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Sample records for photothermal contrast agents

  1. Theranostic Au Cubic Nano-aggregates as Potential Photoacoustic Contrast and Photothermal Therapeutic Agents

    PubMed Central

    Hu, Juan; Zhu, Xianglong; Li, Hui; Zhao, Zhenghuan; Chi, Xiaoqin; Huang, Guoming; Huang, Dengtong; Liu, Gang; Wang, Xiaomin; Gao, Jinhao

    2014-01-01

    Multifunctional nanostructures combining diagnosis and therapy modalities into one entity have drawn much attention in the biomedical applications. Herein, we report a simple and cost-effective method to synthesize a novel cubic Au nano-aggregates structure with edge-length of 80 nm (Au-80 CNAs), which display strong near-infrared (NIR) absorption, excellent water-solubility, good photothermal stability, and high biocompatibility. Under 808 nm laser irradiation for 5 min, the temperature of the solution containing Au-80 CNAs (100 μg/mL) increased by ~38 °C. The in vitro and in vivo studies demonstrated that Au-80 CNAs could act as both photothermal therapeutic (PTT) agents and photoacoustic imaging (PAI) contrast agents, indicating that the only one nano-entity of Au-80 CNAs shows great potentials for theranostic applications. Moreover, this facile and cost-effective synthetic method provides a new strategy to prepare stable Au nanomaterials with excellent optical properties for biomedical applications. PMID:24672584

  2. In vivo photothermal optical coherence tomography of gold nanorod contrast agents

    PubMed Central

    Tucker-Schwartz, J. M.; Meyer, T. A.; Patil, C. A.; Duvall, C. L.; Skala, M. C.

    2012-01-01

    Photothermal optical coherence tomography (PT-OCT) is a potentially powerful tool for molecular imaging. Here, we characterize PT-OCT imaging of gold nanorod (GNR) contrast agents in phantoms, and we apply these techniques for in vivo GNR imaging. The PT-OCT signal was compared to the bio-heat equation in phantoms, and in vivo PT-OCT images were acquired from subcutaneous 400 pM GNR Matrigel injections into mice. Experiments revealed that PT-OCT signals varied as predicted by the bio-heat equation, with significant PT-OCT signal increases at 7.5 pM GNR compared to a scattering control (p < 0.01) while imaging in common path configuration. In vivo PT-OCT images demonstrated an appreciable increase in signal in the presence of GNRs compared to controls. Additionally, in vivo PT-OCT GNR signals were spatially distinct from blood vessels imaged with Doppler OCT. We anticipate that the demonstrated in vivo PT-OCT sensitivity to GNR contrast agents is sufficient to image molecular expression in vivo. Therefore, this work demonstrates the translation of PT-OCT to in vivo imaging and represents the next step towards its use as an in vivo molecular imaging tool. PMID:23162726

  3. Gold nanorods as contrast agents for biological imaging: optical properties, surface conjugation, and photothermal effects†

    PubMed Central

    Tong, Ling; Wei, Qingshan; Wei, Alexander; Cheng, Ji-Xin

    2009-01-01

    Gold nanorods (NRs) have plasmon-resonant absorption and scattering in the near-infrared (NIR) region, making them attractive probes for in vitro and in vivo imaging. In the cellular environment, NRs can provide scattering contrast for darkfield microscopy, or emit a strong two-photon luminescence (TPL) due to plasmon-enhanced two-photon absorption. NRs have also been employed in biomedical imaging modalities such as optical coherence tomography (OCT) or photoacoustic tomography (PAT). Careful control over surface chemistry enhances the capacity of NRs as biological imaging agents by enabling cell-specific targeting, and by increasing their dispersion stability and circulation lifetimes. NRs can also efficiently convert optical energy into heat, and inflict localized damage to tumor cells. Laser-induced heating of NRs can disrupt cell membrane integrity and homeostasis, resulting in Ca2+ influx and the depolymerization of the intracellular actin network. The combination of plasmon-resonant optical properties, intense local photothermal effects, and robust surface chemistry render gold NRs as promising theragnostic agents. PMID:19161395

  4. Targeted Aucore-Agshell nanorods as a dual-functional contrast agent for photoacoustic imaging and photothermal therapy

    PubMed Central

    Shi, Yiwen; Peng, Dong; Wang, Kun; Chai, Xinyu; Ren, Qiushi; Tian, Jie; Zhou, Chuanqing

    2016-01-01

    Optimizing contrast enhancement is essential for producing specific signals in biomedical imaging and therapy. The potential of using Aucore-Agshell nanorods (Au@Ag NRs) as a dual-functional theranostic contrast agent is demonstrated for effective cancer imaging and treatments. Due to its strong NIR absorption and high efficiency of photothermal conversion, effects of both photoacoustic tomography (PAT) and photothermal therapy (PTT) are enhanced significantly. The PAT signal grows by 45.3% and 82% in the phantom and in vivo experiments, respectively, when compared to those using Au NRs. In PTT, The maximum increase of tissue temperature treated with Au@Ag NRs is 22.8 °C, twice that with Au NRs. Results of the current study show the feasibility of using Au@Ag NRs for synergetic PAT with PTT. And it will enhance the potential application on real-time PAT guided PTT, which will greatly benefit the customized PTT treatment of cancer. PMID:27231624

  5. PEGylated Cu3BiS3 hollow nanospheres as a new photothermal agent for 980 nm-laser-driven photothermochemotherapy and a contrast agent for X-ray computed tomography imaging

    NASA Astrophysics Data System (ADS)

    Zhou, Shu-Mei; Ma, De-Kun; Zhang, Sheng-Hui; Wang, Wei; Chen, Wei; Huang, Shao-Ming; Yu, Kang

    2016-01-01

    Developing multifunctional near-infrared (NIR) light-driven photothermal agents is in high demand for efficient cancer therapy. Herein, PEGylated Cu3BiS3 hollow nanospheres (HNSs) with an average diameter of 80 nm were synthesized through a facile ethylene glycol-mediated solvothermal route. The obtained PEGylated Cu3BiS3 HNSs exhibited strong NIR optical absorption with a large molar extinction coefficient of 4.1 × 109 cm-1 M-1 at 980 nm. Under the irradiation of a 980 nm laser with a safe power density of 0.72 W cm-2, Cu3BiS3 HNSs produced significant photothermal heating with a photothermal transduction efficiency of 27.5%. The Cu3BiS3 HNSs also showed a good antitumoral drug doxorubicin (DOX) loading capacity and pH- and NIR-responsive DOX release behaviors. At a low dosage of 10 μg mL-1, HeLa cells could be efficiently killed through a synergistic effect of chemo- and photothermo-therapy respectively based on the DOX release and the photothermal effect of Cu3BiS3 HNSs. In addition, Cu3BiS3 HNSs displayed a good X-ray computed tomography (CT) imaging capability. Furthermore, Cu3BiS3 HNSs could be used for efficient in vivo photothermochemotherapy and X-ray CT imaging of mice bearing melanoma skin cancer. This multifunctional theranostic nanomaterial shows potential promise for cancer therapy.Developing multifunctional near-infrared (NIR) light-driven photothermal agents is in high demand for efficient cancer therapy. Herein, PEGylated Cu3BiS3 hollow nanospheres (HNSs) with an average diameter of 80 nm were synthesized through a facile ethylene glycol-mediated solvothermal route. The obtained PEGylated Cu3BiS3 HNSs exhibited strong NIR optical absorption with a large molar extinction coefficient of 4.1 × 109 cm-1 M-1 at 980 nm. Under the irradiation of a 980 nm laser with a safe power density of 0.72 W cm-2, Cu3BiS3 HNSs produced significant photothermal heating with a photothermal transduction efficiency of 27.5%. The Cu3BiS3 HNSs also showed a good

  6. PEGylated Cu3BiS3 hollow nanospheres as a new photothermal agent for 980 nm-laser-driven photothermochemotherapy and a contrast agent for X-ray computed tomography imaging.

    PubMed

    Zhou, Shu-Mei; Ma, De-Kun; Zhang, Sheng-Hui; Wang, Wei; Chen, Wei; Huang, Shao-Ming; Yu, Kang

    2016-01-21

    Developing multifunctional near-infrared (NIR) light-driven photothermal agents is in high demand for efficient cancer therapy. Herein, PEGylated Cu3BiS3 hollow nanospheres (HNSs) with an average diameter of 80 nm were synthesized through a facile ethylene glycol-mediated solvothermal route. The obtained PEGylated Cu3BiS3 HNSs exhibited strong NIR optical absorption with a large molar extinction coefficient of 4.1 × 10(9) cm(-1) M(-1) at 980 nm. Under the irradiation of a 980 nm laser with a safe power density of 0.72 W cm(-2), Cu3BiS3 HNSs produced significant photothermal heating with a photothermal transduction efficiency of 27.5%. The Cu3BiS3 HNSs also showed a good antitumoral drug doxorubicin (DOX) loading capacity and pH- and NIR-responsive DOX release behaviors. At a low dosage of 10 μg mL(-1), HeLa cells could be efficiently killed through a synergistic effect of chemo- and photothermo-therapy respectively based on the DOX release and the photothermal effect of Cu3BiS3 HNSs. In addition, Cu3BiS3 HNSs displayed a good X-ray computed tomography (CT) imaging capability. Furthermore, Cu3BiS3 HNSs could be used for efficient in vivo photothermochemotherapy and X-ray CT imaging of mice bearing melanoma skin cancer. This multifunctional theranostic nanomaterial shows potential promise for cancer therapy. PMID:26488908

  7. Ferrimagnetic susceptibility contrast agents.

    PubMed

    Bach-Gansmo, T

    1993-01-01

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

  8. A dual function theranostic agent for near-infrared photoacoustic imaging and photothermal therapy

    NASA Astrophysics Data System (ADS)

    Upputuri, Paul Kumar; Huang, Shuo; Wang, Mingfeng; Pramanik, Manojit

    2016-03-01

    Theranostic, defined as combining diagnostic and therapeutic agents, has attracted more attention in biomedical application. It is essential to monitor diseased tissue before treatment. Photothermal therapy (PTT) is a promising treatment of cancer tissue due to minimal invasion, unharmful to normal tissue and high efficiency. Photoacoustic tomography (PAT) is a hybrid nonionizing biomedical imaging modality that combines rich optical contrast and high ultrasonic resolution in a single imaging modality. The near infra-red (NIR) wavelengths, usually used in PAT, can provide deep penetration at the expense of reduced contrast, as the blood absorption drops in the NIR range. Exogenous contrast agents with strong absorption in the NIR wavelength range can enhance the photoacoustic imaging contrast as well as imaging depth. Most theranostic agents incorporating PAT and PTT are inorganic nanomaterials that suffer from poor biocompatibility and biodegradability. Herein, we present an benzo[1,2-c;4,5-c'] bis[1,2,5] thiadiazole (BBT), based theranostic agent which not only acts as photoacoustic contrast agent but also a photothermal therapy agent. Experiments were performed on animal blood and organic nanoparticles embedded in a chicken breast tissue using PAT imaging system at ~803 nm wavelengths. Almost ten time contrast enhancement was observed from the nanoparticle in suspension. More than 6.5 time PA signal enhancement was observed in tissue at 3 cm depth. HeLa cell lines was used to test photothermal effect showing 90% cells were killed after 10 min laser irradiation. Our results indicate that the BBT - based naoparticles are promising theranostic agents for PAT imaging and cancer treatment by photothermal therapy.

  9. Cu7.2S4 nanocrystals: a novel photothermal agent with a 56.7% photothermal conversion efficiency for photothermal therapy of cancer cells

    NASA Astrophysics Data System (ADS)

    Li, Bo; Wang, Qian; Zou, Rujia; Liu, Xijian; Xu, Kaibing; Li, Wenyao; Hu, Junqing

    2014-02-01

    Copper sulphides, as a novel kind of photothermal agent for photothermal therapy (PTT) of cancer cells, have attracted increasing attention in recent years due to good photostability, synthetic simplicity, low toxicity and low cost. However, the unsatisfactory photothermal conversion efficiency of copper sulphides limits their bioapplication as PTT agents. Herein, Cu7.2S4 NCs with a mean size of ~20 nm as a novel photothermal agent have been prepared by a simple thermal decomposition route. Moreover, these NCs exhibit strong near-infrared (NIR) absorption, good photostability and significant photothermal conversion efficiency up to 56.7% due to strong NIR absorption, good dispersity and suitable size. Importantly, these NCs can be very compatibly used as a 980 nm laser-driven PTT agent for the efficient PTT of cancer cells in vitro and in vivo.Copper sulphides, as a novel kind of photothermal agent for photothermal therapy (PTT) of cancer cells, have attracted increasing attention in recent years due to good photostability, synthetic simplicity, low toxicity and low cost. However, the unsatisfactory photothermal conversion efficiency of copper sulphides limits their bioapplication as PTT agents. Herein, Cu7.2S4 NCs with a mean size of ~20 nm as a novel photothermal agent have been prepared by a simple thermal decomposition route. Moreover, these NCs exhibit strong near-infrared (NIR) absorption, good photostability and significant photothermal conversion efficiency up to 56.7% due to strong NIR absorption, good dispersity and suitable size. Importantly, these NCs can be very compatibly used as a 980 nm laser-driven PTT agent for the efficient PTT of cancer cells in vitro and in vivo. Electronic supplementary information (ESI) available: Figures. See DOI: 10.1039/c3nr06242b

  10. Photoacoustic cell for ultrasound contrast agent characterization.

    PubMed

    Alippi, A; Bettucci, A; Biagioni, A; D'Orazio, A; Germano, M; Passeri, D

    2010-10-01

    Photoacoustics has emerged as a tool for the study of liquid gel suspension behavior and has been recently employed in a number of new biomedical applications. In this paper, a photoacoustic sensor is presented which was designed and realized for analyzing photothermal signals from solutions filled with microbubbles, commonly used as ultrasound contrast agents in echographic imaging techniques. It is a closed cell device, where photothermal volume variation of an aqueous solution produces the periodic deflection of a thin membrane closing the cell at the end of a short pipe. The cell then acts as a Helmholtz resonator, where the displacement of the membrane is measured through a laser probe interferometer, whereas photoacoustic signal is generated by a laser chopped light beam impinging onto the solution through a glass window. Particularly, the microbubble shell has been modeled through an effective surface tension parameter, which has been then evaluated from experimental data through the shift of the resonance frequencies of the photoacoustic sensor. This shift of the resonance frequencies of the photoacoustic sensor caused by microbubble solutions is high enough for making such a cell a reliable tool for testing ultrasound contrast agent, particularly for bubble shell characterization. PMID:21034110

  11. PEGylated Copper Nanowires as a Novel Photothermal Therapy Agent.

    PubMed

    Li, Kuei-Chang; Chu, Hsun-Chen; Lin, Yow; Tuan, Hsing-Yu; Hu, Yu-Chen

    2016-05-18

    Metal nanowires are promising for their applications including electrical connectors, transparent conductive electrodes and conductive additives, but the use of metal nanowires as photothermal agents to convert light to heat has yet to be reported. Here we synthesized dispersible polyethylene glycol-coated (PEGylated) copper nanowires (CuNWs) and showed for the first time that PEGylated CuNWs were able to convert near-infrared (NIR, 808 nm) light into heat at a photothermal efficiency of 12.5%. The PEGylated CuNWs exhibited good reusability and enabled rapid temperature rise to >50 °C in 6 min by NIR irradiation. The PEGylated CuNWs were flexible and intertwined around the cancer cells, which, upon NIR irradiation, allowed for direct heat transmission to cells and effectively triggered cancer cell ablation in vitro. Intratumoral injection of PEGylated CuNWs into colon tumor-bearing mice and ensuing NIR irradiation for 6 min significantly raised the local temperature to >50 °C, induced necrosis, and suppressed tumor growth. Compared with other NIR light absorbing noble metal-based nanomaterials, PEGylated CuNWs are relatively easy to synthesize in both laboratory and large scales using the low cost copper. This study demonstrated the potential of PEGylated CuNWs as a new cost-effective photothermal agent, and paved a new avenue to using CuNWs for cancer therapy. PMID:27111420

  12. Polypyrrole Hollow Microspheres as Echogenic Photothermal Agent for Ultrasound Imaging Guided Tumor Ablation

    NASA Astrophysics Data System (ADS)

    Zha, Zhengbao; Wang, Jinrui; Qu, Enze; Zhang, Shuhai; Jin, Yushen; Wang, Shumin; Dai, Zhifei

    2013-08-01

    Ultrasound (US) imaging provides a valuable opportunity to administer photothermal therapy (PTT) of cancer with real-time guidance to ensure proper targeting, but only a few theranostic agents were developed by physically grafting near infrared (NIR)-absorbing inorganic nanomaterials to ready-made ultrasound contrast agents (UCAs) for US imaging guided PTT. In this paper, NIR absorbing hollow microspheres were generated from polypyrrole merely using a facile one-step microemulsion method. It was found that the obtained polypyrrole hollow microspheres (PPyHMs) can act as an efficient theranostic agent not only to enhance US imaging greatly, but also exhibit excellent photohyperthermic effects. The contrast consistently sustained the echo signals for no less than 5 min and the NIR laser light ablated the tumor completely within two weeks in the presence of PPyHMs. More importantly, no use of additional NIR absorber substantially minimizes an onetime dose of the theranostic agent.

  13. Polypyrrole Hollow Microspheres as Echogenic Photothermal Agent for Ultrasound Imaging Guided Tumor Ablation

    PubMed Central

    Zha, Zhengbao; Wang, Jinrui; Qu, Enze; Zhang, Shuhai; Jin, Yushen; Wang, Shumin; Dai, Zhifei

    2013-01-01

    Ultrasound (US) imaging provides a valuable opportunity to administer photothermal therapy (PTT) of cancer with real-time guidance to ensure proper targeting, but only a few theranostic agents were developed by physically grafting near infrared (NIR)-absorbing inorganic nanomaterials to ready-made ultrasound contrast agents (UCAs) for US imaging guided PTT. In this paper, NIR absorbing hollow microspheres were generated from polypyrrole merely using a facile one-step microemulsion method. It was found that the obtained polypyrrole hollow microspheres (PPyHMs) can act as an efficient theranostic agent not only to enhance US imaging greatly, but also exhibit excellent photohyperthermic effects. The contrast consistently sustained the echo signals for no less than 5 min and the NIR laser light ablated the tumor completely within two weeks in the presence of PPyHMs. More importantly, no use of additional NIR absorber substantially minimizes an onetime dose of the theranostic agent. PMID:23912977

  14. Advanced contrast nanoagents for photoacoustic molecular imaging, cytometry, blood test and photothermal theranostics†

    PubMed Central

    de la Zerda, Adam; Kim, Jin-Woo; Galanzha, Ekaterina I.; Gambhir, Sanjiv S.; Zharov, Vladimir P.

    2013-01-01

    Various nanoparticles have raised significant interest over the past decades for their unique physical and optical properties and biological utilities. Here we summarize the vast applications of advanced nanoparticles with a focus on carbon nanotube (CNT)-based or CNT-catalyzed contrast agents for photoacoustic (PA) imaging, cytometry and theranostics applications based on the photothermal (PT) effect. We briefly review the safety and potential toxicity of the PA/PT contrast nanoagents, while showing how the physical properties as well as multiple biological coatings change their toxicity profiles and contrasts. We provide general guidelines needed for the validation of a new molecular imaging agent in living subjects, and exemplify these guidelines with single-walled CNTs targeted to αvβ3, an integrin associated with tumor angiogenesis, and golden carbon nanotubes targeted to LYVE-1, endothelial lymphatic receptors. An extensive review of the potential applications of advanced contrast agents is provided, including imaging of static targets such as tumor angiogenesis receptors, in vivo cytometry of dynamic targets such as circulating tumor cells and nanoparticles in blood, lymph, bones and plants, methods to enhance the PA and PT effects with transient and stationary bubble conjugates, PT/PA Raman imaging and multispectral histology. Finally, theranostic applications are reviewed, including the nanophotothermolysis of individual tumor cells and bacteria with clustered nanoparticles, nanothrombolysis of blood clots, detection and purging metastasis in sentinel lymph nodes, spectral hole burning and multiplex therapy with ultrasharp rainbow nanoparticles. PMID:22025336

  15. Nuclear magnetic resonance contrast agents

    DOEpatents

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

    1997-12-30

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

  16. Nuclear magnetic resonance contrast agents

    DOEpatents

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

    1997-01-01

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

  17. Polycatechol Nanoparticle MRI Contrast Agents.

    PubMed

    Li, Yiwen; Huang, Yuran; Wang, Zhao; Carniato, Fabio; Xie, Yijun; Patterson, Joseph P; Thompson, Matthew P; Andolina, Christopher M; Ditri, Treffly B; Millstone, Jill E; Figueroa, Joshua S; Rinehart, Jeffrey D; Scadeng, Miriam; Botta, Mauro; Gianneschi, Nathan C

    2016-02-01

    Amphiphilic triblock copolymers containing Fe(III) -catecholate complexes formulated as spherical- or cylindrical-shaped micellar nanoparticles (SMN and CMN, respectively) are described as new T1-weighted agents with high relaxivity, low cytotoxicity, and long-term stability in biological fluids. Relaxivities of both SMN and CMN exceed those of established gadolinium chelates across a wide range of magnetic field strengths. Interestingly, shape-dependent behavior is observed in terms of the particles' interactions with HeLa cells, with CMN exhibiting enhanced uptake and contrast via magnetic resonance imaging (MRI) compared with SMN. These results suggest that control over soft nanoparticle shape will provide an avenue for optimization of particle-based contrast agents as biodiagnostics. The polycatechol nanoparticles are proposed as suitable for preclinical investigations into their viability as gadolinium-free, safe, and effective imaging agents for MRI contrast enhancement. PMID:26681255

  18. Dendrimer-Templated Ultrasmall and Multifunctional Photothermal Agents for Efficient Tumor Ablation.

    PubMed

    Zhou, Zhengjie; Wang, Yitong; Yan, Yang; Zhang, Qiang; Cheng, Yiyun

    2016-04-26

    Ultrasmall and multifunctional nanoparticles are highly desirable for photothermal cancer therapy, but the synthesis of these nanoparticles remains a huge challenge. Here, we used a dendrimer as a template to synthesize ultrasmall photothermal agents and further modified them with multifunctional groups. Dendrimer-encapsulated nanoparticles (DENPs) including copper sulfide, platinum, and palladium nanoparticles possessed a sub-5 nm size and exhibited an excellent photothermal effect. DENPs were further modified with TAT or RGD peptides to facilitate their cellular uptake and targeting delivery to tumors. They were also decorated with fluorescent probes for real-time imaging and tracking of the particles' distribution. The in vivo study revealed RGD-modified DENPs efficiently reduced the tumor growth upon near-infrared irradiation. In all, our study provides a facile and flexible scaffold to prepare ultrasmall and multifunctional photothermal agents. PMID:27054555

  19. Gold nanorods as photothermal agents and autofluorescence enhancer to track cell death during plasmonic photothermal therapy

    NASA Astrophysics Data System (ADS)

    Kannadorai, Ravi Kumar; Chiew, Geraldine Giap Ying; Luo, Kathy Qian; Liu, Quan

    2015-07-01

    The transverse and longitudinal plasmon resonance in gold nanorods can be exploited to localize the photothermal therapy and influence the fluorescence to monitor the treatment outcome at the same time. While the longitudinal plasmon peak contributes to the photothermal effect, the transverse peak can enhance fluorescence. After cells take in PEGylated nanorods through endocytosis, autofluorescence from endogenous fluorophores such as nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) in the mitochondria is enhanced two times, which is a good indicator of the respiratory status of the cell. When cells are illuminated continuously with near infrared laser, the temperature reaches the hyperthermic region within the first four minutes, which demonstrates the efficiency of gold nanorods in photothermal therapy. The cell viability test and autofluorescence intensity show good correlation indicating the progress of cell death over time.

  20. Single Walled Carbon Nanohorns as Photothermal Cancer Agents

    SciTech Connect

    Whitney, John; Sarkar, Saugata; Zhang, Jianfei; Do, Thao; Manson, Mary kyle; Campbell, Tom; Puretzky, Alexander A; Rouleau, Christopher M; More, Karren Leslie; Geohegan, David B; Rylander, Christopher; Dorn, Harry C; Rylander, Nichole M

    2011-01-01

    heating or SWNH treatment alone. Samples heated for 6 minutes with 0.085 mg/ml SWNHs demonstrated increasing viability as the radial distance from the incident laser beam increased. The significant increases in absorption, temperature elevation, and cell death with inclusion of SWNHs in laser therapy demonstrate the potential of their use as agents for enhancing photothermal tumor destruction.

  1. Contrast Agents for Photoacoustic and Thermoacoustic Imaging: A Review

    PubMed Central

    Wu, Dan; Huang, Lin; Jiang, Max S.; Jiang, Huabei

    2014-01-01

    Photoacoustic imaging (PAI) and thermoacoustic imaging (TAI) are two emerging biomedical imaging techniques that both utilize ultrasonic signals as an information carrier. Unique advantages of PAI and TAI are their abilities to provide high resolution functional information such as hemoglobin and blood oxygenation and tissue dielectric properties relevant to physiology and pathology. These two methods, however, may have a limited detection depth and lack of endogenous contrast. An exogenous contrast agent is often needed to effectively resolve these problems. Such agents are able to greatly enhance the imaging contrast and potentially break through the imaging depth limit. Furthermore, a receptor-targeted contrast agent could trace the molecular and cellular biological processes in tissues. Thus, photoacoustic and thermoacoustic molecular imaging can be outstanding tools for early diagnosis, precise lesion localization, and molecular typing of various diseases. The agents also could be used for therapy in conjugation with drugs or in photothermal therapy, where it functions as an enhancer for the integration of diagnosis and therapy. In this article, we present a detailed review about various exogenous contrast agents for photoacoustic and thermoacoustic molecular imaging. In addition, challenges and future directions of photoacoustic and thermoacoustic molecular imaging in the field of translational medicine are also discussed. PMID:25530615

  2. Semimetal nanomaterials of antimony as highly efficient agent for photoacoustic imaging and photothermal therapy.

    PubMed

    Li, Wanwan; Rong, Pengfei; Yang, Kai; Huang, Peng; Sun, Kang; Chen, Xiaoyuan

    2015-03-01

    In this study we report semimetal nanomaterials of antimony (Sb) as highly efficient agent for photoacoustic imaging (PAI) and photothermal therapy (PTT). The Sb nanorod bundles have been synthesized through a facile route by mixing 1-octadecane (ODE) and oleyl amine (OAm) as the solvent. The aqueous dispersion of PEGylated Sb NPs, due to its broad and strong photoabsorption ranging from ultraviolet (UV) to near-infrared (NIR) wavelengths, is applicable as a photothermal agent driven by 808 nm laser with photothermal conversion efficiency up to 41%, noticeably higher than most of the PTT agents reported before. Our in vitro experiments also showed that cancer cell ablation effect of PEGylated Sb NPs was dependent on laser power. By intratumoral administration of PEGylated Sb NPs, 100% tumor ablation can be realized by using NIR laser irradiation with a lower power of 1 W/cm(2) for 5 min (or 0.5 W/cm(2) for 10 min) and no obvious toxic side effect is identified after photothermal treatment. Moreover, intense PA signal was also observed after intratumoral injection of PEGylated Sb NPs and NIR laser irradiation due to their strong NIR photoabsorption, suggesting PEGylated Sb NPs as a potential NIR PA agent. Based on the findings of this work, further development of using other semimetal nanocrystals as highly efficient NIR agents can be achieved for vivo tumor imaging and PTT.

  3. Ultrasmall Black Phosphorus Quantum Dots: Synthesis and Use as Photothermal Agents.

    PubMed

    Sun, Zhengbo; Xie, Hanhan; Tang, Siying; Yu, Xue-Feng; Guo, Zhinan; Shao, Jundong; Zhang, Han; Huang, Hao; Wang, Huaiyu; Chu, Paul K

    2015-09-21

    Black phosphorus quantum dots (BPQDs) were synthesized using a liquid exfoliation method that combined probe sonication and bath sonication. With a lateral size of approximately 2.6 nm and a thickness of about 1.5 nm, the ultrasmall BPQDs exhibited an excellent NIR photothermal performance with a large extinction coefficient of 14.8 L g(-1) cm(-1) at 808 nm, a photothermal conversion efficiency of 28.4%, as well as good photostability. After PEG conjugation, the BPQDs showed enhanced stability in physiological medium, and there was no observable toxicity to different types of cells. NIR photoexcitation of the BPQDs in the presence of C6 and MCF7 cancer cells led to significant cell death, suggesting that the nanoparticles have large potential as photothermal agents.

  4. BSA-directed synthesis of CuS nanoparticles as a biocompatible photothermal agent for tumor ablation in vivo.

    PubMed

    Zhang, Cai; Fu, Yan-Yan; Zhang, Xuejun; Yu, Chunshui; Zhao, Yan; Sun, Shao-Kai

    2015-08-01

    Photothermal therapy as a physical therapeutic approach has greatly attracted research interest due to its negligible systemic effects. Among the various photothermal agents, CuS nanoparticles have been widely used due to their easy preparation, low cost, high stability and strong absorption in the NIR region. However, the ambiguous biotoxicity of CuS nanoparticles limited their bio-application. So it is highly desirable to develop biocompatible CuS photothermal agents with the potential of clinical translation. Herein, we report a novel method to synthesize biocompatible CuS nanoparticles for photothermal therapy using bovine serum albumin (BSA) as a template via mimicking biomaterialization processes. Owing to the inherent biocompatibility of BSA, the toxicity assays in vitro and in vivo showed that BSA-CuS nanoparticles possessed good biocompatibility. In vitro and in vivo photothermal therapies were performed and good results were obtained. The bulk of the HeLa cells treated with BSA-CuS nanoparticles under laser irradiation (808 nm) were killed, and the tumor tissues of mice were also successfully eliminated without causing any obvious systemic damage. In summary, a novel strategy for the synthesis of CuS nanoparticles was developed using BSA as the template, and the excellent biocompatibility and efficient photothermal therapy effects of BSA-CuS nanoparticles show great potential as an ideal photothermal agent for cancer treatment.

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

    PubMed

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

    2015-05-14

    A size and shape tuned, multifunctional metal chalcogenide, Cu2S-based nanotheranostic agent is developed for trimodal imaging and multimodal therapeutics against brain cancer cells. This theranostic agent was highly efficient in optical, photoacoustic and X-ray contrast imaging systems. The folate targeted NIR-responsive photothermal ablation in synergism with the chemotherapeutic action of doxorubicin proved to be a rapid precision guided cancer-killing module. The multi-stimuli, i.e., pH-, thermo- and photo-responsive drug release behavior of the nanoconjugates opens up a wider corridor for on-demand triggered drug administration. The simple synthesis protocol, combined with the multitudes of interesting features packed into a single nanoformulation, clearly demonstrates the competing role of this Cu2S nanosystem in future cancer treatment strategies. PMID:25797920

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  7. "Basic MR Relaxation Mechanisms & Contrast Agent Design"

    PubMed Central

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

    2015-01-01

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

  8. Engineering phosphopeptide-decorated magnetic nanoparticles as efficient photothermal agents for solid tumor therapy.

    PubMed

    Wu, Man; Guo, Qiaoyan; Xu, Feng; Liu, Shujun; Lu, Xuehong; Wang, Jing; Gao, Hongwen; Luo, Ping

    2016-08-15

    Due to the high therapeutic efficiency and minimum damage towards normal tissues, phototherapy has drawn a great deal of attention in recent decades. Herein, we reported the synthesis of novel phosphopeptide-decorated magnetic nanoparticles (peptide-Fe3O4 nanoparticles), and their usages in photothermal therapy against solid tumor. By using a classical coprecipitation method and a facile ligand exchange route, these peptide-Fe3O4 nanoparticles were prepared with inexpensive inhesion. Upon the irradiation of a near-infrared (NIR) light, these nanoagents exhibited great photothermal effect with high photo-stability. In vitro biocompatibility studies of these peptide-Fe3O4 nanoparticles indicated their low cytotoxicity, negligible hemolysis, and no effect on blood coagulation. As expected, 4T1 murine breast cancer cells could be effectively damaged by these light-mediated nanoagents. Significantly, animal experiments demonstrated that these nanoagents held great solid tumor ablation effect with the assistance of a NIR laser irradiation. Additional studies focused on the long-term toxicity of these nanoagents indicated their high bio-compatibility. Thus, these peptide-Fe3O4 nanoparticles could bring more opportunities to a new generation of photothermal agents in the field of biomedicine. PMID:27214146

  9. Hybrid graphene/Au activatable theranostic agent for multimodalities imaging guided enhanced photothermal therapy.

    PubMed

    Gao, Shi; Zhang, Liwen; Wang, Guohao; Yang, Kai; Chen, Minglong; Tian, Rui; Ma, Qingjie; Zhu, Lei

    2016-02-01

    Photothermal therapy (PTT) has been increasingly investigated. However, there are still challenges in strategies that can further enhance photoconversion efficiency and improve photothermal tumor ablation effect of current nanomaterials. Herein, we developed a fluorescent/photoacoustic imaging guided PTT agent by seeding Gold (Au) nanoparticles onto graphene oxide (GO). Near infrared dye (Cy5.5) labeled-matrix metalloproteinase-14 (MMP-14) substrate (CP) was conjugated onto the GO/Au complex (GA) forming tumor targeted theranostic probe (CPGA), whereCy5.5 fluorescent signal is quenched by Surface Plasmon Resonance (SPR) capacity from both GO and Au, yet it can boost strong fluorescence signals after degradation by MMP-14. The photothermal effect of GA hybrid was found significantly elevated compared with Au or GO alone. After intravenous administration of CPGA into SCC7 tumor-bearing mice, high fluorescence and PA signals were observed in the tumor area over time, which peaked at the 6 h time point (tumor-to-normal tissue ratio of 3.64 ± 0.51 for optical imaging and 2.5 ± 0.27 for PA imaging). The tumors were then irradiated with a laser, and an excellent tumor inhibition was observedwithoutrecurrence. Our studies further encourage applications of the hybrid nanocomposite for image-guided enhanced PTT in biomedical applications, especially in cancer theranostics. PMID:26691399

  10. Gold-copper nanostars as photo-thermal agents: synthesis and advanced electron microscopy characterization

    NASA Astrophysics Data System (ADS)

    Bazán-Díaz, Lourdes; Mendoza-Cruz, Rubén; Velázquez-Salazar, J. Jesús; Plascencia-Villa, Germán; Romeu, David; Reyes-Gasga, José; Herrera-Becerra, Raúl; José-Yacamán, Miguel; Guisbiers, Grégory

    2015-12-01

    Nanoalloys have emerged as multi-functional nanoparticles with applications in biomedicine and catalysis. This work reports the efficient production and the advanced transmission electron microscopy characterization of gold-copper pentagonal nanostars. The morphology of the branches is controlled by the adequate choice of the capping agent. When oleylamine is used rounded nanostars are produced, while pointed nanostars are obtained by using hexadecylamine. Both types of nanostars were proved to be thermally stable and could therefore be used as therapeutic agents in photo-thermal therapies as confirmed by the near-infrared absorption spectra.Nanoalloys have emerged as multi-functional nanoparticles with applications in biomedicine and catalysis. This work reports the efficient production and the advanced transmission electron microscopy characterization of gold-copper pentagonal nanostars. The morphology of the branches is controlled by the adequate choice of the capping agent. When oleylamine is used rounded nanostars are produced, while pointed nanostars are obtained by using hexadecylamine. Both types of nanostars were proved to be thermally stable and could therefore be used as therapeutic agents in photo-thermal therapies as confirmed by the near-infrared absorption spectra. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06491k

  11. Contrast agent choice for intravenous coronary angiography

    SciTech Connect

    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.

  12. Contrast agent choice for intravenous coronary angiography

    NASA Astrophysics Data System (ADS)

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

    1990-05-01

    The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with monochromatic synchrotron radiation X-rays and an iodine-containing contrast agent at the Stanford Synchrotron Radiation Laboratory have shown that such an intravenous angiography procedure would be possible with an adequately intense monochromatic X-ray source. Because of the size and cost of synchrotron radiation facilities it would be desirable to make the most efficient use of the intensity available, while reducing as much as possible the radiation dose experienced by the patient. By choosing contrast agents containing elements with a higher atomic number than iodine, it is possible to both improve the image quality and reduce the patient radiation dose, while using the same synchrotron radiation source. By using Si monochromator crystals with a small mosaic spread, it is possible to increase the X-ray flux available for imaging by over an order of magnitude, without any changes in the storage ring or wiggler magnet. The most critical imaging task for intravenous coronary angiography utilizing synchrotron radiation X-rays is visualizing a coronary artery through the left ventricle or aorta which also contain contrast agent. Calculations have been made of the signal to noise ratio expected for this imaging task for various contrast agents with atomic numbers between that of iodine and bismuth. The X-ray energy spectrum of the X-17 superconduction wiggler beam line at the National Synchrotron Light Source at Brookhaven National Laboratory has been used for these calculations. Both perfect Si crystals and Si crystals with a small mosaic spread are considered as monochromators. Contrast agents containing Gd or Yb seem to have about the optimal calculated signal to noise ratio. Gd-DTPA is already approved for use as a contrast agent for

  13. Novel Cs-Based Upconversion Nanoparticles as Dual-Modal CT and UCL Imaging Agents for Chemo-Photothermal Synergistic Therapy.

    PubMed

    Liu, Yuxin; Li, Luoyuan; Guo, Quanwei; Wang, Lu; Liu, Dongdong; Wei, Ziwei; Zhou, Jing

    2016-01-01

    Lanthanide-based contrast agents have attracted increasing attention for their unique properties and potential applications in cancer theranostics. To date, many of these agents have been studied extensively in cells and small animal models. However, performance of these theranostic nanoparticles requires further improvement. In this study, a novel CsLu2F7:Yb,Er,Tm-based visual therapeutic platform was developed for imaging-guided synergistic cancer therapy. Due to the presence of the heavy alkali metal Cesium (Cs) in host lattice, the nanoplatform can provide a higher resolution X-ray CT imaging than many other reported lanthanide-based CT contrast agents. Furthermore, by using the targeted RGD motif, chemotherapy drug alpha-tocopheryl succinate (α-TOS), and photothermal coupling agent ICG, this nanoplatform simultaneously provides multifunctional imaging and targeted synergistic therapy. To demonstrate the theranostic performance of this novel nanoplatform in vivo, visual diagnosis in the small animal model was realized by UCL/CT imaging which was further integrated with targeted chemo-photothermal synergistic therapy. These results provided evidence for the successful construction of a novel lanthanide-based nanoplatform coupled with multimodal imaging diagnosis and potential application in synergistic cancer theranostics. PMID:27446485

  14. Novel Cs-Based Upconversion Nanoparticles as Dual-Modal CT and UCL Imaging Agents for Chemo-Photothermal Synergistic Therapy

    PubMed Central

    Liu, Yuxin; Li, Luoyuan; Guo, Quanwei; Wang, Lu; Liu, Dongdong; Wei, Ziwei; Zhou, Jing

    2016-01-01

    Lanthanide-based contrast agents have attracted increasing attention for their unique properties and potential applications in cancer theranostics. To date, many of these agents have been studied extensively in cells and small animal models. However, performance of these theranostic nanoparticles requires further improvement. In this study, a novel CsLu2F7:Yb,Er,Tm-based visual therapeutic platform was developed for imaging-guided synergistic cancer therapy. Due to the presence of the heavy alkali metal Cesium (Cs) in host lattice, the nanoplatform can provide a higher resolution X-ray CT imaging than many other reported lanthanide-based CT contrast agents. Furthermore, by using the targeted RGD motif, chemotherapy drug alpha-tocopheryl succinate (α-TOS), and photothermal coupling agent ICG, this nanoplatform simultaneously provides multifunctional imaging and targeted synergistic therapy. To demonstrate the theranostic performance of this novel nanoplatform in vivo, visual diagnosis in the small animal model was realized by UCL/CT imaging which was further integrated with targeted chemo-photothermal synergistic therapy. These results provided evidence for the successful construction of a novel lanthanide-based nanoplatform coupled with multimodal imaging diagnosis and potential application in synergistic cancer theranostics. PMID:27446485

  15. Image-guided synergistic photothermal therapy using photoresponsive imaging agent-loaded graphene-based nanosheets.

    PubMed

    Miao, Wenjun; Shim, Gayong; Kim, Gunwoo; Lee, Soondong; Lee, Hee-Jung; Kim, Young Bong; Byun, Youngro; Oh, Yu-Kyoung

    2015-08-10

    We report the image-guided synergistic photothermal antitumor effects of photoresponsive near-infrared (NIR) imaging agent, indocyanine green (ICG), by loading onto hyaluronic acid-anchored, reduced graphene oxide (HArGO) nanosheets. Loading of ICG onto either rGO (ICG/rGO) or HArGO (ICG/HArGO) substantially improved the photostability of photoresponsive ICG upon NIR irradiation. After 1min of irradiation, the NIR absorption peak of ICG almost disappeared whereas the peak of ICG on rGO or HArGO was retained even after 5min of irradiation. Compared with plain rGO, HArGO provided greater cellular delivery of ICG and photothermal tumor cell-killing effects upon laser irradiation in CD44-positive KB cells. The temperature of cell suspensions treated with ICG/HArGO was 2.4-fold higher than that of cells treated with free ICG. Molecular imaging revealed that intravenously administered ICG/HArGO accumulated in KB tumor tissues higher than ICG/rGO or free ICG. Local temperatures in tumor tissues of laser-irradiated KB cell-bearing nude mice were highest in those intravenously administered ICG/HArGO, and were sufficient to trigger thermal-induced complete tumor ablation. Immunohistologically stained tumors also showed the highest percentages of apoptotic cells in the group treated with ICG/HArGO. These results suggest that photoresponsive ICG-loaded HArGO nanosheets could serve as a potential theranostic nano-platform for image-guided and synergistic photothermal antitumor therapy.

  16. Gene delivery using ultrasound contrast agents.

    PubMed

    Unger, E C; Hersh, E; Vannan, M; McCreery, T

    2001-05-01

    With the human genome product and continuing advances in molecular biology many therapeutic genes have been discovered. In the cardiovascular system, gene therapy has the potential to improve myocardial vascularization and ameliorate congestive heart failure. For successful development of clinical gene therapy, however, effective gene delivery vectors are needed. Ultrasound contrast agents can be used to develop new, more effective vectors for gene delivery. Ultrasound contrast agents lower the threshold for cavitation by ultrasound energy. Using physical properties of microbubbles and coating materials, genetic drugs have been incorporated into ultrasound contrast agents. Gene-bearing microbubbles can be injected IV and ultrasound energy applied to the target region. As the microbubbles enter the region of insonation, the microbubbles cavitate, locally releasing DNA. Cavitation also likely causes a local shockwave that improves cellular uptake of DNA. With transthoracic ultrasound, using commercially available diagnostic ultrasound system and an IV injection of gene-bearing microbubbles, high levels of transgene expression are observed in the insonated region of the myocardium. This new technology using microbubbles and ultrasound for gene delivery merits further study and development.

  17. Activatable hyaluronic acid nanoparticle as a theranostic agent for optical/photoacoustic image-guided photothermal therapy.

    PubMed

    Zhang, Liwen; Gao, Shi; Zhang, Fan; Yang, Kai; Ma, Qingjie; Zhu, Lei

    2014-12-23

    Photothermal therapy (PTT) is an emerging treatment modality that is under intensive preclinical investigations for the treatment of various medical conditions, including cancer. However, the lack of targeting function of PTT agents hampers its clinical application. An effective and nontoxic delivery vehicle that can carry PTT agents into tumor areas is still needed urgently. In this study, we developed a multifunctional nanocomposite by loading copper sulfide (CuS) into Cy5.5-conjugated hyaluronic acid nanoparticles (HANP), obtaining an activatable Cy5.5-HANP/CuS (HANPC) nanocomposite. In this system, Cy5.5 fluorescent signal is quenched by CuS inside the particle until the whole nanocomposite is degraded by hyaluronidase present in tumor, giving strong fluorescence signals delineating the tumor. Importantly, CuS with strong NIR absorbance appears to be an excellent contrast agent for photoacoustic (PA) imaging and an effective PTT agent. After intravenous administration of HANPC into SCC7 tumor-bearing mice, high fluorescence and PA signals were observed in the tumor area over time, which peaked at the 6 h time point (tumor-to-normal tissue ratio of 3.25±0.25 for optical imaging and 3.8±0.42 for PA imaging). The tumors were then irradiated with a laser, and a good tumor inhibition rate (89.74% on day 5) was observed. Our studies further encourage application of this HA-based multifunctional nanocomposite for image-guided PTT in biomedical applications, especially in cancer theranostics. PMID:25402600

  18. Thiadiazole molecules and poly(ethylene glycol)-block-polylactide self-assembled nanoparticles as effective photothermal agents.

    PubMed

    Sun, Tingting; Qi, Ji; Zheng, Min; Xie, Zhigang; Wang, Zhiyuan; Jing, Xiabin

    2015-12-01

    A new photothermal nano-agent was obtained by the coprecipitation of 2,5-Bis(2,5-bis(2-thienyl)-N-dodecyl pyrrole) thieno[3,4-b][1,2,5] thiadiazole (TPT-TT) and a biodegradable amphiphilic block copolymer, methoxypoly(ethylene glycol)2K-block-poly(D,L-lactide)2K (mPEG2K-PDLLA2K). TPT-TT, a donor-acceptor-donor (D-A-D) type small molecule, with bis(2-thienyl)-N-alkylpyrrole (TPT) as the donor and thieno[3,4-b]thiadiazole (TT) as the acceptor was a strong near infrared (NIR) absorber, which could convert the absorbed light energy into heat. The formation of TPT-TT nanoparticles (TPT-NPs), which possessed high stability in water, was confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). TPT-NPs showed high photothermal conversion efficiency (32%) and excellent photostability and heating reproducibility. The photostability of TPT-TT NPs was much better than that of indocyanine green (ICG), a federal drug administration (FDA) approved NIR dye. Besides, TPT-TT NPs exhibited significant photothermal therapeutic effect toward human cervical carcinoma (HeLa) and human liver hepatocellular carcinoma (HepG2) cells, while no appreciable dark cytotoxicity was observed. These results highlight the potential of TPT-TT NPs as an effective photothermal agent for cancer therapy. PMID:26398145

  19. PEGylated Prussian blue nanocubes as a theranostic agent for simultaneous cancer imaging and photothermal therapy.

    PubMed

    Cheng, Liang; Gong, Hua; Zhu, Wenwen; Liu, Jingjing; Wang, Xiaoyong; Liu, Gang; Liu, Zhuang

    2014-12-01

    Theranostic agents with both imaging and therapeutic functions have attracted enormous interests in cancer diagnosis and treatment in recent years. In this work, we develop a novel theranostic agent based on Prussian blue nanocubes (PB NCs), a clinically approved agent with strong near-infrared (NIR) absorbance and intrinsic paramagnetic property, for in vivo bimodal imaging-guided photothermal therapy. After being coated with polyethylene glycol (PEG), the obtained PB-PEG NCs are highly stable in various physiological solutions. In vivo T1-weighted magnetic resonance (MR) and photoacoustic tomography (PAT) bimodal imaging uncover that PB-PEG NCs after intravenous (i.v.) injection show high uptake in the tumor. Utilizing the strong and super stable NIR absorbance of PB, in vivo cancer treatment is then conducted upon i.v. injection of PB-PEG NCs followed by NIR laser irradiation of the tumors, achieving excellent therapeutic efficacy in a mouse tumor model. Comprehensive blood tests and careful histological examinations reveal no apparent toxicity of PB-PEG NCs to mice at our tested dose, which is two-fold of the imaging/therapy dose, within two months. Our work highlights the great promise of Prussian blue with well engineered surface coating as a multifunctional nanoprobe for imaging-guided cancer therapy. PMID:25239041

  20. Nanoparticle contrast agents for optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Gabriele, Michelle Lynn

    Optical coherence tomography (OCT) provides real-time, objective, in-vivo, optical cross-sectional representations of the retina and optic nerve. Recent innovations in image acquisition, including the incorporation of Fourier/spectral-domain detection, have improved imaging speed, sensitivity and resolution. Still, there remain specific structures within ocular OCT images, such as retinal ganglion cells (RGCs), which are of clinical interest but consistently have low contrast. This makes it difficult to differentiate between surrounding layers and structures. The objectives of this project were: (1) To establish a reliable method for OCT imaging of the healthy and diseased mouse eye in order to provide a platform for testing the utility of OCT contrast agents for ocular imaging, (2) To develop antibody-conjugated gold nanoparticles suitable for targeting specific structures and enhancing OCT image contrast in the mouse eye, and (3) To examine the localized contrast-enhancing ability and biocompatibility of gold nanoparticle contrast agents in-vivo. Our organizing hypotheses were that nanoparticles could improve contrast by modulating the intensity of backscattered light detected by OCT and that they could be directed to ocular structures of interest using antibodies specific to cellular markers. A reproducible method for imaging the mouse retina and quantifying retinal thickness was developed and this technique was then applied to a mouse model for retinal ganglion cell loss, optic nerve crush. Gold nanorods were designed specifically to augment the backscattering OCT signal at the same wavelengths of light used in current ophthalmic OCT imaging schemes (resonant wavelength lambda = 840 nm). Anti-CD90.1 (Thy1.1) antibodies were conjugated to the gold nanorods and a protocol for characterization of the success of antibody conjugation was developed. Upon injection, the gold nanorods were found to remain in the vitreous post-injection, with many consumed by an early

  1. MMP-14 Triggered Fluorescence Contrast Agent.

    PubMed

    Nguyen, Mai-Dung; Kang, Kyung A

    2016-01-01

    Matrix metalloproteinase-14 (MMP-14) is involved in cancer invasion, metastasis, and angiogenesis. Therefore, it is considered to be a biomarker for aggressive cancer types, including some of the triple-negative breast cancer. Accurate (i.e., specific) and sensitive detection of MMP-14 can, thus, be important for the early diagnosis of and accurate prognosis for aggressive cancer, including the breast cancer caused by cell line MDA-MB 231. Fluorophore-mediated molecular sensing has been used for detecting biomarkers, for a long time. One way to increase the specificity of the sensing is designing the fluorophore to emit its fluorescence only when it encounters the biomarker of interest. When a fluorophore is placed on the surface of, or very close to a gold nanoparticle (GNP), its fluorescence is quenched. Applying this relationship between the GNP and fluorophore, we have developed a GNP-based, near-infrared fluorescent contrast agent that is highly specific for MMP-14. This agent normally emits only 14-17 % fluorescence of the free fluorophore. When the agent encounters MMP-14, its fluorescence gets fully restored, allowing MMP-14 specific optical signal emission. PMID:27526171

  2. Advances in Magnetic Resonance Imaging Contrast Agents for Biomarker Detection

    NASA Astrophysics Data System (ADS)

    Sinharay, Sanhita; Pagel, Mark D.

    2016-06-01

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

  3. Advances in Magnetic Resonance Imaging Contrast Agents for Biomarker Detection

    PubMed Central

    Sinharay, Sanhita; Pagel, Mark D.

    2016-01-01

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

  4. Intraoperative imaging using intravascular contrast agent

    NASA Astrophysics Data System (ADS)

    Watson, Jeffrey R.; Martirosyan, Nikolay; Garland, Summer; Lemole, G. Michael; Romanowski, Marek

    2016-03-01

    Near-infrared (NIR) contrast agents are becoming more frequently studied in medical imaging due to their advantageous characteristics, most notably the ability to capture near-infrared signal across the tissue and the safety of the technique. This produces a need for imaging technology that can be specific for both the NIR dye and medical application. Indocyanine green (ICG) is currently the primary NIR dye used in neurosurgery. Here we report on using the augmented microscope we described previously for image guidance in a rat glioma resection. Luc-C6 cells were implanted in a rat in the left-frontal lobe and grown for 22 days. Surgical resection was performed by a neurosurgeon using augmented microscopy guidance with ICG contrast. Videos and images were acquired to evaluate image quality and resection margins. ICG accumulated in the tumor tissue due to enhanced permeation and retention from the compromised bloodbrain- barrier. The augmented microscope was capable of guiding the rat glioma resection and intraoperatively highlighted tumor tissue regions via ICG fluorescence under normal illumination of the surgical field.

  5. Physically-synthesized gold nanoparticles containing multiple nanopores for enhanced photothermal conversion and photoacoustic imaging.

    PubMed

    Park, Jisoo; Kang, Heesung; Kim, Young Heon; Lee, Sang-Won; Lee, Tae Geol; Wi, Jung-Sub

    2016-08-25

    Physically-synthesized gold nanoparticles having a narrow size distribution and containing multiple nanopores have been utilized as photothermal converters and imaging contrast agents. Nanopores within the gold nanoparticles make it possible to increase the light-absorption cross-section and consequently exhibit distinct improvements in photothermal conversion and photoacoustic imaging efficiencies.

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

    PubMed

    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.

  7. Plasmon-resonant nanorods as multimodal agents for two-photon luminescent imaging and photothermal therapy

    NASA Astrophysics Data System (ADS)

    Huff, Terry B.; Hansen, Matthew N.; Tong, Ling; Zhao, Yan; Wang, Haifeng; Zweifel, Daniel A.; Cheng, Ji-Xin; Wei, Alexander

    2007-02-01

    Plasmon-resonant gold nanorods have outstanding potential as multifunctional agents for image-guided therapies. Nanorods have large absorption cross sections at near-infrared (NIR) frequencies, and produce two-photon luminescence (TPL) when excited by fs-pulsed laser irradiation. The TPL signals can be detected with single-particle sensitivity, enabling nanorods to be imaged in vivo while passing through blood vessels at subpicomolar concentrations. Furthermore, cells labeled with nanorods become highly susceptible to photothermal damage when irradiated at plasmon resonance, often resulting in a dramatic blebbing of the cell membrane. However, the straightforward application of gold nanorods for cell-specific labeling is obstructed by the presence of CTAB, a cationic surfactant carried over from nanorod synthesis which also promotes their nonspecific uptake into cells. Careful exchange and replacement of CTAB can be achieved by introducing oligoethyleneglycol (OEG) units capable of chemisorption onto nanorod surfaces by in situ dithiocarbamate formation, a novel method of surface functionalization. Nanorods with a dense coating of methyl-terminated OEG chains are shielded from nonspecific cell uptake, whereas nanorods functionalized with folate-terminated OEG chains accumulate on the surface of tumor cells overexpressing their cognate receptor, with subsequent delivery of photoinduced cell damage at low laser fluence.

  8. Iron(II) PARACEST MRI contrast agents.

    PubMed

    Dorazio, Sarina J; Tsitovich, Pavel B; Siters, Kevin E; Spernyak, Joseph A; Morrow, Janet R

    2011-09-14

    The first examples of Fe(II) PARACEST magnetic resonance contrast agents are reported (PARACEST = paramagnetic chemical exchange saturation transfer). The iron(II) complexes contain a macrocyclic ligand, either 1,4,7-tris(carbamoylmethyl)-1,4,7-triazacyclononane (L1) or 1,4,7-tris[(5-amino-6-methyl-2-pyridyl)methyl]-1,4,7-triazacyclononane (L2). The macrocycles bind Fe(II) in aqueous solution with formation constants of log K = 13.5 and 19.2, respectively, and maintain the Fe(II) state in the presence of air. These complexes each contain six exchangeable protons for CEST which are amide protons in [Fe(L1)](2+) or amino protons in [Fe(L2)](2+). The CEST peak for the [Fe(L1)](2+) amide protons is at 69 ppm downfield of the bulk water resonance whereas the CEST peak for the [Fe(L2)](2+) amine protons is at 6 ppm downfield of bulk water. CEST imaging using a MRI scanner shows that the CEST effect can be observed in solutions containing low millimolar concentrations of complex at neutral pH, 100 mM NaCl, 20 mM buffer at 25 °C or 37 °C.

  9. MRI Contrast Agents: Evolution of Clinical Practice and Dose Optimization.

    PubMed

    Khan, Rihan

    2016-08-01

    Accurate detection of lesions throughout the body is of paramount importance in contrast-enhanced magnetic resonance imaging (MRI). Optimal contrast agent performance is therefore of great importance and given the number of MRI contrast agent options today, this topic is of much ongoing study. The goal of this review article is to bring the read up to date on pertinent articles that relate to the evolution of radiological clinical practice and dose optimization pertaining to gadolinium contrast agents. PMID:27367313

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

    SciTech Connect

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

    1984-12-01

    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.

  11. Hydroquinone-assisted synthesis of branched au-ag nanoparticles with polydopamine coating as highly efficient photothermal agents.

    PubMed

    Li, Jing; Wang, Wenjing; Zhao, Liang; Rong, Li; Lan, Shijie; Sun, Hongchen; Zhang, Hao; Yang, Bai

    2015-06-01

    Despite the success of galvanic replacement in preparing hollow nanostructures with diversified morphologies via the replacement reaction between sacrificial metal nanoparticles (NPs) seeds and less active metal ions, limited advances are made for producing branched alloy nanostructures. In this paper, we report an extended galvanic replacement for preparing branched Au-Ag NPs with Au-rich core and Ag branches using hydroquinone (HQ) as the reductant. In the presence of HQ, the preformed Ag seeds are replaceable by Au and, in turn, supply the growth of Ag branches. By altering the feed ratio of Ag seeds, HAuCl4, and HQ, the size and morphology of the NPs are tunable. Accordingly, the surface plasmon resonance absorption is tuned to near-infrared (NIR) region, making the branched NPs as potential materials in photothermal therapy. The branched NPs are further coated with polydopamine (PDA) shell via dopamine polymerization at room temperature. In comparison with bare NPs, PDA-coated branched Au-Ag (Au-Ag@PDA) NPs exhibit improved stability, biocompatibility, and photothermal performance. In vitro experiments indicate that the branched Au-Ag@PDA NPs are competitive agents for photothermal ablation of cancer cells. PMID:25969998

  12. Biocompatible PEGylated Fe3O4 Nanoparticles as Photothermal Agents for Near-Infrared Light Modulated Cancer Therapy

    PubMed Central

    Yuan, Gang; Yuan, Yongjie; Xu, Kan; Luo, Qi

    2014-01-01

    In accordance with the World Cancer Report, cancer has become the leading cause of mortality worldwide, and various therapeutic strategies have been developed at the same time. In the present study, biocompatible magnetic nanoparticles were designed and synthesized as high-performance photothermal agents for near-infrared light mediated cancer therapy in vitro. Via a facile one-pot solvothermal method, well-defined PEGylated magnetic nanoparticles (PEG–Fe3O4) were prepared with cheap inhesion as a first step. Due to the successful coating of PEG molecules on the surface of PEG–Fe3O4, these nanoparticles exhibited excellent dispersibility and dissolvability in physiological condition. Cytotoxicity based on MTT assays indicated these nanoparticles revealed high biocompatibility and low toxicity towards both Hela cells and C6 cells. After near-infrared (NIR) laser irradiation, the viabilities of C6 cells were effectively suppressed when incubated with the NIR laser activated PEG–Fe3O4. In addition, detailed photothermal anti-cancer efficacy was evaluated via visual microscope images, demonstrating that our PEG–Fe3O4 were promising for photothermal therapy of cancer cells. PMID:25329618

  13. Hydroquinone-assisted synthesis of branched au-ag nanoparticles with polydopamine coating as highly efficient photothermal agents.

    PubMed

    Li, Jing; Wang, Wenjing; Zhao, Liang; Rong, Li; Lan, Shijie; Sun, Hongchen; Zhang, Hao; Yang, Bai

    2015-06-01

    Despite the success of galvanic replacement in preparing hollow nanostructures with diversified morphologies via the replacement reaction between sacrificial metal nanoparticles (NPs) seeds and less active metal ions, limited advances are made for producing branched alloy nanostructures. In this paper, we report an extended galvanic replacement for preparing branched Au-Ag NPs with Au-rich core and Ag branches using hydroquinone (HQ) as the reductant. In the presence of HQ, the preformed Ag seeds are replaceable by Au and, in turn, supply the growth of Ag branches. By altering the feed ratio of Ag seeds, HAuCl4, and HQ, the size and morphology of the NPs are tunable. Accordingly, the surface plasmon resonance absorption is tuned to near-infrared (NIR) region, making the branched NPs as potential materials in photothermal therapy. The branched NPs are further coated with polydopamine (PDA) shell via dopamine polymerization at room temperature. In comparison with bare NPs, PDA-coated branched Au-Ag (Au-Ag@PDA) NPs exhibit improved stability, biocompatibility, and photothermal performance. In vitro experiments indicate that the branched Au-Ag@PDA NPs are competitive agents for photothermal ablation of cancer cells.

  14. Biocompatible PEGylated Fe₃O₄ nanoparticles as photothermal agents for near-infrared light modulated cancer therapy.

    PubMed

    Yuan, Gang; Yuan, Yongjie; Xu, Kan; Luo, Qi

    2014-01-01

    In accordance with the World Cancer Report, cancer has become the leading cause of mortality worldwide, and various therapeutic strategies have been developed at the same time. In the present study, biocompatible magnetic nanoparticles were designed and synthesized as high-performance photothermal agents for near-infrared light mediated cancer therapy in vitro. Via a facile one-pot solvothermal method, well-defined PEGylated magnetic nanoparticles (PEG-Fe3O4) were prepared with cheap inhesion as a first step. Due to the successful coating of PEG molecules on the surface of PEG-Fe3O4, these nanoparticles exhibited excellent dispersibility and dissolvability in physiological condition. Cytotoxicity based on MTT assays indicated these nanoparticles revealed high biocompatibility and low toxicity towards both Hela cells and C6 cells. After near-infrared (NIR) laser irradiation, the viabilities of C6 cells were effectively suppressed when incubated with the NIR laser activated PEG-Fe3O4. In addition, detailed photothermal anti-cancer efficacy was evaluated via visual microscope images, demonstrating that our PEG-Fe3O4 were promising for photothermal therapy of cancer cells. PMID:25329618

  15. Single agent nanoparticle for radiotherapy and radio-photothermal therapy in anaplastic thyroid cancer.

    PubMed

    Zhou, Min; Chen, Yunyun; Adachi, Makoto; Wen, Xiaoxia; Erwin, Bill; Mawlawi, Osama; Lai, Stephen Y; Li, Chun

    2015-07-01

    Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies. The aggressive behavior of ATC and its resistance to traditional treatment limit the efficacy of radiotherapy, chemotherapy, and surgery. The purpose of this study is aimed at enhancing the therapeutic efficacy of radiotherapy (RT) combined with photothermal therapy (PTT) in murine orthotopic model of ATC, based on our developed single radioactive copper sulfide (CuS) nanoparticle platform. We prepare a new dual-modality therapy for ATC consisting of a single-compartment nanoplatform, polyethylene glycol-coated [(64)Cu]CuS NPs, in which the radiotherapeutic property of (64)Cu is combined with the plasmonic properties of CuS NPs. Mice with Hth83 ATC were treated with PEG-[(64)Cu]CuS NPs and/or near infrared laser. Antitumor effects were assessed by tumor growth and animal survival. We found that in mice bearing orthotopic human Hth83 ATC tumors, micro-PET/CT imaging and biodistribution studies showed that about 50% of the injected dose of PEG-[(64)Cu]CuS NPs was retained in tumor 48 h after intratumoral injection. Human absorbed doses were calculated from biodistribution data. In antitumor experiments, tumor growth was delayed by PEG-[(64)Cu]CuS NP-mediated RT, PTT, and combined RT/PTT, with combined RT/PTT being most effective. In addition, combined RT/PTT significantly prolonged the survival of Hth83 tumor-bearing mice compared to no treatment, laser treatment alone, or NP treatment alone without producing acute toxic effects. These findings indicate that this single-compartment multifunctional NPs platform merits further development as a novel therapeutic agent for ATC.

  16. Single Agent Nanoparticle for Radiotherapy and Radio-Photothermal Therapy in Anaplastic Thyroid Cancer

    PubMed Central

    Zhou, Min; Chen, Yunyun; Adachi, Makoto; Wen, Xiaoxia; Erwin, Bill; Mawlawi, Osama; Lai, Stephen Y.; Li, Chun

    2015-01-01

    Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies. The aggressive behavior of ATC and its resistance to traditional treatment limit the efficacy of radiotherapy, chemotherapy, and surgery. The purpose of this study is aimed at enhancing the therapeutic efficacy of radiotherapy (RT) combined with photothermal therapy (PTT) in murine orthotopic model of ATC, based on our developed single radioactive copper sulfide (CuS) nanoparticle platform. We prepare a new dual-modality therapy for ATC consisting of a single-compartment nanoplatform, polyethylene glycol-coated [64Cu]CuS NPs, in which the radiotherapeutic property of 64Cu is combined with the plasmonic properties of CuS NPs. Mice with Hth83 ATC were treated with PEG[64Cu]CuS NPs and/or near infrared laser. Antitumor effects were assessed by tumor growth and animal survival. We found that in mice bearing orthotopic human Hth83 ATC tumors, micro-PET/CT imaging and biodistribution studies showed that about 50% of the injected dose of PEG-[64Cu]CuS NPs was retained in tumor 48 h after intratumoral injection. Human absorbed doses were calculated from biodistribution data. In antitumor experiments, tumor growth was delayed by PEG-[64Cu]CuS NP-mediated RT, PTT, and combined RT/PTT, with combined RT/PTT being most effective. In addition, combined RT/PTT significantly prolonged the survival of Hth83 tumor-bearing mice compared to no treatment, laser treatment alone, or NP treatment alone without producing acute toxic effects. These findings indicate that this single-compartment multifunctional NPs platform merits further development as a novel therapeutic agent for ATC. PMID:25913249

  17. Hydrophilic MoSe2 Nanosheets as Effective Photothermal Therapy Agents and Their Application in Smart Devices.

    PubMed

    Lei, Zhouyue; Zhu, Wencheng; Xu, Shengjie; Ding, Jian; Wan, Jiaxun; Wu, Peiyi

    2016-08-17

    A facile poly(vinylpyrrolidone) (PVP)-assisted exfoliation method is utilized to simultaneously exfoliate and noncovalently modify MoSe2 nanosheets. The resultant hydrophilic nanosheets are shown to be promising candidates for biocompatible photothermal therapy (PTT) agents, and they could also be encapsulated into a hydrogel matrix for some intelligent devices. This work not only provides novel insights into exfoliation and modification of transition metal dichalcogenide (TMD) nanosheets but also might spark more research into engineering multifunctional TMD-related nanocomposites, which is in favor of further exploiting the attractive properties of these emerging layered two-dimensional (2D) nanomaterials. PMID:27467718

  18. Nd{sup 3+} doped LaF{sub 3} nanoparticles as self-monitored photo-thermal agents

    SciTech Connect

    Rocha, Uéslen; Upendra Kumar, K.; Jacinto, Carlos; Ramiro, Julio; Caamaño, Antonio J.; García Solé, José; Jaque, Daniel

    2014-02-03

    In this work, we demonstrate how LaF{sub 3} nanoparticles activated with large concentrations (up to 25%) of Nd{sup 3+} ions can simultaneously operate as biologically compatible efficient nanoheaters and fluorescent nanothermometers under single beam (808 nm) infrared laser excitation. Nd{sup 3+}:LaF{sub 3} nanoparticles emerge as unique multifunctional agents that could constitute the first step towards the future development of advanced platforms capable of simultaneous deep tissue fluorescence bio-imaging and controlled photo-thermal therapies.

  19. Magnetic resonance imaging using gadolinium-based contrast agents.

    PubMed

    Mitsumori, Lee M; Bhargava, Puneet; Essig, Marco; Maki, Jeffrey H

    2014-02-01

    The purpose of this article was to review the basic properties of available gadolinium-based magnetic resonance contrast agents, discuss their fundamental differences, and explore common and evolving applications of gadolinium-based magnetic resonance contrast throughout the body excluding the central nervous system. A more specific aim of this article was to explore novel uses of these gadolinium-based contrast agents and applications where a particular agent has been demonstrated to behave differently or be better suited for certain applications than the other contrast agents in this class.

  20. In vivo photoacoustic flow cytometry for monitoring of circulating single cancer cells and contrast agents

    NASA Astrophysics Data System (ADS)

    Zharov, Vladimir P.; Galanzha, Ekaterina I.; Shashkov, Evgeny V.; Khlebtsov, Nicolai G.; Tuchin, Valery V.

    2006-12-01

    A new photoacoustic flow cytometry was developed for real-time detection of circulating cells, nanoparticles, and contrast agents in vivo. Its capability, integrated with photothermal and optical clearing methods, was demonstrated using a near-infrared tunable laser to characterize the in vivo kinetics of Indocyanine Green alone and single cancer cells labeled with gold nanorods and Indocyanine Green in the vasculature of the mouse ear. In vivo applications are discussed, including selective nanophotothermolysis of metastatic squamous cells, label-free detection of melanoma cells, study of pharmokinetics, and immune response to apoptotic and necrotic cells, with potential translation to humans. The threshold sensitivity is estimated as one cancer cell in the background of 107 normal blood cells.

  1. Preclinical evaluation of biodegradable macromolecular contrast agents for magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Feng, Yi

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

  2. Nanoparticle Contrast Agents for Computed Tomography: A Focus on Micelles

    PubMed Central

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

    2014-01-01

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

  3. [Iodinated contrast agents used in Radiology].

    PubMed

    Ramírez Ribelles, C; Sánchez Fuster, M A; Pamies Guilabert, J

    2014-06-01

    Iodinated contrast media are widely used in Radiology practices with a very low rate of adverse effects, being contrast-induced nephropathy the most serious one. In the majority of cases it is temporary and reversible, even though it can increase the inhospital morbidity and mortality in patients with risk factors. We will describe the various measures of prevention, being hydration and use of non-ionic contrast low osmolality those which have demonstrated greater effectiveness. Precautions to be taken in some risk situations, as patients treated with metformin or with impaired renal function, are also discussed.

  4. Theoretical study on the possible use of SiC microparticles as photothermal agents for the heating of bacteria

    NASA Astrophysics Data System (ADS)

    Rosenberg, M.; Petrie, T. A.

    2012-02-01

    Gold nanoparticles exhibiting surface plasmon resonances have been considered as photothermal agents for the selective destruction of bacteria by visible to near-infrared radiation. Here, we consider theoretically the possible complementary use of sub-micron silicon carbide (SiC) particles as photothermal agents for the heating of bacteria by pulsed mid-infrared (MIR) radiation. A SiC microparticle can exhibit surface phonon resonances in the MIR. Similar to the effect of surface plasmon resonances in gold nanoparticles, this could lead to enhanced absorption at the resonant wavelength and strong heating of the microparticle locally. If the heating is sufficient, this might lead to damage of bacterial cells adjacent to SiC particles. We estimate the heating of sub-micron SiC particles in a water medium under various pulse lengths of radiation at wavelength 10.6 µm. Noting that SiC is being investigated as a biocompatible material that could be functionalized for biomedical applications, and that an appropriately roughened SiC surface could be expected to exhibit similar surface phonon resonances, we speculate that enhanced heating under MIR radiation may be useful for in vitro sterilization of such surfaces.

  5. Modified natural nanoparticles as contrast agents for medical imaging

    PubMed Central

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

    2009-01-01

    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 advantages as delivery platforms such as biodegradability. In addition, our understanding of natural nanoparticles is quite advanced, allowing their adaptation as contrast agents. They can be labeled with small molecules or ions such as Gd3+ to act as contrast agents for magnetic resonance imaging, 18F to act as positron emission tomography contrast agents or fluorophores to act as contrast agents for fluorescence techniques. Additionally, inorganic nanoparticles such as iron oxide, gold nanoparticles or quantum dots can be incorporated to add further contrast functionality. Furthermore, these natural nanoparticle contrast agents can be rerouted from their natural targets via the attachment of targeting molecules. In this review, we discuss the various modified natural nanoparticles that have been exploited as contrast agents. PMID:19900496

  6. Iopamidol as a gastrointestinal contrast agent. Lack of peritoneal reactivity.

    PubMed

    Ferrante, S L; Schreiman, J S; Rouse, J W; Rysavy, J A; Cheng, S C; Frick, M P

    1990-02-01

    The ideal contrast agent in patients suspected of having gastrointestinal perforation is an iso-osmolar, or nearly iso-osmolar substance, that causes no peritoneal reaction. Iopamidol is a nonionic water-soluble contrast medium that may be considered in such situations. Intraperitoneal injections of ionic and nonionic contrast agents were compared in rats to study potentially harmful peritoneal inflammation. Only intraperitoneal barium injection produced any significant tissue reaction, such as adhesions and ascites. There was no difference between iopamidol and the other water-soluble contrast agents. Iopamidol may satisfy the need for nonreactive and nearly iso-osmolar contrast agents for evaluating patients with possible bowel perforation. However, the high cost of this agent may make its clinical application impractical.

  7. Intravascular contrast agents suitable for magnetic resonance imaging. [Dogs

    SciTech Connect

    Runge, V.M.; Clanton, J.A.; Herzer, W.A.; Gibbs, S.J.; Price, A.C.; Partain, C.L.; James, A.E. Jr.

    1984-10-01

    Two paramagnetic chelates, chromium EDTA and gadolinium DTPA, were evaluated as potential intravenous contrast agents for magnetic resonance imaging. After evaluating both agents in vitro, in vivo studies were conducted in dogs to document changes in renal appearance produced by contrast injection. Acute splenic and renal infarction were diagnosed with contrast-enhanced MR and confirmed by gamma camera imaging following administration of Tc-99m-labeled DMSA and sulfur colloid. The authors conclude that intravenous paramagnetic contrast agents presently offer the best mechanism for assessment of tissue function and changes in perfusion with MR.

  8. Basic MR relaxation mechanisms and contrast agent design.

    PubMed

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

    2015-09-01

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

  9. Electric and magnetic properties of contrast agents for thermoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Ogunlade, Olumide; Beard, Paul

    2014-03-01

    The endogenous contrast in thermoacoustic imaging is due to the water and ionic content in tissue. This results in poor tissue speci city between high water content tissues. As a result, exogenous contrast agents have been employed to improve tissue speci city and also increase the SNR. An investigation into the sources of contrast produced by several exogenous contrast agents is described. These include three gadolinium based MRI contrast agents, iron oxide particles, single wall carbon nanotubes, saline and sucrose solutions. Both the dielectric and magnetic properties of contrast agents at 3GHz have been measured using microwave resonant cavities. The DC conductivity of the contrast agents were also measured. It is shown that the measured increase in dielectric contrast, relative to water, is due to dipole rotational loss of polar non electrolytes, ionic loss of electrolytes or a combination of both. It is shown that for the same dielectric contrast, electrolytes make better thermoacoustic contrast agents than non-electrolytes, for thermoacoustic imaging.

  10. Inorganic nanoparticle-based contrast agents for molecular imaging

    PubMed Central

    Cho, Eun Chul; Glaus, Charles; Chen, Jingyi; Welch, Michael J.; Xia, Younan

    2010-01-01

    Inorganic nanoparticles including semiconductor quantum dots, iron oxide nanoparticles, and gold nanoparticles have been developed as contrast agents for diagnostics by molecular imaging. Compared to traditional contrast agents, nanoparticles offer several advantages: their optical and magnetic properties can be tailored by engineering the composition, structure, size, and shape; their surfaces can be modified with ligands to target specific biomarkers of disease; the contrast enhancement provided can be equivalent to millions of molecular counterparts; and they can be integrated with a combination of different functions for multi-modal imaging. Here, we review recent advances in the development of contrast agents based on inorganic nanoparticles for molecular imaging, with a touch on contrast enhancement, surface modification, tissue targeting, clearance, and toxicity. As research efforts intensify, contrast agents based on inorganic nanoparticles that are highly sensitive, target-specific, and safe to use are expected to enter clinical applications in the near future. PMID:21074494

  11. Contrast agents in diagnostic imaging: Present and future.

    PubMed

    Caschera, Luca; Lazzara, Angelo; Piergallini, Lorenzo; Ricci, Domenico; Tuscano, Bruno; Vanzulli, Angelo

    2016-08-01

    Specific contrast agents have been developed for x ray examinations (mainly CT), sonography and Magnetic Resonance Imaging. Most of them are extracellular agents which create different enhancement on basis of different vascularization or on basis of different interstitial network in tissues, but some can be targeted to a particular cell line (e.g. hepatocyte). Microbubbles can be used as carrier for therapeutic drugs which can be released in specific targets under sonographic guidance, decreasing systemic toxicity and increasing therapeutic effect. Radiologists have to choose a particular contrast agent knowing its physical and chemical properties and the possibility of adverse reactions and balancing them with the clinical benefits of a more accurate diagnosis. As for any drug, contrast agents can cause adverse events, which are more frequent with Iodine based CA, but also with Gd based CA and even with sonographic contrast agents hypersensitivity reaction can occur. PMID:27168225

  12. Current topics in ultrasound contrast agent application and design

    NASA Astrophysics Data System (ADS)

    Allen, John S.; Kruse, Dustin E.; May, Donovan J.

    2001-05-01

    Ultrasound contrast agents are bubbles, 1-10 microns in radius, encapsulated by a lipid, protein, polymer or fluid shell. The agents have been used to distinguish the acoustic scattering signatures of blood from those of the surrounding tissue. This is possible due to the nonlinear response of the agent, which is similar to that of a free gas bubble. Upon sufficient forcing the agents will oscillate nonlinearly about their equilibrium radius, and for specific conditions, produce nonlinear resonance responses which are integer multiples of the primary resonance. Ultrasound tissue perfusion studies have been developed which are based on the destruction of contract agents coupled to the measurement of blood flow. Nevertheless, many outstanding issues remain in contrast agent design especially with respect to emerging applications. Even with the use of higher order harmonics there is a lack of an acoustic signature or destruction mechanism at frequencies above approximately 5.0 MHz with conventional agents. The design and use of a high frequency contrast agent is addressed by exploiting the multiple scattering response of agents modled as spherical elastic shells. Also considered is the nonlinear response of elastic-shelled agents. The considerations of shells modeled as linear and nonlinear elastic materials are discussed. The use of contrast agents for targeted drug delivery has recently received much attention. More specifically, the ImaRx Corporation (Tucson, Arizona) has developed thick fluid shelled agents, which release suspended taxol-based drugs from their shells upon destruction. Shape instabilities and surface waves correspond with the fragmentation and destruction of the agents. Finally, the interaction of multiple contrast agents has received little attention with respect to these emerging applications.

  13. Superparamagnetic nanoparticle-inclusion microbubbles for ultrasound contrast agents

    NASA Astrophysics Data System (ADS)

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

    2008-11-01

    We have developed a new type of ultrasound (US) contrast agent, consisting of a gas core, a layer of superparamagnetic iron oxide Fe3O4 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.

  14. Intravital confocal Raman microscopy with multiplexed SERS contrast agents

    NASA Astrophysics Data System (ADS)

    McVeigh, Patrick Z.; Wilson, Brian C.

    2012-03-01

    Intravital microscopy has been demonstrated to be a powerful technique for studying the delivery of contrast or therapeutic agents to tumours growing in a realistic 3D environment at high resolution. Surface enhanced Raman scattering (SERS)-active nanoparticle contrast agents provide the ability to improve in-vivo detection of tumour tissue through multiplex detection of their uniquely bright spectral lines. However, most work to date has been carried out in-vitro or in ex-vivo tissues. Here we present the results from confocal Raman microscopy in a dorsal skinfold window chamber in mice using SERS-active gold nanoparticle contrast agents directed towards an overexpressed tumour receptor tyrosine kinase.

  15. Iron Oxide as an MRI Contrast Agent for Cell Tracking

    PubMed Central

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

    2015-01-01

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

  16. A review of responsive MRI contrast agents: 2005–2014

    PubMed Central

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

    2014-01-01

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

  17. Hydrous RuO2 nanoparticles as an efficient NIR-light induced photothermal agent for ablation of cancer cells in vitro and in vivo.

    PubMed

    Xiao, Zhiyin; Jiang, Xiaohong; Li, Bo; Liu, Xijian; Huang, Xiaojuan; Zhang, Yuxin; Ren, Qilong; Luo, Jie; Qin, Zongyi; Hu, Junqing

    2015-07-28

    Metal oxides are receiving an incremental attention in recent years for their potential applications in ablation of cancer cells due to their efficient photothermal conversion and good biocompatibility, but the large sizes and poor photo-stability will seriously limit their practical application. Herein, hydrous RuO2 nanoparticles were synthesized by a facile hydrothermal treatment and surface-modified with polyvinylpyrrolidone (PVP) coating. PVP-coated RuO2 nanoparticles exhibit a well dispertion in saline solution, strong characteristic plasmonic absorption in NIR region, enhanced photothermal conversion efficiency of 54.8% and remarkable photo-stability under the irridation of an 808 nm laser. The nanoparticles were further employed as a new photothermal ablation agent for cancer cells which led rapidly to cellular deaths both in vitro and in vivo. PMID:26055486

  18. Novel nanomedicine-based MRI contrast agents for gynecological malignancies.

    PubMed

    Mody, Vicky V; Nounou, Mohamed Ismail; Bikram, Malavosklish

    2009-08-10

    Gynecological cancers result in significant morbidity and mortality in women despite advances in treatment and diagnosis. This is due to detection of the disease in the late stages following metastatic spread in which treatment options become limited and may not result in positive outcomes. In addition, traditional contrast agents are not very effective in detecting primary metastatic tumors and cells due to a lack of specificity and sensitivity of the diagnostic tools, which limits their effectiveness. Recently, the field of nanomedicine-based contrast agents offers a great opportunity to develop highly sophisticated devices that can overcome many traditional hurdles of contrast agents including solubility, cell-specific targeting, toxicities, and immunological responses. These nanomedicine-based contrast agents including liposomes, micelles, dendrimers, multifunctional magnetic polymeric nanohybrids, fullerenes, and nanotubes represent improvements over their traditional counterparts, which can significantly advance the field of molecular imaging.

  19. Gold nanorods/mesoporous silica-based nanocomposite as theranostic agents for targeting near-infrared imaging and photothermal therapy induced with laser

    PubMed Central

    Liu, Yang; Xu, Ming; Chen, Qing; Guan, Guannan; Hu, Wen; Zhao, Xiuli; Qiao, Mingxi; Hu, Haiyang; Liang, Ying; Zhu, Heyun; Chen, Dawei

    2015-01-01

    Photothermal therapy (PTT) is widely regarded as a promising technology for cancer treatment. Gold nanorods (GNRs), as excellent PTT agent candidates, have shown high-performance photothermal conversion ability under laser irradiation, yet two major obstacles to their clinical application are the lack of selective accumulation in the target site following systemic administration and the greatly reduced photothermal conversion efficiency caused by self-aggregating in aqueous environment. Herein, we demonstrate that tLyp-1 peptide-functionalized, indocyanine green (ICG)-containing mesoporous silica-coated GNRs (I-TMSG) possessed dual-function as tumor cells-targeting near-infrared (NIR) fluorescent probe and PTT agents. The construction of the nanostructure began with synthesis of GNRs by seed-mediated growth method, followed by the coating of mesoporous silica, the chemical conjugation of PEG and tLyp-1 peptide, and the enclosure of ICG as an NIR imaging agent in the mesoporous. The as-prepared nanoparticles could shield the GNRs against their self-aggregation, improve the stability of ICG, and exhibit negligible dark cytotoxicity. More importantly, such a theranostic nanocomposite could realize the combination of GNRs-based photothermal ablation under NIR illumination, ICG-mediated fluorescent imaging, and tLyp-1-enabled more easy endocytosis into breast cancer cells. All in all, I-TMSG nanoparticles, in our opinion, possessed the strong potential to realize the effective diagnosis and PTT treatment of human mammary cancer. PMID:26251596

  20. Gold nanorods/mesoporous silica-based nanocomposite as theranostic agents for targeting near-infrared imaging and photothermal therapy induced with laser.

    PubMed

    Liu, Yang; Xu, Ming; Chen, Qing; Guan, Guannan; Hu, Wen; Zhao, Xiuli; Qiao, Mingxi; Hu, Haiyang; Liang, Ying; Zhu, Heyun; Chen, Dawei

    2015-01-01

    Photothermal therapy (PTT) is widely regarded as a promising technology for cancer treatment. Gold nanorods (GNRs), as excellent PTT agent candidates, have shown high-performance photothermal conversion ability under laser irradiation, yet two major obstacles to their clinical application are the lack of selective accumulation in the target site following systemic administration and the greatly reduced photothermal conversion efficiency caused by self-aggregating in aqueous environment. Herein, we demonstrate that tLyp-1 peptide-functionalized, indocyanine green (ICG)-containing mesoporous silica-coated GNRs (I-TMSG) possessed dual-function as tumor cells-targeting near-infrared (NIR) fluorescent probe and PTT agents. The construction of the nanostructure began with synthesis of GNRs by seed-mediated growth method, followed by the coating of mesoporous silica, the chemical conjugation of PEG and tLyp-1 peptide, and the enclosure of ICG as an NIR imaging agent in the mesoporous. The as-prepared nanoparticles could shield the GNRs against their self-aggregation, improve the stability of ICG, and exhibit negligible dark cytotoxicity. More importantly, such a theranostic nanocomposite could realize the combination of GNRs-based photothermal ablation under NIR illumination, ICG-mediated fluorescent imaging, and tLyp-1-enabled more easy endocytosis into breast cancer cells. All in all, I-TMSG nanoparticles, in our opinion, possessed the strong potential to realize the effective diagnosis and PTT treatment of human mammary cancer. PMID:26251596

  1. Hydrous RuO2 nanoparticles as an efficient NIR-light induced photothermal agent for ablation of cancer cells in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Xiao, Zhiyin; Jiang, Xiaohong; Li, Bo; Liu, Xijian; Huang, Xiaojuan; Zhang, Yuxin; Ren, Qilong; Luo, Jie; Qin, Zongyi; Hu, Junqing

    2015-07-01

    Metal oxides are receiving an incremental attention in recent years for their potential applications in ablation of cancer cells due to their efficient photothermal conversion and good biocompatibility, but the large sizes and poor photo-stability will seriously limit their practical application. Herein, hydrous RuO2 nanoparticles were synthesized by a facile hydrothermal treatment and surface-modified with polyvinylpyrrolidone (PVP) coating. PVP-coated RuO2 nanoparticles exhibit a well dispertion in saline solution, strong characteristic plasmonic absorption in NIR region, enhanced photothermal conversion efficiency of 54.8% and remarkable photo-stability under the irridation of an 808 nm laser. The nanoparticles were further employed as a new photothermal ablation agent for cancer cells which led rapidly to cellular deaths both in vitro and in vivo.Metal oxides are receiving an incremental attention in recent years for their potential applications in ablation of cancer cells due to their efficient photothermal conversion and good biocompatibility, but the large sizes and poor photo-stability will seriously limit their practical application. Herein, hydrous RuO2 nanoparticles were synthesized by a facile hydrothermal treatment and surface-modified with polyvinylpyrrolidone (PVP) coating. PVP-coated RuO2 nanoparticles exhibit a well dispertion in saline solution, strong characteristic plasmonic absorption in NIR region, enhanced photothermal conversion efficiency of 54.8% and remarkable photo-stability under the irridation of an 808 nm laser. The nanoparticles were further employed as a new photothermal ablation agent for cancer cells which led rapidly to cellular deaths both in vitro and in vivo. Electronic supplementary information (ESI) available: Characterizations including TEM, TG, EDS, etc. See DOI: 10.1039/c5nr00965k

  2. Targeted PARACEST nanoparticle contrast agent for the detection of fibrin.

    PubMed

    Winter, Patrick M; Cai, Kejia; Chen, Junjie; Adair, Christopher R; Kiefer, Garry E; Athey, Phillip S; Gaffney, Patrick J; Buff, Carolyn E; Robertson, J David; Caruthers, Shelton D; Wickline, Samuel A; Lanza, Gregory M

    2006-12-01

    A lipid-encapsulated perfluorocarbon nanoparticle molecular imaging contrast agent that utilizes a paramagnetic chemical exchange saturation transfer (PARACEST) chelate is presented. PARACEST agents are ideally suited for molecular imaging applications because one can switch the contrast on and off at will simply by adjusting the pulse sequence parameters. This obviates the need for pre- and postinjection images to define contrast agent binding. Spectroscopy (4.7T) of PARACEST nanoparticles revealed a bound water peak at 52 ppm, in agreement with results from the water-soluble chelate. Imaging of control nanoparticles showed no appreciable contrast, while PARACEST nanoparticles produced >10% signal enhancement. PARACEST nanoparticles were targeted to clots via antifibrin antibodies and produced a contrast-to-noise ratio (CNR) of 10 at the clot surface.

  3. A Brief Account of Nanoparticle Contrast Agents for Photoacoustic Imaging

    PubMed Central

    Pan, Dipanjan; Kim, Benjamin; Wang, Lihong V.; Lanza, Gregory M

    2014-01-01

    Photoacoustic imaging (PAI) is a hybrid, nonionizing modality offering excellent spatial resolution, deep penetration, and high soft tissue contrast. In PAI, signal is generated based on the absorption of laser-generated optical energy by endogenous tissues or exogenous contrast agents leading to acoustic emissions detected by an ultrasound transducer. Research in this area over the years has shown that PAI has the ability to provide both physiological and molecular imaging, which can be viewed alone or used in a hybrid modality fashion to extend the anatomic and hemodynamic sensitivities of clinical ultrasound. PAI may be performed using inherent contrast afforded by light absorbing molecules such as hemoglobin, myoglobin, and melanin or exogenous small molecule contrast agent such as near infrared dyes and porphyrins. However, this review summarizes the potential of exogenous nanoparticle-based agents for PAI applications including contrast based on gold particles, carbon nanotubes, and encapsulated copper compounds. PMID:23983210

  4. Monitoring SERS-based contrast agents in atherosclerosis experimental models

    NASA Astrophysics Data System (ADS)

    Machtoub, Lina H.

    2011-03-01

    There have been enormous progresses in developing a class of multimodal contrast agents, which combine MRI with optical imaging. Contrast agent targeting can provide enhanced diagnostic information, allowing differentiation between variable and stable atherosclerotic plaques. Recently an intensive efforts have been working on the development of contrast agents that can improve the ability to detect and characterize atherosclerosis in clinical and preclinical applications. Earlier studies on hyperlipidemic rabbits using in vivo MRI have shown accumulation of USPIOs in plaques with a high macrophage content that induces magnetic resonance (MR) signal changes correlated to the absolute iron content in the aortic arch. A potent new class of nanoparticles contrast agents have recently drawn much attention for its wide diverse diagnostic and potential therapeutic applications particularly in monitoring the inflammatory responses. In our previous studies we have investigated SPIO contrast agents uptakes in hepatic and spleen tissues taken from NZW rabbits. The scope of this work encompasses application of an emerging hybrid imaging modality, SERSbased nonlinear optical microscopy, in investigating atherosclerosis experimental models. In this work experiments are performed on contrast treated tissue sections taken from aortic arch of atherosclerotic animal model. Marked contrast enhancement has been observed in the treated aortic sections compared with the untreated control. The obtained images are compared with immunohistochemistry .The work presented can be promising for future studies on in vivo detection of macrophages in human plaques and early detection of atherosclerotic diseases.

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

    PubMed

    Rinck, P A; Muller, R N

    1999-01-01

    The relaxivities r1 and r2 of magnetic resonance contrast agents and the T1 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 (R1 = 1/T1 and R2 = 1/T2) 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.

  6. Multiwalled carbon nanotube hybrids as MRI contrast agents.

    PubMed

    Kuźnik, Nikodem; Tomczyk, Mateusz Michał

    2016-01-01

    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.

  7. Multiwalled carbon nanotube hybrids as MRI contrast agents

    PubMed Central

    Tomczyk, Mateusz Michał

    2016-01-01

    Summary 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. PMID:27547627

  8. Multiwalled carbon nanotube hybrids as MRI contrast agents.

    PubMed

    Kuźnik, Nikodem; Tomczyk, Mateusz Michał

    2016-01-01

    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. PMID:27547627

  9. Gadolinium Endohedral Metallofullerene-Based MRI Contrast Agents

    NASA Astrophysics Data System (ADS)

    Bolskar, Robert D.

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

  10. Targeting cancer chemotherapeutic agents by use of lipiodol contrast medium

    SciTech Connect

    Konno, T. )

    1990-11-01

    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.

  11. Methods for blood flow measurements using ultrasound contrast agents

    NASA Astrophysics Data System (ADS)

    Fowlkes, J. Brian

    2003-10-01

    Blood flow measurements using ultrasound contrast agents are being investigated for myocardial perfusion and more recently in other organ systems. The methods are based largely on the relative increase in echogenicity due to the concentration of bubbles present in the ultrasound beam. In the simplest form, regional differences in blood volume can be inferred but the possibility exists to extract perfusion from the transit of contrast agent through tissue. Perfusion measurements rely on determining the flux of blood through a tissue volume and as such require knowledge of the fractional blood volume (FBV), i.e., ml blood/g tissue and the rate of exchange, commonly measured as the mean transit time (MTT). This presentation will discuss methods of determining each of these values and their combination to estimate tissue perfusion. Underlying principles of indicator-dilution theory will be provided in the context of ultrasound contrast agents. Current methods for determining MTT will include imaging of the intravenous bolus, in-plane contrast disruption with interval and real-time contrast recovery imaging, and control of contrast agent flow using arterial disruption (contrast interruption). The advantages and limitations of the methods will be examined along with current applications. [Work supported in part by NIH.

  12. Chlorotoxin-modified macromolecular contrast agent for MRI tumor diagnosis.

    PubMed

    Huang, Rongqin; Han, Liang; Li, Jianfeng; Liu, Shuhuan; Shao, Kun; Kuang, Yuyang; Hu, Xing; Wang, Xuxia; Lei, Hao; Jiang, Chen

    2011-08-01

    Clinical diagnosis of cancers using magnetic resonance imaging (MRI) is highly dependent on contrast agents, especially for brain tumors which contain blood-brain barrier (BBB) at the early stage. However, currently mostly used low molecular weight contrast agents such as Gd-DTPA suffer from rapid renal clearance, non-specificity, and low contrast efficiency. The aim of this paper is to investigate the potential of a macromolecular MRI contrast agent based on dendrigraft poly-l-lysines (DGLs), using chlorotoxin (CTX) as a tumor-specific ligand. The contrast agent using CTX-modified conjugate as the main scaffold and Gd-DTPA as the payload was successfully synthesized. The results of fluorescent microscopy showed that the modification of CTX could markedly enhance the cellular uptake in C6 glioma and liver tumor cell lines, but not in normal cell line. Significantly increased accumulation of CTX-modified conjugate within glioma and liver tumor was further demonstrated in tumor-bearing nude mice using in vivo imaging system. The MRI results showed that the signal enhancement of mice treated with CTX-modified contrast reached peak level at 5 min for both glioma and liver tumor, 144.97% ± 19.54% and 158.69% ± 12.41%, respectively, significantly higher than that of unmodified counterpart and commercial control. And most importantly, the signal enhancement of CTX-modified contrast agent maintained much longer compared to that of controls, which might be useful for more exact diagnosis for tumors. CTX-modified dendrimer-based conjugate might be applied as an efficient MRI contrast agent for targeted and accurate tumor diagnosis. This finding is especially important for tumors such as brain glioma which is known hard to be diagnosed due to the presence of BBB.

  13. In situ gold nanoparticles formation: contrast agent for dental optical coherence tomography.

    PubMed

    Braz, Ana K S; de Araujo, Renato E; Ohulchanskyy, Tymish Y; Shukla, Shoba; Bergey, Earl J; Gomes, Anderson S L; Prasad, Paras N

    2012-06-01

    In this work we demonstrate the potential use of gold nanoparticles as contrast agents for the optical coherence tomography (OCT) imaging technique in dentistry. Here, a new in situ photothermal reduction procedure was developed, producing spherical gold nanoparticles inside dentinal layers and tubules. Gold ions were dispersed in the primer of commercially available dental bonding systems. After the application and permeation in dentin by the modified adhesive systems, the dental bonding materials were photopolymerized concurrently with the formation of gold nanoparticles. The gold nanoparticles were visualized by scanning electron microscopy (SEM). The SEM images show the presence of gold nanospheres in the hybrid layer and dentinal tubules. The diameter of the gold nanoparticles was determined to be in the range of 40 to 120 nm. Optical coherence tomography images were obtained in two- and three-dimensions. The distribution of nanoparticles was analyzed and the extended depth of nanosphere production was determined. The results show that the OCT technique, using in situ formed gold nanoparticles as contrast enhancers, can be used to visualize dentin structures in a non-invasive and non-destructive way.

  14. Functionalized multiwalled carbon nanotubes as ultrasound contrast agents.

    PubMed

    Delogu, Lucia Gemma; Vidili, Gianpaolo; Venturelli, Enrica; Ménard-Moyon, Cécilia; Zoroddu, Maria Antonietta; Pilo, Giovannantonio; Nicolussi, Paola; Ligios, Ciriaco; Bedognetti, Davide; Sgarrella, Francesco; Manetti, Roberto; Bianco, Alberto

    2012-10-01

    Ultrasonography is a fundamental diagnostic imaging tool in everyday clinical practice. Here, we are unique in describing the use of functionalized multiwalled carbon nanotubes (MWCNTs) as hyperechogenic material, suggesting their potential application as ultrasound contrast agents. Initially, we carried out a thorough investigation to assess the echogenic property of the nanotubes in vitro. We demonstrated their long-lasting ultrasound contrast properties. We also showed that ultrasound signal of functionalized MWCNTs is higher than graphene oxide, pristine MWCNTs, and functionalized single-walled CNTs. Qualitatively, the ultrasound signal of CNTs was equal to that of sulfur hexafluoride (SonoVue), a commercially available contrast agent. Then, we found that MWCNTs were highly echogenic in liver and heart through ex vivo experiments using pig as an animal model. In contrast to the majority of ultrasound contrast agents, we observed in a phantom bladder that the tubes can be visualized within a wide variety of frequencies (i.e., 5.5-10 MHz) and 12.5 MHz using tissue harmonic imaging modality. Finally, we demonstrated in vivo in the pig bladder that MWCNTs can be observed at low frequencies, which are appropriate for abdominal organs. Importantly, we did not report any toxicity of CNTs after 7 d from the injection by animal autopsy, organ histology and immunostaining, blood count, and chemical profile. Our results reveal the enormous potential of CNTs as ultrasound contrast agents, giving support for their future applications as theranostic nanoparticles, combining diagnostic and therapeutic modalities.

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

    SciTech Connect

    Ogunlade, Olumide Beard, Paul

    2015-01-15

    Purpose: Thermoacoustic imaging at microwave excitation frequencies is limited by the low differential contrast exhibited by high water content tissues. To overcome this, exogenous thermoacoustic contrast agents based on gadolinium compounds, iron oxide, and single wall carbon nanotubes have previously been suggested and investigated. However, these previous studies did not fully characterize the electric, magnetic, and thermodynamic properties of these agents thus precluding identification of the underlying sources of contrast. To address this, measurements of the complex permittivity, complex permeability, DC conductivity, and Grüneisen parameter have been made. These measurements allowed the origins of the contrast provided by each 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

  16. Gd-HOPO Based High Relaxivity MRI Contrast Agents

    SciTech Connect

    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.

  17. Manganese Oxide-Coated Carbon Nanotubes As Dual-Modality Lymph Mapping Agents for Photothermal Therapy of Tumor Metastasis.

    PubMed

    Wang, Sheng; Zhang, Qin; Yang, Peng; Yu, Xiangrong; Huang, Li-Yong; Shen, Shun; Cai, Sanjun

    2016-02-17

    Lymph node (LN) status is a major indicator of stage and survival of lung cancer patients. LN dissection is a primary option for lung cancer LN metastasis; however, this strategy elicits adverse effects and great trauma. Therefore, developing a minimally invasive technique to cure LN metastasis of lung cancer is desired. In this study, multiwalled carbon nanotubes (MWNTs) coated with manganese oxide (MnO) and polyethylene glycol (PEG) (namely MWNTs-MnO-PEG) was employed as a lymphatic theranostic agent to diagnose and treat metastatic LNs. After single local injection and lymph drainage were performed, regional LNs were clearly mapped by T1-weighted magnetic resonance (MR) of MnO and dark dye imaging of MWNTs. Meanwhile, metastatic LNs could be simultaneously ablated by near-infrared (NIR) irradiation under the guidance of dual-modality mapping. The excellent result was obtained in mice bearing LNs metastasis models, showing that MWNTs-MnO-PEG as a multifunctional theranostic agent was competent for dual-modality mapping guided photothermal therapy of metastatic LNs.

  18. Revisiting an old friend: manganese-based MRI contrast agents

    PubMed Central

    Pan, Dipanjan; Caruthers, Shelton D.; Senpan, Angana; Schmieder, Ann H.; Wickline, Samuel A.; Lanza, Gregory M.

    2011-01-01

    Non-invasive cellular and molecular imaging techniques are emerging as a multidisciplinary field that offers promise in understanding the components, processes, dynamics and therapies of disease at a molecular level. Magnetic resonance imaging (MRI) is an attractive technique due to the absence of radiation and high spatial resolution which makes it advantageous over techniques involving radioisotopes. Typically paramagnetic and superparamagnetic metals are used as contrast materials for MR based techniques. Gadolinium has been the predominant paramagnetic contrast metal until the discovery and association of the metal with nephrogenic systemic fibrosis (NSF) in some patients with severe renal or kidney disease. Manganese was one of the earliest reported examples of paramagnetic contrast material for MRI because of its efficient positive contrast enhancement. In this review manganese based contrast agent approaches will be presented with a particular emphasis on nanoparticulate agents. We have discussed both classically used small molecule based blood pool contrast agents and recently developed innovative nanoparticle-based strategies highlighting a number of successful molecular imaging examples. PMID:20860051

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

    PubMed

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

    2016-01-01

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

  20. Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration

    PubMed Central

    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

  1. Molecular Imaging and Contrast Agent Database (MICAD): Evolution and Progress

    PubMed Central

    Chopra, Arvind; Shan, Liang; Eckelman, W. C.; Leung, Kam; Latterner, Martin; Bryant, Stephen H.; Menkens, Anne

    2011-01-01

    The purpose of writing this review is to showcase the Molecular Imaging and Contrast Agent Database (MICAD; www.micad.nlm.nih.gov) to students, researchers and clinical investigators interested in the different aspects of molecular imaging. This database provides freely accessible, current, online scientific information regarding molecular imaging (MI) probes and contrast agents (CA) used for positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging, x-ray/computed tomography, optical imaging and ultrasound imaging. Detailed information on >1000 agents in MICAD is provided in a chapter format and can be accessed through PubMed. Lists containing >4250 unique MI probes and CAs published in peer-reviewed journals and agents approved by the United States Food and Drug Administration (FDA) as well as a CSV file summarizing all chapters in the database can be downloaded from the MICAD homepage. Users can search for agents in MICAD on the basis of imaging modality, source of signal/contrast, agent or target category, preclinical or clinical studies, and text words. Chapters in MICAD describe the chemical characteristics (structures linked to PubChem), the in vitro and in vivo activities and other relevant information regarding an imaging agent. All references in the chapters have links to PubMed. A Supplemental Information Section in each chapter is available to share unpublished information regarding an agent. A Guest Author Program is available to facilitate rapid expansion of the database. Members of the imaging community registered with MICAD periodically receive an e-mail announcement (eAnnouncement) that lists new chapters uploaded to the database. Users of MICAD are encouraged to provide feedback, comments or suggestions for further improvement of the database by writing to the editors at: micad@nlm.nih.gov PMID:21989943

  2. Polyethylenimine mediated silver nanoparticle-decorated magnetic graphene as a promising photothermal antibacterial agent

    NASA Astrophysics Data System (ADS)

    Wang, Ning; Hu, Bo; Chen, Ming-Li; Wang, Jian-Hua

    2015-05-01

    A novel bactericidal material, Ag@rGO-Fe3O4-PEI composite is prepared by in situ growth of silver nanoparticles onto the polyethylenimine (PEI)-mediated magnetic reduced graphene oxide (GO). The antibacterial performances of the composite are investigated by using the gram-negative bacteria Escherichia coli O157:H7 (E. coli O157:H7) as a model. The results indicate that the Ag@rGO-Fe3O4-PEI composite exhibits excellent antibacterial performance against E. coli O157:H7, with an antibacterial performance superior to those for the ever-reported photothermal materials. The bactericidal capability or the inhibition capability for bacteria growth is found to depend on the dosage of the Ag@rGO-Fe3O4-PEI and Ag/rGO-Fe3O4-PEI mass ratio within a certain range. By using a dosage of 0.1 μg mL-1, a killing rate of 99.9% is achieved for the E. coli O157:H7 (1 × 107 cfu mL-1) under a 0.5 min NIR laser irradiation (785 nm/50 mW cm-2). In addition, a minimum bactericidal concentration (MBC) of 0.100 μg mL-1 is achieved under near infrared (NIR) laser irradiation for 10 min, for which case there is absolutely no colony of E. coli O157:H7 found in the broth agar plate.

  3. "Keyhole" method for accelerating imaging of contrast agent uptake.

    PubMed

    van Vaals, J J; Brummer, M E; Dixon, W T; Tuithof, H H; Engels, H; Nelson, R C; Gerety, B M; Chezmar, J L; den Boer, J A

    1993-01-01

    Magnetic resonance (MR) imaging methods with good spatial and contrast resolution are often too slow to follow the uptake of contrast agents with the desired temporal resolution. Imaging can be accelerated by skipping the acquisition of data normally taken with strong phase-encoding gradients, restricting acquisition to weak-gradient data only. If the usual procedure of substituting zeroes for the missing data is followed, blurring results. Substituting instead reference data taken before or well after contrast agent injection reduces this problem. Volunteer and patient images obtained by using such reference data show that imaging can be usefully accelerated severalfold. Cortical and medullary regions of interest and whole kidney regions were studied, and both gradient- and spin-echo images are shown. The method is believed to be compatible with other acceleration methods such as half-Fourier reconstruction and reading of more than one line of k space per excitation.

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

    PubMed

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

    2007-07-01

    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 1.5T. Dynamic MR-studies over 11h 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 2.5mmol/L contrast solution. Simultaneous measurements of T(1) and T(2) were performed every 30min using a high-spatial-resolution "MIX"-sequence. T(1), T(2) and DeltaR(1), DeltaR(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 11h of diffusion. The absolute DeltaR(2)-effect in cartilage is at least as large as the DeltaR(1)-effect for all contrast agents. Maximum changes were 5-12s(-1) for DeltaR(1) and 8-15s(-1) for DeltaR(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, DeltaR(2) can be considered for quantification of contrast agent concentrations, since it is of the same magnitude and less time consuming to measure than DeltaR(1).

  5. Polyethylenimine mediated silver nanoparticle-decorated magnetic graphene as a promising photothermal antibacterial agent.

    PubMed

    Wang, Ning; Hu, Bo; Chen, Ming-Li; Wang, Jian-Hua

    2015-05-15

    A novel bactericidal material, Ag@rGO-Fe3O4-PEI composite is prepared by in situ growth of silver nanoparticles onto the polyethylenimine (PEI)-mediated magnetic reduced graphene oxide (GO). The antibacterial performances of the composite are investigated by using the gram-negative bacteria Escherichia coli O157:H7 (E. coli O157:H7) as a model. The results indicate that the Ag@rGO-Fe3O4-PEI composite exhibits excellent antibacterial performance against E. coli O157:H7, with an antibacterial performance superior to those for the ever-reported photothermal materials. The bactericidal capability or the inhibition capability for bacteria growth is found to depend on the dosage of the Ag@rGO-Fe3O4-PEI and Ag/rGO-Fe3O4-PEI mass ratio within a certain range. By using a dosage of 0.1 μg mL(-1), a killing rate of 99.9% is achieved for the E. coli O157:H7 (1 × 10(7) cfu mL(-1)) under a 0.5 min NIR laser irradiation (785 nm/50 mW cm(-2)). In addition, a minimum bactericidal concentration (MBC) of 0.100 μg mL(-1) is achieved under near infrared (NIR) laser irradiation for 10 min, for which case there is absolutely no colony of E. coli O157:H7 found in the broth agar plate.

  6. CMCTS stabilized Fe3O4 particles with extremely low toxicity as highly efficient near-infrared photothermal agents for in vivo tumor ablation

    NASA Astrophysics Data System (ADS)

    Shen, Song; Kong, Fenfen; Guo, Xiaomeng; Wu, Lin; Shen, Haijun; Xie, Meng; Wang, Xinshi; Jin, Yi; Ge, Yanru

    2013-08-01

    With the potential uses of photothermal therapy (PTT) in cancer treatment with excellent efficacy, and the growing concerns about the nanotoxicity of hyperthermia agents such as carbon nanotubes and gold-based nanomaterials, the importance of searching for a biocompatible hyperthermia agent cannot be emphasized too much. In this work, a novel promising hyperthermia agent employing magnetic Fe3O4 particles with fairly low toxicity was proposed. This hyperthermia agent showed rapid heat generation under NIR irradiation. After modification with carboxymethyl chitosan (CMCTS), the obtained Fe3O4@CMCTS particles could disperse stably in PBS and serum without any aggregation. The modification of CMCTS could decrease the adsorption of bovine serum albumin (BSA) and improve the cellular uptake. In a comparative study with hollow gold nanospheres (HAuNS), Fe3O4@CMCTS particles exhibited a comparable photothermal effect and fairly low cytotoxicity. The in vivo magnetic resonance (MR) images of mice revealed that by attaching a magnet to the tumor, Fe3O4@CMCTS particles accumulated in the tumor after intravenous injection and showed a low distribution in the liver. After being exposed to a 808 nm laser for 5 min at a low power density of 1.5 W cm-2, the tumors on Fe3O4@CMCTS-injected mice reached a temperature of ~52 °C and were completely destroyed. Thus, a kind of multifunctional magnetic nanoparticle with extremely low toxicity and a simple structure for simultaneous MR imaging, targeted drug delivery and photothermal therapy can be easily fabricated.With the potential uses of photothermal therapy (PTT) in cancer treatment with excellent efficacy, and the growing concerns about the nanotoxicity of hyperthermia agents such as carbon nanotubes and gold-based nanomaterials, the importance of searching for a biocompatible hyperthermia agent cannot be emphasized too much. In this work, a novel promising hyperthermia agent employing magnetic Fe3O4 particles with fairly low

  7. Nanoengineered multimodal contrast agent for medical image guidance

    NASA Astrophysics Data System (ADS)

    Perkins, Gregory J.; Zheng, Jinzi; Brock, Kristy; Allen, Christine; Jaffray, David A.

    2005-04-01

    Multimodality imaging has gained momentum in radiation therapy planning and image-guided treatment delivery. Specifically, computed tomography (CT) and magnetic resonance (MR) imaging are two complementary imaging modalities often utilized in radiation therapy for visualization of anatomical structures for tumour delineation and accurate registration of image data sets for volumetric dose calculation. The development of a multimodal contrast agent for CT and MR with prolonged in vivo residence time would provide long-lasting spatial and temporal correspondence of the anatomical features of interest, and therefore facilitate multimodal image registration, treatment planning and delivery. The multimodal contrast agent investigated consists of nano-sized stealth liposomes encapsulating conventional iodine and gadolinium-based contrast agents. The average loading achieved was 33.5 +/- 7.1 mg/mL of iodine for iohexol and 9.8 +/- 2.0 mg/mL of gadolinium for gadoteridol. The average liposome diameter was 46.2 +/- 13.5 nm. The system was found to be stable in physiological buffer over a 15-day period, releasing 11.9 +/- 1.1% and 11.2 +/- 0.9% of the total amounts of iohexol and gadoteridol loaded, respectively. 200 minutes following in vivo administration, the contrast agent maintained a relative contrast enhancement of 81.4 +/- 13.05 differential Hounsfield units (ΔHU) in CT (40% decrease from the peak signal value achieved 3 minutes post-injection) and 731.9 +/- 144.2 differential signal intensity (ΔSI) in MR (46% decrease from the peak signal value achieved 3 minutes post-injection) in the blood (aorta), a relative contrast enhancement of 38.0 +/- 5.1 ΔHU (42% decrease from the peak signal value achieved 3 minutes post-injection) and 178.6 +/- 41.4 ΔSI (62% decrease from the peak signal value achieved 3 minutes post-injection) in the liver (parenchyma), a relative contrast enhancement of 9.1 +/- 1.7 ΔHU (94% decrease from the peak signal value achieved 3 minutes

  8. Redox- and hypoxia-responsive MRI contrast agents.

    PubMed

    Do, Quyen N; Ratnakar, James S; Kovács, Zoltán; Sherry, A Dean

    2014-06-01

    The development of responsive or "smart" magnetic resonance imaging (MRI) contrast agents that can report specific biomarker or biological events has been the focus of MRI contrast agent research over the past 20 years. Among various biological hallmarks of interest, tissue redox and hypoxia are particularly important owing to their roles in disease states and metabolic consequences. Herein we review the development of redox-/hypoxia-sensitive T1 shortening and paramagnetic chemical exchange saturation transfer (PARACEST) MRI contrast agents. Traditionally, the relaxivity of redox-sensitive Gd(3+) -based complexes is modulated through changes in the ligand structure or molecular rotation, while PARACEST sensors exploit the sensitivity of the metal-bound water exchange rate to electronic effects of the ligand-pendant arms and alterations in the coordination geometry. Newer designs involve complexes of redox-active metal ions in which the oxidation states have different magnetic properties. The challenges of translating redox- and hypoxia-sensitive agents in vivo are also addressed. PMID:24825674

  9. Redox- and hypoxia-responsive MRI contrast agents.

    PubMed

    Do, Quyen N; Ratnakar, James S; Kovács, Zoltán; Sherry, A Dean

    2014-06-01

    The development of responsive or "smart" magnetic resonance imaging (MRI) contrast agents that can report specific biomarker or biological events has been the focus of MRI contrast agent research over the past 20 years. Among various biological hallmarks of interest, tissue redox and hypoxia are particularly important owing to their roles in disease states and metabolic consequences. Herein we review the development of redox-/hypoxia-sensitive T1 shortening and paramagnetic chemical exchange saturation transfer (PARACEST) MRI contrast agents. Traditionally, the relaxivity of redox-sensitive Gd(3+) -based complexes is modulated through changes in the ligand structure or molecular rotation, while PARACEST sensors exploit the sensitivity of the metal-bound water exchange rate to electronic effects of the ligand-pendant arms and alterations in the coordination geometry. Newer designs involve complexes of redox-active metal ions in which the oxidation states have different magnetic properties. The challenges of translating redox- and hypoxia-sensitive agents in vivo are also addressed.

  10. Redox- and Hypoxia-Responsive MRI Contrast Agents

    PubMed Central

    Do, Quyen N.; Ratnakar, James S.; Kovács, Zoltán

    2014-01-01

    The development of responsive or “smart” magnetic resonance imaging (MRI) contrast agents that can report specific biomarker or biological events has been the focus of MRI contrast agent research over the past 20 years. Among various biological hallmarks of interest, tissue redox and hypoxia are particularly important owing to their roles in disease states and metabolic consequences. Herein we review the development of redox-/hypoxia-sensitive T1 shortening and paramagnetic chemical exchange saturation transfer (PARACEST) MRI contrast agents. Traditionally, the relaxivity of redox-sensitive Gd3+-based complexes is modulated through changes in the ligand structure or molecular rotation, while PARACEST sensors exploit the sensitivity of the metal-bound water exchange rate to electronic effects of the ligand-pendant arms and alterations in the coordination geometry. Newer designs involve complexes of redox-active metal ions in which the oxidation states have different magnetic properties. The challenges of translating redox- and hypoxia-sensitive agents in vivo are also addressed. PMID:24825674

  11. Effects of ultrasound and ultrasound contrast agent on vascular tissue

    PubMed Central

    2012-01-01

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

  12. Magnetic nanobeads as potential contrast agents for magnetic resonance imaging.

    PubMed

    Pablico-Lansigan, Michele H; Hickling, William J; Japp, Emily A; Rodriguez, Olga C; Ghosh, Anup; Albanese, Chris; Nishida, Maki; Van Keuren, Edward; Fricke, Stanley; Dollahon, Norman; Stoll, Sarah L

    2013-10-22

    Metal-oxo clusters have been used as building blocks to form hybrid nanomaterials and evaluated as potential MRI contrast agents. We have synthesized a biocompatible copolymer based on a water stable, nontoxic, mixed-metal-oxo cluster, Mn8Fe4O12(L)16(H2O)4, where L is acetate or vinyl benzoic acid, and styrene. The cluster alone was screened by NMR for relaxivity and was found to be a promising T2 contrast agent, with r1 = 2.3 mM(-1) s(-1) and r2 = 29.5 mM(-1) s(-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. The metal-oxo cluster Mn8Fe4(VBA)16 (VBA = vinyl benzoic acid) can be copolymerized with styrene under miniemulsion conditions. Miniemulsion allows for the formation of nanometer-sized paramagnetic beads (~80 nm diameter), which were also evaluated as a contrast agent for MRI. These highly monodispersed, hybrid nanoparticles have enhanced properties, with the option for surface functionalization, making them a promising tool for biomedicine. Interestingly, both relaxivity measurements and MRI studies show that embedding the Mn8Fe4 core within a polymer matrix decreases r2 effects with little effect on r1, resulting in a positive T1 contrast enhancement.

  13. A Multifunctional Biomaterial with NIR Long Persistent Phosphorescence, Photothermal Response and Magnetism.

    PubMed

    Wu, Yiling; Li, Yang; Qin, Xixi; Qiu, Jianrong

    2016-09-20

    There are many reports on long persistent phosphors (LPPs) applied in bioimaging. However, there are few reports on LPPs applied in photothermal therapy (PTT), and an integrated system with multiple functions of diagnosis and therapy. In this work, we fabricate effective multifunctional phosphors Zn3 Ga2 SnO8 : Cr(3+) , Nd(3+) , Gd(3+) with NIR persistent phosphorescence, photothermal response and magnetism. Such featured materials can act as NIR optical biolabels and magnetic resonance imaging (MRI) contrast agents for tracking the early cancer cells, but also as photothermal therapeutic agent for killing the cancer cells. This new multifunctional biomaterial is expected to open a new possibility of setting up an advanced imaging-guided therapy system featuring a high resolution for bioimaging and low side effects for the photothermal ablation of tumors.

  14. Screening CEST contrast agents using ultrafast CEST imaging

    NASA Astrophysics Data System (ADS)

    Xu, Xiang; Yadav, Nirbhay N.; Song, Xiaolei; McMahon, Michael T.; Jerschow, Alexej; van Zijl, Peter C. M.; Xu, Jiadi

    2016-04-01

    A chemical exchange saturation transfer (CEST) experiment can be performed in an ultrafast fashion if a gradient field is applied simultaneously with the saturation pulse. This approach has been demonstrated for studying dia- and para-magnetic CEST agents, hyperpolarized Xe gas and in vivo spectroscopy. In this study we present a simple method for the simultaneous screening of multiple samples. Furthermore, by interleaving a number of saturation and readout periods within the TR, a series of images with different saturation times can be acquired, allowing for the quantification of exchange rates using the variable saturation time (QUEST) approach in a much accelerated fashion, thus enabling high throughput screening of CEST contrast agents.

  15. Phase-Change Contrast Agents for Imaging and Therapy

    PubMed Central

    Sheeran, Paul S.; Dayton, Paul A.

    2016-01-01

    Phase-change contrast agents (PCCAs) for ultrasound-based applications have resulted in novel ways of approaching diagnostic and therapeutic techniques beyond what is possible with microbubble contrast agents and liquid emulsions. When subjected to sufficient pressures delivered by an ultrasound transducer, stabilized droplets undergo a phase-transition to the gaseous state and a volumetric expansion occurs. This phenomenon, termed acoustic droplet vaporization, has been proposed as a means to address a number of in vivo applications at the microscale and nanoscale. In this review, the history of PCCAs, physical mechanisms involved, and proposed applications are discussed with a summary of studies demonstrated in vivo. Factors that influence the design of PCCAs are discussed, as well as the need for future studies to characterize potential bioeffects for administration in humans and optimization of ultrasound parameters. PMID:22352770

  16. Nanoshells as an optical coherence tomography contrast agent

    NASA Astrophysics Data System (ADS)

    Barton, Jennifer K.; Halas, Naomi J.; West, Jennifer L.; Drezek, Rebekah A.

    2004-07-01

    Nanoshells are a layered dielectric core/metal shell composite nanostructure with an optical resonance geometrically tunable through the visible and near infrared. Due to their small size, ability to generate a strong backscattering signal, and potential for surface modification, they may be an ideal in vivo optical coherence tomography contrast agent. We performed a pilot study to assess their capabilities. Images of a cuvette filled with dilute nanoshells, 2 μm polystyrene microspheres, or a combination were obtained. When compared to microspheres, images of the nanoshells where much brighter and attenuation of the bottom cuvette interface less. Injection of micropheres into the tail vein of mice and hamsters caused a noticeable brightening of OCT images of the dorsal skin. These pilot studies indicate that nanoshells may be an excellent OCT contrast agent; work is continuing to determine optimum nanoshell parameters and applications.

  17. Hyperpolarized lithium-6 as a sensor of nanomolar contrast agents.

    PubMed

    van Heeswijk, Ruud B; Uffmann, Kai; Comment, Arnaud; Kurdzesau, Fiodar; Perazzolo, Chiara; Cudalbu, Cristina; Jannin, Sami; Konter, Jacobus A; Hautle, Patrick; van den Brandt, Ben; Navon, Gil; van der Klink, Jacques J; Gruetter, Rolf

    2009-06-01

    Lithium is widely used in psychotherapy. The (6)Li isotope has a long intrinsic longitudinal relaxation time T(1) on the order of minutes, making it an ideal candidate for hyperpolarization experiments. In the present study we demonstrated that lithium-6 can be readily hyperpolarized within 30 min, while retaining a long polarization decay time on the order of a minute. We used the intrinsically long relaxation time for the detection of 500 nM contrast agent in vitro. Hyperpolarized lithium-6 was administered to the rat and its signal retained a decay time on the order of 70 sec in vivo. Localization experiments imply that the lithium signal originated from within the brain and that it was detectable up to 5 min after administration. We conclude that the detection of submicromolar contrast agents using hyperpolarized NMR nuclei such as (6)Li may provide a novel avenue for molecular imaging.

  18. Tunable Diacetylene Polymerized Shell Microbubbles as Ultrasound Contrast Agents

    PubMed Central

    Park, Yoonjee; Luce, Adam C.; Whitaker, Ragnhild D.; Amin, Bhumica; Cabodi, Mario; Nap, Rikkert J.; Szleifer, Igal; Cleveland, Robin O.; Nagy, Jon O.; Wong, Joyce Y.

    2012-01-01

    Monodisperse gas microbubbles, encapsulated with a shell of photopolymerizable diacetylene lipids and phospholipids, were produced by microfluidic flow focusing, for use as ultrasound contrast agents. The stability of the polymerized shell microbubbles against both aggregation and gas dissolution under physiological conditions was studied. Polyethylene glycol (PEG) 5000, which was attached to the diacetylene lipids, was predicted by molecular theory to provide more steric hindrance against aggregation than PEG 2000 and this was confirmed experimentally. The polymerized shell microbubbles were found to have higher shell-resistance than nonpolymerizable shell microbubbles and commercially available microbubbles (Vevo MicroMarker). The acoustic stability under 7.5 MHz ultrasound insonation was significantly greater than for the two comparison microbubbles. The acoustic stability was tunable by varying the amount of diacetylene lipid. Thus, our polymerized shell microbubbles are a promising platform for ultrasound contrast agents. PMID:22260537

  19. The in vivo relaxivity of MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Shuter, Borys

    1999-11-01

    Post-contrast clinical 1H Magnetic Resonance Images have to date been interpreted with little regard for possible variations in the in-vivo properties of injected magnetic pharmaceuticals (contrast agents), particularly in their relaxivity or ability to alter tissue relaxation rates, T2-1 and T 2-1, per unit concentration. The relaxivities of contrast agents have only rarely been measured in-vivo, measurements usually being performed on excised tissues and at magnetic field strengths lower than used in clinical practice. Some researchers have simply assumed that relaxivities determined in homogeneous tissue phantoms were applicable in-vivo. In this thesis, the relaxivities of two contrast agents, Gd-DTPA and Gd-EOB-DTPA, were measured in simple tissue phantoms and in the kidney and liver of intact, but sacrificed, Wistar rats using a clinical MR scanner with a magnetic field of 1.5 Tesla. T1 and T2 were determined from sets of images acquired using a standard clinical spin-echo pulse sequence. The contrast agent concentration in tissue was assessed by radioassay of 153Gd-DTPA or 153Gd-EOB-DTPA, mixed with the normal compound prior to injection. Relaxivity was taken as the slope of a linear regression fit of relaxation rate against Gd concentration. The relaxivities of Gd-EOB-DTPA were similarly determined in normal and biliary- obstructed guinea pigs. Relaxivities in tissue differed significantly from values obtained in simple phantoms. Kidney T1 relaxivity was reduced for both compounds in normal animals. Three days or more of biliary obstruction produced further reductions in kidney T1 relaxivity of Gd-EOB-DTPA, providing strong evidence that disease affects contrast agent relaxivity. Kidney T2 relaxivity was much greater than T1 relaxivity and was also depressed by biliary obstruction. Liver T1 and T 2 relaxivites were increased above phantom values, but were not affected by the biliary obstruction. Water compartmentalisation, macromolecular binding, proton

  20. Beat frequency ultrasonic microsphere contrast agent detection system

    NASA Technical Reports Server (NTRS)

    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.

  1. The emerging role of contrast agents in echocardiography.

    PubMed

    DeMaria, A N

    1997-10-01

    Because of an outstanding track record for diagnostic accuracy, noninvasive properties, ease of use, and relatively low expense, echocardiography has become a leading technique in the evaluation of cardiac disorders. In the three decades since echocardiography entered the ranks of standard cardiac diagnostic tools, refinements and technological advances have progressively increased its usefulness. One of the most noteworthy advancements has been the development of ultrasound contrast agents, which investigators are avidly seeking to apply to a broad spectrum of clinical settings and issues.

  2. Acoustic properties of organic powders as ultrasonic contrast agents

    NASA Astrophysics Data System (ADS)

    Burov, V. A.; Loginov, S. V.; Dmitriev, K. V.

    2011-11-01

    The results of experiments on measuring attenuation and the effective acoustic nonlinear parameter of the second order are given for a suspension of cocoa-powder in water at different concentrations of the suspension. In the process of evaluating the value of the nonlinear parameter the attenuation in the suspension and generation of the second harmonic not only in the suspension but also in water are taken into account. The obtained results are evidence of the possibility of using a suspension of cocoa-powder in water as a technical substitute for ultrasonic contrast agents. The values of attenuation (up to 60 m-1 at the concentration of 1 g of the powder per 1 l of water) and the nonlinear parameter (up to 120 m-1 at the same concentration) mean that the suspension of cocoa-powder in water has smaller attenuation and the nonlinear parameter than ultrasonic contrast agents at the same concentration. However, these values for the suspension differ considerably from corresponding values for water or blood and, therefore, a suspension of cocoa-powder in water is a promising "substitute" for ultrasonic contrast agents in the case of technical testing of systems for nonlinear tomography of a blood flow, but cannot replace them in medical studies.

  3. Simulation model for contrast agent dynamics in brain perfusion scans.

    PubMed

    Bredno, Jörg; Olszewski, Mark E; Wintermark, Max

    2010-07-01

    Standardization efforts are currently under way to reduce the heterogeneity of quantitative brain perfusion methods. A brain perfusion simulation model is proposed to generate test data for an unbiased comparison of these methods. This model provides realistic simulated patient data and is independent of and different from any computational method. The flow of contrast agent solute and blood through cerebral vasculature with disease-specific configurations is simulated. Blood and contrast agent dynamics are modeled as a combination of convection and diffusion in tubular networks. A combination of a cerebral arterial model and a microvascular model provides arterial-input and time-concentration curves for a wide range of flow and perfusion statuses. The model is configured to represent an embolic stroke in one middle cerebral artery territory and provides physiologically plausible vascular dispersion operators for major arteries and tissue contrast agent retention functions. These curves are fit to simpler template curves to allow the use of the simulation results in multiple validation studies. A gamma-variate function with fit parameters is proposed as the vascular dispersion operator, and a combination of a boxcar and exponential decay function is proposed as the retention function. Such physiologically plausible operators should be used to create test data that better assess the strengths and the weaknesses of various analysis methods.

  4. Target-specific contrast agents for magnetic resonance microscopy

    PubMed Central

    Blackwell, Megan L.; Farrar, Christian T.; Fischl, Bruce; Rosen, Bruce R.

    2009-01-01

    High-resolution ex vivo magnetic resonance (MR) imaging can be used to delineate prominent architectonic features in the human brain, but increased contrast is required to visualize more subtle distinctions. To aid MR sensitivity to cell density and myelination, we have begun the development of target-specific paramagnetic contrast agents. This work details the first application of luxol fast blue (LFB), an optical stain for myelin, as a white matter-selective MR contrast agent for human ex vivo brain tissue. Formalin-fixed human visual cortex was imaged with an isotropic resolution between 80 and 150 μm at 4.7 and 14 T before and after en bloc staining with LFB. Longitudinal (R1) and transverse (R2) relaxation rates in LFB-stained tissue increased proportionally with myelination at both field strengths. Changes in R1 resulted in larger contrast-to-noise ratios (CNR), per unit time, on T1-weighted images between more myelinated cortical layers (IV–VI) and adjacent, superficial layers (I–III) at both field strengths. Specifically, CNR for LFB-treated samples increased by 229±13% at 4.7 T and 269±25% at 14 T when compared to controls. Also, additional cortical layers (IVca, IVd, and Va) were resolvable in 14T-MR images of LFB-treated samples but not in control samples. After imaging, samples were sliced in 40-micron sections, mounted, and photographed. Both the macroscopic and microscopic distributions of LFB were found to mimic those of traditional histological preparations. Our results suggest target-specific contrast agents will enable more detailed MR images with applications in imaging pathological ex vivo samples and constructing better MR atlases from ex vivo brains. PMID:19385012

  5. Hepatobiliary MR Imaging with Gadolinium Based Contrast Agents

    PubMed Central

    Frydrychowicz, Alex; Lubner, Meghan G.; Brown, Jeffrey J.; Merkle, Elmar M.; Nagle, Scott K.; Rofsky, Neil M.; Reeder, Scott B.

    2011-01-01

    The advent of gadolinium-based “hepatobiliary” contrast agents offers new opportunities for diagnostic MRI and has triggered a great interest for innovative imaging approaches to the liver and bile ducts. In this review article we will discuss the imaging properties of the two gadolinium-based hepatobiliary contrast agents currently available in the USA, gadobenate dimeglumine and gadoxetic acid, as well as important pharmacokinetic differences that affect their diagnostic performance. We will review potential applications, protocol optimization strategies, as well as diagnostic pitfalls. A variety of illustrative case examples will be used to demonstrate the role of these agents in detection and characterization of liver lesions as well as for imaging the biliary system. Changes in MR protocols geared towards optimizing workflow and imaging quality will also be discussed. It is our aim that the information provided in this article will facilitate the optimal utilization of these agents, and will stimulate the reader‘s pursuit of new applications for future benefit. PMID:22334493

  6. The Paramagnetic Pillared Bentonites as Digestive Tract MRI Contrast Agents

    NASA Astrophysics Data System (ADS)

    Mojović, Miloš; Daković, Marko; Omerašević, Mia; Mojović, Zorica; Banković, Predrag; Milutinović-Nikolić, Aleksandra; Jovanović, Dušan

    The increased use of imaging techniques in diagnostic studies, such as MRI, has contributed to the development of the wide range of new materials which could be successfully used as image improving agents. However, there is a lack of such substances in the area of gastrointestinal tract MRI. Many of the traditionally popular relaxation altering agents show poor results and disadvantages provoking black bowel, side effects of diarrhea and the presence of artifacts arising from clumping. Paramagnetic species seem to be potentially suitable agents for these studies, but contrast opacification has been reported and less than 60% of the gastrointestinal tract magnetic resonance scans showed improved delineation of abdominal pathologies. The new solution has been proposed as zeolites or smectite clays (hectorite and montmorillonite) enclosing of paramagnetic metal ions obtained by ion-exchange methods. However, such materials have problems of leakage of paramagnetic ions causing the appearance of the various side-effects. In this study we show that Co+2 and Dy+3 paramagnetic-pillared bentonites could be successfully used as MRI digestive tract non-leaching contrast agents, altering the longitudinal and transverse relaxation times of fluids in contact with the clay minerals.

  7. Necrosis avid contrast agents: functional similarity versus structural diversity.

    PubMed

    Ni, Yicheng; Bormans, Guy; Chen, Feng; Verbruggen, Alfons; Marchal, Guy

    2005-08-01

    Two categories of necrosis-avid contrast agents (NACAs), namely porphyrin- and nonporphyrin-based complexes, have thus far been discovered as necrosis-targeting markers for noninvasive magnetic resonance imaging (MRI) identification of acute myocardial infarction, assessment of tissue or organ viability, and therapeutic evaluation after interventional therapies. In addition to necrosis labeling, other less-specific functions, such as first-pass perfusion, blood pool contrast effect, hepatobiliary contrast enhancement (CE), adrenal and spleen CE, and renal functional imaging, also are demonstrated with NACAs. Despite various investigations with a collection of clues in favor of certain hypotheses, the mechanisms of such a unique targetability for NACAs still remain to be elucidated. However, a few things have become clear that porphyrin-like structures are not necessary for necrosis avidity and the albumin binding is not the supposed driving force but only a parallel nonspecific feature shared by both NACAs and non-NACA substances. Although the research and development of NACAs still remain in preclinical stage at a relatively small scale, their significance rests upon striking enhancement effects, which may warrant their eventual versatile clinical applications. The present review article is intended to summarize the cumulated facts about the evolving research on this topic, to demonstrate experimental observations for better understanding of the mechanisms, to trigger broader public interests and more intensive research activities, and to advocate, toward both academics and industries, further promotion of preclinical and clinical development of this unique and promising class of contrast agents. PMID:16024991

  8. Biocompatible Nanocomplexes for Molecular Targeted MRI Contrast Agent

    NASA Astrophysics Data System (ADS)

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

    2009-07-01

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

  9. Nanomaterials incorporated ultrasound contrast agents for cancer theranostics

    PubMed Central

    Fu, Lei; Ke, Heng-Te

    2016-01-01

    Nanotechnology provides various nanomaterials with tremendous functionalities for cancer diagnostics and therapeutics. Recently, theranostics has been developed as an alternative strategy for efficient cancer treatment through combination of imaging diagnosis and therapeutic interventions under the guidance of diagnostic results. Ultrasound (US) imaging shows unique advantages with excellent features of real-time imaging, low cost, high safety and portability, making US contrast agents (UCAs) an ideal platform for construction of cancer theranostic agents. This review focuses on the development of nanomaterials incorporated multifunctional UCAs serving as theranostic agents for cancer diagnostics and therapeutics, via conjugation of superparamagnetic iron oxide nanoparticles (SPIOs), CuS nanoparticles, DNA, siRNA, gold nanoparticles (GNPs), gold nanorods (GNRs), gold nanoshell (GNS), graphene oxides (GOs), polypyrrole (PPy) nanocapsules, Prussian blue (PB) nanoparticles and so on to different types of UCAs. The cancer treatment could be more effectively and accurately carried out under the guidance and monitoring with the help of the achieved theranostic agents. Furthermore, nanomaterials incorporated theranostic agents based on UCAs can be designed and constructed by demand for personalized and accurate treatment of cancer, demonstrating their great potential to address the challenges of cancer heterogeneity and adaptation, which can provide alternative strategies for cancer diagnosis and therapeutics. PMID:27807499

  10. Contrast Agent Dose Effects in Cerebral Dynamic Susceptibility Contrast Magnetic Resonance Perfusion Imaging

    PubMed Central

    Alger, Jeffry R.; Schaewe, Timothy J.; Lai, Tom C.; Frew, Andrew J.; Vespa, Paul M.; Etchepare, Maria; Liebeskind, David S.; Saver, Jeffrey L.; Kidwell, S. Chelsea

    2009-01-01

    Purpose To study the contrast agent dose sensitivity of hemodynamic parameters derived from brain dynamic susceptibility contrast MRI (DSC-MRI). Materials and Methods Sequential DSC-MRI (1.5T gradient-echo echo-planar imaging using an echo time of 61–64 msec) was performed using contrast agent doses of 0.1 and 0.2 mmol/kg delivered at a fixed rate of 5.0 mL/second in 12 normal subjects and 12 stroke patients. Results 1) Arterial signal showed the expected doubling in relaxation response (ΔR2*) to dose doubling. 2) The brain signal showed a less than doubled ΔR2* response to dose doubling. 3) The 0.2 mmol/kg dose studies subtly under-estimated cerebral blood volume (CBV) and cerebral blood flow (CBF) relative to the 0.1 mmol/kg studies. 4) In the range of low CBV and CBF, the 0.2 mmol/kg studies over-estimated the CBV and CBF compared with the 0.1 mmol/kg studies. 5) The 0.1 mmol/kg studies reported larger ischemic volumes in stroke. Conclusion Subtle but statistically significant dose sensitivities were found. Therefore, it is advisable to carefully control the contrast agent dose when DSC-MRI is used in clinical trials. The study also suggests that a 0.1 mmol/kg dose is adequate for hemodynamic measurements. PMID:19097106

  11. Perfusion Imaging with a Freely Diffusible Hyperpolarized Contrast Agent

    PubMed Central

    Grant, Aaron K.; Vinogradov, Elena; Wang, Xiaoen; Lenkinski, Robert E.; Alsop, David C.

    2011-01-01

    Contrast agents that can diffuse freely into or within tissue have numerous attractive features for perfusion imaging. Here we present preliminary data illustrating the suitability of hyperpolarized 13C labeled 2-methylpropan-2-ol (also known as dimethylethanol, tertiary butyl alcohol and tert-butanol) as a freely diffusible contrast agent for magnetic resonance perfusion imaging. Dynamic 13C images acquired in rat brain with a balanced steady-state free precession (bSSFP) sequence following administration of hyperpolarized 2-methylpropan-2-ol show that this agent can be imaged with 2–4s temporal resolution, 2mm slice thickness, and 700 micron in-plane resolution while retaining adequate signal-to-noise ratio. 13C relaxation measurements on 2-methylpropan-2-ol in blood at 9.4T yield T1=46±4s and T2=0.55±0.03s. In the rat brain at 4.7T, analysis of the temporal dynamics of the bSSFP image intensity in tissue and venous blood indicate that 2-methylpropan-2-ol has a T2 of roughly 2–4s and a T1 of 43±24s. In addition, the images indicate that 2-methylpropan-2-ol is freely diffusible in brain and hence has a long residence time in tissue; this in turn makes it possible to image the agent continuously for tens of seconds. These characteristics show that 2-methylpropan-2-ol is a promising agent for robust and quantitative perfusion imaging in the brain and body. PMID:21432901

  12. Multifunctional Photosensitizer-Based Contrast Agents for Photoacoustic Imaging

    NASA Astrophysics Data System (ADS)

    Ho, Chris Jun Hui; Balasundaram, Ghayathri; Driessen, Wouter; McLaren, Ross; Wong, Chi Lok; Dinish, U. S.; Attia, Amalina Binte Ebrahim; Ntziachristos, Vasilis; Olivo, Malini

    2014-06-01

    Photoacoustic imaging is a novel hybrid imaging modality combining the high spatial resolution of optical imaging with the high penetration depth of ultrasound imaging. Here, for the first time, we evaluate the efficacy of various photosensitizers that are widely used as photodynamic therapeutic (PDT) agents as photoacoustic contrast agents. Photoacoustic imaging of photosensitizers exhibits advantages over fluorescence imaging, which is prone to photobleaching and autofluorescence interference. In this work, we examined the photoacoustic activity of 5 photosensitizers: zinc phthalocyanine, protoporphyrin IX, 2,4-bis [4-(N,N-dibenzylamino)-2,6-dihydroxyphenyl] squaraine, chlorin e6 and methylene blue in phantoms, among which zinc phthalocyanine showed the highest photoacoustic activity. Subsequently, we evaluated its tumor localization efficiency and biodistribution at multiple time points in a murine model using photoacoustic imaging. We observed that the probe localized at the tumor within 10 minutes post injection, reaching peak accumulation around 1 hour and was cleared within 24 hours, thus, demonstrating the potential of photosensitizers as photoacoustic imaging contrast agents in vivo. This means that the known advantages of photosensitizers such as preferential tumor uptake and PDT efficacy can be combined with photoacoustic imaging capabilities to achieve longitudinal monitoring of cancer progression and therapy in vivo.

  13. Multifunctional photosensitizer-based contrast agents for photoacoustic imaging.

    PubMed

    Ho, Chris Jun Hui; Balasundaram, Ghayathri; Driessen, Wouter; McLaren, Ross; Wong, Chi Lok; Dinish, U S; Attia, Amalina Binte Ebrahim; Ntziachristos, Vasilis; Olivo, Malini

    2014-01-01

    Photoacoustic imaging is a novel hybrid imaging modality combining the high spatial resolution of optical imaging with the high penetration depth of ultrasound imaging. Here, for the first time, we evaluate the efficacy of various photosensitizers that are widely used as photodynamic therapeutic (PDT) agents as photoacoustic contrast agents. Photoacoustic imaging of photosensitizers exhibits advantages over fluorescence imaging, which is prone to photobleaching and autofluorescence interference. In this work, we examined the photoacoustic activity of 5 photosensitizers: zinc phthalocyanine, protoporphyrin IX, 2,4-bis [4-(N,N-dibenzylamino)-2,6-dihydroxyphenyl] squaraine, chlorin e6 and methylene blue in phantoms, among which zinc phthalocyanine showed the highest photoacoustic activity. Subsequently, we evaluated its tumor localization efficiency and biodistribution at multiple time points in a murine model using photoacoustic imaging. We observed that the probe localized at the tumor within 10 minutes post injection, reaching peak accumulation around 1 hour and was cleared within 24 hours, thus, demonstrating the potential of photosensitizers as photoacoustic imaging contrast agents in vivo. This means that the known advantages of photosensitizers such as preferential tumor uptake and PDT efficacy can be combined with photoacoustic imaging capabilities to achieve longitudinal monitoring of cancer progression and therapy in vivo. PMID:24938638

  14. Multifunctional photosensitizer-based contrast agents for photoacoustic imaging.

    PubMed

    Ho, Chris Jun Hui; Balasundaram, Ghayathri; Driessen, Wouter; McLaren, Ross; Wong, Chi Lok; Dinish, U S; Attia, Amalina Binte Ebrahim; Ntziachristos, Vasilis; Olivo, Malini

    2014-06-18

    Photoacoustic imaging is a novel hybrid imaging modality combining the high spatial resolution of optical imaging with the high penetration depth of ultrasound imaging. Here, for the first time, we evaluate the efficacy of various photosensitizers that are widely used as photodynamic therapeutic (PDT) agents as photoacoustic contrast agents. Photoacoustic imaging of photosensitizers exhibits advantages over fluorescence imaging, which is prone to photobleaching and autofluorescence interference. In this work, we examined the photoacoustic activity of 5 photosensitizers: zinc phthalocyanine, protoporphyrin IX, 2,4-bis [4-(N,N-dibenzylamino)-2,6-dihydroxyphenyl] squaraine, chlorin e6 and methylene blue in phantoms, among which zinc phthalocyanine showed the highest photoacoustic activity. Subsequently, we evaluated its tumor localization efficiency and biodistribution at multiple time points in a murine model using photoacoustic imaging. We observed that the probe localized at the tumor within 10 minutes post injection, reaching peak accumulation around 1 hour and was cleared within 24 hours, thus, demonstrating the potential of photosensitizers as photoacoustic imaging contrast agents in vivo. This means that the known advantages of photosensitizers such as preferential tumor uptake and PDT efficacy can be combined with photoacoustic imaging capabilities to achieve longitudinal monitoring of cancer progression and therapy in vivo.

  15. Intrinsically Mn2+-Chelated Polydopamine Nanoparticles for Simultaneous Magnetic Resonance Imaging and Photothermal Ablation of Cancer Cells.

    PubMed

    Miao, Zhao-Hua; Wang, Hui; Yang, Huanjie; Li, Zheng-Lin; Zhen, Liang; Xu, Cheng-Yan

    2015-08-12

    Theranostic agents for magnetic resonance imaging (MRI) guided photothermal therapy have attracted intensive interest in cancer diagnosis and treatment. However, the development of biocompatible theranostic agents with high photothermal conversion efficiency and good MRI contrast effect remains a challenge. Herein, PEGylated Mn2+-chelated polydopamine (PMPDA) nanoparticles were successfully developed as novel theranostic agents for simultaneous MRI signal enhancement and photothermal ablation of cancer cells, based on intrinsic manganese-chelating properties and strong near-infrared absorption of polydopamine nanomaterials. The obtained PMPDA nanoparticles showed significant MRI signal enhancement for both in vitro and in vivo imaging. Highly effective photothermal ablation of HeLa cells exposed to PMPDA nanoparticles was then achieved upon laser irradiation for 10 min. Furthermore, the excellent biocompatibility of PMPDA nanoparticles, because of the use of Mn2+ ions as diagnostic agents and biocompatible polydopamine as photothermal agents, was confirmed by a standard MTT assay. Therefore, the developed PMPDA nanoparticles could be used as a promising theranostic agent for MRI-guided photothermal therapy of cancer cells.

  16. Intrinsically Mn2+-Chelated Polydopamine Nanoparticles for Simultaneous Magnetic Resonance Imaging and Photothermal Ablation of Cancer Cells.

    PubMed

    Miao, Zhao-Hua; Wang, Hui; Yang, Huanjie; Li, Zheng-Lin; Zhen, Liang; Xu, Cheng-Yan

    2015-08-12

    Theranostic agents for magnetic resonance imaging (MRI) guided photothermal therapy have attracted intensive interest in cancer diagnosis and treatment. However, the development of biocompatible theranostic agents with high photothermal conversion efficiency and good MRI contrast effect remains a challenge. Herein, PEGylated Mn2+-chelated polydopamine (PMPDA) nanoparticles were successfully developed as novel theranostic agents for simultaneous MRI signal enhancement and photothermal ablation of cancer cells, based on intrinsic manganese-chelating properties and strong near-infrared absorption of polydopamine nanomaterials. The obtained PMPDA nanoparticles showed significant MRI signal enhancement for both in vitro and in vivo imaging. Highly effective photothermal ablation of HeLa cells exposed to PMPDA nanoparticles was then achieved upon laser irradiation for 10 min. Furthermore, the excellent biocompatibility of PMPDA nanoparticles, because of the use of Mn2+ ions as diagnostic agents and biocompatible polydopamine as photothermal agents, was confirmed by a standard MTT assay. Therefore, the developed PMPDA nanoparticles could be used as a promising theranostic agent for MRI-guided photothermal therapy of cancer cells. PMID:26196160

  17. What We Can Really Do with Bioresponsive MRI Contrast Agents.

    PubMed

    Angelovski, Goran

    2016-06-13

    Bioresponsive MRI contrast agents hold great promise for monitoring major physiological and pathological processes in a non-invasive manner. They are capable of altering the acquired MRI signal as a consequence of changes in their microenvironment, thus allowing real-time functional reporting in living organisms. Importantly, chemistry offers diverse solutions for the design of agents which respond to a great number of specific targets. However, the path to the successful utilization of these biomarkers in the desired functional MRI studies involves careful consideration of multiple scientific, technical, and practical issues across various research disciplines. This Minireview highlights the critical steps for planning and executing such multidisciplinary projects with an aim to substantially improve our knowledge of essential biological processes. PMID:27112329

  18. Impact of dispersants on relaxivities of magnetite contrast agents

    NASA Astrophysics Data System (ADS)

    Ma, Ji; Cheng, Lingchao; Chen, Kezheng

    2015-04-01

    Particle size is normally thought to be a major factor to evaluate MRI performance of contrast agents in biological systems. In this regard, three size-relevant regimes, including motional averaging regime, static dephasing regime, and echo-limited regime, have been well developed. In this study, we find the dispersant, which is often used as the subordinate additive in MRI measurements, is another key factor that determines the application of these three regimes in real systems. Our results show that the identically sized particle systems can separately exhibit static dephasing and echo-limited behaviors merely by altering the dispersants in aqueous solution.

  19. Gadolinium nanoparticles and contrast agent as radiation sensitizers

    NASA Astrophysics Data System (ADS)

    Taupin, Florence; Flaender, Mélanie; Delorme, Rachel; Brochard, Thierry; Mayol, Jean-François; Arnaud, Josiane; Perriat, Pascal; Sancey, Lucie; Lux, François; Barth, Rolf F.; Carrière, Marie; Ravanat, Jean-Luc; Elleaume, Hélène

    2015-06-01

    The goal of the present study was to evaluate and compare the radiosensitizing properties of gadolinium nanoparticles (NPs) with the gadolinium contrast agent (GdCA) Magnevist® in order to better understand the mechanisms by which they act as radiation sensitizers. This was determined following either low energy synchrotron irradiation or high energy gamma irradiation of F98 rat glioma cells exposed to ultrasmall gadolinium NPs (GdNPs, hydrodynamic diameter of 3 nm) or GdCA. Clonogenic assays were used to quantify cell survival after irradiation in the presence of Gd using monochromatic x-rays with energies in the 25 keV-80 keV range from a synchrotron and 1.25 MeV gamma photons from a cobalt-60 source. Radiosensitization was demonstrated with both agents in combination with X-irradiation. At the same concentration (2.1 mg mL-1), GdNPS had a greater effect than GdCA. The maximum sensitization-enhancement ratio at 4 Gy (SER4Gy) was observed at an energy of 65 keV for both the nanoparticles and the contrast agent (2.44   ±   0.33 and 1.50   ±   0.20, for GdNPs and GdCA, respectively). At a higher energy (1.25 MeV), radiosensitization only was observed with GdNPs (1.66   ±   0.17 and 1.01   ±   0.11, for GdNPs and GdCA, respectively). The radiation dose enhancements were highly ‘energy dependent’ for both agents. Secondary-electron-emission generated after photoelectric events appeared to be the primary mechanism by which Gd contrast agents functioned as radiosensitizers. On the other hand, other biological mechanisms, such as alterations in the cell cycle may explain the enhanced radiosensitizing properties of GdNPs.

  20. Gadolinium nanoparticles and contrast agent as radiation sensitizers.

    PubMed

    Taupin, Florence; Flaender, Mélanie; Delorme, Rachel; Brochard, Thierry; Mayol, Jean-François; Arnaud, Josiane; Perriat, Pascal; Sancey, Lucie; Lux, François; Barth, Rolf F; Carrière, Marie; Ravanat, Jean-Luc; Elleaume, Hélène

    2015-06-01

    The goal of the present study was to evaluate and compare the radiosensitizing properties of gadolinium nanoparticles (NPs) with the gadolinium contrast agent (GdCA) Magnevist(®) in order to better understand the mechanisms by which they act as radiation sensitizers. This was determined following either low energy synchrotron irradiation or high energy gamma irradiation of F98 rat glioma cells exposed to ultrasmall gadolinium NPs (GdNPs, hydrodynamic diameter of 3 nm) or GdCA. Clonogenic assays were used to quantify cell survival after irradiation in the presence of Gd using monochromatic x-rays with energies in the 25 keV-80 keV range from a synchrotron and 1.25 MeV gamma photons from a cobalt-60 source. Radiosensitization was demonstrated with both agents in combination with X-irradiation. At the same concentration (2.1 mg mL(-1)), GdNPS had a greater effect than GdCA. The maximum sensitization-enhancement ratio at 4 Gy (SER4Gy) was observed at an energy of 65 keV for both the nanoparticles and the contrast agent (2.44   ±   0.33 and 1.50   ±   0.20, for GdNPs and GdCA, respectively). At a higher energy (1.25 MeV), radiosensitization only was observed with GdNPs (1.66   ±   0.17 and 1.01   ±   0.11, for GdNPs and GdCA, respectively). The radiation dose enhancements were highly 'energy dependent' for both agents. Secondary-electron-emission generated after photoelectric events appeared to be the primary mechanism by which Gd contrast agents functioned as radiosensitizers. On the other hand, other biological mechanisms, such as alterations in the cell cycle may explain the enhanced radiosensitizing properties of GdNPs. PMID:25988839

  1. Gadolinium nanoparticles and contrast agent as radiation sensitizers.

    PubMed

    Taupin, Florence; Flaender, Mélanie; Delorme, Rachel; Brochard, Thierry; Mayol, Jean-François; Arnaud, Josiane; Perriat, Pascal; Sancey, Lucie; Lux, François; Barth, Rolf F; Carrière, Marie; Ravanat, Jean-Luc; Elleaume, Hélène

    2015-06-01

    The goal of the present study was to evaluate and compare the radiosensitizing properties of gadolinium nanoparticles (NPs) with the gadolinium contrast agent (GdCA) Magnevist(®) in order to better understand the mechanisms by which they act as radiation sensitizers. This was determined following either low energy synchrotron irradiation or high energy gamma irradiation of F98 rat glioma cells exposed to ultrasmall gadolinium NPs (GdNPs, hydrodynamic diameter of 3 nm) or GdCA. Clonogenic assays were used to quantify cell survival after irradiation in the presence of Gd using monochromatic x-rays with energies in the 25 keV-80 keV range from a synchrotron and 1.25 MeV gamma photons from a cobalt-60 source. Radiosensitization was demonstrated with both agents in combination with X-irradiation. At the same concentration (2.1 mg mL(-1)), GdNPS had a greater effect than GdCA. The maximum sensitization-enhancement ratio at 4 Gy (SER4Gy) was observed at an energy of 65 keV for both the nanoparticles and the contrast agent (2.44   ±   0.33 and 1.50   ±   0.20, for GdNPs and GdCA, respectively). At a higher energy (1.25 MeV), radiosensitization only was observed with GdNPs (1.66   ±   0.17 and 1.01   ±   0.11, for GdNPs and GdCA, respectively). The radiation dose enhancements were highly 'energy dependent' for both agents. Secondary-electron-emission generated after photoelectric events appeared to be the primary mechanism by which Gd contrast agents functioned as radiosensitizers. On the other hand, other biological mechanisms, such as alterations in the cell cycle may explain the enhanced radiosensitizing properties of GdNPs.

  2. Polydopamine-Coated Magnetic Composite Particles with an Enhanced Photothermal Effect.

    PubMed

    Zheng, Rui; Wang, Sheng; Tian, Ye; Jiang, Xinguo; Fu, Deliang; Shen, Shun; Yang, Wuli

    2015-07-29

    Recently, photothermal therapy (PTT) that utilizes photothermal conversion (PTC) agents to ablate cancer under near-infrared (NIR) irradiation has attracted a growing amount of attention because of its excellent therapeutic efficacy and improved target selectivity. Therefore, exploring novel PTC agents with an outstanding photothermal effect is a current research focus. Herein, we reported a polydopamine-coated magnetic composite particle with an enhanced PTC effect, which was synthesized simply through coating polydopamine (PDA) on the surface of magnetic Fe3O4 particles. Compared with magnetic Fe3O4 particles and PDA nanospheres, the core-shell nanomaterials exhibited an increased NIR absorption, and thus, an enhanced photothermal effect was obtained. We demonstrated the in vitro and in vivo effects of the photothermal therapy using our composite particles and their ability as a contrast agent in the T2-weighted magnetic resonance imaging. These results indicated that the multifunctional composite particles with enhanced photothermal effect are superior to magnetic Fe3O4 particles and PDA nanospheres alone. PMID:26151502

  3. Polydopamine-Coated Magnetic Composite Particles with an Enhanced Photothermal Effect.

    PubMed

    Zheng, Rui; Wang, Sheng; Tian, Ye; Jiang, Xinguo; Fu, Deliang; Shen, Shun; Yang, Wuli

    2015-07-29

    Recently, photothermal therapy (PTT) that utilizes photothermal conversion (PTC) agents to ablate cancer under near-infrared (NIR) irradiation has attracted a growing amount of attention because of its excellent therapeutic efficacy and improved target selectivity. Therefore, exploring novel PTC agents with an outstanding photothermal effect is a current research focus. Herein, we reported a polydopamine-coated magnetic composite particle with an enhanced PTC effect, which was synthesized simply through coating polydopamine (PDA) on the surface of magnetic Fe3O4 particles. Compared with magnetic Fe3O4 particles and PDA nanospheres, the core-shell nanomaterials exhibited an increased NIR absorption, and thus, an enhanced photothermal effect was obtained. We demonstrated the in vitro and in vivo effects of the photothermal therapy using our composite particles and their ability as a contrast agent in the T2-weighted magnetic resonance imaging. These results indicated that the multifunctional composite particles with enhanced photothermal effect are superior to magnetic Fe3O4 particles and PDA nanospheres alone.

  4. Assessment of tumor angiogenesis using fluorescence contrast agents

    NASA Astrophysics Data System (ADS)

    Chen, Yu; Liu, Qian; Huang, Ping; Hyman, Shay; Intes, Xavier; Lee, William; Chance, Britton

    2003-12-01

    Angiogenesis is an important factor for further tumor growth and thus could be an attractive therapeutic target. Optical imaging can provide a non-invasive way to measure the permeability of tumor blood vessels and assess the tumor vasculature. We have developed a dual-channel near-infrared fluorescence system for simultaneous measurement of the pharmacokinetics of tumorous and normal tissues with exogenous contrast agents. This frequency-domain system consists of the light source (780 nm laser diode), fiber optics, interference filter (830 nm) and the detector (PMT). The fluorescent contrast agent used in this study is Indocyanine Green (ICG), and the normal dosage is 100 μl at a concentration of 5 μM. In vivo animal study is performed on the K1735 melanoma-bearing mouse. The fluorescence signals both tumorous and normal tissues after the bolus injection of ICG through the tail vein are continuously recorded as a function of time. The data is fitted by a double-exponential model to reveal the wash-in and wash-out parameters of different tissues. We observed an elongated wash-out from the tumor compared with normal tissue (leg). The effect of radiation therapy on the tumor vasculature is also discussed.

  5. Development of Multifunctional Luminomagnetic Nanoparticles as Bioimaging Contrast Agents

    NASA Astrophysics Data System (ADS)

    Mimun, Lawrence C.; Rightsell, Chris; Kumar, G. A.; Pedraza, Francisco; Montelongo, Sergio A.; Guda, Teja; Dravid, Vinayak P.; Sardar, Dhiraj K.

    2015-03-01

    Trivalent rare earth doped nanocrystalline materials with multiple functionalities have drawn special attention in biomedical industry. Current research is focused on the use of various materials with dual functionality for potential multifunctional applications. In this project, we are developing near infrared(NIR) based nanocrystals (NCs) as contrast agents with multimodal features comprising of strong NIR fluorescence, X-ray fluorescence and magnetic properties by utilizing the superparamagnetic features of Gd3+, the high X-ray excitation cross section of Lu3+, and the NIR fluorescence of Nd3+. Halides, such as MGdLuF4 (M=K,Na), were doped with NIR active rare earth ions, Nd3+, where synthesis conditions have been optimized to obtain the brightest phosphor with a size of sub-50 nm. Characterization of the NCs were performed to explore the excitation and emission properties, crystal structure, morphology, magnetization properties, and X-ray fluorescence properties. The potential use of these NCs can be utilized as contrast agents for medical imaging application such as optical imaging, magnetic resonance (MRI) and X-ray imaging. This research was, in part, funded by NIGMS MBRS-RISE GM060655 and from the National Science Foundation Partnerships for Research and Education in Materials (NSF-PREM) Grant N0-DMR-0934218.

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

    NASA Astrophysics Data System (ADS)

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

    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.

  7. Repositioning Clofazimine as a Macrophage-Targeting Photoacoustic Contrast Agent

    PubMed Central

    Keswani, Rahul K.; Tian, Chao; Peryea, Tyler; Girish, Gandikota; Wang, Xueding; Rosania, Gus R.

    2016-01-01

    Photoacoustic Tomography (PAT) is a deep-tissue imaging modality, with potential clinical applications in the diagnosis of arthritis, cancer and other disease conditions. Here, we identified Clofazimine (CFZ), a red-pigmented dye and anti-inflammatory FDA-approved drug, as a macrophage-targeting photoacoustic (PA) imaging agent. Spectroscopic experiments revealed that CFZ and its various protonated forms yielded optimal PAT signals at wavelengths −450 to 540 nm. CFZ’s macrophage-targeting chemical and structural forms were detected with PA microscopy at a high contrast-to-noise ratio (CNR > 22 dB) as well as with macroscopic imaging using synthetic gelatin phantoms. In vivo, natural and synthetic CFZ formulations also demonstrated significant anti-inflammatory activity. Finally, the injection of CFZ was monitored via a real-time ultrasound-photoacoustic (US-PA) dual imaging system in a live animal and clinically relevant human hand model. These results demonstrate an anti-inflammatory drug repurposing strategy, while identifying a new PA contrast agent with potential applications in the diagnosis and treatment of arthritis. PMID:27000434

  8. Molecular photoacoustic imaging using gold nanoparticles as a contrast agent

    NASA Astrophysics Data System (ADS)

    Kim, Chulhong; Cho, Eun Chul; Chen, Jingyi; Song, Kwang Hyun; Au, Leslie; Favazza, Christopher P.; Zhang, Qiang; Cobley, Claire M.; Xia, Younan; Wang, Lihong V.

    2010-02-01

    Gold nanoparticles have received much attention due to their potential diagnostic and therapeutic applications. Gold nanoparticles are attractive in many biomedical applications because of their biocompatibility, easily modifiable surfaces for targeting, lack of heavy metal toxicity, wide range of sizes (35-100 nm), tunable plasmonic resonance peak, encapsulated site-specific drug delivery, and strong optical absorption in the near-infrared regime. Specifically, due to their strong optical absorption, gold nanoparticles have been used as a contrast agent for molecular photoacoustic (PA) imaging of tumor. The plasmonic resonance peak of the gold nanocages (AuNCs) was tuned to the near-infrared region, and the ratio of the absorption cross-section to the extinction cross-section was approximately ~70%, as measured by PA sensing. We used PEGylated gold nanocages (PEG-AuNCs) as a passive targeting contrast agent on melanomas. After 6-h intravenous injection of PEG-AuNCs, PA amplitude was increased by ~14 %. These results strongly suggest PA imaging paired with AuNCs is a promising diagnostic tool for early cancer detection.

  9. HIFU Hemostasis of Liver Injuries Enhanced by Ultrasound Contrast Agents

    NASA Astrophysics Data System (ADS)

    Zderic, Vesna; Vaezy, Shahram; Brayman, Andrew A.; Matula, Thomas J.; O'Keefe, Grant E.; Crum, Lawrence A.

    2005-03-01

    Our objective was to investigate whether High-Intensity Focused Ultrasound (HIFU) hemostasis can be achieved faster in the presence of ultrasound contrast agents (UCA). Incisions (3 cm long and 0.5 cm deep) were made in surgically exposed rabbit liver. Optison at a concentration of 0.18 ml/kg was injected into the mesenteric vein, immediately before the incision was made. The HIFU applicator (frequency of 5.5 MHz, and intensity of 3,700 W/cm2) was scanned manually over the incision (at an approximate rate of 1 mm/s) until hemostasis was achieved. The times to complete hemostasis were measured and normalized with the initial blood loss. The hemostasis times were 59±23 s in the presence of Optison and 70±23 s without Optison. The presence of Optison produced a 37% reduction in the normalized hemostasis times (p<0.05). Optison also provided faster (by 34%) formation of the coagulum seal over the lesion. Gross observations showed that the lesion size did not change due to the presence of Optison. Histological analysis showed that lesions consisted of an area of coagulation necrosis in vicinity of the incision, occasionally surrounded by a congestion zone filled with blood. Our results suggest the potential utility of microbubble contrast agents for increasing efficiency of HIFU hemostasis of internal organ injuries.

  10. Modified Gadonanotubes as a promising novel MRI contrasting agent

    PubMed Central

    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 (Gdn3+) clusters. Methods In this study equated Gdn3+ clusters were loaded in the sidewall defects of oxidized multiwalled (MW) CNTs. The amount of loaded gadolinium ion into the MWCNTs was quantified by inductively coupled plasma (ICP) method. To improve water solubility and biocompatibility of the system, the complexes were functionalized using diamine-terminated oligomeric poly (ethylene glycol) via a thermal reaction method. Results Gdn3+ loaded PEGylated oxidized CNTs (Gdn3+@CNTs-PEG) is freely soluble in water and stable in phosphate buffer saline having particle size of about 200 nm. Transmission electron microscopy (TEM) images clearly showed formation of PEGylated CNTs. MRI analysis showed that the prepared solution represents 10% more signal intensity even in half concentration of Gd3+ in comparison with commerciality available contrasting agent Magnevist®. In addition hydrophilic layer of PEG at the surface of CNTs could prepare stealth nanoparticles to escape RES. Conclusion It was shown that Gdn3+@CNTs-PEG was capable to accumulate in tumors through enhanced permeability and retention effect. Moreover this system has a potential for early detection of diseases or tumors at the initial stages. PMID:23815852

  11. Synthesis, functionalization, and characterization of rod-shaped gold nanoparticles as potential optical contrast agents

    NASA Astrophysics Data System (ADS)

    Rayavarapu, R. G.; Petersen, W.; Le Gac, S.; Ungureanu, C.; van Leeuwen, T. G.; Manohar, S.

    2007-07-01

    Gold nanoparticles exhibit intense and narrow optical extinction bands due to the phenomenon of plasmon resonance making them useful as contrast agents for light-based imaging techniques. Localized heating results from the absorbed light energy, which shows potential for these particles in photothermal therapy as well. The bioconjugation of gold nanoparticles to appropriate antibodies targeted to tumors in vivo, could make highly selective detection and therapy of tumors possible. We have synthesised gold nanorods based on seed mediated protocols using two methods. The first method is based on using a mono-surfactant silver assisted method which produces gold nanorods having plasmon peaks between 670-850 nm within the "optical imaging and therapeutic window". These nanorods have aspect ratios between 2.3 - 3.7. A second method is a silver assisted bi-surfactant method which produce nanorods with peaks in the range of 850-1100 nm having aspect ratios between 5 - 11. Typical concentrations of these particles in aqueous dispersions are in the range of 1x10 10 - 1x10 11 particles per mL. We have bioconjugated these gold nanorods with anti-HER2/neu mouse monoclonal antibodies (MAb). Since the as-prepared CTAB-stabilized nanorods were found to be toxic to SKBR3 cells, we decided to coat the gold nanorods with polyethylene glycol (PEG). Characterization and size estimation of the nanoparticles were performed using electron microscopies, optical spectroscopy and confocal microscopy. We present these results and implications for use of these nanoparticles for in vivo biomedical applications.

  12. Optical and acoustical dynamics of microbubble contrast agents inside neutrophils.

    PubMed Central

    Dayton, P A; Chomas, J E; Lum, A F; Allen, J S; Lindner, J R; Simon, S I; Ferrara, K W

    2001-01-01

    Acoustically active microbubbles are used for contrast-enhanced ultrasound assessment of organ perfusion. In regions of inflammation, contrast agents are captured and phagocytosed by activated neutrophils adherent to the venular wall. Using direct optical observation with a high-speed camera and acoustical interrogation of individual bubbles and cells, we assessed the physical and acoustical responses of both phagocytosed and free microbubbles. Optical analysis of bubble radial oscillations during insonation demonstrated that phagocytosed microbubbles experience viscous damping within the cytoplasm and yet remain acoustically active and capable of large volumetric oscillations during an acoustic pulse. Fitting a modified version of the Rayleigh-Plesset equation that describes mechanical properties of thin shells to optical radius-time data of oscillating bubbles provided estimates of the apparent viscosity of the intracellular medium. Phagocytosed microbubbles experienced a viscous damping approximately sevenfold greater than free microbubbles. Acoustical comparison between free and phagocytosed microbubbles indicated that phagocytosed microbubbles produce an echo with a higher mean frequency than free microbubbles in response to a rarefaction-first single-cycle pulse. Moreover, this frequency increase is predicted using the modified Rayleigh-Plesset equation. We conclude that contrast-enhanced ultrasound can detect distinct acoustic signals from microbubbles inside of neutrophils and may provide a unique tool to identify activated neutrophils at sites of inflammation. PMID:11222315

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

    NASA Astrophysics Data System (ADS)

    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 (p<0.05) elevated relative to the control group with n=3 mice in each group, and dose and signal had a linear relationship at R2>0.96 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

  14. Multifunctional PEG modified DOX loaded mesoporous silica nanoparticle@CuS nanohybrids as photo-thermal agent and thermal-triggered drug release vehicle for hepatocellular carcinoma treatment

    NASA Astrophysics Data System (ADS)

    Wu, Lingjie; Wu, Ming; Zeng, Yongyi; Zhang, Da; Zheng, Aixian; Liu, Xiaolong; Liu, Jingfeng

    2015-01-01

    The combination of a multi-therapeutic mode with a controlled fashion is a key improvement in nanomedicine. Here, we synthesized polyethylene glycol (PEG)-modified doxorubicin (DOX)-loaded mesoporous silica nanoparticle (MSN) @CuS nanohybrids as efficient drug delivery carriers, combined with photothermal therapy and chemotherapy to enhance the therapeutic efficacy on hepatocellular carcinoma (HCC). The physical properties of the nanohybrids were characterized by transmission electron microscopy (TEM), N2 adsorption and desorption experiments and by the Vis-NIR absorption spectra. The results showed that the doxorubicin could be stored in the inner pores of mesoporous silica nanoparticles; the CuS nanoparticles, which are coated on the surface of a mesoporous silica nanoparticle, could serve as efficient photothermal therapy (PTT) agents; the loaded drug release could be easily triggered by NIR irradiation. The combination of the PTT treatment with controlled chemotherapy could further enhance the cancer ablation ability compared to any of the single approaches alone. Hence, the reported PEG-modified DOX-loaded mesoporous silica nanoparticle@CuS nanohybrids might be very promising therapeutic agents for HCC treatment.

  15. Needle Size and Injection Rate Impact Microbubble Contrast Agent Population

    PubMed Central

    Talu, Esra; Powell, Robert L.; Longo, Marjorie L.; Dayton, Paul A.

    2008-01-01

    The most common type of ultrasound contrast agents are encapsulated microbubbles, typically 1–5 microns in diameter. These microbubbles are injected into the bloodstream to provide image enhancement during an ultrasound exam. Due to their compressibility, these microbubbles are inherently sensitive to changes in pressure. For imaging, this is beneficial in that these microbubbles oscillate in an acoustic field and allow imaging systems to detect their response uniquely from tissue. However, this sensitivity also means that microbubbles can be readily destroyed by significant hydrostatic pressure. Injection of these microbubbles through a small-gauge catheter, such as sometimes performed in small animal imaging studies, can result in microbubble destruction. In this manuscript, the effects of microbubble injection through catheters of varying diameter are examined. Our results indicate that the concentration and size distribution of microbubbles can be substantially altered in cases of rapid injection through small needles. PMID:18295967

  16. Biological in situ characterization of polymeric microbubble contrast agents.

    PubMed

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

    2016-06-01

    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. Due to their buoyancy, the commonly available approaches to study their behaviour in complex media are not easily applicable and their use in modern medicine requires such behaviour to be fully elucidated. Here we have used for the first time flow cytometry as a new high throughput approach that allows characterisation of the MB dispersion, prior to and after exposure in different biological media and we have additionally developed a method that allows characterisation of the strongly bound proteins adsorbed on the MBs, to fully predict their biological behaviour in biological milieu. PMID:26993210

  17. Cardiovascular therapeutic uses of targeted ultrasound contrast agents

    PubMed Central

    Laing, Susan T.; McPherson, David D.

    2009-01-01

    The therapeutic use of ultrasound contrast agents (UCAs) is an emerging methodology with high potential for enhanced directed therapeutic gene, bioactive gas, drug, and stem cell delivery. Ultrasound-targeted microbubble destruction has already demonstrated feasibility for plasmid DNA delivery. Similarly, therapeutic ultrasound for thrombolysis treatment has been taken into the clinical setting, and the addition of UCAs for therapeutic delivery or enhanced effect through cavitation is a natural progression to this investigation. However, as with any new technique, safety needs to be first demonstrated before translation into clinical practice. This review article will focus on the development of UCAs for cardiac and vascular therapeutics as well as the limitations/concerns for the use of therapeutic ultrasound in clinical medicine in order to lay a foundation for investigators planning to enter this exciting field or for those who want to broaden their understanding. PMID:19581314

  18. Metallic nanoparticles as optoacoustic contrast agents for medical imaging

    NASA Astrophysics Data System (ADS)

    Conjusteau, Andre; Ermilov, Sergey A.; Lapotko, Dmitri; Liao, Hongwei; Hafner, Jason; Eghtedari, Mohammad; Motamedi, Massoud; Kotov, Nicholas; Oraevsky, Alexander A.

    2006-02-01

    A contrast agent for optoacoustic imaging and laser therapy of early tumors is being developed based on gold nanocolloids strongly absorbing visible and near-infrared light. The optoacoustic signals obtained from gold nanospheres and gold nanorods solutions are studied. In the case of 100 nm nanospheres as an example, a sharp increase in the total area under the curve of the optoacoustic signal is observed when the laser fluence is increased beyond a threshold value of about 0.1 J/cm2. The change in the optoacoustic signal profile is attributed to the formation of water vapor bubbles around heated nanoparticles, as evidenced via thermoacoustic microscopy experiments. It has been determined that, surprisingly, gold nanoparticles fail to generate detectable nanobubbles upon irradiation at the laser fluence of ~2 mJ/cm2, which heats the nanoparticles up to 374°C, the critical temperature of water. Only when the estimated temperature of the particle reaches about 10,000°C, a marked increase of the optoacoustic pressure amplitude and a changed profile of the optoacoustic signals indicate nanobubble formation. A nanoparticle based contrast agent is the most effective if it can be activate by laser pulses with low fluence attainable in the depth of tissue. With this goal in mind, we develop targeting protocols that form clusters of gold nanocolloid in the target cells in order to lower the bubble formation threshold below the level of optical fluence allowed for safe laser illumination of skin. Experiments and modeling suggest that formation of clusters of nanocolloids may improve the sensitivity of optoacoustic imaging in the detection of early stage tumors.

  19. The most effective gold nanorod size for plasmonic photothermal therapy: theory and in vitro experiments.

    PubMed

    Mackey, Megan A; Ali, Moustafa R K; Austin, Lauren A; Near, Rachel D; El-Sayed, Mostafa A

    2014-02-01

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

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

    PubMed Central

    2015-01-01

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

  1. Mechanically Tunable Hollow Silica Ultrathin Nanoshells for Ultrasound Contrast Agents

    PubMed Central

    Liberman, A.; Wang, J.; Lu, N.; Viveros, R.D.; Allen, C. A.; Mattrey, R.F.; Blair, S.L.; Trogler, W.C.; Kim, M. J.; Kummel, A.C.

    2015-01-01

    Perfluoropentane (PFP) gas filled biodegradable iron-doped silica nanoshells have been demonstrated as long-lived ultrasound contrast agents. Nanoshells are synthesized by a sol-gel process with tetramethyl orthosilicate (TMOS) and iron ethoxide. Substituting a fraction of the TMOS with R-substituted trialkoxysilanes produces ultrathin nanoshells with varying shell thicknesses and morphologies composed of fused nanoflakes. The ultrathin nanoshells had continuous ultrasound Doppler imaging lifetimes exceeding 3 hours, were twice as bright using contrast specific imaging, and had decreased pressure thresholds compared to control nanoshells synthesized with just TMOS. Transmission electron microscopy (TEM) showed that the R-group substituted trialkoxysilanes could reduce the mechanically critical nanoshell layer to 1.4 nm. These ultrathin nanoshells have the mechanical behavior of weakly linked nanoflakes but the chemical stability of silica. The synthesis can be adapted for general fabrication of three-dimensional nanostructures composed of nanoflakes, which have thicknesses from 1.4–3.8 nm and diameters from 2–23 nm. PMID:26955300

  2. High-Frequency Dynamics of Ultrasound Contrast Agents

    PubMed Central

    Sun, Yang; Kruse, Dustin E.; Dayton, Paul A.; Ferrara, Katherine W.

    2006-01-01

    Ultrasound contrast agents enhance echoes from the microvasculature and enable the visualization of flow in smaller vessels. Here, we optically and acoustically investigate microbubble oscillation and echoes following insonation with a 10 MHz center frequency pulse. A high-speed camera system with a temporal resolution of 10 ns, which provides two-dimensional (2-D) frame images and streak images, is used in optical experiments. Two confocally aligned transducers, transmitting at 10 MHz and receiving at 5 MHz, are used in acoustical experiments in order to detect subharmonic components. Results of a numerical evaluation of the modified Rayleigh-Plesset equation are used to predict the dynamics of a microbubble and are compared to results of in vitro experiments. From the optical observations of a single microbubble, nonlinear oscillation, destruction, and radiation force are observed. The maximum bubble expansion, resulting from insonation with a 20-cycle, 10-MHz linear chirp with a peak negative pressure of 3.5 MPa, has been evaluated. For an initial diameter ranging from 1.5 to 5 μm, a maximum diameter less than 8 μm is produced during insonation. Optical and acoustical experiments provide insight into the mechanisms of destruction, including fragmentation and active diffusion. High-frequency pulse transmission may provide the opportunity to detect contrast echoes resulting from a single pulse, may be robust in the presence of tissue motion, and may provide the opportunity to incorporate high-frequency ultrasound into destruction-replenishment techniques. PMID:16422410

  3. Ultrasound contrast agents for bleeding detection and acoustic hemostasis

    NASA Astrophysics Data System (ADS)

    Zderic, Vesna; Luo, Wenbo; Brayman, Andrew; Crum, Lawrence; Vaezy, Shahram

    2005-04-01

    Objective: To investigate the application of ultrasound contrast agents (UCA) in improving both therapeutic and diagnostic aspects of ultrasound-guided High Intensity Focused Ultrasound (HIFU) therapy. Methods: Incisions (3 cm long, 0.5 cm deep) were made in rabbit livers (in anterior surface for HIFU treatment, or posterior surface for bleeding detection). UCA Optison (~0.1 ml/kg) was injected into mesenteric vein or ear vein. A HIFU applicator (5.5 MHz, 6400 W/cm2) was scanned manually over the incision until hemostasis was achieved. Occult bleeding was monitored with Doppler ultrasound. Results: The presence of Optison produced 37% reduction in hemostasis times normalized to initial bleeding rates. Gross and histological observations showed similar appearance of HIFU lesions produced in the presence of Optison and control HIFU lesions. The temperature reached 100°C in both HIFU only and HIFU+UCA treatments. Tension strength of hemostatic liver incisions was 0.9+/-0.5 N. Almost no bleeding could be detected before Optison injection. First appearance of contrast enhancement localized at the bleeding site was 15 s after Optison injection, and lasted for ~50 s. Conclusion: The presence of UCA during HIFU treatment of liver incisions resulted in shortening of HIFU application times and better visualization of bleeding sites.

  4. Nanoparticle-Based Systems for T1-Weighted Magnetic Resonance Imaging Contrast Agents

    PubMed Central

    Zhu, Derong; Liu, Fuyao; Ma, Lina; Liu, Dianjun; Wang, Zhenxin

    2013-01-01

    Because magnetic resonance imaging (MRI) contrast agents play a vital role in diagnosing diseases, demand for new MRI contrast agents, with an enhanced sensitivity and advanced functionalities, is very high. During the past decade, various inorganic nanoparticles have been used as MRI contrast agents due to their unique properties, such as large surface area, easy surface functionalization, excellent contrasting effect, and other size-dependent properties. This review provides an overview of recent progress in the development of nanoparticle-based T1-weighted MRI contrast agents. The chemical synthesis of the nanoparticle-based contrast agents and their potential applications were discussed and summarized. In addition, the recent development in nanoparticle-based multimodal contrast agents including T1-weighted MRI/computed X-ray tomography (CT) and T1-weighted MRI/optical were also described, since nanoparticles may curtail the shortcomings of single mode contrast agents in diagnostic and clinical settings by synergistically incorporating functionality. PMID:23698781

  5. Magnetic graphene-based nanotheranostic agent for dual-modality mapping guided photothermal therapy in regional lymph nodal metastasis of pancreatic cancer.

    PubMed

    Wang, Sheng; Zhang, Qin; Luo, Xian F; Li, Ji; He, Hang; Yang, Feng; Di, Yang; Jin, Chen; Jiang, Xin G; Shen, Shun; Fu, De L

    2014-11-01

    Although regional lymph nodes (RLN) dissection remains the only way to cure pancreatic cancer metastasis, it is unavoidably associated with sizable trauma, multiple complications, and low surgical resection rates. Thus, exploring a treatment approach for the ablation of drug-resistant pancreatic cancer is always of great concern. Moreover, reoperative and intraoperative mapping of RLN is also important during treatment, because only a few lymph nodes can be detected by the naked eye. In our study, graphene oxides modified with iron oxide nanoparticles (GO-IONP) as a nanotheranostic agent is firstly developed to diagnose and treat RLN metastasis of pancreatic cancer. The approach was designed based on clinical practice, the GO-IONP agent directly injected into the tumor was transported to RLN via lymphatic vessels. Compared to commercial carbon nanoparticles currently used in the clinic operation, the GO-IONP showed powerful ability of dual-modality mapping of regional lymphatic system by magnetic resonance imaging (MRI), as well as dark color of the agent providing valuable information that was instrumental for surgeon in making the preoperative plan before operation and intraoperatively distinguish RLN from surrounding tissue. Under the guidance of dual-modality mapping, we further demonstrated that metastatic lymph nodes including abdominal nodes could be effectively ablated by near-infrared (NIR) irradiation with an incision operation. The lower systematic toxicity of GO-IONP and satisfying safety of photothermal therapy (PTT) to neighbor tissues have also been clearly illustrated in our animal experiments. Using GO-IONP as a nanotheranostic agent presents an approach for mapping and photothermal ablation of RLN, the later may serve as an alternative to lymph node dissection by invasive surgery.

  6. Optical contrast agents to visualize molecular expression in breast cancer

    NASA Astrophysics Data System (ADS)

    Langsner, Robert James

    Breast cancer is the second leading cause of death of women in the United States. Improvements in screening technology have increased the breast cancer incidence rate, as smaller lesions are being detected. Due to the small size of lesions, patients can choose to receive breast conservation therapy (BCT) rather than a modified radical mastectomy. Even though the breast retains cosmesis after BCT, there is an increased risk of the patient having residual microscopic disease, known as positive margins. Patients with positive margins receive increased radiation and have an increased chance of second surgery. Pathology with hematoxylin and eosin (H&E) remains the gold standard for diagnosing margin status in patients. Intraoperative pathology has been shown to reduce the rate of positive margins in BCT. However, a minority of surgery centers have intraoperative pathology centers, limiting the number of patients that receive this standard of care. The expression profiles of surface receptors such as ErbB2 (HER2-positive) and epidermal growth factor receptor (EGFR) provide information about the aggressiveness of a particular tumor. Recent research has shown that there was elevated EGFR expression in patients with a local recurrence even though the biopsies were assessed to be disease free using standard H&E. If the physicians had known the molecular expression of these biopsies, a different treatment regimen or excision of more tissue might have prevented the recurrence. This thesis investigates targeted molecular contrast agents that enhance the visualization of molecular markers such as glucose transporters (GLUTs) and growth factor receptors in tissue specimens. First, application of 2-NBDG, a fluorescent deoxyglucose, enhances signal in cancerous tissue with a 20-minute incubation. Then, antibody functionalized silica-gold nanoshells enhance the visualization of ErbB2 overexpression in specimens with a 5-minute incubation. To image these contrast agents in cancerous

  7. Highly efficient ablation of metastatic breast cancer using ammonium-tungsten-bronze nanocube as a novel 1064 nm-laser-driven photothermal agent.

    PubMed

    Guo, Chongshen; Yu, Haijun; Feng, Bing; Gao, Weidong; Yan, Mei; Zhang, Zhiwen; Li, Yaping; Liu, Shaoqin

    2015-06-01

    Photothermal ablation (PTA) therapy has been viewed as an invasive option for cancer therapy with minimal deconstruction of healthy tissues. In this study, a potent candidate of (NH4)xWO3 nanocube was developed for PTA treatment of metastatic breast cancer in the second near-infrared (NIR) window. It was found that the as-synthesized (NH4)xWO3 nanocube had significant photoabsorption across the whole NIR window of 780-2500 nm and exhibited considerable photo-heat conversion efficiency. Moreover, the as-prepared (NH4)xWO3 nanocube displayed good biocompatibility and high cellular uptake efficiency through endocytosis pathway without nuclei entry. The PTA study employing 1064 nm laser in the second NIR window revealed that (NH4)xWO3 nanocubes induced significant cell necrosis and apoptosis by producing obviously hyperthermia effect inside cancer cells. Using an orthotopicly implanted breast tumor model, it demonstrated that the (NH4)xWO3 nanocube was a promising photothermal agent for effective ablation of solid tumors and suppressing their distant metastasis.

  8. Photothermal imaging of melanin

    NASA Astrophysics Data System (ADS)

    Kerimo, Josef; DiMarzio, Charles A.

    2013-02-01

    We present photothermal images of melanin using modulation with two laser beams. Strong melanin absorption followed by efficient nonradiative relaxation caused heating and an increase in temperature. This temperature effect was used as an imaging contrast to detect melanin. Melanin from several samples including Sepia officinalis, black human hair, and live zebra fish, were imaged with a high signal-to-noise ratio. For the imaging, we focused two near infrared laser beams (pump and probe) collinearly with different wavelengths and the pump was modulated in amplitude. The thermally induced variations in the refractive index, at the modulation frequency, were detected by the scattering of the probe beam. The Photothermal method brings several imaging benefits including the lack of background interference and the possibility of imaging for an extended period of time without photodamage to the melanin. The dependence of the photothermal signal on the laser power, modulation frequency, and spatial offset of the probe is discussed. The new photothermal imaging method is promising and provides background-free and label-free imaging of melanin and can be implemented with low-cost CW lasers.

  9. Ultrasound Induced Fluorescence of Nanoscale Liposome Contrast Agents

    PubMed Central

    Zhang, Qimei; Morgan, Stephen P.; O’Shea, Paul; Mather, Melissa L.

    2016-01-01

    A new imaging contrast agent is reported that provides an increased fluorescent signal upon application of ultrasound (US). Liposomes containing lipids labelled with pyrene were optically excited and the excimer fluorescence emission intensity was detected in the absence and presence of an ultrasound field using an acousto-fluorescence setup. The acousto-fluorescence dynamics of liposomes containing lipids with pyrene labelled on the fatty acid tail group (PyPC) and the head group (PyPE) were compared. An increase in excimer emission intensity following exposure to US was observed for both cases studied. The increased intensity and time constants were found to be different for the PyPC and PyPE systems, and dependent on the applied US pressure and exposure time. The greatest change in fluorescence intensity (130%) and smallest rise time constant (0.33 s) are achieved through the use of PyPC labelled liposomes. The mechanism underlying the observed increase of the excimer emission intensity in PyPC labelled liposomes is proposed to arise from the “wagging” of acyl chains which involves fast response and requires lower US pressure. This is accompanied by increased lipid lateral diffusivity at higher ultrasound pressures, a mechanism that is also active in the PyPE labelled liposomes. PMID:27467748

  10. In vivo near-infrared photothermal therapy and computed tomography imaging of cancer cells using novel tungsten-based theranostic probe

    NASA Astrophysics Data System (ADS)

    Liu, Jianhua; Han, Jianguo; Kang, Zhichen; Golamaully, Reza; Xu, Nannan; Li, Hongpeng; Han, Xueli

    2014-05-01

    Photothermal therapy, as a physical therapeutic technique to kill cancer, has generated a great deal of interest. Photothermal agents hence play a critical role in this modern therapy. We report the use of transition metal oxides as photothermal agents based on PEGylated WO3-x nanoparticles. The well-prepared nanoparticles presented effective results during photothermal therapy both in vitro and in vivo by using near-IR laser irradiation (980 nm, 0.5 W cm-2). The tumor cells were effectively damaged using low power density during a short irradiation time without destroying healthy tissues. In vitro results of photothermal therapy with PEGylated WO3-x nanoparticles proved to be effective on 4T1 murine breast cancer cells via a confocal microscopy method and MTT assay. In vivo results were further confirmed by hematoxylin and eosin (H & E) histological staining. Additionally, PEGylated WO3-x nanoparticles were shown to be effective as a CT imaging contrast agent on a tumor-bearing mouse model. Our results suggest that this generation of PEGylated WO3-x nanoparticles can potentially be used in oncological CT imaging and photothermal therapy.Photothermal therapy, as a physical therapeutic technique to kill cancer, has generated a great deal of interest. Photothermal agents hence play a critical role in this modern therapy. We report the use of transition metal oxides as photothermal agents based on PEGylated WO3-x nanoparticles. The well-prepared nanoparticles presented effective results during photothermal therapy both in vitro and in vivo by using near-IR laser irradiation (980 nm, 0.5 W cm-2). The tumor cells were effectively damaged using low power density during a short irradiation time without destroying healthy tissues. In vitro results of photothermal therapy with PEGylated WO3-x nanoparticles proved to be effective on 4T1 murine breast cancer cells via a confocal microscopy method and MTT assay. In vivo results were further confirmed by hematoxylin and eosin

  11. Comparisons of EPR imaging and T1-weighted MRI for efficient imaging of nitroxyl contrast agents.

    PubMed

    Matsumoto, Ken-ichiro; Narazaki, Michiko; Ikehira, Hiroo; Anzai, Kazunori; Ikota, Nobuo

    2007-07-01

    The resolution and signal to noise ratio of EPR imaging and T(1)-weighted MRI were compared using an identical phantom. Several solutions of nitroxyl contrast agents with different EPR spectral shapes were tested. The feasibility of T(1)-weighted MRI to detect nitroxyl contrast agents was described. T(1)-weighted MRI can detect nitroxyl contrast agents with a complicated EPR spectrum easier and quicker; however, T(1)-weighted MRI has less quantitative ability especially for lipophilic nitroxyl contrast agents, because T(1)-relaxivity, i.e. accessibility to water, is affected by the hydrophilic/hydrophobic micro-environment of a nitroxyl contrast agent. The less quantitative ability of T(1)-weighted MRI may not be a disadvantage of redox imaging, which obtains reduction rate of a nitroxyl contrast. Therefore, T(1)-weighted MRI has a great advantage to check the pharmacokinetics of newly modified and/or designed nitroxyl contrast agents. PMID:17433743

  12. Novel paramagnetic contrast agents for molecular imaging and targeted drug delivery.

    PubMed

    Lanza, Gregory M; Winter, Patrick; Caruthers, Shelton; Schmeider, Anne; Crowder, Kathy; Morawski, Anne; Zhang, Huiying; Scott, Michael J; Wickline, Samuel A

    2004-12-01

    Molecular biology and genomic sciences are revealing the early biological signatures for many diseases. In response, the Molecular Imaging community is rapidly developing contrast agents to visualize the nascent pathological changes and to concomitantly deliver treatment directly to the site of disease. The evaluation, development and use of these new agents require a complementary understanding of contrast chemistry and imaging techniques. The fundamental issues surrounding magnetic contrast agent development, rational drug delivery, MR molecular imaging, and their interdependence are elucidated.

  13. Targeted contrast agents--an adjunct to whole-body imaging: current concepts.

    PubMed

    Foran, Paul; Bolster, Ferdia; Crosbie, Ian; MacMahon, Peter; O'Kennedy, Richard; Eustace, Stephen J

    2010-03-01

    This article reviews the potential use of a combination of whole-body imaging and targeted contrast agents in improving diagnostics, with a particular focus on oncology imaging. It looks at the rationale for nanoparticles and their development as targeted contrast agents. It subsequently describes many of the advances made thus far in developing tissue-specific contrast agents capable of targeting tumors that combined with whole-body imaging may enable superior cancer detection and characterization.

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

    NASA Astrophysics Data System (ADS)

    Ma, J.; Chen, K.

    2016-04-01

    Traditional magnetic resonance imaging (MRI) contrast agents mainly include superparamagnetic (SPM) iron oxide nanoparticle as T 2 contrast agent for liver and paramagnetic Gd (III)-chelate as T 1 contrast agent for all organs. In this work, weak ferromagnetic kale-like and SPM cabbage-like Ni3S2@Ni hybrid architectures were synthesized and evaluated as potential T 1 MRI contrast agents. Their relatively small r 2/r 1 ratios of 2.59 and 2.38, and high r 1 values of 11.27 and 4.89 mmol-1 L s-1 (for the kale-like and cabbage-like Ni3S2@Ni, respectively) will shed some light on the development of new-type MRI contrast agents.

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

    NASA Astrophysics Data System (ADS)

    Ma, J.; Chen, K.

    2016-04-01

    Traditional magnetic resonance imaging (MRI) contrast agents mainly include superparamagnetic (SPM) iron oxide nanoparticle as T 2 contrast agent for liver and paramagnetic Gd (III)-chelate as T 1 contrast agent for all organs. In this work, weak ferromagnetic kale-like and SPM cabbage-like Ni3S2@Ni hybrid architectures were synthesized and evaluated as potential T 1 MRI contrast agents. Their relatively small r 2/r 1 ratios of 2.59 and 2.38, and high r 1 values of 11.27 and 4.89 mmol‑1 L s‑1 (for the kale-like and cabbage-like Ni3S2@Ni, respectively) will shed some light on the development of new-type MRI contrast agents.

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

    PubMed

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

    2015-12-01

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

  17. Development and characterization of a nano-scale contrast agent.

    PubMed

    Oeffinger, Brian E; Wheatley, Margaret A

    2004-04-01

    Agents injected parenterally must be less than approximately 8 microm diameter in order to traverse the capillaries in the pulmonary bed, but these agents remain in the vasculature until they are eliminated from the body by a variety of mechanisms. Targeting of cells outside the capillaries requires agent diameters of less than approximately 700 nm to enable escape through the larger-than-usual pores that have been noted in the leaky vasculature of a tumor. The objective of this study was to test the feasibility of creating a surfactant-stabilized nano-bubble with favorable acoustic properties, and identify the key parameters that influence size, yield and stability. Size distribution was characterized using laser light scattering. In vitro acoustic enhancement was assessed by generation of dose and time response curves. We previously developed a successful protocol to generate gas-filled microbubbles (containing perfluorocarbon, sulfur hexafluoride or air) with mean diameter of 1.5 microm, using sonication of carefully selected surfactant mixtures. This presentation describes generation of nano-bubbles with mean diameters ranging from 700 to 450 nm, depending on process variables. In all cases a centrifugation step was employed to separate the nano-sized particles. The in vitro dose response curves gave a maximum of 23-27 dB enhancement compared to buffer in the absence of agent, with the maximum enhancement and presence of shadowing at higher doses being dependent on the fabrication protocol. The effect of sonication time for solutions containing a mixture of the surfactants (Span 60 and Tween 80) was also tested, but was determined not to be an influencing factor. Future studies will involve development of a mathematical model characterizing the mean size as a function of centrifugal force, spin time and initial size distribution. Future work will also include imaging of tumor-bearing mice and measuring imaging potential in vivo in New Zealand white rabbits

  18. Contrast Agents for Quantitative MicroCT of Lung Tumors in Mice

    PubMed Central

    Lalwani, Kush; Giddabasappa, Anand; Li, Danan; Olson, Peter; Simmons, Brett; Shojaei, Farbod; Arsdale, Todd Van; Christensen, James; Jackson-Fisher, Amy; Wong, Anthony; Lappin, Patrick B; Eswaraka, Jeetendra

    2013-01-01

    The identification and quantitative evaluation of lung tumors in mouse models is challenging and an unmet need in preclinical arena. In this study, we developed a noninvasive contrast-enhanced microCT (μCT) method to longitudinally evaluate and quantitate lung tumors in mice. Commercially available μCT contrast agents were compared to determine the optimal agent for visualization of thoracic blood vessels and lung tumors in naïve mice and in non-small-cell lung cancer models. Compared with the saline control, iopamidol and iodinated lipid agents provided only marginal increases in contrast resolution. The inorganic nanoparticulate agent provided the best contrast and visualization of thoracic vascular structures; the density contrast was highest at 15 min after injection and was stable for more than 4 h. Differential contrast of the tumors, vascular structures, and thoracic air space by the nanoparticulate agent enabled identification of tumor margins and accurate quantification. μCT data correlated closely with traditional histologic measurements (Pearson correlation coefficient, 0.995). Treatment of ELM4–ALK mice with crizotinib yielded 65% reduction in tumor size and thus demonstrated the utility of quantitative μCT in longitudinal preclinical trials. Overall and among the 3 agents we tested, the inorganic nanoparticulate product was the best commercially available contrast agent for visualization of thoracic blood vessels and lung tumors. Contrast-enhanced μCT imaging is an excellent noninvasive method for longitudinal evaluation during preclinical lung tumor studies. PMID:24326223

  19. In vivo near-infrared photothermal therapy and computed tomography imaging of cancer cells using novel tungsten-based theranostic probe.

    PubMed

    Liu, Jianhua; Han, Jianguo; Kang, Zhichen; Golamaully, Reza; Xu, Nannan; Li, Hongpeng; Han, Xueli

    2014-06-01

    Photothermal therapy, as a physical therapeutic technique to kill cancer, has generated a great deal of interest. Photothermal agents hence play a critical role in this modern therapy. We report the use of transition metal oxides as photothermal agents based on PEGylated WO3-x nanoparticles. The well-prepared nanoparticles presented effective results during photothermal therapy both in vitro and in vivo by using near-IR laser irradiation (980 nm, 0.5 W cm(-2)). The tumor cells were effectively damaged using low power density during a short irradiation time without destroying healthy tissues. In vitro results of photothermal therapy with PEGylated WO3-x nanoparticles proved to be effective on 4T1 murine breast cancer cells via a confocal microscopy method and MTT assay. In vivo results were further confirmed by hematoxylin and eosin (H & E) histological staining. Additionally, PEGylated WO3-x nanoparticles were shown to be effective as a CT imaging contrast agent on a tumor-bearing mouse model. Our results suggest that this generation of PEGylated WO3-x nanoparticles can potentially be used in oncological CT imaging and photothermal therapy.

  20. Depth-resolved photothermal optical coherence tomography by local optical path length change measurement (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Makita, Shuichi; Hong, Young-Joo; Li, En; Yasuno, Yoshiaki

    2016-03-01

    Photothermal OCT has been emerged to contrast absorbers in biological tissues. The tissues response to photothermal excitation as change of thermal strain and refractive index. To resolve the depth of absorption agents, the measurements of the local thermal strain change and local refractive index change due to photothermal effect is required. In this study, we developed photothermal OCT for depth-resolved absorption contrast imaging. The phase-resolved OCT can measure the axial strain change and local refractive index change as local optical path length change. A swept-source OCT system is used with a wavelength swept laser at 1310 nm with a scanning rate of 50 kHz. The sensitivity of 110 dB is achieved. At the sample arm, the excitation beam from a fiber-coupled laser diode of 406 nm wavelength is combined with the OCT probe beam co-linearly. The slowly modulated excitation beam around 300 Hz illuminate biological tissues. M-mode scan is applied during one-period modulation duration. The local optical path length change is measured by temporal and axial phase difference. The theoretical prediction of the photothermal response is derived and in good agreement with experimental results. In the case of slow modulation, the delay of photothermal response can be neglected. The local path length changes are averaged over the half period of the excitation modulation, and then demodulated. This method exhibits 3-dB gain in the sensitivity of the local optical path length change measurement over the direct Fourier transform method. In vivo human skin imaging of endogenous absorption agent will be demonstrated.

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

    PubMed

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

    2015-10-01

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

  2. Hexabrix as a contrast agent for ascending leg phlebography

    SciTech Connect

    Murphy, W.A.; Destouet, J.M.; Gilula, L.A.; Monsees, B.; Reinus, W.R.; Totty, W.G.

    1985-06-01

    Fifty patients were analyzed after a randomized double-blind study comparing Hexabrix and Hexabrix-20 in ascending phlebography. Measures of safety and patient tolerance indicated that both concentrations of Hexabrix appeared safe and were well tolerated. All studies were diagnostic, and the image quality was rated as excellent in 80% of the Hexabrix group and 72% of the Hexabrix-20 group. The authors conclude that Hexabrix and Hexabrix-20 are acceptable contrast media for ascending phlebography.

  3. Improved molecular imaging contrast agent for detection of human thrombus.

    PubMed

    Winter, Patrick M; Caruthers, Shelton D; Yu, Xin; Song, Sheng-Kwei; Chen, Junjie; Miller, Brad; Bulte, Jeff W M; Robertson, J David; Gaffney, Patrick J; Wickline, Samuel A; Lanza, Gregory M

    2003-08-01

    Molecular imaging of microthrombus within fissures of unstable atherosclerotic plaques requires sensitive detection with a thrombus-specific agent. Effective molecular imaging has been previously demonstrated with fibrin-targeted Gd-DTPA-bis-oleate (BOA) nanoparticles. In this study, the relaxivity of an improved fibrin-targeted paramagnetic formulation, Gd-DTPA-phosphatidylethanolamine (PE), was compared with Gd-DTPA-BOA at 0.05-4.7 T. Ion- and particle-based r(1) relaxivities (1.5 T) for Gd-DTPA-PE (33.7 (s*mM)(-1) and 2.48 x 10(6) (s*mM)(-1), respectively) were about twofold higher than for Gd-DTPA-BOA, perhaps due to faster water exchange with surface gadolinium. Gd-DTPA-PE nanoparticles bound to thrombus surfaces via anti-fibrin antibodies (1H10) induced 72% +/- 5% higher change in R(1) values at 1.5 T (deltaR(1) = 0.77 +/- 0.02 1/s) relative to Gd-DTPA-BOA (deltaR(1) = 0.45 +/- 0.02 1/s). These studies demonstrate marked improvement in a fibrin-specific molecular imaging agent that might allow sensitive, early detection of vascular microthrombi, the antecedent to stroke and heart attack.

  4. Phthalocyanine photosensitizers as contrast agents for in vivo photoacoustic tumor imaging.

    PubMed

    Attia, Amalina Bte Ebrahim; Balasundaram, Ghayathri; Driessen, Wouter; Ntziachristos, Vasilis; Olivo, Malini

    2015-02-01

    There is a need for contrast agents for non-invasive diagnostic imaging of tumors. Herein, Multispectral Optoacoustic Tomography (MSOT) was employed to evaluate phthalocyanines commonly used in photodynamic therapy as photoacoustic contrast agents. We studied the photoacoustic activity of three water-soluble phthalocyanine photosensitizers: phthalocyanine tetrasulfonic acid (PcS4), Zn(II) phthalocyanine tetrasulfonic acid (ZnPcS4) and Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) in phantom and in tumor-bearing mice to investigate the biodistribution and fate of the phthalocyanines in the biological tissues. PcS4 was observed to grant good contrast between the different reticuloendothelial organs and accumulate in the tumor within an hour of post-administration. ZnPcS4 and AlPcS4 offered little contrast in photoacoustic signals between the organs. PcS4 is a promising photoacoustic contrast agent and can be exploited as a photodiagnostic agent.

  5. Iopamidol: a non-ionic contrast agent for peripheral arteriography.

    PubMed

    Widrich, W C; Robbins, A H; Rommel, A J; Andrews, R

    1982-10-01

    Ten patients undergoing peripheral arteriography with iopamidol were evaluated in a carefully controlled Phase I study using a variety of objective and subjective tests of discomfort. There was minimal objective evidence of pain, and the patients reported that they perceived minor discomfort and a warm sensation during the contrast injections. Five patients who had previously undergone arteriography using 2 mg of lidocaine per ml of methylglucamine diatrizoate noted a marked decrease in discomfort when iopamidol was used. Opacification of peripheral arteries was excellent. Multiple physical examinations, chemical tests, electrocardiograms, and intra-arterial pressure recordings showed that iopamidol is safe.

  6. Effects of nonlinear propagation in ultrasound contrast agent imaging.

    PubMed

    Tang, Meng-Xing; Kamiyama, Naohisa; Eckersley, Robert J

    2010-03-01

    This paper investigates two types of nonlinear propagation and their effects on image intensity and contrast-to-tissue ratio (CTR) in contrast ultrasound images. Previous studies have shown that nonlinear propagation can occur when ultrasound travels through tissue and microbubble clouds, making tissue farther down the acoustic path appear brighter in pulse inversion (PI) images, thus reducing CTR. In this study, the effect of nonlinear propagation through tissue or microbubbles on PI image intensity and CTR are compared at low mechanical index. A combination of simulation and experiment with SonoVue microbubbles were performed using a microbubble dynamics model, a laboratory ultrasound system and a clinical prototype scanner. The results show that, close to the bubble resonance frequency, nonlinear propagation through a bubble cloud of a few centimeter thickness with a modest concentration (1:10000 dilution of SonoVue microbubbles) is much more significant than through tissue-mimicking material. Consequently, CTR in regions distal to the imaging probe is greatly reduced for nonlinear propagation through the bubble cloud, with as much as a 12-dB reduction compared with nonlinear propagation through tissue-mimicking material. Both types of nonlinear propagation cause only a small change in bubble PI signals at the bubble resonance frequency. When the driving frequency increases beyond bubble resonance, nonlinear propagation through bubbles is greatly reduced in absolute values. However because of a greater reduction in nonlinear scattering from bubbles at higher frequencies, the corresponding CTR is much lower than that at bubble resonance frequency.

  7. Tailored Near-Infrared Contrast Agents for Image Guided Surgery

    PubMed Central

    Njiojob, Costyl N.; Owens, Eric A.; Narayana, Lakshminarayana; Hyun, Hoon; Choi, Hak Soo; Henary, Maged

    2015-01-01

    The success of near-infrared (NIR) fluorescence to be employed for intraoperative imaging relies on the ability to develop a highly stable, NIR fluorescent, nontoxic, biocompatible, and highly excreted compound that retains a reactive functionality for conjugation to a cancer-recognizing peptide. Herein, systematic modifications to previously detailed fluorophore ZW800-1 are explored. Specific modifications, including the isosteric replacement of the O atom of ZW800-1, include nucleophilic amine and sulfur species attached to the heptamethine core. These novel compounds have shown similar satisfactory results in biodistribution and clearance while also expressing increased stability in serum. Most importantly, all of the synthesized and evaluated compounds display a reactive functionality (either a free amino group or carboxylic acid moiety) for further bioconjugation. The results obtained from the newly prepared derivatives demonstrate that the central substitution with the studied linking agents retains the ultralow background in vivo performance of the fluorophores regardless of the total net charge. PMID:25711712

  8. Tailored near-infrared contrast agents for image guided surgery.

    PubMed

    Njiojob, Costyl N; Owens, Eric A; Narayana, Lakshminarayana; Hyun, Hoon; Choi, Hak Soo; Henary, Maged

    2015-03-26

    The success of near-infrared (NIR) fluorescence to be employed for intraoperative imaging relies on the ability to develop a highly stable, NIR fluorescent, nontoxic, biocompatible, and highly excreted compound that retains a reactive functionality for conjugation to a cancer-recognizing peptide. Herein, systematic modifications to previously detailed fluorophore ZW800-1 are explored. Specific modifications, including the isosteric replacement of the O atom of ZW800-1, include nucleophilic amine and sulfur species attached to the heptamethine core. These novel compounds have shown similar satisfactory results in biodistribution and clearance while also expressing increased stability in serum. Most importantly, all of the synthesized and evaluated compounds display a reactive functionality (either a free amino group or carboxylic acid moiety) for further bioconjugation. The results obtained from the newly prepared derivatives demonstrate that the central substitution with the studied linking agents retains the ultralow background in vivo performance of the fluorophores regardless of the total net charge.

  9. Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging

    PubMed Central

    Wang, Taejun; Jang, Won Hyuk; Lee, Seunghun; Yoon, Calvin J.; Lee, Jun Ho; Kim, Bumju; Hwang, Sekyu; Hong, Chun-Pyo; Yoon, Yeoreum; Lee, Gilgu; Le, Viet-Hoan; Bok, Seoyeon; Ahn, G-One; Lee, Jaewook; Gho, Yong Song; Chung, Euiheon; Kim, Sungjee; Jang, Myoung Ho; Myung, Seung-Jae; Kim, Myoung Joon; So, Peter T. C.; Kim, Ki Hean

    2016-01-01

    Multiphoton microscopy (MPM) is a nonlinear fluorescence microscopic technique widely used for cellular imaging of thick tissues and live animals in biological studies. However, MPM application to human tissues is limited by weak endogenous fluorescence in tissue and cytotoxicity of exogenous probes. Herein, we describe the applications of moxifloxacin, an FDA-approved antibiotic, as a cell-labeling agent for MPM. Moxifloxacin has bright intrinsic multiphoton fluorescence, good tissue penetration and high intracellular concentration. MPM with moxifloxacin was demonstrated in various cell lines, and animal tissues of cornea, skin, small intestine and bladder. Clinical application is promising since imaging based on moxifloxacin labeling could be 10 times faster than imaging based on endogenous fluorescence. PMID:27283889

  10. Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging

    NASA Astrophysics Data System (ADS)

    Wang, Taejun; Jang, Won Hyuk; Lee, Seunghun; Yoon, Calvin J.; Lee, Jun Ho; Kim, Bumju; Hwang, Sekyu; Hong, Chun-Pyo; Yoon, Yeoreum; Lee, Gilgu; Le, Viet-Hoan; Bok, Seoyeon; Ahn, G.-One; Lee, Jaewook; Gho, Yong Song; Chung, Euiheon; Kim, Sungjee; Jang, Myoung Ho; Myung, Seung-Jae; Kim, Myoung Joon; So, Peter T. C.; Kim, Ki Hean

    2016-06-01

    Multiphoton microscopy (MPM) is a nonlinear fluorescence microscopic technique widely used for cellular imaging of thick tissues and live animals in biological studies. However, MPM application to human tissues is limited by weak endogenous fluorescence in tissue and cytotoxicity of exogenous probes. Herein, we describe the applications of moxifloxacin, an FDA-approved antibiotic, as a cell-labeling agent for MPM. Moxifloxacin has bright intrinsic multiphoton fluorescence, good tissue penetration and high intracellular concentration. MPM with moxifloxacin was demonstrated in various cell lines, and animal tissues of cornea, skin, small intestine and bladder. Clinical application is promising since imaging based on moxifloxacin labeling could be 10 times faster than imaging based on endogenous fluorescence.

  11. Contrasting actions of pressor agents in severe autonomic failure

    NASA Technical Reports Server (NTRS)

    Jordan, J.; Shannon, J. R.; Biaggioni, I.; Norman, R.; Black, B. K.; Robertson, D.

    1998-01-01

    BACKGROUND: Orthostatic hypotension is the most disabling symptom of autonomic failure. The choice of a pressor agent is largely empiric, and it would be of great value to define predictors of a response. PATIENTS AND METHODS: In 35 patients with severe orthostatic hypotension due to multiple system atrophy or pure autonomic failure, we determined the effect on seated systolic blood pressure (SBP) of placebo, phenylpropanolamine (12.5 mg and 25 mg), yohimbine (5.4 mg), indomethacin (50 mg), ibuprofen (600 mg), caffeine (250 mg), and methylphenidate (5 mg). In a subgroup of patients, we compared the pressor effect of midodrine (5 mg) with the effect of phenylpropanolamine (12.5 mg). RESULTS: There were no significant differences in the pressor responses between patients with multiple system atrophy or pure autonomic failure. When compared with placebo, the pressor response was significant for phenylpropanolamine, yohimbine, and indomethacin. In a subgroup of patients, we confirmed that this pressor effect of phenylpropanolamine, yohimbine, and indomethacin corresponded to a significant increase in standing SBP. The pressor responses to ibuprofen, caffeine, and methylphenidate were not significantly different from placebo. Phenylpropanolamine and midodrine elicited similar pressor responses. There were no significant associations between drug response and autonomic function testing, postprandial hypotension, or plasma catecholamine levels. CONCLUSIONS: We conclude that significant increases in systolic blood pressure can be obtained in patients with orthostatic hypotension due to primary autonomic failure with phenylpropanolamine in low doses or yohimbine or indomethacin in moderate doses. The response to a pressor agent cannot be predicted by autonomic function testing or plasma catecholamines. Therefore, empiric testing with a sequence of medications, based on the risk of side effects in the individual patient and the probability of a response, is a useful approach.

  12. Liver-specific agents for contrast-enhanced MRI: role in oncological imaging

    PubMed Central

    Thian, Yee Liang; Riddell, Angela M.

    2013-01-01

    Abstract Liver-specific magnetic resonance (MR) contrast agents are increasingly used in evaluation of the liver. They are effective in detection and morphological characterization of lesions, and can be useful for evaluation of biliary tree anatomy and liver function. The typical appearances and imaging pitfalls of various tumours at MR imaging performed with these agents can be understood by the interplay of pharmacokinetics of these contrast agents and transporter expression of the tumour. This review focuses on the applications of these agents in oncological imaging. PMID:24434892

  13. Design Principles of Nanoparticles as Contrast Agents for Magnetic Resonance Imaging

    NASA Astrophysics Data System (ADS)

    Shan, Liang; Gu, Xinbin; Wang, Paul

    2013-09-01

    Molecular imaging is an emerging field that introduces molecular agents into traditional imaging techniques, enabling visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems. The promise of molecular imaging lies in its potential for selective potency by targeting biomarkers or molecular targets and the imaging agents serve as reporters for the selectivity of targeting. Development of an efficient molecular imaging agent depends on well-controlled high-quality experiment design involving target selection, agent synthesis, in vitro characterization, and in vivo animal characterization before it is applied in humans. According to the analysis from the Molecular Imaging and Contrast Agent Database (MICAD, ), more than 6000 molecular imaging agents with sufficient preclinical evaluation have been reported to date in the literature and this number increases by 250-300 novel agents each year. The majority of these agents are radionuclides, which are developed for positron emission tomography (PET) and single photon emission computed tomography (SPECT). Contrast agents for magnetic resonance imaging (MRI) account for only a small part. This is largely due to the fact that MRI is currently not a fully quantitative imaging technique and is less sensitive than PET and SPECT. However, because of the superior ability to simultaneously extract molecular and anatomic information, molecular MRI is attracting significant interest and various targeted nanoparticle contrast agents have been synthesized for MRI. The first and one of the most critical steps in developing a targeted nanoparticle contrast agent is target selection, which plays the central role and forms the basis for success of molecular imaging. This chapter discusses the design principles of targeted contrast agents in the emerging frontiers of molecular MRI.

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

    PubMed Central

    Estelrich, Joan; Sánchez-Martín, María Jesús; Busquets, Maria Antònia

    2015-01-01

    Magnetic resonance imaging (MRI) has become one of the most widely used and powerful tools for noninvasive clinical diagnosis owing to its high degree of soft tissue contrast, spatial resolution, and depth of penetration. MRI signal intensity is related to the relaxation times (T1, spin–lattice relaxation and T2, spin–spin relaxation) of in vivo water protons. To increase contrast, various inorganic nanoparticles and complexes (the so-called contrast agents) are administered prior to the scanning. Shortening T1 and T2 increases the corresponding relaxation rates, 1/T1 and 1/T2, producing hyperintense and hypointense signals respectively in shorter times. Moreover, the signal-to-noise ratio can be improved with the acquisition of a large number of measurements. The contrast agents used are generally based on either iron oxide nanoparticles or ferrites, providing negative contrast in T2-weighted images; or complexes of lanthanide metals (mostly containing gadolinium ions), providing positive contrast in T1-weighted images. Recently, lanthanide complexes have been immobilized in nanostructured materials in order to develop a new class of contrast agents with functions including blood-pool and organ (or tumor) targeting. Meanwhile, to overcome the limitations of individual imaging modalities, multimodal imaging techniques have been developed. An important challenge is to design all-in-one contrast agents that can be detected by multimodal techniques. Magnetoliposomes are efficient multimodal contrast agents. They can simultaneously bear both kinds of contrast and can, furthermore, incorporate targeting ligands and chains of polyethylene glycol to enhance the accumulation of nanoparticles at the site of interest and the bioavailability, respectively. Here, we review the most important characteristics of the nanoparticles or complexes used as MRI contrast agents. PMID:25834422

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

    PubMed

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

    2016-05-19

    Gadolinium-based contrast agents are extensively used as magnetic resonance imaging (MRI) contrast agents due to their outstanding signal enhancement and ease of chemical modification. However, it is increasingly recognized that information obtained from single modal molecular imaging cannot satisfy the higher requirements on the efficiency and accuracy for clinical diagnosis and medical research, due to its limitation and default rooted in single molecular imaging technique itself. To compensate for the deficiencies of single function magnetic resonance imaging contrast agents, the combination of multi-modality imaging has turned to be the research hotpot in recent years. This review presents an overview on the recent developments of the functionalization of gadolinium-based contrast agents, and their application in biomedicine applications. PMID:27159645

  16. Synthesis and characterization of ethosomal contrast agents containing iodine for computed tomography (CT) imaging applications.

    PubMed

    Shin, Hanjin; Cho, Young-Min; Lee, Kangtaek; Lee, Chang-Ha; Choi, Byoung Wook; Kim, Bumsang

    2014-06-01

    As a first step in the development of novel liver-specific contrast agents using ethosomes for computed tomography (CT) imaging applications, we entrapped iodine within ethosomes, which are phospholipid vesicular carriers containing relatively high alcohol concentrations, synthesized using several types of alcohol, such as methanol, ethanol, and propanol. The iodine containing ethosomes that were prepared using methanol showed the smallest vesicle size (392 nm) and the highest CT density (1107 HU). The incorporation of cholesterol into the ethosomal contrast agents improved the stability of the ethosomes but made the vesicle size large. The ethosomal contrast agents were taken up well by macrophage cells and showed no cellular toxicity. The results demonstrated that ethosomes containing iodine, as prepared in this study, have potential as contrast agents for applications in CT imaging.

  17. Prolonged in vivo circulation time by zwitterionic modification of magnetite nanoparticles for blood pool contrast agents.

    PubMed

    Xiao, Wangchuan; Lin, Jiang; Li, Mingli; Ma, Yongjie; Chen, Yuxin; Zhang, Chunfu; Li, Dan; Gu, Hongchen

    2012-01-01

    Long circulation time is critical for blood pool contrast agents used in high-resolution magnetic resonance angiography. For iron oxide particle contrast agents, size and surface properties significantly influence their in vivo performance. We developed a novel long-circulating blood pool contrast agent by introducing zwitterionic structure onto the particle surface. Zwitterionic structure was fabricated by 3-(diethylamino)propylamine (DEAPA) grafted onto the surface of ployacrylic acid coated magnetite nanoparticles via EDC/NHS [N-(3-dimethylaminopropyl)-N'-ethylcarbo-diimide hydrochloride/N-hydroxysuccinimide] coupling chemistry. Zwitterionic particles demonstrated five times lower macrophage cell uptake than the original particles and low cell toxicity. Magnetic resonance angiography indicated that zwitterionic nanoparticles had much longer in vivo circulation time than the original particles and were an ideal candidate for blood pool contrast agent. We suppose that zwitterionic modification by DEAPA and EDC/NHS can be used generally for coating nanoparticles with carboxyl surface and to prolong their circulating time.

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

  19. Synthesis and characterization of ethosomal contrast agents containing iodine for computed tomography (CT) imaging applications.

    PubMed

    Shin, Hanjin; Cho, Young-Min; Lee, Kangtaek; Lee, Chang-Ha; Choi, Byoung Wook; Kim, Bumsang

    2014-06-01

    As a first step in the development of novel liver-specific contrast agents using ethosomes for computed tomography (CT) imaging applications, we entrapped iodine within ethosomes, which are phospholipid vesicular carriers containing relatively high alcohol concentrations, synthesized using several types of alcohol, such as methanol, ethanol, and propanol. The iodine containing ethosomes that were prepared using methanol showed the smallest vesicle size (392 nm) and the highest CT density (1107 HU). The incorporation of cholesterol into the ethosomal contrast agents improved the stability of the ethosomes but made the vesicle size large. The ethosomal contrast agents were taken up well by macrophage cells and showed no cellular toxicity. The results demonstrated that ethosomes containing iodine, as prepared in this study, have potential as contrast agents for applications in CT imaging. PMID:24188576

  20. Copper-D-penicillamine complex as potential contrast agent for MRI.

    PubMed

    Kupka, T; Dziegielewski, J O; Pasterna, G; Małecki, J G

    1992-01-01

    In vitro and in vivo proton T1 data are reported that demonstrate that the paramagnetic copper-D-penicillamine complex can be applied as a potential contrast agent to magnetic resonance imaging. PMID:1461082

  1. Classification and basic properties of contrast agents for magnetic resonance imaging.

    PubMed

    Geraldes, Carlos F G C; Laurent, Sophie

    2009-01-01

    A comprehensive classification of contrast agents currently used or under development for magnetic resonance imaging (MRI) is presented. Agents based on small chelates, macromolecular systems, iron oxides and other nanosystems, as well as responsive, chemical exchange saturation transfer (CEST) and hyperpolarization agents are covered in order to discuss the various possibilities of using MRI as a molecular imaging technique. The classification includes composition, magnetic properties, biodistribution and imaging applications. Chemical compositions of various classes of MRI contrast agents are tabulated, and their magnetic status including diamagnetic, paramagnetic and superparamagnetic are outlined. Classification according to biodistribution covers all types of MRI contrast agents including, among others, extracellular, blood pool, polymeric, particulate, responsive, oral, and organ specific (hepatobiliary, RES, lymph nodes, bone marrow and brain). Various targeting strategies of molecular, macromolecular and particulate carriers are also illustrated.

  2. Exploring silver as a contrast agent for contrast-enhanced dual-energy X-ray breast imaging

    PubMed Central

    Tsourkas, A; Maidment, A D A

    2014-01-01

    Objective: Through prior monoenergetic modelling, we have identified silver as a potential alternative to iodine in dual-energy (DE) X-ray breast imaging. The purpose of this study was to compare the performance of silver and iodine contrast agents in a commercially available DE imaging system through a quantitative analysis of signal difference-to-noise ratio (SDNR). Methods: A polyenergetic simulation algorithm was developed to model the signal intensity and noise. The model identified the influence of various technique parameters on SDNR. The model was also used to identify the optimal imaging techniques for silver and iodine, so that the two contrast materials could be objectively compared. Results: The major influences on the SDNR were the low-energy dose fraction and breast thickness. An increase in the value of either of these parameters resulted in a decrease in SDNR. The SDNR for silver was on average 43% higher than that for iodine when imaged at their respective optimal conditions, and 40% higher when both were imaged at the optimal conditions for iodine. Conclusion: A silver contrast agent should provide benefit over iodine, even when translated to the clinic without modification of imaging system or protocol. If the system were slightly modified to reflect the lower k-edge of silver, the difference in SDNR between the two materials would be increased. Advances in knowledge: These data are the first to demonstrate the suitability of silver as a contrast material in a clinical contrast-enhanced DE image acquisition system. PMID:24998157

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

    PubMed

    Lancharro Zapata, Á M; Rodríguez, C Marín

    2016-05-01

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

  4. A cationic gadolinium contrast agent for magnetic resonance imaging of cartilage.

    PubMed

    Freedman, Jonathan D; Lusic, Hrvoje; Wiewiorski, Martin; Farley, Michelle; Snyder, Brian D; Grinstaff, Mark W

    2015-06-30

    A new cationic gadolinium contrast agent is reported for delayed gadolinium enhanced magnetic resonance imaging of cartilage (dGEMRIC). The agent partitions into the glycosaminoglycan rich matrix of articular cartilage, based on Donnan equilibrium theory, and its use enables imaging of the human cadaveric metacarpal phalangeal joint.

  5. Detection of Sulfatase Enzyme Activity with a CatalyCEST MRI Contrast Agent.

    PubMed

    Sinharay, Sanhita; Fernández-Cuervo, Gabriela; Acfalle, Jasmine P; Pagel, Mark D

    2016-05-01

    A chemical exchange saturation transfer (CEST) MRI contrast agent has been developed that detects sulfatase enzyme activity. The agent produces a CEST signal at δ=5.0 ppm before enzyme activity, and a second CEST signal appears at δ=9.0 ppm after the enzyme cleaves a sulfate group from the agent. The comparison of the two signals improved detection of sulfatase activity.

  6. Nanoshell-enabled photothermal cancer therapy: impending clinical impact.

    PubMed

    Lal, Surbhi; Clare, Susan E; Halas, Naomi J

    2008-12-01

    Much of the current excitement surrounding nanoscience is directly connected to the promise of new nanoscale applications in cancer diagnostics and therapy. Because of their strongly resonant light-absorbing and light-scattering properties that depend on shape, noble metal nanoparticles provide a new and powerful tool for innovative light-based approaches. Nanoshellsspherical, dielectric core, gold shell nanoparticleshave been central to the development of photothermal cancer therapy and diagnostics for the past several years. By manipulating nanoparticle shape, researchers can tune the optical resonance of nanoshells to any wavelength of interest. At wavelengths just beyond the visible spectrum in the near-infrared, blood and tissue are maximally transmissive. When nanoshell resonances are tuned to this region of the spectrum, they become useful contrast agents in the diagnostic imaging of tumors. When illuminated, they can serve as nanoscale heat sources, photothermally inducing cell death and tumor remission. As nanoshell-based diagnostics and therapeutics move from laboratory studies to clinical trials, this Account examines the highly promising achievements of this approach in the context of the challenges of this complex disease. More broadly, these materials present a concrete example of a highly promising application of nanochemistry to a biomedical problem. We describe the properties of nanoshells that are relevant to their preparation and use in cancer diagnostics and therapy. Specific surface chemistries are necessary for passive uptake of nanoshells into tumors and for targeting specific cell types by bioconjugate strategies. We also describe the photothermal temperature increases that can be achieved in surrogate structures known as tissue phantoms and the accuracy of models of this effect using heat transport analysis. Nanoshell-based photothermal therapy in several animal models of human tumors have produced highly promising results, and we include

  7. Nanoshell-enabled photothermal cancer therapy: impending clinical impact.

    PubMed

    Lal, Surbhi; Clare, Susan E; Halas, Naomi J

    2008-12-01

    Much of the current excitement surrounding nanoscience is directly connected to the promise of new nanoscale applications in cancer diagnostics and therapy. Because of their strongly resonant light-absorbing and light-scattering properties that depend on shape, noble metal nanoparticles provide a new and powerful tool for innovative light-based approaches. Nanoshellsspherical, dielectric core, gold shell nanoparticleshave been central to the development of photothermal cancer therapy and diagnostics for the past several years. By manipulating nanoparticle shape, researchers can tune the optical resonance of nanoshells to any wavelength of interest. At wavelengths just beyond the visible spectrum in the near-infrared, blood and tissue are maximally transmissive. When nanoshell resonances are tuned to this region of the spectrum, they become useful contrast agents in the diagnostic imaging of tumors. When illuminated, they can serve as nanoscale heat sources, photothermally inducing cell death and tumor remission. As nanoshell-based diagnostics and therapeutics move from laboratory studies to clinical trials, this Account examines the highly promising achievements of this approach in the context of the challenges of this complex disease. More broadly, these materials present a concrete example of a highly promising application of nanochemistry to a biomedical problem. We describe the properties of nanoshells that are relevant to their preparation and use in cancer diagnostics and therapy. Specific surface chemistries are necessary for passive uptake of nanoshells into tumors and for targeting specific cell types by bioconjugate strategies. We also describe the photothermal temperature increases that can be achieved in surrogate structures known as tissue phantoms and the accuracy of models of this effect using heat transport analysis. Nanoshell-based photothermal therapy in several animal models of human tumors have produced highly promising results, and we include

  8. Potential of high-Z contrast agents in clinical contrast-enhanced computed tomography

    SciTech Connect

    Nowak, Tristan; Hupfer, Martin; Brauweiler, Robert; Eisa, Fabian; Kalender, Willi A.

    2011-12-15

    Purpose: Currently, only iodine- and barium-based contrast media (CM) are used in clinical contrast-enhanced computed tomography (CE-CT). High-Z metals would produce a higher contrast at equal mass density for the x-ray spectra used in clinical CT. Using such materials might allow for significant dose reductions in CE-CT. The purpose of this study was to quantify the potential for dose reduction when using CM based on heavy metals. Methods: The contrast-to-noise ratio weighted by dose (CNRD) was determined as a function of scan protocol by means of measurements and simulations on a clinical CT scanner. For simulations, water cylinders with diameters 160, 320, 480, and 640 mm were used to cover a broad range of patient sizes. Measurements were conducted with 160 and 320 mm water-equivalent plastic cylinders. A central bore of 13 mm diameter was present in all phantoms. The tube voltage was varied from 80 to 140 kV for measurements and from 60 to 180 kV for simulations. Additional tin filtration of thicknesses 0.4, 0.8, and 1.2 mm was applied in the simulation to evaluate a range of spectral hardness. The bore was filled with a mixture of water and 10 mg/ml of pure iodine, holmium, gadolinium, ytterbium, osmium, tungsten, gold, and bismuth for the simulations and with aqueous solutions of ytterbium, tungsten, gold, and bismuth salts as well as Iopromid containing 10 mg/ml of the pure materials for the measurements. CNRDs were compared to iodine at phantom size-dependent reference voltages for all high-Z materials and the resulting dose reduction was calculated for equal contrast-to-noise ratio. Results: Dose reduction potentials strongly depended on phantom size, spectral hardness, and tube voltage. Depending on the added filtration, a dose reduction of 19%-60% could be reached at 80 kV with gadolinium for the 160 mm phantom, 52%-69% at 100 kV with holmium for the 320 mm phantom, 62%-78% with 120 kV for hafnium and the 480 mm phantom and 74%-86% with 140 kV for gold

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

    PubMed Central

    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. PMID:23625065

  10. A liposomal Gd contrast agent does not cross the mouse placental barrier.

    PubMed

    Shetty, Anil N; Pautler, Robia; Ghagahda, Ketan; Rendon, David; Gao, Haijun; Starosolski, Zbigniew; Bhavane, Rohan; Patel, Chandreshkumar; Annapragada, Ananth; Yallampalli, Chandrasekhar; Lee, Wesley

    2016-06-14

    The trans-placental permeability of liposomal Gadolinium (Gd) nanoparticle contrast agents was evaluated in a pregnant mouse model. Pregnant Balb/c mice at 16.5 (±1) days of gestation were imaged using a 3D Spoiled Gradient Echo method at 9.4 T using two contrast agents: a clinically approved Gd chelate, Multihance(®) (gadobenate dimeglumine), and a novel experimental liposomal Gd agent. A Dynamic Contrast Enhancement (DCE) protocol was used to capture the dynamics of contrast entry and distribution in the placenta, and clearance from circulation. A blinded clinical radiologist evaluated both sets of images. A reference region model was used to measure the placental flow and physiological parameters; volume transfer constant (K(trans)), efflux rate constant (K(ep)). The Gd content of excised placentae and fetuses was measured, using inductively coupled plasma mass spectrometry (ICP-MS). MRI images of pregnant mice and ICP-MS analyses of placental and fetal tissue demonstrated undetectably low transplacental permeation of the liposomal Gd agent, while the clinical agent (Multihance) avidly permeated the placental barrier. Image interpretation and diagnostic quality was equivalent between the two contrast agents. Additional testing to determine both maternal and fetal safety of liposomal Gd is suggested.

  11. Efficient mucosal delivery of optical contrast agents using imidazole-modified chitosan

    NASA Astrophysics Data System (ADS)

    Ghosn, Bilal; van de Ven, Anne L.; Tam, Justina; Gillenwater, Ann; Sokolov, Konstantin V.; Richards-Kortum, Rebecca; Roy, Krishnendu

    2010-01-01

    The clinical applicability of antibodies and plasmonic nanosensors as topically applied, molecule-specific optical diagnostic agents for noninvasive early detection of cancer and precancer is severely limited by our inability to efficiently deliver macromolecules and nanoparticles through mucosal tissues. We have developed an imidazole-functionalized conjugate of the polysaccharide chitosan (chitosan-IAA) to enhance topical delivery of contrast agents, ranging from small molecules and antibodies to gold nanoparticles up to 44 nm in average diameter. Contrast agent uptake and localization in freshly resected mucosal tissues was monitored using confocal microscopy. Chitosan-IAA was found to reversibly enhance mucosal permeability in a rapid, reproducible manner, facilitating transepithelial delivery of optical contrast agents. Permeation enhancement occurred through an active process, resulting in the delivery of contrast agents via a paracellular or a combined paracellular/transcellular route depending on size. Coadministration of epidermal growth factor receptor-targeted antibodies with chitosan-IAA facilitated specific labeling and discrimination between paired normal and malignant human oral biopsies. Together, these data suggest that chitosan-IAA is a promising topical permeation enhancer for mucosal delivery of optical contrast agents.

  12. A liposomal Gd contrast agent does not cross the mouse placental barrier

    PubMed Central

    Shetty, Anil N.; Pautler, Robia; Ghagahda, Ketan; Rendon, David; Gao, Haijun; Starosolski, Zbigniew; Bhavane, Rohan; Patel, Chandreshkumar; Annapragada, Ananth; Yallampalli, Chandrasekhar; Lee, Wesley

    2016-01-01

    The trans-placental permeability of liposomal Gadolinium (Gd) nanoparticle contrast agents was evaluated in a pregnant mouse model. Pregnant Balb/c mice at 16.5 (±1) days of gestation were imaged using a 3D Spoiled Gradient Echo method at 9.4 T using two contrast agents: a clinically approved Gd chelate, Multihance® (gadobenate dimeglumine), and a novel experimental liposomal Gd agent. A Dynamic Contrast Enhancement (DCE) protocol was used to capture the dynamics of contrast entry and distribution in the placenta, and clearance from circulation. A blinded clinical radiologist evaluated both sets of images. A reference region model was used to measure the placental flow and physiological parameters; volume transfer constant (Ktrans), efflux rate constant (Kep). The Gd content of excised placentae and fetuses was measured, using inductively coupled plasma mass spectrometry (ICP-MS). MRI images of pregnant mice and ICP-MS analyses of placental and fetal tissue demonstrated undetectably low transplacental permeation of the liposomal Gd agent, while the clinical agent (Multihance) avidly permeated the placental barrier. Image interpretation and diagnostic quality was equivalent between the two contrast agents. Additional testing to determine both maternal and fetal safety of liposomal Gd is suggested. PMID:27298076

  13. The evaluation of NIR-absorbing porphyrin derivatives as contrast agents in photoacoustic imaging

    PubMed Central

    Abuteen, Akram; Zanganeh, Saeid; Akhigbe, Joshua; Samankumara, Lalith P.; Aguirre, Andres; Biswal, Nrusingh; Braune, Marcel; Vollertsen, Anke; Röder, Beate; Brückner, Christian; Zhu, Quing

    2016-01-01

    Six free base tetrapyrrolic chromophores, three quinoline-annulated porphyrins and three morpholinobacteriochlorins, that absorb light in the near-IR range and possess, in comparison to regular porphyrins, unusually low fluorescence emission and 1O2 quantum yields were tested with respect to their efficacy as novel molecular photo-acoustic imaging contrast agents in a tissue phantom, providing an up to ~2.5-fold contrast enhancement over that of the benchmark contrast agent ICG. The testing protocol compares the photoacoustic signal output strength upon absorption of approximately the same light energy. Some relationships between photophysical parameters of the dyes and the resulting photoacoustic signal strength could be derived. PMID:24071709

  14. Silica-coated super paramagnetic iron oxide nanoparticles (SPION) as biocompatible contrast agent in biomedical photoacoustics

    PubMed Central

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

    2012-01-01

    In this study, we report for the first time the use of silica-coated superparamagnetic iron oxide nanoparticles (SPION) as contrast agents in biomedical photoacoustic imaging. Using frequency-domain photoacoustic correlation (the photoacoustic radar), we investigated the effects of nanoparticle size, concentration and biological media (e.g. serum, sheep blood) on the photoacoustic response in turbid media. Maximum detection depth and the minimum measurable SPION concentration were determined experimentally. The nanoparticle-induced optical contrast ex vivo in dense muscular tissues (avian pectus and murine quadricept) was evaluated and the strong potential of silica-coated SPION as a possible photoacoustic contrast agents was demonstrated. PMID:23082291

  15. Quantitative imaging of cell-permeable magnetic resonance contrast agents using x-ray fluorescence.

    PubMed

    Endres, Paul J; Macrenaris, Keith W; Vogt, Stefan; Allen, Matthew J; Meade, Thomas J

    2006-01-01

    The inability to transduce cellular membranes is a limitation of current magnetic resonance imaging probes used in biologic and clinical settings. This constraint confines contrast agents to extracellular and vascular regions of the body, drastically reducing their viability for investigating processes and cycles in developmental biology. Conversely, a contrast agent with the ability to permeate cell membranes could be used in visualizing cell patterning, cell fate mapping, gene therapy, and, eventually, noninvasive cancer diagnosis. Therefore, we describe the synthesis and quantitative imaging of four contrast agents with the capability to cross cell membranes in sufficient quantity for detection. Each agent is based on the conjugation of a Gd(III) chelator with a cellular transduction moiety. Specifically, we coupled Gd(III)-diethylenetriaminepentaacetic acid DTPA and Gd(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid with an 8-amino acid polyarginine oligomer and an amphipathic stilbene molecule, 4-amino-4'-(N,N-dimethylamino)stilbene. The imaging modality that provided the best sensitivity and spatial resolution for direct detection of the contrast agents is synchrotron radiation x-ray fluorescence (SR-XRF). Unlike optical microscopy, SR-XRF provides two-dimensional images with resolution 10(3) better than (153)Gd gamma counting, without altering the agent by organic fluorophore conjugation. The transduction efficiency of the intracellular agents was evaluated by T(1) analysis and inductively coupled plasma mass spectrometry to determine the efficacy of each chelate-transporter combination. PMID:17150161

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

    PubMed

    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.

  17. Longitudinal vascular imaging using a novel nano-encapsulated CT and MR contrast agent

    NASA Astrophysics Data System (ADS)

    Zheng, Jinzi; Hoisak, Jeremy D.; Allen, Christine; Jaffray, David A.

    2007-03-01

    Contrast agents are widely employed in medical imaging for improved visualization of anatomy and disease characterization. In recent years, there is increasing interest in developing novel contrast agents and using their tissue accumulation and clearance patterns to obtain physiological information. The goal of this investigation is to assess the utility of a long circulating dual modality liposomal contrast agent for longitudinal imaging applications in computed tomography (CT) and magnetic resonance (MR) imaging. It was demonstrated that this high molecular weight contrast agent is retained in healthy vasculature (circulation half-life of ~20 hours in mice and ~100 hours in rabbits), but it is able to leak through abnormal tumor vasculature into the tumor interstitium. The rate of its differential tumor uptake was monitored in CT and MR longitudinally over a 48-hour period and a map of the rate of change of contrast enhancement was produced. This contrast agent has shown potential for anatomic and physiological imaging of healthy and abnormal blood vessels in CT and MR. It may become a useful tool for tumor vasculature assessment before, during and after antitumor treatments.

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

    PubMed

    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.

  19. Structural and functional photoacoustic molecular tomography aided by emerging contrast agents

    PubMed Central

    Nie, Liming

    2015-01-01

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

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

    SciTech Connect

    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.

  1. Development of functional gold nanorods for bioimaging and photothermal therapy

    NASA Astrophysics Data System (ADS)

    Niidome, T.

    2010-06-01

    Gold nanorods have strong surface plasmon band at near-infrared light region, and are used as a photothermal converter. Since the near-infrared light penetrates into tissues deeply, it has been expected as a contrast agent for near infrared light bioimaging, a photosensitizer for photothermal therapy, and functional device for drug delivery system responding to near-infrared light irradiation. In this study, the surface plasmon bands of intravenously injected gold nanorods were monitored in the mouse abdomen using a spectrophotometer equipped with an integrating sphere, then we determined pharmacokinetics parameters of the gold nanorods after intravenous injection. Next, the PEG-modified gold nanorods were directly injected into subcutaneous tumors in mice, then, near-infrared pulsed laser light was irradiated the tumors. Significant tumor damage and suppression of the tumor growth was observed. We constructed targeted delivery system of the gold nanorods by modifying with a thermo-responsive polymer and a peptide responding to a protease activity. These modified gold nanorods are expected as functional nanodevices for photothermal therapy and drug delivery system.

  2. Manganese (II) Chelate Functionalized Copper Sulfide Nanoparticles for Efficient Magnetic Resonance/Photoacoustic Dual-Modal Imaging Guided Photothermal Therapy.

    PubMed

    Liu, Renfa; Jing, Lijia; Peng, Dong; Li, Yong; Tian, Jie; Dai, Zhifei

    2015-01-01

    The integration of diagnostic and therapeutic functionalities into one nanoplatform shows great promise in cancer therapy. In this research, manganese (II) chelate functionalized copper sulfide nanoparticles were successfully prepared using a facile hydrothermal method. The obtained ultrasmall nanoparticles exhibit excellent photothermal effect and photoaoustic activity. Besides, the high loading content of Mn(II) chelates makes the nanoparticles attractive T1 contrast agent in magnetic resonance imaging (MRI). In vivo photoacoustic imaging (PAI) results showed that the nanoparticles could be efficiently accumulated in tumor site in 24 h after systematic administration, which was further validated by MRI tests. The subsequent photothermal therapy of cancer in vivo was achieved without inducing any observed side effects. Therefore, the copper sulfide nanoparticles functionalized with Mn(II) chelate hold great promise as a theranostic nanomedicine for MR/PA dual-modal imaging guided photothermal therapy of cancer.

  3. Magnetic gold-nanorod/ PNIPAAmMA nanoparticles for dual magnetic resonance and photoacoustic imaging and targeted photothermal therapy.

    PubMed

    Yang, Hung-Wei; Liu, Hao-Li; Li, Meng-Lin; Hsi, I-Wen; Fan, Chih-Tai; Huang, Chiung-Yin; Lu, Yu-Jen; Hua, Mu-Yi; Chou, Hsin-Yi; Liaw, Jiunn-Woei; Ma, Chen-Chi M; Wei, Kuo-Chen

    2013-07-01

    Nanomedicine can provide a multi-functional platform for image-guided diagnosis and treatment of cancer. Although gold nanorods (GNRs) have been developed for photoacoustic (PA) imaging and near infra-red (NIR) photothermal applications, their efficiency has remained limited by low thermal stability. Here we present the synthesis, characterization, and functional evaluation of non-cytotoxic magnetic polymer-modified gold nanorods (MPGNRs), designed to act as dual magnetic resonance imaging (MRI) and PA imaging contrast agents. In addition, their high magnetization allowed MPGNRs to be actively localized and concentrated by targeting with an external magnet. Finally, MPGNRs significantly enhanced the NIR-laser-induced photothermal effect due to their increased thermal stability. MPGNRs thus provide a promising new theranostic platform for cancer diagnosis and treatment by combining dual MR/PA imaging with highly effective targeted photothermal therapy.

  4. Manganese (II) Chelate Functionalized Copper Sulfide Nanoparticles for Efficient Magnetic Resonance/Photoacoustic Dual-Modal Imaging Guided Photothermal Therapy

    PubMed Central

    Liu, Renfa; Jing, Lijia; Peng, Dong; Li, Yong; Tian, Jie; Dai, Zhifei

    2015-01-01

    The integration of diagnostic and therapeutic functionalities into one nanoplatform shows great promise in cancer therapy. In this research, manganese (II) chelate functionalized copper sulfide nanoparticles were successfully prepared using a facile hydrothermal method. The obtained ultrasmall nanoparticles exhibit excellent photothermal effect and photoaoustic activity. Besides, the high loading content of Mn(II) chelates makes the nanoparticles attractive T1 contrast agent in magnetic resonance imaging (MRI). In vivo photoacoustic imaging (PAI) results showed that the nanoparticles could be efficiently accumulated in tumor site in 24 h after systematic administration, which was further validated by MRI tests. The subsequent photothermal therapy of cancer in vivo was achieved without inducing any observed side effects. Therefore, the copper sulfide nanoparticles functionalized with Mn(II) chelate hold great promise as a theranostic nanomedicine for MR/PA dual-modal imaging guided photothermal therapy of cancer. PMID:26284144

  5. Photothermal imaging

    NASA Astrophysics Data System (ADS)

    Lapotko, Dmitry; Antonishina, Elena

    1995-02-01

    An automated image analysis system with two imaging regimes is described. Photothermal (PT) effect is used for imaging of a temperature field or absorption structure of the sample (the cell) with high sensitivity and spatial resolution. In a cell study PT-technique enables imaging of live non-stained cells, and the monitoring of the cell shape/structure. The system includes a dual laser illumination unit coupled to a conventional optical microscope. A sample chamber provides automated or manual loading of up to 3 samples and cell positioning. For image detection a 256 X 256 10-bit CCD-camera is used. The lasers, scanning stage, and camera are controlled by PC. The system provides optical (transmitted light) image, probe laser optical image, and PT-image acquisition. Operation rate is 1 - 1.5 sec per cell for a cycle: cell positioning -- 3 images acquisition -- image parameters calculation. A special database provides image/parameters storage, presentation, and cell diagnostic according to quantitative image parameters. The described system has been tested during live and stained blood cell studies. PT-images of the cells have been used for cell differentiation. In experiments with the red blood cells (RBC) that originate from normal and anaemia blood parameters for disease differentiation have been found. For white blood cells in PT-images the details of cell structure have found that absent in their optical images.

  6. Thermal Excitation of Gadolinium-Based Contrast Agents Using Spin Resonance

    PubMed Central

    Fridjhon, Peter; Rubin, David M.

    2016-01-01

    Theoretical and experimental investigations into the thermal excitation of liquid paramagnetic contrast agents using the spin resonance relaxation mechanism are presented. The electronic spin-lattice relaxation time τ1e of gadolinium-based contrast agents, which is estimated at 0.1 ns, is ten orders of magnitude faster than the relaxation time of protons in water. The shorter relaxation time is found to significantly increase the rate of thermal energy deposition. To the authors’ knowledge this is the first study of gadolinium based contrast agents in a liquid state used as thermal agents. Analysis shows that when τ1e and other experimental parameters are optimally selected, a maximum theoretical heating rate of 29.4 °C.s−1 could be achieved which would suffice for clinical thermal ablation of neoplasms. The experimental results show a statistically significant thermal response for two out of the four contrast agents tested. The results are compared to the simulated estimates via analysis of a detailed model of the system. While these experimentally determined temperature rises are small and thus of no clinical utility, their presence supports the theoretical analysis and strongly suggests that the chemical structure of the selected compounds plays an important role in this mechanism of heat deposition. There exists an opportunity for the development of alternative gadolinium-based compounds with an order of magnitude longer τ1e in a diluted form to be used as an efficient hyperthermia agent for clinical use. PMID:27341338

  7. Thermal Excitation of Gadolinium-Based Contrast Agents Using Spin Resonance.

    PubMed

    Dinger, Steven C; Fridjhon, Peter; Rubin, David M

    2016-01-01

    Theoretical and experimental investigations into the thermal excitation of liquid paramagnetic contrast agents using the spin resonance relaxation mechanism are presented. The electronic spin-lattice relaxation time τ1e of gadolinium-based contrast agents, which is estimated at 0.1 ns, is ten orders of magnitude faster than the relaxation time of protons in water. The shorter relaxation time is found to significantly increase the rate of thermal energy deposition. To the authors' knowledge this is the first study of gadolinium based contrast agents in a liquid state used as thermal agents. Analysis shows that when τ1e and other experimental parameters are optimally selected, a maximum theoretical heating rate of 29.4 °C.s-1 could be achieved which would suffice for clinical thermal ablation of neoplasms. The experimental results show a statistically significant thermal response for two out of the four contrast agents tested. The results are compared to the simulated estimates via analysis of a detailed model of the system. While these experimentally determined temperature rises are small and thus of no clinical utility, their presence supports the theoretical analysis and strongly suggests that the chemical structure of the selected compounds plays an important role in this mechanism of heat deposition. There exists an opportunity for the development of alternative gadolinium-based compounds with an order of magnitude longer τ1e in a diluted form to be used as an efficient hyperthermia agent for clinical use. PMID:27341338

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

    PubMed

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

    2014-04-01

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

  9. Contrast-agent-enhanced magnetic resonance imaging: early detection of neoplastic lesions of the CNS

    NASA Astrophysics Data System (ADS)

    Carvlin, Mark J.; Rosa, Louis; Rajan, Sunder S.; Francisco, John

    1991-06-01

    Even though the intrinsic soft tissue contrast sensitivity of magnetic resonance imaging (MRI) affords excellent visualization of anatomic detail, certain pathologic processes may be diagnosed earlier with the administration of a contrast-enhancing agent. At present there is one agent, gadopentetate dimeglumine, GdDTPA, that has received FDA approval for use in the MR scanning of the brain and spine in human patients. This paramagnetic chelate distributes throughout the extracellular fluid space as dictated by capillary permeability so that abnormal vascularity and sites of blood-CNS barrier breakdown are highlighted. Primary neoplastic disease, metastases, meningeal extension, residual and recurrent tumor have been found to be better distinguished in MR images acquired after administration of GdDTPA. Routine administration of GdDTPA for cranial imaging has resulted in the discovery of otherwise occult lesions in approximately 3 of patients. Although the clinical utility and high therapeutic safety index of the first approved magnetic resonance contrast agent, GdDTPA, have been well established, other contrast agents, having different physical, chemical and biological properties, may offer improved sensitivity and bio-specificity. Agents currently being evaluated in vivo include: low osmolal paramagnetic chelates, superparamagnetic particles, metalloporphyrins, liposome encapsulated agents, perfluorocarbons, intravascular macromolecular chelate complexes and labeled monoclonal antibodies. Concurrent with advances in the development of new compounds, innovations in scanning hardware, pulse sequence design and image post-processing are helping to extend the efficacy of contrast media. Additional clinical experience will indicate which contrast agents and which MR techniques can best facilitate the early detection of specific neoplastic lesions.

  10. The delayed onset of subharmonic and ultraharmonic emissions from a phospholipid-shelled microbubble contrast agent

    PubMed Central

    Shekhar, Himanshu; Awuor, Ivy; Thomas, Keri; Rychak, Joshua J.; Doyley, Marvin M.

    2014-01-01

    Characterizing the nonlinear response of microbubble contrast agents is important for their efficacious use in imaging and therapy. In this paper, we report that the subharmonic and ultraharmonic response of lipid-shelled microbubble contrast agents exhibits a strong temporal dependence. We characterized nonlinear emissions from Targestar-P® microbubbles (Targeson Inc., San Diego, CA, USA) periodically for 60 minutes, at 10 MHz excitation frequency. The results revealed a considerable increase in the subharmonic and ultraharmonic response (nearly 12–15 and 5–8 dB) after 5–10 minutes of agent preparation. However, the fundamental and the harmonic response remained almost unchanged in this period. During the next 50 minutes, the subharmonic, fundamental, ultraharmonic, and harmonic responses decreased steadily by 2–5 dB. The temporal changes in the nonlinear behavior of the agent appeared to be primarily mediated by gas-exchange through the microbubble shell; temperature and prior acoustic excitation based mechanisms were ruled out. Further, there was no measurable change in the agent size distribution by static diffusion. We envisage that these findings will help obtain reproducible measurements from agent characterization, nonlinear imaging, and fluid-pressure sensing. These findings also suggest the possibility for improving nonlinear imaging by careful design of ultrasound contrast agents. PMID:24582298

  11. Poly(Lactic-co-Glycolic) Acid as a Carrier for Imaging Contrast Agents

    PubMed Central

    Doiron, Amber L.; Homan, Kimberly A.; Emelianov, Stanislav; Brannon-Peppas, Lisa

    2010-01-01

    Purpose With the broadening field of nanomedicine poised for future molecular level therapeutics, nano-and microparticles intended for the augmentation of either single- or multimodal imaging are created with PLGA as the chief constituent and carrier. Methods Emulsion techniques were used to encapsulate hydrophilic and hydrophobic imaging contrast agents in PLGA particles. The imaging contrast properties of these PLGA particles were further enhanced by reducing silver onto the PLGA surface, creating a silver cage around the polymeric core. Results The MRI contrast agent Gd-DTPA and the exogenous dye rhodamine 6G were both encapsulated in PLGA and shown to enhance MR and fluorescence contrast, respectively. The silver nanocage built around PLGA nanoparticles exhibited strong near infrared light absorbance properties, making it a suitable contrast agent for optical imaging strategies such as photoacoustic imaging. Conclusions The biodegradable polymer PLGA is an extremely versatile nano- and micro-carrier for several imaging contrast agents with the possibility of targeting diseased states at a molecular level. PMID:19034628

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

    PubMed Central

    Balint, Richard; Lowe, Tristan

    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. PMID:27078030

  13. A contrast agent recognizing activated platelets reveals murine cerebral malaria pathology undetectable by conventional MRI

    PubMed Central

    von zur Muhlen, Constantin; Sibson, Nicola R.; Peter, Karlheinz; Campbell, Sandra J.; Wilainam, Panop; Grau, Georges E.; Bode, Christoph; Choudhury, Robin P.; Anthony, Daniel C.

    2008-01-01

    Human and murine cerebral malaria are associated with elevated levels of cytokines in the brain and adherence of platelets to the microvasculature. Here we demonstrated that the accumulation of platelets in the brain microvasculature can be detected with MRI, using what we believe to be a novel contrast agent, at a time when the pathology is undetectable by conventional MRI. Ligand-induced binding sites (LIBS) on activated platelet glycoprotein IIb/IIIa receptors were detected in the brains of malaria-infected mice 6 days after inoculation with Plasmodium berghei using microparticles of iron oxide (MPIOs) conjugated to a single-chain antibody specific for the LIBS (LIBS-MPIO). No binding of the LIBS-MPIO contrast agent was detected in uninfected animals. A combination of LIBS-MPIO MRI, confocal microscopy, and transmission electron microscopy revealed that the proinflammatory cytokine TNF-α, but not IL-1β or lymphotoxin-α (LT-α), induced adherence of platelets to cerebrovascular endothelium. Peak platelet adhesion was found 12 h after TNF-α injection and was readily detected with LIBS-MPIO contrast-enhanced MRI. Temporal studies revealed that the level of MPIO-induced contrast was proportional to the number of platelets bound. Thus, the LIBS-MPIO contrast agent enabled noninvasive detection of otherwise undetectable cerebral pathology by in vivo MRI before the appearance of clinical disease, highlighting the potential of targeted contrast agents for diagnostic, mechanistic, and therapeutic studies. PMID:18274670

  14. Laser speckle imaging based on photothermally driven convection.

    PubMed

    Regan, Caitlin; Choi, Bernard

    2016-02-01

    Laser speckle imaging (LSI) is an interferometric technique that provides information about the relative speed of moving scatterers in a sample. Photothermal LSI overcomes limitations in depth resolution faced by conventional LSI by incorporating an excitation pulse to target absorption by hemoglobin within the vascular network. Here we present results from experiments designed to determine the mechanism by which photothermal LSI decreases speckle contrast. We measured the impact of mechanical properties on speckle contrast, as well as the spatiotemporal temperature dynamics and bulk convective motion occurring during photothermal LSI. Our collective data strongly support the hypothesis that photothermal LSI achieves a transient reduction in speckle contrast due to bulk motion associated with thermally driven convection. The ability of photothermal LSI to image structures below a scattering medium may have important preclinical and clinical applications.

  15. Gd-based macromolecules and nanoparticles as magnetic resonance contrast agents for molecular imaging

    PubMed Central

    Huang, Ching-Hui; Tsourkas, Andrew

    2013-01-01

    As we move towards an era of personalized medicine, molecular imaging contrast agents are likely to see an increasing presence in routine clinical practice. Magnetic resonance (MR) imaging has garnered particular interest as a platform for molecular imaging applications due its ability to monitor anatomical changes concomitant with physiologic and molecular changes. One promising new direction in the development of MR contrast agents involves the labeling and/or loading of nanoparticles with gadolinium (Gd). These nanoplatforms are capable of carrying large payloads of Gd, thus providing the requisite sensitivity to detect molecular signatures within disease pathologies. In this review, we discuss some of the progress that has recently been made in the development of Gd-based macromolecules and nanoparticles and outline some of the physical and chemical properties that will be important to incorporate into the next generation of contrast agents, including high Gd chelate stability, high “relaxivity per particle” and “relaxivity density”, and biodegradability. PMID:23432004

  16. Multiwall carbon nanotubes as MRI contrast agents for tracking stem cells

    NASA Astrophysics Data System (ADS)

    Vittorio, Orazio; Duce, Suzanne L.; Pietrabissa, Andrea; Cuschieri, Alfred

    2011-03-01

    In this study we investigate the potential of multiwall carbon nanotubes (MWCNTs) with low metal impurities (2.57% iron) as magnetic resonance imaging (MRI) contrast agents. Taking into account probable aggregation at high MWCNTs concentration analysis shows that the r2 relaxivity of MWCNTs in 1% agarose gels at 19 °C is 564 ± 41 s - 1 mM - 1; this is attributed to both the presence of iron oxide impurities and also to the carbon MWCNT structure itself. Stem cells were labelled with MWCNTs to demonstrate the effectiveness of MWCNTs as MRI contrast agents for cellular MRI. The MWCNTs did not impair cell viability or proliferation. These results suggest that the MRI contrast agent properties of the MWCNTs could be used in vivo for stem cell tracking/imaging and during MWCNT-mediated targeted electro-chemotherapy of tumours.

  17. A spatially-distributed computational model to quantify behaviour of contrast agents in MR perfusion imaging

    PubMed Central

    Cookson, A.N.; Lee, J.; Michler, C.; Chabiniok, R.; Hyde, E.; Nordsletten, D.; Smith, N.P.

    2014-01-01

    Contrast agent enhanced magnetic resonance (MR) perfusion imaging provides an early, non-invasive indication of defects in the coronary circulation. However, the large variation of contrast agent properties, physiological state and imaging protocols means that optimisation of image acquisition is difficult to achieve. This situation motivates the development of a computational framework that, in turn, enables the efficient mapping of this parameter space to provide valuable information for optimisation of perfusion imaging in the clinical context. For this purpose a single-compartment porous medium model of capillary blood flow is developed which is coupled with a scalar transport model, to characterise the behaviour of both blood-pool and freely-diffusive contrast agents characterised by their ability to diffuse through the capillary wall into the extra-cellular space. A parameter space study is performed on the nondimensionalised equations using a 2D model for both healthy and diseased myocardium, examining the sensitivity of system behaviour to Peclet number, Damköhler number (Da), diffusivity ratio and fluid porosity. Assuming a linear MR signal response model, sample concentration time series data are calculated, and the sensitivity of clinically-relevant properties of these signals to the model parameters is quantified. Both upslope and peak values display significant non-monotonic behaviour with regard to the Damköhler number, with these properties showing a high degree of sensitivity in the parameter range relevant to contrast agents currently in use. However, the results suggest that signal upslope is the more robust and discerning metric for perfusion quantification, in particular for correlating with perfusion defect size. Finally, the results were examined in the context of nonlinear signal response, flow quantification via Fermi deconvolution and perfusion reserve index, which demonstrated that there is no single best set of contrast agent parameters

  18. Clinical superiority of a new nonionic contrast agent (iopamidol) for cardiac angiography.

    PubMed

    Gertz, E W; Wisneski, J A; Chiu, D; Akin, J R; Hu, C

    1985-02-01

    The hemodynamic and electrophysiologic alterations induced by ionic contrast agents during cardiac angiography are well described. Recently nonionic contrast agents have become available for cardiac angiography. To evaluate the safety of these new agents, a double-blind randomized study was performed comparing a new nonionic agent (iopamidol) with a commonly used ionic contrast agent (Renografin-76). Eighty-one patients undergoing left ventriculography and coronary angiography were included; 41 received iopamidol and 40 received sodium meglumine diatrizoate (Renografin-76). After left ventriculography, there was a decrease in the arterial pressure with both contrast agents. However, the severity and the duration of hypotension were both significantly greater with Renografin-76 compared with the new nonionic agent (p less than 0.001). After selective injections of the coronary arteries, electrocardiographic analysis demonstrated that the increase in the QT interval (p less than 0.0002) and the changes in both the ST segment and T wave amplitude (p less than 0.001) were significantly greater in the Renografin-76 group compared with the iopamidol group. During coronary angiography, 8 of the 40 patients receiving Renografin-76 required temporary pacing for sinus pauses of 2.5 seconds or more, and 2 of the 40 also developed ventricular fibrillation. None of the 41 patients receiving iopamidol had these complications. This report demonstrates that the electrocardiographic changes, the severity and duration of hypotension and the incidence of serious arrhythmias are significantly greater with Renografin-76 than with iopamidol. Thus, this new nonionic agent appears to enhance the safety of cardiac angiography.

  19. Multifunctional magnetic-hollow gold nanospheres for bimodal cancer cell imaging and photothermal therapy.

    PubMed

    Bai, Ling-Yu; Yang, Xiao-Quan; An, Jie; Zhang, Lin; Zhao, Kai; Qin, Meng-Yao; Fang, Bi-Yun; Li, Cheng; Xuan, Yang; Zhang, Xiao-Shuai; Zhao, Yuan-Di; Ma, Zhi-Ya

    2015-08-01

    Multifunctional nanocomposites combining imaging and therapeutic functions have great potential for cancer diagnosis and therapy. In this work, we developed a novel theranostic agent based on hollow gold nanospheres (HGNs) and superparamagnetic iron oxide nanoparticles (SPIO). Taking advantage of the excellent magnetic properties of SPIO and strong near-infrared (NIR) absorption property of HGNs, such nanocomposites were applied to targeted magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) of cancer cells. In vitro results demonstrated they displayed significant contrast enhancement for T2-weighted MRI and strong PAI signal enhancement. Simultaneously, the nanocomposites exhibited a high photothermal effect under the irradiation of the near-infrared laser and can be used as efficient photothermal therapy (PTT) agents for selective killing of cancer cells. All these results indicated that such nanocomposites combined with MRI-PAI and PTT functionality can have great potential for effective cancer diagnosis and therapy.

  20. Multifunctional magnetic-hollow gold nanospheres for bimodal cancer cell imaging and photothermal therapy

    NASA Astrophysics Data System (ADS)

    Bai, Ling-Yu; Yang, Xiao-Quan; An, Jie; Zhang, Lin; Zhao, Kai; Qin, Meng-Yao; Fang, Bi-Yun; Li, Cheng; Xuan, Yang; Zhang, Xiao-Shuai; Zhao, Yuan-Di; Ma, Zhi-Ya

    2015-08-01

    Multifunctional nanocomposites combining imaging and therapeutic functions have great potential for cancer diagnosis and therapy. In this work, we developed a novel theranostic agent based on hollow gold nanospheres (HGNs) and superparamagnetic iron oxide nanoparticles (SPIO). Taking advantage of the excellent magnetic properties of SPIO and strong near-infrared (NIR) absorption property of HGNs, such nanocomposites were applied to targeted magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) of cancer cells. In vitro results demonstrated they displayed significant contrast enhancement for T2-weighted MRI and strong PAI signal enhancement. Simultaneously, the nanocomposites exhibited a high photothermal effect under the irradiation of the near-infrared laser and can be used as efficient photothermal therapy (PTT) agents for selective killing of cancer cells. All these results indicated that such nanocomposites combined with MRI-PAI and PTT functionality can have great potential for effective cancer diagnosis and therapy.

  1. Gadolinium-complexed Aβ-binding contrast agents for MRI diagnosis of Alzheimer's Disease.

    PubMed

    Matharu, Balpreet; Spencer, Nick; Howe, Franklyn; Austen, Brian

    2015-10-01

    MRI contrast agents, containing peptide sequences that bind β-amyloid and gadolinium ions ligated to DOTA have been synthesized for evaluation in early diagnosis of Alzheimer's Disease in transgenic mice models. A number of brain penetration modifications were incorporated and sufficient amounts of contrast agent in the brain were achieved only by addition of a cationic cell penetration sequence along with the use of microparticle assisted ultrasound activation. In the T1 mode of a MRI scan, the peptide (R2) illuminated areas of brain rich in amyloid plaques.

  2. Intradermal administration of fluorescent contrast agents for delivery to axillary lymph nodes

    NASA Astrophysics Data System (ADS)

    Rasmussen, John C.; Meric-Berstam, Funda; Krishnamurthy, Savitri; Tan, I.-Chih; Zhu, Banghe; Wagner, Jamie L.; Babiera, Gildy V.; Mittendorf, Elizabeth A.; Sevick-Muraca, Eva M.

    2014-05-01

    In this proof-of-concept study we seek to demonstrate the delivery of fluorescent contrast agent to the tumor-draining lymph node basin following intraparenchymal breast injections and intradermal arm injection of micrograms of indocyanine green in 20 breast cancer patients undergoing complete axillary lymph node dissection. Individual lymph nodes were assessed ex vivo for presence of fluorescent signal. In all, 88% of tumor-negative lymph nodes and 81% of tumor-positive lymph nodes were fluorescent. These results indicate that future studies utilizing targeted fluorescent contrast agents may demonstrate improved surgical and therapeutic intervention.

  3. [Case of the month. Acute generalized exanthematous pustulosis due to an iodinated contrast radiodiagnostic agent].

    PubMed

    Paquet, P; Vandenbossche, G; Nikkels, A F; Henry, F; Piérard, G E

    2009-12-01

    Iodinated contrast agents are frequently involved in delayed polymorphic adverse skin reactions. Acute generalized exanthematous pustulosis following administration of iodinated contrast agents is a rare but severe form of such reactions. The disease is characterized by the sudden occurrence of an erosive and pustular erythroderma with fever, leukocytosis and sometimes peripheral adenopathies and liver involvement. This condition is considered as an immunologic reaction, primarily involving T lymphocytes. The overall mortality reaches about 1%. Elucidating the differential diagnosis with other acute paroxysmal drug eruptions (toxic epidermal necrolysis, Steven-Johnson syndrome and drug hypersensitivity syndrome) is of paramount importance for establishing the adequate treatment of PEAG.

  4. A new bifunctional hybrid nanostructure as an active platform for photothermal therapy and MR imaging.

    PubMed

    Khafaji, Mona; Vossoughi, Manouchehr; Hormozi-Nezhad, M Reza; Dinarvand, Rassoul; Börrnert, Felix; Irajizad, Azam

    2016-01-01

    As a bi-functional cancer treatment agent, a new hybrid nanostructure is presented which can be used for photothermal therapy by exposure to one order of magnitude lower laser powers compared to similar nanostructures in addition to substantial enhancment in magnetic resonance imaging (MRI) contrast. This gold-iron oxide hybrid nanostructure (GIHN) is synthesized by a cost-effective and high yield water-based approach. The GIHN is sheilded by PEG. Therefore, it shows high hemo and biocompatibility and more than six month stability. Alongside earlier nanostructures, the heat generation rate of GIHN is compareable with surfactnat-capped gold nanorods (GNRs). Two reasons are behind this enhancement: Firstly the distance between GNRs and SPIONs is adjusted in a way that the surface plasmon resonance of the new nanostructure is similar to bare GNRs and secondly the fraction of GNRs is raised in the hybrid nanostructure. GIHN is then applied as a photothermal agent using laser irradiation with power as low as 0.5 W.cm(-2) and only 32% of human breast adenocarcinoma cells could survive. The GIHN also acts as a dose-dependent transvers relaxation time (T2) MRI contrast agent. The results show that the GINH can be considered as a good candidate for multimodal photothermal therapy and MRI. PMID:27297588

  5. A new bifunctional hybrid nanostructure as an active platform for photothermal therapy and MR imaging

    PubMed Central

    Khafaji, Mona; Vossoughi, Manouchehr; Hormozi-Nezhad, M. Reza; Dinarvand, Rassoul; Börrnert, Felix; Irajizad, Azam

    2016-01-01

    As a bi-functional cancer treatment agent, a new hybrid nanostructure is presented which can be used for photothermal therapy by exposure to one order of magnitude lower laser powers compared to similar nanostructures in addition to substantial enhancment in magnetic resonance imaging (MRI) contrast. This gold-iron oxide hybrid nanostructure (GIHN) is synthesized by a cost-effective and high yield water-based approach. The GIHN is sheilded by PEG. Therefore, it shows high hemo and biocompatibility and more than six month stability. Alongside earlier nanostructures, the heat generation rate of GIHN is compareable with surfactnat-capped gold nanorods (GNRs). Two reasons are behind this enhancement: Firstly the distance between GNRs and SPIONs is adjusted in a way that the surface plasmon resonance of the new nanostructure is similar to bare GNRs and secondly the fraction of GNRs is raised in the hybrid nanostructure. GIHN is then applied as a photothermal agent using laser irradiation with power as low as 0.5 W.cm−2 and only 32% of human breast adenocarcinoma cells could survive. The GIHN also acts as a dose-dependent transvers relaxation time (T2) MRI contrast agent. The results show that the GINH can be considered as a good candidate for multimodal photothermal therapy and MRI. PMID:27297588

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

    PubMed

    Croisille, Pierre; Revel, Didier; Saeed, Maythem

    2006-09-01

    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. PMID:16633792

  7. Combined ultrasound and photoacoustic imaging of pancreatic cancer using nanocage contrast agents

    NASA Astrophysics Data System (ADS)

    Homan, Kimberly; Shah, Jignesh; Gomez, Sobeyda; Gensler, Heidi; Karpiouk, Andrei; Brannon-Peppas, L.; Emelianov, Stanislav

    2009-02-01

    A new metallodielectric nanoparticle consisting of a silica core and silver outer cage was developed for the purpose of enhancing photoacoustic imaging contrast in pancreatic tissue. These nanocages were injected into an ex vivo porcine pancreas and imaged using a combined photoacoustic and ultrasound (PAUS) assembly. This custom-designed PAUS assembly delivered 800 nm light through a fiber optical light delivery system integrated with 128 element linear array transducer operating at 7.5 MHz center frequency. Imaging results prove that the nanocage contrast agents have the ability to enhance photoacoustic imaging contrast. Furthermore, the value of the combined PAUS imaging modality was demonstrated as the location of nanocages against background native tissue was evident. Future applications of these nanocage contrast agents could include targeting them to pancreatic cancer for enhancement of photoacoustic imaging for diagnosis and therapy.

  8. Improved sensitivity of computed tomography towards iodine and gold nanoparticle contrast agents via iterative reconstruction methods

    PubMed Central

    Bernstein, Ally Leigh; Dhanantwari, Amar; Jurcova, Martina; Cheheltani, Rabee; Naha, Pratap Chandra; Ivanc, Thomas; Shefer, Efrat; Cormode, David Peter

    2016-01-01

    Computed tomography is a widely used medical imaging technique that has high spatial and temporal resolution. Its weakness is its low sensitivity towards contrast media. Iterative reconstruction techniques (ITER) have recently become available, which provide reduced image noise compared with traditional filtered back-projection methods (FBP), which may allow the sensitivity of CT to be improved, however this effect has not been studied in detail. We scanned phantoms containing either an iodine contrast agent or gold nanoparticles. We used a range of tube voltages and currents. We performed reconstruction with FBP, ITER and a novel, iterative, modal-based reconstruction (IMR) algorithm. We found that noise decreased in an algorithm dependent manner (FBP > ITER > IMR) for every scan and that no differences were observed in attenuation rates of the agents. The contrast to noise ratio (CNR) of iodine was highest at 80 kV, whilst the CNR for gold was highest at 140 kV. The CNR of IMR images was almost tenfold higher than that of FBP images. Similar trends were found in dual energy images formed using these algorithms. In conclusion, IMR-based reconstruction techniques will allow contrast agents to be detected with greater sensitivity, and may allow lower contrast agent doses to be used. PMID:27185492

  9. Improved sensitivity of computed tomography towards iodine and gold nanoparticle contrast agents via iterative reconstruction methods

    NASA Astrophysics Data System (ADS)

    Bernstein, Ally Leigh; Dhanantwari, Amar; Jurcova, Martina; Cheheltani, Rabee; Naha, Pratap Chandra; Ivanc, Thomas; Shefer, Efrat; Cormode, David Peter

    2016-05-01

    Computed tomography is a widely used medical imaging technique that has high spatial and temporal resolution. Its weakness is its low sensitivity towards contrast media. Iterative reconstruction techniques (ITER) have recently become available, which provide reduced image noise compared with traditional filtered back-projection methods (FBP), which may allow the sensitivity of CT to be improved, however this effect has not been studied in detail. We scanned phantoms containing either an iodine contrast agent or gold nanoparticles. We used a range of tube voltages and currents. We performed reconstruction with FBP, ITER and a novel, iterative, modal-based reconstruction (IMR) algorithm. We found that noise decreased in an algorithm dependent manner (FBP > ITER > IMR) for every scan and that no differences were observed in attenuation rates of the agents. The contrast to noise ratio (CNR) of iodine was highest at 80 kV, whilst the CNR for gold was highest at 140 kV. The CNR of IMR images was almost tenfold higher than that of FBP images. Similar trends were found in dual energy images formed using these algorithms. In conclusion, IMR-based reconstruction techniques will allow contrast agents to be detected with greater sensitivity, and may allow lower contrast agent doses to be used.

  10. Improved sensitivity of computed tomography towards iodine and gold nanoparticle contrast agents via iterative reconstruction methods.

    PubMed

    Bernstein, Ally Leigh; Dhanantwari, Amar; Jurcova, Martina; Cheheltani, Rabee; Naha, Pratap Chandra; Ivanc, Thomas; Shefer, Efrat; Cormode, David Peter

    2016-05-17

    Computed tomography is a widely used medical imaging technique that has high spatial and temporal resolution. Its weakness is its low sensitivity towards contrast media. Iterative reconstruction techniques (ITER) have recently become available, which provide reduced image noise compared with traditional filtered back-projection methods (FBP), which may allow the sensitivity of CT to be improved, however this effect has not been studied in detail. We scanned phantoms containing either an iodine contrast agent or gold nanoparticles. We used a range of tube voltages and currents. We performed reconstruction with FBP, ITER and a novel, iterative, modal-based reconstruction (IMR) algorithm. We found that noise decreased in an algorithm dependent manner (FBP > ITER > IMR) for every scan and that no differences were observed in attenuation rates of the agents. The contrast to noise ratio (CNR) of iodine was highest at 80 kV, whilst the CNR for gold was highest at 140 kV. The CNR of IMR images was almost tenfold higher than that of FBP images. Similar trends were found in dual energy images formed using these algorithms. In conclusion, IMR-based reconstruction techniques will allow contrast agents to be detected with greater sensitivity, and may allow lower contrast agent doses to be used.

  11. Single-walled carbon nanotubes as a multimodal — thermoacoustic and photoacoustic — contrast agent

    PubMed Central

    Pramanik, Manojit; Swierczewska, Magdalena; Green, Danielle; Sitharaman, Balaji; Wang, Lihong V.

    2009-01-01

    We have developed a novel carbon nanotube-based contrast agent for both thermoacoustic and photoacoustic tomography. In comparison with de-ionized water, single-walled carbon nanotubes exhibited more than two-fold signal enhancement for thermoacoustic tomography at 3 GHz. In comparison with blood, they exhibited more than six-fold signal enhancement for photoacoustic tomography at 1064 nm wavelength. The large contrast enhancement of single-walled carbon nanotubes was further corroborated by tissue phantom imaging studies. PMID:19566311

  12. Real-time phase-contrast imaging of photothermal treatment of head and neck squamous cell carcinoma: an in vitro study of macrophages as a vector for the delivery of gold nanoshells

    NASA Astrophysics Data System (ADS)

    Yang, Taeseok Daniel; Choi, Wonshik; Yoon, Tai Hyun; Lee, Kyoung Jin; Lee, Jae-Seung; Han, Sang Hun; Lee, Min-Goo; Yim, Hong Soon; Choi, Kyung Min; Park, Min Woo; Jung, Kwang-Yoon; Baek, Seung-Kuk

    2012-12-01

    Photothermal treatment (PTT) using nanoparticles has gained attention as a promising alternative therapy for malignant tumors. One strategy for increasing the selectivity of PTT is the use of macrophages as a cellular vector for delivering nanoparticles. The aim of the present study is to examine the use of macrophages as a cellular vector for efficient PTT and determine the appropriate irradiation power and time of a near-infrared (NIR) laser using real-time phase-contrast imaging. Thermally induced injury and death of cancer cells were found to begin at 44°C to 45°C, which was achieved using the PTT effect with gold nanoshells (NS) and irradiation with a NIR laser at a power of 2 W for 5 min. The peritoneal macrophage efficiently functioned as a cellular vector for the NS, and the cancer cells surrounding the NS-loaded macrophages selectively lost their cellular viability after being irradiated with the NIR laser.

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

    NASA Astrophysics Data System (ADS)

    Laoui, Samir

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

  14. Specific binding of molecularly targeted agents to pancreas tumors and impact on observed optical contrast

    NASA Astrophysics Data System (ADS)

    Samkoe, Kimberley S.; Hextrum, Shannon K.; Pardesi, Omar; O'Hara, Julia A.; Hasan, Tayyaba; Pogue, Brian W.

    2010-02-01

    In optical imaging it is thought that optimum tumor contrast can be achieved with the use of small-labeled molecular tracers that have high affinity to their targets and fast clearance rates from the blood stream and healthy tissues. An example of this is fluorescently tagged EGF to monitor the molecular activity of tumors, such as pancreatic cancer. Extensive fluorescence contrast analysis for fluorescence molecular tomography has been performed on the AsPC-1 pancreas tumor, grown orthotopically in mice; yet, the binding dynamics of the EGF-fluorescent agent in vivo is not completely known. The bulk pancreatic tumor displays 3:1 contrast relative to the normal pancreas at long times after injection; however, even higher levels of fluorescence in the liver, kidney and intestine suggest that molecular specificity for the tumor may be low. Mice were administered a fluorescently labeled EGF agent and were sacrificed at various time points post-injection. To analyze the amount of specific binding at each time point frozen tissue samples were fluorescently imaged, washed with saline to remove the interstitially distributed contrast agent, and then imaged again. This technique demonstrated that approximately ~10% of the molecular target was firmly bound to the cell, while 90% was mobile or unbound. This low binding ratio suggests that the contrast observed is from inherent properties of the tumor (i.e. enhanced permeability and retention effect) and not from specific bound contrast as previously anticipated. The use of EGF contrast agents in MRI-guided fluorescence tomography and the impact of low binding specificity are discussed.

  15. Absolute perfusion measurements and associated iodinated contrast agent time course in brain metastasis: a study for contrast-enhanced radiotherapy.

    PubMed

    Obeid, Layal; Deman, Pierre; Tessier, Alexandre; Balosso, Jacques; Estève, François; Adam, Jean-François

    2014-04-01

    Contrast-enhanced radiotherapy is an innovative treatment that combines the selective accumulation of heavy elements in tumors with stereotactic irradiations using medium energy X-rays. The radiation dose enhancement depends on the absolute amount of iodine reached in the tumor and its time course. Quantitative, postinfusion iodine biodistribution and associated brain perfusion parameters were studied in human brain metastasis as key parameters for treatment feasibility and quality. Twelve patients received an intravenous bolus of iodinated contrast agent (CA) (40 mL, 4 mL/s), followed by a steady-state infusion (160 mL, 0.5 mL/s) to ensure stable intratumoral amounts of iodine during the treatment. Absolute iodine concentrations and quantitative perfusion maps were derived from 40 multislice dynamic computed tomography (CT) images of the brain. The postinfusion mean intratumoral iodine concentration (over 30 minutes) reached 1.94 ± 0.12 mg/mL. Reasonable correlations were obtained between these concentrations and the permeability surface area product and the cerebral blood volume. To our knowledge, this is the first quantitative study of CA biodistribution versus time in brain metastasis. The study shows that suitable and stable amounts of iodine can be reached for contrast-enhanced radiotherapy. Moreover, the associated perfusion measurements provide useful information for the patient recruitment and management processes.

  16. Hypoxia targeted carbon nanotubes as a sensitive contrast agent for photoacoustic imaging of tumors

    NASA Astrophysics Data System (ADS)

    Zanganeh, Saeid; Aguirre, Andres; Biswal, Nrusingh C.; Pavlik, Christopher; Smith, Michael B.; Alqasemi, Umar; Li, Hai; Zhu, Quing

    2011-03-01

    Development of new and efficient contrast agents is of fundamental importance to improve detection sensitivity of smaller lesions. Within the family of nanomaterials, carbon nanotubes (CNT) not only have emerged as a new alternative and efficient transporter and translocater of therapeutic molecules but also as a photoacoustic molecular imaging agent owing to its strong optical absorption in the near-infrared region. Drugs, Antibodies and nucleic acids could functionalize the CNT and prepare an appropriate system for delivering the cargos to cells and organs. In this work, we present a novel photoacoustic contrast agent which is based on a unique hypoxic marker in the near infrared region, 2-nitroimidazole -bis carboxylic acid derivative of Indocyanine Green conjugated to single walled carbon nanotube (SWCNT-2nitroimidazole-ICG). The 2-nitroimidazole-ICG has an absorption peak at 755 nm and an extinction coefficient of 20,5222 M-1cm-1. The conjugation of this marker with SWCNT shows more than 25 times enhancement of optical absorption of carbon nanotubes in the near infrared region. This new conjugate has been optically evaluated and shows promising results for high contrast photoacoustic imaging of deeply located tumors. The conjugate specifically targets tumor hypoxia, an important indicator of tumor metabolism and tumor therapeutic response. The detection sensitivity of the new contrast agent has been evaluated in-vitro cell lines and with in-vivo tumors in mice.

  17. In vivo small animal micro-CT using nanoparticle contrast agents

    PubMed Central

    Ashton, Jeffrey R.; West, Jennifer L.; Badea, Cristian T.

    2015-01-01

    Computed tomography (CT) is one of the most valuable modalities for in vivo imaging because it is fast, high-resolution, cost-effective, and non-invasive. Moreover, CT is heavily used not only in the clinic (for both diagnostics and treatment planning) but also in preclinical research as micro-CT. Although CT is inherently effective for lung and bone imaging, soft tissue imaging requires the use of contrast agents. For small animal micro-CT, nanoparticle contrast agents are used in order to avoid rapid renal clearance. A variety of nanoparticles have been used for micro-CT imaging, but the majority of research has focused on the use of iodine-containing nanoparticles and gold nanoparticles. Both nanoparticle types can act as highly effective blood pool contrast agents or can be targeted using a wide variety of targeting mechanisms. CT imaging can be further enhanced by adding spectral capabilities to separate multiple co-injected nanoparticles in vivo. Spectral CT, using both energy-integrating and energy-resolving detectors, has been used with multiple contrast agents to enable functional and molecular imaging. This review focuses on new developments for in vivo small animal micro-CT using novel nanoparticle probes applied in preclinical research. PMID:26581654

  18. Functional Hyperbranched Polylysine as Potential Contrast Agent Probes for Magnetic Resonance Imaging.

    PubMed

    Zu, Guangyue; Liu, Min; Zhang, Kunchi; Hong, Shanni; Dong, Jingjin; Cao, Yi; Jiang, Bin; Luo, Liqiang; Pei, Renjun

    2016-06-13

    Researchers have never stopped questing contrast agents with high resolution and safety to overcome the drawbacks of small-molecule contrast agents in clinic. Herein, we reported the synthesis of gadolinium-based hyperbranched polylysine (HBPLL-DTPA-Gd), which was prepared by thermal polymerization of l-lysine via one-step polycondensation. After conjugating with folic acid, its potential application as MRI contrast agent was then evaluated. This contrast agent had no obvious cytotoxicity as verified by WST assay and H&E analysis. Compared to Gd(III)-diethylenetriaminepentaacetic acid (Gd-DTPA) (r1 = 4.3 mM(-1) s(-1)), the FA-HBPLL-DTPA-Gd exhibited much higher longitudinal relaxivity value (r1 = 13.44 mM(-1) s(-1)), up to 3 times higher than Gd-DTPA. The FA-HBPLL-DTPA-Gd showed significant signal intensity enhancement in the tumor region at various time points and provided a long time window for MR examination. The results illustrate that FA-HBPLL-DTPA-Gd will be a potential candidate for tumor-targeted MRI. PMID:27187578

  19. CoCEST: cobalt(II) amide-appended paraCEST MRI contrast agents.

    PubMed

    Dorazio, Sarina J; Olatunde, Abiola O; Spernyak, Joseph A; Morrow, Janet R

    2013-11-01

    The first examples of air-stable Co(II) paraCEST MRI contrast agents are reported. Amide NH protons on the complexes give rise to CEST peaks that are shifted up to 112 ppm from the bulk water resonance. One complex has multiple CEST peaks that may be useful for ratiometric mapping of pH.

  20. An efficient nano-based theranostic system for multi-modal imaging-guided photothermal sterilization in gastrointestinal tract.

    PubMed

    Liu, Zhen; Liu, Jianhua; Wang, Rui; Du, Yingda; Ren, Jinsong; Qu, Xiaogang

    2015-07-01

    Since understanding the healthy status of gastrointestinal tract (GI tract) is of vital importance, clinical implementation for GI tract-related disease have attracted much more attention along with the rapid development of modern medicine. Here, a multifunctional theranostic system combining X-rays/CT/photothermal/photoacoustic mapping of GI tract and imaging-guided photothermal anti-bacterial treatment is designed and constructed. PEGylated W18O49 nanosheets (PEG-W18O49) are created via a facile solvothermal method and an in situ probe-sonication approach. In terms of excellent colloidal stability, low cytotoxicity, and neglectable hemolysis of PEG-W18O49, we demonstrate the first example of high-performance four-modal imaging of GI tract by using these nanosheets as contrast agents. More importantly, due to their intrinsic absorption of NIR light, glutaraldehyde-modified PEG-W18O49 are successfully applied as fault-free targeted photothermal agents for imaging-guided killing of bacteria on a mouse infection model. Critical to pre-clinical and clinical prospects, long-term toxicity is further investigated after oral administration of these theranostic agents. These kinds of tungsten-based nanomaterials exhibit great potential as multi-modal contrast agents for directed visualization of GI tract and anti-bacterial agents for phothothermal sterilization. PMID:25934293

  1. Evaluation of a targeted nanobubble ultrasound contrast agent for potential tumor imaging

    NASA Astrophysics Data System (ADS)

    Li, Chunfang; Shen, Chunxu; Liu, Haijuan; Wu, Kaizhi; Zhou, Qibing; Ding, Mingyue

    2015-03-01

    Targeted nanobubbles have been reported to improve the contrast effect of ultrasound imaging due to the enhanced permeation and retention effects at tumor vascular leaks. In this work, the contrast enhancement abilities and the tumor targeting potential of a self-made VEGFR2-targeted nanobubble ultrasound contrast agent was evaluated in-vitro and in-vivo. Size distribution and zeta potential were assessed. Then the contrast-enhanced ultrasound imaging of the VEGFR2 targeted nanobubbles were evaluated with a custom-made experimental apparatus and in normal Wistar rats. Finally, the in-vivo tumor-targeting ability was evaluated on nude mice with subcutaneous tumor. The results showed that the target nanobubbles had uniform distribution with the average diameter of 208.1 nm, polydispersity index (PDI) of 0.411, and zeta potential of -13.21 mV. Significant contrast enhancement was observed in both in-vitro and in-vivo ultrasound imaging, demonstrating that the self-made target nanobubbles can enhance the contrast effect of ultrasound imaging efficiently. Targeted tumor imaging showed less promising result, due to the fact that the targeted nanobubbles arriving and permeating through tumor vessels were not many enough to produce significant enhancement. Future work will focus on exploring new imaging algorithm which is sensitive to targeted nanobubbles, so as to correctly detect the contrast agent, particularly at a low bubble concentration.

  2. Liposomes loaded with hydrophilic magnetite nanoparticles: Preparation and application as contrast agents for magnetic resonance imaging.

    PubMed

    German, S V; Navolokin, N A; Kuznetsova, N R; Zuev, V V; Inozemtseva, O A; Anis'kov, A A; Volkova, E K; Bucharskaya, A B; Maslyakova, G N; Fakhrullin, R F; Terentyuk, G S; Vodovozova, E L; Gorin, D A

    2015-11-01

    Magnetic fluid-loaded liposomes (MFLs) were fabricated using magnetite nanoparticles (MNPs) and natural phospholipids via the thin film hydration method followed by extrusion. The size distribution and composition of MFLs were studied using dynamic light scattering and spectrophotometry. The effective ranges of magnetite concentration in MNPs hydrosol and MFLs for contrasting at both T2 and T1 relaxation were determined. On T2 weighted images, the MFLs effectively increased the contrast if compared with MNPs hydrosol, while on T1 weighted images, MNPs hydrosol contrasting was more efficient than that of MFLs. In vivo magnetic resonance imaging (MRI) contrasting properties of MFLs and their effects on tumor and normal tissues morphology, were investigated in rats with transplanted renal cell carcinoma upon intratumoral administration of MFLs. No significant morphological changes in rat internal organs upon intratumoral injection of MFLs were detected, suggesting that the liposomes are relatively safe and can be used as the potential contrasting agents for MRI.

  3. Development of nanostars as a biocompatible tumor contrast agent: toward in vivo SERS imaging.

    PubMed

    D'Hollander, Antoine; Mathieu, Evelien; Jans, Hilde; Vande Velde, Greetje; Stakenborg, Tim; Van Dorpe, Pol; Himmelreich, Uwe; Lagae, Liesbet

    2016-01-01

    The need for sensitive imaging techniques to detect tumor cells is an important issue in cancer diagnosis and therapy. Surface-enhanced Raman scattering (SERS), realized by chemisorption of compounds suitable for Raman spectroscopy onto gold nanoparticles, is a new method for detecting a tumor. As a proof of concept, we studied the use of biocompatible gold nanostars as sensitive SERS contrast agents targeting an ovarian cancer cell line (SKOV3). Due to a high intracellular uptake of gold nanostars after 6 hours of exposure, they could be detected and located with SERS. Using these nanostars for passive targeting after systemic injection in a xenograft mouse model, a detectable signal was measured in the tumor and liver in vivo. These signals were confirmed by ex vivo SERS measurements and darkfield microscopy. In this study, we established SERS nanostars as a highly sensitive contrast agent for tumor detection, which opens the potential for their use as a theranostic agent against cancer. PMID:27536107

  4. Development of nanostars as a biocompatible tumor contrast agent: toward in vivo SERS imaging

    PubMed Central

    D’Hollander, Antoine; Mathieu, Evelien; Jans, Hilde; Vande Velde, Greetje; Stakenborg, Tim; Van Dorpe, Pol; Himmelreich, Uwe; Lagae, Liesbet

    2016-01-01

    The need for sensitive imaging techniques to detect tumor cells is an important issue in cancer diagnosis and therapy. Surface-enhanced Raman scattering (SERS), realized by chemisorption of compounds suitable for Raman spectroscopy onto gold nanoparticles, is a new method for detecting a tumor. As a proof of concept, we studied the use of biocompatible gold nanostars as sensitive SERS contrast agents targeting an ovarian cancer cell line (SKOV3). Due to a high intracellular uptake of gold nanostars after 6 hours of exposure, they could be detected and located with SERS. Using these nanostars for passive targeting after systemic injection in a xenograft mouse model, a detectable signal was measured in the tumor and liver in vivo. These signals were confirmed by ex vivo SERS measurements and darkfield microscopy. In this study, we established SERS nanostars as a highly sensitive contrast agent for tumor detection, which opens the potential for their use as a theranostic agent against cancer. PMID:27536107

  5. Angiofil: a novel radio-contrast agent for post-mortem micro-angiography

    NASA Astrophysics Data System (ADS)

    Grabherr, Silke; Dominietto, Marco; Yu, Lisa; Djonov, Valentin; Müller, Bert; Friess, Sebastian

    2008-08-01

    The radio-contrast agent Angiofil has recently been developed to be predominantely applied in forensic medicine. Angiofil is a liquid radio-contrast agent based on iodine. Its viscosity is easy to adjust by the choice and the concentration of the solvent. Therefore, it is well suited for penetrating vessels of different diameters. The liquid Angiofil avoids the sedimentation of suspensions containing radio-opaque materials such as barium sulfate. The injection of Angiofil into the vascular system of mice post-mortem results in remarkable data showing the vascular trees of tissues and entire organs. Penetration into the surrounding tissue was not observed. Consequently, Angiofil has the potential to reach the performance of the established casting agent Microfil.

  6. Alk5 inhibition increases delivery of macromolecular and protein-bound contrast agents to tumors

    PubMed Central

    Daldrup-Link, Heike E.; Mohanty, Suchismita; Ansari, Celina; Ito, Ken; Hong, Su Hyun; Hoffmann, Matthias; Pisani, Laura; Boudreau, Nancy; Gambhir, Sanjiv Sam; Coussens, Lisa M.

    2016-01-01

    Limited transendothelial permeability across tumor microvessels represents a significant bottleneck in the development of tumor-specific diagnostic agents and theranostic drugs. Here, we show an approach to increase transendothelial permeability of macromolecular and nanoparticle-based contrast agents via inhibition of the type I TGF-β receptor, activin-like kinase 5 (Alk5), in tumors. Alk5 inhibition significantly increased tumor contrast agent delivery and enhancement on imaging studies, while healthy organs remained relatively unaffected. Imaging data correlated with significantly decreased tumor interstitial fluid pressure, while tumor vascular density remained unchanged. This immediately clinically translatable concept involving Alk5 inhibitor pretreatment prior to an imaging study could be leveraged for improved tumor delivery of macromolecular and nanoparticle-based imaging probes and, thereby, facilitate development of more sensitive imaging tests for cancer diagnosis, enhanced tumor characterization, and personalized, image-guided therapies. PMID:27182558

  7. Preparation of near-infrared-labeled targeted contrast agents for clinical translation

    NASA Astrophysics Data System (ADS)

    Olive, D. Michael

    2011-03-01

    Targeted fluorophore-labeled contrast agents are moving toward translation to human surgical use. To prepare for future clinical use, we examined the performance of potential ligands targeting the epidermal growth factor receptor, α5β3 integrins, and GLUT transporters for their suitability as directed contrast agents. Each agent was labeled with IRDye 800CW, and near-infrared dye with excitation/emission wavelengths of 789/805 nm, which we determined had favorable toxicity characteristics. The probe molecules examined consisted of Affibodies, nanobodies, peptides, and the sugar 2-deoxy-D-glucose. Each probe was tested for specific and non-specific binding in cell based assays. All probe types showed good performance in mouse models for detecting either spontaneous tumors or tumor xenografts in vivo. Each of the probes tested show promise for future human clinical studies.

  8. Small animal imaging platform for quantitative assessment of short-wave infrared-emitting contrast agents

    NASA Astrophysics Data System (ADS)

    Hu, Philip; Mingozzi, Marco; Higgins, Laura M.; Ganapathy, Vidya; Zevon, Margot; Riman, Richard E.; Roth, Charles M.; Moghe, Prabhas V.; Pierce, Mark C.

    2015-03-01

    We report the design, calibration, and testing of a pre-clinical small animal imaging platform for use with short-wave infrared (SWIR) emitting contrast agents. Unlike materials emitting at visible or near-infrared wavelengths, SWIR-emitting agents require detection systems with sensitivity in the 1-2 μm wavelength region, beyond the range of commercially available small animal imagers. We used a collimated 980 nm laser beam to excite rare-earth-doped NaYF4:Er,Yb nanocomposites, as an example of a SWIR emitting material under development for biomedical imaging applications. This beam was raster scanned across the animal, with fluorescence in the 1550 nm wavelength region detected by an InGaAs area camera. Background adjustment and intensity non-uniformity corrections were applied in software. The final SWIR fluorescence image was overlaid onto a standard white-light image for registration of contrast agent uptake with respect to anatomical features.

  9. Pineapple juice as a negative oral contrast agent in magnetic resonance cholangiopancreatography: a preliminary evaluation.

    PubMed

    Riordan, R D; Khonsari, M; Jeffries, J; Maskell, G F; Cook, P G

    2004-12-01

    The quality of magnetic resonance cholangiopancreatography (MRCP) images is frequently degraded by high signal from the gastrointestinal tract. The aim of this study is to evaluate pineapple juice (PJ) as an oral negative contrast agent in MRCP. Preliminary in vitro evaluation demonstrated that PJ shortened T(2) relaxation time and hence decreased T(2) signal intensity on a standard MRCP sequence to a similar degree to a commercially available negative contrast agent (ferumoxsil). Electrothermal atomic absorption spectrometry assay demonstrated a high manganese concentration in PJ of 2.76 mg dl(-1), which is likely to be responsible for its T(2) imaging properties. MRCP was subsequently performed in 10 healthy volunteers, before and at 15 min and 30 min following ingestion of 400 ml of PJ. Images were assessed blindly by two Consultant Radiologists using a standard grading technique based on contrast effect (degree of suppression of bowel signal), and image effect (diagnostic quality). There were statistically significant improvements in contrast and image effect between pre and post PJ images. There was particularly significant improvement in visualization of the pancreatic duct, but no significant difference between 15 min and 30 min post PJ images. Visualization of the ampulla, common bile duct, common hepatic and central intrahepatic ducts were also significantly improved at 15 min following PJ. Our results demonstrate that PJ, may be used as an alternative to commercially available negative oral contrast agent in MRCP.

  10. Iron-Based Superparamagnetic Nanoparticle Contrast Agents for MRI of Infection and Inflammation

    PubMed Central

    Neuwelt, Alexander; Sidhu, Navneet; Hu, Chien-An A.; Mlady, Gary; Eberhardt, Steven C.; Sillerud, Laurel O.

    2015-01-01

    OBJECTIVE In this article, we summarize the progress to date on the use of superparamagnetic iron oxide nanoparticles (SPIONs) as contrast agents for MRI of inflammatory processes. CONCLUSION Phagocytosis by macrophages of injected SPIONs results in a prolonged shortening of both T2 and T2* leading to hypointensity of macrophage-infiltrated tissues in contrast-enhanced MR images. SPIONs as contrast agents are therefore useful for the in vivo MRI detection of macrophage infiltration, and there is substantial research and clinical interest in the use of SPION-based contrast agents for MRI of infection and inflammation. This technique has been used to identify active infection in patients with septic arthritis and osteomyelitis; importantly, the MRI signal intensity of the tissue has been found to return to its un-enhanced value on successful treatment of the infection. In SPION contrast-enhanced MRI of vascular inflammation, animal studies have shown decreased macrophage uptake in atherosclerotic plaques after treatment with statin drugs. Human studies have shown that both coronary and carotid plaques that take up SPIONs are more prone to rupture and that abdominal aneurysms with increased SPION uptake are more likely to grow. Studies of patients with multiple sclerosis suggest that MRI using SPIONs may have increased sensitivity over gadolinium for plaque detection. Finally, SPIONs have enabled the tracking and imaging of transplanted stem cells in a recipient host. PMID:25714316

  11. Comparison of the optoacoustic signal generation efficiency of different nanoparticular contrast agents.

    PubMed

    Bost, Wolfgang; Lemor, Robert; Fournelle, Marc

    2012-11-20

    Optoacoustic imaging represents a new modality that allows noninvasive in vivo molecular imaging with optical contrast and acoustical resolution. Whereas structural or functional imaging applications such as imaging of vasculature do not require contrast enhancing agents, nanoprobes with defined biochemical binding behavior are needed for molecular imaging tasks. Since the contrast of this modality is based on the local optical absorption coefficient, all particle or molecule types that show significant absorption cross sections in the spectral range of the laser wavelength used for signal generation are suitable contrast agents. Currently, several particle types such as gold nanospheres, nanoshells, nanorods, or polymer particles are used as optoacoustic contrast agents. These particles have specific advantages with respect to their absorption properties, or in terms of biologically relevant features (biodegradability, binding to molecular markers). In the present study, a comparative analysis of the signal generation efficiency of gold nanorods, polymeric particles, and magnetite particles using a 1064 nm Nd:YAG laser for signal generation is described. PMID:23207315

  12. Comparison of the optoacoustic signal generation efficiency of different nanoparticular contrast agents.

    PubMed

    Bost, Wolfgang; Lemor, Robert; Fournelle, Marc

    2012-11-20

    Optoacoustic imaging represents a new modality that allows noninvasive in vivo molecular imaging with optical contrast and acoustical resolution. Whereas structural or functional imaging applications such as imaging of vasculature do not require contrast enhancing agents, nanoprobes with defined biochemical binding behavior are needed for molecular imaging tasks. Since the contrast of this modality is based on the local optical absorption coefficient, all particle or molecule types that show significant absorption cross sections in the spectral range of the laser wavelength used for signal generation are suitable contrast agents. Currently, several particle types such as gold nanospheres, nanoshells, nanorods, or polymer particles are used as optoacoustic contrast agents. These particles have specific advantages with respect to their absorption properties, or in terms of biologically relevant features (biodegradability, binding to molecular markers). In the present study, a comparative analysis of the signal generation efficiency of gold nanorods, polymeric particles, and magnetite particles using a 1064 nm Nd:YAG laser for signal generation is described.

  13. THE ANTIVASCULAR ACTION OF PHYSIOTHERAPY ULTRASOUND ON A MURINE TUMOR: ROLE OF A MICROBUBBLE CONTRAST AGENT

    PubMed Central

    Wood, Andrew K. W.; Bunte, Ralph M.; Cohen, Jennie D.; Tsai, Jeff H.; Lee, William M-F.; Sehgal, Chandra M.

    2008-01-01

    This study investigated whether a microbubble-containing ultrasound contrast agent had a role in the antivascular action of physiotherapy ultrasound on tumor neovasculature. Ultrasound images (B-mode and contrast-enhanced power Doppler [0.02mL Definity]) were made of 22 murine melanomas (K173522). The tumor was insonated (ISATA = 1.7 W cm−2, 1 MHz, continuous output) for 3 min and the power Doppler observations of the pre- and post-insonation tumor vascularities were analyzed. Significant reductions (p = 0.005 for analyses of color weighted fractional area) in vascularity occurred when a contrast-enhanced power Doppler study occurred prior to insonation. Vascularity was unchanged in tumors without a pre-therapy Doppler study. Histological studies revealed tissue structural changes that correlated with the ultrasound findings. The underlying etiology of the interaction between the physiotherapy ultrasound beam, the microbubble-containing contrast agent and the tumor neovasculature is unknown. It was concluded that contrast agents play an important role in the antivascular effects induced by physiotherapy ultrasound. PMID:17720299

  14. Near-infrared dye-loaded magnetic nanoparticles as photoacoustic contrast agent for enhanced tumor imaging

    PubMed Central

    Gao, Chuang; Deng, Zi-Jian; Peng, Dong; Jin, Yu-Shen; Ma, Yan; Li, Yan-Yan; Zhu, Yu-Kun; Xi, Jian-Zhong; Tian, Jie; Dai, Zhi-Fei; Li, Chang-Hui; Liang, Xiao-Long

    2016-01-01

    Objective: Photoacoustic (PA) tomography (PAT) has attracted extensive interest because of its optical absorption contrast and ultrasonic detection. This study aims to develop a biocompatible and biodegradable PA contrast agent particularly promising for clinical applications in human body. Methods: In this study, we presented a PA contrast agent: 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine- N-[methoxy (polyethylene glycol)] (DSPE-PEG)-coated superparamagnetic iron oxide (SPIO) nanoparticles (NPs) loaded with indocyanine green (ICG). We used ICG and SPIO NPs because both drugs are approved by the U.S. Food and Drug Administration. Given the strong absorption of near-infrared laser pulses, SPIO@DSPE-PEG/ICG NPs with a uniform diameter of ~28 nm could significantly enhance PA signals. Results: We demonstrated the contrast enhancement of these NPs in phantom and animal experiments, in which the in vivo circulation time of SPIO@DSPE-PEG/ICG NPs was considerably longer than that of free ICG. These novel NPs also displayed a high efficiency of tumor targeting. Conclusions: SPIO@DSPE-PEG/ICG NPs are promising PAT contrast agents for clinical applications. PMID:27807502

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

    SciTech Connect

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

    2011-02-15

    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.

  16. Photothermal measurements of superconductors

    SciTech Connect

    Kino, G.S.; Studenmund, W.R.; Fishman, I.M.

    1996-12-31

    A photothermal technique has been used to measure diffusion and critical temperature in high temperature superconductors. The technique is particularly suitable for determining material quality and inhomogeneity.

  17. Targeted Multifunctional Multimodal Protein-Shell Microspheres as Cancer Imaging Contrast Agents

    PubMed Central

    John, Renu; Nguyen, Freddy T.; Kolbeck, Kenneth J.; Chaney, Eric J.; Marjanovic, Marina; Suslick, Kenneth S.; Boppart, Stephen A.

    2012-01-01

    Purpose In this study, protein-shell microspheres filled with a suspension of iron oxide nanoparticles in oil are demonstrated as multimodal contrast agents in magnetic resonance imaging (MRI), magnetomotive optical coherence tomography (MM-OCT), and ultrasound imaging. The development, characterization, and use of multifunctional multimodal microspheres are described for targeted contrast and therapeutic applications. Procedures A preclinical rat model was used to demonstrate the feasibility of the multimodal multifunctional microspheres as contrast agents in ultrasound, MM-OCT and MRI. Microspheres were functionalized with the RGD peptide ligand, which is targeted to αvβ3 integrin receptors that are over-expressed in tumors and atherosclerotic lesions. Results These microspheres, which contain iron oxide nanoparticles in their cores, can be modulated externally using a magnetic field to create dynamic contrast in MM-OCT. With the presence of iron oxide nanoparticles, these agents also show significant negative T2 contrast in MRI. Using ultrasound B-mode imaging at a frequency of 30 MHz, a marked enhancement of scatter intensity from in vivo rat mammary tumor tissue was observed for these targeted protein microspheres. Conclusions Preliminary results demonstrate multimodal contrast-enhanced imaging of these functionalized microsphere agents with MRI, MM-OCT, ultrasound imaging, and fluorescence microscopy, including in vivo tracking of the dynamics of these microspheres in real-time using a high-frequency ultrasound imaging system. These targeted oil-filled protein microspheres with the capacity for high drug-delivery loads offer the potential for local delivery of lipophilic drugs under image guidance. PMID:21298354

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

    PubMed

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

    2015-01-01

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

  19. Multimeric Near IR-MR Contrast Agent for Multimodal In Vivo Imaging.

    PubMed

    Harrison, Victoria S R; Carney, Christiane E; MacRenaris, Keith W; Waters, Emily A; Meade, Thomas J

    2015-07-22

    Multiple imaging modalities are often required for in vivo imaging applications that require both high probe sensitivity and excellent spatial and temporal resolution. In particular, MR and optical imaging are an attractive combination that can be used to determine both molecular and anatomical information. Herein, we describe the synthesis and in vivo testing of two multimeric NIR-MR contrast agents that contain three Gd(III) chelates and an IR-783 dye moiety. One agent contains a PEG linker and the other a short alkyl linker. These agents label cells with extraordinary efficacy and can be detected in vivo using both imaging modalities. Biodistribution of the PEGylated agent shows observable fluorescence in xenograft MCF7 tumors and renal clearance by MR imaging.

  20. Computed Tomography Imaging of Primary Lung Cancer in Mice Using a Liposomal-Iodinated Contrast Agent

    PubMed Central

    Badea, Cristian T.; Athreya, Khannan K.; Espinosa, Gabriela; Clark, Darin; Ghafoori, A. Paiman; Li, Yifan; Kirsch, David G.; Johnson, G. Allan; Annapragada, Ananth; Ghaghada, Ketan B.

    2012-01-01

    Purpose To investigate the utility of a liposomal-iodinated nanoparticle contrast agent and computed tomography (CT) imaging for characterization of primary nodules in genetically engineered mouse models of non-small cell lung cancer. Methods Primary lung cancers with mutations in K-ras alone (KrasLA1) or in combination with p53 (LSL-KrasG12D;p53FL/FL) were generated. A liposomal-iodine contrast agent containing 120 mg Iodine/mL was administered systemically at a dose of 16 µl/gm body weight. Longitudinal micro-CT imaging with cardio-respiratory gating was performed pre-contrast and at 0 hr, day 3, and day 7 post-contrast administration. CT-derived nodule sizes were used to assess tumor growth. Signal attenuation was measured in individual nodules to study dynamic enhancement of lung nodules. Results A good correlation was seen between volume and diameter-based assessment of nodules (R2>0.8) for both lung cancer models. The LSL-KrasG12D;p53FL/FL model showed rapid growth as demonstrated by systemically higher volume changes compared to the lung nodules in KrasLA1 mice (p<0.05). Early phase imaging using the nanoparticle contrast agent enabled visualization of nodule blood supply. Delayed-phase imaging demonstrated significant differential signal enhancement in the lung nodules of LSL-KrasG12D;p53FL/FL mice compared to nodules in KrasLA1 mice (p<0.05) indicating higher uptake and accumulation of the nanoparticle contrast agent in rapidly growing nodules. Conclusions The nanoparticle iodinated contrast agent enabled visualization of blood supply to the nodules during the early-phase imaging. Delayed-phase imaging enabled characterization of slow growing and rapidly growing nodules based on signal enhancement. The use of this agent could facilitate early detection and diagnosis of pulmonary lesions as well as have implications on treatment response and monitoring. PMID:22485175

  1. Nanoparticle-mediated photothermal effect enables a new method for quantitative biochemical analysis using a thermometer.

    PubMed

    Fu, Guanglei; Sanjay, Sharma T; Dou, Maowei; Li, XiuJun

    2016-03-14

    A new biomolecular quantitation method, nanoparticle-mediated photothermal bioassay, using a common thermometer as the signal reader was developed. Using an immunoassay as a proof of concept, iron oxide nanoparticles (NPs) captured in the sandwich-type assay system were transformed into a near-infrared (NIR) laser-driven photothermal agent, Prussian blue (PB) NPs, which acted as a photothermal probe to convert the assay signal into heat through the photothermal effect, thus allowing sensitive biomolecular quantitation using a thermometer. This is the first report of biomolecular quantitation using a thermometer and also serves as the first attempt to introduce the nanoparticle-mediated photothermal effect for bioassays.

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

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

    NASA Astrophysics Data System (ADS)

    Siddiqui, Talha S.

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

  4. Contrast agents for diagnostic ultrasound: development and evaluation of polymer-coated microbubbles.

    PubMed

    Wheatley, M A; Schrope, B; Shen, P

    1990-11-01

    Although the concept of an ultrasound contrast agent dates from Gramiak's work in 1968 in which indocyanine green was injected into the ascending aorta and heart, no universally accepted contrast agent for ultrasound now exists. This is primarily due to problems with stability, size and/or toxicity of the agents which have been investigated. Development of an effective ultrasound contrast agent would be highly significant for the health care industry, since it would greatly expand the scope of ultrasound (a noninvasive and safe procedure) as a diagnostic technique. While encapsulated gas bubbles offer particular advantages in stability over hand-agitated systems, they frequently present problems with size. Capsules larger than 10 microns in diameter become entrapped in the capillary bed of the lung. This paper describes the use of ionotropic gelation of the naturally occurring polysaccharide, alginate, for microencapsulation of air. Two procedures have been investigated. A novel jet head has been developed which allows co-extrusion of a solution of sodium alginate and air to produce nascent microencapsulated air bubbles which fall into a hardening solution of calcium ions. A second method employs ultrasound to introduce cavitation-induced bubbles into the alginate before capsule formation by spraying. Power spectra of these preparations demonstrate echogenicity (that is strong scatter of the incident ultrasound wave back to the emitting transducer, which also acts as a receiver), with resonant peaks that are a function of capsule size and wall characteristics. PMID:2090309

  5. NOTE: The effects of paramagnetic contrast agents on metabolite protons in aqueous solution

    NASA Astrophysics Data System (ADS)

    Murphy, Philip S.; Leach, Martin O.; Rowland, Ian J.

    2002-03-01

    The longitudinal (R1) and transverse (R2) relaxivities of the clinically used contrast agents Gd(DTPA)2-, Gd(DOTA)- and Gd(DTPA-BMA) have been determined in mixed aqueous metabolite solutions for choline, creatine and N-acetylaspartate. Measurements were performed at 1.5 T using a STEAM sequence on 25 mM metabolite solutions at pH = 7.4 and 22 °C. The data showed that for all the contrast agents and metabolites, R1 ~ R2. The largest range of relaxivity values was found for Gd(DTPA)2-, where R2 = 6.8 +/- 0.3 mM-1 s-1 for choline and 1.5 +/- 0.4 mM-1 s-1 for N-acetylaspartate. Variation in relaxivity values was attributed primarily to differences between the charges of the paramagnetic agent and metabolite. The maximum potential influence of the contrast agents on in vivo metabolite signals was calculated using the measured relaxivities.

  6. Conception of the first magnetic resonance imaging contrast agents: a brief history.

    PubMed

    de Haën, C

    2001-08-01

    About 20 years ago, a technological innovation process started that eventually led to the affirmation of magnetic resonance imaging (MRI) contrast agents, which are used today in about 25% of all MRI procedures, as medical diagnostic tools. The process began with exploration of various technical possibilities and the conception in the years 1981 to 1982 of two types of agents (soluble paramagnetic chelates and protection colloid-stabilized colloidal particle solutions of magnetite) that eventually found embodiments in commercially available products. The pioneering products that eventually reached the market were gadopentetate dimeglumine (Magnevist, Schering AG) and the ferumoxides (Endorem, Guerbet SA; or Ferridex , Berlex Laboratories Inc.). The history of the conception phase of the technology is reconstructed here, focusing on the social dynamics rather than on technological aspects. In the period 1981 to 1982, a number of independent inventors from industry and academia conceived of water-soluble paramagnetic chelates and protection colloid-stabilized colloidal solutions of small particles of magnetite, both of acceptable tolerability, as contrast agents for MRI. Priorities on patents conditioned the further course of events. The analyzed history helps in understanding the typical roles of different institutions in technological innovation. The foundation of MRI contrast agent technology in basic science clearly was laid in academia. During the conception of practical products, industry assumed a dominant role. Beginning with the radiological evaluation of candidate products, the collaboration between industry and academia became essential.

  7. Reference tissue quantification of DCE-MRI data without a contrast agent calibration

    NASA Astrophysics Data System (ADS)

    Walker-Samuel, Simon; Leach, Martin O.; Collins, David J.

    2007-02-01

    The quantification of dynamic contrast-enhanced (DCE) MRI data conventionally requires a conversion from signal intensity to contrast agent concentration by measuring a change in the tissue longitudinal relaxation rate, R1. In this paper, it is shown that the use of a spoiled gradient-echo acquisition sequence (optimized so that signal intensity scales linearly with contrast agent concentration) in conjunction with a reference tissue-derived vascular input function (VIF), avoids the need for the conversion to Gd-DTPA concentration. This study evaluates how to optimize such sequences and which dynamic time-series parameters are most suitable for this type of analysis. It is shown that signal difference and relative enhancement provide useful alternatives when full contrast agent quantification cannot be achieved, but that pharmacokinetic parameters derived from both contain sources of error (such as those caused by differences between reference tissue and region of interest proton density and native T1 values). It is shown in a rectal cancer study that these sources of uncertainty are smaller when using signal difference, compared with relative enhancement (15 ± 4% compared with 33 ± 4%). Both of these uncertainties are of the order of those associated with the conversion to Gd-DTPA concentration, according to literature estimates.

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

    NASA Astrophysics Data System (ADS)

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

    2005-08-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  10. Dynamical analysis of the nonlinear response of ultrasound contrast agent microbubbles.

    PubMed

    Carroll, James M; Calvisi, Michael L; Lauderbaugh, Leal K

    2013-05-01

    The nonlinear response of spherical ultrasound contrast agent microbubbles is investigated to understand the effects of common shells on the dynamics. A compressible form of the Rayleigh-Plesset equation is combined with a thin-shell model developed by Lars Hoff to simulate the radial response of contrast agents subject to ultrasound. The responses of Albunex, Sonazoid, and polymer shells are analyzed through the application of techniques from dynamical systems theory such as Poincaré sections, phase portraits, and bifurcation diagrams to illustrate the qualitative dynamics and transition to chaos that occurs under certain changes in system parameters. Corresponding calculations of Lyapunov exponents provide quantitative data on the system dynamics. The results indicate that Albunex and polymer shells sufficiently stabilize the response to prevent transition to the chaotic regime throughout typical clinical ranges of ultrasound pressure and frequency. By contrast, Sonazoid shells delay the onset of chaos relative to an unshelled bubble but do not prevent it. A contour plot identifying regions of periodic and chaotic behavior over clinical ranges of ultrasound pressure and frequency is provided for Sonazoid. This work characterizes the nonlinear response of various ultrasound contrast agents, and shows that shell properties have a profound influence on the dynamics. PMID:23654372

  11. Molecular imaging of EGFR/HER2 cancer biomarkers by protein MRI contrast agents

    PubMed Central

    Qiao, Jingjuan; Xue, Shenghui; Pu, Fan; White, Natalie; Jiang, Jie; Liu, Zhi-Ren

    2014-01-01

    Epidermal growth factor receptor (EGFR) and HER2 are major prognosis biomarkers and drug targets overexpressed in various types of cancer cells. There is a pressing need to develop MRI contrast agents capable of enhancing the contrast between normal tissues and tumors with high relaxivity, capable of targeting tumors, and with high intratumoral distribution and minimal toxicity. In this review, we first discuss EGFR signaling and its role in tumor progression as a major drug target. We then report our progress in the development of protein contrast agents with significant improvement of both r1 and r2 relaxivities, pharmacokinetics, in vivo retention time, and in vivo dose efficiency. Finally, we report our effort in the development of EGFR-targeted protein contrast agents with the capability to cross the endothelial boundary and with good tissue distribution across the entire tumor mass. The noninvasive capability of MRI to visualize spatially and temporally the intratumoral distribution as well as quantify the levels of EGFR and HER2 would greatly improve our ability to track changes of the biomarkers during tumor progression, monitor treatment efficacy, aid in patient selection, and further develop novel targeted therapies for clinical application. PMID:24366655

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

    PubMed

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

    2014-04-18

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

    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.

  14. Comparison of synthetic HDL contrast agents for MR imaging of atherosclerosis

    PubMed Central

    Cormode, David P.; Chandrasekar, Rohith; Delshad, Amanda; Briley-Saebo, Karen C.; Calcagno, Claudia; Barazza, Alessandra; Mulder, Willem J. M.

    2009-01-01

    Determining arterial macrophage expression is an important goal in the molecular imaging of atherosclerosis. Here we compare the efficacy of two synthetic, HDL-based contrast agents for magnetic resonance imaging (MRI) of macrophage burden. Each form of HDL was labeled with gadolinium and rhodamine to allow MRI and fluorescence microscopy. Either the 37 or 18 amino acid peptide replaced the apolipoprotein A-I in these agents, which were termed 37pA-Gd or 18A-Gd. The diameters of 37pA-Gd and 18A-Gd are 7.6 nm and 8.0 nm, respectively, while the longitudinal relaxivities are 9.8 and 10.0 (mMs)-1. 37pA has better lipid binding properties. In vitro tests with J774A.1 macrophages proved the particles possessed the functionality of HDL by eliciting cholesterol efflux and were taken up in a receptor-like fashion by the cells. Both agents produced enhancements in atherosclerotic plaques of apolipoprotein E knockout mice of ~90% (n=7 per agent) and are macrophage specific as evidenced by confocal microscopy on aortic sections. The half-lives of 37pA-Gd and 18A-Gd are 2.6 and 2.1 hours, respectively. Despite the more favorable lipid interactions of 37pA, both agents gave similar, excellent contrast for the detection of atherosclerotic macrophages using MRI. PMID:19378935

  15. Virus-based nanomaterials as PET and MR contrast agents: from technology development to translational medicine

    PubMed Central

    Shukla, Sourabh; Steinmetz, Nicole F.

    2015-01-01

    Viruses have recently emerged as ideal protein scaffolds for a new class of contrast agents that can be used in medical imaging procedures such as positron emission tomography (PET) and magnetic resonance imaging (MRI). Whereas synthetic nanoparticles are difficult to produce as homogeneous formulations due to the inherently stochastic nature of the synthesis process, virus-based nanoparticles are genetically encoded and are therefore produced as homogeneous and monodisperse preparations with a high degree of quality control. Because the virus capsids have a defined chemical structure that has evolved to carry cargoes of nucleic acids, they can be modified to carry precisely defined cargoes of contrast agents and can be decorated with spatially defined contrast reagents on the internal or external surfaces. Viral nanoparticles can also be genetically programed or conjugated with targeting ligands to deliver contrast agents to specific cells, and the natural biocompatibility of viruses means they are cleared rapidly from the body. Nanoparticles based on bacteriophages and plant viruses are safe for use in humans and can be produced inexpensively in large quantities as self-assembling recombinant proteins. Based on these considerations, a new generation of contrast agents has been developed using bacteriophages and plant viruses as scaffolds to carry positron-emitting radioisotopes such as [18F] fluorodeoxyglucose for PET imaging and iron oxide or Gd3+ for MRI. Although challenges such as immunogenicity, loading efficiency and regulatory compliance remain to be address, virus-based nanoparticles represent a promising new enabling technology for a new generation of highly biocompatible and biodegradable targeted imaging reagents. PMID:25683790

  16. Gold nanoshelled liquid perfluorocarbon nanocapsules for combined dual modal ultrasound/CT imaging and photothermal therapy of cancer.

    PubMed

    Ke, Hengte; Yue, Xiuli; Wang, Jinrui; Xing, Sen; Zhang, Qian; Dai, Zhifei; Tian, Jie; Wang, Shumin; Jin, Yushen

    2014-03-26

    The integration of multimodal contrast-enhanced diagnostic imaging and therapeutic capabilities could utilize imaging guided therapy to plan the treatment strategy based on the diagnostic results and to guide/monitor the therapeutic procedures. Herein, gold nanoshelled perfluorooctylbromide (PFOB) nanocapsules with PEGylation (PGsP NCs) are constructed by oil-in-water emulsion method to form polymeric PFOB nanocapsules, followed by the formation of PEGylated gold nanoshell on the surface. PGsP NCs could not only provide excellent contrast enhancement for dual modal ultrasound and CT imaging in vitro and in vivo, but also serve as efficient photoabsorbers for photothermal ablation of tumors on xenografted nude mouse model. To our best knowledge, this is the first report of gold nanoshell serving as both CT contrast agents and photoabsorbers for photothermal therapy. The novel multifunctional nanomedicine would be of great value to offer more comprehensive diagnostic information to guide more accurate and effective cancer therapy. PMID:24500926

  17. Gold nanoparticles as novel agents for cancer therapy

    PubMed Central

    Jain, S; Hirst, D G; O'Sullivan, J M

    2012-01-01

    Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. This review introduces the field of nanotechnology with a focus on recent gold nanoparticle research which has led to early-phase clinical trials. In particular, the pre-clinical evidence for gold nanoparticles as sensitisers with ionising radiation in vitro and in vivo at kilovoltage and megavoltage energies is discussed. PMID:22010024

  18. Nanoparticles as magnetic resonance imaging contrast agents for vascular and cardiac diseases

    PubMed Central

    Chen, Wei; Cormode, David P.; Fayad, Zahi A.; Mulder, Willem J. M.

    2011-01-01

    Advances in nanoparticle contrast agents for molecular imaging have made magnetic resonance imaging a promising modality for noninvasive visualization and assessment of vascular and cardiac disease processes. This review provides a description of the various nanoparticles exploited for imaging cardiovascular targets. Nanoparticle probes detecting inflammation, apoptosis, extracellular matrix, and angiogenesis may provide tools for assessing the risk of progressive vascular dysfunction and heart failure. The utility of nanoparticles as multimodal probes and/or theranostic agents has also been investigated. Although clinical application of these nanoparticles is largely unexplored, the potential for enhancing disease diagnosis and treatment is considerable. PMID:20967875

  19. Research into europium complexes as magnetic resonance imaging contrast agents (Review)

    PubMed Central

    HAN, GUOCAN; DENG, YANGWEI; SUN, JIHONG; LING, JUN; SHEN, ZHIQUAN

    2015-01-01

    Europium (Eu) is a paramagnetic lanthanide element that possesses an outstanding luminescent property. Eu complexes are ideal fluorescence imaging (FI) agents. Eu2+ has satisfactory relaxivity and optical properties, and can realize magnetic resonance (MRI)-FI dual imaging applications when used with appropriate cryptands that render it oxidatively stable. By contrast, based on the chemical exchange saturation transfer (CEST) mechanism, Eu3+ complexes can provide enhanced MRI sensitivity when used with optimal cryptands, incorporated into polymeric CEST agents or blended with Gd3+. Eu complexes are promising in MRI-FI dual imaging applications and have a bright future. PMID:26136858

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

    PubMed

    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.

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

    PubMed

    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. PMID:27388945

  2. Safety of intravenous application of second-generation ultrasound contrast agent in children: prospective analysis.

    PubMed

    Piskunowicz, Maciej; Kosiak, Wojciech; Batko, Tomasz; Piankowski, Arkadiusz; Połczyńska, Katarzyna; Adamkiewicz-Drożyńska, Elżbieta

    2015-04-01

    The goal of the work described here was to assess the safety profile of intravenous second-generation ultrasound contrast agents (UCAs) containing sulfur hexafluoride in pediatric contrast-enhanced ultrasound. Between 2010 and 2013, a total of 167 examinations were performed in 137 children referred by the Oncology Department. Approval by an Independent Ethical Review Board on Scientific Research for the intravenous use of an UCA containing sulfur hexafluoride in children with oncologic diseases was obtained. Consent for UCA administration was acquired from the parents or legal guardians. Severe anaphylactic reaction was observed in 0.6% (n = 1). No other adverse events during or after intravenous administration of contrast were observed in the examined group (no changes in heart rate and rhythm, blood pressure, oxygen saturation or respiratory rate). There were no reports of subjective flushing, nausea, transient headaches or altered taste. Although second-generation ultrasound contrast agents are considered potentially safe, all investigators should be prepared for the development of adverse reactions and have provisions in place for all pediatric intravenous contrast-enhanced ultrasound examinations. More multicenter studies are essential to determination of an accurate UCA safety profile.

  3. In vitro acoustic characterization of three phospholipid ultrasound contrast agents from 12 to 43 MHz.

    PubMed

    Sun, Chao; Sboros, Vassilis; Butler, Mairead B; Moran, Carmel M

    2014-03-01

    The acoustic properties of two clinical (Definity, Lantheus Medical Imaging, North Billerica, MA, USA; SonoVue, Bracco S.P.A., Milan, Italy) and one pre-clinical (MicroMarker, untargeted, Bracco, Geneva, Switzerland; VisualSonics, Toronto, ON, Canada) ultrasound contrast agent were characterized using a broadband substitution technique over the ultrasound frequency range 12-43 MHz at 20 ± 1°C. At the same number concentration, the acoustic attenuation and contrast-to-tissue ratio of the three native ultrasound contrast agents are comparable at frequencies below 30 MHz, though their size distributions and encapsulated gases and shells differ. At frequencies above 30 MHz, native MicroMarker has higher attenuation values and contrast-to-tissue ratios than native Definity and SonoVue. Decantation was found to be an effective method to alter the size distribution and concentration of native clinical microbubble populations, enabling further contrast enhancement for specific pre-clinical applications.

  4. Synthesis of ferrofluid with magnetic nanoparticles by sonochemical method for MRI contrast agent

    NASA Astrophysics Data System (ADS)

    Hee Kim, Eun; Sook Lee, Hyo; Kook Kwak, Byung; Kim, Byung-Kee

    2005-03-01

    Superparamagnetic iron oxide nanoparticles (SPIO) having high magnetization (83 emu/g) and crystallinity were synthesized by using a sonochemical method. Ferrofluids from these nanoparticles coated with oleic acid as a surfactant were prepared for magnetic resonance imaging (MRI) contrast agent. The coated SPIO could be easily dispersed in chitosan, and the hydrodynamic diameter of the coated SPIO in the chitosan solution was estimated to be 65 nm. The ferrofluids of various concentrations did not agglomerate for 30 days, indicating their good stability. The T1- and T2-weighted MR images of these ferrofluids were obtained and the MRI image contrasts were similar to those of Resovist ®.

  5. Gadolinium contrast agent selection and optimal use for body MR imaging.

    PubMed

    Guglielmo, Flavius F; Mitchell, Donald G; Gupta, Shiva

    2014-07-01

    Proper selection of a gadolinium-based contrast agent (GBCA) for body magnetic resonance imaging (MRI) cases requires understanding the indication for the MRI exam, the key features of the different GBCAs, and the effect that the GBCA has on the selected imaging protocol. The different categories of GBCAs require timing optimization on postcontrast sequences and adjusting imaging parameters to obtain the highest T1 contrast. Gadoxetate disodium has many advantages when evaluating liver lesions, although there are caveats and limitations that need to be understood. Gadobenate dimeglumine, a high-relaxivity GBCA, can be used for indications when stronger T1 relaxivity is needed.

  6. Imaging translucent cell bodies in the living mouse retina without contrast agents

    PubMed Central

    Guevara-Torres, A.; Williams, D. R.; Schallek, J. B.

    2015-01-01

    The transparency of most retinal cell classes typically precludes imaging them in the living eye; unless invasive methods are used that deploy extrinsic contrast agents. Using an adaptive optics scanning light ophthalmoscope (AOSLO) and capitalizing on the large numerical aperture of the mouse eye, we enhanced the contrast from otherwise transparent cells by subtracting the left from the right half of the light distribution in the detector plane. With this approach, it is possible to image the distal processes of photoreceptors, their more proximal cell bodies and the mosaic of horizontal cells in the living mouse retina. PMID:26114032

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

    NASA Astrophysics Data System (ADS)

    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.

  8. Molecular imaging of atherosclerosis with nanoparticle-based fluorinated MRI contrast agents

    PubMed Central

    Palekar, Rohun U; Jallouk, Andrew P; Lanza, Gregory M; Pan, Hua; Wickline, Samuel A

    2015-01-01

    As atherosclerosis remains one of the most prevalent causes of patient mortality, the ability to diagnose early signs of plaque rupture and thrombosis represents a significant clinical need. With recent advances in nanotechnology, it is now possible to image specific molecular processes noninvasively with MRI, using various types of nanoparticles as contrast agents. In the context of cardiovascular disease, it is possible to specifically deliver contrast agents to an epitope of interest for detecting vascular inflammatory processes, which serve as predecessors to atherosclerotic plaque development. Herein, we review various applications of nanotechnology in detecting atherosclerosis using MRI, with an emphasis on perfluorocarbon nanoparticles and fluorine imaging, along with theranostic prospects of nanotechnology in cardiovascular disease. PMID:26080701

  9. Hybrid gadolinium oxide nanoparticles: multimodal contrast agents for in vivo imaging.

    PubMed

    Bridot, Jean-Luc; Faure, Anne-Charlotte; Laurent, Sophie; Rivière, Charlotte; Billotey, Claire; Hiba, Bassem; Janier, Marc; Josserand, Véronique; Coll, Jean-Luc; Elst, Luce Vander; Muller, Robert; Roux, Stéphane; Perriat, Pascal; Tillement, Olivier

    2007-04-25

    Luminescent hybrid nanoparticles with a paramagnetic Gd2O3 core were applied as contrast agents for both in vivo fluorescence and magnetic resonance imaging. These hybrid particles were obtained by encapsulating Gd2O3 cores within a polysiloxane shell which carries organic fluorophores and carboxylated PEG covalently tethered to the inorganic network. Longitudinal proton relaxivities of these particles are higher than the positive contrast agents like Gd-DOTA which are commonly used for clinical magnetic resonance imaging. Moreover these particles can be followed up by fluorescence imaging. This study revealed that these particles suited for dual modality imaging freely circulate in the blood vessels without undesirable accumulation in lungs and liver.

  10. Gadolinium-based hybrid nanoparticles as a positive MR contrast agent.

    PubMed

    Hifumi, Hiroki; Yamaoka, Seiichi; Tanimoto, Akihiro; Citterio, Daniel; Suzuki, Koji

    2006-11-29

    A new nanoparticulate inorganic-organic hybrid-type positive contrast agent (CA), PGP/dextran-K01, was synthesized based on a GdPO4 inorganic core as a relaxation-time-shortening moiety and a dextran-coating, which generates monodispersibility in water, a high relaxation-time-shortening effect by retaining a large number of water molecules in proximity of the core and toxicity reduction in in-vivo studies. This PGP/dextran-K01 nanoparticle has high r1 and r2 values and a significantly low r2/r1 value, 1.1, which is unprecedented and which is the lowest value among existing nanoparticulate CAs indicating that PGP/dextran-K01 is a positive contrast agent. Because of this low r2/r1 value and the nanoparticulate shape, PGP/dextran-K01 will be a useful clinical substitute for negative CAs based on iron oxides.

  11. Characteristics of Gadolinium Oxide Nanoparticles as Contrast Agents for Terahertz Imaging

    NASA Astrophysics Data System (ADS)

    Lee, Dong-Kyu; Kim, Hyeongmun; Kim, Taekhoon; Cho, Byungkyu; Lee, Kwangyeol; Son, Joo-Hiuk

    2011-04-01

    For the application of gadolinium oxide (Gd2O3) nanoparticles as terahertz contrast agents, their optical properties in a solvent were studied using terahertz time-domain spectroscopy. The power absorption and refractive index of the samples were measured with various concentrations of nanoparticles. The power absorption was extremely large, as much as three orders of magnitude higher than that of water, so that a few ppms of Gd2O3 nanoparticles were distinguished in terms of their power absorption capacity. The results show that the interaction between the terahertz electromagnetic waves and the Gd2O3 nanoparticles is strong enough to allow their exploitation as contrast agents for terahertz medical imaging.

  12. Hydroxy double salts intercalated with Mn(II) complexes as potential contrast agents

    NASA Astrophysics Data System (ADS)

    Jin, Miao; Li, Wanjing; Spillane, Dominic E. M.; Geraldes, Carlos F. G. C.; Williams, Gareth R.; Bligh, S. W. Annie

    2016-03-01

    A series of Mn(II) aminophosphonate complexes were successfully synthesized and intercalated into the hydroxy double salt [Zn5(OH)8]Cl2·yH2O. Complex incorporation led to an increase in the interlayer spacing from 7.8 to 10-12 Å. Infrared spectroscopy showed the presence of the characteristic vibration peaks of the Mn(II) complexes in the intercalates' spectra, indicating successful incorporation. The complex-loaded composites had somewhat lower proton relaxivities than the pure complexes. Nevertheless, these intercalates may have use as MRI contrast agents for patients with poor kidney function, where traditional Gd(III)-based contrast agents cause severe renal failure.

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

    NASA Astrophysics Data System (ADS)

    Yazdani, Farshad; Fattahi, Bahare; Azizi, Najmodin

    2016-05-01

    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, Fe3O4 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 Fe3O4-SiO2-mebrofenin composite is an effective MRI contrast agent for liver targeting.

  14. [Ultrasonography with contrast agent for diagnosis of benign retroperitoneal cyst. Case report].

    PubMed

    Guzmán-Valdivia Gómez, Gilberto; Morinelli-Urustizaga, Alejandra; Martínez-Sánchez, Silvia; Ortiz-Valdivia, Miriam

    2005-01-01

    Intraabdominal tumors require precise diagnosis for patient preparation for optimal surgical procedure. For diagnosis of these lesions, the principal studies used are ultrasonography, computed axial tomography (CAT) and occasionally the use of magnetic resonance imaging, a study not always possible to accomplish in all hospitals. We present the case of a patient with a giant retroperitoneal cyst whose diagnosis was missed by means of conventional ultrasound and CAT. For this reason, we chose to use ultrasound with echography using contrast agent (Levovist) to determine if the tumor was dependent on the liver or pancreas. By means of this technique, we were able to make the diagnosis that the tumor did not depend on any organ, but rather was an independent retroperitoneal tumor. Final surgical and histopathological diagnosis was a retroperitoneal multilocular lymphangioma. We conclude that ultrasonography with contrast agent (Levovist) is an alternative method for studying intraabdominal tumors.

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

    NASA Astrophysics Data System (ADS)

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

    2010-12-01

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

  16. A responsive particulate MRI contrast agent for copper (I): a cautionary tale

    PubMed Central

    Smolensky, Eric D.; Marjańska, Małgorzata

    2013-01-01

    A responsive MION-based MRI contrast agent for the detection of copper(I) is presented. Induced agglomeration of azide and acetylene-functionalized magnetite nanoparticles via Cu(I) catalysed Huisgen cycloaddition leads to significant decrease in longitudinal relaxivity due to the slow exchange of water molecules trapped within the cluster with bulk solvent. Agglomeration leads to an initial two fold increase followed by a sharp and almost complete loss in transverse relaxivity for clusters larger than 200 nm in size. The decrease in r2 for clusters reaching the static dephasing regime has two significant implications for particulate responsive MRI contrast agents. First, the maximum increase in r2 is barely two fold, second, since r2 does not increase continuously with increasing cluster size, the r1/r2 ratio cannot be used to determine the concentration of an analyte ratiometrically. PMID:22585342

  17. Advances in biodegradable nanomaterials for photothermal therapy of cancer

    PubMed Central

    He, Chao-Feng; Wang, Shun-Hao; Yu, Ying-Jie; Shen, He-Yun; Zhao, Yan; Gao, Hui-Ling; Wang, Hai; Li, Lin-Lin; Liu, Hui-Yu

    2016-01-01

    Photothermal cancer therapy is an alternative to chemotherapy, radiotherapy, and surgery. With the development of nanophotothermal agents, this therapy holds immense potential in clinical translation. However, the toxicity issues derived from the fact that nanomaterials are trapped and retained in the reticuloendothelial systems limit their biomedical application. Developing biodegradable photothermal agents is the most practical route to address these concerns. In addition to the physicochemical properties of nanomaterials, various internal and external stimuli play key roles on nanomaterials uptake, transport, and clearance. In this review, we summarized novel nanoplatforms for photothermal therapy; these nanoplatforms can elicit stimuli-triggered degradation. We focused on the recent innovative designs endowed with biodegradable photothermal agents under different stimuli, including enzyme, pH, and near-infrared (NIR) laser. PMID:27807498

  18. Evaluation of a novel gadolinium-based contrast agent for intraoperative magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Madsen, Steen J.; Wu, Genevieve N.; Chow, Rayland; Kim, Sung-Yop; Hirschberg, Henry

    2008-02-01

    The aim of this experimental study was to determine whether Motexafin Gadolinium (MGd) could serve as an efficient intraoperative contrast agent avoiding problems that arise with surgically-induced intracranial enhancement. F98 orthotopic brain tumors or surgical lesions were induced in Fisher rats. T1-weighted MRI studies were performed with either a single or multiple daily doses of MGd. The last contrast dose was administered either 7 or 24 h prior to scanning in both tumor-bearing and surgically treated animals. Animals receiving either 30 or 60 mg/kg MGd i.v. developed clinical signs of impaired motor activity, and increasing lethargy. MGd given i.p. was tolerated up to a dose of 140 mg/kg. Despite multiple dosages, and several administration modes (i.p. and i.v.), no significant enhancement was observed if the scans were performed 7 or 24 h following the last MGd dose. Clear enhancement was observed if the scans were performed 30 min. following MGd administration. Scans of necrotic lesions were positive 7 h post MGd injection. MGd scans showed no significant enhancement following surgically-induced lesions while scans with conventional contrast agents showed both meningeal and intraparenchymal enhancement. This study suggests that MGd is not sequestered in viable tumor for the necessary time interval required to allow delayed imaging in this model. The agent does seem to remain in necrotic tissue for longer time intervals. MGd therefore would not be suitable as a contrast agent in iMRI for the detection of residual tumor tissue during surgery.

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

    NASA Astrophysics Data System (ADS)

    Pablico, Michele Huelar

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

  20. Comparison of Divalent Transition Metal Ion ParaCEST MRI Contrast Agents

    PubMed Central

    Dorazio, Sarina J.; Olatunde, Abiola O.; Tsitovich, Pavel B.

    2013-01-01

    Transition metal ion-based paraCEST agents (TM-CEST) are a promising new class of compounds for MRI contrast. Members in this class of compounds include paramagnetic complexes of FeII, CoII and NiII. The development of the coordination chemistry for these paraCEST agents is presented with an emphasis on the choice of azamacrocycle backbone and pendent groups with the goals of controlling oxidation state, spin state and stability of the complexes. CEST spectra and images are compared for different macrocyclic complexes containing amide or heterocyclic pendent groups. The potential of paraCEST agents that function as pH and redox-activated MRI probes is discussed. PMID:24253281

  1. A model for ultrasound absorption and dispersion in dilute suspensions of nanometric contrast agents.

    PubMed

    Coulouvrat, François; Thomas, Jean-Louis; Astafyeva, Ksenia; Taulier, Nicolas; Conoir, Jean-Marc; Urbach, Wladimir

    2012-12-01

    Ultrasound dispersion and absorption are examined in dilute suspensions of contrast agents of nanometric size, with a typical radius around 100 nm. These kinds of contrast agents are designed for targeted delivery of drugs for cancer treatment. Compared to standard contrast agents used for imaging, particles are of smaller size to pass through the endothelial barrier, their shell, made up of biocompatible polymer, is stiffer to undergo a longer lifetime, and they have a liquid core instead of a gaseous one. Ultrasound propagation in dilute suspension is modeled by combining two modes for particle oscillations. The first one is a dilatational mode assuming an incompressible shell with a rheological behavior of Kelvin-Voigt or Maxwell type. The second one is a translational mode induced by visco-inertial interaction with the ambient fluid. The relative importance of these two modes of interaction on both dispersion and absorption is quantified and analyzed for a model system and for two radii (75 and 150 nm) and the two rheological models. The influence of shell parameters (Young modulus, viscosity, and relative thickness) is finally discussed.

  2. Development of Ultrasound-switchable Fluorescence Imaging Contrast Agents based on Thermosensitive Polymers and Nanoparticles

    PubMed Central

    Cheng, Bingbing; Wei, Ming-Yuan; Liu, Yuan; Pitta, Harish; Xie, Zhiwei; Hong, Yi; Nguyen, Kytai T.; Yuan, Baohong

    2015-01-01

    In this work we first introduced a recently developed high-resolution, deep-tissue imaging technique, ultrasound-switchable fluorescence (USF). The imaging principles based on two types of USF contrast agents were reviewed. To improve USF imaging techniques further, excellent USF contrast agents were developed based on high-performance thermoresponsive polymers and environment-sensitive fluorophores. Herein, such contrast agents were synthesized and characterized with five key parameters: (1) peak excitation and emission wavelengths (λex and λem), (2) the fluorescence intensity ratio between on and off states (IOn/IOff), (3) the fluorescence lifetime ratio between on and off states (τOn/τOff), (4) the temperature threshold to switch on fluorophores (Tth), and (5) the temperature transition bandwidth (TBW). We mainly investigated fluorescence intensity and lifetime changes of four environment-sensitive dyes [7-(2-Aminoethylamino)-N,N-dimethyl-4-benzofurazansulfonamide (DBD-ED), St633, Sq660, and St700] as a function of temperature, while the dye was attached to poly(N-isopropylacrylamide) linear polymers or encapsulated in nanoparticles. Six fluorescence resonance energy transfer systems were invented in which both the donor (DBD-ED or ST425) and the acceptor (Sq660) were adopted. Our results indicate that three Förster resonance energy transfer systems, where both IOn/IOff and τOn/τOff are larger than 2.5, are promising for application in future surface tissue bioimaging by USF technique. PMID:26052192

  3. Ultrasmall Nanoplatforms as Calcium-Responsive Contrast Agents for Magnetic Resonance Imaging.

    PubMed

    Moussaron, Albert; Vibhute, Sandip; Bianchi, Andrea; Gündüz, Serhat; Kotb, Shady; Sancey, Lucie; Motto-Ros, Vincent; Rizzitelli, Silvia; Crémillieux, Yannick; Lux, Francois; Logothetis, Nikos K; Tillement, Olivier; Angelovski, Goran

    2015-10-01

    The preparation of ultrasmall and rigid platforms (USRPs) that are covalently coupled to macrocycle-based, calcium-responsive/smart contrast agents (SCAs), and the initial in vitro and in vivo validation of the resulting nanosized probes (SCA-USRPs) by means of magnetic resonance imaging (MRI) is reported. The synthetic procedure is robust, allowing preparation of the SCA-USRPs on a multigram scale. The resulting platforms display the desired MRI activity—i.e., longitudinal relaxivity increases almost twice at 7 T magnetic field strength upon saturation with Ca(2+). Cell viability is probed with the MTT assay using HEK-293 cells, which show good tolerance for lower contrast agent concentrations over longer periods of time. On intravenous administration of SCA-USRPs in living mice, MRI studies indicate their rapid accumulation in the renal pelvis and parenchyma. Importantly, the MRI signal increases in both kidney compartments when CaCl2 is also administrated. Laser-induced breakdown spectroscopy experiments confirm accumulation of SCA-USRPs in the renal cortex. To the best of our knowledge, these are the first studies which demonstrate calcium-sensitive MRI signal changes in vivo. Continuing contrast agent and MRI protocol optimizations should lead to wider application of these responsive probes and development of superior functional methods for monitoring calcium-dependent physiological and pathological processes in a dynamic manner. PMID:26179212

  4. Chitosan oligosaccharide based Gd-DTPA complex as a potential bimodal magnetic resonance imaging contrast agent.

    PubMed

    Huang, Yan; Cao, Juan; Zhang, Qi; Lu, Zheng-rong; Hua, Ming-qing; Zhang, Xiao-yan; Gao, Hu

    2016-01-01

    A new gadolinium diethylenetriamine pentaacetic acid (DTPA) complex (Gd-DTPA-DMABA-CS11) as a potential bimodal magnetic resonance imaging (MRI) contrast agent with fluorescence was synthesized. It was synthesized by the incorporation of 4-dimethylaminobenzaldehyde (DMABA) and chitosan oligosaccharide (CSn; n=11) with low polydispersity index to DTPA anhydride and then chelated with gadolinium chloride. The structure was characterized by Fourier transform infrared (FTIR), (1)H NMR, elemental analysis and size exclusion chromatography (SEC). MRI measurements in vitro were evaluated. The results indicated that Gd-DTPA-DMABA-CS11 provided higher molar longitudinal relaxivity (r1) (12.95mM(-1)·s(-1)) than that of commercial Gd-DTPA (3.63mM(-1)·s(-1)) at 0.5T. Gd-DTPA-DMABA-CS11 also emitted fluorescence, and the intensity was much stronger than that of Gd-DTPA. Therefore, it can be meanwhile used in fluorescent imaging for improving the sensitivity in clinic diagnosis. Gd-DTPA-DMABA-CS11 as a potential contrast agent is preliminarily stable in vitro. The results of thermodynamic action between Gd-DTPA-DMABA-CS11 and bovine serum albumin (BSA) illustrated that the binding process was exothermic and spontaneous, and the main force was van der Waals' interaction and hydrogen bond. The preliminary study suggested that Gd-DTPA-DMABA-CS11 could be used in both magnetic resonance and fluorescent imaging as a promising bimodal contrast agent.

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

    We report evidence for the possible application of chitosan-coated nickel-ferrite (NiFe2O4) nanoparticles as both T1 and T2 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 T1 and T2 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 T1-weighted mage and a 71% signal loss in the T2-weighted image were observed. This demonstrated that chitosan-coated nickel-ferrite nanoparticles are suitable as both T1 and T2 contrast agents in MRI. We note that the applicability of our nanoparticles as both T1 and T2 contrast agents is due to their cylindrical shape, which gives rise to both inner and outer sphere processes of nanoparticles.

  6. Ultrasmall Nanoplatforms as Calcium-Responsive Contrast Agents for Magnetic Resonance Imaging.

    PubMed

    Moussaron, Albert; Vibhute, Sandip; Bianchi, Andrea; Gündüz, Serhat; Kotb, Shady; Sancey, Lucie; Motto-Ros, Vincent; Rizzitelli, Silvia; Crémillieux, Yannick; Lux, Francois; Logothetis, Nikos K; Tillement, Olivier; Angelovski, Goran

    2015-10-01

    The preparation of ultrasmall and rigid platforms (USRPs) that are covalently coupled to macrocycle-based, calcium-responsive/smart contrast agents (SCAs), and the initial in vitro and in vivo validation of the resulting nanosized probes (SCA-USRPs) by means of magnetic resonance imaging (MRI) is reported. The synthetic procedure is robust, allowing preparation of the SCA-USRPs on a multigram scale. The resulting platforms display the desired MRI activity—i.e., longitudinal relaxivity increases almost twice at 7 T magnetic field strength upon saturation with Ca(2+). Cell viability is probed with the MTT assay using HEK-293 cells, which show good tolerance for lower contrast agent concentrations over longer periods of time. On intravenous administration of SCA-USRPs in living mice, MRI studies indicate their rapid accumulation in the renal pelvis and parenchyma. Importantly, the MRI signal increases in both kidney compartments when CaCl2 is also administrated. Laser-induced breakdown spectroscopy experiments confirm accumulation of SCA-USRPs in the renal cortex. To the best of our knowledge, these are the first studies which demonstrate calcium-sensitive MRI signal changes in vivo. Continuing contrast agent and MRI protocol optimizations should lead to wider application of these responsive probes and development of superior functional methods for monitoring calcium-dependent physiological and pathological processes in a dynamic manner.

  7. Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging.

    PubMed

    Xue, Shenghui; Yang, Hua; Qiao, Jingjuan; Pu, Fan; Jiang, Jie; Hubbard, Kendra; Hekmatyar, Khan; Langley, Jason; Salarian, Mani; Long, Robert C; Bryant, Robert G; Hu, Xiaoping Philip; Grossniklaus, Hans E; Liu, Zhi-Ren; Yang, Jenny J

    2015-05-26

    With available MRI techniques, primary and metastatic liver cancers that are associated with high mortality rates and poor treatment responses are only diagnosed at late stages, due to the lack of highly sensitive contrast agents without Gd(3+) toxicity. We have developed a protein contrast agent (ProCA32) that exhibits high stability for Gd(3+) and a 10(11)-fold greater selectivity for Gd(3+) over Zn(2+) compared with existing contrast agents. ProCA32, modified from parvalbumin, possesses high relaxivities (r1/r2: 66.8 mmol(-1)⋅s(-1)/89.2 mmol(-1)⋅s(-1) per particle). Using T1- and T2-weighted, as well as T2/T1 ratio imaging, we have achieved, for the first time (to our knowledge), robust MRI detection of early liver metastases as small as ∼0.24 mm in diameter, much smaller than the current detection limit of 10-20 mm. Furthermore, ProCA32 exhibits appropriate in vivo preference for liver sinusoidal spaces and pharmacokinetics for high-quality imaging. ProCA32 will be invaluable for noninvasive early detection of primary and metastatic liver cancers as well as for monitoring treatment and guiding therapeutic interventions, including drug delivery.

  8. Open-Source Automated Parahydrogen Hyperpolarizer for Molecular Imaging Using (13)C Metabolic Contrast Agents.

    PubMed

    Coffey, Aaron M; Shchepin, Roman V; Truong, Milton L; Wilkens, Ken; Pham, Wellington; Chekmenev, Eduard Y

    2016-08-16

    An open-source hyperpolarizer producing (13)C hyperpolarized contrast agents using parahydrogen induced polarization (PHIP) for biomedical and other applications is presented. This PHIP hyperpolarizer utilizes an Arduino microcontroller in conjunction with a readily modified graphical user interface written in the open-source processing software environment to completely control the PHIP hyperpolarization process including remotely triggering an NMR spectrometer for efficient production of payloads of hyperpolarized contrast agent and in situ quality assurance of the produced hyperpolarization. Key advantages of this hyperpolarizer include: (i) use of open-source software and hardware seamlessly allowing for replication and further improvement as well as readily customizable integration with other NMR spectrometers or MRI scanners (i.e., this is a multiplatform design), (ii) relatively low cost and robustness, and (iii) in situ detection capability and complete automation. The device performance is demonstrated by production of a dose (∼2-3 mL) of hyperpolarized (13)C-succinate with %P13C ∼ 28% and 30 mM concentration and (13)C-phospholactate at %P13C ∼ 15% and 25 mM concentration in aqueous medium. These contrast agents are used for ultrafast molecular imaging and spectroscopy at 4.7 and 0.0475 T. In particular, the conversion of hyperpolarized (13)C-phospholactate to (13)C-lactate in vivo is used here to demonstrate the feasibility of ultrafast multislice (13)C MRI after tail vein injection of hyperpolarized (13)C-phospholactate in mice. PMID:27478927

  9. Neurosurgical confocal endomicroscopy: A review of contrast agents, confocal systems, and future imaging modalities

    PubMed Central

    Zehri, Aqib H.; Ramey, Wyatt; Georges, Joseph F.; Mooney, Michael A.; Martirosyan, Nikolay L.; Preul, Mark C.; Nakaji, Peter

    2014-01-01

    Background: The clinical application of fluorescent contrast agents (fluorescein, indocyanine green, and aminolevulinic acid) with intraoperative microscopy has led to advances in intraoperative brain tumor imaging. Their properties, mechanism of action, history of use, and safety are analyzed in this report along with a review of current laser scanning confocal endomicroscopy systems. Additional imaging modalities with potential neurosurgical utility are also analyzed. Methods: A comprehensive literature search was performed utilizing PubMed and key words: In vivo confocal microscopy, confocal endomicroscopy, fluorescence imaging, in vivo diagnostics/neoplasm, in vivo molecular imaging, and optical imaging. Articles were reviewed that discussed clinically available fluorophores in neurosurgery, confocal endomicroscopy instrumentation, confocal microscopy systems, and intraoperative cancer diagnostics. Results: Current clinically available fluorescent contrast agents have specific properties that provide microscopic delineation of tumors when imaged with laser scanning confocal endomicroscopes. Other imaging modalities such as coherent anti-Stokes Raman scattering (CARS) microscopy, confocal reflectance microscopy, fluorescent lifetime imaging (FLIM), two-photon microscopy, and second harmonic generation may also have potential in neurosurgical applications. Conclusion: In addition to guiding tumor resection, intraoperative fluorescence and microscopy have the potential to facilitate tumor identification and complement frozen section analysis during surgery by providing real-time histological assessment. Further research, including clinical trials, is necessary to test the efficacy of fluorescent contrast agents and optical imaging instrumentation in order to establish their role in neurosurgery. PMID:24872922

  10. Preserving Enhancement in Freeze-Dried Contrast Agent ST68: Examination of Excipients

    PubMed Central

    Solis, Carl; Forsberg, Flemming; Wheatley, Margaret A.

    2013-01-01

    The perfluorcarbon (perfluorobutane) ultrasound contrast agent ST68, composed of sonicated mixtures of non-ionic surfactants, is stable in solution for only a few weeks at 4°C. Freeze-drying critically diminished ST68’s ability to reflect ultrasound (its echogenicity). A method of incorporating specific lyoprotectants before lyophilization was investigated. Reintroduction of perfluorobutane to the protected freeze-dried sample, followed by reconstituting with preserved echogenicity. Glucose, trehalose, sucrose, and mannitol were tested at 100 mM and in vitro echogenicity data was collected from samples with dose concentrations of 50 µl/l to 300 µl/l. Glucose was found to be the best lyoprotectant providing an average (n=3) maximum peak enhancement of 23.2 ± 1.2 dB in vitro, measured at 5 MHz, 684 kPa, and a pulse repetition frequency (PRF) of 100 Hz (p<0.05 over freeze-dried ST68 control) and 20.8 ± 0.8 dB in vivo in New Zealand white rabbits at 5 MHz and a PRF of 6.7 kHz. Pulse inversion harmonic US images of a rabbit kidney, pre- and post-contrast injection (0.1 ml/kg), showed excellent enhancement and clear vascular delineation, similar to that of the original agent. For the first time this contrast agent can be successfully freeze-dried yielding a longer self-life without the need for refrigeration. PMID:20540998

  11. Preserving enhancement in freeze-dried contrast agent ST68: Examination of excipients.

    PubMed

    Solis, Carl; Forsberg, Flemming; Wheatley, Margaret A

    2010-08-30

    The perfluorcarbon (perfluorobutane) ultrasound contrast agent ST68, composed of sonicated mixtures of non-ionic surfactants, is stable in solution for only a few weeks at 4 degrees C. Freeze-drying critically diminished ST68's ability to reflect ultrasound (its echogenicity). A method of incorporating specific lyoprotectants before lyophilization was investigated. Reintroduction of perfluorobutane to the protected freeze-dried sample, followed by reconstituting with water preserved echogenicity. Glucose, trehalose, sucrose, and mannitol were tested at 100mM and in vitro echogenicity data was collected from samples with dose concentrations of 50-300microl/l. Glucose was found to be the best lyoprotectant providing an average (n=3) maximum peak enhancement of 23.2+/-1.2dB in vitro, measured at 5MHz, 684kPa, and a pulse repetition frequency (PRF) of 100Hz (p<0.05 over freeze-dried ST68 control) and 20.8+/-0.8dB in vivo in New Zealand white rabbits at 5MHz and a PRF of 6.7kHz. Pulse inversion harmonic US images of a rabbit kidney, pre- and post-contrast injection (0.1ml/kg), showed excellent enhancement and clear vascular delineation, similar to that of the original agent. For the first time this contrast agent can be successfully freeze-dried yielding a longer self-life without the need for refrigeration.

  12. Physical characteristics of lanthanide complexes that act as magnetization transfer (MT) contrast agents

    NASA Astrophysics Data System (ADS)

    Zhang, Shanrong; Sherry, A. Dean

    2003-02-01

    Rapid water exchange is normally considered a prerequisite for efficient Gd 3+-based MRI contrast agents. Yet recent measures of exchange rates in some Gd 3+ complexes have shown that water exchange can become limiting when such complexes are attached to larger macromolecular structures. A new class of lanthanide complexes that display unusually slow water exchange (bound water lifetimes ( τM298) > 10 μs) has recently been reported. This apparent disadvantage may be taken advantage of by switching the metal ion from gadolinium(III) to a lanthanide that shifts the bound water resonance substantially away from bulk water. Given appropriate water exchange kinetics, one can then alter the intensity of the bulk water signal by selective presaturation of this highly shifted, Ln3+-bound water resonance. This provides the basis of a new method to alter MR image contrast in tissue. We have synthesized a variety of DOTA-tetra(amide) ligands to evaluate as potential magnetization transfer (MT) contrast agents and found that the bound water lifetimes in these complexes are sensitive to both ligand structure (a series of Eu 3+ complexes have τM298 values that range from 1 to 1300 μs) and the identity of the paramagnetic Ln3+ cation (from 3 to 800 μs for a single ligand). This demonstrates that it may be possible either to fine-tune the ligand structure or to select proper lanthanide cation to create an optimal MT agent for any clinical imaging field.

  13. Dextran coated bismuth-iron oxide nanohybrid contrast agents for computed tomography and magnetic resonance imaging

    PubMed Central

    Naha, Pratap C.; Zaki, Ajlan Al; Hecht, Elizabeth; Chorny, Michael; Chhour, Peter; Blankemeyer, Eric; Yates, Douglas M.; Witschey, Walter R. T.; Litt, Harold I.; Tsourkas, Andrew; Cormode, David P.

    2014-01-01

    Bismuth nanoparticles have been proposed as a novel CT contrast agent, however few syntheses of biocompatible bismuth nanoparticles have been achieved. We herein report the synthesis of composite bismuth-iron oxide nanoparticles (BION) that are based on a clinically approved, dextran-coated iron oxide formulation; the particles have the advantage of acting as contrast agents for both CT and MRI. BION were synthesized and characterized using various analytical methods. BION CT phantom images revealed that the X-ray attenuation of the different formulations was dependent upon the amount of bismuth present in the nanoparticle, while T2-weighted MRI contrast decreased with increasing bismuth content. No cytotoxicity was observed in Hep G2 and BJ5ta cells after 24 hours incubation with BION. The above properties, as well as the yield of synthesis and bismuth inclusion efficiency, led us to select the Bi-30 formulation for in vivo experiments, performed in mice using a micro-CT and a 9.4 T MRI system. X-ray contrast was observed in the heart and blood vessels over a 2 hour period, indicating that Bi-30 has a prolonged circulation half-life. Considerable signal loss in T2-weighted MR images was observed in the liver compared to pre-injection scans. Evaluation of the biodistribution of Bi-30 revealed that bismuth is excreted via the urine, with significant concentrations found in the kidneys and urine. In vitro experiments confirmed the degradability of Bi-30. In summary, dextran coated BION are biocompatible, biodegradable, possess strong X-ray attenuation properties and also can be used as T2-weighted MR contrast agents. PMID:25485115

  14. Dextran coated bismuth-iron oxide nanohybrid contrast agents for computed tomography and magnetic resonance imaging.

    PubMed

    Naha, Pratap C; Zaki, Ajlan Al; Hecht, Elizabeth; Chorny, Michael; Chhour, Peter; Blankemeyer, Eric; Yates, Douglas M; Witschey, Walter R T; Litt, Harold I; Tsourkas, Andrew; Cormode, David P

    2014-12-14

    Bismuth nanoparticles have been proposed as a novel CT contrast agent, however few syntheses of biocompatible bismuth nanoparticles have been achieved. We herein report the synthesis of composite bismuth-iron oxide nanoparticles (BION) that are based on a clinically approved, dextran-coated iron oxide formulation; the particles have the advantage of acting as contrast agents for both CT and MRI. BION were synthesized and characterized using various analytical methods. BION CT phantom images revealed that the X-ray attenuation of the different formulations was dependent upon the amount of bismuth present in the nanoparticle, while T2-weighted MRI contrast decreased with increasing bismuth content. No cytotoxicity was observed in Hep G2 and BJ5ta cells after 24 hours incubation with BION. The above properties, as well as the yield of synthesis and bismuth inclusion efficiency, led us to select the Bi-30 formulation for in vivo experiments, performed in mice using a micro-CT and a 9.4 T MRI system. X-ray contrast was observed in the heart and blood vessels over a 2 hour period, indicating that Bi-30 has a prolonged circulation half-life. Considerable signal loss in T2-weighted MR images was observed in the liver compared to pre-injection scans. Evaluation of the biodistribution of Bi-30 revealed that bismuth is excreted via the urine, with significant concentrations found in the kidneys and urine. In vitro experiments confirmed the degradability of Bi-30. In summary, dextran coated BION are biocompatible, biodegradable, possess strong X-ray attenuation properties and also can be used as T2-weighted MR contrast agents.

  15. Multispectral photoacoustic decomposition with localized regularization for detecting targeted contrast agent

    NASA Astrophysics Data System (ADS)

    Tavakoli, Behnoosh; Chen, Ying; Guo, Xiaoyu; Kang, Hyun Jae; Pomper, Martin; Boctor, Emad M.

    2015-03-01

    Targeted contrast agents can improve the sensitivity of imaging systems for cancer detection and monitoring the treatment. In order to accurately detect contrast agent concentration from photoacoustic images, we developed a decomposition algorithm to separate photoacoustic absorption spectrum into components from individual absorbers. In this study, we evaluated novel prostate-specific membrane antigen (PSMA) targeted agents for imaging prostate cancer. Three agents were synthesized through conjugating PSMA-targeting urea with optical dyes ICG, IRDye800CW and ATTO740 respectively. In our preliminary PA study, dyes were injected in a thin wall plastic tube embedded in water tank. The tube was illuminated with pulsed laser light using a tunable Q-switch ND-YAG laser. PA signal along with the B-mode ultrasound images were detected with a diagnostic ultrasound probe in orthogonal mode. PA spectrums of each dye at 0.5 to 20 μM concentrations were estimated using the maximum PA signal extracted from images which are obtained at illumination wavelengths of 700nm-850nm. Subsequently, we developed nonnegative linear least square optimization method along with localized regularization to solve the spectral unmixing. The algorithm was tested by imaging mixture of those dyes. The concentration of each dye was estimated with about 20% error on average from almost all mixtures albeit the small separation between dyes spectrums.

  16. Fluorescent and scattering contrast agents in a mouse model of colorectal cancer

    NASA Astrophysics Data System (ADS)

    Winkler, Amy M.; Rice, Photini F. S.; Troutman, Timothy S.; Backer, Marina V.; Backer, Joseph M.; Drezek, Rebekah A.; Romanowski, Marek; Barton, Jennifer K.

    2008-02-01

    In previous work we have demonstrated the utility of laser-induced fluorescence (LIF) and optical coherence tomography (OCT) to identify adenoma in mouse models of colorectal cancer with high sensitivity and specificity. However, improved sensitivity to early disease, as well as the ability to distinguish confounders (e.g. fecal contamination, natural variations in mucosal thickness), is desired. In this study, we investigated the signal enhancement of fluorescent and scattering contrast agents in the colons of AOM-treated mice. The fluorescent tracer scVEGF/Cy, targeted to receptors for vascular endothelial growth factor, was visualized on a dual modality OCT/LIF endoscopic system with 1300-nm center wavelength OCT source and 635-nm LIF excitation. Scattering agents were tested with an 890-nm center wavelength endoscopic OCT system. Agents included nanoshells, 120-nm in diameter, and nanorods, 20-nm in diameter by 80-nm in length. Following imaging, colons were excised. Tissue treated with fluorophore was imaged on an epifluorescence microscope. Histological sections were obtained and stained with H&E and silver enhancer to verify disease and identify regions of gold uptake, respectively. Non-specific signal enhancement was observed with the scattering contrast agents. Specificity for adenoma was seen with the scVEGF/Cy dye.

  17. Bismuth@US-tubes as a Potential Contrast Agent for X-ray Imaging Applications

    PubMed Central

    Rivera, Eladio J.; Tran, Lesa A.; Hernández-Rivera, Mayra; Yoon, Diana; Mikos, Antonios G.; Rusakova, Irene A.; Cheong, Benjamin Y.; Cabreira-Hansen, Maria da Graça; Willerson, James T.; Perin, Emerson C.; Wilson, Lon J.

    2013-01-01

    The encapsulation of bismuth as BiOCl/Bi2O3 within ultra-short (ca. 50 nm) single-walled carbon nanocapsules (US-tubes) has been achieved. The Bi@US-tubes have been characterized by high-resolution transmission electron microscopy (HR-TEM), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Bi@US-tubes have been used for intracellular labeling of pig bone marrow-derived mesenchymal stem cells (MSCs) to show high X-ray contrast in computed tomography (CT) cellular imaging for the first time. The relatively high contrast is achieved with low bismuth loading (2.66% by weight) within the US-tubes and without compromising cell viability. X-ray CT imaging of Bi@US-tubes-labeled MSCs showed a nearly two-fold increase in contrast enhancement when compared to unlabeled MSCs in a 100 kV CT clinical scanner. The CT signal enhancement from the Bi@US-tubes is 500 times greater than polymer-coated Bi2S3 nanoparticles and several-fold that of any clinical iodinated contrast agent (CA) at the same concentration. Our findings suggest that the Bi@US-tubes can be used as a potential new class of X-ray CT agent for stem cell labeling and possibly in vivo tracking. PMID:24288589

  18. Gadolinium contrast agent-induced CD163+ ferroportin+ osteogenic cells in nephrogenic systemic fibrosis.

    PubMed

    Swaminathan, Sundararaman; Bose, Chhanda; Shah, Sudhir V; Hall, Kimberly A; Hiatt, Kim M

    2013-09-01

    Gadolinium-based contrast agents are linked to nephrogenic systemic fibrosis in patients with renal insufficiency. The pathology of nephrogenic systemic fibrosis is characterized by abnormal tissue repair: fibrosis and ectopic ossification. The mechanisms by which gadolinium could induce fibrosis and ossification are not known. We examined in vitro the effect of a gadolinium-based contrast agent on human peripheral blood mononuclear cells for phenotype and function relevant to the pathology of nephrogenic systemic fibrosis using immunofluorescence, flow cytometry, real-time PCR, and osteogenic assays. We also examined tissues from patients with nephrogenic systemic fibrosis, using IHC to identify the presence of cells with phenotype induced by gadolinium. Gadolinium contrast induced differentiation of human peripheral blood mononuclear cells into a unique cellular phenotype--CD163(+) cells expressing proteins involved in fibrosis and bone formation. These cells express fibroblast growth factor (FGF)23, osteoblast transcription factors Runt-related transcription factor 2, and osterix, and show an osteogenic phenotype in in vitro assays. We show in vivo the presence of CD163(+)/procollagen-1(+)/osteocalcin(+) cells in the fibrotic and calcified tissues of nephrogenic systemic fibrosis patients. Gadolinium contrast-induced CD163(+)/ferroportin(+)/FGF23(+) cells with osteogenic potential may play a role in systemic fibrosis and ectopic ossification in nephrogenic systemic fibrosis.

  19. Pump-probe optical coherence tomography using microencapsulated methylene blue as a contrast agent (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Kim, Wihan; Zebrowski, Erin; Lopez, Hazel C.; Applegate, Brian E.; Charoenphol, Phapanin; Jo, Javier A.

    2016-03-01

    Molecular contrast imaging can target specific molecules or receptors to provide detailed information on the local biochemistry and yield enhanced visualization of pathological and physiological processes. When paired with Optical Coherence Tomography (OCT) it can simultaneously supply the morphological context for the molecular information. We recently demonstrated in vivo molecular contrast imaging of methylene blue (MB) using a 663 nm diode laser as a pump in a Pump-Probe OCT (PPOCT) system. The simple addition of a dichroic mirror in the sample arm enabled PPOCT imaging with a typical 830-nm band spectral-domain OCT system. Here we report on the development of a microencapsulated MB contrast agent. The poly lactic-co-glycolic acid (PLGA) microspheres loaded with MB offer several advantages over bare MB. The microsphere encapsulation improves the PPOCT signal both by enhancing the scattering and preventing the reduction of MB to leucomethylene blue. The surface of the microsphere can readily be functionalized to enable active targeting of the contrast agent without modifying the excited state dynamics of MB that enable PPOCT imaging. Both MB and PLGA are used clinically. PLGA is FDA approved and used in drug delivery and tissue engineering applications. 2.5 μm diameter microspheres were synthesized with an inner core containing 0.01% (w/v) aqueous MB. As an initial demonstration the MB microspheres were imaged in a 100 μm diameter capillary tube submerged in a 1% intralipid emulsion.

  20. Biocompatible polypyrrole nanoparticles as a novel organic photoacoustic contrast agent for deep tissue imaging

    NASA Astrophysics Data System (ADS)

    Zha, Zhengbao; Deng, Zijian; Li, Yanyan; Li, Changhui; Wang, Jinrui; Wang, Shumin; Qu, Enze; Dai, Zhifei

    2013-05-01

    Photoacoustic tomography (PAT) has emerged as a hybrid, nonionizing imaging modality because of its satisfactory spatial resolution and high soft tissue contrast. Here, we demonstrate the application of a novel organic PAT contrast agent based on polypyrrole nanoparticles (PPy NPs). Monodisperse PPy NPs are ~46 nm in diameter with strong absorption in the near-infrared (NIR) range, which allowed visualization of PPy NP-containing agar gel embedded in chicken breast muscle at a depth of ~4.3 cm. Compared with PAT images based on the intrinsic optical contrast in mice, the PAT images acquired within 1 h after intravenous administration of PPy NPs showed the brain vasculature with greater clarity than hemoglobin in blood. Preliminary results showed no acute toxicity to the vital organs (heart, liver, spleen, lungs and kidneys) in mice following a single imaging dose of PPy NPs. Our results indicate that PPy NPs are promising contrast agents for PAT with good biocompatibility, high spatial resolution and enhanced sensitivity.

  1. Differential structured illumination microendoscopy for in vivo imaging of molecular contrast agents

    PubMed Central

    Keahey, Pelham; Ramalingam, Preetha; Schmeler, Kathleen

    2016-01-01

    Fiber optic microendoscopy has shown promise for visualization of molecular contrast agents used to study disease in vivo. However, fiber optic microendoscopes have limited optical sectioning capability, and image contrast is limited by out-of-focus light generated in highly scattering tissue. Optical sectioning techniques have been used in microendoscopes to remove out-of-focus light but reduce imaging speed or rely on bulky optical elements that prevent in vivo imaging. Here, we present differential structured illumination microendoscopy (DSIMe), a fiber optic system that can perform structured illumination in real time for optical sectioning without any opto-mechanical components attached to the distal tip of the fiber bundle. We demonstrate the use of DSIMe during in vivo fluorescence imaging in patients undergoing surgery for cervical adenocarcinoma in situ. Images acquired using DSIMe show greater contrast than standard microendoscopy, improving the ability to detect cellular atypia associated with neoplasia. PMID:27621464

  2. The effects of acoustic radiation force on contrast agents: Experimental and theoretial analysis

    NASA Astrophysics Data System (ADS)

    Dayton, Paul Alexander

    The goal of this research is to understand the response of ultrasound contrast agents to acoustic radiation force. Ultrasound contrast agents are encapsulated microbubbles similar in size and rheologic behavior to human erythrocytes. A core of either air or a high- molecular weight gas makes these microbubbles extremely compressible and highly echogenic. Clinically, the detection of blood is difficult without contrast agents because the echoes from blood cells are typically 30-40 dB less than tissue echoes. Ultrasound contrast agents have been shown to be extremely useful in assisting delineation of perfused tissue in echocardiography, and are being increasingly used for tumor detection in radiology. The high compressibility of gas-filled contrast agents makes these microbubbles susceptible to translation due to radiation force. Thus, it is important to understand the effects of this force in order to avoid erroneous measurements based on the location and flow velocity of microbubbles. In addition, the ability to displace and concentrate microbubbles may be an advantage in targeted imaging, targeted therapy, or industrial applications where it is desired to localize microbubbles in a region. In this study, experimental and theoretical tools are combined to investigate the interaction between microbubbles and an acoustic pulse. Several unique experimental systems allow visualization and analysis of the radius-time curves of individual microbubbles, the displacement of individual microbubbles in-vitro, and the displacement of microbubbles in-vivo. Theoretical analysis illustrates that the effect of radiation force on microbubbles is directly proportional to the product of the bubble volume and the acoustic pressure gradient. A model designed to simulate the radius-time behavior of individual microbubbles is verified from experimental data, and used to estimate the magnitude of radiation force. The resulting bubble translation is determined using a second model

  3. Clinical Pharmacology, Uses, and Adverse Reactions of Iodinated Contrast Agents: A Primer for the Non-radiologist

    PubMed Central

    Pasternak, Jeffrey J.; Williamson, Eric E.

    2012-01-01

    Iodinated contrast agents have been in use since the 1950s to facilitate radiographic imaging modalities. Physicians in almost all specialties will either administer these agents or care for patients who have received these drugs. Different iodinated contrast agents vary greatly in their properties, uses, and toxic effects. Therefore, clinicians should be at least superficially familiar with the clinical pharmacology, administration, risks, and adverse effects associated with iodinated contrast agents. This primer offers the non-radiologist physician the opportunity to gain insight into the use of this class of drugs. PMID:22469351

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

    PubMed

    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. PMID:27075920

  5. Highly monodisperse low-magnetization magnetite nanocubes as simultaneous T1-T2 MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Sharma, V. K.; Alipour, A.; Soran-Erdem, Z.; Aykut, Z. G.; Demir, H. V.

    2015-06-01

    We report the first study of highly monodisperse and crystalline iron oxide nanocubes with sub-nm controlled size distribution (9.7 +/- 0.5 nm in size) that achieve simultaneous contrast enhancement in both T1- and T2-weighted magnetic resonance imaging (MRI). Here, we confirmed the magnetite structure of iron oxide nanocubes by X-ray diffraction (XRD), selected area electron diffraction (SAED) pattern, optical absorption and Fourier transformed infrared (FT-IR) spectra. These magnetite nanocubes exhibit superparamagnetic and paramagnetic behavior simultaneously by virtue of their finely controlled shape and size. The magnetic measurements reveal that the magnetic moment values are favorably much lower because of the small size and cubic shape of the nanoparticles, which results in an enhanced spin canting effect. As a proof-of-concept demonstration, we showed their potential as dual contrast agents for both T1- and T2-weighted MRI via phantom studies, in vivo imaging and relaxivity measurements. Therefore, these low-magnetization magnetite nanocubes, while being non-toxic and bio-compatible, hold great promise as excellent dual-mode T1 and T2 contrast agents for MRI.We report the first study of highly monodisperse and crystalline iron oxide nanocubes with sub-nm controlled size distribution (9.7 +/- 0.5 nm in size) that achieve simultaneous contrast enhancement in both T1- and T2-weighted magnetic resonance imaging (MRI). Here, we confirmed the magnetite structure of iron oxide nanocubes by X-ray diffraction (XRD), selected area electron diffraction (SAED) pattern, optical absorption and Fourier transformed infrared (FT-IR) spectra. These magnetite nanocubes exhibit superparamagnetic and paramagnetic behavior simultaneously by virtue of their finely controlled shape and size. The magnetic measurements reveal that the magnetic moment values are favorably much lower because of the small size and cubic shape of the nanoparticles, which results in an enhanced spin

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

    PubMed Central

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

    2013-01-01

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

  7. Generation of superparamagnetic liposomes revealed as highly efficient MRI contrast agents for in vivo imaging.

    PubMed

    Martina, Marie-Sophie; Fortin, Jean-Paul; Ménager, Christine; Clément, Olivier; Barratt, Gillian; Grabielle-Madelmont, Cécile; Gazeau, Florence; Cabuil, Valérie; Lesieur, Sylviane

    2005-08-01

    Maghemite (gamma-Fe2O3) nanocrystals stable at neutral pH and in isotonic aqueous media were synthesized and encapsulated within large unilamellar vesicles of egg phosphatidylcholine (EPC) and distearoyl-SN-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE-PEG(2000), 5 mol %), formed by film hydration coupled with sequential extrusion. The nonentrapped particles were removed by flash gel exclusion chromatography. The magnetic-fluid-loaded liposomes (MFLs) were homogeneous in size (195 +/- 33 hydrodynamic diameters from quasi-elastic light scattering). Iron loading was varied from 35 up to 167 Fe(III)/lipid mol %. Physical and superparamagnetic characteristics of the iron oxide particles were preserved after liposome encapsulation as shown by cryogenic transmission electron microscopy and magnetization curve recording. In biological media, MFLs were highly stable and avoided ferrofluid flocculation while being nontoxic toward the J774 macrophage cell line. Moreover, steric stabilization ensured by PEG-surface-grafting significantly reduced liposome association with the macrophages. The ratios of the transversal (r2) and longitudinal (r1) magnetic resonance (MR) relaxivities of water protons in MFL dispersions (6 < r2/r1 < 18) ranked them among the best T2 contrast agents, the higher iron loading the better the T2 contrast enhancement. Magnetophoresis demonstrated the possible guidance of MFLs by applying a magnetic field gradient. Mouse MR imaging assessed MFLs efficiency as contrast agents in vivo: MR angiography performed 24 h after intravenous injection of the contrast agent provided the first direct evidence of the stealthiness of PEG-ylated magnetic-fluid-loaded liposomes. PMID:16045355

  8. Dimeric versus monomeric nonionic contrast agents in visualization of coronary arteries.

    PubMed

    Rienmüller, R; Brekke, O; Kampenes, V B; Reiter, U

    2001-06-01

    A cubital intravenous iodine contrast agent enhancement is used to visualize coronary arteries using EBT. The quality of the coronary artery visualization however is limited by the nearly simultaneous approximation of CT values in coronary arteries and myocardial tissue. The objective of the study was to evaluate if "under real clinical circumstances" the lower iodine concentration and the dimeric based characteristic of iodixanol may effect the kinetic of the applied contrast agent and the visualization of coronary arteries studied noninvasively by EBT. A double-blind, randomized, parallel study was performed in 111 cardiac patients, using iodixanol 270 mg I/ml or iohexol 300 mg I/ml. The kinetics of contrast enhancement was studied in the flow mode measuring following parameters: mean arrival time and mean time to reach peak CT values in the pulmonary trunk, transit time from the pulmonary trunk to the aorta as well as mean and maximum CT values in the left ventricular chamber and in the myocardium with respect to the body mass index. The mean difference of CT values in the left ventricular chamber and the myocardium was calculated. The length of the visualized coronary arteries was assessed and the diagnostic quality of coronary artery visualization scored on a visual analogue scale. Although iodixanol was used with a lower iodine concentration than iohexol there was no significant statistical difference between both groups with respect to the diagnostic visualization and length assessment of the coronary arteries as well as in the mean difference of CT values in the left ventricular chamber and the myocardium. This means that the advantageous dimeric characteristics of iodixanol may be used to reduce the amount of applicated iodine in contrast agents without loss of diagnostic image quality and information.

  9. Tunable, biodegradable gold nanoparticles as contrast agents for computed tomography and photoacoustic imaging.

    PubMed

    Cheheltani, Rabee; Ezzibdeh, Rami M; Chhour, Peter; Pulaparthi, Kumidini; Kim, Johoon; Jurcova, Martina; Hsu, Jessica C; Blundell, Cassidy; Litt, Harold I; Ferrari, Victor A; Allcock, Harry R; Sehgal, Chandra M; Cormode, David P

    2016-09-01

    Gold nanoparticles (AuNP) have been proposed for many applications in medicine. Although large AuNP (>5.5 nm) are desirable for their longer blood circulation and accumulation in diseased tissues, small AuNP (<5.5 nm) are required for excretion via the kidneys. We present a novel platform where small, excretable AuNP are encapsulated into biodegradable poly di(carboxylatophenoxy)phosphazene (PCPP) nanospheres. These larger nanoparticles (Au-PCPP) can perform their function as contrast agents, then subsequently break down into harmless byproducts and release the AuNP for swift excretion. Homogeneous Au-PCPP were synthesized using a microfluidic device. The size of the Au-PCPP can be controlled by the amount of polyethylene glycol-polylysine (PEG-PLL) block co-polymer in the formulation. Synthesis of Au-PCPP nanoparticles and encapsulation of AuNP in PCPP were evaluated using transmission electron microscopy and their biocompatibility and biodegradability confirmed in vitro. The Au-PCPP nanoparticles were found to produce strong computed tomography contrast. The UV-Vis absorption peak of Au-PCPP can be tuned into the near infrared region via inclusion of varying amounts of AuNP and controlling the nanoparticle size. In vitro and in vivo experiments demonstrated the potential of Au-PCPP as contrast agents for photoacoustic imaging. Therefore, Au-PCPP nanoparticles have high potency as contrast agents for two imaging modalities, as well as being biocompatible and biodegradable, and thus represent a platform with potential for translation into the clinic. PMID:27322961

  10. Nanoparticle-based highly sensitive MRI contrast agents with enhanced relaxivity in reductive milieu.

    PubMed

    Sigg, Severin J; Santini, Francesco; Najer, Adrian; Richard, Pascal U; Meier, Wolfgang P; Palivan, Cornelia G

    2016-08-01

    Current magnetic resonance imaging (MRI) contrast agents often produce insufficient contrast for diagnosis of early disease stages, and do not sense their biochemical environments. Herein, we report a highly sensitive nanoparticle-based MRI probe with r1 relaxivity up to 51.7 ± 1.2 mM(-1) s(-1) (3T). Nanoparticles were co-assembled from Gd(3+) complexed to heparin-poly(dimethylsiloxane) copolymer, and a reduction-sensitive amphiphilic peptide serving to induce responsiveness to environmental changes. The release of the peptide components leads to a r1 relaxivity increase under reducing conditions and increases the MRI contrast. In addition, this MRI probe has several advantages, such as a low cellular uptake, no apparent cellular toxicity (tested up to 1 mM Gd(3+)), absence of an anticoagulation property, and a high shelf stability (no increase in free Gd(3+) over 7 months). Thus, this highly sensitive T1 MRI contrast nanoparticle system represents a promising probe for early diagnosis through possible accumulation and contrast enhancement within reductive extracellular tumour tissue. PMID:27435820

  11. Linear Gadolinium-Based Contrast Agents Are Associated With Brain Gadolinium Retention in Healthy Rats

    PubMed Central

    Robert, Philippe; Violas, Xavier; Grand, Sylvie; Lehericy, Stéphane; Idée, Jean-Marc; Ballet, Sébastien; Corot, Claire

    2016-01-01

    Objectives The aim of this study was to evaluate Gd retention in the deep cerebellar nuclei (DCN) of linear gadolinium-based contrast agents (GBCAs) compared with a macrocyclic contrast agent. Materials and Methods The brain tissue retention of Gd of 3 linear GBCAs (gadobenate dimeglumine, gadopentetate dimeglumine, and gadodiamide) and a macrocyclic GBCA (gadoterate meglumine) was compared in healthy rats (n = 8 per group) that received 20 intravenous injections of 0.6 mmol Gd/kg (4 injections per week for 5 weeks). An additional control group with saline was included. T1-weighted magnetic resonance imaging was performed before injection and once a week during the 5 weeks of injections and for another 4 additional weeks after contrast period. Total gadolinium concentration was measured with inductively coupled plasma mass spectrometry. Blinded qualitative and quantitative evaluations of the T1 signal intensity in DCN were performed, as well as a statistical analysis on quantitative data. Results At completion of the injection period, all the linear contrast agents (gadobenate dimeglumine, gadopentetate dimeglumine, and gadodiamide) induced a significant increase in signal intensity in DCN, unlike the macrocyclic GBCA (gadoterate meglumine) or saline. The T1 hypersignal enhancement kinetic was fast for gadodiamide. Total Gd concentrations for the 3 linear GBCAs groups at week 10 were significantly higher in the cerebellum (1.21 ± 0.48, 1.67 ± 0.17, and 3.75 ± 0.18 nmol/g for gadobenate dimeglumine, gadopentetate dimeglumine, and gadodiamide, respectively) than with the gadoterate meglumine (0.27 ± 0.16 nmol/g, P < 0.05) and saline (0.09 ± 0.12 nmol/g, P < 0.05). No significant difference was observed between the macrocyclic agent and saline. Conclusions Repeated administrations of the linear GBCAs gadodiamide, gadobenate dimeglumine, and gadopentetate dimeglumine to healthy rats were associated with progressive and significant T1 signal hyperintensity in the

  12. The NiCEST approach: nickel(II) paraCEST MRI contrast agents.

    PubMed

    Olatunde, Abiola O; Dorazio, Sarina J; Spernyak, Joseph A; Morrow, Janet R

    2012-11-14

    Paramagnetic Ni(II) complexes are shown here to form paraCEST MRI contrast agents (paraCEST = paramagnetic chemical exchange saturation transfer; NiCEST = Ni(II) based CEST agents). Three azamacrocycles with amide pendent groups bind Ni(II) to form stable NiCEST contrast agents including 1,4,7-tris(carbamoylmethyl)-1,4,7-triazacyclononane (L1), 1,4,8,11-tetrakis(carbamoylmethyl)-1,4,8,11-tetraazacyclotetradecane (L2), and 7,13-bis(carbamoylmethyl)-1,4,10-trioxa-7,13-diazacyclopentadecane (L3). [Ni(L3)](2+), [Ni(L1)](2+), and [Ni(L2)](2+) have CEST peaks attributed to amide protons that are shifted 72, 76, and 76 ppm from the bulk water resonance, respectively. Both CEST MR images and CEST spectroscopy show that [Ni(L3)](2+) has the largest CEST effect in 100 mM NaCl, 20 mM HEPES pH 7.4 at 37 °C. This larger CEST effect is attributed to the sharper proton resonances of the complex which arise from a rigid structure and low relaxivity.

  13. Photoacoustic imaging and surface-enhanced Raman spectroscopy using dual modal contrast agents

    NASA Astrophysics Data System (ADS)

    Park, Sungjo; Lee, Seunghyun; Cha, Myeonggeun; Jeong, Cheolhwan; Kang, Homan; Park, So Yeon; Lee, Yoon-sik; Jeong, Daehong; Kim, Chulhong

    2016-03-01

    Recently, photoacoustic tomography (PAT) has emerged as a remarkable non-invasive imaging modality that provides a strong optical absorption contrast, high ultrasonic resolution, and great penetration depth. Thus, PAT has been widely used as an in vivo preclinical imaging tool. Surface-enhanced Raman spectroscopy (SERS) is another attractive sensing technology in biological research because it offers highly sensitive chemical analyses and multiplexed detection. By performing dual-modal imaging of SERS and PAT, high-resolution structural PAT imaging and high-sensitivity SERS sensing can be achieved. At the same time, it is equally important to develop a dual modal contrast agent for this purpose. To perform both PAT and SERS, we synthesized PEGylated silver bumpy nanoshells (AgBSs). The AgBSs generate strong PA signals owing to their strong optical absorption properties as well as sensitive SERS signals because of the surface plasmon resonance effect. Then, multiplexed Raman chemicals were synthesized to enhance the sensitivity of Raman. We have photoacoustically imaged the sentinel lymph nodes of small animals after intradermal injection of multiplexed agents. Furthermore, the chemical composition of each agent has been distinguished through SERS.

  14. Copper oxide nanoparticles as contrast agents for MRI and ultrasound dual-modality imaging

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

    Multimodal medical imaging is gaining increased popularity in the clinic. This stems from the fact that data acquired from different physical phenomena may provide complementary information resulting in a more comprehensive picture of the pathological state. In this context, nano-sized contrast agents may augment the potential sensitivity of each imaging modality and allow targeted visualization of physiological points of interest (e.g. tumours). In this study, 7 nm copper oxide nanoparticles (CuO NPs) were synthesized and characterized. Then, in vitro and phantom specimens containing CuO NPs ranging from 2.4 to 320 μg · mL-1 were scanned, using both 9.4 T MRI and through-transmission ultrasonic imaging. The results show that the CuO NPs induce shortening of the magnetic T1 relaxation time on the one hand, and increase the speed of sound and ultrasonic attenuation coefficient on the other. Moreover, these visible changes are NP concentration-dependent. The change in the physical properties resulted in a substantial increase in the contrast-to-noise ratio (3.4-6.8 in ultrasound and 1.2-19.3 in MRI). In conclusion, CuO NPs are excellent candidates for MRI-ultrasound dual imaging contrast agents. They offer radiation-free high spatial resolution scans by MRI, and cost-effective high temporal resolution scans by ultrasound.

  15. New generation ICG-based contrast agents for ultrasound-switchable fluorescence imaging

    PubMed Central

    Yu, Shuai; Cheng, Bingbing; Yao, Tingfeng; Xu, Cancan; Nguyen, Kytai T.; Hong, Yi; Yuan, Baohong

    2016-01-01

    Recently, we developed a new technology, ultrasound-switchable fluorescence (USF), for high-resolution imaging in centimeter-deep tissues via fluorescence contrast. The success of USF imaging highly relies on excellent contrast agents. ICG-encapsulated poly(N-isopropylacrylamide) nanoparticles (ICG-NPs) are one of the families of the most successful near-infrared (NIR) USF contrast agents. However, the first-generation ICG-NPs have a short shelf life (<1 month). This work significantly increases the shelf life of the new-generation ICG-NPs (>6 months). In addition, we have conjugated hydroxyl or carboxyl function groups on the ICG-NPs for future molecular targeting. Finally, we have demonstrated the effect of temperature-switching threshold (Tth) and the background temperature (TBG) on the quality of USF images. We estimated that the Tth of the ICG-NPs should be controlled at ~38–40 °C (slightly above the body temperature of 37 °C) for future in vivo USF imaging. Addressing these challenges further reduces the application barriers of USF imaging. PMID:27775014

  16. Optically tunable nanoparticle contrast agents for early cancer detection: model-based analysis of gold nanoshells.

    PubMed

    Lin, Alex W H; Lewinski, Nastassja A; West, Jennifer L; Halas, Naomi J; Drezek, Rebekah A

    2005-01-01

    Many optical diagnostic approaches rely on changes in scattering and absorption properties to generate optical contrast between normal and diseased tissue. Recently, there has been increasing interest in using exogenous agents to enhance this intrinsic contrast with particular emphasis on the development for targeting specific molecular features of disease. Gold nanoshells are a class of core-shell nanoparticles with an extremely tunable peak optical resonance ranging from the near-UV to the mid-IR wavelengths. Using current chemistries, nanoshells of a wide variety of core and shell sizes can easily be fabricated to scatter and/or absorb light with optical cross sections often several times larger than the geometric cross section. Using gold nanoshells of different size and optical parameters, we employ Monte Carlo models to predict the effect of varying concentrations of nanoshells on tissue reflectance. The models demonstrate the importance of absorption from the nanoshells on remitted signals even when the optical extinction is dominated by scattering. Furthermore, because of the strong optical response of nanoshells, a considerable change in reflectance is observed with only a very small concentration of nanoshells. Characterizing the optical behavior of gold nanoshells in tissue will aid in developing nanoshells as contrast agents for optical diagnostics. PMID:16409100

  17. Properties evaluation of a new MRI contrast agent based on Gd-loaded nanoparticles.

    PubMed

    Riyahi-Alam, Nader; Behrouzkia, Zhaleh; Seifalian, Alexander; Haghgoo Jahromi, Soheila

    2010-12-01

    Nanosized materials of gadolinium oxide can provide high-contrast enhancement in magnetic resonance imaging (MRI). The aim of this research was to characterize a novel emulsion composed of a silicon-based nanocomposite polymer (NCP) and gadolinium (III) oxide (Gd₂O₃) nanoparticles. The size and morphological structure of this nanoparticle are determined by particle size analysis device (zeta sizer) and transmission electronic microscope. We determined composition of Gd₂O₃ nanoparticles with energy dispersive X-ray analysis (EDXA) and magnetic resonance signal by T₁-weighted MRI. Cytotoxicity of Gd₂O₃ nanoparticles in SK-MEL-3 cancer cells was evaluated. Zeta sizer showed Gd₂O₃ nanoparticles to be 75 nm in size. EDXA indicated the two main chemical components of gadolinium-nanocomposite polymer emulsion: gadolinium and silicon and MRI also showed a significantly higher incremental relaxivity for Gd₂O₃ nanoparticles compared to Magnevist (conventional contrast agent). In such concentrations, the slope of R₁ relaxivity (1/T₁) vs. concentration curve of Magnevist and Gd₂O₃ were 4.33, 7.98 s⁻¹ mM⁻¹. The slope of R₂ relaxivity (1/T₂) vs. concentration curve of Magnevist and Gd₂O₃ were 5.06, 13.75 s⁻¹ mM⁻¹. No appreciable toxicity was observed with Gd₂O₃ nanoparticles. Gadolinium-nanocomposite polymer emulsion is well characterized and has potential as a useful contrast agent for magnetic resonance molecular imaging.

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

    SciTech Connect

    Deli, Martin; Mateiescu, Serban Busch, Martin; Becker, Jan Garmer, Marietta Groenemeyer, Dietrich

    2013-06-15

    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.

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

    PubMed Central

    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

  20. Ultrasound contrast agent fabricated from microbubbles containing instant adhesives, and its ultrasound imaging ability

    NASA Astrophysics Data System (ADS)

    Makuta, T.; Tamakawa, Y.

    2012-04-01

    Non-invasive surgery techniques and drug delivery system with acoustic characteristics of ultrasound contrast agent have been studied intensively in recent years. Ultrasound contrast agent collapses easily under the blood circulating and the ultrasound irradiating because it is just a stabilized bubble without solid-shell by surface adsorption of surfactant or lipid. For improving the imaging stability, we proposed the fabrication method of the hollow microcapsule with polymer shell, which can be fabricated just blowing vapor of commonly-used instant adhesive (Cyanoacrylate monomer) into water as microbubbles. Therefore, the cyanoacrylate vapor contained inside microbubble initiates polymerization on the gasliquid interface soon after microbubbles are generated in water. Consequently, hollow microspheres coated by cyanoacrylate thin film are generated. In this report, we revealed that diameter distributions of microbubbles and microcapsules were approximately same and most of them were less than 10 μm, that is, smaller than blood capillary. In addition, we also revealed that hollow microcapsules enhanced the acoustic signal especially in the harmonic contrast imaging and were broken or agglomerated under the ultrasound field. As for the yield of hollow microcapsules, we revealed that sodium dodecyl sulfate addition to water phase instead of deoxycolic acid made the fabrication yield increased.

  1. Mesoporous Bamboo Charcoal Nanoparticles as a New Near-Infrared Responsive Drug Carrier for Imaging-Guided Chemotherapy/Photothermal Synergistic Therapy of Tumor.

    PubMed

    Dong, Xinghua; Yin, Wenyan; Yu, Jie; Dou, Ruixia; Bao, Tao; Zhang, Xiao; Yan, Liang; Yong, Yuan; Su, Chunjian; Wang, Qing; Gu, Zhanjun; Zhao, Yuliang

    2016-07-01

    Near-infrared-(NIR)-light-triggered photothermal nanocarriers have attracted much attention for the construction of more smart and effective therapeutic platforms in nanomedicine. Here, a multifunctional drug carrier based on a low cost, natural, and biocompatible material, bamboo charcoal nanoparticles (BCNPs), which are prepared by the pyrolysis of bamboo followed by physical grinding and ultrasonication is reported. The as-prepared BCNPs with porous structure possess not only large surface areas for drug loading but also an efficient photothermal effect, making them become both a suitable drug carrier and photothermal agent for cancer therapy. After loading doxorubicin (DOX) into the BCNPs, the resulting DOX-BCNPs enhance drug potency and more importantly can overcome the drug resistance of DOX in a MCF-7 cancer cell model by significantly increasing cellular uptake while remarkably decreasing drug efflux. The in vivo synergistic effect of combining chemotherapy and photothermal therapy in this drug delivery system is also demonstrated. In addition, the BCNPs enhance optoacoustic imaging contrast due to their high NIR absorbance. Collectively, it is demonstrated that the BCNP drug delivery system constitutes a promising and effective nanocarrier for simultaneous bioimaging and chemo-photothermal synergistic therapy of cancer.

  2. Mesoporous Bamboo Charcoal Nanoparticles as a New Near-Infrared Responsive Drug Carrier for Imaging-Guided Chemotherapy/Photothermal Synergistic Therapy of Tumor.

    PubMed

    Dong, Xinghua; Yin, Wenyan; Yu, Jie; Dou, Ruixia; Bao, Tao; Zhang, Xiao; Yan, Liang; Yong, Yuan; Su, Chunjian; Wang, Qing; Gu, Zhanjun; Zhao, Yuliang

    2016-07-01

    Near-infrared-(NIR)-light-triggered photothermal nanocarriers have attracted much attention for the construction of more smart and effective therapeutic platforms in nanomedicine. Here, a multifunctional drug carrier based on a low cost, natural, and biocompatible material, bamboo charcoal nanoparticles (BCNPs), which are prepared by the pyrolysis of bamboo followed by physical grinding and ultrasonication is reported. The as-prepared BCNPs with porous structure possess not only large surface areas for drug loading but also an efficient photothermal effect, making them become both a suitable drug carrier and photothermal agent for cancer therapy. After loading doxorubicin (DOX) into the BCNPs, the resulting DOX-BCNPs enhance drug potency and more importantly can overcome the drug resistance of DOX in a MCF-7 cancer cell model by significantly increasing cellular uptake while remarkably decreasing drug efflux. The in vivo synergistic effect of combining chemotherapy and photothermal therapy in this drug delivery system is also demonstrated. In addition, the BCNPs enhance optoacoustic imaging contrast due to their high NIR absorbance. Collectively, it is demonstrated that the BCNP drug delivery system constitutes a promising and effective nanocarrier for simultaneous bioimaging and chemo-photothermal synergistic therapy of cancer. PMID:27276383

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

    PubMed

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

    2016-01-20

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

  4. Mesoporous silica nanoparticles as a breast cancer targeting contrast agent for ultrasound imaging

    NASA Astrophysics Data System (ADS)

    Milgroom, Andrew Carson

    Current clinical use of ultrasound for breast cancer diagnostics is strictly limited to a role as a supplementary detection method to other modalities, such as mammography or MRI. A major reason for ultrasound’s role as a secondary method is its inability to discern between cancerous and non-cancerous bodies of similar density, like dense calcifications or benign fibroadenomas. Its detection capabilities are further diminished by the variable density of the surrounding breast tissue with the progression of age. Preliminary studies suggest that mesoporous silica nanoparticles (MSNs) are a good candidate as an in situ contrast agent for ultrasound. By tagging the silica particle surface with the cancer-targeting antibody trastuzumab (Herceptin), suspect regions of interest can be better identified in real time with standard ultrasound equipment. Once the silica-antibody conjugate is injected into the bloodstream and enters the cancerous growth’s vasculature, the antibody arm will bind to HER2, a cell surface receptor known to be dysfunctional or overexpressed in certain types of breast cancer. As more particles aggregate at the cell surface, backscatter of the ultrasonic waves increases as a result of the higher porous silica concentration. This translates to an increased contrast around the lesion boundary. Tumor detection through ultrasound contrast enhancement provides a tremendous advantage over current cancer diagnostics because is it significantly cheaper and can be monitored in real time. Characterization of MCM-41 type MSNs suggests that these particles have sufficient stability and particle size distribution to penetrate through fenestrated tumor vasculature and accumulate in HER2+ breast cancer cells through the enhanced permeation and retention (EPR) effect. A study of acoustic properties showed that particle concentration is linearly correlated to image contrast in clinical frequency-range ultrasound, although less pronounced than typical microbubble

  5. Microwave breast tumor detection and size estimation using contrast-agent-loaded magnetotactic bacteria.

    PubMed

    Chen, Yifan; Kosmas, Panagiotis; Martel, Sylvain

    2013-01-01

    We propose a new approach to microwave breast tumor detection based on the use of bio-compatible flagellated magnetotactic bacteria (MTB). Previous work has shown that the directions and speeds of these bacterial microrobots adapted to operate in human microvasculature can be guided along preplanned paths deep inside the human body through external magnetic fields. Furthermore, a microwave contrast agent can be loaded onto MTB to alter the dielectric properties of tissues near the agent. Based on these two phenomena, we illustrate how multiple agglomerations of MTB released into human breast could be tracked simultaneously and monitored using differential microwave imaging (DMI) techniques. We also present novel strategies to detect and localize a breast cancerous mass as well as estimate its size through this new DMI-trackable bacterial propulsion and steering approach, and use an anatomically realistic breast model as a testbed to verify the feasibility of this breast cancer diagnostic technique.

  6. T₁ and T₂ dual-mode MRI contrast agent for enhancing accuracy by engineered nanomaterials.

    PubMed

    Shin, Tae-Hyun; Choi, Jin-sil; Yun, Seokhwan; Kim, Il-Sun; Song, Ho-Taek; Kim, Youngmee; Park, Kook In; Cheon, Jinwoo

    2014-04-22

    One of the holy grails in biomedical imaging technology is to achieve accurate imaging of biological targets. The development of sophisticated instrumentation and the use of contrast agents have improved the accuracy of biomedical imaging. However, the issue of false imaging remains a problem. Here, we developed a dual-mode artifact filtering nanoparticle imaging agent (AFIA) that comprises a combination of paramagnetic and superparamagnetic nanomaterials. This AFIA has the ability to perform "AND logic gate" algorithm to eliminate false errors (artifacts) from the raw images to enhance accuracy of the MRI. We confirm the artifact filtering capability of AFIA in MRI phantoms and further demonstrate that artifact-free imaging of stem cell migration is possible in vivo.

  7. Investigating the stability of gadolinium based contrast agents towards UV radiation.

    PubMed

    Birka, Marvin; Roscher, Jörg; Holtkamp, Michael; Sperling, Michael; Karst, Uwe

    2016-03-15

    Since the 1980s, the broad application of gadolinium(Gd)-based contrast agents for magnetic resonance imaging (MRI) has led to significantly increased concentrations of Gd in the aqueous environment. Little is known about the stability of these highly polar xenobiotics under environmental conditions, in wastewater and in drinking water treatment. Therefore, the stability of frequently applied Gd-based MRI contrast agents towards UV radiation was investigated. The hyphenation of hydrophilic interaction liquid chromatography (HILIC) with inductively coupled plasma mass spectrometry (ICP-MS) and of HILIC with electrospray ionization mass spectrometry (ESI-MS) provided quantitative elemental information as well as structural information. The contrast agents Gd-DTPA, Gd-DOTA and Gd-BT-DO3A showed a high stability in irradiation experiments applying a wavelength range from 220 nm to 500 nm. Nevertheless, the degradation of Gd-BOPTA as well as the formation of Gd-containing transformation products was observed by means of HILIC-ICP-MS. Matrix-dependent irradiation experiments showed a degradation of Gd-BOPTA down to 3% of the initial amount in purified water after 300 min, whereas the degradation was slowed down in drinking water and surface water. Furthermore, it was observed that the sum of species continuously decreased with proceeding irradiation in all matrices. After irradiation in purified water for 300 min only 16% of the sum of species was left. This indicates a release of Gd(III) ions from the complex in course of irradiation. HILIC-ESI-MS measurements revealed that the transformation products mostly resulted from O-dealkylation and N-dealkylation reactions. In good correlation with retention times, the majority of transformation products were found to be more polar than Gd-BOPTA itself. Based on accurate masses, sum formulas were obtained and structures could be proposed.

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

    NASA Astrophysics Data System (ADS)

    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 (< 40 nm) but different coatings of diethyleneglycol (DEG) as Gd2O3-DEG and methoxy polyethylene glycol-silane (mPEG-silane: 550 and 2000 Dalton) as SPGO-mPEG-silane550 and SPGO-mPEG-silane2000, respectively, in the SK-MEL3 cell line, by light microscopy, MTT assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, and the LDH assay detecting lactate dehydrogenase activity. The viability values were not statistically different between the three nanoparticles and Gd-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.

  9. Relationship between surface area of nonperfused myocardium and extravascular extraction of contrast agent following coronary microembolization.

    PubMed

    Malyar, Nasser M; Lerman, Lilach O; Gössl, Mario; Beighley, Patricia E; Ritman, Erik L

    2011-08-01

    Myocardial microvascular permeability and coronary sinus concentration of muscle metabolites have been shown to increase after myocardial ischemia due to epicardial coronary artery occlusion and reperfusion. However, their association with coronary microembolization is not well defined. This study tested the hypothesis that acute coronary microembolization increases microvascular permeability in the porcine heart. The left anterior descending perfusion territories of 34 anesthetized pigs (32 ± 3 kg) were embolized with equal volumes of microspheres of one of three diameters (10, 30, or 100 μm) and at three different doses for each size. Electron beam computed tomography (EBCT) was used to assess in vivo, microvascular extraction of a nonionic contrast agent (an index of microvascular permeability) before and after microembolization with microspheres at baseline and during adenosine infusion. A high-resolution three-dimensional microcomputed tomography (micro-CT) scanner was subsequently used to obtain ex vivo, the volume and corresponding surface area of the embolized myocardial islands within the perfusion territories of the microembolized coronary artery. EBCT-derived microvascular extraction of contrast agent increased within minutes after coronary microembolization (P < 0.001 vs. baseline and vs. control values). The increase in coronary microvascular permeability was highly correlated to the micro-CT-derived total surface area of the nonperfused myocardium (r = 0.83, P < 0.001). In conclusion, myocardial extravascular accumulation of contrast agent is markedly increased after coronary microembolization and its magnitude is in proportion to the surface area of the interface between the nonperfused and perfused territories. PMID:21543631

  10. Hyperosmolaric contrast agents in cartilage tomography may expose cartilage to overload-induced cell death.

    PubMed

    Turunen, M J; Töyräs, J; Lammi, M J; Jurvelin, J S; Korhonen, R K

    2012-02-01

    In clinical arthrographic examination, strong hypertonic contrast agents are injected directly into the joint space. This may reduce the stiffness of articular cartilage, which is further hypothesized to lead to overload-induced cell death. We investigated the cell death in articular cartilage while the tissue was compressed in situ in physiological saline solution and in full strength hypertonic X-ray contrast agent Hexabrix(TM). Samples were prepared from bovine patellae and stored in Dulbecco's Modified Eagle's Medium overnight. Further, impact tests with or without creep were conducted for the samples with contact stresses and creep times changing from 1 MPa to 10 MPa and from 0 min to 15 min, respectively. Finally, depth-dependent cell viability was assessed with a confocal microscope. In order to characterize changes in the biomechanical properties of cartilage as a result of the use of Hexabrix™, stress-relaxation tests were conducted for the samples immersed in Hexabrix™ and phosphate buffered saline (PBS). Both dynamic and equilibrium modulus of the samples immersed in Hexabrix™ were significantly (p<0.05) lower than those of the samples immersed in PBS. Cartilage samples immersed in physiological saline solution showed load-induced cell death primarily in the superficial and middle zones. However, under high 8-10 MPa contact stresses, the samples immersed in full strength Hexabrix™ showed significantly (p<0.05) higher number of dead cells than the samples compressed in physiological saline, especially in the deep zone of cartilage. In conclusion, excessive loading stresses followed by tissue creep might increase the risk for chondrocyte death in articular cartilage when immersed in hypertonic X-ray contrast agent, especially in the deep zone of cartilage.

  11. Flower-like PEGylated MoS2 nanoflakes for near-infrared photothermal cancer therapy

    PubMed Central

    Feng, Wei; Chen, Liang; Qin, Ming; Zhou, Xiaojun; Zhang, Qianqian; Miao, Yingke; Qiu, Kexin; Zhang, Yanzhong; He, Chuanglong

    2015-01-01

    Photothermal cancer therapy has attracted considerable interest for cancer treatment in recent years, but the effective photothermal agents remain to be explored before this strategy can be applied clinically. In this study, we therefore develop flower-like molybdenum disulfide (MoS2) nanoflakes and investigate their potential for photothermal ablation of cancer cells. MoS2 nanoflakes are synthesized via a facile hydrothermal method and then modified with lipoic acid-terminated polyethylene glycol (LA-PEG), endowing the obtained nanoflakes with high colloidal stability and very low cytotoxicity. Upon irradiation with near infrared (NIR) laser at 808 nm, the nanoflakes showed powerful ability of inducing higher temperature, good photothermal stability and high photothermal conversion efficiency. The in vitro photothermal effects of MoS2-PEG nanoflakes with different concentrations were also evaluated under various power densities of NIR 808-nm laser irradiation, and the results indicated that an effective photothermal killing of cancer cells could be achieved by a low concentration of nanoflakes under a low power NIR 808-nm laser irradiation. Furthermore, cancer cell in vivo could be efficiently destroyed via the photothermal effect of MoS2-PEG nanoflakes under the irradiation. These results thus suggest that the MoS2-PEG nanoflakes would be as promising photothermal agents for future photothermal cancer therapy. PMID:26632249

  12. Flower-like PEGylated MoS2 nanoflakes for near-infrared photothermal cancer therapy

    NASA Astrophysics Data System (ADS)

    Feng, Wei; Chen, Liang; Qin, Ming; Zhou, Xiaojun; Zhang, Qianqian; Miao, Yingke; Qiu, Kexin; Zhang, Yanzhong; He, Chuanglong

    2015-12-01

    Photothermal cancer therapy has attracted considerable interest for cancer treatment in recent years, but the effective photothermal agents remain to be explored before this strategy can be applied clinically. In this study, we therefore develop flower-like molybdenum disulfide (MoS2) nanoflakes and investigate their potential for photothermal ablation of cancer cells. MoS2 nanoflakes are synthesized via a facile hydrothermal method and then modified with lipoic acid-terminated polyethylene glycol (LA-PEG), endowing the obtained nanoflakes with high colloidal stability and very low cytotoxicity. Upon irradiation with near infrared (NIR) laser at 808 nm, the nanoflakes showed powerful ability of inducing higher temperature, good photothermal stability and high photothermal conversion efficiency. The in vitro photothermal effects of MoS2-PEG nanoflakes with different concentrations were also evaluated under various power densities of NIR 808-nm laser irradiation, and the results indicated that an effective photothermal killing of cancer cells could be achieved by a low concentration of nanoflakes under a low power NIR 808-nm laser irradiation. Furthermore, cancer cell in vivo could be efficiently destroyed via the photothermal effect of MoS2-PEG nanoflakes under the irradiation. These results thus suggest that the MoS2-PEG nanoflakes would be as promising photothermal agents for future photothermal cancer therapy.

  13. Contrast agent free detection of bowel perforation using chlorophyll derivatives from food plants

    NASA Astrophysics Data System (ADS)

    Han, Jung Hyun; Jo, Young Goun; Kim, Jung Chul; Lee, Jee-Bum; Kim, Yong-Chul; Kang, Hoonsoo; Hwang, In-Wook

    2016-01-01

    Chlorophylls occur abundantly in food plants and show bright emission bands at long-wavelength regions (∼675 and ∼720 nm) compared to the autofluorescence of animal organs and peritoneal fluids. The use of these emissions as biomarkers for monitoring bowel perforation with a modality that does not involve synthetic contrast agents seems promising. To validate this, we measured the fluorescence spectra of rat organs, human peritoneal and intestinal fluids, and human intestinal fluids diluted with physiological saline. The developed technique showed a high detection sensitivity (∼50 ppm) under irrigation for abdominal surgery, highlighting the potential of this tool in the surgical setting.

  14. Site-targeted acoustic contrast agent detects molecular expression of tissue factor after balloon angioplasty

    NASA Astrophysics Data System (ADS)

    Hall, Christopher S.; Abendschein, Dana R.; Scherrer, David E.; Scott, Michael J.; Marsh, Jon N.; Wickline, Samuel A.; Lanza, Gregory M.

    2000-04-01

    Complex molecular signaling heralds the early stages of pathologies such as angiogenesis, inflammation, and cellular responses to mechanically damaged coronary arteries after balloon angioplasty. In previous studies, we have demonstrated acoustic enhancement of blood clot morphology with the use of a nongaseous, ligand-targeted acoustic nanoparticle emulsion delivered to areas of thrombosis both in vitro and in vivo. In this paper, we characterize the early expression of tissue factor which contributes to subsequent arterial restenosis. Tissue factor is a 42kd glycoprotein responsible for blood coagulation but also plays a well-described role in cancer metastasis, angiogenesis, and vascular restenosis. This study was designed to determine whether the targeted contrast agent could localize tissue factor expressed within the wall of balloon-injured arteries. Both carotid arteries of five pigs (20 kg) were injured using an 8 X 20 mm angioplasty balloon. The carotids were treated in situ with a perfluorocarbon nanoparticle emulsion covalently complexed to either specific anti-tissue factor polyclonal F(ab) fragments (treatment) or non-specific IgG F(ab) fragments (control). Intravascular ultrasound (30 MHz) images of the arteries were obtained before and after exposure to the emulsions. Tissue- factor targeted ultrasonic contrast agent acoustically enhanced the subintima and media at the site of balloon- induced injury compared with control contrast arteries (p less than 0.05). Immunohistochemical staining confirmed the presence of increased tissue factor at the sites of acoustic enhancement. Binding of the targeted agents was demonstrated in vitro by scanning electron microscope images of cultured smooth muscle cells that constitutively express tissue factor. This study demonstrates the concept of molecular imaging and localization of carotid arteries' tissue factor in vivo using a new, nanoparticulate emulsion. Enhancement of the visualization of the molecular

  15. Gold nanoclusters as contrast agents for fluorescent and X-ray dual-modality imaging.

    PubMed

    Zhang, Aili; Tu, Yu; Qin, Songbing; Li, Yan; Zhou, Juying; Chen, Na; Lu, Qiang; Zhang, Bingbo

    2012-04-15

    Multimodal imaging technique is an alternative approach to improve sensitivity of early cancer diagnosis. In this study, highly fluorescent and strong X-ray absorption coefficient gold nanoclusters (Au NCs) are synthesized as dual-modality imaging contrast agents (CAs) for fluorescent and X-ray dual-modality imaging. The experimental results show that the as-prepared Au NCs are well constructed with ultrasmall sizes, reliable fluorescent emission, high computed tomography (CT) value and fine biocompatibility. In vivo imaging results indicate that the obtained Au NCs are capable of fluorescent and X-ray enhanced imaging.

  16. Porous silicon nanoparticles as biocompatible contrast agents for magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Gongalsky, M. B.; Kargina, Yu. V.; Osminkina, L. A.; Perepukhov, A. M.; Gulyaev, M. V.; Vasiliev, A. N.; Pirogov, Yu. A.; Maximychev, A. V.; Timoshenko, V. Yu.

    2015-12-01

    We propose porous silicon nanoparticles (PSi NPs) with natural oxide coating as biocompatible and bioresorbable contrast agents for magnetic resonant imaging (MRI). A strong shortening of the transversal proton relaxation time (T2) was observed for aqueous suspensions of PSi NPs, whereas the longitudinal relaxation time (T1) changed moderately. The longitudinal and transversal relaxivities are estimated to be 0.03 and 0.4 l/(g.s), respectively, which are promising for biomedical studies. The proton relaxation is suggested to undergo via the magnetic dipole-dipole interaction with Si dangling bonds on surfaces of PSi NPs. MRI experiments with phantoms have revealed the remarkable contrasting properties of PSi NPs for medical diagnostics.

  17. Porous silicon nanoparticles as biocompatible contrast agents for magnetic resonance imaging

    SciTech Connect

    Gongalsky, M. B. Kargina, Yu. V.; Osminkina, L. A.; Perepukhov, A. M.; Maximychev, A. V.; Gulyaev, M. V.; Vasiliev, A. N.; Pirogov, Yu. A.; Timoshenko, V. Yu.

    2015-12-07

    We propose porous silicon nanoparticles (PSi NPs) with natural oxide coating as biocompatible and bioresorbable contrast agents for magnetic resonant imaging (MRI). A strong shortening of the transversal proton relaxation time (T{sub 2}) was observed for aqueous suspensions of PSi NPs, whereas the longitudinal relaxation time (T{sub 1}) changed moderately. The longitudinal and transversal relaxivities are estimated to be 0.03 and 0.4 l/(g·s), respectively, which are promising for biomedical studies. The proton relaxation is suggested to undergo via the magnetic dipole-dipole interaction with Si dangling bonds on surfaces of PSi NPs. MRI experiments with phantoms have revealed the remarkable contrasting properties of PSi NPs for medical diagnostics.

  18. Development and evaluation of a novel VEGFR2-targeted nanoscale ultrasound contrast agents

    NASA Astrophysics Data System (ADS)

    Yu, Houqiang; Li, Chunfang; He, Xiaoling; Zhou, Qibing; Ding, Mingyue

    2016-04-01

    Recent literatures have reported that the targeted nanoscale ultrasound contrast agents are becoming more and more important in medical application, like ultrasound imaging, detection of perfusion, drug delivery and molecular imaging and so on. In this study, we fabricated an uniform nanoscale bubbles (257 nm with the polydispersity index of 0.458) by incorporation of antibody targeted to vascular endothelial growth factor receptor 2 (VEGFR2) into the nanobubbles membrane by using avidin-biotin interaction. Some fundamental characterizations such as nanobubble suspension, surface morphology, particle size distribution and zeta potential were investigated. The concentration and time-intensity curves (TICs) were obtained with a self-made ultrasound experimental setup in vitro evaluation. In addition, in order to evaluate the contrast enhancement ability and the potential tumor-targeted ability in vivo, normal Wistar rats and nude female BALB/c mice were intravascular administration of the nanobubbles via tail vein injection, respectively. Significant contrast enhancement of ultrasound imaging within liver and tumor were visualized. These experiments demonstrated that the targeted nanobubbles is efficient in ultrasound molecular imaging by enhancement of the contrast effect and have potential capacity for targeted tumor diagnosis and therapy in the future.

  19. Object reconstruction in scattering medium using multiple elliptical polarized speckle contrast projections and optical clearing agents

    NASA Astrophysics Data System (ADS)

    Moshe, Tomer; Firer, Michael A.; Abookasis, David

    2015-05-01

    In this paper, we present a hybrid method for improving the imaging quality of objects obscured within a scattering environment by combining multiple elliptical polarized speckle contrast projections with the use of optical clearing agents (OCAs). Elliptically polarized light enables the probing of subsurface volumes, where OCAs decrease light scattering while increasing photons' penetration depth through the medium. Experiments were conducted on object sample and prostate cancer cells embedded within ex vivo biological samples (chicken breasts) in reflection configuration. After immersion with OCAs, the medium was irradiated with an elliptically polarized laser beam and multiple polarized speckled images obtained from a lens array were first converted to speckled contrast images and then processed using a self-deconvolution shift-and-add algorithm. The conversion to contrast images and multiple perspectives acquisition was found to emphasize contrast. Analysis of image quality indicated improvement in object visualization by the combination of elliptical polarization and OCAs. This enhanced imaging strategy may advance the development of improved methods in biomedicine field, specifically biomedical tomography.

  20. Facile Fabrication of Near-Infrared-Resonant and Magnetic Resonance Imaging-Capable Nanomediators for Photothermal Therapy.

    PubMed

    Chen, Hongwei; Ren, Xiaoqing; Paholak, Hayley J; Burnett, Joseph; Ni, Feng; Fang, Xiaoling; Sun, Duxin

    2015-06-17

    Although many techniques exist for fabricating near-infrared (NIR)-resonant and magnetic resonance imaging (MRI)-capable nanomediators for photothermal cancer therapy, preparing them in an efficient and scalable process remains a significant challenge. In this report, we exploit one-step siloxane chemistry to facilely conjugate NIR-absorbing satellites onto a well-developed polysiloxane-containing polymer-coated iron oxide nanoparticle (IONP) core to generate dual functional core-satellite nanomediators for photothermal therapy. An advantage of this nanocomposite design is the variety of potential satellites that can be simply attached to impart NIR resonance, which we demonstrate using NIR-resonant gold sulfide nanoparticles (Au2SNPs) and the NIR dye IR820 as two example satellites. The core-satellite nanomediators are fully characterized by using absorption spectra, dynamic light scattering, ζ potential measurements, and transmission electron microscopy. The enhanced photothermal effect under the irradiation of NIR laser light is identified through in vitro solutions and in vivo mice studies. The MRI capabilities as contrast agents are demonstrated in mice. Our data suggest that polysiloxane-containing polymer-coated IONPs can be used as a versatile platform to build such dual functional nanomediators for translatable, MRI-guided photothermal cancer therapy. PMID:26010660

  1. Multifunctional Rbx WO3 nanorods for simultaneous combined chemo-photothermal therapy and photoacoustic/CT imaging.

    PubMed

    Tian, Gan; Zhang, Xiao; Zheng, Xiaopeng; Yin, Wenyan; Ruan, Longfei; Liu, Xiaodong; Zhou, Liangjun; Yan, Liang; Li, Shoujian; Gu, Zhanjun; Zhao, Yuliang

    2014-10-29

    Light-triggered drug delivery based on near-infrared (NIR)-mediated photothermal nanocarriers has received tremendous attention for the construction of cooperative therapeutic systems in nanomedicine. Herein, a new paradigm of light-responsive drug carrier that doubles as a photothermal agent is reported based on the NIR light-absorber, Rb(x) WO3 (rubidium tungsten bronze, Rb-TB) nanorods. With doxorubicin (DOX) payload, the DOX-loaded Rb-TB composite (Rb-TB-DOX) simultaneously provides a burst-like drug release and intense heating effect upon 808-nm NIR light exposure. MTT assays show the photothermally enhanced antitumor activity of Rb-TB-DOX to the MCF-7 cancer cells. Most remarkably, Rb-TB-DOX combined with NIR irradiation also shows dramatically enhanced chemotherapeutic effect to DOX-resistant MCF-7 cells compared with free DOX, demonstrating the enhanced efficacy of combinational chemo-photothermal therapy for potentially overcoming drug resistance in cancer chemotherapy. Furthermore, in vivo study of combined chemo-photothermal therapy is also conducted and realized on pancreatic (Pance-1) tumor-bearing nude mice. Apart from its promise for cancer therapy, the as-prepared Rb-TB can also be employed as a new dual-modal contrast agent for photoacoustic tomography and (PAT) X-ray computed tomography (CT) imaging because of its high NIR optical absorption capability and strong X-ray attenuation ability, respectively. The results presented in the current study suggest promise of the multifunctional Rb(x)WO3 nanorods for applications in cancer theranostics.

  2. Parallel Comparative Studies on Mouse Toxicity of Oxide Nanoparticle- and Gadolinium-Based T1 MRI Contrast Agents.

    PubMed

    Chen, Rui; Ling, Daishun; Zhao, Lin; Wang, Shuaifei; Liu, Ying; Bai, Ru; Baik, Seungmin; Zhao, Yuliang; Chen, Chunying; Hyeon, Taeghwan

    2015-12-22

    Magnetic resonance imaging (MRI) contrast agents with high relaxivity are highly desirable because they can significantly increase the accuracy of diagnosis. However, they can be potentially toxic to the patients. In this study, using a mouse model, we investigate the toxic effects and subsequent tissue damage induced by three T1 MRI contrast agents: gadopentetate dimeglumine injection (GDI), a clinically used gadolinium (Gd)-based contrast agent (GBCAs), and oxide nanoparticle (NP)-based contrast agents, extremely small-sized iron oxide NPs (ESIONs) and manganese oxide (MnO) NPs. Biodistribution, hematological and histopathological changes, inflammation, and the endoplasmic reticulum (ER) stress responses are evaluated for 24 h after intravenous injection. These thorough assessments of the toxic and stress responses of these agents provide a panoramic description of safety concerns and underlying mechanisms of the toxicity of contrast agents in the body. We demonstrate that ESIONs exhibit fewer adverse effects than the MnO NPs and the clinically used GDI GBCAs, providing useful information on future applications of ESIONs as potentially safe MRI contrast agents.

  3. Porphyrin Nanodroplets: Sub-micrometer Ultrasound and Photoacoustic Contrast Imaging Agents.

    PubMed

    Paproski, Robert J; Forbrich, Alexander; Huynh, Elizabeth; Chen, Juan; Lewis, John D; Zheng, Gang; Zemp, Roger J

    2016-01-20

    A novel class of all-organic nanoscale porphyrin nanodroplet agents is presented which is suitable for multimodality ultrasound and photoacoustic molecular imaging. Previous multimodality photoacoustic-ultrasound agents are either not organic, or not yet demonstrated to exhibit enhanced accumulation in leaky tumor vasculature, perhaps because of large diameters. In the current study, porphyrin nanodroplets are created with a mean diameter of 185 nm which is small enough to exhibit the enhanced permeability and retention effect. Porphyrin within the nanodroplet shell has strong optical absorption at 705 nm with an estimated molar extinction coefficient >5 × 10(9) m(-1) cm(-1) , allowing both ultrasound and photoacoustic contrast in the same nanoparticle using all organic materials. The potential of nanodroplets is that they may be phase-changed into microbubbles using high pressure ultrasound, providing ultrasound contrast with single-bubble sensitivity. Multispectral photoacoustic imaging allows visualization of nanodroplets when injected intratumorally in an HT1080 tumor in the chorioallantoic membrane of a chicken embryo. Intravital microscopy imaging of Hep3-GFP and HT1080-GFP tumors in chicken embryos determines that nanodroplets accumulated throughout or at the periphery of tumors, suggesting that porphyrin nanodroplets may be useful for enhancing the visualization of tumors with ultrasound and/or photoacoustic imaging.

  4. Improved pH measurements with a single PARACEST MRI contrast agent

    PubMed Central

    Sheth, Vipul R.; Liu, Guanshu; Li, Yuguo; Pagel, Mark D.

    2016-01-01

    The measurement of extracellular pH has potential utility for assessing the therapeutic effects of pH-dependent and pH-altering therapies. A PARAmagnetic chemical exchange saturation transfer (PARACEST) MRI contrast agent, Yb–DO3A–oAA, has two CEST effects that are dependent on pH. A ratio derived from these CEST effects was linearly correlated with pH throughout the physiological pH range. The pH can be measured with a precision of 0.21 pH units and an accuracy of 0.09 pH units. The pH measurement is independent of concentration and T1 relaxation times, but is dependent on temperature. Although MR coalescence affects the CEST measurements, especially at high pH, the ratiometric analysis of the CEST effects can account for incomplete saturation of the agent’s amide and amine that results from MR coalescence. Provided that an empirical calibration is determined with saturation conditions, magnetic field strength and temperature that can be used for subsequent studies, these results demonstrate that this single PARACEST MRI contrast agent can accurately measure pH. PMID:22344877

  5. Paramagnetic water-soluble metallofullerenes having the highest relaxivity for MRI contrast agents.

    PubMed

    Mikawa, M; Kato, H; Okumura, M; Narazaki, M; Kanazawa, Y; Miwa, N; Shinohara, H

    2001-01-01

    Water-soluble gadolinium (Gd) endohedral metallofullerenes have been synthesized as polyhydroxyl forms (Gd@C(82)(OH)(n)(), Gd-fullerenols) and their paramagnetic properties were evaluated by in vivo as well as in vitro for the novel magnetic resonance imaging (MRI) contrast agents for next generation. The in vitro water proton relaxivity, R(1) (the effect on 1/T(1)), of Gd-fullerenols is significantly higher (20-folds) than that of the commercial MRI contrast agent, Magnevist (gadolinium-diethylenetriaminepentaacetic acid, Gd-DTPA) at 1.0 T close to the common field of clinical MRI. This unusually high proton relaxivity of Gd-fullerenols leads to the highest signal enhancement at extremely lower Gd concentration in MRI studies. The strong signal was confirmed in vivo MRI at lung, liver, spleen, and kidney of CDF1 mice after i.v. administration of Gd-fullerenols at a dose of 5 micromol Gd/kg, which was 1/20 of the typical clinical dose (100 micromol Gd/kg) of Gd-DTPA.

  6. GRPR-targeted Protein Contrast Agents for Molecular Imaging of Receptor Expression in Cancers by MRI

    PubMed Central

    Pu, Fan; Qiao, Jingjuan; Xue, Shenghui; Yang, Hua; Patel, Anvi; Wei, Lixia; Hekmatyar, Khan; Salarian, Mani; Grossniklaus, Hans E.; Liu, Zhi-Ren; Yang, Jenny J.

    2015-01-01

    Gastrin-releasing peptide receptor (GRPR) is differentially expressed on the surfaces of various diseased cells, including prostate and lung cancer. However, monitoring temporal and spatial expression of GRPR in vivo by clinical MRI is severely hampered by the lack of contrast agents with high relaxivity, targeting capability and tumor penetration. Here, we report the development of a GRPR-targeted MRI contrast agent by grafting the GRPR targeting moiety into a scaffold protein with a designed Gd3+ binding site (ProCA1.GRPR). In addition to its strong binding affinity for GRPR (Kd = 2.7 nM), ProCA1.GRPR has high relaxivity (r1 = 42.0 mM−1s−1 at 1.5 T and 25 °C) and strong Gd3+ selectivity over physiological metal ions. ProCA1.GRPR enables in vivo detection of GRPR expression and spatial distribution in both PC3 and H441 tumors in mice using MRI. ProCA1.GRPR is expected to have important preclinical and clinical implications for the early detection of cancer and for monitoring treatment effects. PMID:26577829

  7. A new biodegradable and biocompatible gadolinium (III) -polymer for liver magnetic resonance imaging contrast agent.

    PubMed

    Xiao, Yan; Xue, Rong; You, Tianyan; Li, Xiaojing; Pei, Fengkui

    2015-07-01

    A new biodegradable and biocompatible gadolinium (III) -copolymer (ACL-A2-DOTA-Gd) has been developed as a potential liver magnetic resonance imaging (MRI) contrast agent. ACL-A2-DOTA-Gd consisted of a poly (aspartic acid-co-leucine) unit bound with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (Gd-DOTA) via the linkage of ethylenediamine. In vitro, the biodegradable experiment and cytotoxicity assay showed the biodegradability and biocompatibility of this gadolinium-polymer. ACL-A2-DOTA-Gd presented an increase in relaxivity of 2.4 times than the clinical Gd-DOTA. In vivo, gadolinium (III)-copolymer was mainly accumulated in the liver, and it could be excreted via the renal and hepatobiliary mechanism. The average enhancement of ACL-A2-DOTA-Gd (60.71±5.93%, 50-80 min) in liver was 2.62-fold greater than that of Gd-DOTA (23.16±3.55%, 10-30 min). ACL-A2-DOTA-Gd could be as a potential liver MRI contrast agent with a long time-window.

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

    NASA Astrophysics Data System (ADS)

    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.

  9. Virus-mimicking nano-constructs as a contrast agent for near infrared photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Gupta, Sharad; Chatni, Muhammad R.; Rao, Ayala L. N.; Vullev, Valentine I.; Wang, Lihong V.; Anvari, Bahman

    2013-02-01

    We report the first proof-of-principle demonstration of photoacoustic imaging using a contrast agent composed of a plant virus protein shell, which encapsulates indocyanine green (ICG), the only FDA-approved near infrared chromophore. These nano-constructs can provide higher photoacoustic signals than blood in tissue phantoms, and display superior photostability compared to non-encapsulated ICG. Our preliminary results suggest that the constructs do not elicit an acute immunogenic response in healthy mice.We report the first proof-of-principle demonstration of photoacoustic imaging using a contrast agent composed of a plant virus protein shell, which encapsulates indocyanine green (ICG), the only FDA-approved near infrared chromophore. These nano-constructs can provide higher photoacoustic signals than blood in tissue phantoms, and display superior photostability compared to non-encapsulated ICG. Our preliminary results suggest that the constructs do not elicit an acute immunogenic response in healthy mice. Electronic supplemental information (ESI) available: Information on experimental procedure for fabrication of the nano-constructs, photoacoustic imaging, and immunogenic studies. See DOI: 10.1039/c3nr34124k

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

    NASA Astrophysics Data System (ADS)

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

    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.

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

    NASA Astrophysics Data System (ADS)

    Jedlovszky-Hajdú, Angéla; Tombácz, Etelka; Bányai, István; Babos, Magor; Palkó, András

    2012-09-01

    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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26511147

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

    PubMed Central

    Paefgen, Vera; Doleschel, Dennis; Kiessling, Fabian

    2015-01-01

    Ultrasound (US) 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 (CAs). 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 CAs 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 US pulses to locally release the entrapped agent. Recent studies show that US CAs 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 US CAs and introduces the current clinical applications of contrast-enhanced US. Additionally, an overview of the recent developments in US probe design for functional and molecular diagnosis as well as for drug delivery is given. PMID:26441654

  14. Material characterization of poly-lactic acid shelled ultrasound contrast agent and their dynamics

    NASA Astrophysics Data System (ADS)

    Paul, Shirshendu; Russakow, Daniel; Rodgers, Tyler; Sarkar, Kausik; Cochran, Michael; Wheatley, Margaret

    2011-11-01

    Micron-size gas bubbles encapsulated with lipids and proteins are used as contrast enhancing agents for ultrasound imaging. Biodegradable polymer poly-lactic acid (PLA) has recently been suggested as a possible means of encapsulation. Here, we report in vitro measurement of attenuation and scattering of ultrasound through an emulsion of PLA agent as well as theoretical modeling of the encapsulated bubble dynamics. The attenuation measured with three different transducers of central frequencies 2.25, 3.5 and 5 MHz, shows a peak around 2-3 MHz. These bubbles also show themselves to possess excellent scattering characteristics including strong non-linear response that can be used for harmonic and sub-harmonic contrast imaging. Our recently developed interfacial rheological models are applied to describe the dynamics of these bubbles; rheological model properties are estimated using measured attenuation data. The model is then applied to predict nonlinear scattered response, and the prediction is compared against experimental observation. Partially supported by NSF and NIH.

  15. Small animal optoacoustic tomography system for molecular imaging of contrast agents

    NASA Astrophysics Data System (ADS)

    Su, Richard; Liopo, Anton; Ermilov, Sergey A.; Oraevsky, Alexander A.

    2016-03-01

    We developed a new and improved Laser Optoacoustic Imaging System, LOIS-3D for preclinical research applications in small animal models. The advancements include (i) a new stabilized imaging module with a more homogeneous illumination of the mouse yielding a better spatial resolution (<0.2 mm) and (ii) a new low noise amplifier incorporated into the ultrasonic probe and providing the noise equivalent pressure around 2 Pa resulting in increased signal-to-noise ratio and the optical absorption sensitivity of about 0.15 cm-1. We also improved scan time and the image reconstruction times. This prototype has been commercialized for a number of biomedical research applications, such as imaging vascularization and measuring hemoglobin / oxyhemoglobin distribution in the organs as well as imaging exogenous or endogenous optoacoustic contrast agents. As examples, we present in vivo experiments using phantoms and mice with and without tumor injected with contrast agents with indocyanine green (ICG). LOIS-3D was capable of detecting ~1-2 pmole of the ICG, in tissues with relatively low blood content. With its high sensitivity and excellent spatial resolution LOIS-3D is an advanced alternative to fluorescence and bioluminescence based modalities for molecular imaging in live mice.

  16. Water-dispersible magnetic carbon nanotubes as T2-weighted MRI contrast agents.

    PubMed

    Liu, Yue; Hughes, Timothy C; Muir, Benjamin W; Waddington, Lynne J; Gengenbach, Thomas R; Easton, Christopher D; Hinton, Tracey M; Moffat, Bradford A; Hao, Xiaojuan; Qiu, Jieshan

    2014-01-01

    An efficient MRI T2-weighted contrast agent incorporating a potential liver targeting functionality was synthesized via the combination of superparamagnetic iron oxide (SPIO) nanoparticles with multiwalled carbon nanotubes (MWCNTs). Poly(diallyldimethylammonium chloride) (PDDA) was coated on the surface of acid treated MWCNTs via electrostatic interactions and SPIO nanoparticles modified with a potential targeting agent, lactose-glycine adduct (Lac-Gly), were subsequently immobilized on the surface of the PDDA-MWCNTs. A narrow magnetic hysteresis loop indicated that the product displayed superparamagnetism at room temperature which was further confirmed by ZFC (zero field cooling)/FC (field cooling) curves measured by SQUID. The multifunctional MWCNT-based magnetic nanocomposites showed low cytotoxicity in vitro to HEK293 and Huh7 cell lines. Enhanced T2 relaxivities were observed for the hybrid material (186 mM(-1) s(-1)) in comparison with the pure magnetic nanoparticles (92 mM(-1) s(-1)) due to the capacity of the MWCNTs to "carry" more nanoparticles as clusters. More importantly, after administration of the composite material to an in vivo liver cancer model in mice, a significant increase in tumor to liver contrast ratio (277%) was observed in T2 weighted magnetic resonance images. PMID:24120046

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

    PubMed

    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. PMID:25723091

  18. X-ray scatter imaging of hepatocellular carcinoma in a mouse model using nanoparticle contrast agents

    SciTech Connect

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

    2015-10-29

    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. As a result, 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.

  19. Targeted Nanodiamonds as Phenotype Specific Photoacoustic Contrast Agents for Breast Cancer

    PubMed Central

    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

  20. Water-dispersible magnetic carbon nanotubes as T2-weighted MRI contrast agents.

    PubMed

    Liu, Yue; Hughes, Timothy C; Muir, Benjamin W; Waddington, Lynne J; Gengenbach, Thomas R; Easton, Christopher D; Hinton, Tracey M; Moffat, Bradford A; Hao, Xiaojuan; Qiu, Jieshan

    2014-01-01

    An efficient MRI T2-weighted contrast agent incorporating a potential liver targeting functionality was synthesized via the combination of superparamagnetic iron oxide (SPIO) nanoparticles with multiwalled carbon nanotubes (MWCNTs). Poly(diallyldimethylammonium chloride) (PDDA) was coated on the surface of acid treated MWCNTs via electrostatic interactions and SPIO nanoparticles modified with a potential targeting agent, lactose-glycine adduct (Lac-Gly), were subsequently immobilized on the surface of the PDDA-MWCNTs. A narrow magnetic hysteresis loop indicated that the product displayed superparamagnetism at room temperature which was further confirmed by ZFC (zero field cooling)/FC (field cooling) curves measured by SQUID. The multifunctional MWCNT-based magnetic nanocomposites showed low cytotoxicity in vitro to HEK293 and Huh7 cell lines. Enhanced T2 relaxivities were observed for the hybrid material (186 mM(-1) s(-1)) in comparison with the pure magnetic nanoparticles (92 mM(-1) s(-1)) due to the capacity of the MWCNTs to "carry" more nanoparticles as clusters. More importantly, after administration of the composite material to an in vivo liver cancer model in mice, a significant increase in tumor to liver contrast ratio (277%) was observed in T2 weighted magnetic resonance images.

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

    SciTech Connect

    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.

  2. X-ray scatter imaging of hepatocellular carcinoma in a mouse model using nanoparticle contrast agents

    DOE PAGES

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

    2015-10-29

    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 anmore » 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. As a result, 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.« less

  3. Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods.

    PubMed

    Huang, Xiaohua; El-Sayed, Ivan H; Qian, Wei; El-Sayed, Mostafa A

    2006-02-15

    Due to strong electric fields at the surface, the absorption and scattering of electromagnetic radiation by noble metal nanoparticles are strongly enhanced. These unique properties provide the potential of designing novel optically active reagents for simultaneous molecular imaging and photothermal cancer therapy. It is desirable to use agents that are active in the near-infrared (NIR) region of the radiation spectrum to minimize the light extinction by intrinsic chromophores in native tissue. Gold nanorods with suitable aspect ratios (length divided by width) can absorb and scatter strongly in the NIR region (650-900 nm). In the present work, we provide an in vitro demonstration of gold nanorods as novel contrast agents for both molecular imaging and photothermal cancer therapy. Nanorods are synthesized and conjugated to anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies and incubated in cell cultures with a nonmalignant epithelial cell line (HaCat) and two malignant oral epithelial cell lines (HOC 313 clone 8 and HSC 3). The anti-EGFR antibody-conjugated nanorods bind specifically to the surface of the malignant-type cells with a much higher affinity due to the overexpressed EGFR on the cytoplasmic membrane of the malignant cells. As a result of the strongly scattered red light from gold nanorods in dark field, observed using a laboratory microscope, the malignant cells are clearly visualized and diagnosed from the nonmalignant cells. It is found that, after exposure to continuous red laser at 800 nm, malignant cells require about half the laser energy to be photothermally destroyed than the nonmalignant cells. Thus, both efficient cancer cell diagnostics and selective photothermal therapy are realized at the same time.

  4. Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods.

    PubMed

    Huang, Xiaohua; El-Sayed, Ivan H; Qian, Wei; El-Sayed, Mostafa A

    2006-02-15

    Due to strong electric fields at the surface, the absorption and scattering of electromagnetic radiation by noble metal nanoparticles are strongly enhanced. These unique properties provide the potential of designing novel optically active reagents for simultaneous molecular imaging and photothermal cancer therapy. It is desirable to use agents that are active in the near-infrared (NIR) region of the radiation spectrum to minimize the light extinction by intrinsic chromophores in native tissue. Gold nanorods with suitable aspect ratios (length divided by width) can absorb and scatter strongly in the NIR region (650-900 nm). In the present work, we provide an in vitro demonstration of gold nanorods as novel contrast agents for both molecular imaging and photothermal cancer therapy. Nanorods are synthesized and conjugated to anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies and incubated in cell cultures with a nonmalignant epithelial cell line (HaCat) and two malignant oral epithelial cell lines (HOC 313 clone 8 and HSC 3). The anti-EGFR antibody-conjugated nanorods bind specifically to the surface of the malignant-type cells with a much higher affinity due to the overexpressed EGFR on the cytoplasmic membrane of the malignant cells. As a result of the strongly scattered red light from gold nanorods in dark field, observed using a laboratory microscope, the malignant cells are clearly visualized and diagnosed from the nonmalignant cells. It is found that, after exposure to continuous red laser at 800 nm, malignant cells require about half the laser energy to be photothermally destroyed than the nonmalignant cells. Thus, both efficient cancer cell diagnostics and selective photothermal therapy are realized at the same time. PMID:16464114

  5. Detection of right-to-left shunt with ultrasound contrast agent and transcranial Doppler sonography.

    PubMed

    Jauss, M; Zanette, E

    2000-01-01

    An international Consensus Meeting to determine a standard in the examination technique for the detection of right-to-left shunt (RLS) using contrast transcranial Doppler sonography (TCD) led to the following recommendations to standardize the examination procedure: The patient should be prepared with an 18-gauge needle inserted into the cubital vein and should be in the supine position. Insonation of at least one middle cerebral artery (MCA) using TCD is performed. The contrast agent is prepared using 9 ml isotonic saline solution and 1 ml air mixed with a three-way stopcock by exchange of saline/air mixture between the syringes and injected as a bolus. In case of little or no detection of microbubbles (MB) in the MCA under basal conditions, the examination will be repeated using the Valsalva maneuver (VM). Contrast agent will be injected 5 s before the start of the VM; the overall VM duration should be 10 s. The patient should start the VM on examiner's command. The strength of the VM can be controlled by peak flow velocity of the Doppler curve. The time when the first MB appears at the MCA level will be noted. A four-level categorization according to the MB count should be applied: (1) 0 MB (negative result); (2) 1-10 MB; (3) >10 MB and no curtain, and (4) curtain. ('Curtain' refers to a shower of MB, where a single bubble cannot be identified.) The results should be documented for basal condition and VM testing separately. The clinical significance of the diagnosis of a RLS in a particular patient is not fully evaluated and requires further studies. A minimum amount of MB suggestive of a clinical relevant RLS is not yet established. It probably depends on interindividual differences in hemodynamics that are currently not fully understood. Transesophageal echocardiography remains the gold standard for detection of a patent foramen ovale or an atrial septum defect. However, TCD with a contrast agent has been turned out as a potential method to diagnose a RLS in

  6. In vivo comparison of tantalum, tungsten, and bismuth enteric contrast agents to complement intravenous iodine for double-contrast dual-energy CT of the bowel.

    PubMed

    Rathnayake, Samira; Mongan, John; Torres, Andrew S; Colborn, Robert; Gao, Dong-Wei; Yeh, Benjamin M; Fu, Yanjun

    2016-07-01

    To assess the ability of dual-energy CT (DECT) to separate intravenous contrast of bowel wall from intraluminal contrast, we scanned 16 rabbits on a clinical DECT scanner: n = 3 using only iodinated intravenous contrast, and n = 13 double-contrast enhanced scans using iodinated intravenous contrast and experimental enteric non-iodinated contrast agents in the bowel lumen (five bismuth, four tungsten, and four tantalum based). Representative image pairs from conventional CT images and DECT iodine density maps of small bowel (116 pairs from 232 images) were viewed by four abdominal imaging attending radiologists to independently score each comparison pair on a visual analog scale (-100 to +100%) for (1) preference in small bowel wall visualization and (2) preference in completeness of intraluminal enteric contrast subtraction. Median small bowel wall visualization was scored 39 and 42 percentage points (95% CI 30-44% and 36-45%, both p < 0.001) higher for double-contrast DECT than for conventional CT with enteric tungsten and tantalum contrast, respectively. Median small bowel wall visualization for double-contrast DECT was scored 29 and 35 percentage points (95% CI 20-35% and 33-39%, both p < 0.001) higher with enteric tungsten and tantalum, respectively, than with bismuth contrast. Median completeness of intraluminal enteric contrast subtraction in double-contrast DECT iodine density maps was scored 28 and 29 percentage points (95% CI 15-31% and 28-33%, both p < 0.001) higher with enteric tungsten and tantalum, respectively, than with bismuth contrast. Results suggest that in vivo double-contrast DECT with iodinated intravenous and either tantalum- or tungsten-based enteric contrast provides better visualization of small bowel than conventional CT. Copyright © 2016 John Wiley & Sons, Ltd.

  7. In vivo comparison of tantalum, tungsten, and bismuth enteric contrast agents to complement intravenous iodine for double-contrast dual-energy CT of the bowel.

    PubMed

    Rathnayake, Samira; Mongan, John; Torres, Andrew S; Colborn, Robert; Gao, Dong-Wei; Yeh, Benjamin M; Fu, Yanjun

    2016-07-01

    To assess the ability of dual-energy CT (DECT) to separate intravenous contrast of bowel wall from intraluminal contrast, we scanned 16 rabbits on a clinical DECT scanner: n = 3 using only iodinated intravenous contrast, and n = 13 double-contrast enhanced scans using iodinated intravenous contrast and experimental enteric non-iodinated contrast agents in the bowel lumen (five bismuth, four tungsten, and four tantalum based). Representative image pairs from conventional CT images and DECT iodine density maps of small bowel (116 pairs from 232 images) were viewed by four abdominal imaging attending radiologists to independently score each comparison pair on a visual analog scale (-100 to +100%) for (1) preference in small bowel wall visualization and (2) preference in completeness of intraluminal enteric contrast subtraction. Median small bowel wall visualization was scored 39 and 42 percentage points (95% CI 30-44% and 36-45%, both p < 0.001) higher for double-contrast DECT than for conventional CT with enteric tungsten and tantalum contrast, respectively. Median small bowel wall visualization for double-contrast DECT was scored 29 and 35 percentage points (95% CI 20-35% and 33-39%, both p < 0.001) higher with enteric tungsten and tantalum, respectively, than with bismuth contrast. Median completeness of intraluminal enteric contrast subtraction in double-contrast DECT iodine density maps was scored 28 and 29 percentage points (95% CI 15-31% and 28-33%, both p < 0.001) higher with enteric tungsten and tantalum, respectively, than with bismuth contrast. Results suggest that in vivo double-contrast DECT with iodinated intravenous and either tantalum- or tungsten-based enteric contrast provides better visualization of small bowel than conventional CT. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26892945

  8. Development of fluorescent contrast agents for optical imaging of mouse disease models

    NASA Astrophysics Data System (ADS)

    Kovar, J.; Simpson, M.; Schutz-Geschwender, A.; Xu, X.; Volcheck, W. M.; Sevick-Muraca, E.; Olive, D. M.

    2008-02-01

    Optical imaging is a rapidly developing field of research aimed at non-invasively interrogating animals for disease progression, determining the effects of a drug on a particular pathology, assessing the pharmacokinetic behavior of a drug, or identifying molecular biomarkers of disease. One of the key components of molecular imaging is the development of specific, targeted imaging contrast agents to assess these biological processes. The development of robust fluorochrome-labeled optical agents is a process that is often underestimated in terms of its complexity. We describe here the development process and performance issues for three different optical agents: IRDye 800CW EGF (epidermal growth factor), IRDye (R) 800CW 2-DG (2-deoxy D-glucose), and an IRDye 680 BoneTag TM. In vitro competitive assays were developed for two of the markers to demonstrate specificity. Specificity was confirmed in animal studies. Uptake of IRDye 800CW 2-DG was also examined by near-infrared confocal microscopy. Histological examinations were performed on target and non-target tissues following the completion of the imaging studies. The issues unique to the development of each labeled marker are discussed.

  9. Update on the safety and efficacy of commercial ultrasound contrast agents in cardiac applications

    PubMed Central

    Tracy, Melissa J; Feinstein, Steven B

    2015-01-01

    Ultrasound contrast agents (UCAs) are currently used throughout the world in both clinical and research settings. The concept of contrast-enhanced ultrasound imaging originated in the late 1960s, and the first commercially available agents were initially developed in the 1980s. Today's microbubbles are designed for greater utility and are used for both approved and off-label indications. In October 2007, the US Food and Drug Administration (FDA) imposed additional product label warnings that included serious cardiopulmonary reactions, several new disease-state contraindications, and a mandated 30 min post-procedure monitoring period for the agents Optison and Definity. These additional warnings were prompted by reports of cardiopulmonary reactions that were temporally related but were not clearly attributable to these UCAs. Subsequent published reports over the following months established not only the safety but also the improved efficacy of clinical ultrasound applications with UCAs. The FDA consequently updated the product labeling in June 2008 and reduced contraindications, although it continued to monitor select patients. In addition, a post-marketing program was proposed to the sponsors for a series of safety studies to further assess the risk of UCAs. Then in October 2011, the FDA leadership further downgraded the warnings after hearing the results of the post-marketing data, which revealed continued safety and improved efficacy. The present review focuses on the use of UCAs in today's clinical practice, including the approved indications, a variety of off-label uses, and the most recent data, which affirms the safety and efficacy of UCAs. PMID:26693339

  10. Acoustic backscatter properties of the particle/bubble ultrasound contrast agent.

    PubMed

    Phillips, D; Chen, X; Baggs, R; Rubens, D; Violante, M; Parker, K J

    1998-07-01

    Bubble-based suspensions with diameters in the 1-5 microns range have been developed for use as ultrasound contrast agents. Bubbles of these dimensions have resonance frequencies in the diagnostic ultrasonic range, thus improving their backscatter enhancement capabilities. The durability of these bubbles in the blood stream has been found to be limited, providing impetus for a number of approaches to further stabilize them. One of the approaches has been the development of micrometer-size porous particles or 'nano-sponges' with properties suitable for the entrapment and stabilization of gas bubbles. However, the complex morphology and surface chemistry involved in the production of this type of agent makes it unfeasible to directly measure the volume of the entrained gas. A model based on acoustic scattering principles is proposed which indicates that only a small volume fraction of gas should be necessary to significantly enhance the echogenicity of this type of particle-based contrast agent. In the model, the effective scattering cross-section is evaluated as a function of the volume fraction of gas contained in the overall scatterer and the overall scatterer diameter. Initially, the volume fraction of gas is considered as a discrete entity of single bubble. Using common mixture rules, it is then shown that the gas can be considered to be distributed throughout the particle and still arrive at a result that is similar to that for a single, discrete volume of gas. The main contribution to the increased scattering cross-section is due to the compressibility difference between gas and water. The backscatter coefficient is computed as the product of the resulting differential scattering cross-section and the scatterer number density. This approach facilitates comparison with known backscatter coefficients of biological targets such as liver and blood. Simple experimental results are presented for comparison with the model, and the implications relevant to clinical

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

    PubMed Central

    da Silva, Yvana Lopes Pinheiro; Costa, Rita Zanlorensi Visneck; Pinho, Kátia Elisa Prus; Ferreira, Ricardo Rabello; Schuindt, Sueliton Miyamoto

    2015-01-01

    Objective To investigate the effects of dilution of paramagnetic contrast agent with iodinated contrast and xylocaine on the signal intensity during magnetic resonance arthrography, and to improve the paramagnetic contrast agent concentration utilized in this imaging modality. Materials and Methods Samples specially prepared for the study with three different concentrations of paramagnetic contrast agent diluted in saline, iodinated contrast agent and xylocaine were imaged with fast spin echo T1-weighted sequences with fat saturation. The samples were placed into flasks and graphical analysis of the signal intensity was performed as a function of the paramagnetic contrast concentration. Results As compared with samples of equal concentrations diluted only with saline, the authors have observed an average signal intensity decrease of 20.67% for iodinated contrast agent, and of 28.34% for xylocaine. However, the increased gadolinium concentration in the samples caused decrease in signal intensity with all the dilutions. Conclusion Minimizing the use of iodinated contrast media and xylocaine and/or the use of a gadolinium concentration of 2.5 mmol/L diluted in saline will improve the sensitivity of magnetic resonance arthrography. PMID:25987746

  12. Evaluation of Gd-DTPA-monophytanyl and phytantriol nanoassemblies as potential MRI contrast agents.

    PubMed

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

    2015-02-01

    Supramolecular self-assembling amphiphiles have been widely used in drug delivery and diagnostic imaging. In this report, we present the self-assembly of Gd (III) chelated DTPA-monophytanyl (Gd-DTPA-MP) amphiphiles incorporated within phytantriol (PT), an inverse bicontinuous cubic phase forming matrix at various compositions. The dispersed colloidal nanoassemblies were evaluated as potential MRI contrast agents at various magnetic field strengths. The homogeneous incorporation of Gd-DTPA-MP in PT was confirmed by polarized optical microscopy (POM) and synchrotron small-angle X-ray scattering (SAXS) of the bulk phases of the mixtures. The liquid crystalline nanostructures, morphology, and the size distribution of the nanoassemblies were studied by SAXS, cryogenic transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS). The dispersions with up to 2 mol % of Gd-DTPA-MP in PT retained inverse cubosomal nanoassemblies, whereas the rest of the dispersions transformed to liposomal nanoassemblies. In vitro relaxivity studies were performed on all the dispersions at 0.54, 9.40, and 11.74 T and compared to Magnevist, a commercially available contrast agent. All the dispersions showed much higher relaxivities compared to Magnevist at both low and high magnetic field strengths. Image contrast of the nanoassemblies was also found to be much better than Magnevist at the same Gd concentration at 11.74 T. Moreover, the Gd-DTPA-MP/PT dispersions showed improved relaxivities over the pure Gd-DTPA-MP dispersion at high magnetic fields. These stable colloidal nanoassemblies have high potential to be used as combined delivery matrices for diagnostics and therapeutics.

  13. Paramagnetic dysprosium oxide nanoparticles and dysprosium hydroxide nanorods as T₂ MRI contrast agents.

    PubMed

    Kattel, Krishna; Park, Ja Young; Xu, Wenlong; Kim, Han Gyeol; Lee, Eun Jung; Bony, Badrul Alam; Heo, Woo Choul; Jin, Seonguk; Baeck, Jong Su; Chang, Yongmin; Kim, Tae Jeong; Bae, Ji Eun; Chae, Kwon Seok; Lee, Gang Ho

    2012-04-01

    We report here paramagnetic dysprosium nanomaterial-based T(2) MRI contrast agents. A large r(2) and a negligible r(1) is an ideal condition for T(2) MR imaging. At this condition, protons are strongly and nearly exclusively induced for T(2) MR imaging. The dysprosium nanomaterials fairly satisfy this because they are found to possess a decent r(2) but a negligible r(1) arising from L + S state 4f-electrons in Dy(III) ion ((6)H(15/2)). Their r(2) will also further increase with increasing applied field because of unsaturated magnetization at room temperature. Therefore, MR imaging and various physical properties of the synthesized d-glucuronic acid coated ultrasmall dysprosium oxide nanoparticles (d(avg) = 3.2 nm) and dysprosium hydroxide nanorods (20 × 300 nm) are investigated. These include hydrodynamic diameters, magnetic properties, MR relaxivities, cytotoxicities, and 3 tesla in vivo T(2) MR images. Here, MR imaging properties of dysprosium hydroxide nanorods have not been reported so far. These two samples show r(2)s of 65.04 and 181.57 s(-1)mM(-1), respectively, with negligible r(1)s at 1.5 tesla and at room temperature, no in vitro cytotoxicity up to 100 μM Dy, and clear negative contrast enhancements in 3 tesla in vivo T(2) MR images of a mouse liver, which will be even more improved at higher MR fields. Therefore, d-glucuronic acid coated ultrasmall dysprosium oxide nanoparticles with renal excretion can be a potential candidate as a sensitive T(2) MRI contrast agent at MR field greater than 3 tesla.

  14. Correction: Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Hachani, Roxanne; Lowdell, Mark; Birchall, Martin; Hervault, Aziliz; Mertz, Damien; Begin-Colin, Sylvie; Thanh, Nguy&Ecirtil; N. Thi&Cmb. B. Dot; Kim

    2016-02-01

    Correction for `Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents' by Roxanne Hachani et al., Nanoscale, 2015, DOI: 10.1039/c5nr03867g.

  15. High-resolution MRI characterization of human thrombus using a novel fibrin-targeted paramagnetic nanoparticle contrast agent.

    PubMed

    Yu, X; Song, S K; Chen, J; Scott, M J; Fuhrhop, R J; Hall, C S; Gaffney, P J; Wickline, S A; Lanza, G M

    2000-12-01

    In this study, the sensitivity of a novel fibrin-targeted contrast agent for fibrin detection was defined in vitro on human thrombus. The contrast agent was a lipid-encapsulated perfluorocarbon nanoparticle with numerous Gd-DTPA complexes incorporated into the outer surface. After binding to fibrin clots, scanning electron microscopy of treated clots revealed dense accumulation of nanoparticles on the clot surfaces. Fibrin clots with sizes ranging from 0.5-7.0 mm were imaged at 4.7 T with or without treatment with the targeted contrast agent. Regardless of sizes, untreated clots were not detectable by T(1)-weighted MRI, while targeted contrast agent dramatically improved the detectability of all clots. Decreases in T(1) and T(2) relaxation times (20-40%) were measured relative to the surrounding media and the control clots. These results suggest the potential for sensitive and specific detection of microthrombi that form on the intimal surfaces of unstable atherosclerotic plaque.

  16. Correction: Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents.

    PubMed

    Hachani, Roxanne; Lowdell, Mark; Birchall, Martin; Hervault, Aziliz; Mertz, Damien; Begin-Colin, Sylvie; Thanh, Nguyen Thi Kim

    2016-02-21

    Correction for 'Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents' by Roxanne Hachani et al., Nanoscale, 2015, DOI: 10.1039/c5nr03867g. PMID:26823197

  17. Engineered iron-oxide-based nanoparticles as enhanced T1 contrast agents for efficient tumor imaging.

    PubMed

    Zhou, Zijian; Wang, Lirong; Chi, Xiaoqin; Bao, Jianfeng; Yang, Lijiao; Zhao, Wenxiu; Chen, Zhong; Wang, Xiaomin; Chen, Xiaoyuan; Gao, Jinhao

    2013-04-23

    We report the design and synthesis of small-sized zwitterion-coated gadolinium-embedded iron oxide (GdIO) nanoparticles, which exhibit a strong T1 contrast effect for tumor imaging through enhanced permeation and retention effect and the ability to clear out of the body in living subjects. The combination of spin-canting effects and the collection of gadolinium species within small-sized GdIO nanoparticles led to a significantly enhanced T1 contrast effect. For example, GdIO nanoparticles with a diameter of ∼4.8 nm exhibited a high r1 relaxivity of 7.85 mM(-1)·S(-1) and a low r2/r1 ratio of 5.24. After being coated with zwitterionic dopamine sulfonate molecules, the 4.8 nm GdIO nanoparticles showed a steady hydrodynamic diameter (∼5.2 nm) in both PBS buffer and fetal bovine serum solution, indicating a low nonspecific protein absorption. This study provides a valuable strategy for the design of highly sensitive iron-oxide-based T1 contrast agents with relatively long circulation half-lives (∼50 min), efficient tumor passive targeting (SKOV3, human ovarian cancer xenograft tumor as a model), and the possibility of rapid renal clearance after tumor imaging.

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

    PubMed Central

    Martínez-González, Raquel; Estelrich, Joan; Busquets, Maria Antònia

    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 T2 relaxation times by decreasing the MR signal in the regions to which they are delivered, consequently yielding darker images or negative contrast. Given the potential of these nanoparticles to enhance detection of alterations in soft tissues, we studied the MRI response of hydrophobic or hydrophilic SPIONs loaded into liposomes (magnetoliposomes) of different lipid composition obtained by sonication. These hybrid nanostructures were characterized by measuring several parameters such as size and polydispersity, and number of SPIONs encapsulated or embedded into the lipid systems. We then studied the influence of acyl chain length as well as its unsaturation, charge, and presence of cholesterol in the lipid bilayer at high field strength (7 T) to mimic the conditions used in preclinical assays. Our results showed a high variability depending on the nature of the magnetic particles. Focusing on the hydrophobic SPIONs, the cholesterol-containing samples showed a slight reduction in r2, while unsaturation of the lipid acyl chain and inclusion of a negatively charged lipid into the bilayer appeared to yield a marked increase in negative contrast, thus rendering these magnetoliposomes suitable candidates as CAs, especially as a liver CA. PMID:27472319

  19. Improving Sensitivity in Ultrasound Molecular Imaging by Tailoring Contrast Agent Size Distribution: In Vivo Studies

    PubMed Central

    Streeter, Jason E.; Gessner, Ryan; Miles, Iman; Dayton, Paul A.

    2010-01-01

    Molecular imaging with ultrasound relies on microbubble contrast agents (MCAs) selectively adhering to a ligand-specific target. Prior studies have shown that only small quantities of microbubbles are retained at their target sites, therefore, enhancing contrast sensitivity to low concentrations of microbubbles is essential to improve molecular imaging techniques. In order to assess the effect of MCA diameter on imaging sensitivity, perfusion and molecular imaging studies were performed with microbubbles of varying size distributions. To assess signal improvement and MCA circulation time as a function of size and concentration, blood perfusion was imaged in rat kidneys using nontargeted size-sorted MCAs with a Siemens Sequoia ultrasound system (Siemans, Mountain View, CA) in cadence pulse sequencing (CPS) mode. Molecular imaging sensitivity improvements were studied with size-sorted αvβ3-targeted bubbles in both fibrosarcoma and R3230 rat tumor models. In perfusion imaging studies, video intensity and contrast persistence was ≈8 times and ≈3 times greater respectively, for “sorted 3-micron” MCAs (diameter, 3.3 ± 1.95 μm) when compared to “unsorted” MCAs (diameter, 0.9 ± 0.45 μm) at low concentrations. In targeted experiments, application of sorted 3-micron MCAs resulted in a ≈20 times video intensity increase over unsorted populations. Tailoring size-distributions results in substantial imaging sensitivity improvement over unsorted populations, which is essential in maximizing sensitivity to small numbers of MCAs for molecular imaging. PMID:20236606

  20. Tyrosinase-catalyzed melanin as a contrast agent for photoacoustic tomography

    NASA Astrophysics Data System (ADS)

    Krumholz, Arie; Chavez, Sarah; Yao, Junjie; Fleming, Timothy; Gillanders, William E.; Wang, Lihong V.

    2011-03-01

    It is difficult to distinguish between tumor cells and surrounding cells without staining as is done in histology. We developed tyrosinase-catalyzed melanin as a reporter gene for photoacoustic tomography. Tyrosinase is the primary enzyme responsible for the production of melanin and alone is sufficient to produce melanin in non-melanogenic cells. Two cell lines were created: a stably transfected HeLa line and a transiently transfected 293 line. A phantom experiment was performed with the 293 transfected cells 48 hours post transfection and the results compared with oxygenated whole blood, B16 melanoma and 293 control cells. An in vivo experiment was performed using the transfected HeLa cells xenografted into a nude mouse ear, and then imaged. The results show strong contrast for tyrosinase-catalyzed melanin in both the 293 cells in the tube phantom as well as the in vivo result showing melanin in a nude mouse ear. Transfection increased expression in 293 cells 159 fold and image contrast compared to blood by as much as 50 fold. Due to the strong signal obtained at longer wavelengths and the decrease of blood signal at the same wavelengths, tyrosinase catalyzed melanin is a good candidate as a molecular imaging contrast agent for photoacoustic tomography.

  1. TREG coated iron oxide nanoparticles as contrast agent for MRI in-vivo use

    NASA Astrophysics Data System (ADS)

    Gutierrez-Garcia, Eric; Hidalgo-Tobon, Silvia; Lopez, Ciro; Gonzalez-Rodriguez, Roberto; Coffer, Jeffery; De Celis Alonso, Benito; Dies Suarez, Pilar; Obregon, Manuel; Perez-Pena, Mario; Platas-Neri, Diana; Mendez-Rojas, Miguel

    2014-11-01

    Super-paramagnetic iron oxide nanoparticles (SPIONs) are of interest due to their great potential applications in diverse fields such as biomedicine. In this work we have prepared SPION nanoparticles using the polyol technique and characterized the magnetic properties of them for MRI in-vivo use. Nanoparticle preparation: All reagents were purchased from commercial sources (Sigma-Aldrich, St. Louis, USA) Iron (III) acetylacetonate, [Fe(acac)3], was used as the iron oxide precursor and thermally decomposed at high temperatures in triethyleneglycol (TREG). Nano-sized magnetite particles were prepared by an adaptation of the method proposed by Wei Cai et al[1-3]. A healthy rabbit was scanned on a clinical 1.5 T Philips MR scanner. Images were taken in 2D mode with a mFFE sequence. Relaxation time T2 was obtained from the MR images using a Matlab algorithm where the signal intensity decay was calculated at each image and then adjusted to a mono-exponential curve. Images were obtained before contrast injection, 24 hours and 36 hours following SPIONs administration. Signal decay at different Echo times for the prepared magnetic SPIONs, before and after contrast injection was measured. It was visualized a concentration of the agent contrast in brain and liver and the results were compared with images obtained from histopathology.

  2. Recent advances in ytterbium-based contrast agents for in vivo X-ray computed tomography imaging: promises and prospects.

    PubMed

    Liu, Yanlan; Liu, Jianhua; Ai, Kelong; Yuan, Qinghai; Lu, Lehui

    2014-01-01

    X-ray computed tomography (CT) imaging is one of the most widely used diagnostic imaging techniques in the clinic, and has raised significant interest in recent years both in research and practice owing to its many advantages such as deep penetration depth, high resolution and facile image processing. Developing heavy metal-based CT contrast agents, especially heavy metal-containing nanoparticulate CT contrast agents, has become a key focus in research fields to address issues of clinical iodinated agents involving short circulation time, low contrast efficiency and potential renal toxicity. In this review, we summarize the development of ytterbium (Yb)-based CT contrast agents and highlight the design and applications of Yb-based nanoparticulate CT contrast agents. Yb has high atomic number and higher abundance in the earth's crust relative to Au, Ta and Bi, which have received much attention as a CT contrast agents. In particular, in contrast to these metal elements, as well as I, Yb has K-edge energy that is located just within the higher-intensity region of X-ray spectra, which can induce significant enhancement in the contrast efficiency. When encapsulated in nanoparticles, Yb can remain in the circulation for a long time. This long in vivo circulation time, combined with the proper K-edge energy and a large absorption cross-section of Yb in the near-infrared region, makes Yb-based nanoparticles particularly promising in angiography, 'multicolor' spectral CT imaging, and multimodal imaging. Finally, we also discuss the prospects and the challenges in the development of Yb-based CT contrast agents.

  3. Optical characterization and feasibility study of multifunctional polylactic-co-glycolic acid (PLGA) nanoparticles designed for photo-thermal optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Subhash, Hrebesh M.; Xie, Hui; Smith, Jeffrey W.; McCarty, Owen

    2011-06-01

    Nanoparticles with plasmon-resonance absorption in the near-IR (NIR) optical range are of great interest in optical coherence tomography (OCT) for contrast enhancement and diagnostic interventions in molecular imaging. In this study, we characterized the optical properties of multifunctional NIR dye-loaded PLGA nanoparticles (approved by the U.S. Food and Drug Administration) to assess the feasibility of using contrast agent for photo-thermal OCT (PT-OCT) imaging. Tissue phantoms containing NIR dye-doped PLGA nanoparticles were prepared in 2% agarose solution. To study the feasibility of detecting the particles using PT-OCT, imaging was performed with a custom built PT-OCT system, and specific contrast was obtained with the prepared tissue mimicking phantoms. The excellent photo-thermal properties in combination with the positive tissue phantom results qualify the feasibility of dye-loaded PLGA particles as promising candidate for PT-OCT imaging applications.

  4. Ultrasound examination using contrast agent and elastosonography in the evaluation of single thyroid nodules: Preliminary results

    PubMed Central

    Ferrari, F.S.; Megliola, A.; Scorzelli, A.; Guarino, E.; Pacini, F.

    2008-01-01

    Aim To evaluate the usefulness of ultrasound (US) using contrast agent and elastosonography in the characterization of thyroid nodules. Materials and methods From November 2006 to July 2007, 23 patients with single thyroid nodules underwent B-mode US and power Doppler, US examination using contrast agent, elastosonography and fine needle aspiration cytology (FNAC). Sixteen patients underwent thyroidectomy. Results The 23 nodules included 14 benign and 9 malignant lesions. Analysis of time/intensity curves showed that wash-in (8.8 ± 1.3 vs 12.1 ± 2.6 s; p = 0.002, t-test) and peak enhancement (15.3 ± 4.6 vs 22.2 ± 3.9 s; p = 0.001, t-test) occurred significantly earlier in the malignant nodules than in the benign nodules. Wash-out was monophasic in 70% of benign nodules, but in none of the malignant nodules; polyphasic in 30% of benign nodules and in 100% of malignant nodules. Polyphasic wash-out showed a statistically significant association with malignancy (p = 0.0007, χ2). Polyphasic wash-out yielded a sensitivity of 100%, specificity of 71%, positive predictive value (PPV) of 69%, negative predictive value (NPV) of 100% and diagnostic accuracy of 83%. In 78% of the benign nodules (11/14) elastosonographic patterns was 1–2 (elevated elasticity); in 88% of the malignant nodules (8/9) elastosonographic patterns was 3–4 (reduced elasticity). Elastosonography yielded a sensitivity of 88%, specificity of 78%, PPV of 72%, NPV of 91% and diagnostic accuracy of 82%. Elastosonographic patterns 3–4 is associated with malignancy (p = 0.001, χ2). Conclusion US using contrast agent and elastosonography can be a useful diagnostic tool in the evaluation of single thyroid nodules, particularly when FNAC result is non-diagnostic or suggests a follicular lesion, and in nodules <1 cm. PMID:23396751

  5. Ultrasound contrast agent imaging: Real-time imaging of the superharmonics

    SciTech Connect

    Peruzzini, D.; Viti, J.; Tortoli, P.; Verweij, M. D.; Jong, N. de; Vos, H. J.

    2015-10-28

    Currently, in medical ultrasound contrast agent (UCA) imaging the second harmonic scattering of the microbubbles is regularly used. This scattering is in competition with the signal that is caused by nonlinear wave propagation in tissue. It was reported that UCA imaging based on the third or higher harmonics, i.e. “superharmonic” imaging, shows better contrast. However, the superharmonic scattering has a lower signal level compared to e.g. second harmonic signals. This study investigates the contrast-to-tissue ratio (CTR) and signal to noise ratio (SNR) of superharmonic UCA scattering in a tissue/vessel mimicking phantom using a real-time clinical scanner. Numerical simulations were performed to estimate the level of harmonics generated by the microbubbles. Data were acquired with a custom built dual-frequency cardiac phased array probe. Fundamental real-time images were produced while beam formed radiofrequency (RF) data was stored for further offline processing. The phantom consisted of a cavity filled with UCA surrounded by tissue mimicking material. The acoustic pressure in the cavity of the phantom was 110 kPa (MI = 0.11) ensuring non-destructivity of UCA. After processing of the acquired data from the phantom, the UCA-filled cavity could be clearly observed in the images, while tissue signals were suppressed at or below the noise floor. The measured CTR values were 36 dB, >38 dB, and >32 dB, for the second, third, and fourth harmonic respectively, which were in agreement with those reported earlier for preliminary contrast superharmonic imaging. The single frame SNR values (in which ‘signal’ denotes the signal level from the UCA area) were 23 dB, 18 dB, and 11 dB, respectively. This indicates that noise, and not the tissue signal, is the limiting factor for the UCA detection when using the superharmonics in nondestructive mode.

  6. Ultrasound contrast agent imaging: Real-time imaging of the superharmonics

    NASA Astrophysics Data System (ADS)

    Peruzzini, D.; Viti, J.; Tortoli, P.; Verweij, M. D.; de Jong, N.; Vos, H. J.

    2015-10-01

    Currently, in medical ultrasound contrast agent (UCA) imaging the second harmonic scattering of the microbubbles is regularly used. This scattering is in competition with the signal that is caused by nonlinear wave propagation in tissue. It was reported that UCA imaging based on the third or higher harmonics, i.e. "superharmonic" imaging, shows better contrast. However, the superharmonic scattering has a lower signal level compared to e.g. second harmonic signals. This study investigates the contrast-to-tissue ratio (CTR) and signal to noise ratio (SNR) of superharmonic UCA scattering in a tissue/vessel mimicking phantom using a real-time clinical scanner. Numerical simulations were performed to estimate the level of harmonics generated by the microbubbles. Data were acquired with a custom built dual-frequency cardiac phased array probe. Fundamental real-time images were produced while beam formed radiofrequency (RF) data was stored for further offline processing. The phantom consisted of a cavity filled with UCA surrounded by tissue mimicking material. The acoustic pressure in the cavity of the phantom was 110 kPa (MI = 0.11) ensuring non-destructivity of UCA. After processing of the acquired data from the phantom, the UCA-filled cavity could be clearly observed in the images, while tissue signals were suppressed at or below the noise floor. The measured CTR values were 36 dB, >38 dB, and >32 dB, for the second, third, and fourth harmonic respectively, which were in agreement with those reported earlier for preliminary contrast superharmonic imaging. The single frame SNR values (in which `signal' denotes the signal level from the UCA area) were 23 dB, 18 dB, and 11 dB, respectively. This indicates that noise, and not the tissue signal, is the limiting factor for the UCA detection when using the superharmonics in nondestructive mode.

  7. Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents

    NASA Astrophysics Data System (ADS)

    Lovell, Jonathan F.; Jin, Cheng S.; Huynh, Elizabeth; Jin, Honglin; Kim, Chulhong; Rubinstein, John L.; Chan, Warren C. W.; Cao, Weiguo; Wang, Lihong V.; Zheng, Gang

    2011-04-01

    Optically active nanomaterials promise to advance a range of biophotonic techniques through nanoscale optical effects and integration of multiple imaging and therapeutic modalities. Here, we report the development of porphysomes; nanovesicles formed from self-assembled porphyrin bilayers that generated large, tunable extinction coefficients, structure-dependent fluorescence self-quenching and unique photothermal and photoacoustic properties. Porphysomes enabled the sensitive visualization of lymphatic systems using photoacoustic tomography. Near-infrared fluorescence generation could be restored on dissociation, creating opportunities for low-background fluorescence imaging. As a result of their organic nature, porphysomes were enzymatically biodegradable and induced minimal acute toxicity in mice with intravenous doses of 1,000 mg kg-1. In a similar manner to liposomes, the large aqueous core of porphysomes could be passively or actively loaded. Following systemic administration, porphysomes accumulated in tumours of xenograft-bearing mice and laser irradiation induced photothermal tumour ablation. The optical properties and biocompatibility of porphysomes demonstrate the multimodal potential of organic nanoparticles for biophotonic imaging and therapy.

  8. Iron oxide nanorods as high-performance magnetic resonance imaging contrast agents

    NASA Astrophysics Data System (ADS)

    Mohapatra, Jeotikanta; Mitra, Arijit; Tyagi, Himanshu; Bahadur, D.; Aslam, M.

    2015-05-01

    An efficient magnetic resonance imaging (MRI) contrast agent with a high R2 relaxivity value is achieved by controlling the shape of iron oxide to rod like morphology with a length of 30-70 nm and diameter of 4-12 nm. Fe3O4 nanorods of 70 nm length, encapsulated with polyethyleneimine show a very high R2 relaxivity value of 608 mM-1 s-1. The enhanced MRI contrast of nanorods is attributed to their higher surface area and anisotropic morphology. The higher surface area induces a stronger magnetic field perturbation over a larger volume more effectively for the outer sphere protons. The shape anisotropy contribution is understood by calculating the local magnetic field of nanorods and spherical nanoparticles under an applied magnetic field (3 Tesla). As compared to spherical geometry, the induced magnetic field of a rod is stronger and hence the stronger magnetic field over a large volume leads to a higher R2 relaxivity of nanorods.An efficient magnetic resonance imaging (MRI) contrast agent with a high R2 relaxivity value is achieved by controlling the shape of iron oxide to rod like morphology with a length of 30-70 nm and diameter of 4-12 nm. Fe3O4 nanorods of 70 nm length, encapsulated with polyethyleneimine show a very high R2 relaxivity value of 608 mM-1 s-1. The enhanced MRI contrast of nanorods is attributed to their higher surface area and anisotropic morphology. The higher surface area induces a stronger magnetic field perturbation over a larger volume more effectively for the outer sphere protons. The shape anisotropy contribution is understood by calculating the local magnetic field of nanorods and spherical nanoparticles under an applied magnetic field (3 Tesla). As compared to spherical geometry, the induced magnetic field of a rod is stronger and hence the stronger magnetic field over a large volume leads to a higher R2 relaxivity of nanorods. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr00055f

  9. Oxidation-responsive Eu(2+/3+)-liposomal contrast agent for dual-mode magnetic resonance imaging.

    PubMed

    Ekanger, Levi A; Ali, Meser M; Allen, Matthew J

    2014-12-01

    An oxidation-responsive contrast agent for magnetic resonance imaging was synthesized using Eu(2+) and liposomes. Positive contrast enhancement was observed with Eu(2+), and chemical exchange saturation transfer was observed before and after oxidation of Eu(2+). Orthogonal detection modes render the concentration of Eu inconsequential to molecular information provided through imaging.

  10. Detection of brain tumors using fluorescence diffuse optical tomography and nanoparticles as contrast agents.

    PubMed

    Fortin, Pierre-Yves; Genevois, Coralie; Koenig, Anne; Heinrich, Emilie; Texier, Isabelle; Couillaud, Franck

    2012-12-01

    Near-infrared fluorescence-enhanced diffuse optical tomography (fDOT) is used to localize tumors in mice using fluorescent nanoparticles as a blood pool contrast agent. The infrared dye DiR is loaded in the lipid core of nontargeted nanoparticles (DiR-lipidots) and injected systemically via the tail vein in mice bearing U87 tumors. Distribution and time-course of DiR-lipidots are followed using in vivo fluorescence reflectance imaging and reveal enhanced fluorescent signal within the subcutaneous tumors up to seven days due to the enhanced permeability and retention effect. Tumor growth into the brain is followed using bioluminescent imaging, and tumor localization is further determined by magnetic resonance imaging. The fDOT provides three-dimensional fluorescent maps that allow for consistent localization for both subcutaneous and brain tumors. PMID:23208215

  11. Detection of brain tumors using fluorescence diffuse optical tomography and nanoparticles as contrast agents

    NASA Astrophysics Data System (ADS)

    Fortin, Pierre-Yves; Genevois, Coralie; Koenig, Anne; Heinrich, Emilie; Texier, Isabelle; Couillaud, Franck

    2012-12-01

    Near-infrared fluorescence-enhanced diffuse optical tomography (fDOT) is used to localize tumors in mice using fluorescent nanoparticles as a blood pool contrast agent. The infrared dye DiR is loaded in the lipid core of nontargeted nanoparticles (DiR-lipidots) and injected systemically via the tail vein in mice bearing U87 tumors. Distribution and time-course of DiR-lipidots are followed using in vivo fluorescence reflectance imaging and reveal enhanced fluorescent signal within the subcutaneous tumors up to seven days due to the enhanced permeability and retention effect. Tumor growth into the brain is followed using bioluminescent imaging, and tumor localization is further determined by magnetic resonance imaging. The fDOT provides three-dimensional fluorescent maps that allow for consistent localization for both subcutaneous and brain tumors.

  12. The study of N-isopropylacrylamide gel dosimeter doped iodinated contrast agents

    NASA Astrophysics Data System (ADS)

    Chang, Y. J.; Hsieh, L. L.; Liu, M. H.; Liu, J. S.; Hsieh, B. T.

    2013-06-01

    Low toxicity of N-isopropylacrylamide (NIPAM) dosimeter was doped with clinical iodinated contrast medium agents(Iobitridol (Xenetix® 350) and organically bound iodine (Conray® 60) as radiation sensitizers; The suitable gel dosimeter preparation formula in this research was 5 w/w% gelatin, 5 w/w% N-isopropylacrylamide, 3 w/w% N,N-methylene-bis-acrylamide, and 5 mM Tetrakis phosphonium chloride. The spiral CT was irradiator, and 120 kVp was the operating tube voltage. The maximum radiation dose was 0.6 Gy, and optical CT was the gel measurement device used. The results showed SERs with the addition of radiosensitizers were 10.70 (Xenetix® 350) and 9.67 (Conray® 60), respectively. Thus, the polymerized gel dosimeter could be used in the efficacy evaluation of low-energy and low-radiation dose.

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

    PubMed Central

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

    2015-01-01

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

  14. Aptamer-Modified Temperature-Sensitive Liposomal Contrast Agent for Magnetic Resonance Imaging.

    PubMed

    Zhang, Kunchi; Liu, Min; Tong, Xiaoyan; Sun, Na; Zhou, Lu; Cao, Yi; Wang, Jine; Zhang, Hailu; Pei, Renjun

    2015-09-14

    A novel aptamer modified thermosensitive liposome was designed as an efficient magnetic resonance imaging probe. In this paper, Gd-DTPA was encapsulated into an optimized thermosensitive liposome (TSL) formulation, followed by conjugation with AS1411 for specific targeting against tumor cells that overexpress nucleolin receptors. The resulting liposomes were extensively characterized in vitro as a contrast agent. As-prepared TSLs-AS1411 had a diameter about 136.1 nm. No obvious cytotoxicity was observed from MTT assay, which illustrated that the liposomes exhibited excellent biocompatibility. Compared to the control incubation at 37 °C, the liposomes modified with AS1411 exhibited much higher T1 relaxivity in MCF-7 cells incubated at 42 °C. These data indicate that the Gd-encapsulated TSLs-AS1411 may be a promising tool in early cancer diagnosis.

  15. Cellulose nanoparticles are a biodegradable photoacoustic contrast agent for use in living mice

    PubMed Central

    Jokerst, Jesse V.; Van de Sompel, Dominique; Bohndiek, Sarah E.; Gambhir, Sanjiv S.

    2014-01-01

    Molecular imaging with photoacoustic ultrasound is an emerging field that combines the spatial and temporal resolution of ultrasound with the contrast of optical imaging. However, there are few imaging agents that offer both high signal intensity and biodegradation into small molecules. Here we describe a cellulose-based nanoparticle with peak photoacoustic signal at 700 nm and an in vitro limit of detection of 6 pM (0.02 mg/mL). Doses down to 0.35 nM (1.2 mg/mL) were used to image mouse models of ovarian cancer. Most importantly, the nanoparticles were shown to biodegrade in the presence of cellulase both through a glucose assay and electron microscopy. PMID:25225633

  16. Anionic cyclodextrins as versatile hosts for pharmaceutical nanotechnology: Synthesis, drug delivery, enantioselectivity, contrast agents for MRI.

    PubMed

    Mavridis, Irene M; Yannakopoulou, Konstantina

    2015-08-15

    The review presents a full library of single-isomer primary rim per-carboxylate- and per-sulfate-α-, -β- and -γ-cyclodextrin (CD) derivatives and their potential for pharmaceutical nanotechnology. Recent advances in cyclodextrin chemistry have enabled robust methods for the synthesis of single-isomer anionic CDs. Numerous nanobio-applications have been already reported for these negatively charged derivatives, which alone or in combination with other biodegradable molecular platforms can become important carriers for targeted drug delivery and release. Specialized applications are also discussed, such as chiral separations, as well as the ability of per-6-carboxylated-cyclodextrins to coordinate with metal cations and especially with lanthanide cations that makes them candidates as contrast agents for Magnetic Resonance Imaging.

  17. Detection of brain tumors using fluorescence diffuse optical tomography and nanoparticles as contrast agents.

    PubMed

    Fortin, Pierre-Yves; Genevois, Coralie; Koenig, Anne; Heinrich, Emilie; Texier, Isabelle; Couillaud, Franck

    2012-12-01

    Near-infrared fluorescence-enhanced diffuse optical tomography (fDOT) is used to localize tumors in mice using fluorescent nanoparticles as a blood pool contrast agent. The infrared dye DiR is loaded in the lipid core of nontargeted nanoparticles (DiR-lipidots) and injected systemically via the tail vein in mice bearing U87 tumors. Distribution and time-course of DiR-lipidots are followed using in vivo fluorescence reflectance imaging and reveal enhanced fluorescent signal within the subcutaneous tumors up to seven days due to the enhanced permeability and retention effect. Tumor growth into the brain is followed using bioluminescent imaging, and tumor localization is further determined by magnetic resonance imaging. The fDOT provides three-dimensional fluorescent maps that allow for consistent localization for both subcutaneous and brain tumors.

  18. Optical contrast agents and imaging systems for detection and diagnosis of cancer

    PubMed Central

    Pierce, Mark C.; Javier, David J.; Richards-Kortum, Rebecca

    2010-01-01

    Molecular imaging has rapidly emerged as a discipline with the potential to impact fundamental biomedical research and clinical practice. Within this field, optical imaging offers several unique capabilities, based on the ability of cells and tissues to effect quantifiable changes in the properties of visible and near-infrared light. Beyond endogenous optical properties, the development of molecularly targeted contrast agents enables disease-specific morphologic and biochemical processes to be labeled with unique optical signatures. Optical imaging systems can then provide real-time visualization of pathophysiology at spatial scales from the sub-cellular to whole organ levels. In this article, we review fundamental techniques and recent developments in optical molecular imaging, emphasizing laboratory and clinical systems that aim to visualize the microscopic and macroscopic hallmarks of cancer. PMID:18712733

  19. Carbon-coated iron oxide nanoparticles as contrast agents in magnetic resonance imaging.

    PubMed

    Bae, Hongsub; Ahmad, Tanveer; Rhee, Ilsu; Chang, Yongmin; Jin, Seong-Uk; Hong, Sungwook

    2012-01-01

    Coprecipitated ferrite nanoparticles were coated with carbon using a hydrothermal method. From transmission electron microscope pictures, we could see that the coated iron oxide nanoparticles were spherical in shape with an average diameter of 90 nm. The strong bonding of carbon on the nanoparticle surfaces was checked by noting the C = O and C = C vibrations in Fourier transform infrared spectra. The spin-lattice relaxation process [T1] and spin-spin relaxation process [T2] relaxivities of hydrogen protons in the aqueous solution of coated nanoparticles were determined to be 1.139 (mM·s)-1 and 1.115 (mM·s)-1, respectively. These results showed that the carbon-coated iron oxide nanoparticles are applicable as both T1 and T2 contrast agents in magnetic resonance imaging.PACS: 81.05.y; 76.60.Es; 61.46; 75.50.k; 87.61.

  20. Gadolinium-labeled dendronized gold nanoparticles as new targeted MRI contrast agent

    NASA Astrophysics Data System (ADS)

    Pan, Hongmu; Daniel, Marie-Christine

    2010-04-01

    Early diagnosis is critical for positive outcome of cancer treatments. In many cases, lives would be saved if the tumor could be detected at a very early stage. Nanoparticles have the property of passively targeting tumor sites due to their enhanced permeation and retention (EPR) effect. Thus they can play a critical role in improving the ability to find cancer in its earliest and most treatable stages. Furthermore magnetic resonance imaging is one of the most precise techniques for cancer screening since it can show 3D images of the tumors. For a better enhancement of the sensitivity of this method, MRI contrast agent (DOTA)Gd was attached to poly(propylene imine) dendrons of third generation and the obtained dendrons were used for modification of gold nanoparticles.

  1. Increased antibiotic release and equivalent biomechanics of a spacer cement without hard radio contrast agents.

    PubMed

    Bitsch, R G; Kretzer, J P; Vogt, S; Büchner, H; Thomsen, M N; Lehner, B

    2015-10-01

    We compared a novel calcium carbonate spacer cement (Copal® spacem) to well-established bone cements. Electron microscopic structure and elution properties of the antibiotics ofloxacin, vancomycin, clindamycin, and gentamicin were examined. A knee wear simulator model for articulating cement spacers was established. Mechanical tests for bending strength, flexural modulus, and compressive and fatigue strength were performed. The electron microscopic analysis showed a microporous structure of the spacer cement, and this promoted a significantly higher and longer antibiotic elution. All spacer cement specimens released the antibiotics for a period of up to 50days with the exception of the vancomycin loading. The spacer cement showed significantly less wear scars and fulfilled the ISO 5833 requirements. The newly developed spacer cement is a hydrophilic antibiotic carrier with an increased release. Cement without hard radio contrast agents can improve tribological behaviour of spacers, and this may reduce reactive wear particles and abrasive bone defects.

  2. Graphene oxide mediated delivery of methylene blue for combined photodynamic and photothermal therapy.

    PubMed

    Sahu, Abhishek; Choi, Won Il; Lee, Jong Hyun; Tae, Giyoong

    2013-08-01

    Nano graphene oxide sheet (nanoGO) was non-covalently functionalized with Pluronic block copolymer and complexed with methylene blue, a hydrophilic and positively charged photosensitizer, via electrostatic interaction for combined photodynamic-photothermal therapy of cancer. Pluronic coating of nanoGO ensured its stability in biological fluids. NanoGO plays dual role of a photothermal material as well as a delivery agent for photosensitizer. The release of the photosensitizer from nanoGO surface was pH-dependent and an acidic condition increased the release rate considerably. This nanocomplex showed enhanced uptake by cancer cells than normal cells and in the absence of light it showed no major toxicity towards the cells. In contrast, when irradiated with selective NIR laser lights, it induced significant cell death. Intravenous injection of the complex into tumor bearing mice showed high tumor accumulation, and when the tumors were exposed to NIR lights, it caused total ablation of tumor tissue through the combined action of photodynamic and photothermal effects. This work shows the potential of nanoGO for synergistic combination phototherapy of tumor in vivo.

  3. Graphene oxide/manganese ferrite nanohybrids for magnetic resonance imaging, photothermal therapy and drug delivery.

    PubMed

    Yang, Yan; Shi, Haili; Wang, Yapei; Shi, Benzhao; Guo, Linlin; Wu, Dongmei; Yang, Shiping; Wu, Huixia

    2016-01-01

    Superparamagnetic manganese ferrite (MnFe2O4) nanoparticles have been deposited on graphene oxide (GO) by the thermal decomposition of manganese (II) acetylacetonate and iron (III) acetylacetonate precursors in triethylene glycol. The resulting GO/MnFe2O4 nanohybrids show very low cytotoxicity, negligible hemolytic activity, and imperceptible in vivo toxicity. In vitro and in vivo magnetic resonance imaging experiments demonstrate that GO/MnFe2O4 nanohybrids could be used as an effective T2 contrast agent. The strong optical absorbance in the near-infrared (NIR) region and good photothermal stability of GO/MnFe2O4 nanohybrids result in the highly efficient photothermal ablation of cancer cells. GO/MnFe2O4 nanohybrids can be further loaded with doxorubicin (DOX) by π-π conjugate effect for chemotherapy. DOX release from GO/MnFe2O4 is significantly influenced by pH and can be triggered by NIR laser. The enhanced cancer cell killing by GO/MnFe2O4/DOX composites has been achieved when irradiated with near-infrared light, suggesting that the nanohybrids could deliver both DOX chemotherapy and photothermal therapy with a synergistic effect.

  4. Clean Photothermal Heating and Controlled Release From Near Infrared Dye Doped Nanoparticles Without Oxygen Photosensitization

    PubMed Central

    Guha, Samit; Shaw, Scott K.; Spence, Graeme T.; Roland, Felicia M.; Smith, Bradley D.

    2015-01-01

    The photothermal heating and release properties of biocompatible organic nanoparticles, doped with a near-infrared croconaine (Croc) dye, were compared with analogous nanoparticles doped with the common near-infrared dyes ICG and IR780. Separate formulations of lipid-polymer-hybrid nanoparticles and liposomes, each containing Croc dye, absorbed strongly at 808 nm and generated clean laser-induced heating (no production of 1O2 and no photobleaching of the dye). In contrast, laser-induced heating of nanoparticles containing ICG or IR780 produced reactive 1O2 leading to bleaching of the dye and also decomposition of co-encapsulated payload such as the drug Doxorubicin. Croc dye was especially useful as a photothermal agent for laser controlled release of chemically sensitive payload from nanoparticles. Solution state experiments demonstrated repetitive fractional release of water soluble fluorescent dye from the interior of thermosensitive liposomes. Additional experiments used a focused laser beam to control leakage from immobilized liposomes with very high spatial and temporal precision. The results indicate that fractional photothermal leakage from nanoparticles doped with Croc dye is a promising method for a range of controlled release applications. PMID:26149326

  5. Immunological evaluation of the new stable ultrasound contrast agent LK565: a phase one clinical trial

    PubMed Central

    Funke, B; Maerz, HK; Okorokow, S; Polata, S; Lehmann, I; Sack, U; Wild, P; Geisler, T; Zotz, RJ

    2004-01-01

    Background Ultrasound contrast agents (UCAs) allow the enhancement of vascular definition, thereby providing more diagnostic information. LK565 is a new second-generation UCA based on synthetic polymers of aspartic acid which is eliminated from the blood stream via phagocytosis. LK565 forms very stable air-filled microspheres and is capable of repeated passage through the pulmonary capillary bed after peripheral intravenous injection. This characteristic allows examination of the cardiac function or extracardiac vessel abnormalities up to 15 minutes. Methods A phase one clinical study was conducted on 15 healthy volunteers to identify the development of an undesirable immune response. Phagocytosis capacity, TNF-α secretion, and MHC class II upregulation of monocytes was monitored, as well as microsphere specific antibody development (IgM, IgG). Furthermore, the kinetics of the activation surface markers CD69, CD25, CD71, and CD11b on leukocytes were analyzed. Results Due to LK565-metabolism the administration of the UCA led to saturation of phagocytes which was reversible after 24 hrs. Compared to positive controls neither significant TNF-α elevation, neither MHC class II and activation surface markers upregulation, nor specific antibody development was detectable. Conclusion The administration of LK565 provides a comfortable duration of signal enhancement, esp. in echocardiography, without causing a major activation cascade or triggering an adaptive immune response. To minimize the risk of undesirable adverse events such as anaphylactoid reactions, immunological studies should be included in clinical trials for new UCAs. The use of LK565 as another new ultrasound contrast agent should be encouraged as a safe means to provide additional diagnostic information. PMID:15357870

  6. Experimental evaluation of a hyperspectral imager for near-infrared fluorescent contrast agent studies

    NASA Astrophysics Data System (ADS)

    Luthman, A. S.; Bohndiek, Sarah E.

    2015-03-01

    Hyperspectral imaging (HSI) systems have the potential to combine morphological and spectral information to provide detailed and high sensitivity readouts in biological and medical applications. As HSI enables simultaneous detection in several spectral bands, the technology has significant potential for use in real-time multiplexed contrast agent studies. Examples include tumor detection in intraoperative and endoscopic imaging as well as histopathology. A multiplexed readout from multiple disease targets, such as cell surface receptors overexpressed in cancer cells, could improve both sensitivity and specificity of tumor identification. Here, we evaluate a commercial, compact, near-infrared HSI sensor that has the potential to enable low cost, video rate HSI for multiplexed fluorescent contrast agent studies in biomedical applications. The hyperspectral imager, based on a monolithically integrated Fabry-Perot etalon, has 70 spectral bands between 600-900 nm, making it ideal for this application. Initial calibration of the imager was performed to determine wavelength band response, quantum efficiency and the effect of F-number on the spectral response. A platform for wide-field fluorescence imaging in reflectance using fluorophore specific LED excitation was then developed. The applicability of the imaging platform for simultaneous readout of multiple fluorophore signals was demonstrated using a dilution series of Alexa Fluor 594 and Alexa Fluor 647, showing that nanomolar fluorophore concentrations can be detected. Our results show that the HSI system can clearly resolve the emission spectra of the two fluorophores in mixtures of concentrations across several orders of magnitude, indicating a high dynamic range performance. We therefore conclude that the HSI sensor tested here is suitable for detecting fluorescence in biomedical imaging applications.

  7. A Reference Agent Model for DCE MRI can be used to quantify the relative vascular permeability of two MRI contrast agents

    PubMed Central

    Cárdenas-Rodríguez, Julio; Howison, Christine M.; Matsunaga, Terry O.; Pagel, Mark D.

    2013-01-01

    Dynamic Contrast Enhancement (DCE) MRI has been used to measure the kinetic transport constant, Ktrans, which is used to assess tumor angiogenesis and the effects of anti-angiogenic therapies. Standard DCE MRI methods must measure the pharmacokinetics of a contrast agent in the blood stream, known as the Arterial Input Function (AIF), which is then used as a reference for the pharmacokinetics of the agent in tumor tissue. However, the AIF is difficult to measure in pre-clinical tumor models and in patients. Moreover the AIF is dependent on the Fahraeus effect that causes a highly variable hematocrit (Hct) in tumor microvasculature, leading to erroneous estimates of Ktrans. To overcome these problems, we have developed the Reference Agent Model (RAM) for DCE MRI analyses, which determines the ratio of Ktrans values of two contrast agents that are simultaneously co-injected and detected during a single DCE-MRI scan session. The RAM obviates the need to monitor the AIF because one contrast agent effectively serves as an internal reference in the tumor tissue for the other agent, and it also eliminates the systematic errors in the estimated Ktrans caused by assuming an erroneous Hct. Simulations demonstrated that the RAM can accurately and precisely estimate the relative Ktrans (RKtrans) of two agents. To experimentally evaluate the utility of RAM for analyzing DCE MRI results, we optimized a previously reported multiecho 19F MRI method to detect two perfluorocarbon contrast agents that were co-injected during a single in vivo study and selectively detected in the same tumor location. The results demonstrated that RAM determined RKtrans with excellent accuracy and precision. PMID:23583323

  8. Amplifying the sensitivity of zinc(II) responsive MRI contrast agents by altering water exchange rates.

    PubMed

    Yu, Jing; Martins, André F; Preihs, Christian; Clavijo Jordan, Veronica; Chirayil, Sara; Zhao, Piyu; Wu, Yunkou; Nasr, Khaled; Kiefer, Garry E; Sherry, A Dean

    2015-11-11

    Given the known water exchange rate limitations of a previously reported Zn(II)-sensitive MRI contrast agent, GdDOTA-diBPEN, new structural targets were rationally designed to increase the rate of water exchange to improve MRI detection sensitivity. These new sensors exhibit fine-tuned water exchange properties and, depending on the individual structure, demonstrate significantly improved longitudinal relaxivities (r1). Two sensors in particular demonstrate optimized parameters and, therefore, show exceptionally high longitudinal relaxivities of about 50 mM(-1) s(-1) upon binding to Zn(II) and human serum albumin (HSA). This value demonstrates a 3-fold increase in r1 compared to that displayed by the original sensor, GdDOTA-diBPEN. In addition, this study provides important insights into the interplay between structural modifications, water exchange rate, and kinetic stability properties of the sensors. The new high relaxivity agents were used to successfully image Zn(II) release from the mouse pancreas in vivo during glucose stimulated insulin secretion. PMID:26462412

  9. Preservation of imaging capability in sensitive ultrasound contrast agents after indirect plasma sterilization.

    PubMed

    Albala, Lorenzo; Ercan, Utku K; Joshi, Suresh G; Eisenbrey, John R; Teraphongphom, Nutte; Wheatley, Margaret A

    2015-10-15

    Many injectables are not amenable to standard sterilization methods, which destroy sensitive materials. This is particularly true for ultrasound contrast agents (UCA) consisting of gas bubbles stabilized by a surfactant or polymer shell. We investigated a new method to achieve safe and effective sterilization in production by introducing dielectric-barrier discharge non-thermal plasma. A dielectric-barrier discharge was generated to first produce plasma-treated phosphate-buffered saline (PTPBS), which was used as a sterilant solution for our UCA SE61, avoiding direct heat, pressure, chemicals, or radiation. Treated samples were tested for acoustic properties in vitro and in a flow phantom, and for sterility by standard methods. Three minutes plasma treatment of phosphate-buffered saline (PBS) proved effective. The samples showed significant inactivation of inoculated bacteria upon PTPBS treatment as compared to un-treated-PBS (p=0.0022). The treated and untreated samples showed no statistical significance (p>0.05) in acoustic response or bubble diameter (mean±SEM: 2.52±0.31 μm). Nile Red was used to model intercalation of drug in the hydrophobic shell, intercalated successfully into SE61, and was unaffected by plasma treatment. The PTPBS completely sterilized suspensions of UCA, and it did not compromise the acoustic properties of the agent or its ability to retain a hydrophobic compound. PMID:26241754

  10. Surfactant-stabilized contrast agent on the nanoscale for diagnostic ultrasound imaging.

    PubMed

    Wheatley, Margaret A; Forsberg, Flemming; Dube, Neal; Patel, Mihir; Oeffinger, Brian E

    2006-01-01

    Ultrasound contrast agents (CA) are generally micron-sized stabilized gas bubbles, injected IV. However, to penetrate beyond the vasculature and accumulate in targets such as tumors, CA must be an order of magnitude smaller. We describe a method of achieving nanometer-sized, surfactant-stabilized CA by differential centrifugation. High g force was shown to destroy bubble integrity. Optimal conditions (300 rpm for 3 min) produced an agent with a mean diameter of 450 nm, which gave 25.5 dB enhancement in vitro at a dose of 10 microL/mL, with a 13 min half-life. In vivo, the CA produced excellent power Doppler and grey-scale pulse inversion harmonic images at low acoustic power when administered. In vivo dose-response curves obtained in three rabbits showed enhancement between 20 and 25 dB for dosages above 0.025 mL/kg. These results encourage further investigation of the possible diagnostic and therapeutic benefits of using nanoparticles as CA, including passive targeting and accumulation in tumors.

  11. Preservation of imaging capability in sensitive ultrasound contrast agents after indirect plasma sterilization.

    PubMed

    Albala, Lorenzo; Ercan, Utku K; Joshi, Suresh G; Eisenbrey, John R; Teraphongphom, Nutte; Wheatley, Margaret A

    2015-10-15

    Many injectables are not amenable to standard sterilization methods, which destroy sensitive materials. This is particularly true for ultrasound contrast agents (UCA) consisting of gas bubbles stabilized by a surfactant or polymer shell. We investigated a new method to achieve safe and effective sterilization in production by introducing dielectric-barrier discharge non-thermal plasma. A dielectric-barrier discharge was generated to first produce plasma-treated phosphate-buffered saline (PTPBS), which was used as a sterilant solution for our UCA SE61, avoiding direct heat, pressure, chemicals, or radiation. Treated samples were tested for acoustic properties in vitro and in a flow phantom, and for sterility by standard methods. Three minutes plasma treatment of phosphate-buffered saline (PBS) proved effective. The samples showed significant inactivation of inoculated bacteria upon PTPBS treatment as compared to un-treated-PBS (p=0.0022). The treated and untreated samples showed no statistical significance (p>0.05) in acoustic response or bubble diameter (mean±SEM: 2.52±0.31 μm). Nile Red was used to model intercalation of drug in the hydrophobic shell, intercalated successfully into SE61, and was unaffected by plasma treatment. The PTPBS completely sterilized suspensions of UCA, and it did not compromise the acoustic properties of the agent or its ability to retain a hydrophobic compound.

  12. New calcium-selective smart contrast agents for magnetic resonance imaging.

    PubMed

    Verma, Kirti Dhingra; Forgács, Attila; Uh, Hyounsoo; Beyerlein, Michael; Maier, Martin E; Petoud, Stéphane; Botta, Mauro; Logothetis, Nikos K

    2013-12-23

    Calcium plays a vital role in the human body and especially in the central nervous system. Precise maintenance of Ca(2+) levels is very crucial for normal cell physiology and health. The deregulation of calcium homeostasis can lead to neuronal cell death and brain damage. To study this functional role played by Ca(2+) in the brain noninvasively by using magnetic resonance imaging, we have synthesized a new set of Ca(2+) -sensitive smart contrast agents (CAs). The agents were found to be highly selective to Ca(2+) in the presence of other competitive anions and cations in buffer and in physiological fluids. The structure of CAs comprises Gd(3+)-DO3A (DO3A=1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane) coupled to a Ca(2+) chelator o-amino phenol-N,N,O-triacetate (APTRA). The agents are designed to sense Ca(2+) present in extracellular fluid of the brain where its concentration is relatively high, that is, 1.2-0.8 mM. The determined dissociation constant of the CAs to Ca(2+) falls in the range required to sense and report changes in extracellular Ca(2+) levels followed by an increase in neural activity. In buffer, with the addition of Ca(2+) the increase in relaxivity ranged from 100-157%, the highest ever known for any T1-based Ca(2+)-sensitive smart CA. The CAs were analyzed extensively by the measurement of luminescence lifetime measurement on Tb(3+) analogues, nuclear magnetic relaxation dispersion (NMRD), and (17)O NMR transverse relaxation and shift experiments. The results obtained confirmed that the large relaxivity enhancement observed upon Ca(2+) addition is due to the increase of the hydration state of the complexes together with the slowing down of the molecular rotation and the retention of a significant contribution of the water molecules of the second sphere of hydration.

  13. Plasma sterilization of poly lactic acid ultrasound contrast agents: surface modification and implications for drug delivery.

    PubMed

    Eisenbrey, John R; Hsu, Jennifer; Wheatley, Margaret A

    2009-11-01

    Poly lactic acid (PLA) ultrasound contrast agents (CA) have been developed previously in our laboratory for ultrasound (US) imaging, as well as surface coated with doxorubicin to create a potential targeted platform of chemotherapeutic delivery using focused US. However, we have previously found it impossible to sterilize these agents while at the same time maintaining their acoustic properties, a task that would probably require fabrication within a clean facility. The purpose of this paper is to investigate the feasibility of using plasma to sterilize these CA while maintaining maximum echogenicity, a step that would greatly facilitate in vivo investigations. Effects of plasma exposure time (1, 3 and 6 min) and intensity (low-10 mA, 6.8 W; medium-15 mA, 10.5 W; and high-25 mA, 18 W) on the CAs' acoustic properties, surface morphology, zeta potential, capacity to carry chemotherapeutics and overall sterility are described. Both increases in plasma intensity and exposure time increased CA zeta potential and also significantly increased drug payload. High-intensity plasma exposure for 3 min was found to be an optimal sterilization protocol for maximal (100%) preservation of CA echogenicity. Plasma exposure resulted in sterile samples and maintained original CA enhancement of 20 dB and acoustic half-life over 75 min, while increasing CA zeta potential by 11 mV and doxorubicin loading efficiency by 10%. This study not only shows how a highly temperature- and pressure-sensitive agent can be sterilized using plasma, but also that surface modification can be used to increase surface binding of the drug. PMID:19766380

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

    NASA Astrophysics Data System (ADS)

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

    2007-05-01

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

  15. Catechin tuned magnetism of Gd-doped orthovanadate through morphology as T1-T2 MRI contrast agents

    PubMed Central

    Vairapperumal, Tamilmani; Saraswathy, Ariya; Ramapurath, Jayasree S.; Kalarical Janardhanan, Sreeram; Balachandran Unni, Nair

    2016-01-01

    Tetragonal (t)-LaVO4 has turned out to be a potential host for luminescent materials. Synthesis of t-LaVO4 till date has been based on chelating effect of EDTA making it not ideal for bioimaging applications. An alternative was proposed by us through the use of catechin. In recent times there is interest for new MRI contrast agents that can through appropriate doping function both as MRI contrast and optical/upconversion materials. It is generally believed that under appropriate doping, t-LaVO4 would be a better upconversion material than monoclinic (m)-LaVO4. Based on these postulations, this work explores the use of gadolinium doped t-LaVO4 as an MRI contrast agent. From literature, gadolinium oxide is a good T1 contrast agent. Through this work, using catechin as a template for the synthesis of Gd doped t-LaVO4, we demonstrate the possible use as a T1 contrast agent. Interestingly, as the catechin concentration changes, morphology changes from nanorods to square nanoplates and spheres. In this process, a switch from T1 to T2 contrast agent was also observed. Under optimal concentration of catechin, with a rod shaped Gd doped t-LaVO4 an r2/r1 value of 21.30 was observed. Similarly, with a spherical shape had an r2/r1 value of 1.48 was observed. PMID:27752038

  16. High-performance dendritic contrast agents for X-ray computed tomography imaging using potent tetraiodobenzene derivatives.

    PubMed

    You, Suyeon; Jung, Hye-Youn; Lee, Chaewoon; Choe, Yun Hui; Heo, Ju Young; Gang, Gil-Tae; Byun, Sang-Kyung; Kim, Won Kon; Lee, Chul-Ho; Kim, Dong-Eog; Kim, Young Il; Kim, Yoonkyung

    2016-03-28

    The use of computed tomography (CT) for vascular imaging is critical in medical emergencies requiring urgent diagnostic decisions, such as cerebral ischemia and many cardiovascular diseases. Small-molecule iodinated contrast media are often injected intravenously as radiopaque agents during CT imaging to achieve high contrast enhancement of vascular systems. The rapid excretion rate of these agents is overcome by injecting a significantly high dose of iodine, which can have serious side effects. Here we report a simple method to prepare blood-pool contrast agents for CT based on dendrimers for the first time using tetraiodobenzene derivatives as potent radiopaque moieties. Excellent in vivo safety has been demonstrated for these small (13-22nm) unimolecular water-soluble dendritic contrast agents, which exhibit high contrast enhancement in the blood-pool and effectively extend their blood half-lives. Our method is applicable to virtually any scaffold with suitable surface groups and may fulfill the current need for safer, next-generation iodinated CT contrast agents. PMID:26812006

  17. Nanobubble-Affibody: Novel ultrasound contrast agents for targeted molecular ultrasound imaging of tumor.

    PubMed

    Yang, Hengli; Cai, Wenbin; Xu, Lei; Lv, Xiuhua; Qiao, Youbei; Li, Pan; Wu, Hong; Yang, Yilin; Zhang, Li; Duan, Yunyou

    2015-01-01

    Nanobubbles (NBs), as novel ultrasound contrast agents (UCAs), have attracted increasing attention in the field of molecular ultrasound imaging for tumors. However, the preparation of uniform-sized NBs is considered to be controversial, and poor tumor selectivity in in vivo imaging has been reported. In this study, we fabricated uniform nano-sized NBs (478.2 ± 29.7 nm with polydispersity index of 0.164 ± 0.044, n = 3) using a thin-film hydration method by controlling the thickness of phospholipid films; we then conjugated the NBs with Affibody molecules to produce nano-sized UCAs referred to as NB-Affibody with specific affinity to human epidermal growth factor receptor type 2 (HER2)-overexpressing tumors. NB-Affibody presented good ultrasound enhancement, demonstrating a peak intensity of 104.5 ± 2.1 dB under ultrasound contrast scanning. Ex vivo experiments further confirmed that the NB-Affibody conjugates were capable of targeting HER2-expressing tumor cells in vivo with high affinity. The newly prepared nano-sized NB-Affibody conjugates were observed to be novel targeted UCAs for efficient and safe specific molecular imaging and may have potential applications in early cancer quantitative diagnosis and targeted therapy in the future.

  18. PEGylated polyethylenimine as enhanced T₁ contrast agent for efficient magnetic resonance imaging.

    PubMed

    Zhou, Shengyuan; Wu, Zhenkai; Chen, Xiongsheng; Jia, Lianshun; Zhu, Wei

    2014-07-23

    Currently used small molecular magnetic resonance (MR) imaging contrast agents (CAs) in clinics have relatively short half-lives, which has limited the acquisition of high-resolution organ and angiographic images. Therefore, development of a facile strategy for the synthesis of long-circulating CAs with the transforming potential for MR imaging still remains a great challenge. Here we communicate the design and synthesis of PEGylated polyethylenimine (PEI) and its application as enhanced T1 CA for the long-circulating blood pool as well as efficient organ and tumor imaging. In this study, PEI was covalently grafted with gadolinium (Gd(III)) chelator and mPEG-NHS, followed by acetylation of the remaining amines to improve biocompatibility and prolong circulation time. With the relatively long circulation time (3.8 h), the formed multifunctional PEI (PEI.NHAc-DTPA(Gd(III))-mPEG) can be used as an enhanced T1 CA for blood pool and major organ imaging, and could be cleared from the body 96 h post administration through the urinary system. Importantly, the PEI.NHAc-DTPA(Gd(III))-mPEG complexes displayed a strong T1 contrast effect for tumor imaging through the enhanced permeation and retention effect. These findings suggest that the synthesized PEI.NHAc-DTPA(Gd(III))-mPEG may be used as a promising CA for T1 MR imaging of various biological systems.

  19. Iron oxide nanorods as high-performance magnetic resonance imaging contrast agents.

    PubMed

    Mohapatra, Jeotikanta; Mitra, Arijit; Tyagi, Himanshu; Bahadur, D; Aslam, M

    2015-01-01

    An efficient magnetic resonance imaging (MRI) contrast agent with a high R2 relaxivity value is achieved by controlling the shape of iron oxide to rod like morphology with a length of 30-70 nm and diameter of 4-12 nm. Fe3O4 nanorods of 70 nm length, encapsulated with polyethyleneimine show a very high R2 relaxivity value of 608 mM(-1) s(-1). The enhanced MRI contrast of nanorods is attributed to their higher surface area and anisotropic morphology. The higher surface area induces a stronger magnetic field perturbation over a larger volume more effectively for the outer sphere protons. The shape anisotropy contribution is understood by calculating the local magnetic field of nanorods and spherical nanoparticles under an applied magnetic field (3 Tesla). As compared to spherical geometry, the induced magnetic field of a rod is stronger and hence the stronger magnetic field over a large volume leads to a higher R2 relaxivity of nanorods.

  20. Localization of near-infrared contrast agents in tumors by intravital microscopy

    NASA Astrophysics Data System (ADS)

    Becker, Andreas; Schneider, Guenther; Riefke, Bjoern; Licha, Kai; Semmler, Wolfhard

    1999-01-01

    In this contribution we use intravital microscopy to study the dynamics of extravasation into normal and tumor tissue of several hydrophilic cyanine dyes used as near-infrared (NIR) contrast agents. The technique provides information about the angiographic properties of the dyes and about their interaction with tumor tissue under dynamic conditions in vivo. In our previous work we demonstrated that several NIR- absorbing fluorescent dyes enable in vivo fluorescence detection of tumors in mice and rats. However, the mechanism leading to dye accumulation and enhanced fluorescence in tumors is not fully understood. Increased extravasation of dyes into tumor tissue due to pathologically altered tumor vessels may be an important factor in this process. Indocyanine green (ICG) displayed predominantly intravascular distribution and rapid elimination resulting in enhanced fluorescence signal of vessels during the first 15 min after administration only. No elevated extravasation into tumor tissue was observed with ICG. A hydrophilic indotricarbocyanine derivative with a high molecular weight displayed prolonged intravascular distribution and increased fluorescence signal of the vasculature compared to surrounding tissue for up to five hours. Rapid extravasation and accumulation in tumor areas, yielding elevated contrast of tumors up to 15 min after administration, was observed with hydrophilic, low molecular weight indotricarbocyanine derivatives.

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

    PubMed Central

    Hou, Lin; Zhang, Huijuan; Wang, Yating; Wang, Lili; Yang, Xiaomin; Zhang, Zhenzhong

    2015-01-01

    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. PMID:26213465

  2. Comparative study of the physicochemical properties of six clinical low molecular weight gadolinium contrast agents.

    PubMed

    Laurent, Sophie; Elst, Luce Vander; Muller, Robert N

    2006-01-01

    This paper compares the physicochemical properties of six low molecular weight clinical complexes of gadolinium studied under identical experimental conditions. Magnevist, Dotarem, Omniscan, ProHance, MultiHance and Gadovist were investigated by oxygen-17 relaxometry at different temperatures and by proton relaxometry at various magnetic fields, temperatures and media [pure water, zinc(II)-containing aqueous solutions and HSA-containing solutions]. Osmolality, viscosity and stability versus transmetallation by zinc(II) ions were added for a more comprehensive description. The relaxivities of the clinical formulations as measured in water are similar in the imaging magnetic field region, with a slightly better performance for MultiHance. This can be explained by a shorter distance between the hydrogen nuclei of the water molecule bound to the Gd(3+) ion and this paramagnetic centre. In contrast to the open-chain complexes, all macrocyclic systems (Dotarem, ProHance and Gadovist) are insensitive to transmetallation by zinc ions. The stability of the open-chain complexes with respect to transmetallation depends on the chemical structure of the ligand, with a better stability for MultiHance. The presence of human serum albumin has no significant effect on the proton relaxivity of Magnevist, Dotarem, Omniscan, ProHance and Gadovist but markedly increases the relaxivity of MultiHance because of a non-covalent interaction with the protein. As a result, the relaxivity of MultiHance in HSA-containing media of fixed concentration decreases with increasing concentration of the contrast agent.

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

    SciTech Connect

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

    2010-12-02

    Magnetic nanoparticles have recently been very attractive for biomedical applications. In this study, we have synthesized ferrite nanoparticles for application as contrast agents in MRI experiments. Fe{sub 3}O{sub 4} and MnFe{sub 2}O{sub 4} spinel ferrites with a mean size of 11-12 nm, were prepared by a modified polyol route in commercially available polyethylene glycol with molecular weight 600 (PEG-600). The reaction takes place in the presence of water soluble and non-toxic tri-block copolymer known as Pluronic registered F-127 (PEO{sub 100}-PPO{sub 65}-PEO{sub 100}). The nanoparticles have saturation magnetization values of 52 and 68 emu/g for MnFe{sub 2}O{sub 4} and Fe{sub 3}O{sub 4}, respectively. Both the Fe{sub 3}O{sub 4}, and MnFe{sub 2}O{sub 4} nanoparticles make stable solutions in water known as ferrofluids. Preliminary data demonstrated the capability of these nanoparticles to induce imaging contrast in T{sub 2} weighted MRI experiments, making these materials suitable for biomedical applications such as medical MRI.

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

    PubMed

    Hou, Lin; Zhang, Huijuan; Wang, Yating; Wang, Lili; Yang, Xiaomin; Zhang, Zhenzhong

    2015-01-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

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

  6. Use of a Genetically Engineered Protein for the Design of a Multivalent MRI Contrast Agent

    PubMed Central

    Karfeld, Lindsay S.; Bull, Steve R.; Davis, Nicolynn E.; Meade, Thomas J.; Barron, Annelise E.

    2008-01-01

    The majority of clinically used contrast agents (CAs) for magnetic resonance imaging have low relaxivities and thus require high concentrations for signal enhancement. Research has turned to multivalent, macromolecular CAs to increase CA efficiency. However, previously developed macromolecular CAs do not provide high relaxivities, have limited biocompatibility, and/or do not have a structure that is readily modifiable to tailor to particular applications. We report a new family of multivalent, biomacromolecular, genetically engineered protein polymer-based CAs; the protein backbone contains evenly spaced lysines that are derivatized with gadolinium (Gd(III)) chelators. The protein's length and repeating amino acid sequence are genetically specified. We reproducibly obtained conjugates with an average of 8 – 9 Gd(III) chelators per protein. These multivalent CAs reproducibly provide a high relaxivity of 7.3 mM-1s-1 per Gd(III) and 62.6 mM-1s-1 per molecule. Furthermore, they can be incorporated into biomaterial hydrogels via chemical crosslinking of remaining free lysines, and provide a dramatic contrast enhancement. Thus, these protein polymer CAs could be a useful tool for following the evolution of tissue engineering scaffolds. PMID:17927227

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  8. Endocardial border delineation capability of a novel multimodal polymer-shelled contrast agent

    PubMed Central

    2014-01-01

    Background A novel polymer-shelled contrast agent (CA) with multimodal and target-specific potential was developed recently. To determine its ultrasonic diagnostic features, we evaluated the endocardial border delineation as visualized in a porcine model and the concomitant effect on physiological variables. Methods Three doses of the novel polymer-shelled CA (1.5 ml, 3 ml, and 5 ml [5 × 108 microbubbles (MBs)/ml]) and the commercially available CA SonoVue (1.5 ml [2–5 × 108 MBs/ml]) were used. Visual evaluations of ultrasound images of the left ventricle were independently performed by three observers who graded each segment in a 6-segment model as either 0 = not visible, 1 = weakly visible, or 2 = visible. Moreover, the duration of clinically useful contrast enhancement and the left ventricular opacification were determined. During anesthesia, oxygen saturation, heart rate, and arterial pressure were sampled every minute and the effect of injection of CA on these physiological variables was evaluated. Results The highest dose of the polymer-shelled CA gave results comparable to SonoVue. Thus, no significant difference in the overall segment score distribution (2-47-95 vs. 1-39-104), time for clinically sufficient contrast enhancement (20–40 s for both) and left ventricular overall opacification was found. In contrast, when comparing the endocardial border delineation capacity for different regions SonoVue showed significantly higher segment scores for base and mid, except for the mid region when injecting 1.5 ml of the polymer-shelled CA. Neither high nor low doses of the polymer-shelled CA significantly affected the investigated physiological variables. Conclusions This study demonstrated that the novel polymer-shelled CA can be used in contrast-enhanced diagnostic imaging without influence on major physiological variables. PMID:24993845

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

    PubMed

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

    2013-02-01

    Third-harmonic generation (THG) microscopy has been reported to provide intrinsic contrast in elastic fibers, cytoplasmic membrane, nucleus, actin filaments, lipid bodies, hemoglobin, and melanin in human skin. For advanced molecular imaging, exogenous contrast agents are developed for a higher structural or molecular specificity. We demonstrate the potential of the commonly adopted tattoo dye as a THG contrast agent for in vivo optical biopsy of human skin. Spectroscopy and microscopy experiments were performed on cultured cells with tattoo dyes, in tattooed mouse skin, and in tattooed human skin to demonstrate the THG enhancement effect. Compared with other absorbing dyes or nanoparticles used as exogenous THG contrast agents, tattoo dyes are widely adopted in human skin so that future clinical biocompatibility evaluation is relatively achievable. Combined with the demonstrated THG enhancement effect, tattoo dyes show their promise for future clinical imaging applications. PMID:23389681

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

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

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

  11. Parametric imaging using subharmonic signals from ultrasound contrast agents in patients with breast lesions.

    PubMed

    Eisenbrey, John R; Dave, Jaydev K; Merton, Daniel A; Palazzo, Juan P; Hall, Anne L; Forsberg, Flemming

    2011-01-01

    Parametric maps showing perfusion of contrast media can be useful tools for characterizing lesions in breast tissue. In this study we show the feasibility of parametric subharmonic imaging (SHI), which allows imaging of a vascular marker (the ultrasound contrast agent) while providing near complete tissue suppression. Digital SHI clips of 16 breast lesions from 14 women were acquired. Patients were scanned using a modified LOGIQ 9 scanner (GE Healthcare, Waukesha, WI) transmitting/receiving at 4.4/2.2 MHz. Using motion-compensated cumulative maximum intensity (CMI) sequences, parametric maps were generated for each lesion showing the time to peak (TTP), estimated perfusion (EP), and area under the time-intensity curve (AUC). Findings were grouped and compared according to biopsy results as benign lesions (n = 12, including 5 fibroadenomas and 3 cysts) and carcinomas (n = 4). For each lesion CMI, TTP, EP, and AUC parametric images were generated. No significant variations were detected with CMI (P = .80), TTP (P = .35), or AUC (P = .65). A statistically significant variation was detected for the average pixel EP (P = .002). Especially, differences were seen between carcinoma and benign lesions (mean ± SD, 0.10 ± 0.03 versus 0.05 ± 0.02 intensity units [IU]/s; P = .0014) and between carcinoma and fibroadenoma (0.10 ± 0.03 versus 0.04 ± 0.01 IU/s; P = .0044), whereas differences between carcinomas and cysts were found to be nonsignificant. In conclusion, a parametric imaging method for characterization of breast lesions using the high contrast to tissue signal provided by SHI has been developed. While the preliminary sample size was limited, results show potential for breast lesion characterization based on perfusion flow parameters.

  12. Development and characterization of hollow polymeric microcapsules for use as contrast agents for diagnostic ultrasound

    NASA Astrophysics Data System (ADS)

    Narayan, Padma Jyothi

    1999-09-01

    This thesis concerns the development and characterization of a new type of rigid-shelled ultrasound contrast agent. A novel method was devised for producing hollow, gas- filled, polymer microcapsules, sized to less than 10 μm in diameter for contrast imaging. This method involved the encapsulation of a solid, volatile core material, and its subsequent evacuation by sublimation. The biodegradable polymer, 50/50 poly(D,L-lactide-co- glycolide), was the main focus of this study. Polymer- based contrast agents have many advantages, such as their applicability for concomitant imaging and drug delivery. Three encapsulation techniques were evaluated: solvent evaporation, coacervation, and spray drying. The polymer molecular weight and polydispersity in the solvent evaporation and coacervation techniques strongly affected microcapsule size and morphology. Efficient mechanical agitation and shear were crucial for obtaining high yields in the desired size range (less than 6 μm). In spray drying, a factorial design approach was used to optimize conditions to produce microcapsules. The main factors affecting spray drying were found to be the temperature driving force for drying and initial polymer concentration. The smallest microcapsule mean diameters were produced by spray drying (3-4 μm) and solvent evaporation (5-6 μm). Zeta potential (ζ) studies for all microcapsule types indicated that the encapsulation technique affected their surface properties due to the orientation of the polymer chains within nascent polymer droplets. Microcapsules with the most hydrophilic tendency were produced with solvent evaporation (ζ ~ -50 mV). In vitro acoustic testing revealed that the 20-41 μm size fractions of coacervate microcapsules were the most echogenic. In vivo ultrasound studies with both solvent evaporation and coacervate microcapsules showed visible enhancement of the color Doppler image in the rabbit kidney for the samples less than 10 μm in diameter. A mathematical

  13. Biological imaging with nonlinear photothermal microscopy using a compact supercontinuum fiber laser source.

    PubMed

    He, Jinping; Miyazaki, Jun; Wang, Nan; Tsurui, Hiromichi; Kobayashi, Takayoshi

    2015-04-20

    Nonlinear photothermal microscopy is applied in the imaging of biological tissues stained with chlorophyll and hematoxylin. Experimental results show that this type of organic molecules, which absorb light but transform dominant part of the absorbed energy into heat, may be ideal probes for photothermal imaging without photochemical toxicity. Picosecond pump and probe pulses, with central wavelengths of 488 and 632 nm, respectively, are spectrally filtered from a compact supercontinuum fiber laser source. Based on the light source, a compact and sensitive super-resolution imaging system is constructed. Further more, the imaging system is much less affected by thermal blurring than photothermal microscopes with continuous-wave light sources. The spatial resolution of nonlinear photothermal microscopy is ~ 188 nm. It is ~ 23% higher than commonly utilized linear photothermal microscopy experimentally and ~43% than conventional optical microscopy theoretically. The nonlinear photothermal imaging technology can be used in the evaluation of biological tissues with high-resolution and contrast. PMID:25969015

  14. Intravascular contrast agent-enhanced MRI measuring contrast clearance and tumor blood volume and the effects of vascular modifiers in an experimental tumor

    SciTech Connect

    Bentzen, Lise . E-mail: lise@oncology.dk; Vestergaard-Poulsen, Peter; Nielsen, Thomas; Overgaard, Jens; Bjornerud, Atle; Briley-Saebo, Karen; Horsman, Michael R.; Ostergaard, Leif

    2005-03-15

    Purpose: To examine the feasibility of using the MRI blood pool agent NC100150 for evaluation of tumor blood volume (TBV) estimates by both dynamic contrast-enhanced MRI (DCE-MRI) and susceptibility contrast MRI assays in an experimental tumor. Contrast agent clearance (K{sup trans}; depends on perfusion and permeability) from the DCE-MRI time curves was estimated, and changes in TBV and K{sup trans} were measured after administration of two drugs that reduce perfusion by different mechanisms. Methods and materials: The DCE-MRI experiments were simulated with expected physiologic values for the C3H mouse mammary carcinoma. The C3H tumor was examined by DCE-MRI and susceptibility contrast MRI with NC100150 (NC100150 Injection, Clariscan; Amersham Health, Oslo, Norway) after treatment with either hydralazine or combretastatin (Oxigene, Boston, MA). Results: Simulations showed that reliable estimates of changes in TBV and K{sup trans} could be performed with DCE-MRI. Hydralazine was shown to reduce TBV as measured by both assays and to reduce K{sup trans}. Dynamic contrast-enhanced MRI also suggested that TBV and K{sup trans} were reduced in combretastatin-treated tumors, and the TBV reduction was confirmed by susceptibility contrast MRI. Data suggested the drug to affect mainly the total TBV, whereas microvessels as such seemed less altered. Conclusion: The study supports the use of the combined DCE-MRI and susceptibility contrast MRI assay with a blood pool agent in characterizing tumors and their response to treatment.

  15. Ultrasound Molecular Imaging of Tumor Angiogenesis with an Integrin Targeted Microbubble Contrast Agent

    PubMed Central

    Anderson, Christopher R.; Hu, Xiaowen; Tlaxca, Jose; Decleves, Anne-Emilie; Houghtaling, Robert; Sharma, Kumar; Lawrence, Michael; Ferrara, Katherine; Rychak, Joshua J.

    2010-01-01

    Rationale and Objectives Ultrasound molecular imaging is an emerging technique for sensitive detection of intravascular targets. Molecular imaging of angiogenesis has strong potential for both clinical use and as a research tool in tumor biology and the development of anti-angiogenic therapies. Our objective is to develop a robust microbubble (MB) ultrasound contrast agent platform to which targeting ligands can be conjugated by biocompatible, covalent conjugation chemistry, and to develop a pure low mechanical index imaging processing method and corresponding quantifying method. The microbubbles and the imaging methods were evaluated in a mouse model of breast cancer in vivo. Materials and Methods We utilized a cyclic RGD (cRGD) pentapeptide containing a terminal cysteine group conjugated to the surface of MB bearing pyridyldithio-propionate (PDP) for targeting αvβ3 integrins. As negative controls, MB without a ligand or MB bearing a scrambled sequence (cRAD) were prepared. To enable characterization of peptides bound to MB surfaces, the cRGD peptide was labeled with FITC and detected by plate fluorometry, flow cytometry, and fluorescence microscopy. Targeted adhesion of cRGD-MB was demonstrated in an in vitro flow adhesion assay against recombinant murine αvβ3 integrin protein and αvβ3 integrin-expressing endothelial cells (bEnd.3). The specificity of cRGD-MB for αvβ3 integrin was demonstrated by treating bEnd.3 EC with a blocking antibody. A murine model of mammary carcinoma was used to assess targeted adhesion and ultrasound molecular imaging in vivo. The targeted microbubbles were visualized using a low mechanical index contrast imaging pulse sequence, and quantified by intensity normalization and two-dimensional Fourier transform analysis, Results The cRGD ligand concentration on the MB surface was ~8.2 × 106 molecules/MB. At a wall shear stress of 1.0 dynes/cm2, cRGD-MB exhibited 5-fold higher adhesion to immobilized recombinant αvβ3 integrin

  16. Molecularly-Targeted Gold-Based Nanoparticles for Cancer Imaging and Near-Infrared Photothermal Therapy

    NASA Astrophysics Data System (ADS)

    Day, Emily Shannon

    2011-12-01

    This thesis advances the use of nanoparticles as multifunctional agents for molecularly-targeted cancer imaging and photothermal therapy. Cancer mortality has remained relatively unchanged for several decades, indicating a significant need for improvements in care. Researchers are evaluating strategies incorporating nanoparticles as exogenous energy absorbers to deliver heat capable of inducing cell death selectively to tumors, sparing normal tissue. Molecular targeting of nanoparticles is predicted to improve photothermal therapy by enhancing tumor retention. This hypothesis is evaluated with two types of nanoparticles. The nanoparticles utilized, silica-gold nanoshells and gold-gold sulfide nanoparticles, can convert light energy into heat to damage cancerous cells. For in vivo applications nanoparticles are usually coated with poly(ethylene glycol) (PEG) to increase blood circulation time. Here, heterobifunctional PEG links nanoparticles to targeting agents (antibodies and growth factors) to provide cell-specific binding. This approach is evaluated through a series of experiments. In vitro, antibody-coated nanoparticles can bind breast carcinoma cells expressing the targeted receptor and act as contrast agents for multiphoton microscopy prior to inducing cell death via photoablation. Furthermore, antibody-coated nanoparticles can bind tissue ex vivo at levels corresponding to receptor expression, suggesting they should bind their target even in the complex biological milieu. This is evaluated by comparing the accumulation of antibody-coated and PEG-coated nanoparticles in subcutaneous glioma tumors in mice. Contrary to expectations, antibody targeting did not yield more nanoparticles within tumors. Nevertheless, these studies established the sensitivity of glioma to photothermal therapy; mice treated with PEG-coated nanoshells experienced 57% complete tumor regression versus no regression in control mice. Subsequent experiments employed intracranial tumors to

  17. Visualization of multimodal polymer-shelled contrast agents using ultrasound contrast sequences: an experimental study in a tissue mimicking flow phantom

    PubMed Central

    2013-01-01

    Background A multimodal polymer-shelled contrast agent (CA) with target specific potential was recently developed and tested for its acoustic properties in a single element transducer setup. Since the developed polymeric CA has different chemical composition than the commercially available CAs, there is an interest to study its acoustic response when using clinical ultrasound systems. The aim of this study was therefore to investigate the acoustic response by studying the visualization capability and shadowing effect of three polymer-shelled CAs when using optimized sequences for contrast imaging. Methods The acoustic response of three types of the multimodal CA was evaluated in a tissue mimicking flow phantom setup by measuring contrast to tissue ratio (CTR) and acoustic shadowing using five image sequences optimized for contrast imaging. The measurements were performed over a mechanical index (MI) range of 0.2-1.2 at three CA concentrations (106, 105, 104 microbubbles/ml). Results The CTR-values were found to vary with the applied contrast sequence, MI and CA. The highest CTR-values were obtained when a contrast sequence optimized for higher MI imaging was used. At a CA concentration of 106 microbubbles/ml, acoustic shadowing was observed for all contrast sequences and CAs. Conclusions The CAs showed the potential to enhance ultrasound images generated by available contrast sequences. A CA concentration of 106 MBs/ml implies a non-linear relation between MB concentration and image intensity. PMID:23987142

  18. Theranostic Self-Assembly Structure of Gold Nanoparticles for NIR Photothermal Therapy and X-Ray Computed Tomography Imaging

    PubMed Central

    Deng, Heng; Zhong, Yanqi; Du, Meihong; Liu, Qinjun; Fan, Zhanming; Dai, Fengying; Zhang, Xin

    2014-01-01

    The controllable self-assembly of amphiphilic mixed polymers grafted gold nanoparitcles (AuNPs) leads to strong interparticle plasmonic coupling, which can be tuned to the near-infrared (NIR) region for enhanced photothermal therapy (PTT). In this study, an improved thiolation method was adopted for ATRP and ROP polymer to obtain amphiphilic brushes of PMEO2MA-SH and PCL-SH. By anchoring PCL-SH and PMEO2MA-SH onto the 14 nm AuNPs, a smart hybrid building block for self-assembly was obtained. Increasing the PCL/PMEO2MA chain ratio from 0.8:1, 2:1 and 3:1 to 7:1, the structure of gold assembl