MRI study indicated that the DSPION–BBN possessed good diagnostic ability as a GRP-specific contrast agent, with appropriate signal reduction in T 2 *-weighted color map MR images in mice with breast tumors. (paper)

  8. 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.)

  9. Toward a new and noninvasive diagnostic method of papillary thyroid cancer by using peptide vectorized contrast agents targeted to galectin-1.

    Science.gov (United States)

    Fanfone, Deborah; Despretz, Nadège; Stanicki, Dimitri; Rubio-Magnieto, Jenifer; Fossépré, Mathieu; Surin, Mathieu; Rorive, Sandrine; Salmon, Isabelle; Vander Elst, Luce; Laurent, Sophie; Muller, Robert N; Saussez, Sven; Burtea, Carmen

    2017-10-06

    The incidence of papillary thyroid cancer has increased these last decades due to a better detection. High prevalence of nodules combined with the low incidence of thyroid cancers constitutes an important diagnostic challenge. We propose to develop an alternative diagnostic method to reduce the number of useless and painful thyroidectomies using a vectorized contrast agent for magnetic resonance imaging. Galectin-1 (gal-1), a protein overexpressed in well-differentiated thyroid cancer, has been targeted with a randomized linear 12-mer peptide library using the phage display technique. Selected peptides have been conjugated to ultrasmall superparamagnetic particles of iron oxide (USPIO). Peptides and their corresponding contrast agents have been tested in vitro for their specific binding and toxicity. Two peptides (P1 and P7) were selected according to their affinity toward gal-1. Their binding has been revealed by immunohistochemistry on human thyroid cancer biopsies, and they were co-localized with gal-1 by immunofluorescence on TPC-1 cell line. Both peptides induce a decrease in TPC-1 cells' adhesion to gal-1 immobilized on culture plates. After coupling to USPIO, the peptides preserved their affinity toward gal-1. Their specific binding has been corroborated by co-localization with gal-1 expressed by TPC-1 cells and by their ability to compete with anti-gal-1 antibody. The peptides and their USPIO derivatives produce no toxicity in HepaRG cells as determined by MTT assay. The vectorized contrast agents are potential imaging probes for thyroid cancer diagnosis. Moreover, the two gal-1-targeted peptides prevent cancer cell adhesion by interacting with the carbohydrate-recognition domain of gal-1.

  10. 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

  11. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-01-15

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

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

  14. 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

  15. 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

  16. 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

  17. 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.)

  18. 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

  19. 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

  20. 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

  1. 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

  2. Use of contrast agents for liver MRI

    International Nuclear Information System (INIS)

    Ward, Janice

    2007-01-01

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

  3. 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...

  4. 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.

  5. 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

  6. 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)

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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.)

  14. 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.

  15. Ultrasound molecular imaging of breast cancer in MCF-7 orthotopic mice using gold nanoshelled poly(lactic-co-glycolic acid) nanocapsules: a novel dual-targeted ultrasound contrast agent

    OpenAIRE

    Xu,Li; Du,Jing; Wan,Caifeng; Zhang,Yu; Xie,Shaowei; Li,Hongli; Yang,Hong; Li,Fenghua

    2018-01-01

    Li Xu,1,* Jing Du,1,* Caifeng Wan,1 Yu Zhang,1 Shaowei Xie,1 Hongli Li,1 Hong Yang,2 Fenghua Li1 1Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; 2Department of Chemistry, College of Life and Environmental Science, Shanghai Normal University, Shanghai, China *These authors contributed equally to this work Background: The development of nanoscale molecularly targeted ultrasound contrast agents (UCAs) with high affinity and specif...

  16. 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.

  17. Novel contrast agent for liver and spleen

    International Nuclear Information System (INIS)

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

    1991-01-01

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

  18. 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

  19. Extracellular gadolinium contrast agents: Differences in stability

    International Nuclear Information System (INIS)

    Morcos, S.K.

    2008-01-01

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

  20. 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.

  1. 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.

  2. 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. .

  3. Synthesis of Laboratory Ultrasound Contrast Agents

    Directory of Open Access Journals (Sweden)

    Jaemin Oh

    2013-10-01

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

  4. 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.

  5. 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

  6. 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)

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

    International Nuclear Information System (INIS)

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

    1992-01-01

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

  8. 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)

  9. [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.

  10. 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.

  11. 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.)

  12. 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

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

    National Research Council Canada - National Science Library

    Josephson, Lee

    2005-01-01

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

  14. Collapse dynamics of ultrasound contrast agent microbubbles

    Science.gov (United States)

    King, Daniel Alan

    Ultrasound contrast agents (UCAs) are micron-sized gas bubbles encapsulated with thin shells on the order of nanometers thick. The damping effects of these viscoelastic coatings are widely known to significantly alter the bubble dynamics for linear and low-amplitude behavior; however, their effects on strongly nonlinear and destruction responses are much less studied. This dissertation examines the behaviors of single collapsing shelled microbubbles using experimental and theoretical methods. The study of their dynamics is particularly relevant for emerging experimental uses of UCAs which seek to leverage localized mechanical forces to create or avoid specialized biomedical effects. The central component in this work is the study of postexcitation rebound and collapse, observed acoustically to identify shell rupture and transient inertial cavitation of single UCA microbubbles. This time-domain analysis of the acoustic response provides a unique method for characterization of UCA destruction dynamics. The research contains a systematic documentation of single bubble postexcitation collapse through experimental measurement with the double passive cavitation detection (PCD) system at frequencies ranging from 0.9 to 7.1 MHz and peak rarefactional pressure amplitudes (PRPA) ranging from 230 kPa to 6.37 MPa. The double PCD setup is shown to improve the quality of collected data over previous setups by allowing symmetric responses from a localized confocal region to be identified. Postexcitation signal percentages are shown to generally follow trends consistent with other similar cavitation metrics such as inertial cavitation, with greater destruction observed at both increased PRPA and lower frequency over the tested ranges. Two different types of commercially available UCAs are characterized and found to have very different collapse thresholds; lipid-shelled Definity exhibits greater postexcitation at lower PRPAs than albumin-shelled Optison. Furthermore, by altering

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

    International Nuclear Information System (INIS)

    Reimer, Peter; Schneider, Guenter; Schima, Wolfgang

    2004-01-01

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

  16. Magnetic Resonance Imaging Contrast Agents: A Review of Literature

    Directory of Open Access Journals (Sweden)

    Zahra Sahraei

    2015-10-01

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

  17. 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

  18. 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.

  19. Molecular imaging with targeted contrast ultrasound.

    Science.gov (United States)

    Piedra, Mark; Allroggen, Achim; Lindner, Jonathan R

    2009-01-01

    Molecular imaging with contrast-enhanced ultrasound uses targeted microbubbles that are retained in diseased tissue. The resonant properties of these microbubbles produce acoustic signals in an ultrasound field. The microbubbles are targeted to diseased tissue by using certain chemical constituents in the microbubble shell or by attaching disease-specific ligands such as antibodies to the microbubble. In this review, we discuss the applications of this technique to pathological states in the cerebrovascular system including atherosclerosis, tumor angiogenesis, ischemia, intravascular thrombus, and inflammation. Copyright 2009 S. Karger AG, Basel.

  20. 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.)

  1. Iodinated contrast agent-induced nephropathy

    International Nuclear Information System (INIS)

    Erley, C.

    2007-01-01

    Contrast-induced nephropathy (CIN) is a well-known complication of therapeutic and diagnostic procedures requiring contrast administration and accounts for 10% of acute renal failure in hospitalized patients. Although the incidence of this complication is relatively low, its consequences can be catastrophic. The development of CIN is associated with increased length of hospital stay, an increased requirement for acute dialysis, and an increased risk of death. Preexisting renal dysfunction, age, diabetes, congestive heart failure, and volume of administered contrast are all associated with a risk of developing CIN. Despite a large number of clinical trials that have evaluated prophylaxis strategies for CIN, no uniform strategies have been developed so far. The use of N-acetyl-L-cysteine (NAC) or theophylline in specific subgroups of patients has been shown to reduce dialysis requirement and mortality in patients undergoing angiographic procedures. Hemofiltration has also shown positive results. In this review we will discuss the epidemiology and the risk factors for CIN and the evidence for commonly employed prophylaxis strategies, and we will provide general recommendations with respect to CIN prevention and management. A practicable strategy to prevent CIN includes: correct identification of individuals at greatest risk, thorough evaluation of whether other diagnostic maneuvers could be employed instead (i.e., sonography), application of low-osmolar contrast media at the minimum acceptable dose, stopping potential nephrotoxic drugs (NSAID), hydration with sodium chloride 0.9% 1 ml/kg per h i.v. 12 h before and after CM application, administration of acetylcysteine 600 mg twice the day before and after (in cases of emergency investigation and high-risk patients 1200 mg i.v.), and theophylline (250-350 mg) the day before and the day after CM application (in cases of emergency investigation 5 mg/kg i.v.). (orig.) [de

  2. 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.

  3. 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

  4. 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)

  5. 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)

  6. A model for ultrasound contrast agent in a phantom vessel

    KAUST Repository

    Qamar, Adnan; Samtaney, Ravi

    2014-01-01

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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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)

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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.)

  3. 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...

  4. 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...

  5. 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.)

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  14. 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

  15. Effervescent agents in the double contrast examination of the stomach

    International Nuclear Information System (INIS)

    Virkkunen, P.; Kreula, J.

    1981-01-01

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

  16. 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

  17. 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)

  18. Biological in situ characterization of polymeric microbubble contrast agents

    NARCIS (Netherlands)

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

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

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  5. [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.

  6. 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.

  7. 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

  8. 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

  9. Multi-Agent Cooperative Target Search

    Directory of Open Access Journals (Sweden)

    Jinwen Hu

    2014-05-01

    Full Text Available This paper addresses a vision-based cooperative search for multiple mobile ground targets by a group of unmanned aerial vehicles (UAVs with limited sensing and communication capabilities. The airborne camera on each UAV has a limited field of view and its target discriminability varies as a function of altitude. First, by dividing the whole surveillance region into cells, a probability map can be formed for each UAV indicating the probability of target existence within each cell. Then, we propose a distributed probability map updating model which includes the fusion of measurement information, information sharing among neighboring agents, information decay and transmission due to environmental changes such as the target movement. Furthermore, we formulate the target search problem as a multi-agent cooperative coverage control problem by optimizing the collective coverage area and the detection performance. The proposed map updating model and the cooperative control scheme are distributed, i.e., assuming that each agent only communicates with its neighbors within its communication range. Finally, the effectiveness of the proposed algorithms is illustrated by simulation.

  10. Novel targeted agents for gastric cancer

    Directory of Open Access Journals (Sweden)

    Liu Lian

    2012-06-01

    Full Text Available Abstract Contemporary advancements have had little impact on the treatment of gastric cancer (GC, the world’s second highest cause of cancer death. Agents targeting human epidermal growth factor receptor mediated pathways have been a common topic of contemporary cancer research, including monoclonal antibodies (mAbs and receptor tyrosine kinase inhibitors (TKIs. Trastuzumab is the first target agent evidencing improvements in overall survival in HER2-positive (human epidermal growth factor receptor 2 gastric cancer patients. Agents targeting vascular epithelial growth factor (VEGF, mammalian target of rapamycin (mTOR, and other biological pathways are also undergoing clinical trials, with some marginally positive results. Effective targeted therapy requires patient selection based on predictive molecular biomarkers. Most phase III clinical trials are carried out without patient selection; therefore, it is hard to achieve personalized treatment and to monitor patient outcome individually. The trend for future clinical trials requires patient selection methods based on current understanding of GC biology with the application of biomarkers.

  11. 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.

  12. 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.

  13. Beat frequency ultrasonic microsphere contrast agent detection system

    Science.gov (United States)

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

    1997-01-01

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

  14. Modified Gadonanotubes as a Promising Novel MRI Contrasting Agent

    OpenAIRE

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

    2013-01-01

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

  15. Delivery of Optical Contrast Agents using Triton-X100, Part 1: Reversible permeabilization of live cells for intracellular labeling

    OpenAIRE

    van de Ven, Anne L; Adler-Storthz, Karen; Richards-Kortum, Rebecca

    2009-01-01

    Effective delivery of optical contrast agents into live cells remains a significant challenge. We sought to determine whether Triton-X100, a detergent commonly used for membrane isolation and protein purification, could be used to effectively and reversibly permeabilize live cells for delivery of targeted optical contrast agents. Although Triton-X100 is widely recognized as a good cell permeabilization agent, no systematic study has evaluated the efficiency, reproducibility, and reversibility...

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

    Science.gov (United States)

    Zhao, Wenjing; Chen, Lina; Wang, Zhiming; Huang, Yuankui; Jia, Nengqin

    2018-02-01

    In pursuit of the biological detection applications, recent years have witnessed the prosperity of novel multi-modal nanoprobes. In this study, biocompatible bovine serum albumin (BSA)-coated gold nanoparticles (Au NPs) containing Gd (III) as the contrast agent for both X-ray CT and T1-weighted MR imaging is reported. Firstly, the Au NPs with BSA coating (Au@BSA) was prepared through a moderate one-pot reduction route in the presence of hydrazine hydrate as reducer. Sequentially, the BSA coating enables modification of diethylenetriaminepentaacetic acid (DTPA) as well as targeting reagent hyaluronic acid (HA), and further chelation of Gd (III) ions led to the formation of biomimetic nanoagent HA-targeted Gd-Au NPs (HA-targeted Au@BSA-Gd-DTPA). Several techniques were used to thoroughly characterize the formed HA-targeted Gd-Au NPs. As expected, the as-prepared nanoagent with mean diameter of 13.82 nm exhibits not only good colloid stablility and water dispersibility, but also satisfying low cytotoxicity and hemocompatibility in the tested concentration range. Additionally, for the CT phantoms, the obtained nanocomplex shows an improved contrast in CT scanning than that of Au@BSA as well as small molecule iodine-based CT contrast agents such as iopromide. Meanwhile, for the T1-weighted MRI images, there is a linear increase of contrast with concentration of Gd for the two cases of HA-targeted Gd-Au NPs and Magnevist. Strikingly, the nanoagent we explored displays a relatively higher r1 relaxivity than that of commercial MR contrast agents. Therefore, this newly constructed nanoagent could be used as contrast agents for synergistically enhanced X-ray CT and MR phantoms, holding promising potential for future biomedical applications.

  17. 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.

  18. 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})

  19. 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

  20. Tumor Vessel Compression Hinders Perfusion of Ultrasonographic Contrast Agents

    Directory of Open Access Journals (Sweden)

    Mirco Galiè

    2005-05-01

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

  1. Tumor Vessel Compression Hinders Perfusion of Ultrasonographic Contrast Agents1

    Science.gov (United States)

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

    2005-01-01

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

  2. Preclinical Studies of a Kidney Safe Iodinated Contrast Agent.

    Science.gov (United States)

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

    2016-09-01

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

  3. Erythrocytes as Carriers for Drugs and Contrast Agents

    Directory of Open Access Journals (Sweden)

    Mauro Magnani

    2014-01-01

    Full Text Available Erythrocytes, also known as Red Blood Cells (RBC, are typically used in transfusion medicine to replace lost blood in patients who underwent different kinds of medical treatments as well as those involved in accidents resulting in blood loss. In addition to these common uses, RBC are being used for a variety of new applications either as therapeutics or as diagnostics. Most of these novel approaches are made possible due to the peculiar properties of these cells. We have invented a technology that allows cells to be opened and resealed without affecting their main physiological characteristics with a minimal amount of patient blood.  Uses of processed RBCs in biomedical engineering include work with drugs, biomedical compounds and/or nanomaterials. These constructs are a new armamentarium available to the physicians for the release of drugs in circulation, for targeting drugs to selected sites in the body, or for in vivo diagnostic procedures based on magnetic and/or optical methods. Autologous human RBC loaded with dexamethasone (EryDex, a common corticosteroid,  have been used in the treatment of Cystic Fibrosis, Crohn’s Disease, and other severe inflammatory conditions. Benefits and safety of this technology have been documented in over 2,500 treatments. EryDel SpA is a company focused on developing and commercializing innovative therapies and diagnostics based on the use of autologous RBCs as agent carriers. More recently, EryDel SpA completed a Phase II Proof of Concept study in patients with Ataxia Telangiectasia (AT, a rare progressive neurological autosomal recessive disorder that leads to mortality in most patients at an early age, with significant benefit seen on primary and secondary end-points. EryDex treatment has received Orphan Drug Designation by EMA for the treatment of Cystic Fibrosis and both by EMA and FDA for the treatment of AT. The encapsulation of superparamagnetic nanoparticles within RBC has lead to the generation

  4. 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.

  5. Lipoprotein Nanoplatform for Targeted Delivery of Diagnostic and Therapeutic Agents

    Directory of Open Access Journals (Sweden)

    Jerry D. Glickson

    2008-03-01

    Full Text Available Low-density lipoprotein (LDL provides a highly versatile natural nanoplatform for delivery of visible or near-infrared fluorescent optical and magnetic resonance imaging (MRI contrast agents and photodynamic therapy and chemotherapeutic agents to normal and neoplastic cells that overexpress low-density lipoprotein receptors (LDLRs. Extension to other lipoproteins ranging in diameter from about 10 nm (high-density lipoprotein [HDL] to over a micron (chylomicrons is feasible. Loading of contrast or therapeutic agents onto or into these particles has been achieved by protein loading (covalent attachment to protein side chains, surface loading (intercalation into the phospholipid monolayer, and core loading (extraction and reconstitution of the triglyceride/cholesterol ester core. Core and surface loading of LDL have been used for delivery of optical imaging agents to tumor cells in vivo and in culture. Surface loading was used for delivery of gadolinium-bis-stearylamide contrast agents for in vivo MRI detection in tumor-bearing mice. Chlorin and phthalocyanine near-infrared photodynamic therapy agents (≤ 400/LDL have been attached by core loading. Protein loading was used to reroute the LDL from its natural receptor (LDLR to folate receptors and could be used to target other receptors. A semisynthetic nanoparticle has been constructed by coating magnetite iron oxide nanoparticles with carboxylated cholesterol and overlaying a monolayer of phospholipid to which apolipoprotein A1 or E was adsorbed for targeting HDL or adsorbing synthetic amphipathic helical peptides ltargeting LDL or folate receptors. These particles can be used for in situ loading of magnetite into cells for MRI-monitored cell tracking or gene expression.

  6. Development of microbubble contrast agents for high frequency ultrasound microscopy

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-05-15

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

  7. 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

  8. The usefulness of US with contrast agent on breast tumors

    International Nuclear Information System (INIS)

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

    2000-01-01

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

  9. A smart magnetic resonance contrast agent for selective copper sensing.

    Science.gov (United States)

    Que, Emily L; Chang, Christopher J

    2006-12-20

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

  10. Acoustic bubble sorting for ultrasound contrast agent enrichment.

    Science.gov (United States)

    Segers, Tim; Versluis, Michel

    2014-05-21

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

  11. Chemical warfare agents. Classes and targets.

    Science.gov (United States)

    Schwenk, Michael

    2018-09-01

    Synthetic toxic chemicals (toxicants) and biological poisons (toxins) have been developed as chemical warfare agents in the last century. At the time of their initial consideration as chemical weapon, only restricted knowledge existed about their mechanisms of action. There exist two different types of acute toxic action: nonspecific cytotoxic mechanisms with multiple chemo-biological interactions versus specific mechanisms that tend to have just a single or a few target biomolecules. TRPV1- and TRPA-receptors are often involved as chemosensors that induce neurogenic inflammation. The present work briefly surveys classes and toxicologically relevant features of chemical warfare agents and describes mechanisms of toxic action. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Magnetic nanoparticles as contrast agents for molecular imaging in medicine

    Science.gov (United States)

    O'Donnell, Matthew

    2018-05-01

    For over twenty years, superparamagnetic nanoparticles have been developed for a number of medical applications ranging from bioseparations, magnetic drug targeting, hyperthermia and imaging. Recent studies have shown that they can be functionalized for in vivo biological targeting, potentially enabling nanoagents for molecular imaging and site-localized drug delivery. Here we review several imaging technologies developed using functionalized superparamagnetic iron oxide nanoparticles (SPIONs) as targeted molecular agents. Several imaging modalities have exploited the large induced magnetic moment of SPIONs to create local mechanical force. Magnetic force microscopy can probe nanoparticle uptake in single cells. For in vivo applications, magnetomotive modulation of primary images in ultrasound (US), photoacoustics (PA), and optical coherence tomography (OCT) can help identify very small concentrations of nanoagents while simultaneously suppressing intrinsic background signals from tissue.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-12-01

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

  15. Viscosity of iodinated contrast agents during renal excretion

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  16. Viscosity of iodinated contrast agents during renal excretion

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-11-15

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

  17. Quinone-fused porphyrins as contrast agents for photoacoustic imaging

    KAUST Repository

    Banala, Srinivas

    2017-06-27

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

  18. 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 ...

  19. Contrast agents for tumor diagnosis in magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-01-01

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

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

    Science.gov (United States)

    Versluis, Michel; Kok, Maarten; Segers, Tim

    2014-11-01

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

  1. 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)

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

    Science.gov (United States)

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

    2014-03-01

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

  3. 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

  4. Tracers and contrast agents in cardiovascular imaging: present and future

    International Nuclear Information System (INIS)

    Marmion, M.; Deutsch, E.

    1996-01-01

    This brief article addresses the current status and future potential of nuclear medicine, X-ray computed tomography (CT), ultrasound (US), and magnetic resonance (MR) imaging in the diagnosis of cardiovascular diseases. The currently perceived advantages and disadvantages, as well as the possible future roles, of each of the modalities with regard to the evaluation of coronary artery disease are delineated. The certain advent of Mr and US myocardial contrast agents, combined with the inexorable pressures of health care reform, will alter the future usage patterns of all four modalities. Future debates about which modality should be used in which clinical situation will be based not on 'anatomy vs function', nor on the issues of cost effectiveness and patient outcomes

  5. Magnetic susceptibility imaging with a nonionic contrast agent

    International Nuclear Information System (INIS)

    Cacheris, W.; Rocklage, S.M.; Quay, S.; Dow, W.; Love, D.; Worah, D.; Lim, K.

    1988-01-01

    The magnetic susceptibility mechanism for MR imaging contrast enhancement has the advantage of providing useful information, such as cerebral blood flow, without crossing the blood-brain barrier. In this paper the authors report the use of a highly effective, relatively nontoxic chelate as a magnetic susceptibility agent. Dy-DTPA-bis(methylamide) (Dy-DTPA-BMA) has an extremely low acute toxicity (LD-50, intravenous, mice ∼ 40 mmol/kg). Doses of 1 mmol/kg and 2 mmol/kg Dy-DTPA-BMA lowered the initial signal intensity 63% to 57%, respectively. The utility of this technique in detecting areas of reduced blood flow within the brain was demonstrated by imaging a rabbit with a cerebral perfusion deficit

  6. A model for ultrasound contrast agent in a phantom vessel

    KAUST Repository

    Qamar, Adnan

    2014-02-01

    A theoretical framework to model the dynamics of Ultrasound Contrast Agent (UCA) inside a phantom vessel is presented. The model is derived from the reduced Navier-Stokes equation and is coupled with the evolving flow field solution inside the vessel by a similarity transformation approach. The results are computed, and compared with experiments available in literature, for the initial UCA radius of Ro=1.5 μm and 2 μm for the vessel diameter of D=12 μm and 200 μm with the acoustic parameters as utilized in the experiments. When compared to other models, better agreement on smaller vessel diameter is obtained with the proposed coupled model. The model also predicts, quite accurately, bubble fragmentation in terms of acoustic and geometric parameters. © 2014 IEEE.

  7. 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

  8. The use of contrast agent for imaging biological samples

    Energy Technology Data Exchange (ETDEWEB)

    Dammer, J; Sopko, V; Jakubek, J [Institute of Experimental and Applied Physics, Czech Technical University in Prague, Horska 3a/22, CZ 12800 Prague 2 (Czech Republic); Weyda, F, E-mail: jiri.dammer@utef.cvut.cz [Biological center of the Academy of Sciences of the Czech Republic, Institute of Entomology, Branisovska 31, CZ-37005 Ceske Budejovice (Czech Republic)

    2011-01-15

    The technique of X-ray transmission imaging has been available for over a century and is still among the fastest and easiest approaches to the studies of internal structure of biological samples. Recent advances in semiconductor technology have led to the development of new types of X-ray detectors with direct conversion of interacting X-ray photon to an electric signal. Semiconductor pixel detectors seem to be specially promising; compared to the film technique, they provide single-quantum and real-time digital information about the objects being studied. We describe the recently developed radiographic apparatus, equipped with Medipix2 semiconductor pixel detector. The detector is used as an imager that counts individual photons of ionizing radiation, emitted by an X-ray tube (micro- or nano-focus FeinFocus). Thanks to the wide dynamic range of the Medipix2 detector and its high spatial resolution better than 1{mu}m, the setup is particularly suitable for radiographic imaging of small biological samples, including in-vivo observations with contrast agent (Optiray). Along with the description of the apparatus we provide examples of the use iodine contrast agent as a tracer in various insects as model organisms. The motivation of our work is to develop our imaging techniques as non-destructive and non-invasive. Microradiographic imaging helps detect organisms living in a not visible environment, visualize the internal biological processes and also to resolve the details of their body (morphology). Tiny live insects are an ideal object for our studies.

  9. 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...

  10. 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.)

  11. 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.

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

    Science.gov (United States)

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

    2018-05-01

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

  13. Are gadolinium contrast agents suitable for gadolinium neutron capture therapy?

    Science.gov (United States)

    De Stasio, Gelsomina; Rajesh, Deepika; Casalbore, Patrizia; Daniels, Matthew J; Erhardt, Robert J; Frazer, Bradley H; Wiese, Lisa M; Richter, Katherine L; Sonderegger, Brandon R; Gilbert, Benjamin; Schaub, Sebastien; Cannara, Rachel J; Crawford, John F; Gilles, Mary K; Tyliszczak, Tolek; Fowler, John F; Larocca, Luigi M; Howard, Steven P; Mercanti, Delio; Mehta, Minesh P; Pallini, Roberto

    2005-06-01

    Gadolinium neutron capture therapy (GdNCT) is a potential treatment for malignant tumors based on two steps: (1) injection of a tumor-specific (157)Gd compound; (2) tumor irradiation with thermal neutrons. The GdNC reaction can induce cell death provided that Gd is proximate to DNA. Here, we studied the nuclear uptake of Gd by glioblastoma (GBM) tumor cells after treatment with two Gd compounds commonly used for magnetic resonance imaging, to evaluate their potential as GdNCT agents. Using synchrotron X-ray spectromicroscopy, we analyzed the Gd distribution at the subcellular level in: (1) human cultured GBM cells exposed to Gd-DTPA or Gd-DOTA for 0-72 hours; (2) intracerebrally implanted C6 glioma tumors in rats injected with one or two doses of Gd-DOTA, and (3) tumor samples from GBM patients injected with Gd-DTPA. In cell cultures, Gd-DTPA and Gd-DOTA were found in 84% and 56% of the cell nuclei, respectively. In rat tumors, Gd penetrated the nuclei of 47% and 85% of the tumor cells, after single and double injection of Gd-DOTA, respectively. In contrast, in human GBM tumors 6.1% of the cell nuclei contained Gd-DTPA. Efficacy of Gd-DTPA and Gd-DOTA as GdNCT agents is predicted to be low, due to the insufficient number of tumor cell nuclei incorporating Gd. Although multiple administration schedules in vivo might induce Gd penetration into more tumor cell nuclei, a search for new Gd compounds with higher nuclear affinity is warranted before planning GdNCT in animal models or clinical trials.

  14. 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

  15. 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

  16. Combining Targeted Agents With Modern Radiotherapy in Soft Tissue Sarcomas

    Science.gov (United States)

    Wong, Philip; Houghton, Peter; Kirsch, David G.; Finkelstein, Steven E.; Monjazeb, Arta M.; Xu-Welliver, Meng; Dicker, Adam P.; Ahmed, Mansoor; Vikram, Bhadrasain; Teicher, Beverly A.; Coleman, C. Norman; Machtay, Mitchell; Curran, Walter J.

    2014-01-01

    Improved understanding of soft-tissue sarcoma (STS) biology has led to better distinction and subtyping of these diseases with the hope of exploiting the molecular characteristics of each subtype to develop appropriately targeted treatment regimens. In the care of patients with extremity STS, adjunctive radiation therapy (RT) is used to facilitate limb and function, preserving surgeries while maintaining five-year local control above 85%. In contrast, for STS originating from nonextremity anatomical sites, the rate of local recurrence is much higher (five-year local control is approximately 50%) and a major cause of death and morbidity in these patients. Incorporating novel technological advancements to administer accurate RT in combination with novel radiosensitizing agents could potentially improve local control and overall survival. RT efficacy in STS can be increased by modulating biological pathways such as angiogenesis, cell cycle regulation, cell survival signaling, and cancer-host immune interactions. Previous experiences, advancements, ongoing research, and current clinical trials combining RT with agents modulating one or more of the above pathways are reviewed. The standard clinical management of patients with STS with pretreatment biopsy, neoadjuvant treatment, and primary surgery provides an opportune disease model for interrogating translational hypotheses. The purpose of this review is to outline a strategic vision for clinical translation of preclinical findings and to identify appropriate targeted agents to combine with radiotherapy in the treatment of STS from different sites and/or different histology subtypes. PMID:25326640

  17. 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)

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

    Science.gov (United States)

    Bader, Kenneth B; Holland, Christy K

    2013-01-07

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

  19. Balancing stealth and echogenic properties in an ultrasound contrast agent with drug delivery potential.

    Science.gov (United States)

    Jablonowski, Lauren J; Alfego, David; Andorko, James I; Eisenbrey, John R; Teraphongphom, Nutte; Wheatley, Margaret A

    2016-10-01

    Contrast agents are currently being modified to combine diagnostic and therapeutic capabilities. For ultrasound (US) imaging with polymeric contrast agents, it is necessary to modify the shell to create "stealth" microbubbles but without these modifications sacrificing the agent's ability to interact with the focused US beam. We hypothesize that addition of the classic immune shielding molecule polyethylene glycol (PEG) to a polylactide (PLA) microbubble shell will affect the acoustic and physical properties of the resulting agents. In an effort to determine the best formulation to achieve a balance between stealth and acoustic activity, we compared two PEGylation techniques; addition of increasing amounts of PEG-PLA copolymer and employing incorporation of a PEG lipid (LipidPEG) into the shell. Loss of acoustic enhancement occurred in a dose-dependent manner for both types of PEGylated agents (loss of signal occurred at >5 wt% PEG-PLA and >1 wt% LipidPEG), while immune activation was also reduced in a dose-dependent manner for the PEG-PLA agents. This study shows that the balance between acoustic behavior and improved immune avoidance was scalable and successful to different degrees with both PEGylation methods, and was best achieved using for PEG-PLA at 5 wt% and for LipidPEG at 1 wt%. Studies are ongoing to evaluate the best method for the targeting and drug delivery capabilities of these agents for applications in cancer treatment. This study represents the basis for understanding the consequences of making modifications to the native polymeric shell. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Can aquatic macrophytes be biofilters for gadolinium based contrasting agents?

    Science.gov (United States)

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

    2018-05-15

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

  1. 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.

  2. 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

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

    Directory of Open Access Journals (Sweden)

    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

  4. 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.

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  6. The use of new contrast media agents in radiology

    International Nuclear Information System (INIS)

    Zerbe, M.

    1992-01-01

    The purpose of the document is to present the importance of different categories of contrast media in radiography. Ionic and non-ionic contrast media are presented. Pharmacology and pathophysiology of Iodine contrast media with their effects on special organs of the body like the heart, vessels, lungs and nervous systems are explained. Paramagnetic contrast media used in NMR imaging are presented too. Emphasis is made on contrast media based on Gadolinium like Gd-DTPA, Gd-CL3, Gd-EDTA. Actions of Gd-DTPA applied to images in urography are pointed out

  7. 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

  8. Ultrasonic microbubble contrast agents and the transplant kidney

    Energy Technology Data Exchange (ETDEWEB)

    Kay, D.H., E-mail: davidhkay@doctors.org.u [Department of Radiology, Western Infirmary, Glasgow (United Kingdom); Mazonakis, M.; Geddes, C. [Department of Renal Medicine, Western Infirmary, Glasgow (United Kingdom); Baxter, G. [Department of Radiology, Western Infirmary, Glasgow (United Kingdom)

    2009-11-15

    Aim: To evaluate the potential application of microbubble agents in the immediate post-transplant period, by studying contrast uptake and washout, and to correlate these values with clinical indices, and thus, assess the potential prognostic value of this technique. Materials and methods: The study group comprised 20 consecutive renal transplant patients within 7 days of transplantation. Sonovue was administered as an intravenous bolus with continuous imaging of the transplant kidney at low mechanical index (MI) for 1 min post-injection. These data were analysed off-line by two observers, and time intensity curves (TIC) for the upper, mid, and lower poles constructed. Within each pole, a region of interest (5 mm square) was placed over the cortex, medullary pyramid, and interlobar artery, resulting in a total of nine TIC for each patient. TIC parameters included the arrival time (AT), time to peak (TTP), peak intensity (Max), gradient of the slope (M), and the area under curve (AUC). Results: For both observers there was good agreement for all values measured from the cortex and medulla, but poor interobserver correlation for the vascular values. In addition, there was only agreement for these values in the upper and mid-pole of the transplant with poor agreement for the lower pole values. The mid-pole of the transplant kidney was chosen as the point of measurement for subsequent studies. Mid-pole values were correlated with clinical data and outcome over the 3-month post-transplant period. Renal microbubble perfusion correlated with the transplant estimated glomerular filtration rate (eGFR) at 3 months post-transplantation (p = 0.016). Discussion: In conclusion, this is the first study to confirm reproducibility of the Sonovue TIC data in transplant patients and to quantify regional variation and perfusion. The statistically significant estimates of transplant perfusion may be of future benefit to transplant recipients and potentially utilized as a prognostic tool

  9. 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)

  10. 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

  11. 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.

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

    Science.gov (United States)

    Pablico, Michele Huelar

    also directed at developing metal-oxo containing hybrid materials using first row transition metals with potential catalytic and magnetic properties as well. We report several screened metal-oxo clusters but this study has centered on the mixed-metal oxo cluster, Mn8Fe4O 12(O2CCH3)16(H2O)4 or Mn8Fe4, mainly because it is highly paramagnetic and is soluble and stable in water. The cluster was screened for potential MRI contrast and was found to be a very promising T2 contrast agent with relaxivity values of r1 = 2.3 mM-1s -1 and r2 = 29.5 mM-1s-1. Initial cell studies on two human prostate cancer cell lines, DU-145 and LNCap, reveal that the cluster has low cytotoxicity and may be potentially used in vivo. One key advantage of Mn8Fe4 is its ability to undergo ligand exchange reactions, thus providing a mechanism for grafting to a variety of supports. By substituting the acetate groups on Mn8Fe4 with polymerizable ligands, we are able to form monodisperse magnetic polymer nanobeads (˜70 nm diameter) via the miniemulsion polymerization technique. To render the nanobead suitable for future in vivo experiments, we coated the surface with biocompatible polysaccharide dextran (40 kDa). Interestingly, relaxivity measurements and MRI studies show that encapsulating the Mn8Fe4 core within a polymer matrix decreased T 2 effects resulting in a positive T1 contrast enhancement. The resulting hybrid particles have the potential for further surface functionalization (i.e., therapeutic drugs, targeting moiety, fluorescent probe, etc.) making them a promising tool for biomedicine.

  13. Intravenous carbon dioxide as an echocardiographic contrast agent

    NARCIS (Netherlands)

    R.S. Meltzer (Richard); P.W.J.C. Serruys (Patrick); P.G. Hugenholtz (Paul); J.R.T.C. Roelandt (Jos)

    1981-01-01

    textabstractIntravenous carbon dioxide (CO2) was employed to cause echocardiographic contrast in 40 patients. One to 3 cc of medically pure CO2 were agitated with 5 to 8 cc of 5% dextrose in water and rapidly injected into an upper extremity vein. Contrast was obtained in all patients. In 33

  14. Acoustic scattering from a contrast agent microbubble near an elastic wall of finite thickness

    International Nuclear Information System (INIS)

    Doinikov, Alexander A; Aired, Leila; Bouakaz, Ayache

    2011-01-01

    Interest in the problem under consideration in this study is motivated by targeted ultrasound imaging where one has to deal with microbubble contrast agents pulsating near blood vessel walls. A modified Rayleigh–Plesset equation is derived that describes the oscillation of a contrast agent microbubble near an elastic wall of finite thickness. It is assumed that the medium behind the wall is a fluid but it is shown that the equation obtained is easily transformable to the case that the medium behind the wall is an elastic solid. In contrast to the model of a rigid wall, which predicts decreasing natural frequency of a bubble near the wall, the elastic wall model reveals that the bubble natural frequency can both decrease and increase, and in cases of interest for medical applications, the bubble natural frequency usually increases. It is found that the influence of an elastic wall on the acoustic response of a bubble is determined by the ratio between a cumulative parameter, which integrally characterizes the mechanical properties of the wall and has the dimension of density, and the density of the liquid surrounding the bubble. It is shown that the acoustic influence of the arterial wall on the bubble is weak and apparently cannot be used to recognize the moment when the bubble approaches the wall. However, in experiments where the behavior of bubbles near various plastic walls is observed, changes in the bubble response, such as increasing natural frequency and decreasing oscillation amplitude, are detectable.

  15. 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

  16. Engineering of Nanoscale Contrast Agents for Optical Coherence Tomography.

    Science.gov (United States)

    Gordon, Andrew Y; Jayagopal, Ashwath

    2014-01-30

    Optical coherence tomography has emerged as valuable imaging modalityin ophthalmology and other fields by enabling high-resolution three-dimensional imaging of tissue. In this paper, we review recent progress in the field of contrast-enhanced optical coherence tomography (OCT). We discuss exogenous and endogenous sources of OCT contrast, focusing on their use with standard OCT systems as well as emerging OCT-based imaging modalities. We include advances in the processing of OCT data that generate improved tissue contrast, including spectroscopic OCT (SOCT), as well as work utilizing secondary light sources and/or detection mechanisms to create and detect enhanced contrast, including photothermal OCT (PTOCT) and photoacoustic OCT (PAOCT). Finally, we conclude with a discussion of the translational potential of these developments as well as barriers to their clinical use.

  17. Cooperative target convergence using multiple agents

    International Nuclear Information System (INIS)

    Kwok, K.S.; Driessen, B.J.

    1997-01-01

    This work considers the problem of causing multiple (100''s) autonomous mobile robots to converge to a target and provides a follow-the-leader approach to the problem. Each robot has only a limited-range sensor for sending the target and also larger but also limited-range robot-to-robot communication capability. Because of the small amount of information available to the robots, a practical approach to improve convergence to the target is to have a robot follow the robot with the best quality of information. Specifically, each robot emits a signal that informs in-range robots what its status is. A robot has a status value of 0 if it is itself in range of the target. A robot has a status of 1 if it is not in range of the target but is in communication range of a robot that is in range of the target. A robot has a status of 2 if it is not in range of the target but is within range of another robot that has status 1, and so on. Of all the mobile robots that any given robot is in range of, it follows the one with the best status. The emergent behavior is the ant-like trails of robots following each other toward the target. If the robot is not in range of another robot that is either in range of the target or following another robot, the robot will assign-1 to its quality-of-information, and will execute an exhaustive search. The exhaustive search will continue until it encounters either the target or another robot with a nonnegative quality-of-information. The quality of information approach was extended to the case where each robot only has two-bit signals informing it of distance to in-range robots

  18. Cooperative target convergence using multiple agents

    Energy Technology Data Exchange (ETDEWEB)

    Kwok, K.S.; Driessen, B.J.

    1997-10-01

    This work considers the problem of causing multiple (100`s) autonomous mobile robots to converge to a target and provides a follow-the-leader approach to the problem. Each robot has only a limited-range sensor for sending the target and also larger but also limited-range robot-to-robot communication capability. Because of the small amount of information available to the robots, a practical approach to improve convergence to the target is to have a robot follow the robot with the best quality of information. Specifically, each robot emits a signal that informs in-range robots what its status is. A robot has a status value of 0 if it is itself in range of the target. A robot has a status of 1 if it is not in range of the target but is in communication range of a robot that is in range of the target. A robot has a status of 2 if it is not in range of the target but is within range of another robot that has status 1, and so on. Of all the mobile robots that any given robot is in range of, it follows the one with the best status. The emergent behavior is the ant-like trails of robots following each other toward the target. If the robot is not in range of another robot that is either in range of the target or following another robot, the robot will assign-1 to its quality-of-information, and will execute an exhaustive search. The exhaustive search will continue until it encounters either the target or another robot with a nonnegative quality-of-information. The quality of information approach was extended to the case where each robot only has two-bit signals informing it of distance to in-range robots.

  19. 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

  20. 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....

  1. 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)....

  2. 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)

  3. Influence of hyperosmotic agent (glycerol) in contrast enhancement

    International Nuclear Information System (INIS)

    Moriyama, Takashi; Suzuki, Shigeharu; Nakaoka, Tsutomu

    1981-01-01

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

  4. 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.

  5. 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)

  6. 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

  7. Strategies for sensing neurotransmitters with responsive MRI contrast agents.

    Science.gov (United States)

    Angelovski, Goran; Tóth, Éva

    2017-01-23

    A great deal of research involving multidisciplinary approaches is currently dedicated to the understanding of brain function. The complexity of physiological processes that underlie neural activity is the greatest hurdle to faster advances. Among imaging techniques, MRI has great potential to enable mapping of neural events with excellent specificity, spatiotemporal resolution and unlimited tissue penetration depth. To this end, molecular imaging approaches using neurotransmitter-sensitive MRI agents have appeared recently to study neuronal activity, along with the first successful in vivo MRI studies. Here, we review the pioneering steps in the development of molecular MRI methods that could allow functional imaging of the brain by sensing the neurotransmitter activity directly. We provide a brief overview of other imaging and analytical methods to detect neurotransmitter activity, and describe the approaches to sense neurotransmitters by means of molecular MRI agents. Based on these initial steps, further progress in probe chemistry and the emergence of innovative imaging methods to directly monitor neurotransmitters can be envisaged.

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

    Science.gov (United States)

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

    2017-04-01

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

  9. Mitochondrially targeted anti-cancer agents

    Czech Academy of Sciences Publication Activity Database

    Biasutto, L.; Dong, L.A.; Zoratti, M.; Neužil, Jiří

    2010-01-01

    Roč. 10, č. 6 (2010), s. 670-681 ISSN 1567-7249 Institutional research plan: CEZ:AV0Z50520701 Keywords : Mitochondrial targeting * pro-oxidant effect * reactive oxygen species Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.238, year: 2010

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

    Science.gov (United States)

    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.

  11. High Relaxivity Gadolinium Hydroxypyridonate-Viral Capsid Conjugates: Nano-sized MRI Contrast Agents

    Energy Technology Data Exchange (ETDEWEB)

    Meux, Susan C.; Datta, Ankona; Hooker, Jacob M.; Botta, Mauro; Francis, Matthew B.; Aime, Silvio; Raymond, Kenneth N.

    2007-08-29

    High relaxivity macromolecular contrast agents based on the conjugation of gadolinium chelates to the interior and exterior surfaces of MS2 viral capsids are assessed. The proton nuclear magnetic relaxation dispersion (NMRD) profiles of the conjugates show up to a five-fold increase in relaxivity, leading to a peak relaxivity (per Gd{sup 3+} ion) of 41.6 mM{sup -1}s{sup -1} at 30 MHz for the internally modified capsids. Modification of the exterior was achieved through conjugation to flexible lysines, while internal modification was accomplished by conjugation to relatively rigid tyrosines. Higher relaxivities were obtained for the internally modified capsids, showing that (1) there is facile diffusion of water to the interior of capsids and (2) the rigidity of the linker attaching the complex to the macromolecule is important for obtaining high relaxivity enhancements. The viral capsid conjugated gadolinium hydroxypyridonate complexes appear to possess two inner-sphere water molecules (q = 2) and the NMRD fittings highlight the differences in the local motion for the internal ({tau}{sub RI} = 440 ps) and external ({tau}{sub RI} = 310 ps) conjugates. These results indicate that there are significant advantages of using the internal surface of the capsids for contrast agent attachment, leaving the exterior surface available for the installation of tissue targeting groups.

  12. 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.

  13. Magnetosomes used as biogenic MRI contrast agent for molecular imaging of glioblastoma model

    International Nuclear Information System (INIS)

    Boucher, Marianne

    2016-01-01

    This work takes place in the context of molecular imaging, which aims at tailoring medical treatments and therapies to the individual context by revealing molecular or cellular phenomenon of medical interest in the less invasive manner. In particular, it can be achieved with MRI molecular imaging using engineered iron-oxide contrast agent.This PhD thesis focuses on the study of a new class of iron-oxide contrast agent for high field MRI. Indeed, magnetosomes are natural iron-oxide vesicles produced by magneto-tactic bacteria. These bacteria synthesized such magnetic vesicles and ordered them like a nano-compass in order to facilitate their navigation in sediments. This explains why magnetosomes are awarded with tremendous magnetic properties: around 50 nm, mono-crystalline, single magnetic domain and high saturation magnetization. Furthermore, a wide variety of bacterial strains exist in nature and size and shape of magnetosomes are highly stable within strain and can be very different between strains. Finally, magnetosomes are naturally coated with a bi-lipidic membrane whose content is genetically determined. Lately, researchers have unravelled magnetosomes membrane protein contents, opening the way to create functionalized magnetosomes thanks to fusion of the gene coding for a protein of interest with the gene coding for an abundant protein at magnetosomes membrane.A new alternative path using living organisms to tackle the production of engineered high efficiency molecular imaging probes have been investigated with magneto-tactic bacteria in this PhD. The production and engineering of magnetosomes have been carried out by our partner, the Laboratoire de Bio-energetique Cellulaire (LBC, CEA Cadarache), and will be presented and discussed. We then characterized magnetosomes as contrast agent for high field MRI. We showed they present very promising contrasting properties in vitro, and assessed this observation in vivo by establishing they can be used as efficient

  14. Nitric oxide: cancer target or anticancer agent?

    Science.gov (United States)

    Mocellin, Simone

    2009-03-01

    Despite the improved understanding of nitric oxide (NO) biology and the large amount of preclinical experiments testing its role in cancer development and progression, it is still debated whether NO should be considered a potential anticancer agent or instead a carcinogen. The complexity of NO effects within a cell and the variability of the final biological outcome depending upon NO levels makes it highly challenging to determine the therapeutic value of interfering with the activity of this intriguing gaseous messenger. This uncertainty has so far halted the clinical implementation of NO-based therapeutics in the field of oncology. Accordingly, only an in depth knowledge of the mechanisms leading to experimental tumor regression or progression in response to NO will allow us to exploit this molecule to fight cancer.

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

    Science.gov (United States)

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

    2017-04-01

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

  16. 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

  17. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-12-15

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

  19. 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.)

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

    Directory of Open Access Journals (Sweden)

    Daniel J. Korchinski

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  2. 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).

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

    Science.gov (United States)

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

    2006-10-03

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

  4. 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

  5. Macromolecular contrast agents for MR mammography: current status

    International Nuclear Information System (INIS)

    Daldrup-Link, Heike E.; Brasch, Robert C.

    2003-01-01

    Macromolecular contrast media (MMCM) encompass a new class of diagnostic drugs that can be applied with dynamic MRI to extract both physiologic and morphologic information in breast lesions. Kinetic analysis of dynamic MMCM-enhanced MR data in breast tumor patients provides useful estimates of tumor blood volume and microvascular permeability, typically increased in cancer. These tumor characteristics can be applied to differentiate benign from malignant lesions, to define the angiogenesis status of cancers, and to monitor tumor response to therapy. The most immediate challenge to the development of MMCM-enhanced mammography is the identification of those candidate compounds that demonstrate the requisite long intravascular distribution and have the high tolerance necessary for clinical use. Potential mammographic applications and limitations of various MMCM, defined by either experimental animal testing or clinical testing in patients, are reviewed in this article. (orig.)

  6. 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)

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

    National Research Council Canada - National Science Library

    Josephson, Lee

    2004-01-01

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

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

    DEFF Research Database (Denmark)

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

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

  9. 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.

  10. 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

  11. 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

  12. 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.

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

    DEFF Research Database (Denmark)

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

    1998-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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

  15. Impact of gadolinium-based contrast agent in the assessment of Crohn's disease activity: Is contrast agent injection necessary?

    Science.gov (United States)

    Quaia, Emilio; Sozzi, Michele; Gennari, Antonio Giulio; Pontello, Michele; Angileri, Roberta; Cova, Maria Assunta

    2016-03-01

    To determine whether magnetic resonance enterography (MRE) performed without intravenous contrast injection is diagnostically noninferior to conventional contrast-enhanced MRE (CE-MRE) in patients with Crohn's disease (CD). This was an Institutional Review Board (IRB)-approved retrospective study. Ninety-six patients (52 male and 44 female; 47.18 years ± 13.6) with a diagnosis of CD underwent MRE at 1.5T including T2 -weighted single-shot turbo-spin-echo, T2 -weighted spectral fat presaturation with inversion recovery (SPAIR), T1 -weighted balanced fast-field-echo MR sequences, and CE-MRE consisting in T1 -weighted breath-hold THRIVE 3D MRI sequences after administration of gadobenate dimeglumine (0.2 mL/kg of body weight). Unenhanced MRE, CE-MRE, and unenhanced MRE plus CE-MRE were reviewed in separate sessions with blinding by two readers in consensus, and subsequently by two other readers independently considering a subgroup of 20 patients. Crohn's Disease Endoscopic Index of Severity (CDEIS) and/or histologic analysis of the surgical specimen were considered as reference standards for the assessment of inflammatory activity. Patients revealed prevalently active (n = 55 patients) or quiescent CD (n = 41 patients). The agreement between unenhanced MRE vs. CE-MRE in interpreting active bowel inflammation was 96% (123/128 bowel segments; one-sided 95% confidence interval [CI], >94.4%). Unenhanced MRE vs. CE-MRE vs. unenhanced MRE plus CE-MRE revealed a diagnostic accuracy of 93% [90/96] vs. 92% [88/96] vs. 97% [93/96] (P > 0.05) in the diagnosis of active CD. Interreader agreement was very good for all variables (κ value = 0.8-0.9) except for the measurement of the length of disease (κ value = 0.45). Unenhanced MRE was noninferior to CE-MRE in diagnosing active inflammation in patients with CD. © 2015 Wiley Periodicals, Inc.

  16. 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.

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

    International Nuclear Information System (INIS)

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

    2003-01-01

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

  18. Possible targets for the aneugenic activity of alkylating agents

    Energy Technology Data Exchange (ETDEWEB)

    Pellerano, P. [IST-National Institute for Research on Cancer, Genova (Italy); Abbondandolo, A. [Univ. of Genova (Italy); Bonatti, S.; Simili, M. [CNR Institute of Mutagenesis and Differentiation, Pisa (Italy)

    1993-12-31

    Alkylating agents have been of invaluable help in mutation research for half a century. In all tested organisms, they have proved able to induce a large variety of genetic effects, including aneuploidy. Credible molecular models exist to explain the ability of alkylating agents to induce gene mutation and to act as initiators in carcinogenesis as a consequence of DNA alkylation at specific sites. On the contrary, neither the mechanism of aneuploidy induction nor the relevant cellular targets are known.

  19. Targeted Anticancer Immunotoxins and Cytotoxic Agents with Direct Killing Moieties

    Directory of Open Access Journals (Sweden)

    Koji Kawakami

    2006-01-01

    Full Text Available Despite the progress of the bioinformatics approach to characterize cell-surface antigens and receptors on tumor cells, it remains difficult to generate novel cancer vaccines or neutralizing monoclonal antibody therapeutics. Among targeted cancer therapeutics, biologicals with targetable antibodies or ligands conjugated or fused to toxins or chemicals for direct cell-killing ability have been developed over the last 2 decades. These conjugated or fused chimeric proteins are termed immunotoxins or cytotoxic agents. Two agents, DAB389IL-2 (ONTAKTM targeting the interleukin-2 receptor and CD33-calicheamicin (Mylotarg®, have been approved by the FDA for cutaneous T-cell lymphoma (CTCL and relapsed acute myeloid leukemia (AML, respectively. Such targetable agents, including RFB4(dsFv-PE38 (BL22, IL13-PE38QQR, and Tf-CRM107, are being tested in clinical trials. Several agents using unique technology such as a cleavable adapter or immunoliposomes with antibodies are also in the preclinical stage. This review summarizes the generation, mechanism, and development of these agents. In addition, possible future directions of this therapeutic approach are discussed.

  20. A Novel Polyacrylamide Magnetic Nanoparticle Contrast Agent for Molecular Imaging using MRI

    Directory of Open Access Journals (Sweden)

    Bradford A. Moffat

    2003-10-01

    Full Text Available A novel Polyacrylamide superparamagnetic iron oxide nanoparticle platform is described which has been synthetically prepared such that multiple crystals of iron oxide are encapsulated within a single Polyacrylamide matrix (PolyAcrylamide Magnetic [PAM] nanoparticles. This formulation provides for an extremely large T2 and T2* relaxivity of between 620 and 1140 sec−1 mM−1. Administration of PAM nanoparticles into rats bearing orthotopic 9L gliomas allowed quantitative pharmacokinetic analysis of the uptake of nanoparticles in the vasculature, brain, and glioma. Addition of polyethylene glycol of varying sizes (0.6, 2, and 10 kDa to the surface of the PAM nanoparticles resulted in an increase in plasma half-life and affected tumor uptake and retention of the nanoparticles as quantified by changes in tissue contrast using MRI. The flexible formulation of these nanoparticles suggests that future modifications could be accomplished allowing for their use as a targeted molecular imaging contrast agent and/or therapeutic platform for multiple indications.

  1. Porphyrin-containing polyaspartamide gadolinium complexes as potential magnetic resonance imaging contrast agents.

    Science.gov (United States)

    Yan, Guo-Ping; Li, Zhen; Xu, Wei; Zhou, Cheng-Kai; Yang, Lian; Zhang, Qiao; Li, Liang; Liu, Fan; Han, Lin; Ge, Yuan-Xing; Guo, Jun-Fang

    2011-04-04

    Porphyrin-containing polyaspartamide ligands (APTSPP-PHEA-DTPA) were synthesized by the incorporation of diethylenetriaminepentaacetic acid (DTPA) and 5-(4'-aminophenyl)-10,15,20-tris(4'-sulfonatophenyl) porphyrin, trisodium salt (APTSPP) into poly-α,β-[N-(2-hydroxyethyl)-l-aspartamide] (PHEA). These ligands were further reacted with gadolinium chloride to produce macromolecule-gadolinium complexes (APTSPP-PHEA-DTPA-Gd). Experimental data of (1)H NMR, IR, UV and elemental analysis evidenced the formation of the polyaspartamide ligands and gadolinium complexes. In vitro and in vivo property tests indicated that APTSPP-PHEA-DTPA-Gd possessed noticeably higher relaxation effectiveness, less toxicity to HeLa cells, and significantly higher enhanced signal intensities (SI) of the VX2 carcinoma in rabbits with lower injection dose requirement than that of Gd-DTPA. Moreover, APTSPP-PHEA-DTPA-Gd was found to greatly enhance the contrast of MR images of the VX2 carcinoma, providing prolonged intravascular duration, and distinguished the VX2 carcinoma and normal tissues in rabbits according to MR image signal enhancements. These porphyrin-containing polyaspartamide gadolinium complexes can be used as the candidates of contrast agents for targeted MRI to tumors. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  2. [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.

  3. 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.)

  4. 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.

  5. 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.

  6. 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.

  7. 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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    International Nuclear Information System (INIS)

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

    1980-01-01

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

  10. 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.)

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-01-15

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

  18. Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

    Science.gov (United States)

    Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M

    2016-05-05

    Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared - non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.

  19. Agent Collaborative Target Localization and Classification in Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Sheng Wang

    2007-07-01

    Full Text Available Wireless sensor networks (WSNs are autonomous networks that have beenfrequently deployed to collaboratively perform target localization and classification tasks.Their autonomous and collaborative features resemble the characteristics of agents. Suchsimilarities inspire the development of heterogeneous agent architecture for WSN in thispaper. The proposed agent architecture views WSN as multi-agent systems and mobileagents are employed to reduce in-network communication. According to the architecture,an energy based acoustic localization algorithm is proposed. In localization, estimate oftarget location is obtained by steepest descent search. The search algorithm adapts tomeasurement environments by dynamically adjusting its termination condition. With theagent architecture, target classification is accomplished by distributed support vectormachine (SVM. Mobile agents are employed for feature extraction and distributed SVMlearning to reduce communication load. Desirable learning performance is guaranteed bycombining support vectors and convex hull vectors. Fusion algorithms are designed tomerge SVM classification decisions made from various modalities. Real world experimentswith MICAz sensor nodes are conducted for vehicle localization and classification.Experimental results show the proposed agent architecture remarkably facilitates WSNdesigns and algorithm implementation. The localization and classification algorithms alsoprove to be accurate and energy efficient.

  20. 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

  1. Use of iohexol as a gastrointestinal contrast agent in three dogs, five cats, and one bird

    International Nuclear Information System (INIS)

    Williams, J.; Biller, D.S.; Myer, C.W.; Miyabayashi, T.; Leveille, R.

    1993-01-01

    Barium sulfate suspension is routinely used as contrast medium for upper gastrointestinal procedures. It has been contraindicated for use in cases of suspected perforation. In such instances, water-soluble iodides are recommended for use. Most of the water-soluble iodides available for use in veterinary medicine at this time are hyperosmolar. This results in in transit dilution of the contrast column. The dilution of the contrast agent within the intestines may prevent visualization of a perforation, especially if the perforation is in the distal portion of the small intestine. Iohexol a nonionic water-soluble iodide of low osmolality, is currently used in veterinary medicine for myelography. We have used it as the contrast agent for upper gastrointestinal studies in cases of suspected obstruction or perforation, with good results, and no adverse effects have been associated with its use. Opacity of the contrast column was adequate, and segmentation or flocculation of the column was not apparent

  2. 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.

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

    Science.gov (United States)

    Kim, Jennifer; Kyung, Richard

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

  4. Potential of probiotics as biotherapeutic agents targeting the innate ...

    African Journals Online (AJOL)

    Potential of probiotics as biotherapeutic agents targeting the innate immune system. ... Some of the positive effects of probiotics are: growth promotion of farm animals, protection of host from intestinal infections, alleviation of lactose intolerance, relief of constipation, anticarcinogenic effect, anticholesterolaemic effects, ...

  5. 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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

  8. Trends in GPCR drug discovery: new agents, targets and indications

    DEFF Research Database (Denmark)

    Hauser, Alexander Sebastian; Gloriam, David E.; Attwood, Misty M.

    2017-01-01

    current trends across molecule types, drug targets and therapeutic indications, including showing that 475 drugs (~34% of all drugs approved by the US Food and Drug Administration (FDA)) act at 108 unique GPCRs. Approximately 321 agents are currently in clinical trials, of which ~20% target 66 potentially...... are also highly represented. The 224 (56%) non-olfactory GPCRs that have not yet been explored in clinical trials have broad untapped therapeutic potential, particularly in genetic and immune system disorders. Finally, we provide an interactive online resource to analyse and infer trends in GPCR drug......G protein-coupled receptors (GPCRs) are the most intensively studied drug targets, mostly due to their substantial involvement in human pathophysiology and their pharmacological tractability. Here, we report an up-to-date analysis of all GPCR drugs and agents in clinical trials, which reveals...

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

    International Nuclear Information System (INIS)

    Perel'man, V.M.

    1980-01-01

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

  10. 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.

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

    Science.gov (United States)

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

    2006-01-01

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

  12. 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.

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2016-10-01

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

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

    Science.gov (United States)

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

    2017-10-15

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

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

    Science.gov (United States)

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

    2018-09-01

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

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

    International Nuclear Information System (INIS)

    Croisille, Pierre; Revel, Didier; Saeed, Maythem

    2006-01-01

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

  18. Liposomes Loaded with Hydrophobic Iron Oxide Nanoparticles: Suitable T2 Contrast Agents for MRI

    OpenAIRE

    Raquel Martínez-González; Joan Estelrich; Maria Antònia Busquets

    2016-01-01

    There has been a recent surge of interest in the use of superparamagnetic iron oxide nanoparticles (SPIONs) as contrast agents (CAs) for magnetic resonance imaging (MRI), due to their tunable properties and their low toxicity compared with other CAs such as gadolinium. SPIONs exert a strong influence on spin-spin T 2 relaxation times by decreasing the MR signal in the regions to which they are delivered, consequently yielding darker images or negative contrast. Given the potential of these na...

  19. 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

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

    Science.gov (United States)

    Wiener, Edzard; Settles, Marcus; Diederichs, Gerd

    2010-01-01

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

  1. The Impact of Injector-Based Contrast Agent Administration on Bolus Shape and Magnetic Resonance Angiography Image Quality.

    Science.gov (United States)

    Jost, Gregor; Endrikat, Jan; Pietsch, Hubertus

    2017-01-01

    To compare injector-based contrast agent (CA) administration with hand injection in magnetic resonance angiography (MRA). Gadobutrol was administered in 6 minipigs with 3 protocols: (a) hand injection (one senior technician), (b) hand injection (6 less-experienced technicians), and (c) power injector administration. The arterial bolus shape was quantified by test bolus measurements. A head and neck MRA was performed for quantitative and qualitative comparison of signal enhancement. A significantly shorter time to peak was observed for protocol C, whereas no significant differences between protocols were found for peak height and bolus width. However, for protocol C, these parameters showed a much lower variation. The MRA revealed a significantly higher signal-to-noise ratio for injector-based administration. A superimposed strong contrast of the jugular vein was found in 50% of the hand injections. Injector-based CA administration results in a more standardized bolus shape, a higher vascular contrast, and a more robust visualization of target vessels.

  2. Magnetic and relaxometric properties of polyethylenimine-coated superparamagnetic MRI contrast agents

    International Nuclear Information System (INIS)

    Corti, M.; Lascialfari, A.; Marinone, M.; Masotti, A.; Micotti, E.; Orsini, F.; Ortaggi, G.; Poletti, G.; Innocenti, C.; Sangregorio, C.

    2008-01-01

    Novel systems to be employed as superparamagnetic contrast agents (CA) for magnetic resonance imaging (MRI) have been synthesized. These compounds are composed of an iron oxide magnetic core coated by polyethylenimine (PEI) or carboxylated polyethylenimine (PEI-COOH). The aim of the present work was to prepare and study new nanostructured systems (with better or at least comparable relaxivities, R 1 and R 2 , with respect to the commercial ones) with controlled, almost monodisperse average dimensions and shape, as candidates for molecular targeting. By means of atomic force microscopy (AFM) measurements we determined the average diameter, of the order of 200 nm, and the shape of the particles. The superparamagnetic behavior was assessed by SQUID measurements. From X-ray data the estimated average diameters of the magnetic cores were found to be ∼5.8 nm for PEI-COOH60 and ∼20 nm for the compound named PEI25. By NMR-dispersion (NMRD), we found that PEI-COOH60 presents R 1 and R 2 relaxivities slightly lower than Endorem. The experimental results suggest that these novel compounds can be used as MRI CA

  3. Artifact reduction method in ultrasound-guided diffuse optical tomography using exogenous contrast agents

    Science.gov (United States)

    Ardeshirpour, Yasaman; Biswal, Nrusingh; Aguirre, Andres; Zhu, Quing

    2011-04-01

    In diffuse optical tomography (DOT), a typical perturbation approach requires two sets of measurements obtained at the lesion breast (lesion or target site) and a contra-lateral location of the normal breast (reference site) for image reconstruction. For patients who have a small amount of breast tissue, the chest-wall underneath the breast tissue at both sites affects the imaging results. In this group of patients, the perturbation, which is the difference between measurements obtained at the lesion and reference sites, may include the information of background mismatch which can generate artifacts or affect the reconstructed quantitative absorption coefficient of the lesion. Also, for patients who have a single breast due to prior surgery, the contra-lateral reference is not available. To improve the DOT performance or overcome its limitation, we introduced a new method based on an exogenous contrast agent and demonstrate its performance using animal models. Co-registered ultrasound was used to guide the lesion localization. The results have shown that artifacts caused by background mismatch can be reduced significantly by using this new method.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-07-01

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

  5. Measuring SPIO and Gd contrast agent magnetization using 3 T MRI

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2014-04-01

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

  7. Preclinical evaluation of molecular-targeted anticancer agents for radiotherapy

    International Nuclear Information System (INIS)

    Krause, Mechthild; Zips, Daniel; Thames, Howard D.; Kummermehr, Johann; Baumann, Michael

    2006-01-01

    The combination of molecular-targeted agents with irradiation is a highly promising avenue for cancer research and patient care. Molecular-targeted agents are in themselves not curative in solid tumours, whereas radiotherapy is highly efficient in eradicating tumour stem cells. Recurrences after high-dose radiotherapy are caused by only one or few surviving tumour stem cells. Thus, even if a novel agent has the potential to kill only few tumour stem cells, or if it interferes in mechanisms of radioresistance of tumours, combination with radiotherapy may lead to an important improvement in local tumour control and survival. To evaluate the effects of novel agents combined with radiotherapy, it is therefore necessary to use experimental endpoints which reflect the killing of tumour stem cells, in particular tumour control assays. Such endpoints often do not correlate with volume-based parameters of tumour response such as tumour regression and growth delay. This calls for radiotherapy specific research strategies in the preclinical testing of novel anti-cancer drugs, which in many aspects are different from research approaches for medical oncology

  8. Imaging efficacy of a targeted imaging agent for fluorescence endoscopy

    Science.gov (United States)

    Healey, A. J.; Bendiksen, R.; Attramadal, T.; Bjerke, R.; Waagene, S.; Hvoslef, A. M.; Johannesen, E.

    2008-02-01

    Colorectal cancer is a major cause of cancer death. A significant unmet clinical need exists in the area of screening for earlier and more accurate diagnosis and treatment. We have identified a fluorescence imaging agent targeted to an early stage molecular marker for colorectal cancer. The agent is administered intravenously and imaged in a far red imaging channel as an adjunct to white light endoscopy. There is experimental evidence of preclinical proof of mechanism for the agent. In order to assess potential clinical efficacy, imaging was performed with a prototype fluorescence endoscope system designed to produce clinically relevant images. A clinical laparoscope system was modified for fluorescence imaging. The system was optimised for sensitivity. Images were recorded at settings matching those expected with a clinical endoscope implementation (at video frame rate operation). The animal model was comprised of a HCT-15 xenograft tumour expressing the target at concentration levels expected in early stage colorectal cancer. Tumours were grown subcutaneously. The imaging agent was administered intravenously at a dose of 50nmol/kg body weight. The animals were killed 2 hours post administration and prepared for imaging. A 3-4mm diameter, 1.6mm thick slice of viable tumour was placed over the opened colon and imaged with the laparoscope system. A receiver operator characteristic analysis was applied to imaging results. An area under the curve of 0.98 and a sensitivity of 87% [73, 96] and specificity of 100% [93, 100] were obtained.

  9. Effect of contrast agent administration on consequences of dosimetry and biology in radiotherapy planning

    International Nuclear Information System (INIS)

    Lo, Ching-Jung; Yang, Pei-Ying; Chao, Tsi-Chian; Tu, Shu-Ju

    2015-01-01

    In the treatment planning of radiation therapy, patients may be administrated with contrast media in CT scanning to assist physicians for accurate delineation of the target or organs. However, contrast media are not used in patients during the treatment delivery. In particular, contrast media contain materials with high atomic numbers and dosimetric variations may occur between scenarios where contrast media are present in treatment planning and absent in treatment delivery. In this study we evaluate the effect of contrast media on the dosimetry and biological consequence. An analytical phantom based on AAPM TG 119 and five sets of CT images from clinical patients are included. Different techniques of treatment planning are considered, including 1-field AP, 2-field AP+PA, 4-field box, 7-field IMRT, and RapidArc. RapidArc is a recent technique of volumetric modulated arc therapy and is used in our study of contrast media in clinical scenarios. The effect of RapidArc on dosimetry and biological consequence for administration of contrast media in radiotherapy is not discussed previously in literature. It is shown that dose difference is reduced as the number of external beams is increased, suggesting RapidArc may be favored to be used in the treatment planning enhanced by contrast media. Linear trend lines are fitted for assessment of percent dose differences in the planning target volume versus concentrations of contrast media between plans where contrast media are present and absent, respectively

  10. Comparison and evaluation of indicator dilution models for bolus of ultrasound contrast agents

    Czech Academy of Sciences Publication Activity Database

    Harabis, V.; Kolář, R.; Mézl, M.; Jiřík, Radovan

    2013-01-01

    Roč. 34, č. 2 (2013), s. 151-162 ISSN 0967-3334 R&D Projects: GA ČR GAP102/12/2380 Institutional support: RVO:68081731 Keywords : perfusion model * ultrasound * contrast agent * intravascular perfusion * tissue phantom Subject RIV: FS - Medical Facilities ; Equipment Impact factor: 1.617, year: 2013

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

    Science.gov (United States)

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

    2015-09-01

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

  12. Ultrasound-triggered local release of lipophilic drugs from a novel polymeric ultrasound contrast agent

    NARCIS (Netherlands)

    Kooiman, K.; Böhmer, M.R.; Emmer, M.; Vos, Hendrik J.; Chlon, C.; Foppen-Harteveld, M.; Versluis, Michel; de Jong, N.; van Wamel, A.; Hennink, W.E.; Feijen, J.; Sam, A.P.

    2008-01-01

    The advantage of ultrasound contrast agents (UCAs) as drug delivery systems is the ability to non-invasively control the local and triggered release of a drug or gene. In this study we designed and characterized a novel UCA-based drug delivery system, based on polymer-shelled microcapsules filled

  13. A novel MR contrast agent for angiography and perfusion: Hyperpolarized water

    DEFF Research Database (Denmark)

    Lipsø, Hans Kasper Wigh

    , hyperpolarized by dissolution Dynamic Nuclear Polarization (d-DNP), can be applied as an MRI contrast agent for angiography and perfusion. The first part of the project focuses on development of a protocol for production of large samples of hyperpolarized protons in D2O. The samples are polarized and dissolved...

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

    National Research Council Canada - National Science Library

    Roeder, Ryan K

    2008-01-01

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

  15. Three-dimensional magnetic resonance coronary angiography using a new blood pool contrast agent : Initial experience

    NARCIS (Netherlands)

    Bedaux, WLF; Hofman, MBM; Wielopolski, PA; de Cock, CC; Hoffmann, [No Value; Oudkerk, M; de Feyter, PJ; van Rossum, AC

    2002-01-01

    Objective: The aim of this feasibility study was to assess the effect of a new blood pool contrast agent on magnetic resonance coronary angiography (MRCA) in patients suspected of having coronary artery disease. Methods: Nine patients referred for diagnostic x-ray coronary, angiography in the

  16. Non-invasive estimation of blood pressure using ultrasound contrast agents

    DEFF Research Database (Denmark)

    Andersen, Klaus Scheldrup; Jensen, Jørgen Arendt

    2009-01-01

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

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

    DEFF Research Database (Denmark)

    Andersen, Klaus Scheldrup

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

  18. Impact of acoustic pressure on ambient pressure estimation using ultrasound contrast agent

    DEFF Research Database (Denmark)

    Andersen, Klaus Scheldrup; Jensen, Jørgen Arendt

    2010-01-01

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

  19. Characterization of Definity™ Ultrasound Contrast Agent at Frequency Range of 5–15 MHz

    NARCIS (Netherlands)

    Faez, Telli; Goertz, David; de Jong, N.

    2011-01-01

    The status of vasa vasorum, which can be imaged using ultrasound contrast agents, is an indication for the progression of atherosclerosis. The preferred ultrasound frequency for this purpose is between 5 and 15 MHz. Therefore, it is essential to have knowledge about the acoustic properties of

  20. Clusters of magnetic nanoparticles as contrast agents for MRI: effect of aggregation on transverse relaxivity

    Czech Academy of Sciences Publication Activity Database

    Dědourková, T.; Kaman, Ondřej; Veverka, Pavel; Koktan, Jakub; Veverka, Miroslav; Kuličková, Jarmila; Jirák, Zdeněk; Herynek, V.

    2015-01-01

    Roč. 51, č. 11 (2015), s. 5300804 ISSN 0018-9464 R&D Projects: GA ČR GA15-10088S; GA MPO FR-TI3/521 Institutional support: RVO:68378271 Keywords : contrast agents * magnetic resonance imaging * magnetic nanoparticles * manganites * transverse relaxivity Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.277, year: 2015

  1. 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.

  2. 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.

  3. Feasibility of contrast-enhanced cone-beam CT for target localization and treatment monitoring

    International Nuclear Information System (INIS)

    Rodal, Jan; Sovik, Aste; Skogmo, Hege Kippenes; Knudtsen, Ingerid Skjei; Malinen, Eirik

    2010-01-01

    A dog with a spontaneous maxillary tumour was given 40 Gy of fractionated radiotherapy. At five out of 10 fractions cone-beam CT (CBCT) imaging before and after administration of an iodinated contrast agent were performed. Contrast enhancement maps were overlaid on the pre-contrast CBCT images. The tumour was clearly visualized in the images thus produced.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    Marshall, Gill; Kasap, Chris

    2012-01-01

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

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

    International Nuclear Information System (INIS)

    Bremer, Christoph; Ntziachristos, Vasilis; Weissleder, Ralph

    2003-01-01

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

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

    Science.gov (United States)

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

    2017-01-25

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

  8. 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.

  9. Self-assembled polymeric nanoparticles as new, smart contrast agents for cancer early detection using magnetic resonance imaging.

    Science.gov (United States)

    Mouffouk, Fouzi; Simão, Teresa; Dornelles, Daniel F; Lopes, André D; Sau, Pablo; Martins, Jorge; Abu-Salah, Khalid M; Alrokayan, Salman A; Rosa da Costa, Ana M; dos Santos, Nuno R

    2015-01-01

    Early cancer detection is a major factor in the reduction of mortality and cancer management cost. Here we developed a smart and targeted micelle-based contrast agent for magnetic resonance imaging (MRI), able to turn on its imaging capability in the presence of acidic cancer tissues. This smart contrast agent consists of pH-sensitive polymeric micelles formed by self-assembly of a diblock copolymer (poly(ethyleneglycol-b-trimethylsilyl methacrylate)), loaded with a gadolinium hydrophobic complex ((t)BuBipyGd) and exploits the acidic pH in cancer tissues. In vitro MRI experiments showed that (t)BuBipyGd-loaded micelles were pH-sensitive, as they turned on their imaging capability only in an acidic microenvironment. The micelle-targeting ability toward cancer cells was enhanced by conjugation with an antibody against the MUC1 protein. The ability of our antibody-decorated micelles to be switched on in acidic microenvironments and to target cancer cells expressing specific antigens, together with its high Gd(III) content and its small size (35-40 nm) reveals their potential use for early cancer detection by MRI.

  10. 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

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

    Directory of Open Access Journals (Sweden)

    Sabine Franckenberg, MD

    2018-02-01

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

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  13. 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.

  14. Trends in GPCR drug discovery: new agents, targets and indications.

    Science.gov (United States)

    Hauser, Alexander S; Attwood, Misty M; Rask-Andersen, Mathias; Schiöth, Helgi B; Gloriam, David E

    2017-12-01

    G protein-coupled receptors (GPCRs) are the most intensively studied drug targets, mostly due to their substantial involvement in human pathophysiology and their pharmacological tractability. Here, we report an up-to-date analysis of all GPCR drugs and agents in clinical trials, which reveals current trends across molecule types, drug targets and therapeutic indications, including showing that 475 drugs (~34% of all drugs approved by the US Food and Drug Administration (FDA)) act at 108 unique GPCRs. Approximately 321 agents are currently in clinical trials, of which ~20% target 66 potentially novel GPCR targets without an approved drug, and the number of biological drugs, allosteric modulators and biased agonists has increased. The major disease indications for GPCR modulators show a shift towards diabetes, obesity and Alzheimer disease, although several central nervous system disorders are also highly represented. The 224 (56%) non-olfactory GPCRs that have not yet been explored in clinical trials have broad untapped therapeutic potential, particularly in genetic and immune system disorders. Finally, we provide an interactive online resource to analyse and infer trends in GPCR drug discovery.

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

    Science.gov (United States)

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

    2018-03-13

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

  16. 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)

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

    Science.gov (United States)

    Siddiqui, Talha S.

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

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

    International Nuclear Information System (INIS)

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

    1992-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-08-01

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

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

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

    Science.gov (United States)

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

    2015-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-07-15

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

  3. 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

  4. 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

  5. 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.

  6. Spectroscopic and photoacoustic characterization of encapsulated iron oxide super-paramagnetic nanoparticles as a new multiplatform contrast agent

    Science.gov (United States)

    Armanetti, Paolo; Flori, Alessandra; Avigo, Cinzia; Conti, Luca; Valtancoli, Barbara; Petroni, Debora; Doumett, Saer; Cappiello, Laura; Ravagli, Costanza; Baldi, Giovanni; Bencini, Andrea; Menichetti, Luca

    2018-06-01

    Recently, a number of photoacoustic (PA) agents with increased tissue penetration and fine spatial resolution have been developed for molecular imaging and mapping of pathophysiological features at the molecular level. Here, we present bio-conjugated near-infrared light-absorbing magnetic nanoparticles as a new agent for PA imaging. These nanoparticles exhibit suitable absorption in the near-infrared region, with good photoacoustic signal generation efficiency and high photo-stability. Furthermore, these encapsulated iron oxide nanoparticles exhibit strong super-paramagnetic behavior and nuclear relaxivities that make them useful as magnetic resonance imaging (MRI) contrast media as well. Their simple bio-conjugation strategy, optical and chemical stability, and straightforward manipulation could enable the development of a PA probe with magnetic and spectroscopic properties suitable for in vitro and in vivo real-time imaging of relevant biological targets.

  7. 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.)

  8. 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.)

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

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

    Science.gov (United States)

    Budjan, Johannes; Attenberger, Ulrike I; Schoenberg, Stefan O; Pietsch, Hubertus; Jost, Gregor

    2018-05-01

    Time-resolved contrast-enhanced MR angiography (4D-MRA), which allows the simultaneous visualization of the vasculature and blood-flow dynamics, is widely used in clinical routine. In this study, the impact of two different contrast agent injection methods on 4D-MRA was examined in a controlled, standardized setting in an animal model. Six anesthetized Goettingen minipigs underwent two identical 4D-MRA examinations at 1.5 T in a single session. The contrast agent (0.1 mmol/kg body weight gadobutrol, followed by 20 ml saline) was injected using either manual injection or an automated injection system. A quantitative comparison of vascular signal enhancement and quantitative renal perfusion analyses were performed. Analysis of signal enhancement revealed higher peak enhancements and shorter time to peak intervals for the automated injection. Significantly different bolus shapes were found: automated injection resulted in a compact first-pass bolus shape clearly separated from the recirculation while manual injection resulted in a disrupted first-pass bolus with two peaks. In the quantitative perfusion analyses, statistically significant differences in plasma flow values were found between the injection methods. The results of both qualitative and quantitative 4D-MRA depend on the contrast agent injection method, with automated injection providing more defined bolus shapes and more standardized examination protocols. • Automated and manual contrast agent injection result in different bolus shapes in 4D-MRA. • Manual injection results in an undefined and interrupted bolus with two peaks. • Automated injection provides more defined bolus shapes. • Automated injection can lead to more standardized examination protocols.

  11. MRI contrast demonstration of antigen-specific targeting with an iron-based ferritin construct

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, Edward G., E-mail: edward_walsh@brown.edu [Brown University, Department of Neuroscience (United States); Mills, David R. [Rhode Island Hospital/Warren Alpert Medical School of Brown University, Division of Hematology and Oncology, Department of Medicine (United States); Lim, Sierin; Sana, Barindra [Nanyang Technological University, Division of Bioengineering (Singapore); Brilliant, Kate E. [Rhode Island Hospital/Warren Alpert Medical School of Brown University, Division of Hematology and Oncology, Department of Medicine (United States); Park, William K. C. [Rhode Island Hospital, Department of Diagnostic Imaging (United States)

    2013-01-15

    A genetically modified ferritin has been examined for its properties as a tumor-selective magnetic resonance imaging (MRI) contrast agent. The engineered ferritin described herein was derived from Archaeoglobus fulgidus (AfFtn-AA), which stores a significantly greater quantity of iron than wild-type ferritins. Relaxivity measurements were taken at 3 Tesla of ferritin particles uniformly distributed in an agarose gel to assess relaxivities r{sub 1} and r{sub 2}. The r{sub 1} and r{sub 2} values of the uniformly distributed modified ferritin were significantly higher (r{sub 1} = 1,290 mM{sup -1} s{sup -1} and r{sub 2} = 5,740 mM{sup -1} s{sup -1}) than values observed for wild-type ferritin (e.g., horse spleen, r{sub 1} = 0.674 mM{sup -1} s{sup -1}, r{sub 2} = 95.54 mM{sup -1} s{sup -1}). The modified iron-enriched ferritin (14.5 nm diameter) was conjugated with a monoclonal antibody (10 nm length) against rat Necl-5, a cell surface glycoprotein overexpressed by many epithelial cancers. In vitro studies showed strong reactivity of the assembled nanoconjugate to transformed Necl-5 positive rat prostate epithelial cells. Furthermore, MRI demonstrated a significant T{sub 2} contrast with negligible T{sub 1} effect when bound to cells. These findings highlight the utility of the modified ferritin construct as a novel MRI contrast agent that can be manipulated to target antigen-specific tissues.

  12. Effects of Resolution, Range, and Image Contrast on Target Acquisition Performance.

    Science.gov (United States)

    Hollands, Justin G; Terhaar, Phil; Pavlovic, Nada J

    2018-05-01

    We sought to determine the joint influence of resolution, target range, and image contrast on the detection and identification of targets in simulated naturalistic scenes. Resolution requirements for target acquisition have been developed based on threshold values obtained using imaging systems, when target range was fixed, and image characteristics were determined by the system. Subsequent work has examined the influence of factors like target range and image contrast on target acquisition. We varied the resolution and contrast of static images in two experiments. Participants (soldiers) decided whether a human target was located in the scene (detection task) or whether a target was friendly or hostile (identification task). Target range was also varied (50-400 m). In Experiment 1, 30 participants saw color images with a single target exemplar. In Experiment 2, another 30 participants saw monochrome images containing different target exemplars. The effects of target range and image contrast were qualitatively different above and below 6 pixels per meter of target for both tasks in both experiments. Target detection and identification performance were a joint function of image resolution, range, and contrast for both color and monochrome images. The beneficial effects of increasing resolution for target acquisition performance are greater for closer (larger) targets.

  13. 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

  14. Magnetic resonance imaging with liver-specific contrast agent in primary amyloidosis and intrahepatic cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, J.M.; Santoni-Rugiu, E.; Chabanova, E.; Logager, V.; Hansen, A.B.; Thomsen, H.S. [Depts. of Radiology and Pathology, Copenhagen Univ. Hospital, Herlev (Denmark)

    2007-02-15

    Magnetic resonance imaging (MRI) findings in hepatic amyloidosis are not well defined. Here, we report on a patient with renal failure caused by primary amyloidosis (AL type) who developed jaundice. Ultrasound and computed tomography were normal except for some ascites. MRI with oral manganese-containing contrast agent revealed several focal areas without contrast uptake in the hepatocytes and no bile secretion after 8 hours. No extrahepatic bile obstructions were found. Liver biopsy showed severe intraportal, vascular, and parenchymal amyloidosis causing severe cholestasis and atrophy of hepatocytes.

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

    Science.gov (United States)

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

    2017-05-15

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

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

    DEFF Research Database (Denmark)

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

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

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

    Science.gov (United States)

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

    2011-01-01

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

  18. An analytical study of photoacoustic and thermoacoustic generation efficiency towards contrast agent and film design optimization

    Directory of Open Access Journals (Sweden)

    Fei Gao

    2017-09-01

    Full Text Available Photoacoustic (PA and thermoacoustic (TA effects have been explored in many applications, such as bio-imaging, laser-induced ultrasound generator, and sensitive electromagnetic (EM wave film sensor. In this paper, we propose a compact analytical PA/TA generation model to incorporate EM, thermal and mechanical parameters, etc. From the derived analytical model, both intuitive predictions and quantitative simulations are performed. It shows that beyond the EM absorption improvement, there are many other physical parameters that deserve careful consideration when designing contrast agents or film composites, followed by simulation study. Lastly, several sets of experimental results are presented to prove the feasibility of the proposed analytical model. Overall, the proposed compact model could work as a clear guidance and predication for improved PA/TA contrast agents and film generator/sensor designs in the domain area.

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

    Directory of Open Access Journals (Sweden)

    Maier Anca

    2016-11-01

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

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

    Science.gov (United States)

    Yuan, Zhen; Zhang, Jian

    2018-02-01

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

  1. Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

    Directory of Open Access Journals (Sweden)

    Kim Hyo Jeong

    2010-01-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

  3. Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents.

    Science.gov (United States)

    Galluzzi, Lorenzo; Buqué, Aitziber; Kepp, Oliver; Zitvogel, Laurence; Kroemer, Guido

    2015-12-14

    The tremendous clinical success of checkpoint blockers illustrates the potential of reestablishing latent immunosurveillance for cancer therapy. Although largely neglected in the clinical practice, accumulating evidence indicates that the efficacy of conventional and targeted anticancer agents does not only involve direct cytostatic/cytotoxic effects, but also relies on the (re)activation of tumor-targeting immune responses. Chemotherapy can promote such responses by increasing the immunogenicity of malignant cells, or by inhibiting immunosuppressive circuitries that are established by developing neoplasms. These immunological "side" effects of chemotherapy are desirable, and their in-depth comprehension will facilitate the design of novel combinatorial regimens with improved clinical efficacy. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    Science.gov (United States)

    2013-05-01

    DCE-MRI analysis typically involves the application of various pharmacokinetic equations to model the movement of contrast agent molecules between...position over a short time interval due to random, thermally-induced motion (ie, Brownian motion). DW-MRI exploits applied gradients of the main...intracel- lular organelles tend to restrict or hinder the free movement of water.47,48 Moreover, cancerous tissues often show sig- nificantly reduced ADC

  6. 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

  7. Aptamer-crosslinked microbubbles: smart contrast agents for thrombin-activated ultrasound imaging.

    Science.gov (United States)

    Nakatsuka, Matthew A; Mattrey, Robert F; Esener, Sadik C; Cha, Jennifer N; Goodwin, Andrew P

    2012-11-27

    Thrombosis, or malignant blood clotting, is associated with numerous cardiovascular diseases and cancers. A microbubble contrast agent is presented that produces ultrasound harmonic signal only when exposed to elevated thrombin levels. Initially silent microbubbles are activated in the presence of both thrombin-spiked and freshly clotting blood in three minutes with detection limits of 20 nM thrombin and 2 aM microbubbles. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    OpenAIRE

    Ai-Ho Liao

    2016-01-01

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

  9. Assessment of myocardial infarction by magnetic resonance imaging with the aid of contrast agents

    International Nuclear Information System (INIS)

    Roos, A. de; Doornbos, J.

    1991-01-01

    The potential of MR imaging in myocardial ischemia with low-temporal-resolution spin-echo techniques both with and without MR contrast agents has been explored. There are indications that early MR imaging after administration of Gd-DTPA is capable to differentiate reperfused from non-reperfused infarcts. Furthermore, MR infarct sizing using Gd-DTPA is feasible to demonstrate infarct size reduction in patients with successful reperfusion. (H.W.). 50 refs.; 9 figs

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  11. 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

  12. Relationship between cavitation and loss of echogenicity from ultrasound contrast agents

    OpenAIRE

    Radhakrishnan, Kirthi; Bader, Kenneth B; Haworth, Kevin J; Kopechek, Jonathan A; Raymond, Jason L; Huang, Shao-Ling; McPherson, David D; Holland, Christy K

    2013-01-01

    Ultrasound contrast agents (UCAs) have the potential to nucleate cavitation and promote both beneficial and deleterious bioeffects in vivo. Previous studies have elucidated the pulse-duration dependent pressure amplitude threshold for rapid loss of echogenicity due to UCA fragmentation. Previous studies have demonstrated that UCA fragmentation was concomitant with inertial cavitation. The purpose of this study was to evaluate the relationship between stable and inertial cavitation thresholds ...

  13. Evaluation of potential practical oral contrast agents for pediatric magnetic resonance imaging

    International Nuclear Information System (INIS)

    Bisset, G.S. III; Cincinnati Univ., OH; Children's Hospital Medical Center, Cincinnati, OH

    1989-01-01

    Development of a practical oral contrast agent for magnetic resonance imaging is necessary to improve differentiation of bowel from adjacent structures. In order to find a readily available, inexpensive, non-toxic, palatable solution for use in the pediatric population, several formulas, milk products and a common oral sedative were evaluated in vitro. T1, T2 and signal intensity measurements were performed on a 1.5 T system. Similac with standard iron proved to be a useful high signal intensity agent on multiple pulse sequences. Early in vivo experience in four normal volunteers indicates that this agent provides excellent delineation of the stomach and duodenum from contiguous viscera. Distal small bowel visualization is less predictabel. Further clinical trials should confirm the utility of this solution, which contains a combination of iron salts and paramagnetic metallic ions. (orig.)

  14. 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.

  15. Hyperintense acute reperfusion marker is associated with higher contrast agent dosage in acute ischaemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Ostwaldt, Ann-Christin; Schaefer, Tabea; Villringer, Kersten; Fiebach, Jochen B. [Charite Universitaetsmedizin Berlin, Academic Neuroradiology, Center for Stroke Research Berlin (CSB), Berlin (Germany); Rozanski, Michal; Ebinger, Martin [Charite Universitaetsmedizin Berlin, Academic Neuroradiology, Center for Stroke Research Berlin (CSB), Berlin (Germany); Charite Universitaetsmedizin, Department of Neurology, Berlin (Germany); Jungehuelsing, Gerhard J. [Stiftung des Buergerlichen Rechts, Juedisches Krankenhaus Berlin, Berlin (Germany)

    2015-11-15

    The hyperintense acute reperfusion marker (HARM) on fluid-attenuated inversion recovery (FLAIR) images is associated with blood-brain barrier (BBB) permeability changes. The aim of this study was to examine the influence of contrast agent dosage on HARM incidence in acute ischaemic stroke patients. We prospectively included 529 acute ischaemic stroke patients (204 females, median age 71 years). Patients underwent a first stroke-MRI within 24 hours from symptom onset and had a follow-up on day 2. The contrast agent Gadobutrol was administered to the patients for perfusion imaging or MR angiography. The total dosage was calculated as ml/kg body weight and ranged between 0.04 and 0.31 mmol/kg on the first examination. The incidence of HARM was evaluated on day 2 FLAIR images. HARM was detected in 97 patients (18.3 %). HARM incidence increased significantly with increasing dosages of Gadobutrol. Also, HARM positive patients were significantly older. HARM was not an independent predictor of worse clinical outcome, and we did not find an association with increase risk of haemorrhagic transformation. A higher dosage of Gadobutrol in acute stroke patients on initial MRI is associated with increased HARM incidence on follow-up. MRI studies on BBB should therefore standardize contrast agent dosages. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-04-09

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2010-04-01

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  20. 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)

  1. ESGAR consensus statement on liver MR imaging and clinical use of liver-specific contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Neri, E.; Boraschi, P.; Bartolozzi, C. [University of Pisa, Department of Diagnostic and Interventional Radiology, Pisa (Italy); Bali, M.A.; Matos, C. [Hopital Erasme, MRI Clinics, Department of Radiology, Bruxelles (Belgium); Ba-Ssalamah, A. [The General Hospital of the Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Brancatelli, G. [University of Palermo, Department of Radiology, Palermo (Italy); Alves, F.C. [University Hospital of Coimbra, Medical Imaging Department and Faculty of Medicine, Coimbra (Portugal); Grazioli, L. [Spedali Civili di Brescia, Department of Radiology, Brescia (Italy); Helmberger, T. [Academic Teaching Hospital of the Technical University, Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Klinikum Bogenhausen, Munich (Germany); Lee, J.M. [Seoul National University College of Medicine, Division of Abdominal Imaging, Department of Radiology, Seoul (Korea, Republic of); Manfredi, R. [University of Verona, Department of Radiology, Verona (Italy); Marti-Bonmati, L. [Hospital Universitario y Politecnico La Fe, Area Clinica de Imagen Medica, Valencia (Spain); Merkle, E.M. [Universitaetsspital Basel, Klinik fuer Radiologie und Nuklearmedizin, Basel (Switzerland); Op De Beeck, B. [Antwerp University Hospital, Department of Radiology, Edegem (Belgium); Schima, W. [KH Goettlicher Heiland, Krankenhaus der Barmherzigen Schwestern and Sankt Josef-Krankenhaus, Department of Diagnostic and Interventional Radiology, Vienna (Austria); Skehan, S. [St Vincent' s University Hospital, Department of Radiology, Dublin (Ireland); Vilgrain, V. [Assistance Publique-Hopitaux de Paris, APHP, Hopital Beaujon, Radiology Department, Clichy, Paris (France); Zech, C. [Universitaetsspital Basel, Abteilungsleiter Interventionelle Radiologie, Klinik fuer Radiologie und Nuklearmedizin, Basel (Switzerland)

    2016-04-15

    To develop a consensus and provide updated recommendations on liver MR imaging and the clinical use of liver-specific contrast agents. The European Society of Gastrointestinal and Abdominal Radiology (ESGAR) formed a multinational European panel of experts, selected on the basis of a literature review and their leadership in the field of liver MR imaging. A modified Delphi process was adopted to draft a list of statements. Descriptive and Cronbach's statistics were used to rate levels of agreement and internal reliability of the consensus. Three Delphi rounds were conducted and 76 statements composed on MR technique (n = 17), clinical application of liver-specific contrast agents in benign, focal liver lesions (n = 7), malignant liver lesions in non-cirrhotic (n = 9) and in cirrhotic patients (n = 18), diffuse and vascular liver diseases (n = 12), and bile ducts (n = 13). The overall mean score of agreement was 4.84 (SD ±0.17). Full consensus was reached in 22 % of all statements in all working groups, with no full consensus reached on diffuse and vascular diseases. The consensus provided updated recommendations on the methodology, and clinical indications, of MRI with liver specific contrast agents in the study of liver diseases. (orig.)

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-05-15

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-12-15

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

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

    Science.gov (United States)

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

    2013-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-06-15

    Purpose: Micro-Computed Tomography (micro-CT) has been widely used as a non-invasive, high-resolution imaging modality in preclinical research. However, tumors cannot be well distinguished, since their density are similar to those of surrounding tissues, and the tumors’ natural contrast is very low. The benefits of using Gold Nanoparticles (AuNPs) as a promising high atomic weight contrast agent have been published in recent years. The aim of this study is to investigate the efficacy of AuNPs as contrast agents using different energy x-rays. Methods: The left flank of an immune-compromised athymic nude mouse was implanted with subcutaneous xenograft model of human lung cancer line, A549 cells (from ATCC). After 14 days, this mouse was imaged with dual energy cone-beam micro-CT. The selected energies were 45 kVp and 65 kVp. 10µg AuNPs (200 µg/ml concentration) approximately 12 nm in size were injected subcutaneously into the tumor. The mouse was imaged 0, 3 and 24 hours post-injection. During scanning, this mouse was anesthetized. All projection raw data have been optimized and then images were reconstructed with the FDK Algorithm. Results: Based on images, at 0 hour, AuNPs provided obvious contrast no matter which energy selected, 45 kVp or 65 kVp; and using 45 kVp X-ray, AuNps showed greater contrast. After 3 hours or evenand longer, AuNPs distributed throughout the whole body of mouse, and they were not shown clearly shown in the images. Conclusion: In this study, we investigated the efficacy of AuNPs as image contrast agents at different energies with dual-energy micro-CT, using 200µg/mL of AuNPs. Sufficiently high concentrations of AuNPs are needed to be able to track intratumoral distribution. Images showed good contrast immediately following the administration of the agent but results were poor after 3 hours.

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    International Nuclear Information System (INIS)

    Doinikov, Alexander A; Bouakaz, Ayache

    2013-01-01

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

  9. 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.

  10. Cell targeting peptides as smart ligands for targeting of therapeutic or diagnostic agents: a systematic review.

    Science.gov (United States)

    Mousavizadeh, Ali; Jabbari, Ali; Akrami, Mohammad; Bardania, Hassan

    2017-10-01

    Cell targeting peptides (CTP) are small peptides which have high affinity and specificity to a cell or tissue targets. They are typically identified by using phage display and chemical synthetic peptide library methods. CTPs have attracted considerable attention as a new class of ligands to delivery specifically therapeutic and diagnostic agents, because of the fact they have several advantages including easy synthesis, smaller physical sizes, lower immunogenicity and cytotoxicity and their simple and better conjugation to nano-carriers and therapeutic or diagnostic agents compared to conventional antibodies. In this systematic review, we will focus on the basic concepts concerning the use of cell-targeting peptides (CTPs), following the approaches of selecting them from peptide libraries. We discuss several developed strategies for cell-specific delivery of different cargos by CTPs, which are designed for drug delivery and diagnostic applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Intravenous, contrast-enhanced MR colonography using air as endoluminal contrast agent: Impact on colorectal polyp detection.

    LENUS (Irish Health Repository)

    Keeling, Aoife N

    2012-02-01

    PURPOSE: To compare diagnostic accuracy and patient tolerance of MR colonography with intravenous contrast and luminal air (MRC) to conventional colonoscopy (CC). MATERIALS AND METHODS: IRB approval and written informed consent were obtained. Forty-six patients, both screening and symptomatic, underwent MRC followed by CC. The MRC technique employed 3D T1W spoiled gradient echo sequences performed after the administration of gadopenetate dimeglumine, with parallel imaging. The diagnostic accuracy and tolerance of patients for MRC was compared to CC. RESULTS: Twenty-four polyps were detected in eighteen patients with CC (5 polyps >\\/=10mm, 4 polyps 6-9mm, 15 polyps <\\/=5mm). MRC was 66.7% (12\\/18) sensitive and 96.4% (27\\/28) specific for polyp detection on a per-patient basis. When analyzed by polyp size, sensitivity and specificity of MRC was 100% (5\\/5) and 100% (19\\/19), respectively, for lesions greater than 10mm, 100% (4\\/4) and 100% (20\\/20) for lesions 6-9mm, and sensitivity of 20% (3\\/15) lesions less than 5mm. The sensitivity and specificity of MRC for detecting significant lesions (>6mm) was 100% (9\\/9) and 100% (15\\/15), respectively. Regarding tolerance of the exams, there were no significant differences between MRC and CC. Thirty-five percent (n=16) of patients preferred MRC as a future screening test compared to 33% (n=15) for CC. CONCLUSION: MRC using air as an intraluminal contrast agent is a feasible and well-tolerated technique for detecting colonic polyps >\\/=6mm in size. Further studies are warranted.

  12. Intravenous, contrast-enhanced MR colonography using air as endoluminal contrast agent: Impact on colorectal polyp detection.

    LENUS (Irish Health Repository)

    Keeling, Aoife N

    2010-12-03

    PURPOSE: To compare diagnostic accuracy and patient tolerance of MR colonography with intravenous contrast and luminal air (MRC) to conventional colonoscopy (CC). MATERIALS AND METHODS: IRB approval and written informed consent were obtained. Forty-six patients, both screening and symptomatic, underwent MRC followed by CC. The MRC technique employed 3D T1W spoiled gradient echo sequences performed after the administration of gadopenetate dimeglumine, with parallel imaging. The diagnostic accuracy and tolerance of patients for MRC was compared to CC. RESULTS: Twenty-four polyps were detected in eighteen patients with CC (5 polyps ≥10mm, 4 polyps 6-9mm, 15 polyps ≤5mm). MRC was 66.7% (12\\/18) sensitive and 96.4% (27\\/28) specific for polyp detection on a per-patient basis. When analyzed by polyp size, sensitivity and specificity of MRC was 100% (5\\/5) and 100% (19\\/19), respectively, for lesions greater than 10mm, 100% (4\\/4) and 100% (20\\/20) for lesions 6-9mm, and sensitivity of 20% (3\\/15) lesions less than 5mm. The sensitivity and specificity of MRC for detecting significant lesions (>6mm) was 100% (9\\/9) and 100% (15\\/15), respectively. Regarding tolerance of the exams, there were no significant differences between MRC and CC. Thirty-five percent (n=16) of patients preferred MRC as a future screening test compared to 33% (n=15) for CC. CONCLUSION: MRC using air as an intraluminal contrast agent is a feasible and well-tolerated technique for detecting colonic polyps ≥6mm in size. Further studies are warranted.

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

    Science.gov (United States)

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

    2014-11-01

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

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

    Science.gov (United States)

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

    2017-06-15

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

  15. Barium sulfate suspension as a negative oral contrast agent for MR imaging

    International Nuclear Information System (INIS)

    Li, K.C.P.; Tart, R.P.; Fitzsimmons, J.R.; Storm, B.; Mao, J.

    1989-01-01

    Proton spectroscopy with linewidth measurements and MR imaging were performed on various commercially available barium sulfate suspensions as well as inorganic sulfates and barium salts. Approximately 500 mL of 20%, 40%, 60%, and 70% wt/wt single-contrast oral barium sulfate suspensions were administered to four normal volunteers, and MR imaging was performed with both a 1.5-T and a 0.15-T MR imager. As much as 80% of the small bowel and the entire colon were well visualized with the 60% or 70% wt/wt single-contrast barium sulfate suspensions. The authors conclude that barium sulfate suspensions are useful as oral MR contrast agents

  16. Effects of microchannel confinement on acoustic vaporisation of ultrasound phase change contrast agents

    Science.gov (United States)

    Lin, Shengtao; Zhang, Ge; Hau Leow, Chee; Tang, Meng-Xing

    2017-09-01

    The sub-micron phase change contrast agent (PCCA) composed of a perfluorocarbon liquid core can be activated into gaseous state and form stable echogenic microbubbles for contrast-enhanced ultrasound imaging. It has shown great promise in imaging microvasculature, tumour microenvironment, and cancer cells. Although PCCAs have been extensively studied for different diagnostic and therapeutic applications, the effect of biologically geometrical confinement on the acoustic vaporisation of PCCAs is still not clear. We have investigated the difference in PCCA-produced ultrasound contrast enhancement after acoustic activation with and without a microvessel confinement on a microchannel phantom. The experimental results indicated more than one-order of magnitude less acoustic vaporisation in a microchannel than that in a free environment taking into account the attenuation effect of the vessel on the microbubble scattering. This may provide an improved understanding in the applications of PCCAs in vivo.

  17. Hysteretic Nonlinearity of Sub-harmonic Emission from Ultrasound Contrast Agent Microbubbles

    International Nuclear Information System (INIS)

    Qiu Yuan-Yuan; Zhang Dong; Zheng Hai-Rong

    2011-01-01

    Sub-harmonic contrast imaging promises to improve ultrasound imaging quality by taking advantage of increased contrast to tissue signal. The aim of this study is to examine the hysteretic nonlinearity of sub-harmonic component emitted from microbubbles. Two kinds of microbubble solutions, i.e. Sonovue® and a self-developed contrast agent, are utilized in the study. The hysteretic curves for increasing and decreasing acoustic pressure are theoretically predicted by the Marmottant model and confirmed by measurements. The results reveal that for both microbubble solutions, the development of the rising ramp undergoes three stages, i.e. occurrence, growth and saturation; while hysteresis effect appears in the descending ramp. Sonovue® microbubbles exhibit better sub-harmonic performance over the self-developed UCAs microbubbles due to the difference of elastic properties of the shell. (fundamental areas of phenomenology(including applications))

  18. Harmonic US imaging of vesicoureteric reflux in children: usefulness of a second generation US contrast agent.

    Science.gov (United States)

    Ascenti, Giorgio; Zimbaro, Giovanni; Mazziotti, Silvio; Chimenz, Roberto; Fede, Carmelo; Visalli, Carmela; Scribano, Emanuele

    2004-06-01

    Contrast-enhanced voiding urosonography (VUS) is largely accepted both for the diagnosis and follow-up of vesicoureteric reflux (VUR) in children. To evaluate the usefulness of contrast-enhanced second-harmonic VUS in the diagnosis and grading of VUR, using a second-generation contrast agent. Eighty consecutive children were prospectively studied with contrast-enhanced second-harmonic VUS. All children received a second-generation contrast medium, constituted by phospholipid-stabilized microbubbles of sulphur-hexafluoride (SonoVue, Bracco, Milan, Italy). US monitoring of the bladder, of the retrovesical space and of the kidneys was performed using, alternatively, both tissue-harmonic and contrast-harmonic modes. In those young boys where VUR was depicted at VUS, examination was completed with transperineal, sagittal urethral exploration during micturition. VUR was graded in five steps and diagnoses were compared with voiding cystourethrography (VCUG). VUR was diagnosed in 52 reno-ureteral units with VUS. In 49 of these reno-ureteral units, VCUG confirmed the presence of VUR. In comparison to VUS, sensitivity and negative predictive value of VCUG were inferior. The grade of VUR detected at VUS was higher than that detected at VCUG in three units. In no case was the grade of VUR detected at VCUG higher than the one detected at VUS. The differences between VUS and VCUG in grading VUR were statistically significant (p=0.02). Imaging of the normal posterior urethra was skilfully demonstrated with US in 15 young boys with VUR. No statistically significant differences were found between tissue-harmonic and contrast-harmonic mode (p=0.102). Contrast-enhanced second-harmonic VUS is a sensitive and easy technique for the evaluation of VUR. A second-generation US contrast medium such as SonoVue, if available, should be the first choice as the dose required for one examination is much lower and consequently significant reduction of contrast agent cost is possible. Copyright

  19. Contrast ultrasound targeted treatment of gliomas in mice via drug-bearing nanoparticle delivery and microvascular ablation.

    Science.gov (United States)

    Burke, Caitlin W; Price, Richard J

    2010-12-15

    We are developing minimally-invasive contrast agent microbubble based therapeutic approaches in which the permeabilization and/or ablation of the microvasculature are controlled by varying ultrasound pulsing parameters. Specifically, we are testing whether such approaches may be used to treat malignant brain tumors through drug delivery and microvascular ablation. Preliminary studies have been performed to determine whether targeted drug-bearing nanoparticle delivery can be facilitated by the ultrasound mediated destruction of "composite" delivery agents comprised of 100nm poly(lactide-co-glycolide) (PLAGA) nanoparticles that are adhered to albumin shelled microbubbles. We denote these agents as microbubble-nanoparticle composite agents (MNCAs). When targeted to subcutaneous C6 gliomas with ultrasound, we observed an immediate 4.6-fold increase in nanoparticle delivery in MNCA treated tumors over tumors treated with microbubbles co-administered with nanoparticles and a 8.5 fold increase over non-treated tumors. Furthermore, in many cancer applications, we believe it may be desirable to perform targeted drug delivery in conjunction with ablation of the tumor microcirculation, which will lead to tumor hypoxia and apoptosis. To this end, we have tested the efficacy of non-theramal cavitation-induced microvascular ablation, showing that this approach elicits tumor perfusion reduction, apoptosis, significant growth inhibition, and necrosis. Taken together, these results indicate that our ultrasound-targeted approach has the potential to increase therapeutic efficiency by creating tumor necrosis through microvascular ablation and/or simultaneously enhancing the drug payload in gliomas.

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  1. 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)

  2. Contrast agent comparison for three-dimensional micro-CT angiography: A cadaveric study.

    Science.gov (United States)

    Kingston, Mitchell J; Perriman, Diana M; Neeman, Teresa; Smith, Paul N; Webb, Alexandra L

    2016-07-01

    Barium sulfate and lead oxide contrast media are frequently used for cadaver-based angiography studies. These contrast media have not previously been compared to determine which is optimal for the visualisation and measurement of blood vessels. In this study, the lower limb vessels of 16 embalmed Wistar rats, and four sets of cannulae of known diameter, were injected with one of three different contrast agents (barium sulfate and resin, barium sulfate and gelatin, and lead oxide combined with milk powder). All were then scanned using micro-computed tomography (CT) angiography and 3-D reconstructions generated. The number of branching generations of the rat lower limb vessels were counted and compared between the contrast agents using ANOVA. The diameter of the contrast-filled cannulae, were measured and used to calculate the accuracy of the measurements by comparing the bias and variance of the estimates. Intra- and inter-observer reliability were calculated using intra-class correlation coefficients. There was no significant difference (mean difference [MD] 0.05; MD 95% confidence interval [CI] -0.83 to 0.93) between the number of branching generations for barium sulfate-resin and lead oxide-milk powder. Barium sulfate-resin demonstrated less bias and less variance of the estimates (MD 0.03; standard deviation [SD] 1.96 mm) compared to lead oxide-milk powder (MD 0.11; SD 1.96 mm) for measurements of contrast-filled cannulae scanned at high resolution. Barium sulfate-resin proved to be more accurate than lead oxide-milk powder for high resolution micro-CT scans and is preferred due to its non-toxicity. This technique could be applied to any embalmed specimen model. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Colour Doppler and microbubble contrast agent ultrasonography do not improve cancer detection rate in transrectal systematic prostate biopsy sampling.

    Science.gov (United States)

    Taverna, Gianluigi; Morandi, Giovanni; Seveso, Mauro; Giusti, Guido; Benetti, Alessio; Colombo, Piergiuseppe; Minuti, Francesco; Grizzi, Fabio; Graziotti, Pierpaolo

    2011-12-01

    What's known on the subject? and What does the study add? Transrectal gray-scale ultrasonography guided prostate biopsy sampling is the method for diagnosing prostate cancer (PC) in patients with an increased prostate specific antigen level and/or abnormal digital rectal examination. Several imaging strategies have been proposed to optimize the diagnostic value of biopsy sampling, although at the first biopsy nearly 10-30% of PC still remains undiagnosed. This study compares the PC detection rate when employing Colour Doppler ultransongraphy with or without the injection of SonoVue™ microbubble contrast agent, versus the transrectal ultrasongraphy-guided systematic biopsy sampling. The limited accuracy, sensitivity, specificity and the additional cost of using the contrast agent do not justify its routine application in PC detection. • To compare prostate cancer (PC) detection rate employing colour Doppler ultrasonography with or without SonoVue™ contrast agent with transrectal ultrasonography-guided systematic biopsy sampling. • A total of 300 patients with negative digital rectal examination and transrectal grey-scale ultrasonography, with PSA values ranging between 2.5 and 9.9 ng/mL, were randomized into three groups: 100 patients (group A) underwent transrectal ultrasonography-guided systematic bioptic sampling; 100 patients (group B) underwent colour Doppler ultrasonography, and 100 patients (group C) underwent colour Doppler ultrasonography before and during the injection of SonoVue™. • Contrast-enhanced targeted biopsies were sampled into hypervascularized areas of peripheral, transitional, apical or anterior prostate zones. • All the patients included in Groups B and C underwent a further 13 systematic prostate biopsies. The cancer detection rate was calculated for each group. • In 88 (29.3%) patients a histological diagnosis of PC was made, whereas 22 (7.4%) patients were diagnosed with high-grade prostatic intraepithelial

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  5. MR angiography of the carotid arteries and intracranial circulation: advantage of a high relaxivity contrast agent

    International Nuclear Information System (INIS)

    Anzalone, N.; Scotti, R.; Iadanza, A.

    2006-01-01

    Several studies have shown the usefulness of contrast-enhanced MR angiography (CE-MRA) for imaging the supraortic vessels, and, as a consequence, it has rapidly become a routine imaging modality. The main advantage over unenhanced techniques is the possibility to acquire larger volumes, allowing demonstration of the carotid artery from its origin to the intracranial portion. Most published studies on CE-MRA of the carotid arteries have been performed with standard Gd-based chelates whose T1 relaxivity values are similar. Recently new gadolinium chelates such as gadobenate dimeglumine (Gd-BOP-TA, MultiHance; Bracco Imaging, Milan, Italy) have been developed which have markedly higher intravascular T1 relaxivity values. When administered at an equivalent dose to that of a standard agent, these newer contrast agents produce significantly greater intravascular signal enhancement. The availability of an appropriate high-relaxivity contrast agent might also help to overcome some of the intrinsic technical problems (e. g. those related to flow) that affect time-of-flight (TOF) and phase contrast (PC) MR angiography of the intracranial vasculature. To avoid the problem of superimposition of veins, ultrafast gradient echo MRA techniques with very short TR and TE have been developed. Although the precise sequence parameters vary between manufacturers, they are basically similar. The choice between performing a time-resolved or high spatial resolution CE-MRA examination depends upon the precise clinical application. The most common applications include the study of cerebral aneurysms, arteriovenous malformations, dural arteriovenous fistulas and dural venous diseases

  6. Risk Stratification of iodine-induced thyrotoxicosis before contrast agent application

    International Nuclear Information System (INIS)

    Fricke, E.

    2004-01-01

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

  7. Risk Stratification of iodine-induced thyrotoxicosis before contrast agent application; Prognosebeurteilung bei geplanter Kontrastmittelexposition

    Energy Technology Data Exchange (ETDEWEB)

    Fricke, E. [Inst. fuer Molekulare Biophysik, Radiochemie und Nuklearmedizin, Herz- und Diabeteszentrum, Nordrheinwestfalen, Bad Oeynhausen (Germany)

    2004-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Wenjun Le

    2016-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1999-07-01

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

  11. 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

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

    Science.gov (United States)

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

    2017-07-01

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

  13. 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.

  14. Magnetic resonance imaging using paramagnetic contrast agents in the clinical evaluation of myocardial infarction. Chapter 15

    International Nuclear Information System (INIS)

    Dijkman, P.R.M. van; Wall, E.E. van der

    1992-01-01

    MRI is noninvasive and specific method for production of high resolution tomographic images in blocks of 3D information. Apart from scintigraphic techniques and computed tomography for evaluation of myocardial ischemia and infarcts, MRI has emerged as a new diagnostic technique to study the extent of anatomical and functional abnormalities in patients with coronary artery disease. Conventional noncontrast MRI can identify acute-infarcted myocardial areas, although the difficulty in identifying myocardial ischemia and infarct with noncontrast MRI suggests a potential role for contrast enhanced MRI. Use of the paramagnetic contrast agent gadolinium diethylene triamine pentaacetic acid (Gd-DTPA) improves depiction of infarcted myocardium on T1-weighted spin -echo MR images that are obtained soon after acute myocardial infarction. This is of particular interest for the estimation of myocardial infarct size. Furthermore, ultrafast subsecond imaging, in combination with Gd-DTPA, offers the potential to analyze cardiac first pass and myocardial perfusion. The development of nontoxic paramagnetic contrast agents which are selectively taken up by viable myocardium would be helpful in assessing the presence of ischemic/infarcted myocardium salvage by MRI following reperfusion. (author). 58 refs., 6 figs

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

    Science.gov (United States)

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

    2018-01-26

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

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

    International Nuclear Information System (INIS)

    Deli, Martin; Fritz, Jan; Mateiescu, Serban; Busch, Martin; Carrino, John A.; Becker, Jan; Garmer, Marietta; Grönemeyer, Dietrich

    2013-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  18. Self-assembled polymeric nanoparticles as new, smart contrast agents for cancer early detection using magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Mouffouk F

    2014-12-01

    Full Text Available Fouzi Mouffouk,1,* Teresa Simão,2,* Daniel F Dornelles,2 André D Lopes,3 Pablo Sau,4 Jorge Martins,2,5 Khalid M Abu-Salah,6 Salman A Alrokayan,6 Ana M Rosa da Costa,3 Nuno R dos Santos2 1Chemistry Department, Faculty of Science, Kuwait University, Safat, Kuwait; 2IBB – Institute for Biotechnology and Bioengineering, CBME – Centre for Molecular and Structural Biomedicine, 3CIQA-Algarve Chemistry Research Center, Department of Chemistry and Pharmacy, Faculty of Sciences and Technology, University of Algarve, Campus de Gambelas, Faro, Portugal; 4Centro Radiológico Computarizado SA (CERCO, Seville, Spain; 5Department of Biological Sciences and Bioengineering, Faculty of Sciences and Technology, University of Algarve, Campus de Gambelas, Faro, Portugal; 6King Abdullah Institute for Nanotechnology, King Saud University, Riyadh, Saudi Arabia *These authors contributed equally to this work Abstract: Early cancer detection is a major factor in the reduction of mortality and cancer management cost. Here we developed a smart and targeted micelle-based contrast agent for magnetic resonance imaging (MRI, able to turn on its imaging capability in the presence of acidic cancer tissues. This smart contrast agent consists of pH-sensitive polymeric micelles formed by self-assembly of a diblock copolymer (poly(ethyleneglycol-b-trimethylsilyl methacrylate, loaded with a gadolinium hydrophobic complex (tBuBipyGd and exploits the acidic pH in cancer tissues. In vitro MRI experiments showed that tBuBipyGd-loaded micelles were pH-sensitive, as they turned on their imaging capability only in an acidic microenvironment. The micelle-targeting ability toward cancer cells was enhanced by conjugation with an antibody against the MUC1 protein. The ability of our antibody-decorated micelles to be switched on in acidic microenvironments and to target cancer cells expressing specific antigens, together with its high Gd(III content and its small size (35–40 nm reveals

  19. 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.

  20. Gaucher disease in the liver on hepatocyte specific contrast agent enhanced MR imaging

    International Nuclear Information System (INIS)

    Ayyala, Rama S.; Teot, Lisa A.; Perez Rossello, Jeanette M.

    2017-01-01

    Gaucher disease is a hereditary lipid storage disorder that affects the enzyme beta glucocerebrosidase, causing accumulation of glucocerebroside in macrophages of the reticuloendothelial system. Accumulation can occur in the liver and spleen, manifesting as hepatosplenomegaly, as well as within the bone marrow. Hepatic involvement is usually diffuse but can occasionally manifest as focal liver lesions. We present a case of a 2-year-old boy with Gaucher disease and an infiltrating liver lesion detected on imaging, which was pathologically shown to be focal changes related to the disease. Imaging characteristics of this lesion using hepatocyte specific contrast agent enhanced MRI, which have not been previously discussed in the literature, are described. (orig.)

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-01

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

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

    Science.gov (United States)

    2011-01-01

    However, cracks in the enamel were readily detected by micro-CT both with and without the use of a con- trast agent (Fig. 2(b)) due to the relatively low x...ray attenua- tion of the fluid space in the crack compared to the enamel . Therefore, the main limitation of the difficulty distinguishing BaSO4 from...Roeder, 2011). Moreover, cracks in whole human molars were also imaged by contrast-enhanced micro-CT (Appendix 5, Landrigan et al., 2010). KEY

  4. Gaucher disease in the liver on hepatocyte specific contrast agent enhanced MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ayyala, Rama S. [Morgan Stanley Children' s Hospital, Department of Radiology, Columbia University Medical Center, New York, NY (United States); Teot, Lisa A. [Boston Children' s Hospital, Department of Pathology, Harvard Medical School, Boston, MA (United States); Perez Rossello, Jeanette M. [Boston Children' s Hospital, Department of Radiology, Harvard Medical School, Boston, MA (United States)

    2017-04-15

    Gaucher disease is a hereditary lipid storage disorder that affects the enzyme beta glucocerebrosidase, causing accumulation of glucocerebroside in macrophages of the reticuloendothelial system. Accumulation can occur in the liver and spleen, manifesting as hepatosplenomegaly, as well as within the bone marrow. Hepatic involvement is usually diffuse but can occasionally manifest as focal liver lesions. We present a case of a 2-year-old boy with Gaucher disease and an infiltrating liver lesion detected on imaging, which was pathologically shown to be focal changes related to the disease. Imaging characteristics of this lesion using hepatocyte specific contrast agent enhanced MRI, which have not been previously discussed in the literature, are described. (orig.)

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

    Science.gov (United States)

    Takeshita, Keizo; Kinoshita, Shota; Okazaki, Shoko

    2012-01-01

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

  6. Power Doppler sonography and ultrasound contrast agent in assessing rheumatoid synovitis

    Directory of Open Access Journals (Sweden)

    F. Salaffi

    2011-09-01

    Full Text Available Pannus formation is a fundamental event in the pathogenesis of rheumatoid arthritis and its hypervascularisation seems to be crucial to the development of joint damage. High-resolution greyscale ultrasonography is a safe, quick, and inexpensive imaging tool that allows an accurate detection of even minimal morphostructural changes in patients with rheumatoid arthritis, including joint effusion, thickening of synovial membrane and bone erosions. More recently, power Doppler sonography has proved to be a reliable tool for semiquantitative assessment of the vascularity of the synovial tissue. The contrast-enhanced power Doppler sonography seems to be a helpful adjunct in assessing synovitis and the therapeutic response to the different therapies in patients with rheumatoid arthritis. The aim of this radiological vignette was to show a representative example of use of power Doppler sonography with contrast agent in assessing rheumatoid synovitis.

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

    International Nuclear Information System (INIS)

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

    1984-01-01

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

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  10. The value of paramagnetic contrast agent gadolinium-DTPA in the diagnosis of pituitary adenomas

    International Nuclear Information System (INIS)

    Nakamura, T.; Schoerner, W.; Bittner, R.C.; Felix, R.

    1988-01-01

    The purpose of this study was to assess the role of MR imaging and the paramagnetic contrast agent Gadolinium-DYPA(Gd-DTPA) in the diagnosis of pituitary macroadenomas. 44 macroadenomas were examined with MRI before and after intravenous application of Gd-DTPA. Gd-DTPA produced excellent enhancement of solid adenoma. The best contrast between adenoma and surrounding structures could be gained on post-Gd T1-weighted images. Post-Gd images were equivalent to pre-Gd images in the evaluation of supra- and infrasellar extensions of macroadenomas. Post-Gd images had advantages in the evaluation of cavernous sinus invasion by adenoma. The difference in degree of contrast enhancement between adenoma and cavernous sinus facilitated the exact evaluation of lateral extension by adenoma in 18 cases. Almost equal degree of enhancement of both structures impaired tumor-sinus contrast in 2 cases. In the other 24 cases the tumor filled the cavernous sinus completely. It is our opinion that Gd-DTPA can be used on a widerspread basis because of its excellent capability to highlight and delineate pituitary adenomas. (orig.)

  11. The Impact of Injector-Based Contrast Agent Administration on Bolus Shape and Magnetic Resonance Angiography Image Quality

    Directory of Open Access Journals (Sweden)

    Gregor Jost

    2017-04-01

    Full Text Available Objective: To compare injector-based contrast agent (CA administration with hand injection in magnetic resonance angiography (MRA. Methods: Gadobutrol was administered in 6 minipigs with 3 protocols: (a hand injection (one senior technician, (b hand injection (6 less-experienced technicians, and (c power injector administration. The arterial bolus shape was quantified by test bolus measurements. A head and neck MRA was performed for quantitative and qualitative comparison of signal enhancement. Results: A significantly shorter time to peak was observed for protocol C, whereas no significant differences between protocols were found for peak height and bolus width. However, for protocol C, these parameters showed a much lower variation. The MRA revealed a significantly higher signal-to-noise ratio for injector-based administration. A superimposed strong contrast of the jugular vein was found in 50% of the hand injections. Conclusions: Injector-based CA administration results in a more standardized bolus shape, a higher vascular contrast, and a more robust visualization of target vessels.

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2010-09-01

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

  14. Experimental investigations of nonlinearities and destruction mechanisms of an experimental phospholipid-based ultrasound contrast agent.

    Science.gov (United States)

    Casciaro, Sergio; Palmizio Errico, Rosa; Errico, Rosa Palmizio; Conversano, Francesco; Demitri, Christian; Distante, Alessandro

    2007-02-01

    We sought to characterize the acoustical behavior of the experimental ultrasound contrast agent BR14 by determining the acoustic pressure threshold above which nonlinear oscillation becomes significant and investigating microbubble destruction mechanisms. We used a custom-designed in vitro setup to conduct broadband attenuation measurements at 3.5 MHz varying acoustic pressure (range, 50-190 kPa). We also performed granulometric analyses on contrast agent solutions to accurately measure microbubble size distribution and to evaluate insonification effects. Attenuation did not depend on acoustic pressure less than 100 kPa, indicating this pressure as the threshold for the appearance of microbubble nonlinear behavior. At the lowest excitation amplitude, attenuation increased during insonification, while, at higher excitation levels, the attenuation decreased over time, indicating microbubble destruction. The destruction rate changed with pressure amplitude suggesting different destruction mechanisms, as it was confirmed by granulometric analysis. Microbubbles showed a linear behavior until 100 kPa, whereas beyond this value significant nonlinearities occurred. Observed destruction phenomena seem to be mainly due to gas diffusion and bubble fragmentation mechanisms.

  15. Effect on renal function of an iso-osmolar contrast agent in patients with monoclonal gammopathies

    International Nuclear Information System (INIS)

    Preda, Lorenzo; Agazzi, Alberto; Martinelli, Giovanni; Raimondi, Sara; Lanfranchi, Carla Federica; Passerini, Rita; Calvetta, Albania; Bellomi, Massimo

    2011-01-01

    To assess the safety of the non-ionic iso-osmolar contrast agent iodixanol on renal function in patients with monoclonal gammopathies undergoing CT. We explored the effect of iodixanol on renal function in 30 patients with monoclonal gammopathies and 20 oncological patients with a normal electrophoretic profile (control group). The parameters used to estimate renal function were: serum creatinine, eGFR (determined 24 h before and 48 h after the administration of iodixanol), and urinary excretion of Neutrophil Gelatinase-Associated Lipocalin (NGAL) determined 2 h and 24 h after. Serum creatinine was also determined 1 month after the administration of iodixanol. No significant increase in serum creatinine values were observed in the monoclonal gammopathies group and in 19/20 patients in the control group. Only 1 patient in the control group developed a transient contrast agent-induced nephropathy. We found no statistically significant difference between the two groups regarding the percentage variation from baseline values of serum creatinine, creatinine clearance, NGAL 2 h after, and eGFR. Whereas NGAL at 24 h showed a statistically significant increase in patients with Monoclonal gammopathies. The use of iodixanol appears to be safe in patients with monoclonal gammopathies and an eGFR ≥ 60 ml/min/1.73 mq. (orig.)

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  17. Carboxylated magnetic nanoparticles as MRI contrast agents: Relaxation measurements at different field strengths

    Energy Technology Data Exchange (ETDEWEB)

    Jedlovszky-Hajdu, Angela, E-mail: angela.hajdu@net.sote.hu [Laboratory of Nanochemistry, Department of Biophysics and Radiation Biology, Semmelweis University, Nagyvarad Sq 4, H-1089 Budapest (Hungary); Tombacz, Etelka, E-mail: tombacz@chem.u-szeged.hu [Department of Physical Chemistry and Material Science, University of Szeged, Aradi Vt. Sq 1, Szeged 6720 (Hungary); Banyai, Istvan, E-mail: banyai.istvan@science.unideb.hu [Department of Colloid and Environmental Chemistry, University of Debrecen (Hungary); Babos, Magor, E-mail: babosmagor@yahoo.com [Euromedic Diagnostics Szeged Ltd., Semmelweis St 6, Szeged 6720 (Hungary); Palko, Andras, E-mail: palko@radio.szote.u-szeged.hu [Faculty of Medicine, Department of Radiology, University of Szeged (Hungary)

    2012-09-15

    At the moment the biomedical applications of magnetic fluids are the subject of intensive scientific interest. In the present work, magnetite nanoparticles (MNPs) were synthesized and stabilized in aqueous medium with different carboxylic compounds (citric acid (CA), polyacrylic acid (PAA), and sodium oleate (NaOA)), in order to prepare well stabilized magnetic fluids (MFs). The magnetic nanoparticles can be used in the magnetic resonance imaging (MRI) as contrast agents. Magnetic resonance relaxation measurements of the above MFs were performed at different field strengths (i.e., 0.47, 1.5 and 9.4 T) to reveal the field strength dependence of their magnetic responses, and to compare them with that of ferucarbotran, a well-known superparamagnetic contrast agent. The measurements showed characteristic differences between the tested magnetic fluids stabilized by carboxylic compounds and ferucarbotran. It is worthy of note that our magnetic fluids have the highest r2 relaxivities at the field strength of 1.5 T, where the most of the MRI works in worldwide. - Highlights: Black-Right-Pointing-Pointer Magnetic resonance relaxation measurements were done at different field strengths. Black-Right-Pointing-Pointer Results show characteristic differences between the tested carboxylated MFs. Black-Right-Pointing-Pointer r1 and r2 relaxivities depend on the thickness of the protecting layer. Black-Right-Pointing-Pointer MFs have high r2/r1 ratios at each magnetic field.

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

    Science.gov (United States)

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

    1998-12-01

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

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

    Science.gov (United States)

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

    1996-03-01

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

  20. A new contrast agent for radiological and dissection studies of the arterial network of anatomic specimens.

    Science.gov (United States)

    Bulla, A; Casoli, C; Farace, F; Mazzarello, V; De Luca, L; Rubino, C; Montella, A

    2014-01-01

    The aim of the present study is to propose a new contrast agent that can be easily applied both to CT and dissection studies to replace lead oxide based formulas for comparative anatomical analyses of the vascularisation of cadaveric specimens. The infusion material was an epoxy resin, especially modified by the addition of barium sulphate to enhance its radiopacity. The final copolymer was toxicologically safe. To test the properties of the new material, several cadaveric limb injections were performed. The injected specimens were both CT scanned to perform 3D vascular reconstructions and dissected by anatomical planes. There was a perfect correspondence between the image studies and the dissections: even the smallest arteries on CT scan can be identified on the specimen and vice versa. The properties of the epoxy allowed an easy dissection of the vessels. The new imaging techniques available today, such as CT scan, can evaluate the vascular anatomy in high detail and 3D. This new contrast agent may help realising detailed vascular studies comparing CT scan results with anatomical dissections. Moreover, it may be useful for teaching surgical skills in the field of plastic surgery.

  1. Vascular imaging with contrast agent in hard and soft tissues using microcomputed-tomography.

    Science.gov (United States)

    Blery, P; Pilet, P; Bossche, A Vanden-; Thery, A; Guicheux, J; Amouriq, Y; Espitalier, F; Mathieu, N; Weiss, P

    2016-04-01

    Vascularization is essential for many tissues and is a main requisite for various tissue-engineering strategies. Different techniques are used for highlighting vasculature, in vivo and ex vivo, in 2-D or 3-D including histological staining, immunohistochemistry, radiography, angiography, microscopy, computed tomography (CT) or micro-CT, both stand-alone and synchrotron system. Vascularization can be studied with or without a contrast agent. This paper presents the results obtained with the latest Skyscan micro-CT (Skyscan 1272, Bruker, Belgium) following barium sulphate injection replacing the bloodstream in comparison with results obtained with a Skyscan In Vivo 1076. Different hard and soft tissues were perfused with contrast agent and were harvested. Samples were analysed using both forms of micro-CT, and improved results were shown using this new micro-CT. This study highlights the vasculature using micro-CT methods. The results obtained with the Skyscan 1272 are clearly defined compared to results obtained with Skyscan 1076. In particular, this instrument highlights the high number of small vessels, which were not seen before at lower resolution. This new micro-CT opens broader possibilities in detection and characterization of the 3-D vascular tree to assess vascular tissue engineering strategies. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

  2. A novel technology: microfluidic devices for microbubble ultrasound contrast agent generation.

    Science.gov (United States)

    Lin, Hangyu; Chen, Junfang; Chen, Chuanpin

    2016-09-01

    Microbubbles are used as ultrasound contrast agents, which enhance ultrasound imaging techniques. In addition, microbubbles currently show promise in disease therapeutics. Microfluidic devices have increased the ability to produce microbubbles with precise size, and high monodispersity compared to microbubbles created using traditional methods. This paper will review several variations in microfluidic device structures used to produce microbubbles as ultrasound contrast agents. Microfluidic device structures include T-junction, and axisymmetric and asymmetric flow-focusing. These devices have made it possible to produce microbubbles that can enter the vascular space; these microbubbles must be less than 10 μm in diameter and have high monodispersity. For different demands of microbubbles production rate, asymmetric flow-focusing devices were divided into individual and integrated devices. In addition, asymmetric flow-focusing devices can produce double layer and multilayer microbubbles loaded with drug or biological components. Details on the mechanisms of both bubble formation and device structures are provided. Finally, microfluidically produced microbubble acoustic responses, microbubble stability, and microbubble use in ultrasound imaging are discussed.

  3. Gadolinium labeled pharmaceuticals as potential MRI contrast agents for liver and biliary tract

    International Nuclear Information System (INIS)

    Najafi, A.; Amparo, E.G.; Johnson, R.F. Jr.

    1987-01-01

    Three gadolinium-labeled compounds, potential nuclear magnetic resonance (NMR) imaging contrast agents for liver and biliary tract, were studied: 1) Gd-DISIDA, 2) Gd-DTPA-Liposomes, and 3) Gd-DTPA dihexadecylamide (Gd-diamide). In each case, ''Carrier Added'' Gd-153 with specific activity of about 5uCi/mg was used. Each labeled compound was evaluated in experimental animals. Gd-DISIDA proved unsatisfactory because of in vivo instability. Gd-DTPA-Liposomes demonstrated strong toxic effects probably due to pulmonary embolism when large amounts of this compound was administered intravenously. Gd-diamide showed good uptake in the hepatocytes with subsequent excretion into the biliary tract. Several rabbits were imaged in a 0.6T NMR imaging system before and after injection of Gd-diamide. Pulse sequences were chosen that would yield T1-weighted images and permit calculation of T1 relaxation times. This compound produced significant shortening of the T1 relaxation times of the liver and observable increase in intensity on the T1-weighted images. Gd-diamide shows promise as potential NMR contrast agent for liver and biliary tract imaging. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-01-15

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

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  6. Gastric stromal tumor: two-phase dynamic CT findings with water as oral contrast agents

    International Nuclear Information System (INIS)

    Lee, Se Hyo; Cho, June Sik; Shin, Kyung Sook; Jeong, Ki Ho; Park, Jin Yong; Yu, Ho Jun; Kim, Young Min; Jeon, Kwang Jin

    2000-01-01

    To evaluate two-phase dynamic CT with water as oral contrast agents in the CT diagnosis of gastric stromal tumors. We retrospectively reviewed the CT findings in 21 patients with pathologically proven gastric stromal tumors. Six were found to be benign, twelve were malignant, and there were three cases of STUMP (stromal tumor uncertain malignant potential). Two-phase dynamic CT scans with water as oral contrast agents were obtained 60-70 secs (portal phase) and 3 mins (equilibrium phase) after the start of IV contrast administration. We determined the size, growth pattern, and enhancement pattern of the tumors and overlying mucosa, the presence or absence of ulceration and necrosis, tumor extent, and lymph nod and distant metastasis. The CT and pathologic findings were correlated. All six benign tumors and three STUMP were less than 5.5 cm in size, and during the portal phase showed round endogastric masses with highly enhanced, intact overlying mucosa. Twelve malignant tumors were 4.5-15.5 cm in size (mean, 11.5 cm); an endogastric mass was seen in three cases, an exogastric mass in one, and a mixed pattern in eight. On portal phase images the tumors were not significantly enhanced, but highly enhanced feeding vessels were noted in five larger tumors (greater than 10 cm). All 12 malignant tumors showed ulceration and necrosis, and interruption of overlying mucosa was clearly seen during the portal phase. We were readily able to evaluate tumor extent during this phase, and in ten malignant tumors there was no invasion of adjacent organs. Seven malignant tumors showed air density within their necrotic portion (p less than 0.05). On equilibrium phase images, all malignant tumors showed heterogeneous enhancement due to necrosis, and poorly enhanced overlying mucosa. Dynamic CT during the portal phase with water as oral contrast agents was useful for depicting the submucosal origin of gastric stromal tumors and for evaluating the extent of malignant stromal tumors. Our

  7. Antitumor efficacy of conventional anticancer drugs is enhanced by the vascular targeting agent ZD6126

    International Nuclear Information System (INIS)

    Siemann, Dietmar W.; Rojiani, Amyn M.

    2002-01-01

    Purpose: The present report reviews the preclinical data on combined chemotherapy/vascular targeting agent treatments. Basic principles are illustrated in studies evaluating the antitumor efficacy of the vascular targeting agent ZD6126 (N-acetylcochinol-O-phosphate) when combined with the anticancer drug cisplatin in experimental rodent (KHT sarcoma) and human renal (Caki-1) tumor models. Methods and Materials: C3H/HeJ and NCR/nu-nu mice bearing i.m. tumors were injected i.p. with ZD6126 (0-150 mg/kg) or cisplatin (0-20 mg/kg) either alone or in combination. Tumor response to treatment was assessed by clonogenic cell survival. Results: Treatment with ZD6126 was found to damage existing neovasculature, leading to a rapid vascular shutdown. Histologic evaluation showed dose-dependent morphologic damage of tumor cells within a few hours after drug exposure, followed by extensive central tumor necrosis and neoplastic cell death as a result of prolonged ischemia. ZD6126 doses that led to pathophysiologic effects also enhanced the tumor cell killing of cisplatin when administered either 24 h before or 1-24 h after chemotherapy. In both tumor models, the administration of a 150 mg/kg dose of ZD6126 1 h after a range of doses of cisplatin resulted in an increase in tumor cell kill 10-500-fold greater than that seen with chemotherapy alone. In contrast, the inclusion of the antivascular agent did not increase bone marrow stem cell toxicity associated with this anticancer drug. Conclusion: The results obtained in the KHT and Caki-1 tumor models indicate that ZD6126 effectively enhanced the antitumor effects of cisplatin therapy. These findings are representative of the marked enhancements generally observed when vascular targeting agents are combined with chemotherapy in solid tumor therapy

  8. Ultrasonic-assisted synthesis of magnetite based MRI contrast agent using cysteine as the biocapping coating

    International Nuclear Information System (INIS)

    Ahmadi, Reza; Malek, Mahrooz; Hosseini, Hamid Reza Madaah; Shokrgozar, Mohammad Ali; Oghabian, Mohammad Ali; Masoudi, Afshin; Gu Ning; Zhang Yu

    2011-01-01

    Highlights: ► We used cysteine as surfactant to synthesize stable magnetite-based ferrofluids. ► pH increase from 11 to 12 led to particle size decrease from 19.58 to 10.02 nm. ► Cytotoxicity assay showed that synthesized particles were biocompatible. ► MRI results showed that magnetite particles were accumulated in lymph nodes. - Abstract: Magnetite nanoparticles (mean particle size ranging from 10 to 20 nm) were prepared by a biomolecule-assisted solution-phase approach under ultrasonic irradiation. Cysteine was used as the capping agent in the solution. The results show that cysteine could be an efficient biocapping agent in producing Fe 3 O 4 nanoparticles. The crystal structure and magnetic properties of the nanoparticles were characterized by XRD and VSM techniques, respectively. FT-IR was used to investigate the presence of cysteine on the nanoparticles surface. The influence of pH value of the solution on the size distribution and hydrodynamic size of nanoparticles were studied by TEM and DLS methods, respectively. The MTT assay performed by incubation of L929 cells, showed the good biocompability of synthesized ferrofluids. In vitro T1 and T2 relaxivity measurements along with in vivo studies, which were conducted on rats, demonstrate that synthesized nanoparticles are applicable as the contrast agents, especially for imaging of the lymphatic system.

  9. Effects of iodinated contrast agent, xylocaine and gadolinium concentration on the signal emitted in magnetic resonance arthrography: a samples study

    Directory of Open Access Journals (Sweden)

    Yvana Lopes Pinheiro da Silva

    2015-04-01

    Full Text Available Objective: To investigate the effects of dilution of paramagnetic contrast agent with iodinated contrast and xylocaine on the signal intensity during magnetic resonance arthrography, and to improve the paramagnetic contrast agent concentration utilized in this imaging modality. Materials and Methods: Samples specially prepared for the study with three different concentrations of paramagnetic contrast agent diluted in saline, iodinated contrast agent and xylocaine were imaged with fast spin echo T1-weighted sequences with fat saturation. The samples were placed into flasks and graphical analysis of the signal intensity was performed as a function of the paramagnetic contrast concentration. Results: As compared with samples of equal concentrations diluted only with saline, the authors have observed an average signal intensity decrease of 20.67% for iodinated contrast agent, and of 28.34% for xylocaine. However, the increased gadolinium concentration in the samples caused decrease in signal intensity with all the dilutions. Conclusion: Minimizing the use of iodinated contrast media and xylocaine and/or the use of a gadolinium concentration of 2.5 mmol/L diluted in saline will improve the sensitivity of magnetic resonance arthrography.

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-09-15

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

  12. 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.

  13. Carbon dioxide as a venous contrast agent: Applications in interventional radiology=20

    International Nuclear Information System (INIS)

    Hahn, Seong Tae; Lee, Jae Mun; Kim, Choon Yul; Shinn, Kyung Sub; Pfammatter, Thomas; Cho, Kyung Jae

    1997-01-01

    To evaluate the safety and usefulness of carbon dioxide(CO 2 ) as a venous contrast agent for upper-arm placement of peripherally inserted central venous catheter (PICC), vena caval filter placement, and for visualization of the portal vein in transjugular intrahepatic portosystemic shunt(TIPS). About 20-30ml of CO 2 was used as an alternative to iodinated contrast material for digital subtraction angiography (DSA) and fluoroscopy to guide upper-arm placement of PICC in 46 patients, for inferior venacavogram before filter placement in five, and for visualization of the portal vein during TIPS in two. Vital signs, peripheral arterial oxygen saturation, and renal function were checked during and after delivery of CO 2 . All CO 2 DSA for PICC placement clearly delineated patency or stenosis of the central veins. In 41 of 46 patients (89 %), PICC placement with CO 2 guidance was successful. The mean number of venipunctures for PICC placement was 1.9, and the mean volume of CO 2 injected for venipuncture was 35ml. In five patients, Titanium Greenfield filters were successfully implanted into the inferior vena cava following CO 2 vena cavography. In two patients in whom hepatopetal portal flow was seen on indirect portography, the portal vein was visualized by CO 2 -wedged hepatic venography. Injection of CO 2 into the splenic vein following TIPS placement revealed shunt patency. Vital signs and oxygen saturation did not change, and there was no evidence of renal