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Sample records for targeted ultrasound contrast

  1. Molecular imaging with targeted contrast ultrasound.

    Science.gov (United States)

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

    2009-01-01

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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  3. Ultrasound Contrast Agent Microbubble Dynamics

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2009-12-01

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

  5. Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging.

    Science.gov (United States)

    Theek, Benjamin; Gremse, Felix; Kunjachan, Sijumon; Fokong, Stanley; Pola, Robert; Pechar, Michal; Deckers, Roel; Storm, Gert; Ehling, Josef; Kiessling, Fabian; Lammers, Twan

    2014-05-28

    The Enhanced Permeability and Retention (EPR) effect is extensively used in drug delivery research. Taking into account that EPR is a highly variable phenomenon, we have here set out to evaluate if contrast-enhanced functional ultrasound (ceUS) imaging can be employed to characterize EPR-mediated passive drug targeting to tumors. Using standard fluorescence molecular tomography (FMT) and two different protocols for hybrid computed tomography-fluorescence molecular tomography (CT-FMT), the tumor accumulation of a ~10 nm-sized near-infrared-fluorophore-labeled polymeric drug carrier (pHPMA-Dy750) was evaluated in CT26 tumor-bearing mice. In the same set of animals, two different ceUS techniques (2D MIOT and 3D B-mode imaging) were employed to assess tumor vascularization. Subsequently, the degree of tumor vascularization was correlated with the degree of EPR-mediated drug targeting. Depending on the optical imaging protocol used, the tumor accumulation of the polymeric drug carrier ranged from 5 to 12% of the injected dose. The degree of tumor vascularization, determined using ceUS, varied from 4 to 11%. For both hybrid CT-FMT protocols, a good correlation between the degree of tumor vascularization and the degree of tumor accumulation was observed, within the case of reconstructed CT-FMT, correlation coefficients of ~0.8 and p-values of EPR, and potentially also to pre-select patients likely to respond to passively tumor-targeted nanomedicine treatments. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    2017-08-01

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

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

    Science.gov (United States)

    Burke, Caitlin W; Price, Richard J

    2010-12-15

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

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

    Science.gov (United States)

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

    2017-10-01

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

  9. Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging

    Czech Academy of Sciences Publication Activity Database

    Theek, B.; Gremse, F.; Kunjachan, S.; Fokong, S.; Pola, Robert; Pechar, Michal; Deckers, R.; Storm, G.; Ehling, J.; Kiessling, F.; Lammers, T.

    2014-01-01

    Roč. 182, 28 May (2014), s. 83-89 ISSN 0168-3659 R&D Projects: GA ČR GCP207/12/J030 Institutional support: RVO:61389013 Keywords : drug targeting * nanomedicine * theranostics Subject RIV: CD - Macromolecular Chemistry Impact factor: 7.705, year: 2014

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

    Science.gov (United States)

    2017-08-01

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

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

    OpenAIRE

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

    2018-01-01

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

  12. Ultrasound contrast agents: an overview.

    Science.gov (United States)

    Cosgrove, David

    2006-12-01

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

  13. Ultrasound contrast agents: An overview

    International Nuclear Information System (INIS)

    Cosgrove, David

    2006-01-01

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

  14. Dynamic contrast enhanced ultrasound for therapy monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Hudson, John M. [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Williams, Ross [Imaging Research, Sunnybrook Research Institute, Toronto, ON (Canada); Tremblay-Darveau, Charles; Sheeran, Paul S. [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Milot, Laurent [Department of Medical Imaging, University of Toronto, Toronto, ON (Canada); Bjarnason, Georg A. [Department of Medical Oncology, University of Toronto, and Sunnybrook Odette Cancer Centre, Toronto, ON (Canada); Burns, Peter N., E-mail: burns@sri.utoronto.ca [Department of Medical Biophysics, University of Toronto, Toronto, ON (Canada); Imaging Research, Sunnybrook Research Institute, Toronto, ON (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON (Canada)

    2015-09-15

    Quantitative imaging is a crucial component of the assessment of therapies that target the vasculature of angiogenic or inflamed tissue. Dynamic contrast-enhanced ultrasound (DCE-US) using microbubble contrast offers the advantages of being sensitive to perfusion, non-invasive, cost effective and well suited to repeated use at the bedside. Uniquely, it employs an agent that is truly intravascular. This papers reviews the principles and methodology of DCE-US, especially as applied to anti-angiogenic cancer therapies. Reproducibility is an important attribute of such a monitoring method: results are discussed. More recent technical advances in parametric and 3D DCE-US imaging are also summarised and illustrated.

  15. Modeling of ultrasound propagation through contrast agents

    NARCIS (Netherlands)

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

    2008-01-01

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

  16. Contrast enhanced ultrasound in liver imaging

    International Nuclear Information System (INIS)

    Nielsen, Michael Bachmann; Bang, Nanna

    2004-01-01

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

  17. Contrast-enhanced harmonic endoscopic ultrasound

    DEFF Research Database (Denmark)

    Săftoiu, A; Dietrich, C F; Vilmann, P

    2012-01-01

    Second-generation intravenous blood-pool ultrasound contrast agents are increasingly used in endoscopic ultrasound (EUS) for characterization of microvascularization, differential diagnosis of benign and malignant focal lesions, and improving staging and guidance of therapeutic procedures. Although...... initially used as Doppler signal enhancers, second-generation microbubble contrast agents are now used with specific contrast harmonic imaging techniques, which benefit from the highly nonlinear behavior of the microbubbles. Contrast-specific modes based on multi-pulse technology are used to perform...... contrast-enhanced harmonic EUS based on a very low mechanical index (0.08 - 0.12). Quantification techniques based on dynamic contrast-enhanced ultrasound have been recommended for perfusion imaging and monitoring of anti-angiogenic treatment, mainly based on time-intensity curve analysis. Most...

  18. Contrast-Enhanced Ultrasound in Vascular Surgery

    DEFF Research Database (Denmark)

    Bredahl, Kim; Mestre, Xavier Marti; Coll, Ramon Vila

    2017-01-01

    modalities. Ultrasound has only challenged these methods in assessment of carotid disease, aortic aneurysms, venous insufficiency, and thromboembolism and in surveillance of in situ bypasses. These practice patterns may change with the introduction of second-generation ultrasound contrast agents which...... are easy to use, manageable, and safe. This topical review attempts to summarize and highlight the current evidence and future prospects for contrast-enhanced ultrasound in vascular surgery, with a particular focus on opportunities in carotid and lower limb arteriosclerotic disease and surveillance after...

  19. Lesion Contrast Enhancement in Medical Ultrasound Imaging

    DEFF Research Database (Denmark)

    Stetson, Paul F.; Sommer, F.G.; Macovski, A.

    1997-01-01

    Methods for improving the contrast-to-noise ratio (CNR) of low-contrast lesions in medical ultrasound imaging are described. Differences in the frequency spectra and amplitude distributions of the lesion and its surroundings can be used to increase the CNR of the lesion relative to the background...

  20. Contrast enhanced ultrasound of sentinel lymph nodes

    Directory of Open Access Journals (Sweden)

    XinWu Cui

    2013-03-01

    Full Text Available Sentinel lymph nodes are the first lymph nodes in the region that receive lymphatic drainage from a primary tumor. The detection or exclusion of sentinel lymph node micrometastases is critical in the staging of cancer, especially breast cancer and melanoma because it directly affects patient’s prognosis and surgical management. Currently, intraoperative sentinel lymph node biopsies using blue dye and radioisotopes are the method of choice for the detection of sentinel lymph node with high identification rate. In contrast, conventional ultrasound is not capable of detecting sentinel lymph nodes in most cases. Contrast enhanced ultrasound with contrast specific imaging modes has been used for the evaluation and diagnostic work-up of peripherally located suspected lymphadenopathy. The method allows for real-time analysis of all vascular phases and the visualization of intranodal focal “avascular” areas that represent necrosis or deposits of neoplastic cells. In recent years, a number of animal and human studies showed that contrast enhanced ultrasound can be also used for the detection of sentinel lymph node, and may become a potential application in clinical routine. Several contrast agents have been used in those studies, including albumin solution, hydroxyethylated starch, SonoVue®, Sonazoid® and Definity®. This review summarizes the current knowledge about the use of ultrasound techniques in detection and evaluation of sentinel lymph node.

  1. Contrast-enhanced Ultrasound for Non-tumor Liver Diseases

    Directory of Open Access Journals (Sweden)

    H Maruyama

    2012-03-01

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

  2. The 'humble' bubble: Contrast-enhanced ultrasound

    International Nuclear Information System (INIS)

    Marshall, Gill; Sykes, Anne; Berry, Jonathan; Jonker, Leon

    2011-01-01

    The use of contrast-enhanced ultrasound (CEUS) is increasing within the field of medical imaging. Ultrasonic contrast agent (UCA) contain gas microbubbles similar in size to red corpuscles which provide highly reflective interfaces, enabling dynamic demonstration of echogenic streams of the contrast within the anatomical area of interest on real-time grey scale ultrasound. Longevity of the microbubbles has been improved by changing their composition. The application of CEUS in the UK continues to grow, bringing it into territories historically occupied by computerised tomography (CT) scanning and magnetic resonance imaging (MRI). Hence, the role of CEUS may be of interest to all diagnostic imaging practitioners. Here we summarise the mode of action and use of CEUS, and its role within a range of applications. The potential risks of CEUS are compared to other contrast-enhanced imaging techniques. The benefits of CEUS and its implications for diagnostic imaging practice are also covered.

  3. Advanced detection strategies for ultrasound contrast agents

    NARCIS (Netherlands)

    J.M.G. Borsboom (Jerome)

    2005-01-01

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

  4. Nonspherical oscilllations of ultrasound contrast agent microbubbles

    NARCIS (Netherlands)

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

    2008-01-01

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

  5. Synthesis of Laboratory Ultrasound Contrast Agents

    Directory of Open Access Journals (Sweden)

    Jaemin Oh

    2013-10-01

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

  6. Contrast-Enhanced Ultrasound with VEGFR2-Targeted Microbubbles for Monitoring Regorafenib Therapy Effects in Experimental Colorectal Adenocarcinomas in Rats with DCE-MRI and Immunohistochemical Validation.

    Directory of Open Access Journals (Sweden)

    Ralf Stefan Eschbach

    Full Text Available To investigate contrast-enhanced ultrasound (CEUS with VEGFR2-targeted microbubbles for monitoring therapy effects of regorafenib on experimental colon carcinomas in rats with correlation to dynamic contrast-enhanced MRI (DCE-MRI and immunohistochemistry.Human colorectal adenocarcinoma xenografts (HT-29 were implanted subcutaneously in n = 21 (n = 11 therapy group; n = 10 control group female athymic nude rats (Hsd: RH-Foxn1rnu. Animals were imaged at baseline and after a one-week daily treatment with regorafenib or a placebo (10 mg/kg bodyweight, using CEUS with VEGFR2-targeted microbubbles and DCE-MRI. In CEUS tumor perfusion was assessed during an early vascular phase (wash-in area under the curve = WiAUC and VEGFR2-specific binding during a late molecular phase (signal intensity after 8 (SI8min and 10 minutes (SI10min, using a conventional 15L8 linear transducer (transmit frequency 7 MHz, dynamic range 80 dB, depth 25 mm. In DCE-MRI functional parameters plasma flow (PF and plasma volume (PV were quantified. For validation purposes, CEUS parameters were correlated with DCE-MRI parameters and immunohistochemical VEGFR2, CD31, Ki-67 and TUNEL stainings.CEUS perfusion parameter WiAUC decreased significantly (116,989 ± 77,048 a.u. to 30,076 ± 27,095a.u.; p = 0.005 under therapy with no significant changes (133,932 ± 65,960 a.u. to 84,316 ± 74,144 a.u.; p = 0.093 in the control group. In the therapy group, the amount of bound microbubbles in the late phase was significantly lower in the therapy than in the control group on day 7 (SI8min: 283 ± 191 vs. 802 ± 460 a.u.; p = 0.006; SI10min: 226 ± 149 vs. 645 ± 461 a.u.; p = 0.009. PF and PV decreased significantly (PF: 147 ± 58 mL/100 mL/min to 71 ± 15 mL/100 mL/min; p = 0.003; PV: 13 ± 3% to 9 ± 4%; p = 0.040 in the therapy group. Immunohistochemistry revealed significantly fewer VEGFR2 (7.2 ± 1.8 vs. 17.8 ± 4.6; p < 0.001, CD31 (8.1 ± 3.0 vs. 20.8 ± 5.7; p < 0.001 and Ki-67 (318.7

  7. Results of vardenafil mediated power Doppler ultrasound, contrast enhanced ultrasound and systematic random biopsies to detect prostate cancer.

    Science.gov (United States)

    Morelli, Girolamo; Pagni, Riccardo; Mariani, Chiara; Minervini, Riccardo; Morelli, Andrea; Gori, Francesco; Ferdeghini, Ezio Maria; Paterni, Marco; Mauro, Eva; Guidi, Elisa; Armillotta, Nicola; Canale, Domenico; Vitti, Paolo; Caramella, Davide; Minervini, Andrea

    2011-06-01

    We evaluated the ability of the phosphodiesterase-5 inhibitor vardenafil to increase prostate microcirculation during power Doppler ultrasound. We also evaluated the results of contrast and vardenafil enhanced targeted biopsies compared to those of standard 12-core random biopsies to detect cancer. Between May 2008 and January 2010, 150 consecutive patients with prostate specific antigen more than 4 ng/ml at first diagnosis with negative digital rectal examination and transrectal ultrasound, and no clinical history of prostatitis underwent contrast enhanced power Doppler ultrasound (bolus injection of 2.4 ml SonoVue® contrast agent), followed by vardenafil enhanced power Doppler ultrasound (1 hour after oral administration of vardenafil 20 mg). All patients underwent standard 12-core transrectal ultrasound guided random prostate biopsy plus 1 further sampling from each suspected hypervascular lesion detected by contrast and vardenafil enhanced power Doppler ultrasound. Prostate cancer was detected in 44 patients (29.3%). Contrast and vardenafil enhanced power Doppler ultrasound detected suspicious, contrast enhanced and vardenafil enhanced areas in 112 (74.6%) and 110 patients (73.3%), and was diagnostic for cancer in 32 (28.5%) and 42 (38%), respectively. Analysis of standard technique, and contrast and vardenafil enhanced power Doppler ultrasound findings by biopsy core showed significantly higher detection using vardenafil vs contrast enhanced power Doppler ultrasound and standard technique (41.2% vs 22.7% and 8.1%, p power Doppler ultrasound was 10% and 11.7% (p not significant). Vardenafil enhanced power Doppler ultrasound enables excellent visualization of the microvasculature associated with cancer and can improve the detection rate compared to contrast enhanced power Doppler ultrasound and the random technique. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  8. Contrast-Enhanced Ultrasound Improves the Pathological Outcomes of US-Guided Core Needle Biopsy That Targets the Viable Area of Anterior Mediastinal Masses

    Directory of Open Access Journals (Sweden)

    Jian-hua Zhou

    2018-01-01

    Full Text Available Based on the option that ultrasound-guided core needle biopsy (US-CNB of the enhanced portion of anterior mediastinal masses (AMMs identified by contrast-enhanced ultrasound (CEUS would harvest viable tissue and benefit the histological diagnoses, a retrospective study was performed to elucidate the correlation between the prebiopsy CEUS and diagnostic yield of AMMs and found that CEUS potentially improved the diagnostic yield of AMMs compared with conventional US with a significant increase in the cellularity of samples. Furthermore, the marginal blood flow signals and absence of necrosis can predict the diagnostic yield of AMM. It was concluded that US-CNB of the viable part of AMMs, as verified by CEUS, was able to harvest sufficient tissue with more cellularity that could be used for ancillary studies and improve the diagnostic yield. And CEUS was recommended to those patients with AMMs undergoing repeated US-CNB, with the absence of marginal blood signals or presence of necrosis.

  9. Estimation of Tumor Angiogenesis With Contrast Enhanced Subharmonic Ultrasound Imaging

    National Research Council Canada - National Science Library

    Forsberg, Flemming

    2005-01-01

    ...) and receiving at the subharmonic (f0). Hence, the current project proposes to increase the ability of breast ultrasound to differentiate between benign and malignant lesions by combining injection of an ultrasound contrast agent with SHI...

  10. Estimation of Tumor Angiogenesis With Contrast Enhanced Subharmonic Ultrasound Imaging

    National Research Council Canada - National Science Library

    Forsberg, Flemming

    2002-01-01

    .... Hence, the current project proposes to increase the ability of breast ultrasound to differentiate between benign and malignant lesions by combining injection of an ultrasound contrast agent with SHI...

  11. Estimation of Tumor Angiogenesis with Contrast Enhanced Subharmonic Ultrasound Imaging

    National Research Council Canada - National Science Library

    Forsberg, Flemming

    2004-01-01

    .... Hence, the current project proposes to increase the ability of breast ultrasound to differentiate between benign and malignant lesions by combining injection of an ultrasound contrast agent with SHI...

  12. Value of contrast-enhanced ultrasound in rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Zordo, Tobias de; Mlekusch, Sabine P.; Feuchtner, Gudrun M. [Department of Radiology II, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck (Austria); Mur, Erich [Department of Internal Medicine, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck (Austria); Schirmer, Michael [Department of Internal Medicine, Hospital of the Elisabethines Klagenfurt, Voelkermarkter Strasse 15-19, 9020 Klagenfurt (Austria); Klauser, Andrea S. [Department of Radiology II, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck (Austria)], E-mail: andrea.klauser@i-med.ac.at

    2007-11-15

    The purpose of this review is to describe the spectrum of sonographic findings in rheumatic diseases with respect to the diagnostic potential using US contrast media which prove activity or inactivity in synovial tissue where new treatment regimes target. Synovial activity can be found in non-erosive and erosive forms of primary and secondary osteoarthritis, and in inflammatory forms of joint diseases like rheumatoid arthritis and peripheral manifestations of spondyloarthritis including, ankylosing spondylitis, Reiter's syndrome, psoriatic arthritis and enteropathic arthritis. It can also be present in metabolic and endocrine forms of arthritis, in connective tissue arthropathies like systemic lupus erythematosus or scleroderma and in infectious arthritis. Ultrasound should be used as first-line imaging modality in suspected early cases of RA and other forms of arthritis, whereas contrast-enhanced ultrasound (CEUS) can further enable for sensitive assessment of vascularity which correlates with disease activity.

  13. Value of contrast-enhanced ultrasound in rheumatoid arthritis

    International Nuclear Information System (INIS)

    Zordo, Tobias de; Mlekusch, Sabine P.; Feuchtner, Gudrun M.; Mur, Erich; Schirmer, Michael; Klauser, Andrea S.

    2007-01-01

    The purpose of this review is to describe the spectrum of sonographic findings in rheumatic diseases with respect to the diagnostic potential using US contrast media which prove activity or inactivity in synovial tissue where new treatment regimes target. Synovial activity can be found in non-erosive and erosive forms of primary and secondary osteoarthritis, and in inflammatory forms of joint diseases like rheumatoid arthritis and peripheral manifestations of spondyloarthritis including, ankylosing spondylitis, Reiter's syndrome, psoriatic arthritis and enteropathic arthritis. It can also be present in metabolic and endocrine forms of arthritis, in connective tissue arthropathies like systemic lupus erythematosus or scleroderma and in infectious arthritis. Ultrasound should be used as first-line imaging modality in suspected early cases of RA and other forms of arthritis, whereas contrast-enhanced ultrasound (CEUS) can further enable for sensitive assessment of vascularity which correlates with disease activity

  14. Musculoskeletal ultrasound in rheumatology in Korea: targeted ultrasound initiative survey.

    Science.gov (United States)

    Kang, Taeyoung; Wakefield, Richard J; Emery, Paul

    2016-04-01

    In collaboration with the Targeted Ultrasound Initiative (TUI), to conduct the first study in Korea to investigate current practices in ultrasound use among Korean rheumatologists. We translated the TUI Global Survey into Korean and added questions to better understand the specific challenges facing rheumatologists in Korea. To target as many rheumatologists in Korea as possible, we created an on-line version of this survey, which was conducted from March to April 2013. Rheumatologists are in charge of ultrasound in many Korean hospitals. Rheumatologists in hospitals and private clinics use ultrasound to examine between one and five patients daily; they use ultrasound for diagnosis more than monitoring and receive compensation of about US$30-50 per patient. There are marked differences in the rates of ultrasound usage between rheumatologists who work in private practice compared with tertiary hospitals. Korean rheumatologists not currently using ultrasound in their practice appear eager to do so. This survey provides important insights into the current status of ultrasound in rheumatology in Korea and highlights several priorities; specifically, greater provision of formal training, standardization of reporting and accrual of greater experience among ultrasound users. If these needs are addressed, all rheumatology departments in Korea are likely to use ultrasound or have access to it in the future. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  15. A contrast-enhanced ultrasound study of benign and malignant ...

    African Journals Online (AJOL)

    A contrast-enhanced ultrasound study of benign and malignant breast tissue. S Barnard, E Leen, T Cooke, W Angerson. Abstract. Objective. To determine the diagnostic value of haemodynamic contrast-enhanced ultrasound assessment in benign and malignant breast tissue, using histological examination as the reference ...

  16. Ultrasound-induced Gas Release from Contrast Agent Microbubbles

    NARCIS (Netherlands)

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

    2005-01-01

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

  17. Contrast enhanced ultrasound of splenic lymphoma involvement

    International Nuclear Information System (INIS)

    Goerg, Christian; Faoro, Charis; Bert, Tillmann; Tebbe, Johannes; Neesse, Albrecht; Wilhelm, Christian

    2011-01-01

    Objective: The aim of this study was to compare the value of contrast-enhanced ultrasonography (CEUS) with standard B-mode ultrasound (US) for diagnosis of splenic lymphoma involvement. Methods: From 04/2005 to 10/2008 n = 250 lymphoma patients were investigated by standard B-mode US. A homogeneous splenic echotexture was found in 199 patients (79%). To clarify the benefit of CEUS in this group a pilot series was performed with 16 of the 199 lymphoma patients. All patients with an abnormal splenic echotexture on standard B-Mode US (n = 51) including focal hypoechoic splenic lesions (n = 41) and an inhomogeneous splenic texture (n = 10) were studied by CEUS. CEUS data were retrospectively evaluated. The diagnoses included indolent lymphoma (n = 27), aggressive lymphoma (n = 14), and Hodgkin's disease (n = 10). Number and size of lesions were determined by B-mode US and CEUS. The visualisation of splenic lymphoma involvement by CEUS in comparison to B-mode US was classified as worse, equal, or better. Results: All patients with a homogeneous spleen on B-mode US (n = 16) had no visible focal lesions on CEUS. Study patients with focal lesions (n = 41) had a hypoechoic (n = 22) or isoechoic (n = 19) enhancement during the arterial phase, and a hypoechoic enhancement during the parenchymal phase (n = 41). The visualisation of focal splenic lymphoma was equal (n = 32), better (n = 6), or worse (n = 3). In all study patients with an inhomogeneous spleen on B-mode US (n = 10) no focal lesions were found by CEUS and the value of CEUS therefore was classified as worse. Conclusion: CEUS has no clear advantage for diagnosis of splenic lymphoma involvement.

  18. Contrast enhanced ultrasound of splenic lymphoma involvement

    Energy Technology Data Exchange (ETDEWEB)

    Goerg, Christian, E-mail: goergc@med.uni-marburg.de [Medizinische Universitaetsklinik, Baldingerstrasse, 35033 Marburg/Lahn (Germany); Faoro, Charis [Medizinische Universitaetsklinik, Baldingerstrasse, 35033 Marburg/Lahn (Germany); Bert, Tillmann [Zentralklinik Bad Berka GmbH, Robert-Koch-Allee 9, 99437 Bad Berka (Germany); Tebbe, Johannes [Klinikum Lippe-Detmold, Roentgenstrasse 18, 32756 Detmold (Germany); Neesse, Albrecht; Wilhelm, Christian [Medizinische Universitaetsklinik, Baldingerstrasse, 35033 Marburg/Lahn (Germany)

    2011-11-15

    Objective: The aim of this study was to compare the value of contrast-enhanced ultrasonography (CEUS) with standard B-mode ultrasound (US) for diagnosis of splenic lymphoma involvement. Methods: From 04/2005 to 10/2008 n = 250 lymphoma patients were investigated by standard B-mode US. A homogeneous splenic echotexture was found in 199 patients (79%). To clarify the benefit of CEUS in this group a pilot series was performed with 16 of the 199 lymphoma patients. All patients with an abnormal splenic echotexture on standard B-Mode US (n = 51) including focal hypoechoic splenic lesions (n = 41) and an inhomogeneous splenic texture (n = 10) were studied by CEUS. CEUS data were retrospectively evaluated. The diagnoses included indolent lymphoma (n = 27), aggressive lymphoma (n = 14), and Hodgkin's disease (n = 10). Number and size of lesions were determined by B-mode US and CEUS. The visualisation of splenic lymphoma involvement by CEUS in comparison to B-mode US was classified as worse, equal, or better. Results: All patients with a homogeneous spleen on B-mode US (n = 16) had no visible focal lesions on CEUS. Study patients with focal lesions (n = 41) had a hypoechoic (n = 22) or isoechoic (n = 19) enhancement during the arterial phase, and a hypoechoic enhancement during the parenchymal phase (n = 41). The visualisation of focal splenic lymphoma was equal (n = 32), better (n = 6), or worse (n = 3). In all study patients with an inhomogeneous spleen on B-mode US (n = 10) no focal lesions were found by CEUS and the value of CEUS therefore was classified as worse. Conclusion: CEUS has no clear advantage for diagnosis of splenic lymphoma involvement.

  19. [Relevance of contrast ultrasound with microbubbles in vascular medecine].

    Science.gov (United States)

    Erdmann, Andreas; Ney, Barbara; Alatri, Adriano; Calanca, Luca; Mazzolai, Lucia

    2016-12-07

    Application of ultrasound contrast media has become a standard in diagnostic imaging in cardiology and in the characterization of focal lesions in multiple organs, especially of the liver. In the past years there was a growing body of evidence for their usefulness in vascular medicine. The development of contrast media, microbubbles with a stabilizing envelope and filled with gaz, small enough to pass through pulmonary capillaries made real-time imaging of organ perfusion possible. Ultrasound contrast media are rapidly eliminated by exhalation and can safely be administered to patients with renal failure. The objective of this review is to describe the basic principles of ultrasound contrast imaging and to inform about vascular applications of contrast ultrasound.

  20. Acoustic bubble sorting for ultrasound contrast agent enrichment

    NARCIS (Netherlands)

    Segers, T.J.; Versluis, Michel

    2014-01-01

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

    KAUST Repository

    Qamar, Adnan; Samtaney, Ravi

    2014-01-01

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

  3. Contrast-enhanced ultrasound of the kidneys

    NARCIS (Netherlands)

    Beemster, P.; Pes, P.L.; Wijkstra, H.

    2009-01-01

    Several imaging techniques can be used for visualization of the kidneys dependent on the indication. Ultrasound (US), computerized tomography (CT), and magnetic resonance imaging (MRI) are most commonly used. US is a safe, relatively inexpensive, noninvasive, and widely available imaging method. It

  4. Collapse dynamics of ultrasound contrast agent microbubbles

    Science.gov (United States)

    King, Daniel Alan

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

  5. Reproducibility of contrast-enhanced transrectal ultrasound of the prostate

    NARCIS (Netherlands)

    Sedelaar, J. P.; Goossen, T. E.; Wijkstra, H.; de la Rosette, J. J.

    2001-01-01

    Transrectal three-dimensional (3-D) contrast-enhanced power Doppler ultrasound (US) is a novel technique for studying possible prostate malignancy. Before studies can be performed to investigate the clinical validity of the technique, reproducibility of the contrast US studies must be proven.

  6. Acoustic bubble sorting for ultrasound contrast agent enrichment.

    Science.gov (United States)

    Segers, Tim; Versluis, Michel

    2014-05-21

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

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

    Directory of Open Access Journals (Sweden)

    Donghee Park

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Vera ePaefgen

    2015-09-01

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

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

    OpenAIRE

    Ai-Ho Liao

    2016-01-01

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

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

    Science.gov (United States)

    Versluis, Michel; Kok, Maarten; Segers, Tim

    2014-11-01

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

  12. Cumulative phase delay imaging for contrast-enhanced ultrasound tomography

    International Nuclear Information System (INIS)

    Demi, Libertario; Van Sloun, Ruud J G; Wijkstra, Hessel; Mischi, Massimo

    2015-01-01

    Standard dynamic-contrast enhanced ultrasound (DCE-US) imaging detects and estimates ultrasound-contrast-agent (UCA) concentration based on the amplitude of the nonlinear (harmonic) components generated during ultrasound (US) propagation through UCAs. However, harmonic components generation is not specific to UCAs, as it also occurs for US propagating through tissue. Moreover, nonlinear artifacts affect standard DCE-US imaging, causing contrast to tissue ratio reduction, and resulting in possible misclassification of tissue and misinterpretation of UCA concentration. Furthermore, no contrast-specific modality exists for DCE-US tomography; in particular speed-of-sound changes due to UCAs are well within those caused by different tissue types. Recently, a new marker for UCAs has been introduced. A cumulative phase delay (CPD) between the second harmonic and fundamental component is in fact observable for US propagating through UCAs, and is absent in tissue. In this paper, tomographic US images based on CPD are for the first time presented and compared to speed-of-sound US tomography. Results show the applicability of this marker for contrast specific US imaging, with cumulative phase delay imaging (CPDI) showing superior capabilities in detecting and localizing UCA, as compared to speed-of-sound US tomography. Cavities (filled with UCA) which were down to 1 mm in diameter were clearly detectable. Moreover, CPDI is free of the above mentioned nonlinear artifacts. These results open important possibilities to DCE-US tomography, with potential applications to breast imaging for cancer localization. (fast track communication)

  13. Ultrasound contrast-agent improves imaging of lower limb occlusive disease

    DEFF Research Database (Denmark)

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

    2003-01-01

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

  14. Superparamagnetic nanoparticle-inclusion microbubbles for ultrasound contrast agents

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  15. Advanced ultrasound applications in the assessment of renal transplants: contrast-enhanced ultrasound, elastography, and B-flow.

    Science.gov (United States)

    Morgan, Tara A; Jha, Priyanka; Poder, Liina; Weinstein, Stefanie

    2018-04-09

    Ultrasound is routinely used as the first imaging exam for evaluation of renal transplants and can identify most major surgical complications and evaluate vascularity with color Doppler. Ultrasound is limited, however, in the detection of parenchymal disease processes and Doppler evaluation is also prone to technical errors. Multiple new ultrasound applications have been developed and are under ongoing investigation which could add additional diagnostic capability to the routine ultrasound exam with minimal additional time, cost, and patient risk. Contrast-enhanced ultrasound (CEUS) can be used off-label in the transplant kidney, and can assist in detection of infection, trauma, and vascular complications. CEUS also can demonstrate perfusion of the transplant assessed quantitatively with generation of time-intensity curves. Future directions of CEUS include monitoring treatment response and microbubble targeted medication delivery. Elastography is an ultrasound application that can detect changes in tissue elasticity, which is useful to diagnose diffuse parenchymal disease, such as fibrosis, otherwise unrecognizable with ultrasound. Elastography has been successfully applied in other organs including the liver, thyroid, and breast; however, it is still under development for use in the transplant kidney. Unique properties of the transplant kidney including its heterogeneity, anatomic location, and other technical factors present challenges in the development of reference standard measurements. Lastly, B-flow imaging is a flow application derived from B-mode. This application can show the true lumen size of a vessel which is useful to depict vascular anatomy and bypasses some of the pitfalls of color Doppler such as demonstration of slow flow.

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  17. Contrast enhanced ultrasound in the assessment of urogenital pathology

    Directory of Open Access Journals (Sweden)

    Libero Barozzi

    2014-12-01

    Full Text Available Contrast enhanced ultrasound (CEUS is an innovative technique that employs microbubble contrast agents to demonstrate parenchymal perfusion. Although initial clinical application was focused on the liver pathology, a wide variety of clinical conditions can be assessed now with CEUS. CEUS is a well-tolerated technique and is acquiring an increasing role in the assessment of renal pathology because contrast agents are not excreted by the kidney and do not affect the renal function. CEUS demonstrated an accuracy similar to contrast enhanced multi-detector computed tomography (CEMDCT in detecting focal lesions, with the advantage of the real-time assessment of microvascular perfusion by using time-intensity curves. The aim of this paper is to review the main indications of CEUS in the assessment of renal and urogenital pathology. Imaging examples are presented and described. Advantages and limitations of CEUS with reference to conventional US and CE-MDCT are discussed.

  18. Safety of ultrasound contrast agents in stress echocardiography.

    Science.gov (United States)

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

    2008-11-01

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

  19. Cavitation and contrast: the use of bubbles in ultrasound imaging and therapy.

    Science.gov (United States)

    Stride, E P; Coussios, C C

    2010-01-01

    Microbubbles and cavitation are playing an increasingly significant role in both diagnostic and therapeutic applications of ultrasound. Microbubble ultrasound contrast agents have been in clinical use now for more than two decades, stimulating the development of a range of new contrast-specific imaging techniques which offer substantial benefits in echocardiography, microcirculatory imaging, and more recently, quantitative and molecular imaging. In drug delivery and gene therapy, microbubbles are being investigated/developed as vehicles which can be loaded with the required therapeutic agent, traced to the target site using diagnostic ultrasound, and then destroyed with ultrasound of higher intensity energy burst to release the material locally, thus avoiding side effects associated with systemic administration, e.g. of toxic chemotherapy. It has moreover been shown that the motion of the microbubbles increases the permeability of both individual cell membranes and the endothelium, thus enhancing therapeutic uptake, and can locally increase the activity of drugs by enhancing their transport across biologically inaccessible interfaces such as blood clots or solid tumours. In high-intensity focused ultrasound (HIFU) surgery and lithotripsy, controlled cavitation is being investigated as a means of increasing the speed and efficacy of the treatment. The aim of this paper is both to describe the key features of the physical behaviour of acoustically driven bubbles which underlie their effectiveness in biomedical applications and to review the current state of the art.

  20. Contrast-enhanced ultrasound for extrahepatic lesions: preliminary experience

    Energy Technology Data Exchange (ETDEWEB)

    Thorelius, Lars E-mail: lars@thorelius.com

    2004-06-01

    Ultrasound imaging (US) is a convenient, inexpensive and non-invasive investigation. Its use is limited by low sensitivity in the detection of a number of parenchymal lesions, especially those produced by trauma, such as infarctions. Contrast enhancement with SonoVue{sup [reg]} improves the sensitivity of ultrasound in the detection and characterization of focal liver lesions to such an extent, that it may replace computed tomography (CT) and magnetic resonance imaging (MRI). Preliminary experience suggests that SonoVue-enhanced sonography may be useful in the detection of lesions in which blood flow is severely reduced as compared to surrounding parenchyma, such as infarctions, lacerations, hematomas, necrotic tissue and non-vascular cysts, especially in the spleen, kidney and pancreas. This technique can also rule out occlusion of the superior mesenteric, splenic and portal veins, and dilation of the biliary tree. Clinical trials comparing contrast-enhanced sonography with contrast-enhanced computed tomography are warranted to establish the role of this inexpensive and non-invasive technique in the routine work-up of patients with abdominal trauma or presenting with sudden flank pain.

  1. Second harmonic inversion for ultrasound contrast harmonic imaging

    Energy Technology Data Exchange (ETDEWEB)

    Pasovic, Mirza; Danilouchkine, Mike; Faez, Telli; Van Neer, Paul L M J; Van der Steen, Antonius F W; De Jong, Nico [THORAXCENTER, Department of Biomedical Engineering Ee2302, Erasmus MC, Rotterdam (Netherlands); Cachard, Christian; Basset, Olivier, E-mail: mirza.pasovic@creatis.insa-lyon.fr [CREATIS-LRMN, Universite de Lyon, INSA-Lyon, Universite Lyon 1, Inserm U630, CNRS UMR 5220 (France)

    2011-06-07

    Ultrasound contrast agents (UCAs) are small micro-bubbles that behave nonlinearly when exposed to an ultrasound wave. This nonlinear behavior can be observed through the generated higher harmonics in a back-scattered echo. In past years several techniques have been proposed to detect or image harmonics produced by UCAs. In these proposed works, the harmonics generated in the medium during the propagation of the ultrasound wave played an important role, since these harmonics compete with the harmonics generated by the micro-bubbles. We present a method for the reduction of the second harmonic generated during nonlinear-propagation-dubbed second harmonic inversion (SHI). A general expression for the suppression signals is also derived. The SHI technique uses two pulses, p' and p'', of the same frequency f{sub 0} and the same amplitude P{sub 0} to cancel out the second harmonic generated by nonlinearities of the medium. Simulations show that the second harmonic is reduced by 40 dB on a large axial range. Experimental SHI B-mode images, from a tissue-mimicking phantom and UCAs, show an improvement in the agent-to-tissue ratio (ATR) of 20 dB compared to standard second harmonic imaging and 13 dB of improvement in harmonic power Doppler.

  2. Second harmonic inversion for ultrasound contrast harmonic imaging

    International Nuclear Information System (INIS)

    Pasovic, Mirza; Danilouchkine, Mike; Faez, Telli; Van Neer, Paul L M J; Van der Steen, Antonius F W; De Jong, Nico; Cachard, Christian; Basset, Olivier

    2011-01-01

    Ultrasound contrast agents (UCAs) are small micro-bubbles that behave nonlinearly when exposed to an ultrasound wave. This nonlinear behavior can be observed through the generated higher harmonics in a back-scattered echo. In past years several techniques have been proposed to detect or image harmonics produced by UCAs. In these proposed works, the harmonics generated in the medium during the propagation of the ultrasound wave played an important role, since these harmonics compete with the harmonics generated by the micro-bubbles. We present a method for the reduction of the second harmonic generated during nonlinear-propagation-dubbed second harmonic inversion (SHI). A general expression for the suppression signals is also derived. The SHI technique uses two pulses, p' and p'', of the same frequency f 0 and the same amplitude P 0 to cancel out the second harmonic generated by nonlinearities of the medium. Simulations show that the second harmonic is reduced by 40 dB on a large axial range. Experimental SHI B-mode images, from a tissue-mimicking phantom and UCAs, show an improvement in the agent-to-tissue ratio (ATR) of 20 dB compared to standard second harmonic imaging and 13 dB of improvement in harmonic power Doppler.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-05-15

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

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

    KAUST Repository

    Qamar, Adnan

    2014-02-01

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

  5. Contrast-enhanced ultrasound for diagnosis of prostate cancer and kidney lesions

    International Nuclear Information System (INIS)

    Mitterberger, Michael; Pelzer, Alexandre; Colleselli, Daniela; Bartsch, Georg; Strasser, Hannes; Pallwein, Leo; Aigner, Friedrich; Gradl, Johann; Frauscher, Ferdinand

    2007-01-01

    Purpose of review: Conventional ultrasonography of both, kidney and prostate, is limited due to the poor contrast of B-mode imaging for parenchymal disease and limited sensitivity of colour Doppler for the detection of capillaries and deep pedicular vessels. Contrast-enhanced ultrasound (CEUS) overcomes these limitations. Recent findings: CEUS investigates the blood flow of the prostate, allows for prostate cancer visualization and for targeted biopsies. Comparisons between systematic and CEUS-targeted biopsies have shown that the targeted approach detects more cancers with a lower number of biopsy cores and with higher Gleason scores compared with the systematic approach. Also the kidney offers promising applications as CEUS improves the detection of abnormal microvascular and macrovascular disorders. Summary: In recent literature CEUS has shown its value for diagnosis of both, prostate cancer and kidney lesions. This paper describes recent improvements and future perspectives of CEUS

  6. Microwave ablation of liver metastases guided by contrast-enhanced ultrasound

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Science.gov (United States)

    Wang, Yu-Hsin; Liao, Ai-Ho; Chen, Jui-Hao; Wang, Churng-Ren Chris; Li, Pai-Chi

    2012-04-01

    This study investigates a photoacoustic/ultrasound dual-modality contrast agent, including extending its applications from image-contrast enhancement to combined diagnosis and therapy with site-specific targeting. The contrast agent comprises albumin-shelled microbubbles with encapsulated gold nanorods (AuMBs). The gas-filled microbubbles, whose diameters range from submicrometer to several micrometers, are not only echogenic but also can serve as drug-delivery vehicles. The gold nanorods are used to enhance the generation of both photoacoustic and photothermal signals. The optical absorption peak of the gold nanorods is tuned to 760 nm and is invariant after microbubble encapsulation. Dual-modality contrast enhancement is first described here, and the applications to cellular targeting and laser-induced thermotherapy in a phantom are demonstrated. Photoacoustic imaging can be used to monitor temperature increases during the treatment. The targeting capability of AuMBs was verified, and the temperature increased by 26°C for a laser power of 980 mW, demonstrating the potential of combined diagnosis and therapy with the dual-modality agent. Targeted photo- or acoustic-mediated delivery is also possible.

  8. Contrast-enhanced versus systematic transrectal ultrasound-guided prostate cancer detection: An overview of techniques and a systematic review

    International Nuclear Information System (INIS)

    Heijmink, Stijn W.T.P.J.; Barentsz, Jelle O.

    2007-01-01

    An overview is given of the current conventional and contrast-specific transrectal ultrasound (TRUS) techniques for prostate imaging that may be used for guiding biopsy. Subsequently, a systematic literature search resulted in inclusion of four studies that directly compared systematic and contrast-enhanced-targeted TRUS-guided biopsy of the prostate. All four studies revealed that contrast-enhanced-targeted TRUS-guided biopsy significantly improved the positive biopsy core rate. In the largest study, the mean Gleason score of the contrast-enhanced-targeted TRUS-guided biopsies was significantly higher than that of the systematic biopsies. Future randomized clinical trials, preferably in a non-academic multi-institutional set-up, will have to be performed to confirm the value of contrast-enhanced-targeted TRUS-guided biopsy in regular clinical practice

  9. Intraoperative Cerebral Glioma Characterization with Contrast Enhanced Ultrasound

    Directory of Open Access Journals (Sweden)

    Francesco Prada

    2014-01-01

    Full Text Available Background. Contrast enhanced ultrasound (CEUS is a dynamic and continuous modality providing real-time view of vascularization and flow distribution patterns of different organs and tumors. Nevertheless its intraoperative use for brain tumors visualization has been performed few times, and a thorough characterization of cerebral glioma had never been performed before. Aim. To perform the first characterization of cerebral glioma using CEUS and to possibly achieve an intraoperative differentiation of different gliomas. Methods. We performed CEUS in an off-label setting in 69 patients undergoing surgery for cerebral glioma. An intraoperative qualitative analysis was performed comparing iCEUS with B-mode imaging. A postprocedural semiquantitative analysis was then performed for each case, according to EFSUMB criteria. Results were related to histopathology. Results. We observed different CE patterns: LGG show a mild, dotted CE with diffuse appearance and slower, delayed arterial and venous phase. HGG have a high CE with a more nodular, nonhomogeneous appearance and fast perfusion patterns. Conclusion. Our study characterizes for the first time human brain glioma with CEUS, providing further insight regarding these tumors’ biology. CEUS is a fast, safe, dynamic, real-time, and economic tool that might be helpful during surgery in differentiating malignant and benign gliomas and refining surgical strategy.

  10. Jetting of a ultrasound contrast microbubble near a rigid wall

    Science.gov (United States)

    Sarkar, Kausik; Mobadersany, Nima

    2017-11-01

    Micron sized gas-bubbles coated with a stabilizing shell of lipids or proteins, are used as contrast enhancing agents for ultrasound imaging. However, they are increasingly being explored for novel applications in drug delivery through a process called sonoporation, the reversible permeabilization of the cell membrane. Under sufficiently strong acoustic excitations, bubbles form a jet and collapse near a wall. The jetting of free bubbles has been extensively studied by boundary element method (BEM). Here, for the first time, we implemented a rigorous interfacial rheological model of the shell into BEM and investigated the jet formation. The code has been carefully validated against past results. Increasing shell elasticity decreases the maximum bubble volume and the collapse time, while the jet velocity increases. The shear stress on the wall is computed and analyzed. A phase diagram as functions of excitation pressure and wall separation describes jet formation. Effects of shell elasticity and frequency on the phase diagram are investigated. Partially supported by National Science Foundation.

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

    Science.gov (United States)

    Bader, Kenneth B; Holland, Christy K

    2013-01-07

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

  12. Usefulness of contrast-enhanced transabdominal ultrasound for tumor classification and tumor staging in the pancreatic head

    DEFF Research Database (Denmark)

    Grossjohann, Hanne Sønder; Rappeport, Eli David; Jensen, Claus Verner

    2010-01-01

    To evaluate contrast-enhanced ultrasound (CEUS) and compare it to ultrasound (US) and 64-slice-CT (64-CT) for diagnosing, staging and evaluation of resectability of pancreatic cancer.......To evaluate contrast-enhanced ultrasound (CEUS) and compare it to ultrasound (US) and 64-slice-CT (64-CT) for diagnosing, staging and evaluation of resectability of pancreatic cancer....

  13. Enhancement pattern of hilar cholangiocarcinoma: Contrast-enhanced ultrasound versus contrast-enhanced computed tomography

    International Nuclear Information System (INIS)

    Xu Huixiong; Chen Lida; Xie Xiaoyan; Xie Xiaohua; Xu Zuofeng; Liu Guangjian; Lin Manxia; Wang Zhu; Lu Mingde

    2010-01-01

    Objective: To compare the enhancement pattern of hilar cholangiocarcinoma on contrast-enhanced ultrasound (CEUS) with that on contrast-enhanced computed tomography (CECT). Methods: Thirty-two consecutive patients with pathologically proven hilar cholangiocarcinomas were evaluated by both low mechanical index CEUS and CECT. The enhancement feature of the tumor, portal vein infiltration, and lesion conspicuity on them was investigated. Results: In the arterial phase, the numbers of the lesions showing hyperenhancement, isoenhancement, and hypoenhancement, were 14 (43.8%), 14 (43.8%), and 4 (12.6%), on CEUS, and 12 (37.5%), 9 (28.1%), and 11 (34.4%), on CECT (P = 0.162). In portal phase, the numbers of the lesions showing hypoenhancement, isoenhancement, and hyperenhancement were 30 (93.8%), 1 (3.1%), and 1 (3.1%), on CEUS, and 23 (71.9%), 8 (25.0%), and 1 (3.1%), on CECT (P = 0.046). The detection rates for portal vein infiltration were 84.2% (16/19) for baseline ultrasound, 89.5% (17/19) for CEUS, and 78.9% (15/19) for CECT (all P > 0.05 between every two groups). CEUS significantly improved the lesion conspicuity in comparison with CECT. CEUS and CECT made correct diagnoses in 30 (93.8%) and 25 (78.1%) lesions prior to pathological examination (P = 0.125). Conclusion: The enhancement pattern of hilar cholangiocarcinoma on CEUS was similar with that on CECT in arterial phase, whereas in portal phase hilar cholangiocarcinoma shows hypoenhancement more likely on CEUS. CEUS and CECT lead to similar results in evaluating portal vein infiltration and diagnosis of this entity.

  14. Enhancement pattern of hilar cholangiocarcinoma: Contrast-enhanced ultrasound versus contrast-enhanced computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Xu Huixiong, E-mail: xuhuixiong@hotmail.co [Department of Medical Ultrasonics, The First Affiliated Hospital, Institute of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou 510080 (China); Chen Lida; Xie Xiaoyan; Xie Xiaohua; Xu Zuofeng; Liu Guangjian; Lin Manxia; Wang Zhu [Department of Medical Ultrasonics, The First Affiliated Hospital, Institute of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou 510080 (China); Lu Mingde, E-mail: lumd@21cn.co [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou 510080 (China)

    2010-08-15

    Objective: To compare the enhancement pattern of hilar cholangiocarcinoma on contrast-enhanced ultrasound (CEUS) with that on contrast-enhanced computed tomography (CECT). Methods: Thirty-two consecutive patients with pathologically proven hilar cholangiocarcinomas were evaluated by both low mechanical index CEUS and CECT. The enhancement feature of the tumor, portal vein infiltration, and lesion conspicuity on them was investigated. Results: In the arterial phase, the numbers of the lesions showing hyperenhancement, isoenhancement, and hypoenhancement, were 14 (43.8%), 14 (43.8%), and 4 (12.6%), on CEUS, and 12 (37.5%), 9 (28.1%), and 11 (34.4%), on CECT (P = 0.162). In portal phase, the numbers of the lesions showing hypoenhancement, isoenhancement, and hyperenhancement were 30 (93.8%), 1 (3.1%), and 1 (3.1%), on CEUS, and 23 (71.9%), 8 (25.0%), and 1 (3.1%), on CECT (P = 0.046). The detection rates for portal vein infiltration were 84.2% (16/19) for baseline ultrasound, 89.5% (17/19) for CEUS, and 78.9% (15/19) for CECT (all P > 0.05 between every two groups). CEUS significantly improved the lesion conspicuity in comparison with CECT. CEUS and CECT made correct diagnoses in 30 (93.8%) and 25 (78.1%) lesions prior to pathological examination (P = 0.125). Conclusion: The enhancement pattern of hilar cholangiocarcinoma on CEUS was similar with that on CECT in arterial phase, whereas in portal phase hilar cholangiocarcinoma shows hypoenhancement more likely on CEUS. CEUS and CECT lead to similar results in evaluating portal vein infiltration and diagnosis of this entity.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-10-15

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

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2008-11-01

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

  18. Radiofrequency ablation guided by contrast-enhanced ultrasound for hepatic malignancies: Preliminary results

    International Nuclear Information System (INIS)

    Dong, Y.; Wang, W.-P.; Gan, Y.-H.; Huang, B.-J.; Ding, H.

    2014-01-01

    Aim: To evaluate whether contrast-enhanced ultrasound (CEUS)-guided radiofrequency ablation (RFA) can be performed effectively in small hepatic malignancies that are invisible or poorly visualized at traditional grey-scale ultrasonography (US). Materials and methods: The institutional ethics committee approved the study, and all patients provided written informed consent before their enrolment. The study focused on 55 patients (43 men, 12 women, age 57.4 ± 10.9 years) with 60 hepatic lesions from May 2010 to March 2011. All lesions were treated with multipolar radiofrequency ablation (RFA). During the RFA procedure, with the injection of ultrasound contrast agent (sulphur hexafluoride; SonoVue, Bracco Imaging Spa, Milan, Italy), RFA was conducted under CEUS guidance when the optimal depiction of a lesion was obtained. Artificial pleural effusions were used in those cases obstructed by the lungs. Twenty-four hours after RFA, contrast-enhanced MRI was used as the reference standard to evaluate the primary effectiveness rate and complete tumour necrosis. The follow-up time was 12–24 months (median 15 months). Results: Among 60 hepatic malignancies, CEUS detected 57 lesions (95%), which was higher than that at US (26.6%). Artificial pleural effusions were performed in three cases, resulting in the detection of three additional lesions. The insertion of RFA electrodes was monitored by CEUS in all lesions. Immediately after RFA, complete tumour necrosis were achieved in all 60 lesions as apparent at MRI, for a primary effectiveness rate of 100%. Conclusion: CEUS-guided RFA is a promising technique for targeting and improving the efficiency of treatment of hepatic malignancies. - Highlights: • CEUS guided RFA improved the detectability of hepatic malignancies indistinctive on gray-scale ultrasound. • Pre-operation CEUS helped localization of indistinctive hepatic malignancies. • CEUS guided RFA of hepatic malignancies achieved a more complete ablation

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  20. Contrast-enhanced ultrasound-guided radiofrequency ablation in inconspicuous hepatocellular carcinoma on B-mode ultrasound.

    Science.gov (United States)

    Kim, Eui Joo; Kim, Yun Soo; Shin, Seung Kak; Kwon, Oh Sang; Choi, Duck Joo; Kim, Ju Hyun

    2017-11-01

    B-mode ultrasound (US) has difficulty targeting small hepatocellular carcinomas (HCCs) with poor conspicuity during radiofrequency ablation (RFA). Contrast-enhanced ultrasound (CEUS) can improve visualization of small or inconspicuous HCCs. This study was conducted to evaluate the effectiveness of CEUS-guided RFA electrode insertion during the arterial phase in inconspicuous HCCs. Ninety-three treatment-naïve HCCs from 80 patients treated with RFA from August 2012 to December 2014 were retrospectively reviewed. Seventy-five HCCs from 65 patients underwent B-mode US-guided RFA, and 15 HCCs from 14 patients that were inconspicuous on B-mode US underwent CEUS-guided RFA during the arterial phase after injection of sulfur hexafluoride microbubbles (SonoVue®). Technical success was assessed by contrast-enhanced computed tomography within 1 week and 3 months after the procedure. The mean size of HCCs treated with CEUS-guided RFA was smaller than that of HCCs treated with B-mode US-guided RFA (1.17±0.36 vs. 1.63±0.55 cm, p=0.003). Technical success rates of CEUS-guided RFA within 1 week and 3 months were 100% (15/15) and 93.3% (14/15), respectively. Technical success rates of B-mode US-guided RFA were 97.3% (73/75) and 94.5% (69/73), respectively. CEUS-guided RFA is highly efficacious for ablation of very small and inconspicuous HCCs.

  1. Real-time 3-dimensional contrast-enhanced ultrasound in detecting hemorrhage of blunt renal trauma.

    Science.gov (United States)

    Xu, Rui-Xue; Li, Ye-Kuo; Li, Ting; Wang, Sha-Sha; Yuan, Gui-Zhong; Zhou, Qun-Fang; Zheng, Hai-Rong; Yan, Fei

    2013-10-01

    The objective of this study is to evaluate the diagnostic value of real-time 3-dimensional contrast-enhanced ultrasound in the hemorrhage of blunt renal trauma. Eighteen healthy New Zealand white rabbits were randomly divided into 3 groups. Blunt renal trauma was performed on each group by using minitype striker. Ultrasonography, color Doppler flow imaging, and contrast-enhanced 2-dimensional and real-time 3-dimensional ultrasound were applied before and after the strike. The time to shock and blood pressure were subjected to statistical analysis. Then, a comparative study of ultrasound and pathology was carried out. All the struck kidneys were traumatic. In the ultrasonography, free fluid was found under the renal capsule. In the color Doppler flow imaging, active hemorrhage was not identified. In 2-dimensional contrast-enhanced ultrasound, active hemorrhage of the damaged kidney was characterized. Real-time 3-dimensional contrast-enhanced ultrasound showed a real-time and stereoscopic ongoing bleeding of the injured kidney. The wider the hemorrhage area in 4-dimensional contrast-enhanced ultrasound was, the faster the blood pressure decreased. Real-time 3-dimensional contrast-enhanced ultrasound is a promising noninvasive tool for stereoscopically and vividly detecting ongoing hemorrhage of blunt renal trauma in real time. © 2013.

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  3. Contrast-enhanced harmonic ultrasound imaging in ablation therapy for primary hepatocellular carcinoma.

    Science.gov (United States)

    Minami, Yasunori; Kudo, Masatoshi

    2009-12-31

    The success rate of percutaneous radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) depends on correct targeting via an imaging technique. However, RF electrode insertion is not completely accurate for residual HCC nodules because B-mode ultrasound (US), color Doppler, and power Doppler US findings cannot adequately differentiate between treated and viable residual tumor tissue. Electrode insertion is also difficult when we must identify the true HCC nodule among many large regenerated nodules in cirrhotic liver. Two breakthroughs in the field of US technology, harmonic imaging and the development of second-generation contrast agents, have recently been described and have demonstrated the potential to dramatically broaden the scope of US diagnosis of hepatic lesions. Contrast-enhanced harmonic US imaging with an intravenous contrast agent can evaluate small hypervascular HCC even when B-mode US cannot adequately characterize tumor. Therefore, contrast-enhanced harmonic US can facilitate RF ablation electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of contrast-enhanced harmonic US in ablation therapy for liver cancer is an efficient approach.

  4. Acoustic microstreaming due to an ultrasound contrast microbubble near a wall

    Science.gov (United States)

    Mobadersany, Nima; Sarkar, Kausik

    2017-11-01

    In an ultrasound field, in addition to the sinusoidal motion of fluid particles, particles experience a steady streaming velocity due to nonlinear second order effects. Here, we have simulated the microstreaming flow near a plane rigid wall caused by the pulsations of contrast microbubbles. Although these microbubbles were initially developed as a contrast enhancing agents for ultrasound imaging, they generate additional therapeutic effects that can be harnessed for targeted drug delivery or blood brain barrier (BBB) opening. The microbubbles have a gas core coated with a stabilizing layer of lipids or proteins. We use analytical models as well as boundary element (BEM) simulation to simulate the flow around these bubbles implementing interfacial rheology models for the coating. The microstreaming flow is characterized by two wall bounded vortices. The size of the vortices decreases with the decrease of the separation from the wall. The vortex-induced shear stress is simulated and analyzed as a function of excitation parameters and geometry. These microstreaming shear stress plays a critical role in increasing the membrane permeability facilitating drug delivery or rupturing biological tissues.

  5. THE EXPERIENCE OF USING ULTRASOUND WITH CONTRAST ENHANCEMENT IN THE DIAGNOSIS OF CERVICAL CANCER

    Directory of Open Access Journals (Sweden)

    M. A. Chekalova

    2017-01-01

    Full Text Available The purpose of the study was to evaluate the value of contrast-enhanced ultrasound in detecting local spread, regional and distant metastases from cervical cancer. Materials and methods. The findings of contrast-enhanced ultrasound examination of 4 cervical cancer patients (IB1–IVB treated at N.N. Blokhin Russian Cancer Research Center from September to October 2016 were evaluated. The HI VISION Ascendus device was used. Ultrasound patterns in different phases of contrast-enhanced accumulation and excretion were analyzed. Results. Our first experience in using contrast-enhanced ultrasound in the detection of local spread, regional and distant metastases from cervical cancer allowed us to study the structure of the tumor and its spread in greater detail. Conclusion. A small number of observations do not yet allow us to draw serious conclusions about the capabilities of this modern technology. 

  6. The role of contrast-enhanced ultrasound in risk assessment of carotid atheroma

    Directory of Open Access Journals (Sweden)

    Silviu Stanciu

    2016-07-01

    Full Text Available Background and objective: Contrast-enhanced ultrasound, used to assess atherosclerotic carotid plaques, improves visualization of vessel wall irregularities and depicts intraplaque neovascularization. This article illustrates the use of contrast-enhanced ultrasound in the risk assessment of carotid atherosclerotic lesions, especially in challenging plaques evaluation. Materials and methods: For 23 patients with difficult duplex ultrasound examination due to carotid tortuosity or calcifications we assessed plaque morphology (contour, echogenicity and stenosis degree using contrast substance (Sonovue, Braco with dedicated vascular low mechanical index CPC software. Conclusion: Contrast-enhanced ultrasound is a new, noninvasive, and safe procedure for imaging carotid atherosclerotic lesions. It is a valuable tool for evaluating the vulnerable plaque at risk for rupture and for the diagnostic of the development and severity of systemic atherosclerotic disease

  7. Volume navigation with contrast enhanced ultrasound and image fusion for percutaneous interventions: first results.

    Directory of Open Access Journals (Sweden)

    Ernst Michael Jung

    Full Text Available OBJECTIVE: Assessing the feasibility and efficiency of interventions using ultrasound (US volume navigation (V Nav with real time needle tracking and image fusion with contrast enhanced (ce CT, MRI or US. METHODS: First an in vitro study on a liver phantom with CT data image fusion was performed, involving the puncture of a 10 mm lesion in a depth of 5 cm performed by 15 examiners with US guided freehand technique vs. V Nav for the purpose of time optimization. Then 23 patients underwent ultrasound-navigated biopsies or interventions using V Nav image fusion of live ultrasound with ceCT, ceMRI or CEUS, which were acquired before the intervention. A CEUS data set was acquired in all patients. Image fusion was established for CEUS and CT or CEUS and MRI using anatomical landmarks in the area of the targeted lesion. The definition of a virtual biopsy line with navigational axes targeting the lesion was achieved by the usage of sterile trocar with a magnetic sensor embedded in its distal tip employing a dedicated navigation software for real time needle tracking. RESULTS: The in vitro study showed significantly less time needed for the simulated interventions in all examiners when V Nav was used (p<0.05. In the study involving patients, in all 10 biopsies of suspect lesions of the liver a histological confirmation was achieved. We also used V Nav for a breast biopsy (intraductal carcinoma, for a biopsy of the abdominal wall (metastasis of ovarial carcinoma and for radiofrequency ablations (4 ablations. In 8 cases of inflammatory abdominal lesions 9 percutaneous drainages were successfully inserted. CONCLUSION: Percutaneous biopsies and drainages, even of small lesions involving complex access pathways, can be accomplished with a high success rate by using 3D real time image fusion together with real time needle tracking.

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

    Science.gov (United States)

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

    2005-10-01

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

  9. Feasibility of contrast-enhanced ultrasound-guided biopsy of sentinel lymph nodes in dogs.

    Science.gov (United States)

    Gelb, Hylton R; Freeman, Lynetta J; Rohleder, Jacob J; Snyder, Paul W

    2010-01-01

    Our goal was to develop and validate a technique to identify the sentinel lymph nodes of the mammary glands of healthy dogs with contrast-enhanced ultrasound, and evaluate the feasibility of obtaining representative samples of a sentinel lymph node under ultrasound guidance using a new biopsy device. Three healthy intact female adult hounds were anesthetized and each received an injection of octafluoropropane-filled lipid microspheres and a separate subcutaneous injection of methylene blue dye around a mammary gland. Ultrasound was then used to follow the contrast agent through the lymphatic channel to the sentinel lymph node. Lymph node biopsy was performed under ultrasound guidance, followed by an excisional biopsy of the lymph nodes and a regional mastectomy procedure. Excised tissues were submitted for histopathologic examination and evaluated as to whether they were representative of the node. The ultrasound contrast agent was easily visualized with ultrasound leading up to the sentinel lymph nodes. Eight normal lymph nodes (two inguinal, one axillary in two dogs; two inguinal in one dog) were identified and biopsied. Lymphoid tissue was obtained from all biopsy specimens. Samples from four of eight lymph nodes contained both cortical and medullary lymphoid tissue. Contrast-enhanced ultrasound can be successfully used to image and guide minimally invasive biopsy of the normal sentinel lymph nodes draining the mammary glands in healthy dogs. Further work is needed to evaluate whether this technique may be applicable in patients with breast cancer or other conditions warranting evaluation of sentinel lymph nodes in animals.

  10. Novel fluorescence nanobubbles for contrast-enhanced ultrasound imaging in rabbit VX2 hepatocellular carcinoma model

    Science.gov (United States)

    Yu, Houqiang; Wang, Wei; He, Xiaoling; Zhou, Qibing; Ding, Mingyue

    2017-03-01

    Ultrasound contrast agents (UCAs) such as SonoVue or Optison have been used widely in clinic for contrast-enhanced vascular imaging. However, microbubbles UCAs display limitations in tumor-targeted imaging due to the large sizes, nanoscaled UCAs has consequently attracted increasing attentions. In this work, we synthesized nanobubbles (NBs) by ultrasonic cavitation method, then a fluorescent marker of Alexa Fluor 680 was conjugated to the shell in order to observe the localization of NBs in tumor tissue. Measurement of fundamental characteristics showed that the NBs had homogeneous distribution of mean diameter of 267.9 +/- 19.2 nm and polydispersity index of 0.410 +/- 0.056. To assess in vivo tumor-selectivity of NBs, we established the rabbits VX2 hepatocellular carcinoma model though surgical implantation method. After the rabbits were intravenous administered of NBs, contrast-enhanced sonograms was observed in the surrounding of VX2 tumor, which showed there are rich capillaries in the tumor periphery. We additionally investigated the toxic of the NBs by hematoxylin-eosin staining. The results indicated that the NBs is a biocompatible non-toxic lipid system. Furthermore, the VX2 tumors and major organs were analyzed using ex vivo fluorescence imaging to confirm the targeted selectivity of NBs, and the results verified that the NBs were capable of targeting VX2 tumor. Confocal laser scanning microscopy examination showed that the NBs can traverse the VX2 tumor capillaries and target to the hepatocellular carcinoma tumor cells. All these results suggested that the newly prepared NBs have a potential application in molecular imaging and tumor-targeting therapy.

  11. Breast tumor size assessment: comparison of conventional ultrasound and contrast-enhanced ultrasound.

    Science.gov (United States)

    Jiang, Yu-Xin; Liu, He; Liu, Ji-Bin; Zhu, Qing-Li; Sun, Qiang; Chang, Xiao-Yan

    2007-12-01

    Accurate assessment of tumor size is necessary when selecting patients for breast-conserving surgery. In the study of breast contrast-enhanced ultrasound (CEUS), we found that tumor size discrepancy between CEUS and conventional ultrasound (US) existed in some breast lesions, for which the reasons are not clear. Breast CEUS examinations were performed in 104 patients with breast lesions. The measurement of the 104 breast tumors on conventional US was obtained and compared with the measurement on CEUS. A difference in measuring tumor size of >3 mm for tumors up to 1.7 cm and 4 mm for tumors >or=1.7 cm, was defined as a significant discrepancy between conventional US and CEUS. The histopathological examination of size discrepancy was performed and the margin characteristics of breast cancers with larger measurements were compared with those with unchanged measurements. Among the 104 lesions (43 malignant, 60 benign, 1 borderline), the size of 27 breast cancers and one granulomatous mastitis appeared larger at CEUS. Pathologic examinations of the region corresponding to the measurement discrepancy were mainly ductal carcinomas in situ (DCIS), invasive carcinoma with a DCIS component, adenosis with lobular hyperplasia in breast cancers and inflammatory cell infiltration in one granulomatous mastitis. Well-defined margin characteristics were significantly different between breast cancers with larger measurements at CEUS and those with unchanged measurements of size (p = 0.002), whereas no significant difference was found between the two groups in ill-defined, spiculated, hyperechoic halo, microlobulated and angulated margins (p = 0.463, 0.117, 0.194, 0.666 and 0.780, respectively). This initial study suggests that significant discrepancy of breast lesion measurement between conventional US and CEUS is more likely presented in breast cancer than benign lesions. The pathologic findings corresponding to the region of size increased at CEUS are malignant in most malignant

  12. Ultrasound-mediated vascular gene transfection by cavitation of endothelial-targeted cationic microbubbles.

    Science.gov (United States)

    Xie, Aris; Belcik, Todd; Qi, Yue; Morgan, Terry K; Champaneri, Shivam A; Taylor, Sarah; Davidson, Brian P; Zhao, Yan; Klibanov, Alexander L; Kuliszewski, Michael A; Leong-Poi, Howard; Ammi, Azzdine; Lindner, Jonathan R

    2012-12-01

    Ultrasound-mediated gene delivery can be amplified by acoustic disruption of microbubble carriers that undergo cavitation. We hypothesized that endothelial targeting of microbubbles bearing cDNA is feasible and, through optimizing proximity to the vessel wall, increases the efficacy of gene transfection. Contrast ultrasound-mediated gene delivery is a promising approach for site-specific gene therapy, although there are concerns with the reproducibility of this technique and the safety when using high-power ultrasound. Cationic lipid-shelled decafluorobutane microbubbles bearing a targeting moiety were prepared and compared with nontargeted microbubbles. Microbubble targeting efficiency to endothelial adhesion molecules (P-selectin or intercellular adhesion molecule [ICAM]-1) was tested using in vitro flow chamber studies, intravital microscopy of tumor necrosis factor-alpha (TNF-α)-stimulated murine cremaster muscle, and targeted contrast ultrasound imaging of P-selectin in a model of murine limb ischemia. Ultrasound-mediated transfection of luciferase reporter plasmid charge coupled to microbubbles in the post-ischemic hindlimb muscle was assessed by in vivo optical imaging. Charge coupling of cDNA to the microbubble surface was not influenced by the presence of targeting ligand, and did not alter the cavitation properties of cationic microbubbles. In flow chamber studies, surface conjugation of cDNA did not affect attachment of targeted microbubbles at microvascular shear stresses (0.6 and 1.5 dyne/cm(2)). Attachment in vivo was also not affected by cDNA according to intravital microscopy observations of venular adhesion of ICAM-1-targeted microbubbles and by ultrasound molecular imaging of P-selectin-targeted microbubbles in the post-ischemic hindlimb in mice. Transfection at the site of high acoustic pressures (1.0 and 1.8 MPa) was similar for control and P-selectin-targeted microbubbles but was associated with vascular rupture and hemorrhage. At 0.6 MPa

  13. Rectal water contrast transvaginal ultrasound versus double-contrast barium enema in the diagnosis of bowel endometriosis

    OpenAIRE

    Jiang, Jipeng; Liu, Ying; Wang, Kun; Wu, Xixiang; Tang, Ying

    2017-01-01

    Objectives The aim of study was to compare the accuracy between rectal water contrast transvaginal ultrasound (RWC-TVS) and double-contrast barium enema (DCBE) in evaluating the bowel endometriosis presence as well as its extent. Design and setting 198 patients at reproductive age with suspicious bowel endometriosis were included. Physicians in two groups specialised at endometriosis performed RWC-TVS as well as DCBE before laparoscopy and both groups were blinded to other groups’ results. Fi...

  14. Microbubble Composition and Preparation for High-Frequency Contrast-Enhanced Ultrasound Imaging : In Vitro and in Vivo Evaluation

    NARCIS (Netherlands)

    Daeichin, Verya; van Rooij, Tom; Skachkov, Ilya; Ergin, Bulent; Specht, Patricia A.C.; Lima, Alexandre; Ince, Can; Bosch, Johan G.; van der Steen, A.F.W.; de Jong, N.; Kooiman, Klazina

    2017-01-01

    Although high-frequency ultrasound imaging is gaining attention in various applications, hardly any ultrasound contrast agents (UCAs) dedicated to such frequencies (>15 MHz) are available for contrast-enhanced ultrasound (CEUS) imaging. Moreover, the composition of the limited commercially

  15. Microbubble Composition and Preparation for High-Frequency Contrast-Enhanced Ultrasound Imaging: In Vitro and In Vivo Evaluation

    NARCIS (Netherlands)

    Daeichin, Verya; van Rooij, Tom; Skachkov, Ilya; Ergin, Bulent; Specht, Patricia A. C.; Lima, Alexandre; Ince, Can; Bosch, Johan G.; van der Steen, Antonius F. W.; de Jong, Nico; Kooiman, Klazina

    2017-01-01

    Although high-frequency ultrasound imaging is gaining attention in various applications, hardly any ultrasound contrast agents (UCAs) dedicated to such frequencies (>15 MHz) are available for contrast-enhanced ultrasound (CEUS) imaging. Moreover, the composition of the limited commercially available

  16. Microbubble Composition and Preparation for High-Frequency Contrast-Enhanced Ultrasound Imaging: In Vitro and in Vivo Evaluation

    NARCIS (Netherlands)

    V. Daeichin (Verya); T. van Rooij (Tom); I. Skachkov (Ilya); B. Ergin (Bulent); P. Specht (Patricia); A.A.P. Lima (Alexandre ); C. Ince (Can); J.G. Bosch (Hans); A.F.W. van der Steen (Ton); N. de Jong (Nico); K. Kooiman (Klazina)

    2017-01-01

    textabstractAlthough high-frequency ultrasound imaging is gaining attention in various applications, hardly any ultrasound contrast agents (UCAs) dedicated to such frequencies (>15 MHz) are available for contrast-enhanced ultrasound (CEUS) imaging. Moreover, the composition of the limited

  17. New image contrast method in magnetic resonance imaging via ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Radicke, Marcus, E-mail: radicke@hiskp.uni-bonn.de; Engelbertz, Andre; Habenstein, Bernd; Lewerenz, Meinert; Oehms, Ole [University of Bonn, Helmholtz-Institut fuer Strahlen-und Kernphysik (Germany); Trautner, Peter; Weber, Bernd [Life and Brain Research Center, Department Neurocognition (Germany); Wrede, Sarah; Maier, Karl [University of Bonn, Helmholtz-Institut fuer Strahlen-und Kernphysik (Germany)

    2008-01-15

    When applied to a sample, ultrasound (US) gives rise to a displacement of tissue and a flow in a liquid due to the acoustic radiation pressure. These movements depend on the viscoelastic properties of the sample and can be visualized precisely with an MRI scanner using diffusion- sensitive pulse sequences. In this paper, measurements will be presented, which show the visualization of the US under variation of its parameters in different liquids and in tissue.

  18. Characterization of Breast Masses Using a New Method of Ultrasound Contrast Agent Imaging in 3D Mapping of Vascular Anomalies

    National Research Council Canada - National Science Library

    LeCarpentier, Gerald

    2002-01-01

    .... The purpose of this work is to develop an innovative dual-transducer method to control the destruction and imaging of ultrasound contrast during 3D ultrasound scanning of suspicious breast masses...

  19. Targeted disruption of the blood-brain barrier with focused ultrasound: association with cavitation activity

    International Nuclear Information System (INIS)

    McDannold, N; Vykhodtseva, N; Hynynen, K

    2006-01-01

    Acoustic emission was monitored during focused ultrasound exposures in conjunction with an ultrasound contrast agent (Optison (registered) ) in order to determine if cavitation activity is associated with the induction of blood-brain barrier disruption (BBBD). Thirty-four locations were sonicated (frequency: 260 kHz) at targets 10 mm deep in rabbit brain (N = 9). The sonications were applied at peak pressure amplitudes ranging from 0.11 to 0.57 MPa (burst length: 10 ms; repetition frequency of 1 Hz; duration: 20 s). Acoustic emission was recorded with a focused passive cavitation detector. This emission was recorded at each location during sonications with and without Optison (registered) . Detectable wideband acoustic emission was observed only at 0.40 and 0.57 MPa. BBBD was observed in contrast MRI after sonication at 0.29-0.57 MPa. The appearance of small regions of extravasated erythrocytes appeared to be associated with this wideband emission signal. The results thus suggest that BBBD resulting from focused ultrasound pulses in the presence of Optison (registered) can occur without indicators for inertial cavitation in vivo, wideband emission and extravasation. If inertial cavitation is not responsible for the BBBD, other ultrasound/microbubble interactions are likely the source. A significant increase in the emission signal due to Optison (registered) at the second and third harmonics of the ultrasound driving frequency was found to correlate with BBBD and might be useful as an online method to indicate when the disruption occurs

  20. Sentinel node detection in melanomas using contrast-enhanced ultrasound

    DEFF Research Database (Denmark)

    Nielsen, K. Rue; Klyver, H.; Chakera, A. Hougaard

    2009-01-01

    in humans. PURPOSE: To investigate the possible use of CEUS in detecting SN in patients with malignant melanomas (MM), and to improve the method by using different concentrations of contrast agent and various positions of the extremity. MATERIAL AND METHODS: Ten patients with MM on an extremity and one...... healthy volunteer were included. One milliliter of a contrast agent (Sonovue; Bracco, Milan, Italy) was injected subcutaneously on both sides of the scar from the excised tumor. Contrast-enhanced lymph channels and lymph nodes (LNs) were searched for using low-mechanical-index CEUS and by stimulated...... tissue damage, as the contrast agent was not registered for subcutaneous administration. RESULTS: In one patient, two contrast-enhanced inguinal LNs were visualized by CEUS, corresponding to two inguinal SNs found by scintigraphic imaging. No contrast-enhanced lymph channels or LNs were visualized in any...

  1. Ultrasound probe and needle-guide calibration for robotic ultrasound scanning and needle targeting.

    Science.gov (United States)

    Kim, Chunwoo; Chang, Doyoung; Petrisor, Doru; Chirikjian, Gregory; Han, Misop; Stoianovici, Dan

    2013-06-01

    Image-to-robot registration is a typical step for robotic image-guided interventions. If the imaging device uses a portable imaging probe that is held by a robot, this registration is constant and has been commonly named probe calibration. The same applies to probes tracked by a position measurement device. We report a calibration method for 2-D ultrasound probes using robotic manipulation and a planar calibration rig. Moreover, a needle guide that is attached to the probe is also calibrated for ultrasound-guided needle targeting. The method is applied to a transrectal ultrasound (TRUS) probe for robot-assisted prostate biopsy. Validation experiments include TRUS-guided needle targeting accuracy tests. This paper outlines the entire process from the calibration to image-guided targeting. Freehand TRUS-guided prostate biopsy is the primary method of diagnosing prostate cancer, with over 1.2 million procedures performed annually in the U.S. alone. However, freehand biopsy is a highly challenging procedure with subjective quality control. As such, biopsy devices are emerging to assist the physician. Here, we present a method that uses robotic TRUS manipulation. A 2-D TRUS probe is supported by a 4-degree-of-freedom robot. The robot performs ultrasound scanning, enabling 3-D reconstructions. Based on the images, the robot orients a needle guide on target for biopsy. The biopsy is acquired manually through the guide. In vitro tests showed that the 3-D images were geometrically accurate, and an image-based needle targeting accuracy was 1.55 mm. These validate the probe calibration presented and the overall robotic system for needle targeting. Targeting accuracy is sufficient for targeting small, clinically significant prostatic cancer lesions, but actual in vivo targeting will include additional error components that will have to be determined.

  2. Epithelial cell biocompatibility of silica nanospheres for contrast-enhanced ultrasound molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Chiriaco, Fernanda; Conversano, Francesco; Soloperto, Giulia; Casciaro, Ernesto [Institute of Clinical Physiology, Bioengineering Division, National Research Council (Italy); Ragusa, Andrea [National Nanotechnology Laboratory of CNR-NANO (Italy); Sbenaglia, Enzo Antonio; Dipaola, Lucia [Institute of Clinical Physiology, Bioengineering Division, National Research Council (Italy); Casciaro, Sergio, E-mail: sergio.casciaro@cnr.it [Istituto di Fisiologia Clinica (CNR-IFC) c/o Campus Universitario Ecotekne, Consiglio Nazionale delle Ricerche (Italy)

    2013-07-15

    Nanosized particles are receiving increasing attention as future contrast agents (CAs) for ultrasound (US) molecular imaging, possibly decorated on its surface with biological recognition agents for targeted delivery and deposition of therapeutics. In particular, silica nanospheres (SiNSs) have been demonstrated to be feasible in terms of contrast enhancement on conventional US systems. In this work, we evaluated the cytotoxicity of SiNSs on breast cancer (MCF-7) and HeLa (cervical cancer) cells employing NSs with sizes ranging from 160 to 330 nm and concentration range of 1.5-5 mg/mL. Cell viability was evaluated in terms of size, dose and time dependence, performing the MTT reduction assay with coated and uncoated SiNSs. Whereas uncoated SiNSs caused a variable significant decrease in cell viability on both cell lines mainly depending on size and exposure time, PEGylated SiNSs (SiNSs-PEG) exhibit a high level of biocompatibility. In fact, after 72-h incubation, viability of both cell types was above the cutoff value of 70 % at concentration up to 5 mg/mL. We also investigated the acoustical behavior of coated and uncoated SiNSs within conventional diagnostic US fields in order to determine a suitable configuration, in terms of particle size and concentration, for their employment as targetable CAs. Our results indicate that the employment of SiNSs with diameters around 240 nm assures the most effective contrast enhancement even at the lowest tested concentration, coupled with the possibility of targeting all tumor tissues, being the SiNSs still in a size range where reticuloendothelial system trapping effect is relatively low.

  3. Epithelial cell biocompatibility of silica nanospheres for contrast-enhanced ultrasound molecular imaging

    International Nuclear Information System (INIS)

    Chiriacò, Fernanda; Conversano, Francesco; Soloperto, Giulia; Casciaro, Ernesto; Ragusa, Andrea; Sbenaglia, Enzo Antonio; Dipaola, Lucia; Casciaro, Sergio

    2013-01-01

    Nanosized particles are receiving increasing attention as future contrast agents (CAs) for ultrasound (US) molecular imaging, possibly decorated on its surface with biological recognition agents for targeted delivery and deposition of therapeutics. In particular, silica nanospheres (SiNSs) have been demonstrated to be feasible in terms of contrast enhancement on conventional US systems. In this work, we evaluated the cytotoxicity of SiNSs on breast cancer (MCF-7) and HeLa (cervical cancer) cells employing NSs with sizes ranging from 160 to 330 nm and concentration range of 1.5–5 mg/mL. Cell viability was evaluated in terms of size, dose and time dependence, performing the MTT reduction assay with coated and uncoated SiNSs. Whereas uncoated SiNSs caused a variable significant decrease in cell viability on both cell lines mainly depending on size and exposure time, PEGylated SiNSs (SiNSs-PEG) exhibit a high level of biocompatibility. In fact, after 72-h incubation, viability of both cell types was above the cutoff value of 70 % at concentration up to 5 mg/mL. We also investigated the acoustical behavior of coated and uncoated SiNSs within conventional diagnostic US fields in order to determine a suitable configuration, in terms of particle size and concentration, for their employment as targetable CAs. Our results indicate that the employment of SiNSs with diameters around 240 nm assures the most effective contrast enhancement even at the lowest tested concentration, coupled with the possibility of targeting all tumor tissues, being the SiNSs still in a size range where reticuloendothelial system trapping effect is relatively low

  4. THE ABILITY OF CONTRAST-ENHANCED ULTRASOUND IN THE DIAGNOSIS OF LIVER METASTASES IN CERVICAL CANCER

    OpenAIRE

    V. S. Kryazheva; M. A. Chekalova; Z. R-B. Musaeva; V. V. Kuznetsov

    2017-01-01

    Objective: to explore the possibilities of contrast-enhanced ultrasound (CEUS) in the diagnosis of liver metastases in patients with a diagnosis of cervical cancer.Materials and methods. We analyzed the results of 4 clinical cases, of which 3 cases according CEUS diagnosed with liver metastases, in 1 case – nodular hyperplasia.Results and conclusions. Despite the small number of observations, we have concluded that the use of CEUS allows to expand possibilities of the ultrasound method in the...

  5. Counter-propagating wave interaction for contrast-enhanced ultrasound imaging

    Science.gov (United States)

    Renaud, G.; Bosch, J. G.; ten Kate, G. L.; Shamdasani, V.; Entrekin, R.; de Jong, N.; van der Steen, A. F. W.

    2012-11-01

    Most techniques for contrast-enhanced ultrasound imaging require linear propagation to detect nonlinear scattering of contrast agent microbubbles. Waveform distortion due to nonlinear propagation impairs their ability to distinguish microbubbles from tissue. As a result, tissue can be misclassified as microbubbles, and contrast agent concentration can be overestimated; therefore, these artifacts can significantly impair the quality of medical diagnoses. Contrary to biological tissue, lipid-coated gas microbubbles used as a contrast agent allow the interaction of two acoustic waves propagating in opposite directions (counter-propagation). Based on that principle, we describe a strategy to detect microbubbles that is free from nonlinear propagation artifacts. In vitro images were acquired with an ultrasound scanner in a phantom of tissue-mimicking material with a cavity containing a contrast agent. Unlike the default mode of the scanner using amplitude modulation to detect microbubbles, the pulse sequence exploiting counter-propagating wave interaction creates no pseudoenhancement behind the cavity in the contrast image.

  6. Estimation of Tumor Angiogenesis With Contrast Enhanced Subharmonic Ultrasound Imaging

    National Research Council Canada - National Science Library

    Forsberg, Flemming

    2001-01-01

    ...) and receiving at the subharmonic (f0) . Because of no subharmonic generation in tissue and significant subharmonic scattering from some new contrast agents SHI has the potential to detect slow, small volume blood flow associated with tumor...

  7. Vascular Structure Identification in Intraoperative 3D Contrast-Enhanced Ultrasound Data

    Directory of Open Access Journals (Sweden)

    Elisee Ilunga-Mbuyamba

    2016-04-01

    Full Text Available In this paper, a method of vascular structure identification in intraoperative 3D Contrast-Enhanced Ultrasound (CEUS data is presented. Ultrasound imaging is commonly used in brain tumor surgery to investigate in real time the current status of cerebral structures. The use of an ultrasound contrast agent enables to highlight tumor tissue, but also surrounding blood vessels. However, these structures can be used as landmarks to estimate and correct the brain shift. This work proposes an alternative method for extracting small vascular segments close to the tumor as landmark. The patient image dataset involved in brain tumor operations includes preoperative contrast T1MR (cT1MR data and 3D intraoperative contrast enhanced ultrasound data acquired before (3D-iCEUS s t a r t and after (3D-iCEUS e n d tumor resection. Based on rigid registration techniques, a preselected vascular segment in cT1MR is searched in 3D-iCEUS s t a r t and 3D-iCEUS e n d data. The method was validated by using three similarity measures (Normalized Gradient Field, Normalized Mutual Information and Normalized Cross Correlation. Tests were performed on data obtained from ten patients overcoming a brain tumor operation and it succeeded in nine cases. Despite the small size of the vascular structures, the artifacts in the ultrasound images and the brain tissue deformations, blood vessels were successfully identified.

  8. Contrast Enhanced Ultrasound of the Kidneys: What Is It Capable of?

    Directory of Open Access Journals (Sweden)

    Demosthenes D. Cokkinos

    2013-01-01

    Full Text Available One of the many imaging uses of contrast enhanced ultrasound (CEUS is studying a wide variety of kidney pathology, due to its ability to detect microvascular blood flow in real time without affecting renal function. CEUS enables dynamic assessment and quantification of microvascularisation up to capillary perfusion. The objective of this paper is to briefly refresh basic knowledge of ultrasound (US contrast agents’ physical properties, to study technical details of CEUS scanning in the kidneys, and to review the commonest renal indications for CEUS, with imaging examples in comparison to baseline unenhanced US and computed tomography when performed. Safety matters and limitations of CEUS of the kidneys are also discussed.

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

    Science.gov (United States)

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

    1998-12-01

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

  10. Comparison of two ultrasound-guided injection techniques targeting the sacroiliac joint region in equine cadavers.

    Science.gov (United States)

    Stack, John David; Bergamino, Chiara; Sanders, Ruth; Fogarty, Ursula; Puggioni, Antonella; Kearney, Clodagh; David, Florent

    2016-09-20

    To compare the accuracy and distribution of injectate for cranial (CR) and caudomedial (CM) ultrasound-guided injections of equine sacroiliac joints. Both sacroiliac joints from 10 lumbosacropelvic specimens were injected using cranial parasagittal (CR; curved 18 gauge, 25 cm spinal needles) and caudomedial (CM; straight 18 gauge, 15 cm spinal needles) ultrasound-guided approaches. Injectate consisted of 4 ml iodinated contrast and 2 ml methylene blue. Computed tomographical (CT) scans were performed before and after injections. Time for needle guidance and repositioning attempts were recorded. The CT sequences were analysed for accuracy and distribution of contrast. Intra-articular contrast was detected in sacroiliac joints following 15/40 injections. The CR and CM approaches deposited injectate ≤2 cm from sacroiliac joint margins following 17/20 and 20/20 injections, respectively. Median distance of closest contrast to the sacroiliac joint was 0.4 cm (interquartile range [IQR]: 1.5 cm) for CR approaches and 0.6 cm (IQR: 0.95 cm) for CM approaches. Cranial injections resulted in injectate contacting lumbosacral intertransverse joints 15/20 times. Caudomedial injections were perivascular 16/20 times. Safety and efficacy could not be established. Cranial and CM ultrasound-guided injections targeting sacroiliac joints were very accurate for periarticular injection, but accuracy was poor for intra-articular injection. Injectate was frequently found in contact with interosseous sacroiliac ligaments, as well as neurovascular and synovial structures in close vicinity of sacroiliac joints.

  11. Sonochemiluminescence observation of lipid- and polymer-shelled ultrasound contrast agents in 1.2 MHz focused ultrasound field.

    Science.gov (United States)

    Qiao, Yangzi; Cao, Hua; Zhang, Shusheng; Yin, Hui; Wan, Mingxi

    2013-01-01

    Ultrasound contrast agents (UCAs) are frequently added into the focused ultrasound field as cavitation nuclei to enhance the therapeutic efficiency. Since their presence will distort the pressure field and make the process unpredictable, comprehension of their behaviors especially the active zone spatial distribution is an important part of better monitoring and using of UCAs. As shell materials can strongly alter the acoustic behavior of UCAs, two different shells coated UCAs, lipid-shelled and polymer-shelled UCAs, in a 1.2 MHz focused ultrasound field were studied by the Sonochemiluminescence (SCL) method and compared. The SCL spatial distribution of lipid-shelled group differed from that of polymer-shelled group. The shell material and the character of focused ultrasound field work together to the SCL distribution, causing the lipid-shelled group to have a maximum SCL intensity in pre-focal region at lower input power than that of polymer-shelled group, and a brighter SCL intensity in post-focal region at high input power. The SCL inactive area of these two groups both increased with the input power. The general behavior of the UCAs can be studied by both the average SCL intensity and the backscatter signals. As polymer-shelled UCAs are more resistant to acoustic pressure, they had a higher destruction power and showed less reactivation than lipid-shelled ones. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Detection of vascularity in wrist tenosynovitis: power doppler ultrasound compared with contrast-enhanced grey-scale ultrasound.

    Science.gov (United States)

    Klauser, Andrea S; Franz, Magdalena; Arora, Rohit; Feuchtner, Gudrun M; Gruber, Johann; Schirmer, Michael; Jaschke, Werner R; Gabl, Markus F

    2010-01-01

    We sought to assess vascularity in wrist tenosynovitis by using power Doppler ultrasound (PDUS) and to compare detection of intra- and peritendinous vascularity with that of contrast-enhanced grey-scale ultrasound (CEUS). Twenty-six tendons of 24 patients (nine men, 15 women; mean age ± SD, 54.4 ± 11.8 years) with a clinical diagnosis of tenosynovitis were examined with B-mode ultrasonography, PDUS, and CEUS by using a second-generation contrast agent, SonoVue (Bracco Diagnostics, Milan, Italy) and a low-mechanical-index ultrasound technique. Thickness of synovitis, extent of vascularized pannus, intensity of peritendinous vascularisation, and detection of intratendinous vessels was incorporated in a 3-score grading system (grade 0 to 2). Interobserver variability was calculated. With CEUS, a significantly greater extent of vascularity could be detected than by using PDUS (P < 0.001). In terms of peri- and intratendinous vessels, CEUS was significantly more sensitive in the detection of vascularization compared with PDUS (P < 0.001). No significant correlation between synovial thickening and extent of vascularity could be found (P = 0.089 to 0.097). Interobserver reliability was calculated to be excellent when evaluating the grading score (κ = 0.811 to 1.00). CEUS is a promising tool to detect tendon vascularity with higher sensitivity than PDUS by improved detection of intra- and peritendinous vascularity.

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

    Czech Academy of Sciences Publication Activity Database

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2015-09-01

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

  15. Feasibility of ultrasound-guided intraarticular contrast injection for MR arthrography

    International Nuclear Information System (INIS)

    Baek, Soo Jin; Lee, Jong Min; Kang, Duck Sick

    2005-01-01

    To assess the feasibility of ultrasound-guided intraarticular contrast injection using the posterior approach for MR arthrography. Between June 2002 and October 2004, 132 patients (29 female, 103 male: mean age, 33.6 years) underwent ultrasound-guided intraarticular contrast media injection (40 ml saline + 10 ml 2% lidocaine + 0.2 ml gadopentetate dimeglumine + 0.4 ml epinephrine) for MR arthrography. The patients were classified into four groups, viz. the no leakage group, the minor leakage with successful intraarticular injection group, the major leakage with unsuccessful intraarticular injection group, and the injection failure group. The 'no leakage' and 'minor leakage' groups were considered to be technical successes, while the 'major leakage' and 'injection failure' groups were regarded as technical failures. The technical success rate of ultrasound-guided intraarticular contrast injection using the posterior approach for MR Arthrography was 99.2% (131/132 patients) and one patients 0.7% (1/132 patients) was included in the 'major leakage' group. Ultrasound-guided intraarticular contrast injection using the posterior approach for MR arthrography was feasible with a high success rate

  16. Use of Ultrasound Contrast Agents in Relation to Percutaneous Interventional Procedures

    DEFF Research Database (Denmark)

    Nolsøe, Christian Pállson; Nolsøe, Alexander Bjørneboe; Klubien, Jeanett

    2018-01-01

    The aim of this article is to provide an inventory of the use of contrast-enhanced ultrasound (CEUS) in relation to percutaneous interventional procedures. The article is structured into a systematic literature review followed by a clinical part relating to percutaneous CEUS-guided procedures...

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

    DEFF Research Database (Denmark)

    Andersen, Klaus Scheldrup

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

  18. Evaluation of the diagnosis on staging of the bladder cancers by contrast-enhanced ultrasound

    International Nuclear Information System (INIS)

    Gao Yong; Xu Haiyan; Huan Haiming; Chen Yane

    2010-01-01

    Objective: To study the value of the staging of the bladder cancers with the contrast-enhanced ultrasound. Methods: After rapid injection of the contrast agent SonoVue through the elbow vein, the staging of images was completed in 18 cases of bladder cancer. Results: The results of contrast-enhanced ultrasound were compared with post-operative pathological analysis, the rate of accuracy of diagnosis on T1, T2, T3 and T4 stage was 100%, 80%, 83% and 100% respectively. The accuracy made by new methods higher than those of other imaging examinations in T1 stage; the other stages were similar to those of other imaging examinations. Conclusion: The evaluation of Contrast-enhanced ultrasound on the staging of the bladder cancer is higher than that of the conventional ultrasound examination, while the observation of blood flow in the tumor can make accurate diagnosis and differential diagnosis, this method can be complement each other with CT and MRI to improve the rate of accuracy on the staging of bladder cancer. (authors)

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

    Science.gov (United States)

    Back, Susan J; Edgar, J Christopher; Canning, Douglas A; Darge, Kassa

    2015-09-01

    Pediatric contrast-enhanced ultrasound (CEUS) is primarily performed outside the United States where a track record for safety in intravenous and intravesical applications has been established. Contrast-enhanced voiding urosonography (ceVUS) has also been shown to have a much higher rate of vesicoureteral reflux detection compared to voiding cystourethrography. US contrast agents available in the United States differ from those abroad. Optison® (GE Healthcare, Princeton, NJ) is such an US contrast agent. While Optison® has similar characteristics to other second-generation agents, it has never been used for ceVUS. In vitro optimization of dose and imaging parameters as well as assessment of contrast visualization when delivered in conditions similar to ceVUS are necessary starting points prior to in vivo applications. To optimize the intravesical use of Optison® in vitro for ceVUS before its use in pediatric studies. The experimental design simulated intravesical use. Using 9- and 12-MHz linear transducers, we scanned 20-mL syringes varying mechanical index, US contrast agent concentration (0.25%, 0.5%, 1.0%), solvent (saline, urine, radiographic contrast agent) and time out of refrigeration. We evaluated mechanical index settings and contrast duration, optimized the contrast dose, measured the effect of urine and radiographic contrast agent, and the impact of length of time of contrast outside of the refrigerator on US contrast appearance. We scanned 50-ml saline bags to assess the appearance and duration of US contrast with different delivery systems (injection vs. infusion). Consistent contrast visualization was achieved at a mechanical index of 0.06-0.17 and 0.11-0.48 for the L9 and L12 MHz transducers (P contrast visualization of the microbubbles with a higher transducer frequency. The lowest mechanical index for earliest visible microbubble destruction was 0.21 for the 9 MHz and 0.39 for the 12 MHz (P contrast agent volume to bladder filling was the

  20. THE ABILITY OF CONTRAST-ENHANCED ULTRASOUND IN THE DIAGNOSIS OF LIVER METASTASES IN CERVICAL CANCER

    Directory of Open Access Journals (Sweden)

    V. S. Kryazheva

    2017-01-01

    Full Text Available Objective: to explore the possibilities of contrast-enhanced ultrasound (CEUS in the diagnosis of liver metastases in patients with a diagnosis of cervical cancer.Materials and methods. We analyzed the results of 4 clinical cases, of which 3 cases according CEUS diagnosed with liver metastases, in 1 case – nodular hyperplasia.Results and conclusions. Despite the small number of observations, we have concluded that the use of CEUS allows to expand possibilities of the ultrasound method in the differential diagnosis of focal changes in the liver.

  1. The role of contrast-enhanced endoscopic ultrasound in pancreatic adenocarcinoma

    DEFF Research Database (Denmark)

    Saftoiu, Adrian; Vilmann, Peter; Bhutani, Manoop S

    2016-01-01

    contrast agents for early detection, tridimensional and fusion techniques for enhanced staging and resectability assessment but also novel applications of perfusion imaging for monitoring ablative therapy, improved local detection through EUS-guided sampling of portal vein flow or enhanced drug delivery......Contrast-enhanced endoscopic ultrasound (CE-EUS) allows characterization, differentiation, and staging of focal pancreatic masses. The method has a high sensitivity and specificity for the diagnosis of pancreatic adenocarcinoma which is visualized as hypo-enhanced as compared to the rest...... of the parenchyma while chronic pancreatitis and neuroendocrine tumors are generally either iso-enhanced or hyper-enhanced. The development of contrast-enhanced low mechanical index harmonic imaging techniques used in real time during endoscopic ultrasound (EUS) allowed perfusion imaging and the quantification...

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

    Science.gov (United States)

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

    2017-09-01

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

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

    Science.gov (United States)

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

    2011-04-01

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

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

    Science.gov (United States)

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

    2016-10-01

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

  5. Feasibility and usefulness of using swallow contrast-enhanced ultrasound to diagnose Zenker's diverticulum: preliminary results.

    Science.gov (United States)

    Cui, Xin-Wu; Ignee, Andre; Baum, Ulrich; Dietrich, Christoph F

    2015-04-01

    Zenker's diverticulum (ZD) may be misdiagnosed on conventional ultrasound as a thyroid nodule or other lesion. A barium esophagram is usually used to confirm the diagnosis; however, this procedure exposes the patient to radiation. The aim of this study was to evaluate the feasibility of using swallow contrast-enhanced ultrasound (swallow-CEUS) to diagnose ZD. Ten consecutive patients with ZD (7 men and 3 women, aged 67 ± 11 y) were included in the study. In 4 patients, ZD was incidentally found on head and neck ultrasound, and in 6 patients, ZD was suspected because of dysphagia. All lesions could be detected on conventional ultrasound before swallow-CEUS. Ten healthy volunteers (8 men and 2 women, aged 60 ± 12 y) were chosen as a control group. Written informed consent was obtained. With the patient in the sitting or upright position, conventional ultrasound was performed first to image the lesion, then the patient was asked to swallow ultrasound contrast agent (UCA) (2-4 drops of SonoVue diluted with about 200 mL of tap water). Transity of the contrast agent in the esophagus was imaged with CEUS. Retention of the UCA in the diverticulum was monitored for at least 3 min. All patients underwent a barium esophagram as the gold standard. Swallow-CEUS revealed that in all patients (100%), the UCA was transported from the pharynx to the esophagus while the patient swallowed. ZD appeared as a pouch-shaped structure at the posterior pharyngo-esophageal junction that retained UCA longer than 3 min. The barium esophagram confirmed the diagnosis of ZD in all patients. For the 10 volunteers, no abnormal structure (retaining UCA) was detected during or after swallowing of UCA. With the advantages of no radiation and bedside availability, swallow-CEUS may become a method of choice in confirmation of the diagnosis of ZD, especially when ZD is suspected on conventional ultrasound. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier

  6. Streaming flow from ultrasound contrast agents by acoustic waves in a blood vessel model.

    Science.gov (United States)

    Cho, Eunjin; Chung, Sang Kug; Rhee, Kyehan

    2015-09-01

    To elucidate the effects of streaming flow on ultrasound contrast agent (UCA)-assisted drug delivery, streaming velocity fields from sonicated UCA microbubbles were measured using particle image velocimetry (PIV) in a blood vessel model. At the beginning of ultrasound sonication, the UCA bubbles formed clusters and translated in the direction of the ultrasound field. Bubble cluster formation and translation were faster with 2.25MHz sonication, a frequency close to the resonance frequency of the UCA. Translation of bubble clusters induced streaming jet flow that impinged on the vessel wall, forming symmetric vortices. The maximum streaming velocity was about 60mm/s at 2.25MHz and decreased to 15mm/s at 1.0MHz for the same acoustic pressure amplitude. The effect of the ultrasound frequency on wall shear stress was more noticeable. Maximum wall shear stress decreased from 0.84 to 0.1Pa as the ultrasound frequency decreased from 2.25 to 1.0MHz. The maximum spatial gradient of the wall shear stress also decreased from 1.0 to 0.1Pa/mm. This study showed that streaming flow was induced by bubble cluster formation and translation and was stronger upon sonication by an acoustic wave with a frequency near the UCA resonance frequency. Therefore, the secondary radiant force, which is much stronger at the resonance frequency, should play an important role in UCA-assisted drug delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Lin, Hangyu; Chen, Junfang; Chen, Chuanpin

    2016-09-01

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

  8. Counter-propagating wave interaction for contrast-enhanced ultrasound imaging

    International Nuclear Information System (INIS)

    Renaud, G; Bosch, J G; Ten Kate, G L; De Jong, N; Van der Steen, A F W; Shamdasani, V; Entrekin, R

    2012-01-01

    Most techniques for contrast-enhanced ultrasound imaging require linear propagation to detect nonlinear scattering of contrast agent microbubbles. Waveform distortion due to nonlinear propagation impairs their ability to distinguish microbubbles from tissue. As a result, tissue can be misclassified as microbubbles, and contrast agent concentration can be overestimated; therefore, these artifacts can significantly impair the quality of medical diagnoses. Contrary to biological tissue, lipid-coated gas microbubbles used as a contrast agent allow the interaction of two acoustic waves propagating in opposite directions (counter-propagation). Based on that principle, we describe a strategy to detect microbubbles that is free from nonlinear propagation artifacts. In vitro images were acquired with an ultrasound scanner in a phantom of tissue-mimicking material with a cavity containing a contrast agent. Unlike the default mode of the scanner using amplitude modulation to detect microbubbles, the pulse sequence exploiting counter-propagating wave interaction creates no pseudoenhancement behind the cavity in the contrast image. (fast track communication)

  9. Evaluation of the equine digital flexor tendon sheath using diagnostic ultrasound and contrast radiography

    International Nuclear Information System (INIS)

    Redding, W.R.

    1994-01-01

    This study was designed to evaluate the normal anatomy of the digital flexor tendon sheath using contrast radiography and diagnostic ultrasound. Iodinated contrast medium was injected into eight cadaver limbs and the limbs immediately frozen. Lateromedial and dorsopalmar/plantar radiographs were made. These limps were then cut transversely and proximal to distal radiographs of each slab were made. This cross sectional contrast methodology allowed the visualization of the relative size and shape of the superficial and deep digital flexor tendons as well as the potential space taken by effusions of the digital flexor tendon sheath. The second part of the study used twelve live animals with normal digital flexor tendon sheaths. Ultrasonographic measurement of the structures of the digital flexor tendon sheath at each level were compiled. This documented the ability of diagnostic ultrasound to image: 1) the superficial and deep digital flexor tendons, 2) the proximal and distal ring of the manica flexoria, 3) the straight and oblique sesamoidean ligaments, and 4) the mesotendinous attachments to the superficial and deep flexor tendons. Iodinated contrast medium was then injected into the digital flexor tendon sheath and the ultrasonography repeated. These images were compared with those obtained from contrast radiography and prosections of twenty normal limbs. The iodinated contrast medium enhanced sonographic imaging of the structures of the digital tendon sheath, particularly the abaxial borders of the superficial digital flexor tendon branches and the mesotendinous attachments to the superficial and deep digital flexor tendons

  10. Ultrasound-sensitive nanoparticle aggregates for targeted drug delivery.

    Science.gov (United States)

    Papa, Anne-Laure; Korin, Netanel; Kanapathipillai, Mathumai; Mammoto, Akiko; Mammoto, Tadanori; Jiang, Amanda; Mannix, Robert; Uzun, Oktay; Johnson, Christopher; Bhatta, Deen; Cuneo, Garry; Ingber, Donald E

    2017-09-01

    Here we describe injectable, ultrasound (US)-responsive, nanoparticle aggregates (NPAs) that disintegrate into slow-release, nanoscale, drug delivery systems, which can be targeted to selective sites by applying low-energy US locally. We show that, unlike microbubble based drug carriers which may suffer from stability problems, the properties of mechanical activated NPAs, composed of polymer nanoparticles, can be tuned by properly adjusting the polymer molecular weight, the size of the nanoparticle precursors as well as the percentage of excipient utilized to hold the NPA together. We then apply this concept to practice by fabricating NPAs composed of nanoparticles loaded with Doxorubicin (Dox) and tested their ability to treat tumors via ultrasound activation. Mouse studies demonstrated significantly increased efficiency of tumor targeting of the US-activated NPAs compared to PLGA nanoparticle controls (with or without US applied) or intact NPAs. Importantly, when the Dox-loaded NPAs were injected and exposed to US energy locally, this increased ability to concentrate nanoparticles at the tumor site resulted in a significantly greater reduction in tumor volume compared to tumors treated with a 20-fold higher dose of the free drug. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2012-11-27

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

  12. Analysis of Achilles tendon vascularity with second generation Contrast-Enhanced Ultrasound (CEUS)

    OpenAIRE

    Genovese , Eugenio; Ronga , Mario; Recaldini , Chiara; Fontana , Federico; Callegari , Leonardo; Fugazzola , Carlo

    2011-01-01

    Abstract Purpose: To compare morphological and power Doppler features of the Achilles tendon and Contrast-Enhanced Ultrasound (CEUS) behaviour between asymptomatic athletes and athletes who had undergone surgery for repair of an Achilles tendon rupture. Materials and Methods: 24 athletes were divided in two groups (A and B). Group A included 14 patients with a median age of 32 years (range 27 to 47 years) who had undergone surgical repair for unilateral Achilles tendon ...

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

    OpenAIRE

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

    2013-01-01

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

  14. Ultrasound image based visual servoing for moving target ablation by high intensity focused ultrasound.

    Science.gov (United States)

    Seo, Joonho; Koizumi, Norihiro; Mitsuishi, Mamoru; Sugita, Naohiko

    2017-12-01

    Although high intensity focused ultrasound (HIFU) is a promising technology for tumor treatment, a moving abdominal target is still a challenge in current HIFU systems. In particular, respiratory-induced organ motion can reduce the treatment efficiency and negatively influence the treatment result. In this research, we present: (1) a methodology for integration of ultrasound (US) image based visual servoing in a HIFU system; and (2) the experimental results obtained using the developed system. In the visual servoing system, target motion is monitored by biplane US imaging and tracked in real time (40 Hz) by registration with a preoperative 3D model. The distance between the target and the current HIFU focal position is calculated in every US frame and a three-axis robot physically compensates for differences. Because simultaneous HIFU irradiation disturbs US target imaging, a sophisticated interlacing strategy was constructed. In the experiments, respiratory-induced organ motion was simulated in a water tank with a linear actuator and kidney-shaped phantom model. Motion compensation with HIFU irradiation was applied to the moving phantom model. Based on the experimental results, visual servoing exhibited a motion compensation accuracy of 1.7 mm (RMS) on average. Moreover, the integrated system could make a spherical HIFU-ablated lesion in the desired position of the respiratory-moving phantom model. We have demonstrated the feasibility of our US image based visual servoing technique in a HIFU system for moving target treatment. © 2016 The Authors The International Journal of Medical Robotics and Computer Assisted Surgery Published by John Wiley & Sons Ltd.

  15. The Use of Acoustic Radiation Force Decorrelation-Weighted Pulse Inversion for Enhanced Ultrasound Contrast Imaging.

    Science.gov (United States)

    Herbst, Elizabeth B; Unnikrishnan, Sunil; Wang, Shiying; Klibanov, Alexander L; Hossack, John A; Mauldin, Frank William

    2017-02-01

    The use of ultrasound imaging for cancer diagnosis and screening can be enhanced with the use of molecularly targeted microbubbles. Nonlinear imaging strategies such as pulse inversion (PI) and "contrast pulse sequences" (CPS) can be used to differentiate microbubble signal, but often fail to suppress highly echogenic tissue interfaces. This failure results in false-positive detection and potential misdiagnosis. In this study, a novel acoustic radiation force (ARF)-based approach was developed for superior microbubble signal detection. The feasibility of this technique, termed ARF decorrelation-weighted PI (ADW-PI), was demonstrated in vivo using a subcutaneous mouse tumor model. Tumors were implanted in the hindlimb of C57BL/6 mice by subcutaneous injection of MC38 cells. Lipid-shelled microbubbles were conjugated to anti-VEGFR2 antibody and administered via bolus injection. An image sequence using ARF pulses to generate microbubble motion was combined with PI imaging on a Verasonics Vantage programmable scanner. ADW-PI images were generated by combining PI images with interframe signal decorrelation data. For comparison, CPS images of the same mouse tumor were acquired using a Siemens Sequoia clinical scanner. Microbubble-bound regions in the tumor interior exhibited significantly higher signal decorrelation than static tissue (n = 9, P < 0.001). The application of ARF significantly increased microbubble signal decorrelation (n = 9, P < 0.01). Using these decorrelation measurements, ADW-PI imaging demonstrated significantly improved microbubble contrast-to-tissue ratio when compared with corresponding CPS or PI images (n = 9, P < 0.001). Contrast-to-tissue ratio improved with ADW-PI by approximately 3 dB compared with PI images and 2 dB compared with CPS images. Acoustic radiation force can be used to generate adherent microbubble signal decorrelation without microbubble bursting. When combined with PI, measurements of the resulting microbubble signal

  16. Radiographic, MR or ultrasound contrast media in pregnant or breast-feeding women. What are the key issues?

    International Nuclear Information System (INIS)

    Froehlich, J.M.; Kubik-Huch, Rahel A.

    2013-01-01

    The use and the safety of radiographic, MR- or ultrasound contrast media in the diagnostic work-up of pregnant or lactating patients is a frequently discussed question. As only sparse clinical data is available, a careful benefit-risk assessment must contain physico-chemical properties, preclinical data including teratogeneity and embryotoxicity, as well as maternal and foetal exposure. With consideration to the individual risks, iodinated contrast media, macrocyclic MR contrast media with increased stability or sulphur hexafluoride ultrasound contrast media may, if clinically justified, be administered in the smallest possible doses throughout pregnancy. After parental administration of an iodinated contrast medium after the 12th week of pregnancy, the neonate's thyroidal function should be checked during the first week after birth. After parental administration of iodinated, stable macrocyclic, gadolinium or ultrasound contrast media, lactation can be continued normally. In any case, contrast media should be used with caution and only if the benefits outweigh the risk. (orig.)

  17. Application of contrast-enhanced ultrasound in the diagnosis of solid pancreatic lesions—A comparison of conventional ultrasound and contrast-enhanced CT

    International Nuclear Information System (INIS)

    Fan, Zhihui; Li, Ying; Yan, Kun; Wu, Wei; Yin, Shanshan; Yang, Wei; Xing, Baocai

    2013-01-01

    Objective: To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) by comparison with conventional ultrasound (US) and contrast-enhanced CT (CECT) in solid pancreatic lesions. Method: Ninety patients with solid pancreatic focal lesions were enrolled, including 36 cases of pancreatic carcinoma, 28 cases of pancreatitis, 6 cases of pancreatic neuroendocrine tumor, 12 cases of solid pseudopapillary tumor of the pancreas, 6 cases of pancreatic metastases, 1 case of cavernous hemolymphangioma and 1 case of lymphoma. US and CEUS were applied respectively for the diagnosis of a total of 90 cases of solid pancreatic lesions. The diagnostic results were scored on a 5-point scale. Results of CEUS were compared with CECT. Results: (1) 3-score cases (undetermined) diagnosed by CEUS were obviously fewer than that of US, while the number of 1-score (definitely benign) and 5-score (definitely malignant) cases diagnosed by CEUS was significantly more than that of US. There was a significant difference in the distribution of final scores using the two methods (p < 0.001). The overall diagnostic accuracies of the 90 cases for CEUS and US were 83.33% and 44.44%, respectively, which indicated an obvious advantage for CEUS (p < 0.001). (2) The diagnostic consistency among three ultrasound doctors: the kappa values calculated for US were 0.537, 0.444 and 0.525, compared with 0.748, 0.645 and 0.795 for CEUS. The interobserver agreement for CEUS was higher than that for US. (3) The sensitivity, specificity and accuracy of the diagnosis of pancreatic carcinoma with CEUS and CECT were 91.7% and 97.2%, 87.0% and 88.9%, and 88.9% and 92.2%, respectively, while for the diagnosis of pancreatitis, the corresponding indices were 82.1% and 67.9%, 91.9% and 100%, and 88.9% and 90%, respectively, showing no significant differences (p > 0.05). Conclusion: CEUS has obvious superiority over conventional US in the general diagnostic accuracy of solid pancreatic lesions and in the

  18. Application of contrast-enhanced ultrasound in the diagnosis of solid pancreatic lesions—A comparison of conventional ultrasound and contrast-enhanced CT

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Zhihui, E-mail: fanzhihui_1026@163.com [Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Ultrasound, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142 (China); Li, Ying, E-mail: 18901033676@126.com [Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Radiology, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142 (China); Yan, Kun, E-mail: ydbz@sina.com [Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Ultrasound, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142 (China); Wu, Wei, E-mail: wuwei@163.com [Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Ultrasound, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142 (China); Yin, Shanshan, E-mail: yshshmd@yahoo.com [Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Ultrasound, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142 (China); Yang, Wei, E-mail: weiwei02032001@gmail.com [Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Ultrasound, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142 (China); Xing, Baocai, E-mail: xinbaocai88@sina.com [Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department of Hepatic Biliary and Pancreatic Surgery, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing 100142 (China); and others

    2013-09-15

    Objective: To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) by comparison with conventional ultrasound (US) and contrast-enhanced CT (CECT) in solid pancreatic lesions. Method: Ninety patients with solid pancreatic focal lesions were enrolled, including 36 cases of pancreatic carcinoma, 28 cases of pancreatitis, 6 cases of pancreatic neuroendocrine tumor, 12 cases of solid pseudopapillary tumor of the pancreas, 6 cases of pancreatic metastases, 1 case of cavernous hemolymphangioma and 1 case of lymphoma. US and CEUS were applied respectively for the diagnosis of a total of 90 cases of solid pancreatic lesions. The diagnostic results were scored on a 5-point scale. Results of CEUS were compared with CECT. Results: (1) 3-score cases (undetermined) diagnosed by CEUS were obviously fewer than that of US, while the number of 1-score (definitely benign) and 5-score (definitely malignant) cases diagnosed by CEUS was significantly more than that of US. There was a significant difference in the distribution of final scores using the two methods (p < 0.001). The overall diagnostic accuracies of the 90 cases for CEUS and US were 83.33% and 44.44%, respectively, which indicated an obvious advantage for CEUS (p < 0.001). (2) The diagnostic consistency among three ultrasound doctors: the kappa values calculated for US were 0.537, 0.444 and 0.525, compared with 0.748, 0.645 and 0.795 for CEUS. The interobserver agreement for CEUS was higher than that for US. (3) The sensitivity, specificity and accuracy of the diagnosis of pancreatic carcinoma with CEUS and CECT were 91.7% and 97.2%, 87.0% and 88.9%, and 88.9% and 92.2%, respectively, while for the diagnosis of pancreatitis, the corresponding indices were 82.1% and 67.9%, 91.9% and 100%, and 88.9% and 90%, respectively, showing no significant differences (p > 0.05). Conclusion: CEUS has obvious superiority over conventional US in the general diagnostic accuracy of solid pancreatic lesions and in the

  19. Analysis of achilles tendon vascularity with second-generation contrast-enhanced ultrasound.

    Science.gov (United States)

    Genovese, Eugenio; Ronga, Mario; Recaldini, Chiara; Fontana, Federico; Callegari, Leonardo; Maffulli, Nicola; Fugazzola, Carlo

    2011-01-01

    To compare morphological, power Doppler, and contrast-enhanced ultrasound (CEUS) features of the Achilles tendon between asymptomatic athletes and athletes who had undergone surgical repair of a previous rupture. Twenty-four athletes were divided in two groups (A and B). Group A included 14 patients with a median age of 32 years (range 27 to 47 years) who had undergone surgical repair for unilateral Achilles tendon rupture. Group B (control group) included 10 subjects with a median age of 34 years (range 27 to 40 years) with no previous or present history of tendinopathy. All patients were evaluated with ultrasound, power Doppler, and CEUS with second-generation contrast agent. We studied the uninjured Achilles tendon in athletes of group A and either the left or the right Achilles tendon of the athletes in group B. CEUS showed a significantly greater ability to detect a greater number of vascular spots within the uninjured tendon of group A compared to group B (power Doppler ultrasound in the uninjured contralateral Achilles tendon. CEUS is useful to evaluate vascularity not detected by other imaging techniques. Vascularity in the uninjured tendon seems to be increased in patients who had a previous rupture. Copyright © 2011 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2014-01-01

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

  1. Detection of cavernous transformation of the portal vein by contrast-enhanced ultrasound.

    Science.gov (United States)

    Hwang, Misun; Thimm, Matthew A; Guerrerio, Anthony L

    2018-06-01

    Cavernous transformation of the portal vein can be missed on color Doppler exam or arterial phase cross-sectional imaging due to their slow flow and delayed enhancement. Contrast-enhanced ultrasound (CEUS) offers many advantages over other imaging techniques and can be used to successfully detect cavernous transformations of the portal vein. A 10-month-old female was followed for repeat episodes of hematemesis. Computed tomography angiography (CTA) and magnetic resonance arteriogram (MRA) and portal venography were performed. Color Doppler exam of the portal vein was performed followed by administration of Lumason, a microbubble US contrast agent. Magnetic resonance arteriogram, CTA, and color Doppler exam at the time of initial presentation was unremarkable without obvious vascular malformation within the limits of motion degraded exam. At 8-month follow-up, esophagogastroduodenoscopy revealed a vascular malformation in the distal esophagus which was sclerosed. At 6 month after sclerosis of the lesion, portal venography revealed occlusion of the portal vein with extensive collateralization. Color Doppler revealed subtle hyperarterialization and periportal collaterals. CEUS following color Doppler exam demonstrated extensive enhancement of periportal collaterals. Repeat color Doppler after contrast administration demonstrated extensive Doppler signal in the collateral vessels, suggestive of cavernous transformation. We describe a case of cavernous transformation of the portal vein missed on initial color Doppler, CTA and MRA, but detected with contrast-enhanced ultrasound technique.

  2. Common and uncommon features of focal splenic lesions on contrast-enhanced ultrasound: a pictorial review

    Energy Technology Data Exchange (ETDEWEB)

    Zavariz, Julia D., E-mail: julia.zavariz@hc.fm.usp.br [Universidade de São Paulo (HC/FMUSP), São Paulo, SP (Brazil). Faculdade de Medicina. Hospital das Clínicas; Konstantatou, Eleni; Deganello Annamaria; Bosanac, Diana; Huang, Dean Y.; Sellars, Maria E.; Sidhu, Paul S. [Department of Radiology, King’s College Hospital, Denmark Hill, London (United Kingdom)

    2017-11-15

    The characterization of focal splenic lesions by ultrasound can be quite challenging. The recent introduction of contrast-enhanced ultrasound (CEUS) has come to play a valuable role in the field of imaging splenic pathologies, offering the possibility of an ionizing radiation-free investigation. Because CEUS has been incorporated into everyday clinical practice, malignant diseases such as focal lymphomatous infiltration, metastatic deposits, benign cysts, traumatic fractures, and hemangiomas can now be accurately depicted and characterized without the need for further imaging. More specifically, splenic traumatic fractures do not require additional imaging by computed tomography (with ionizing radiation exposure) for follow-up, because splenic fractures and their complications are safely imaged with CEUS. In the new era of CEUS, more patients benefit from radiation-free investigation of splenic pathologies with high diagnostic accuracy. (author)

  3. Nonlinear response of ultrasound contrast agent microbubbles: From fundamentals to applications

    International Nuclear Information System (INIS)

    Teng Xu-Dong; Guo Xia-Sheng; Tu Juan; Zhang Dong

    2016-01-01

    Modelling and biomedical applications of ultrasound contrast agent (UCA) microbubbles have attracted a great deal of attention. In this review, we summarize a series of researches done in our group, including (i) the development of an all-in-one solution of characterizing coated bubble parameters based on the light scattering technique and flow cytometry; (ii) a novel bubble dynamic model that takes into consideration both nonlinear shell elasticity and viscosity to eliminate the dependences of bubble shell parameters on bubble size; (iii) the evaluation of UCA inertial cavitation threshold and its relationship with shell parameters; and (iv) the investigations of transfection efficiency and the reduction of cytotoxicity in gene delivery facilitated by UCAs excited by ultrasound exposures. (special topic)

  4. Development of a platform for co-registered ultrasound and MR contrast imaging in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Chandrana, Chaitanya; Bevan, Peter; Hudson, John; Pang, Ian; Burns, Peter; Plewes, Donald; Chopra, Rajiv, E-mail: rajiv.chopra@sri.utoronto.ca [Sunnybrook Health Sciences Centre, Imaging Research, Department of Medical Biophysics, University of Toronto, 2075 Bayview Ave., Toronto, ON, M4N 3M5 (Canada)

    2011-02-07

    Imaging of the microvasculature is often performed using contrast agents in combination with either ultrasound (US) or magnetic resonance (MR) imaging. Contrast agents are used to enhance medical imaging by highlighting microvascular properties and function. Dynamic signal changes arising from the passage of contrast agents through the microvasculature can be used to characterize different pathologies; however, comparisons across modalities are difficult due to differences in the interactions of contrast agents with the microvasculature. Better knowledge of the relationship of contrast enhancement patterns with both modalities could enable better characterization of tissue microvasculature. We developed a co-registration platform for multi-modal US and MR imaging using clinical imaging systems in order to study the relationship between US and MR contrast enhancement. A preliminary validation study was performed in phantoms to determine the registration accuracy of the platform. In phantoms, the in-plane registration accuracy was measured to be 0.2 {+-} 0.2 and 0.3 {+-} 0.2 mm, in the lateral and axial directions, respectively. The out-of-plane registration accuracy was estimated to be 0.5 mm {+-}0.1. Co-registered US and MR imaging was performed in a rabbit model to evaluate contrast kinetics in different tissue types after bolus injections of US and MR contrast agents. The arrival time of the contrast agent in the plane of imaging was relatively similar for both modalities. We studied three different tissue types: muscle, large vessels and fat. In US, the temporal kinetics of signal enhancement were not strongly dependent on tissue type. In MR, however, due to the different amounts of agent extravasation in each tissue type, tissue-specific contrast kinetics were observed. This study demonstrates the feasibility of performing in vivo co-registered contrast US and MR imaging to study the relationships of the enhancement patterns with each modality.

  5. Development of a platform for co-registered ultrasound and MR contrast imaging in vivo

    Science.gov (United States)

    Chandrana, Chaitanya; Bevan, Peter; Hudson, John; Pang, Ian; Burns, Peter; Plewes, Donald; Chopra, Rajiv

    2011-02-01

    Imaging of the microvasculature is often performed using contrast agents in combination with either ultrasound (US) or magnetic resonance (MR) imaging. Contrast agents are used to enhance medical imaging by highlighting microvascular properties and function. Dynamic signal changes arising from the passage of contrast agents through the microvasculature can be used to characterize different pathologies; however, comparisons across modalities are difficult due to differences in the interactions of contrast agents with the microvasculature. Better knowledge of the relationship of contrast enhancement patterns with both modalities could enable better characterization of tissue microvasculature. We developed a co-registration platform for multi-modal US and MR imaging using clinical imaging systems in order to study the relationship between US and MR contrast enhancement. A preliminary validation study was performed in phantoms to determine the registration accuracy of the platform. In phantoms, the in-plane registration accuracy was measured to be 0.2 ± 0.2 and 0.3 ± 0.2 mm, in the lateral and axial directions, respectively. The out-of-plane registration accuracy was estimated to be 0.5 mm ±0.1. Co-registered US and MR imaging was performed in a rabbit model to evaluate contrast kinetics in different tissue types after bolus injections of US and MR contrast agents. The arrival time of the contrast agent in the plane of imaging was relatively similar for both modalities. We studied three different tissue types: muscle, large vessels and fat. In US, the temporal kinetics of signal enhancement were not strongly dependent on tissue type. In MR, however, due to the different amounts of agent extravasation in each tissue type, tissue-specific contrast kinetics were observed. This study demonstrates the feasibility of performing in vivo co-registered contrast US and MR imaging to study the relationships of the enhancement patterns with each modality.

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

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

    International Nuclear Information System (INIS)

    Konno, T.

    1990-01-01

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

  8. Contrast-enhanced ultrasound features of histologically proven focal nodular hyperplasia: diagnostic performance compared with contrast-enhanced CT

    International Nuclear Information System (INIS)

    Wang, Wei; Chen, Li-Da; Liu, Guang-Jian; Xu, Zuo-Feng; Xie, Xiao-Yan; Wang, Yan; Zhou, Lu-Yao; Lu, Ming-De; Shen, Shun-Li

    2013-01-01

    To investigate and compare contrast-enhanced ultrasound (CEUS) in the characterisation of histologically proven focal nodular hyperplasia (FNH) with contrast-enhanced computed tomography (CECT). CEUS was performed in 85 patients with 85 histologically proven FNHs. Enhancement, centrifugal filling, spoke-wheel arteries, feeding artery and central scarring were reviewed and correlated with lesion size or liver background. Independent factors for predicting FNH from other focal liver lesions (FLLs) were evaluated. Forty-seven FLLs with CECT were randomly selected for comparison of diagnostic performance with CEUS. Centrifugal filling was more common (P = 0.002) and the significant predictor (P = 0.003) in FNHs ≤3 cm. Lesion size or liver background has no significant influence on the detection rate of the spoke-wheel arteries and feeding artery (P > 0.05). Central scarring was found in 42.6 % of FNHs ≥3 cm (P = 0.000). The area under the ROC curve, sensitivity and specificity showed no significant differences between CEUS and CECT (P > 0.05), except that the sensitivity of CEUS was better for reader 1 (P = 0.041). CEUS is valuable in characterising centrifugal filling signs or spoke wheels in small FNHs and should be employed as the first-line imaging technique for diagnosis of FNH. (orig.)

  9. Rectal water contrast transvaginal ultrasound versus double-contrast barium enema in the diagnosis of bowel endometriosis.

    Science.gov (United States)

    Jiang, Jipeng; Liu, Ying; Wang, Kun; Wu, Xixiang; Tang, Ying

    2017-09-07

    The aim of study was to compare the accuracy between rectal water contrast transvaginal ultrasound (RWC-TVS) and double-contrast barium enema (DCBE) in evaluating the bowel endometriosis presence as well as its extent. 198 patients at reproductive age with suspicious bowel endometriosis were included. Physicians in two groups specialised at endometriosis performed RWC-TVS as well as DCBE before laparoscopy and both groups were blinded to other groups' results. Findings from RWC-TVS or DCBE were compared with histological results. The severity of experienced pain severity through RWC-TVS or DCBE was assessed by an analogue scale of 10 cm. In total, 110 in 198 women were confirmed to have endometriosis nodules in the bowel by laparoscopy as well as histopathology. For bowel endometriosis diagnosis, DCBE and RWC-TVS demonstrated sensitivities of 96.4% and 88.2%, specificities of 100% and 97.3%, positive prediction values of 100% and 98.0%, negative prediction values of 98.0% and 88.0%, accuracies of 98.0% and 92.4%, respectively. DCBE was related to more tolerance than RWC-TVS. RWC-TVS and DCBE demonstrated similar accuracies in the bowel endometriosis diagnosis; however, patients showed more tolerance for RWC-TVS than those with DCBE. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Contrast-enhanced ultrasound features of hepatocellular carcinoma not detected during the screening procedure.

    Science.gov (United States)

    Dong, Yi; Wang, Wen-Ping; Mao, Feng; Dietrich, Christoph

    2017-08-01

    Aim  The aim of this retrospective study is to report on the characteristics of contrast-enhanced ultrasound (CEUS) of primarily not detected hepatocellular carcinoma (HCC) during the screening procedure of patients at risk. Methods  Sixty-four patients with a finally solitary and histologically proven HCC not detected HCC during the screening procedure were retrospectively analyzed. Most of HCC lesions (90.6 %, 58/64) measured < 20 mm in diameter. All HCC lesions were not detected during the initial screening procedure but suspected using contrast-enhanced magnetic resonance imaging. The final gold standard was biopsy or surgery with histological examination. Results  On CEUS, 62/64 (96.8 %) of HCC were characterized as an obviously hyperenhanced lesion in arterial phase, and 41/64 (64.1 %) of HCC were characterized as hypoenhancing lesions in the portal venous and late phases. During the arterial phase of CEUS, 96.8 % of HCC displayed homogeneous hyperenhancement. Knowing the CEUS and magnetic resonance imaging findings, 45/64 (70.3 %) could have been detected using B-mode ultrasound (BMUS). Conclusion  BMUS as a screening procedure is generally accepted. Contrast-enhanced imaging modalities have improved detection and characterization of HCC. Homogeneous hyperenhancement during the arterial phase and mild washout are indicative for HCC in liver cirrhosis. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Lung surfactant microbubbles increase lipophilic drug payload for ultrasound-targeted delivery.

    Science.gov (United States)

    Sirsi, Shashank R; Fung, Chinpong; Garg, Sumit; Tianning, Mary Y; Mountford, Paul A; Borden, Mark A

    2013-01-01

    The cavitation response of circulating microbubbles to targeted ultrasound can be used for noninvasive, site-specific delivery of shell-loaded materials. One challenge for microbubble-mediated delivery of lipophilic compounds is the limitation of drug loading into the microbubble shell, which is commonly a single phospholipid monolayer. In this study, we investigated the use of natural lung surfactant extract (Survanta(®), Abbott Nutrition) as a microbubble shell material in order to improve drug payload and delivery. Pulmonary surfactant extracts such as Survanta contain hydrophobic surfactant proteins (SP-B and SP-C) that facilitate lipid folding and retention on lipid monolayers. Here, we show that Survanta-based microbubbles exhibit wrinkles in bright-field microscopy and increased lipid retention on the microbubble surface in the form of surface-associated aggregates observed with fluorescence microscopy. The payload of a model lipophilic drug (DiO), measured by flow cytometry, increased by over 2-fold compared to lipid-coated microbubbles lacking SP-B and SP-C. Lung surfactant microbubbles were highly echogenic to contrast enhanced ultrasound imaging at low acoustic intensities. At higher ultrasound intensity, excess lipid was observed to be acoustically cleaved for localized release. To demonstrate targeting, a biotinylated lipopolymer was incorporated into the shell, and the microbubbles were subjected to a sequence of radiation force and fragmentation pulses as they passed through an avidinated hollow fiber. Lung surfactant microbubbles showed a 3-fold increase in targeted deposition of the model fluorescent drug compared to lipid-only microbubbles. Our results demonstrate that lung surfactant microbubbles maintain the acoustic responsiveness of lipid-coated microbubbles with the added benefit of increased lipophilic drug payload.

  12. Hilar biliary neurofibroma without neurofibromatosis: case report with contrast-enhanced ultrasound findings.

    Science.gov (United States)

    Guo, Huan-Ling; Chen, Li-da; Wang, Zhu; Huang, Yang; Liu, Jin-Ya; Shan, Quan-Yuan; Xie, Xiao-Yan; Lu, Ming-de; Wang, Wei

    2016-10-01

    Solitary neurofibroma located in the hilum of the liver is extremely rare, particularly without neurofibromatosis. We herein report a case of hilar biliary neurofibroma without signs of von Recklinghausen's disease. A 36-year-old man was admitted to our department with progressive jaundice. The case was diagnosed as hilar cholangiocarcinoma based on preoperative imaging. The patient consequently received a Roux-en-Y hepaticojejunostomy and was confirmed with neurofibroma pathologically. This is the first reported imaging finding of hilar biliary neurofibroma using contrast-enhanced ultrasound, emphasizing the differential diagnosis of biliary tumors.

  13. In Vitro Investigation of the Individual Contributions of Ultrasound-Induced Stable and Inertial Cavitation in Targeted Drug Delivery.

    Science.gov (United States)

    Gourevich, Dana; Volovick, Alexander; Dogadkin, Osnat; Wang, Lijun; Mulvana, Helen; Medan, Yoav; Melzer, Andreas; Cochran, Sandy

    2015-07-01

    Ultrasound-mediated targeted drug delivery is a therapeutic modality under development with the potential to treat cancer. Its ability to produce local hyperthermia and cell poration through cavitation non-invasively makes it a candidate to trigger drug delivery. Hyperthermia offers greater potential for control, particularly with magnetic resonance imaging temperature measurement. However, cavitation may offer reduced treatment times, with real-time measurement of ultrasonic spectra indicating drug dose and treatment success. Here, a clinical magnetic resonance imaging-guided focused ultrasound surgery system was used to study ultrasound-mediated targeted drug delivery in vitro. Drug uptake into breast cancer cells in the vicinity of ultrasound contrast agent was correlated with occurrence and quantity of stable and inertial cavitation, classified according to subharmonic spectra. During stable cavitation, intracellular drug uptake increased by a factor up to 3.2 compared with the control. Reported here are the value of cavitation monitoring with a clinical system and its subsequent employment for dose optimization. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  14. Self-demodulation effect on subharmonic response of ultrasound contrast agent

    Science.gov (United States)

    Daeichin, V.; Faez, T.; Needles, A.; Renaud, G.; Bosch, J. G.; van der Steen, A. F. W.; de Jong, N.

    2012-03-01

    In this work the use of the self-demodulation (S-D) signal as a mean of microbubble excitation at the subharmonic (SH) frequency to enhance the SH emission of ultrasound contrast agent (UCA) is studied. SH emission from the UCA is of interest since it is produced only by the UCA and is free of the artifacts produced in harmonic imaging modes. The S-D wave is a low-frequency signal produced by nonlinear propagation of an ultrasound wave in the medium. Single element transducer experiments and numerical simulations were conducted at 10 MHz to study the effect of the S-D signal on the SH response of the UCA by modifying the envelope of the excitation bursts. For 6 and 20 transmitted cycles, the SH response is increased up to 25 dB and 22 dB because of the S-D stimulation for a burst with a rectangular envelope compared with a Gaussian envelope burst. Such optimized excitations were used in an array-based micro-ultrasound system (Vevo 2100, VisualSonics Inc., Toronto, ON, Canada) at 18 MHz for in vitro validation of SH imaging. This study suggests that a suitable design of the envelope of the transmit excitation to generate a S-D signal at the SH frequency can enhance the SH emission of UCA and real-time SH imaging is feasible with shorter transmit burst (6- cycle) and low acoustic pressure (~150 KPa) at high frequencies (>15 MHz).

  15. Prospective study of ultrasound with perflutrene contrast compared to magnetic resonance imaging in the diagnosis of hepatic hemangiomas

    Directory of Open Access Journals (Sweden)

    Joel Schmillevitch

    2011-06-01

    Full Text Available CONTEXT:The incidence of hepatic hemangiomas ranges from 0.4% to 20% in the general population. Conventional ultrasound is usually the first diagnostic method to identify these hemangiomas, typically as an incidental finding. Ultrasonography with second generation contrast materials is being used in various areas of hepatology, yielding similar results to those obtained with computerized tomography and magnetic resonance imaging in the diagnosis of hepatic hemangiomas. OBJECTIVE: To evaluate the agreement between ultrasound with perflutrene contrast and magnetic resonance imaging in the diagnosis of hepatic hemangiomas. METHODS: A total of 37 patients were prospectively examined between January 2006 and August 2008. A total of 57 hepatic nodules were documented in this group as incidental findings on routine ultrasound exams. The 37 patients were administered perflutrene contrast without adverse reactions, and were all submitted to magnetic resonance exams. RESULTS: Conventional ultrasound identified 15 patients with nodules typical of hemangiomas and 22 patients with other nodules. In 35 patients, the contrast characteristics were consistent with hepatic hemangiomas. CONCLUSION: Agreement between the data obtained from ultrasound with contrast and magnetic resonance was 94.5%. In discordant cases, the magnetic resonance diagnosis prevailed. In the case which presented indeterminate findings on contrast ultrasonography, magnetic resonance was repeated after 3 months, confirming the diagnosis of a hepatic hemangioma. A biopsy was performed on the suspected malignant nodule which also confirmed the presence of a hepatic hemangioma. Ultrasonography with contrast has the advantages of being more accessible to the public at large and lower cost than magnetic resonance. The results of our study highlight the need for a new protocol in hepatic nodules incidentally identified on conventional ultrasonography. In the case of typical hemangiomas

  16. Contrast-enhanced ultrasound imaging of active bleeding associated with hepatic and splenic trauma.

    Science.gov (United States)

    Lv, F; Tang, J; Luo, Y; Li, Z; Meng, X; Zhu, Z; Li, T

    2011-10-01

    The aim of this study was to evaluate contrast-enhanced ultrasound (CEUS) imaging of active bleeding from hepatic and splenic trauma. Three hundred and ninety-two patients with liver or/and spleen trauma (179 liver and 217 spleen injuries), who underwent CEUS examinations following contrast-enhanced computed tomography (CT), were enrolled in this retrospective study over a period of >4 years. CEUS detected contrast medium extravasation or pooling in 16% (63/396) of liver or spleen lesions in 61 patients, which was confirmed by contrast-enhanced CT. Special attention was paid to observing the presence, location, and characteristics of the extravasated or pooled contrast medium. The CEUS detection rate for active bleeding was not different from that of contrast-enhanced CT (p=0.333). Information from surgery, minimally invasive treatment and conservative treatment was used as reference standard, and the sensitivities of the two techniques were not different (p=0.122). Of 63 lesions in 61 patients, CEUS showed that 74.6% (47/63) (21 liver lesions and 26 spleen lesions) presented contrast medium extravasation or pooling, both in the organ and out the capsule, in 14.3% (9/63) and only outside the capsule in 11.1% (7/63). CEUS imaging of active bleeding from hepatic and splenic trauma presented various characteristics, and the sizes and shapes of the active bleeding due to contrast medium extravasation or pooling were variable. CEUS can show the active bleeding associated with hepatic and splenic trauma with various imaging characteristics, thus making it possible to diagnose active bleeding using CEUS.

  17. Contrast-enhanced ultrasound study of primary hepatic angiosarcoma: A pitfall of non-enhancement

    International Nuclear Information System (INIS)

    Wang, Liang; Lv, Ke; Chang, Xiao-Yan; Xia, Yu; Yang, Zhi-Ying; Jiang, Yu-Xin; Dai, Qing; Tan, Li; Li, Jian-Chu

    2012-01-01

    Highlights: ► The contrast-enhanced ultrasound (CEUS) characteristics of primary hepatic angiosarcoma (PHA) in three patients were retrospectively analyzed. ► PHA appeared similar peripheral enhancement pattern in our series. ► Non-necrotic tumor tissue of PHA unexpectedly demonstrated non-enhancement on CEUS. ► It may be associated with the very low velocity of blood flow in the central region of tumors. ► This interesting finding warrants further investigations, particularly on intratumoral hemodynamics. -- Abstract: Objective: To investigate the contrast-enhanced ultrasound (CEUS) characteristics of primary hepatic angiosarcoma (PHA). Methods: The sonographic findings and CEUS images of PHA in three patients were retrospectively analyzed. Results: In our study, 3 cases of PHA (2 multiple nodules and 1 solitary mass) showed similar enhancement pattern on CEUS, characterized by remarkable central non-enhancement and peripheral irregular enhancement in the arterial and portal phase, and complete wash-out in the late phase. Furthermore, we unexpectedly found that abundant neoplastic tissues were present in the central area of non-enhancement on pathological evaluation. Based on literature review, we supposed that the unusual finding may be associated with the very low velocity of blood flow in the central region of tumors. Conclusion: CEUS could well depict PHA with some common features, which may provide valuable clues in diagnosis of this rare disease. And non-necrotic tumor tissue of PHA could also demonstrate non-enhancement on CEUS, which warrant further investigations

  18. Assessment of renal perfusion with contrast-enhanced ultrasound: Preliminary results in early diabetic nephropathies.

    Science.gov (United States)

    Dong, Yi; Wang, Wen-Ping; Lin, Pan; Fan, Peili; Mao, Feng

    2016-01-01

    We performed a prospective study to evaluate the value of contrast-enhanced ultrasound (CEUS) in quantitative evaluation of renal cortex perfusion in patients suspected of early diabetic nephropathies (DN), with the estimated GFR (MDRD equation) as the gold standard. The study protocol was approved by the hospital review board; each patient gave written informed consent. Our study included 46 cases (21 males and 25 females, mean age 55.6 ± 4.14 years) of clinical confirmed early DN patients. After intravenous bolus injection of 1 ml sulfur hexafluoride microbubbles of ultrasound contrast agent, real time CEUS of renal cortex was performed successively using a 2-5 MHz convex probe. Time-intensity curves (TICs) and quantitative indexes were created with Qlab software. Receiver operating characteristic (ROC) curves were used to predict the diagnostic criteria of CEUS quantitative indexes, and their diagnostic efficiencies were compared with resistance index (RI) and peak systolic velocity (PSV) of renal segmental arteries by chi square test. Our control group included forty-five healthy volunteers. Difference was considered statistically significant with P  0.05). CEUS might be helpful to improve early diagnosis of DN by quantitative analyses. AUC and DPI might be valuable quantitative indexes.

  19. Real-time contrast-enhanced ultrasound in diagnosing of focal spleen lesions

    International Nuclear Information System (INIS)

    Yu Xiaoling; Yu Jie; Liang Ping; Liu Fangyi

    2012-01-01

    Objective: To investigate the features of focal spleen lesions (FSLs) on contrast-enhanced ultrasound (CEUS) imaging. Materials and methods: CEUS with a blot injection of SonoVue was performed in 48 patients with 75 FSLs (median diameter 2.6 cm) and their perfusion characteristics were analyzed by using contrast pulse sequences (CPS) technique. Results: Among 19 malignant lesions (10 metastases, 7 lymphoma, 1 hemangiosarcoma, 1 epithelioid hemangioendothelioma) and 56 benign lesion (23 hemangiomas, 14 cysts, 8 infarctions, 4 splenic ruptures, 3 tuberculosis, 2 abscess, 1 pseudoaneurysm, 1 lymphangioma), 25 benign lesions were demonstrated nonenhancement. For malignancy, 50.0% (5/10) metastases and 57.1% (4/7) lymphomas were showed hypoenhancement in the arterial phase, and 18 (94.7%) of malignant lesions were hypo-enhancement in the parenchymal phase. Among 31 benign lesions with enhancement, 27 (87.1%) were showed isoenhancement or hyperenhancement in the arterial phase and 22 (71.0%) lesions were isoenhancement or hyperenhancement in the parenchymal phase. The sensitivity, specificity and accuracy of diagnosis for FSLs were 91.1%, 95.0% and 92.0% for CEUS and 75.0%, 84.2% and 77.3% respectively, for the conventional baseline ultrasound (BUS). Conclusion: Real-time CEUS can provide valuable information for the diagnosis and differential diagnosis of FSLs.

  20. Voiding Urosonography with Second-Generation Ultrasound Contrast Agent for Diagnosis of Vesicoureteric Reflux: First Local Pilot Study

    Directory of Open Access Journals (Sweden)

    Dafina Kuzmanovska

    2017-04-01

    CONCLUSIONS: Contrast-enhanced voiding urosonography using intravesical second generation ultrasound contrast agent could be recommend  as a valid alternative diagnostic modality for detecting vesicoureteral reflux and evaluation of the distal urinary tract in children, based on its radiation-free, highly efficacious, reliable, and safe characteristics.

  1. Biocompatible Nanocomplexes for Molecular Targeted MRI Contrast Agent

    Science.gov (United States)

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

    2009-07-01

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

  2. Biocompatible Nanocomplexes for Molecular Targeted MRI Contrast Agent

    Directory of Open Access Journals (Sweden)

    Yu Dexin

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Paul A. Dayton

    2004-04-01

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

  4. Comparison of Oral Contrast-Enhanced Transabdominal Ultrasound Imaging With Transverse Contrast-Enhanced Computed Tomography in Preoperative Tumor Staging of Advanced Gastric Carcinoma.

    Science.gov (United States)

    He, Xuemei; Sun, Jing; Huang, Xiaoling; Zeng, Chun; Ge, Yinggang; Zhang, Jun; Wu, Jingxian

    2017-12-01

    This study assessed the diagnostic performance of transabdominal oral contrast-enhanced ultrasound (US) imaging for preoperative tumor staging of advanced gastric carcinoma by comparing it with transverse contrast-enhanced computed tomography (CT). This retrospective study included 42 patients with advanced gastric cancer who underwent laparoscopy, radical surgery, or palliative surgery because of serious complications and had a body mass index of less than 25 kg/m 2 . A cereal-based oral contrast agent was used for transabdominal oral contrast-enhanced US. Retrospective analyses were conducted using preoperative tumor staging data acquired by either transabdominal oral contrast-enhanced US or transverse contrast-enhanced CT. Both contrast-enhanced US and contrast-enhanced CT examinations were reviewed by 2 experienced radiologists independently for preoperative tumor staging according to the seventh edition of the TNM classification. The accuracy, sensitivity, and specificity were calculated by comparing the results of contrast-enhanced US and contrast-enhanced CT with pathologic findings. The overall accuracies of the imaging modalities were compared by the McNemar test. No significant difference was noted in the overall accuracy of transabdominal oral contrast-enhanced US (86% [36 of 42]) and transverse contrast-enhanced CT (83% [35 of 42] P > .999). For stage T2 to T4 gastric cancer, the accuracies of transabdominal oral contrast-enhanced US were 88%, 86%, and 98%, respectively, and those of transverse contrast-enhanced CT were 93%, 83%, and 90%. The overall accuracy of transabdominal oral contrast-enhanced US was comparable with that of transverse contrast-enhanced CT for preoperative tumor staging of advanced gastric cancer. © 2017 by the American Institute of Ultrasound in Medicine.

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

    Science.gov (United States)

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

    2015-06-01

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

  6. Combining multi-pulse excitation and chirp coding in contrast-enhanced ultrasound imaging

    International Nuclear Information System (INIS)

    Crocco, M; Sciallero, C; Trucco, A; Pellegretti, P

    2009-01-01

    The development of techniques to separate the response of the contrast agent from that of the biological tissues is of great importance in ultrasound medical imaging. In the literature, one can find various solutions involving the use of multiple transmitted signals and the weighted sum of related echoes. In this paper, the combination of one of these multi-pulse techniques with a coded excitation is proposed and assessed. Coded excitation has been used mainly to increase the signal-to-noise ratio (SNR) and the penetration depth, provided that a matched filtering is applied in the reception chain. However, it has been shown that a signal with a long duration time also increases the backscattered echoes produced by the microbubbles and, consequently, the contrast-to-tissue ratio. Therefore, the implementation of a multi-pulse technique using a long coded pulse can yield a better contrast-to-tissue ratio and SNR. This paper investigates the combination of the linear chirp pulse with a multi-pulse technique based on the transmission of three pulses. The performance was evaluated using both simulated and real signals, assessing the improvement in the contrast-to-tissue ratio and SNR, the visual quality of the images obtained and the axial accuracy. A comparison with the same multi-pulse technique implemented using a traditional amplitude-modulated pulse revealed that the deployment of a chirp pulse produces several noticeable advantages and only a minor drawback

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

    Science.gov (United States)

    Kim, Tae Kyoung; Jang, Hyun-Jung

    2014-04-07

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

  8. Contrast-enhanced color Doppler ultrasound characteristics in hypervascular breast tumors: comparison with MRI

    International Nuclear Information System (INIS)

    Alamo, L.; Fischer, U.

    2001-01-01

    The aim of this study was to evaluate the accuracy of contrast-enhanced color Doppler ultrasound (CE-US) in comparison with contrast-enhanced MR imaging (CE-MRI) in the discrimination of hypervascularized breast tumors. An additional CE-US of the breast was preoperatively performed in 40 patients with a hypervascular breast lesion detected on CE-MRI. The presence of blood flow signals and the morphological characteristics of the vessels in the breast lesions were evaluated pre- and post-contrast administration, as well as the dynamic aspects of the Doppler signal, including time interval to maximum signal enhancement and persistence of the signal enhancement. Twenty-three carcinomas and 17 fibroadenomas were explored. Considering initial signal enhancement > 100 % after the administration of contrast material as a criterion suggesting malignancy, CE-MRI showed a sensitivity of 100 % and a specificity of 76.5 % in the detection of malignant breast tumors. Color Doppler signals were consistently demonstrated in all carcinomas and in 68.7 % of fibroadenomas after the administration of Levovist, with CE-US showing a sensitivity of 95.6 % and a specificity of 5.9 %. Neither the mean number of vessels per tumor, nor the location of vessels, the time to maximum increase of the Doppler signal or the persistence of signal enhancement showed significant differences between benign and malignant lesions. Additional CE-US does not increase the low specificity of MRI in patients with hypervascularized breast tumors. (orig.)

  9. Rayleigh theory of ultrasound scattering applied to liquid-filled contrast nanoparticles.

    Science.gov (United States)

    Flegg, M B; Poole, C M; Whittaker, A K; Keen, I; Langton, C M

    2010-06-07

    We present a novel modified theory based upon Rayleigh scattering of ultrasound from composite nanoparticles with a liquid core and solid shell. We derive closed form solutions to the scattering cross-section and have applied this model to an ultrasound contrast agent consisting of a liquid-filled core (perfluorooctyl bromide, PFOB) encapsulated by a polymer shell (poly-caprolactone, PCL). Sensitivity analysis was performed to predict the dependence of the scattering cross-section upon material and dimensional parameters. A rapid increase in the scattering cross-section was achieved by increasing the compressibility of the core, validating the incorporation of high compressibility PFOB; the compressibility of the shell had little impact on the overall scattering cross-section although a more compressible shell is desirable. Changes in the density of the shell and the core result in predicted local minima in the scattering cross-section, approximately corresponding to the PFOB-PCL contrast agent considered; hence, incorporation of a lower shell density could potentially significantly improve the scattering cross-section. A 50% reduction in shell thickness relative to external radius increased the predicted scattering cross-section by 50%. Although it has often been considered that the shell has a negative effect on the echogeneity due to its low compressibility, we have shown that it can potentially play an important role in the echogeneity of the contrast agent. The challenge for the future is to identify suitable shell and core materials that meet the predicted characteristics in order to achieve optimal echogenity.

  10. Cavitation thresholds of contrast agents in an in vitro human clot model exposed to 120-kHz ultrasound.

    Science.gov (United States)

    Gruber, Matthew J; Bader, Kenneth B; Holland, Christy K

    2014-02-01

    Ultrasound contrast agents (UCAs) can be employed to nucleate cavitation to achieve desired bioeffects, such as thrombolysis, in therapeutic ultrasound applications. Effective methods of enhancing thrombolysis with ultrasound have been examined at low frequencies (cavitation thresholds for two UCAs exposed to 120-kHz ultrasound. A commercial ultrasound contrast agent (Definity(®)) and echogenic liposomes were investigated to determine the acoustic pressure threshold for ultraharmonic (UH) and broadband (BB) generation using an in vitro flow model perfused with human plasma. Cavitation emissions were detected using two passive receivers over a narrow frequency bandwidth (540-900 kHz) and a broad frequency bandwidth (0.54-1.74 MHz). UH and BB cavitation thresholds occurred at the same acoustic pressure (0.3 ± 0.1 MPa, peak to peak) and were found to depend on the sensitivity of the cavitation detector but not on the nucleating contrast agent or ultrasound duty cycle.

  11. Contrast-Enhanced Ultrasound Guided Biopsy of Undetermined Abdominal Lesions: A Multidisciplinary Decision-Making Approach

    Directory of Open Access Journals (Sweden)

    Feng Mao

    2017-01-01

    Full Text Available Aim. To investigate the value of contrast-enhanced ultrasound (CEUS guided biopsy of undetermined abdominal lesions in multidisciplinary treatment (MDT decision-making approach. Methods. Between Jan 2012 and Dec 2015, 60 consecutive patients (male, 37; female, 23; mean age, 51.3 years ± 14.6 who presented with undetermined abdominal lesions were included. CEUS and core needle percutaneous biopsy was performed under real-time CEUS guidance in all lesions. Data were recorded and compared with conventional ultrasound (US guidance group (n=75. All CEUS findings and clinical data were evaluated in MDT. Results. CEUS enabled the delimitation of more (88.3% versus 41.3% and larger (14.1 ± 10.7 mm versus 32.3 ± 18.5 mm nonenhanced necrotic areas. More inner (20.0% versus 6.7% and surrounding (18.3% versus 2.7% major vessels were visualized and avoided during biopsies. CEUS-guided biopsy increased the diagnostic accuracy from 93.3% to 98.3%, with correct diagnosis in 57 of 60 lesions (95.0%. The therapeutic plan was influenced by CEUS guided biopsies findings in the majority of patients (98.3%. Conclusion. The combination of CEUS guided biopsy and MDT decision-making approach is useful in the diagnostic work-up and therapeutic management.

  12. Contrast-Enhanced Ultrasound Guided Biopsy of Undetermined Abdominal Lesions: A Multidisciplinary Decision-Making Approach.

    Science.gov (United States)

    Mao, Feng; Dong, Yi; Ji, Zhengbiao; Cao, Jiaying; Wang, Wen-Ping

    2017-01-01

    Aim. To investigate the value of contrast-enhanced ultrasound (CEUS) guided biopsy of undetermined abdominal lesions in multidisciplinary treatment (MDT) decision-making approach. Methods. Between Jan 2012 and Dec 2015, 60 consecutive patients (male, 37; female, 23; mean age, 51.3 years ± 14.6) who presented with undetermined abdominal lesions were included. CEUS and core needle percutaneous biopsy was performed under real-time CEUS guidance in all lesions. Data were recorded and compared with conventional ultrasound (US) guidance group ( n = 75). All CEUS findings and clinical data were evaluated in MDT. Results. CEUS enabled the delimitation of more (88.3% versus 41.3%) and larger (14.1 ± 10.7 mm versus 32.3 ± 18.5 mm) nonenhanced necrotic areas. More inner (20.0% versus 6.7%) and surrounding (18.3% versus 2.7%) major vessels were visualized and avoided during biopsies. CEUS-guided biopsy increased the diagnostic accuracy from 93.3% to 98.3%, with correct diagnosis in 57 of 60 lesions (95.0%). The therapeutic plan was influenced by CEUS guided biopsies findings in the majority of patients (98.3%). Conclusion. The combination of CEUS guided biopsy and MDT decision-making approach is useful in the diagnostic work-up and therapeutic management.

  13. Applicability of contrast-enhanced ultrasound in the diagnosis of plantar fasciitis.

    Science.gov (United States)

    Broholm, R; Pingel, J; Simonsen, L; Bülow, J; Johannsen, F

    2017-12-01

    Contrast-enhanced ultrasound (CEUS) is used to visualize the microvascularization in various tissues. The purpose of this study was to investigate whether CEUS could be used to visualize the microvascular volume (MV) in the plantar fascia, and to compare the method to clinical symptoms and B-mode ultrasound (US) in patients with plantar fasciitis (PF). Twenty patients with unilateral PF were included and were divided by US in insertional thickening (10), midsubstance thickening (5), and no US changes (5). The MV was measured simultaneously in both heels. Four areas in the plantar fascia and plantar fat pad were measured independently by two observers. Inter- and intra-observer correlation analyses were performed. The asymptomatic heels showed a constantly low MV, and for the whole group of patients, a significantly higher MV was found in the symptomatic plantar fascia and plantar fat pad. Inter-observer correlation as well as intra-observer agreement was excellent. The MV in the plantar fascia and plantar fat pad can be measured reliably using CEUS, suggesting that it is a reproducible method to examine patients with plantar fasciitis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. International guidelines for contrast-enhanced ultrasonography: Ultrasound imaging in the new millennium

    International Nuclear Information System (INIS)

    Nolsoe, Christian Pallson; Lorentzen, Torben

    2016-01-01

    The intent of this review is to discuss and comment on common clinical scenarios in which contrast-enhanced ultrasonography (CEUS) may play a decisive role and to illustrate important points with typical cases. With the advent of CEUS, the scope of indications for ultrasonography has been dramatically extended, and now includes functional imaging and tissue characterization, which in many cases enable tumor diagnosis without a biopsy. It is virtually impossible to imagine the practice of modern medicine as we know it in high-income countries without the use of imaging, and yet, an estimated two thirds of the global population may receive no such care. Ultrasound imaging with CEUS has the potential to correct this inequity

  15. International guidelines for contrast-enhanced ultrasonography: Ultrasound imaging in the new millennium

    Energy Technology Data Exchange (ETDEWEB)

    Nolsoe, Christian Pallson; Lorentzen, Torben [Ultrasound Section, Dept. of Gastric Surgery, Herlev Hospital, University of Copenhagen, Herlev (Denmark)

    2016-03-15

    The intent of this review is to discuss and comment on common clinical scenarios in which contrast-enhanced ultrasonography (CEUS) may play a decisive role and to illustrate important points with typical cases. With the advent of CEUS, the scope of indications for ultrasonography has been dramatically extended, and now includes functional imaging and tissue characterization, which in many cases enable tumor diagnosis without a biopsy. It is virtually impossible to imagine the practice of modern medicine as we know it in high-income countries without the use of imaging, and yet, an estimated two thirds of the global population may receive no such care. Ultrasound imaging with CEUS has the potential to correct this inequity.

  16. Comparison between maximum radial expansion of ultrasound contrast agents and experimental postexcitation signal results.

    Science.gov (United States)

    King, Daniel A; O'Brien, William D

    2011-01-01

    Experimental postexcitation signal data of collapsing Definity microbubbles are compared with the Marmottant theoretical model for large amplitude oscillations of ultrasound contrast agents (UCAs). After taking into account the insonifying pulse characteristics and size distribution of the population of UCAs, a good comparison between simulated results and previously measured experimental data is obtained by determining a threshold maximum radial expansion (Rmax) to indicate the onset of postexcitation. This threshold Rmax is found to range from 3.4 to 8.0 times the initial bubble radius, R0, depending on insonification frequency. These values are well above the typical free bubble inertial cavitation threshold commonly chosen at 2R0. The close agreement between the experiment and models suggests that lipid-shelled UCAs behave as unshelled bubbles during most of a large amplitude cavitation cycle, as proposed in the Marmottant equation.

  17. Visual detectability of elastic contrast in real-time ultrasound images

    Science.gov (United States)

    Miller, Naomi R.; Bamber, Jeffery C.; Doyley, Marvin M.; Leach, Martin O.

    1997-04-01

    Elasticity imaging (EI) has recently been proposed as a technique for imaging the mechanical properties of soft tissue. However, dynamic features, known as compressibility and mobility, are already employed to distinguish between different tissue types in ultrasound breast examination. This method, which involves the subjective interpretation of tissue motion seen in real-time B-mode images during palpation, is hereafter referred to as differential motion imaging (DMI). The purpose of this study was to develop the methodology required to perform a series of perception experiments to measure elastic lesion detectability by means of DMI and to obtain preliminary results for elastic contrast thresholds for different lesion sizes. Simulated sequences of real-time B-scans of tissue moving in response to an applied force were generated. A two-alternative forced choice (2-AFC) experiment was conducted and the measured contrast thresholds were compared with published results for lesions detected by EI. Although the trained observer was found to be quite skilled at the task of differential motion perception, it would appear that lesion detectability is improved when motion information is detected by computer processing and converted to gray scale before presentation to the observer. In particular, for lesions containing fewer than eight speckle cells, a signal detection rate of 100% could not be achieved even when the elastic contrast was very high.

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

    Science.gov (United States)

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

    2010-12-28

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

  19. Introduction to the ultrasound targeted microbubble destruction technique.

    Science.gov (United States)

    Walton, Chad B; Anderson, Cynthia D; Boulay, Rachel; Shohet, Ralph V

    2011-06-12

    In UTMD, bioactive molecules, such as negatively charged plasmid DNA vectors encoding a gene of interest, are added to the cationic shells of lipid microbubble contrast agents. In mice these vector-carrying microbubbles can be administered intravenously or directly to the left ventricle of the heart. In larger animals they can also be infused through an intracoronary catheter. The subsequent delivery from the circulation to a target organ occurs by acoustic cavitation at a resonant frequency of the microbubbles. It seems likely that the mechanical energy generated by the microbubble destruction results in transient pore formation in or between the endothelial cells of the microvasculature of the targeted region. As a result of this sonoporation effect, the transfection efficiency into and across the endothelial cells is enhanced, and transgene-encoding vectors are deposited into the surrounding tissue. Plasmid DNA remaining in the circulation is rapidly degraded by nucleases in the blood, which further reduces the likelihood of delivery to non-sonicated tissues and leads to highly specific target-organ transfection.

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

    Science.gov (United States)

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

    2010-11-01

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

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

    Science.gov (United States)

    Mitri, F G

    2010-03-01

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

  2. Improvement of diagnostic efficiency in distinguishing the benign and malignant thyroid nodules via conventional ultrasound combined with ultrasound contrast and elastography.

    Science.gov (United States)

    Liu, Mei-Juan; Men, Yan-Ming; Zhang, Yong-Lin; Zhang, Yu-Xi; Liu, Hao

    2017-07-01

    We aimed to evaluate the diagnostic values of conventional ultrasound (US), ultrasound contrast (UC) and ultrasound elastography (UE) in distinguishing the benign and malignant thyroid nodules. A total of 100 patients with thyroid nodules receiving operative treatment were selected; they underwent the conventional US, UE and UC examinations before operation, respectively. The nodules received pathological examination after operation to distinguish benign from malignant lesions. The sensitivity, specificity and diagnostic accordance rate of each diagnostic method was evaluated by receiver operating characteristic (ROC) curve, and the area under the curve (AUC) of ROC was calculated. The manifestations of malignant thyroid nodules in conventional US examination were mostly the hypoecho, heterogeneous echo, irregular shape, unclear boundary, aspect ratio benign and malignant nodules in 2, 3 and 4 points were statistically significant (Pbenign and malignant thyroid nodules.

  3. Contrast-enhanced ultrasound imaging and in vivo circulatory kinetics with low-boiling-point nanoscale phase-change perfluorocarbon agents.

    Science.gov (United States)

    Sheeran, Paul S; Rojas, Juan D; Puett, Connor; Hjelmquist, Jordan; Arena, Christopher B; Dayton, Paul A

    2015-03-01

    Many studies have explored phase-change contrast agents (PCCAs) that can be vaporized by an ultrasonic pulse to form microbubbles for ultrasound imaging and therapy. However, few investigations have been published on the utility and characteristics of PCCAs as contrast agents in vivo. In this study, we examine the properties of low-boiling-point nanoscale PCCAs evaluated in vivo and compare data with those for conventional microbubbles with respect to contrast generation and circulation properties. To do this, we develop a custom pulse sequence to vaporize and image PCCAs using the Verasonics research platform and a clinical array transducer. Results indicate that droplets can produce contrast enhancement similar to that of microbubbles (7.29 to 18.24 dB over baseline, depending on formulation) and can be designed to circulate for as much as 3.3 times longer than microbubbles. This study also reports for the first time the ability to capture contrast washout kinetics of the target organ as a measure of vascular perfusion. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  4. Imaging of vaporised sub-micron phase change contrast agents with high frame rate ultrasound and optics

    Science.gov (United States)

    Lin, Shengtao; Zhang, Ge; Jamburidze, Akaki; Chee, Melisse; Hau Leow, Chee; Garbin, Valeria; Tang, Meng-Xing

    2018-03-01

    Phase-change ultrasound contrast agent (PCCA), or nanodroplet, shows promise as an alternative to the conventional microbubble agent over a wide range of diagnostic applications. Meanwhile, high-frame-rate (HFR) ultrasound imaging with microbubbles enables unprecedented temporal resolution compared to traditional contrast-enhanced ultrasound imaging. The combination of HFR ultrasound imaging and PCCAs can offer the opportunity to observe and better understand PCCA behaviour after vaporisation captures the fast phenomenon at a high temporal resolution. In this study, we utilised HFR ultrasound at frame rates in the kilohertz range (5-20 kHz) to image native and size-selected PCCA populations immediately after vaporisation in vitro within clinical acoustic parameters. The size-selected PCCAs through filtration are shown to preserve a sub-micron-sized (mean diameter  1 µm) that originate from native PCCA emulsion. The results demonstrate imaging signals with different amplitudes and temporal features compared to that of microbubbles. Compared with the microbubbles, both the B-mode and pulse-inversion (PI) signals from the vaporised PCCA populations were reduced significantly in the first tens of milliseconds, while only the B-mode signals from the PCCAs were recovered during the next 400 ms, suggesting significant changes to the size distribution of the PCCAs after vaporisation. It is also shown that such recovery in signal over time is not evident when using size-selective PCCAs. Furthermore, it was found that signals from the vaporised PCCA populations are affected by the amplitude and frame rate of the HFR ultrasound imaging. Using high-speed optical camera observation (30 kHz), we observed a change in particle size in the vaporised PCCA populations exposed to the HFR ultrasound imaging pulses. These findings can further the understanding of PCCA behaviour under HFR ultrasound imaging.

  5. Patterns of appearance and risk of misdiagnosis of intrahepatic cholangiocarcinoma in cirrhosis at contrast enhanced ultrasound.

    Science.gov (United States)

    Galassi, Marzia; Iavarone, Massimo; Rossi, Sandro; Bota, Simona; Vavassori, Sara; Rosa, Laura; Leoni, Simona; Venerandi, Laura; Marinelli, Sara; Sangiovanni, Angelo; Veronese, Letizia; Fraquelli, Mirella; Granito, Alessandro; Golfieri, Rita; Colombo, Massimo; Bolondi, Luigi; Piscaglia, Fabio

    2013-05-01

    Primary aim was to validate the percentage of intrahepatic cholangiocarcinomas (ICC) which have a contrast vascular pattern at contrast enhanced ultrasound (CEUS) at risk of misdiagnosis with hepatocellular carcinoma (HCC) and, secondary aim, to verify if any characteristics in the CEUS pattern helps to identify ICC. All ICC on cirrhosis seen in three Italian centres (Bologna, Milan and Pavia) between 2003 and 2011, in which CEUS and at least another imaging technique (CT or MRI) had been performed, were retrospectively identified. Those patients with ICC size comparable to the early HCC stage (Milan criteria, considered as small ICC) were enrolled for this study. The enhancement pattern at CEUS was analysed and compared with CT or MRI. A total of 25 small ICC made this study group. CEUS was at risk of misdiagnosis of ICC for HCC in a significantly higher number of cases than in CT (performed in 24 ICC) (52% vs. 4.2%, P = 0.009) and MRI (11 ICC) (52% vs. 9.1%, P = 0.02). A different contrast pattern among all techniques was found in 6 of 10 ICC lesions submitted to the three imaging methods. In the arterial phase, ICC lacked global hyperenhacement in approximately 50% of cases at CEUS and the degree of intensity of wash-out in the late phase was marked in 24% of nodules. CEUS misdiagnosed as HCC a significantly higher number of ICC lesions in cirrhotic patients than CT and MRI. However, some CEUS contrast features can help suspect ICC, especially in some cases with inconclusive CT or MRI. © 2013 John Wiley & Sons A/S.

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

    International Nuclear Information System (INIS)

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

    2003-01-01

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

  7. Ultrasound contrast agent imaging: Real-time imaging of the superharmonics

    Energy Technology Data Exchange (ETDEWEB)

    Peruzzini, D.; Viti, J. [MSD lab, Department of Information Engineering, Univ of Florence, Via S.Marta, 3, 50139 Firenze (Italy); Erasmus MC, ’s-Gravendijkwal 230, Faculty Building, Ee 2302, 3015 CE Rotterdam (Netherlands); Tortoli, P. [MSD lab, Department of Information Engineering, Univ of Florence, Via S.Marta, 3, 50139 Firenze (Italy); Verweij, M. D. [Acoustical Wavefield Imaging, ImPhys, Delft Univ Technology, van der Waalsweg 8, 2628 CH Delft (Netherlands); Jong, N. de; Vos, H. J., E-mail: h.vos@erasmusmc.nl [Erasmus MC, ’s-Gravendijkwal 230, Faculty Building, Ee 2302, 3015 CE Rotterdam (Netherlands); Acoustical Wavefield Imaging, ImPhys, Delft Univ Technology, van der Waalsweg 8, 2628 CH Delft (Netherlands)

    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.

  8. [Radiographic, MR or ultrasound contrast media in pregnant or breast-feeding women: what are the key issues?].

    Science.gov (United States)

    Fröhlich, J M; Kubik-Huch, R A

    2013-01-01

    The use and the safety of radiographic, MR- or ultrasound contrast media in the diagnostic work-up of pregnant or lactating patients is a frequently discussed question. As only sparse clinical data is available, a careful benefit-risk assessment must contain physico-chemical properties, preclinical data including teratogeneity and embryotoxicity, as well as maternal and foetal exposure. With consideration to the individual risks, iodinated contrast media, macrocyclic MR contrast media with increased stability or sulphur hexafluoride ultrasound contrast media may, if clinically justified, be administered in the smallest possible doses throughout pregnancy. After parental administration of an iodinated contrast medium after the 12th week of pregnancy, the neonate's thyroidal function should be checked during the first week after birth. After parental administration of iodinated, stable macrocyclic, gadolinium or ultrasound contrast media, lactation can be continued normally. In any case, contrast media should be used with caution and only if the benefits outweigh the risk. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Theranostic gas-generating nanoparticles for targeted ultrasound imaging and treatment of neuroblastoma.

    Science.gov (United States)

    Lee, Jangwook; Min, Hyun-Su; You, Dong Gil; Kim, Kwangmeyung; Kwon, Ick Chan; Rhim, Taiyoun; Lee, Kuen Yong

    2016-02-10

    The development of safe and efficient diagnostic/therapeutic agents for treating cancer in clinics remains challenging due to the potential toxicity of conventional agents. Although the annual incidence of neuroblastoma is not that high, the disease mainly occurs in children, a population vulnerable to toxic contrast agents and therapeutics. We demonstrate here that cancer-targeting, gas-generating polymeric nanoparticles are useful as a theranostic tool for ultrasound (US) imaging and treating neuroblastoma. We encapsulated calcium carbonate using poly(d,l-lactide-co-glycolide) and created gas-generating polymer nanoparticles (GNPs). These nanoparticles release carbon dioxide bubbles under acidic conditions and enhance US signals. When GNPs are modified using rabies virus glycoprotein (RVG) peptide, a targeting moiety to neuroblastoma, RVG-GNPs effectively accumulate at the tumor site and substantially enhance US signals in a tumor-bearing mouse model. Intravenous administration of RVG-GNPs also reduces tumor growth in the mouse model without the use of conventional therapeutic agents. This approach to developing theranostic agents with disease-targeting ability may provide useful strategy for the detection and treatment of cancers, allowing safe and efficient clinical applications with fewer side effects than may occur with conventional agents. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2007-02-01

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

  11. The Feasibility of Contrast-Enhanced Ultrasound During Uterine Artery Embolization: A Pilot Study

    International Nuclear Information System (INIS)

    Dorenberg, Eric J.; Jakobsen, Jarl A.; Brabrand, Knut; Hafsahl, Geir; Smith, Hans-Jorgen

    2007-01-01

    Purpose. To evaluate the feasibility of using contrast-enhanced ultrasound (CEUS) during uterine artery embolization (UAE) in order to define the correct end-point of embolization with complete devascularization of all fibroids. Methods. In this prospective study of 10 consecutive women undergoing UAE, CEUS was performed in the angiographic suite during embolization. When the angiographic end-point, defined as the 'pruned-tree' appearance of the uterine arteries was reached, CEUS was performed while the angiographic catheters to both uterine arteries were kept in place. The decision whether or not to continue the embolization was based on the findings at CEUS. The results of CEUS were compared with those of contrast-enhanced magnetic resonance imaging (MRI) 1 day as well as 3 months following UAE. Results. CEUS was successfully performed in all women. In 4 cases injection of particles was continued based on the findings at CEUS despite angiographically complete embolization. CEUS imaging at completion of UAE correlated well with the findings at MRI. Conclusion. The use of CEUS during UAE is feasible and may increase the quality of UAE

  12. Perfusion characteristics of parotid gland tumors evaluated by contrast-enhanced ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Klotz, Laura V., E-mail: Laura.Klotz@med.uni-muenchen.de [Department of Surgery, University of Munich, Munich (Germany); Gürkov, Robert [Department of Otorhinolaryngology, University of Munich, Munich (Germany); Eichhorn, Martin E. [Department of Surgery, University of Munich, Munich (Germany); Siedek, Vanessa; Krause, Eike [Department of Otorhinolaryngology, University of Munich, Munich (Germany); Jauch, Karl-Walter [Department of Surgery, University of Munich, Munich (Germany); Reiser, Maximilian F.; Clevert, Dirk-Andre [Department of Clinical Radiology, University of Munich, Munich (Germany)

    2013-12-01

    Purpose: Contrast enhanced ultrasound (CE-US) is a promising imaging modality for non-invasive analysis of parotid gland lesions because their vascularisation differs from normal gland tissue. This clinical study should further investigate CE-US as a diagnostic tool for parotid gland tumors. Materials and methods: 39 patients underwent CE-US measurements after intravenous application of a contrast agent (SonoVue, Bracco, Italy) before surgical tumor resection. Time–intensity curves gradients were calculated and parameters of intratumoral microcirculation were analysed. The vascularisation parameters were compared among the different tumor entities as defined per definitive histological diagnosis. Results: Histological analyses revealed 17 pleomorphic adenoma, 15 cystadenolymphoma and 7 malignoma. A significant difference of area below intensity time curve (AUC) and mean transit time (MTT) was measured in the malignant lesions compared to benign tumors (p < 0.05). A significant difference of AUC and maximum of signal increase (ΔSI{sub max}) for pleomorphic adenoma versus cystadenolymphoma was found (p < 0.05). Conclusion: CE-US seems to be a quantitative and independent method for the assessment of malign and benign parotid gland tumors. Further studies and clinical experience will have to validate this method as a reliable diagnostic tool that facilitates preoperative planning.

  13. Thrombin-Activatable Microbubbles as Potential Ultrasound Contrast Agents for the Detection of Acute Thrombosis.

    Science.gov (United States)

    Lux, Jacques; Vezeridis, Alexander M; Hoyt, Kenneth; Adams, Stephen R; Armstrong, Amanda M; Sirsi, Shashank R; Mattrey, Robert F

    2017-11-01

    Acute deep vein thrombosis (DVT) is the formation of a blood clot in the deep veins of the body that can lead to fatal pulmonary embolism. Acute DVT is difficult to distinguish from chronic DVT by ultrasound (US), the imaging modality of choice, and is therefore treated aggressively with anticoagulants, which can lead to internal bleeding. Here we demonstrate that conjugating perfluorobutane-filled (PFB-filled) microbubbles (MBs) with thrombin-sensitive activatable cell-penetrating peptides (ACPPs) could lead to the development of contrast agents that detect acute thrombosis with US imaging. Successful conjugation of ACPP to PFB-filled MBs was confirmed by fluorescence microscopy and flow cytometry. Fluorescein-labeled ACPP was used to evaluate the efficiency of thrombin-triggered cleavage by measuring the mean fluorescence intensity of ACPP-labeled MBs (ACPP-MBs) before and after incubation at 37 °C with thrombin. Lastly, control MBs and ACPP-MBs were infused through a tube containing a clot, and US contrast enhancement was measured with or without the presence of a thrombin inhibitor after washing the clot with saline. With thrombin activity, 91.7 ± 14.2% of the signal was retained after ACPP-MB infusion and washing, whereas only 16.7 ± 4% of the signal was retained when infusing ACPP-MBs in the presence of hirudin, a potent thrombin inhibitor.

  14. Evaluation of the thrombus of abdominal aortic aneurysms using contrast enhanced ultrasound - preliminary results

    Science.gov (United States)

    Łukasiewicz, Adam; Garkowski, Adam; Rutka, Katarzyna; Janica, Jacek; Łebkowska, Urszula

    2016-09-01

    It is hypothesized that the degree of vascularization of the thrombus may have a significant impact on the rupture of aortic aneurysms. The presence of neovascularization of the vessel wall and mural thrombus has been confirmed only in histopathological studies. However, no non-invasive imaging technique of qualitative assessment of thrombus and neovascularization has been implemented so far. Contrast-enhanced ultrasound (CEUS) has been proposed as a feasible and minimally invasive technique for in vivo visualization of neovascularization in the evaluation of tumors and atherosclerotic plaques. The aim of this study was the evaluation of mural thrombus and AAAs wall with CEUS. CEUS was performed in a group of seventeen patients with AAAs. The mural thrombus enhancement was recognized in 12 cases, yet no significant correlation between the degree of contrast enhancement and AAAs diameter, thrombus width, and thrombus echogenicity was found. We observed a rise in AAAs thrombus heterogeneity with the increase in the aneurysm diameter (r = 0.62, p = 0.017). In conclusion CEUS can visualize small channels within AAAs thrombus, which could be a result of an ongoing angiogenesis. There is a need for further research to find out whether the degree of vascularization of the thrombus may have a significant impact on the rupture of aneurysms.

  15. Controlling cavitation-based image contrast in focused ultrasound histotripsy surgery.

    Science.gov (United States)

    Allen, Steven P; Hall, Timothy L; Cain, Charles A; Hernandez-Garcia, Luis

    2015-01-01

    To develop MRI feedback for cavitation-based, focused ultrasound, tissue erosion surgery (histotripsy), we investigate image contrast generated by transient cavitation events. Changes in GRE image intensity are observed while balanced pairs of field gradients are varied in the presence of an acoustically driven cavitation event. The amplitude of the acoustic pulse and the timing between a cavitation event and the start of these gradient waveforms are also varied. The magnitudes and phases of the cavitation site are compared with those of control images. An echo-planar sequence is used to evaluate histotripsy lesions in ex vivo tissue. Cavitation events in water cause localized attenuation when acoustic pulses exceed a pressure threshold. Attenuation increases with increasing gradient amplitude and gradient lobe separation times and is isotropic with gradient direction. This attenuation also depends upon the relative timing between the cavitation event and the start of the balanced gradients. These factors can be used to control the appearance of attenuation while imaging ex vivo tissue. By controlling the timing between cavitation events and the imaging gradients, MR images can be made alternately sensitive or insensitive to cavitation. During therapy, these images can be used to isolate contrast generated by cavitation. © 2014 Wiley Periodicals, Inc.

  16. Ultrasound

    Science.gov (United States)

    Ultrasound is a useful procedure for monitoring the baby's development in the uterus. Ultrasound uses inaudible sound waves to produce a two-dimensional image of the baby while inside the mother's ...

  17. Noninvasive Ambient Pressure Estimation using Ultrasound Contrast Agents -- Invoking Subharmonics for Cardiac and Hepatic Applications

    Science.gov (United States)

    Dave, Jaydev K.

    Ultrasound contrast agents (UCAs) are encapsulated microbubbles that provide a source for acoustic impedance mismatch with the blood, due to difference in compressibility between the gas contained within these microbubbles and the blood. When insonified by an ultrasound beam, these UCAs act as nonlinear scatterers and enhance the echoes of the incident pulse, resulting in scattering of the incident ultrasound beam and emission of fundamental (f0), subharmonic (f0/2), harmonic (n*f0; n ∈ N) and ultraharmonic (((2n-1)/2)*f0; n ∈ N & n > 1) components in the echo response. A promising approach to monitor in vivo pressures revolves around the fact that the ultrasound transmit and receive parameters can be selected to induce an ambient pressure amplitude dependent subharmonic signal. This subharmonic signal may be used to estimate ambient pressure amplitude; such technique of estimating ambient pressure amplitude is referred to as subharmonic aided pressure estimation or SHAPE. This project develops and evaluates the feasibility of SHAPE to noninvasively monitor cardiac and hepatic pressures (using commercially available ultrasound scanners and UCAs) because invasive catheter based pressure measurements are used currently for these applications. Invasive catheter based pressure measurements pose risk of introducing infection while the catheter is guided towards the region of interest in the body through a percutaneous incision, pose risk of death due to structural or mechanical failure of the catheter (which has also triggered product recalls by the USA Food and Drug Administration) and may potentially modulate the pressures that are being measured. Also, catheterization procedures require fluoroscopic guidance to advance the catheter to the site of pressure measurements and such catheterization procedures are not performed in all clinical centers. Thus, a noninvasive technique to obtain ambient pressure values without the catheterization process is clinically

  18. Interobserver Variation of the Bolus-and-Burst Method for Pancreatic Perfusion with Dynamic – Contrast-Enhanced Ultrasound

    Czech Academy of Sciences Publication Activity Database

    Stangeland, M.; Engjom, T.; Mézl, M.; Jiřík, Radovan; Gilja, O.H.; Dimcevski, G.; Nylund, K.

    2017-01-01

    Roč. 3, č. 3 (2017), E99-E106 E-ISSN 2199-7152 Institutional support: RVO:68081731 Keywords : interobserver * dynamic contrast-enhanced ultrasound * perfusion * pancreas Subject RIV: BH - Optics, Masers, Lasers OBOR OECD: Medical engineering https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0043-110475

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

    NARCIS (Netherlands)

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

    2003-01-01

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

  20. Semi-automatic motion compensation of contrast-enhanced ultrasound images from abdominal organs for perfusion analysis

    Czech Academy of Sciences Publication Activity Database

    Schafer, S.; Nylund, K.; Saevik, F.; Engjom, T.; Mézl, M.; Jiřík, Radovan; Dimcevski, G.; Gilja, O.H.; Tönnies, K.

    2015-01-01

    Roč. 63, AUG 1 (2015), s. 229-237 ISSN 0010-4825 R&D Projects: GA ČR GAP102/12/2380 Institutional support: RVO:68081731 Keywords : ultrasonography * motion analysis * motion compensation * registration * CEUS * contrast-enhanced ultrasound * perfusion * perfusion modeling Subject RIV: FS - Medical Facilities ; Equipment Impact factor: 1.521, year: 2015

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

    Science.gov (United States)

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

    2013-09-21

    Ultrasound contrast agents (UCAs) have the potential to nucleate cavitation and promote both beneficial and deleterious bioeffects in vivo. Previous studies have elucidated the pulse-duration-dependent pressure amplitude threshold for rapid loss of echogenicity due to UCA fragmentation. Previous studies have demonstrated that UCA fragmentation was concomitant with inertial cavitation. The purpose of this study was to evaluate the relationship between stable and inertial cavitation thresholds and loss of echogenicity of UCAs as a function of pulse duration. Determining the relationship between cavitation thresholds and loss of echogenicity of UCAs would enable monitoring of cavitation based upon the onscreen echogenicity in clinical applications. Two lipid-shelled UCAs, echogenic liposomes (ELIP) and Definity®, were insonified by a clinical ultrasound scanner in duplex spectral Doppler mode at four pulse durations ('sample volumes') in both a static system and a flow system. Cavitation emissions from the UCAs insonified by Doppler pulses were recorded using a passive cavitation detection system and stable and inertial cavitation thresholds ascertained. Loss of echogenicity from ELIP and Definity® was assessed within regions of interest on B-mode images. A numerical model based on UCA rupture predicted the functional form of the loss of echogenicity from ELIP and Definity®. Stable and inertial cavitation thresholds were found to have a weak dependence on pulse duration. Stable cavitation thresholds were lower than inertial cavitation thresholds. The power of cavitation emissions was an exponential function of the loss of echogenicity over the investigated range of acoustic pressures. Both ELIP and Definity® lost more than 80% echogenicity before the onset of stable or inertial cavitation. Once this level of echogenicity loss occurred, both stable and inertial cavitation were detected in the physiologic flow phantom. These results imply that stable and inertial

  2. Investigation on the inertial cavitation threshold and shell properties of commercialized ultrasound contrast agent microbubbles.

    Science.gov (United States)

    Guo, Xiasheng; Li, Qian; Zhang, Zhe; Zhang, Dong; Tu, Juan

    2013-08-01

    The inertial cavitation (IC) activity of ultrasound contrast agents (UCAs) plays an important role in the development and improvement of ultrasound diagnostic and therapeutic applications. However, various diagnostic and therapeutic applications have different requirements for IC characteristics. Here through IC dose quantifications based on passive cavitation detection, IC thresholds were measured for two commercialized UCAs, albumin-shelled KangRun(®) and lipid-shelled SonoVue(®) microbubbles, at varied UCA volume concentrations (viz., 0.125 and 0.25 vol. %) and acoustic pulse lengths (viz., 5, 10, 20, 50, and 100 cycles). Shell elastic and viscous coefficients of UCAs were estimated by fitting measured acoustic attenuation spectra with Sarkar's model. The influences of sonication condition (viz., acoustic pulse length) and UCA shell properties on IC threshold were discussed based on numerical simulations. Both experimental measurements and numerical simulations indicate that IC thresholds of UCAs decrease with increasing UCA volume concentration and acoustic pulse length. The shell interfacial tension and dilatational viscosity estimated for SonoVue (0.7 ± 0.11 N/m, 6.5 ± 1.01 × 10(-8) kg/s) are smaller than those of KangRun (1.05 ± 0.18 N/m, 1.66 ± 0.38 × 10(-7) kg/s); this might result in lower IC threshold for SonoVue. The current results will be helpful for selecting and utilizing commercialized UCAs for specific clinical applications, while minimizing undesired IC-induced bioeffects.

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

    Science.gov (United States)

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

    2013-09-01

    Ultrasound contrast agents (UCAs) have the potential to nucleate cavitation and promote both beneficial and deleterious bioeffects in vivo. Previous studies have elucidated the pulse-duration-dependent pressure amplitude threshold for rapid loss of echogenicity due to UCA fragmentation. Previous studies have demonstrated that UCA fragmentation was concomitant with inertial cavitation. The purpose of this study was to evaluate the relationship between stable and inertial cavitation thresholds and loss of echogenicity of UCAs as a function of pulse duration. Determining the relationship between cavitation thresholds and loss of echogenicity of UCAs would enable monitoring of cavitation based upon the onscreen echogenicity in clinical applications. Two lipid-shelled UCAs, echogenic liposomes (ELIP) and Definity®, were insonified by a clinical ultrasound scanner in duplex spectral Doppler mode at four pulse durations (‘sample volumes’) in both a static system and a flow system. Cavitation emissions from the UCAs insonified by Doppler pulses were recorded using a passive cavitation detection system and stable and inertial cavitation thresholds ascertained. Loss of echogenicity from ELIP and Definity® was assessed within regions of interest on B-mode images. A numerical model based on UCA rupture predicted the functional form of the loss of echogenicity from ELIP and Definity®. Stable and inertial cavitation thresholds were found to have a weak dependence on pulse duration. Stable cavitation thresholds were lower than inertial cavitation thresholds. The power of cavitation emissions was an exponential function of the loss of echogenicity over the investigated range of acoustic pressures. Both ELIP and Definity® lost more than 80% echogenicity before the onset of stable or inertial cavitation. Once this level of echogenicity loss occurred, both stable and inertial cavitation were detected in the physiologic flow phantom. These results imply that stable and

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

    International Nuclear Information System (INIS)

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

    2013-01-01

    Ultrasound contrast agents (UCAs) have the potential to nucleate cavitation and promote both beneficial and deleterious bioeffects in vivo. Previous studies have elucidated the pulse-duration-dependent pressure amplitude threshold for rapid loss of echogenicity due to UCA fragmentation. Previous studies have demonstrated that UCA fragmentation was concomitant with inertial cavitation. The purpose of this study was to evaluate the relationship between stable and inertial cavitation thresholds and loss of echogenicity of UCAs as a function of pulse duration. Determining the relationship between cavitation thresholds and loss of echogenicity of UCAs would enable monitoring of cavitation based upon the onscreen echogenicity in clinical applications. Two lipid-shelled UCAs, echogenic liposomes (ELIP) and Definity®, were insonified by a clinical ultrasound scanner in duplex spectral Doppler mode at four pulse durations (‘sample volumes’) in both a static system and a flow system. Cavitation emissions from the UCAs insonified by Doppler pulses were recorded using a passive cavitation detection system and stable and inertial cavitation thresholds ascertained. Loss of echogenicity from ELIP and Definity® was assessed within regions of interest on B-mode images. A numerical model based on UCA rupture predicted the functional form of the loss of echogenicity from ELIP and Definity®. Stable and inertial cavitation thresholds were found to have a weak dependence on pulse duration. Stable cavitation thresholds were lower than inertial cavitation thresholds. The power of cavitation emissions was an exponential function of the loss of echogenicity over the investigated range of acoustic pressures. Both ELIP and Definity® lost more than 80% echogenicity before the onset of stable or inertial cavitation. Once this level of echogenicity loss occurred, both stable and inertial cavitation were detected in the physiologic flow phantom. These results imply that stable and

  5. Fabrication and imaging study of ultrasound/fluorescence bi-modal contrast agent based on polymeric microbubbles

    International Nuclear Information System (INIS)

    Xing Zhanwen; Ke Hengte; Wang Jinrui; Zhao Bo; Qu Enze; Yue Xiuli; Dai Zhifei

    2013-01-01

    Objective: To fabricate an ultrasound/fluorescence bi-modal contrast agent by encapsulating fluorescent quantum dots into polymeric ultrasound contrast agent microbubbles. Methods: Polylactic acid (PLA, 500 mg), (1R)-(+)-camphor (50 mg) and CdSe/ZnS quantum dots (0.5 ml, 2.3 μmol/L)were dissolved or dispersed in dichloromethane (10 ml) to form in an organic phase. Ammonium carbonate solution and poly (vinyl alcohol) solution were employed as the internal and external water phase, respectively. The fluorescent microbubbles were generated using double emulsion solvent evaporation and lyophilization methods. The morphology and illumination were characterized by scanning electron microscopy (SEM) and fluorescence spectrophotometry. Synchronized contrast-enhanced ultrasound and fluorescence imaging was acquired by injecting fluorescent microbubbles into the silicone tube coupled to a self-made ultrasound/fluorescence imaging device. Ultrasound/fluorescence bi-modal in vivo imaging was acquired on the kidney of New Zealand rabbits and suckling mice. Results: The fluorescent microbubbles were hollow spheres with an averaged diameter of (1.62 ± 1.47) μm. More than 99% of these microbubbles were less than 8 μm in diameter, which met the size criteria for ultrasound contrast agents. The fluorescence emission peak of the microbubbles appeared at 632 nm, indicating that good luminescence properties of quantum dots were maintained. In vitro ultrasound/fluorescence imaging showed no echoic signal when the silicone tube was filled with saline, but there was a strong echo when filled with fluorescent microbubbles. The liquid column with fluorescent microbubbles emitted red luminescence under ultraviolet irradiation. The kidney of the rabbit was remarkably enhanced after the administration of fluorescent microbubbles. Bright fluorescence could be observed at the injection site of the suckling mice via subcutaneous injection. Conclusions: A bi-modal but single contrast agent

  6. Ultrasound-enhanced delivery of targeted echogenic liposomes in a novel ex vivo mouse aorta model.

    Science.gov (United States)

    Hitchcock, Kathryn E; Caudell, Danielle N; Sutton, Jonathan T; Klegerman, Melvin E; Vela, Deborah; Pyne-Geithman, Gail J; Abruzzo, Todd; Cyr, Peppar E P; Geng, Yong-Jian; McPherson, David D; Holland, Christy K

    2010-06-15

    The goal of this study was to determine whether targeted, Rhodamine-labeled echogenic liposomes (Rh-ELIP) containing nanobubbles could be delivered to the arterial wall, and whether 1-MHz continuous wave ultrasound would enhance this delivery profile. Aortae excised from apolipoprotein-E-deficient (n=8) and wild-type (n=8) mice were mounted in a pulsatile flow system through which Rh-ELIP were delivered in a stream of bovine serum albumin. Half the aortae from each group were treated with 1-MHz continuous wave ultrasound at 0.49 MPa peak-to-peak pressure, and half underwent sham exposure. Ultrasound parameters were chosen to promote stable cavitation and avoid inertial cavitation. A broadband hydrophone was used to monitor cavitation activity. After treatment, aortic sections were prepared for histology and analyzed by an individual blinded to treatment conditions. Delivery of Rh-ELIP to the vascular endothelium was observed, and sub-endothelial penetration of Rh-ELIP was present in five of five ultrasound-treated aortae and was absent in those not exposed to ultrasound. However, the degree of penetration in the ultrasound-exposed aortae was variable. There was no evidence of ultrasound-mediated tissue damage in any specimen. Ultrasound-enhanced delivery within the arterial wall was demonstrated in this novel model, which allows quantitative evaluation of therapeutic delivery. Copyright (c) 2010 Elsevier B.V. All rights reserved.

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

    DEFF Research Database (Denmark)

    Rafaelsen, S R; Jakobsen, A

    2011-01-01

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

  8. Inhibition of prostate cancer growth using doxorubicin assisted by ultrasound-targeted nanobubble destruction

    Directory of Open Access Journals (Sweden)

    Fan X

    2016-07-01

    Full Text Available Xiaozhou Fan,1,* Luofu Wang,2,* Yanli Guo,1 Xingyu Xiong,1 Lianhua Zhu,1 Kejing Fang1 1Department of Ultrasound, Southwest Hospital, 2Department of Urology, Daping Hospital, Third Military Medical University, Chongqing, People’s Republic of China *These authors contributed equally to this work Abstract: Ultrasound (US-targeted microbubble destruction has been widely used as an effective drug-delivery system. However, nanobubbles (NBs have better stability and stronger penetration than microbubbles, and drug delivery assisted by US-targeted NB destruction (UTND still needs to be investigated. Our aim was to investigate the effect of doxorubicin (DOX on the inhibition of prostate cancer growth under UTND. Contrast-enhanced US imaging of transplanted PC3 prostate cancer in mice showed that under a combination of 1 W/cm2 US power and a 100 Hz intermittent pulse with a “5 seconds on, 5 seconds off” mode, NBs with an average size of (485.7±33 nm were effectively destroyed within 15 minutes in the tumor location. PC3 cells and 20 tumor-bearing mice were divided into four groups: a DOX group, a DOX + NB group, a DOX + US group, and a DOX + NB + US group. The cell growth-inhibition rate and DOX concentration of xenografts in the DOX + NB + US group were highest. Based on another control group and these four groups, another 25 tumor-bearing mice were used to observe the treatment effect of nine DOX injections under UTND. The xenografts in the DOX + NB + US group decreased more obviously and had more cellular apoptosis than other groups. Finally, electron microscopy was used to estimate the cavitation effect of NBs under US irradiation in the control group, NB group, US group, and NB + US group. The results of scanning electron microscopy showed that PC3 cells in the DOX + NB + US group had more holes and significantly increased cell-surface folds. Meanwhile, transmission electric microscopy confirmed that more lanthanum nitrate particles entered

  9. First-in-Human Ultrasound Molecular Imaging With a VEGFR2-Specific Ultrasound Molecular Contrast Agent (BR55) in Prostate Cancer: A Safety and Feasibility Pilot Study.

    Science.gov (United States)

    Smeenge, Martijn; Tranquart, François; Mannaerts, Christophe K; de Reijke, Theo M; van de Vijver, Marc J; Laguna, M Pilar; Pochon, Sibylle; de la Rosette, Jean J M C H; Wijkstra, Hessel

    2017-07-01

    BR55, a vascular endothelial growth factor receptor 2 (VEGFR2)-specific ultrasound molecular contrast agent (MCA), has shown promising results in multiple preclinical models regarding cancer imaging. In this first-in-human, phase 0, exploratory study, we investigated the feasibility and safety of the MCA for the detection of prostate cancer (PCa) in men using clinical standard technology. Imaging with the MCA was performed in 24 patients with biopsy-proven PCa scheduled for radical prostatectomy using a clinical ultrasound scanner at low acoustic power. Safety monitoring was done by physical examination, blood pressure and heart rate measurements, electrocardiogram, and blood sampling. As first-in-human study, MCA dosing and imaging protocol were necessarily fine-tuned along the enrollment to improve visualization. Imaging data were correlated with radical prostatectomy histopathology to analyze the detection rate of ultrasound molecular imaging with the MCA. Imaging with MCA doses of 0.03 and 0.05 mL/kg was adequate to obtain contrast enhancement images up to 30 minutes after administration. No serious adverse events or clinically meaningful changes in safety monitoring data were identified during or after administration. BR55 dosing and imaging were fine-tuned in the first 12 patients leading to 12 subsequent patients with an improved MCA dosing and imaging protocol. Twenty-three patients underwent radical prostatectomy. A total of 52 lesions were determined to be malignant by histopathology with 26 (50%) of them seen during BR55 imaging. In the 11 patients that were scanned with the improved protocol and underwent radical prostatectomy, a total of 28 malignant lesions were determined: 19 (68%) were seen during BR55 ultrasound molecular imaging, whereas 9 (32%) were not identified. Ultrasound molecular imaging with BR55 is feasible with clinical standard technology and demonstrated a good safety profile. Detectable levels of the MCA can be reached in patients

  10. Application of parametric ultrasound contrast agent perfusion studies for differentiation of hyperplastic adrenal nodules from adenomas—Initial study

    Energy Technology Data Exchange (ETDEWEB)

    Slapa, Rafal Z., E-mail: rz.slapa@gmail.com [Diagnostic Imaging Department, Medical University of Warsaw, Second Faculty of Medicine with English and Physiotherapy Divisions, Warsaw (Poland); Kasperlik–Zaluska, Anna A. [Endocrinology Department, Center for Postgraduate Medical Education, Bielanski Hospital, Warsaw (Poland); Migda, Bartosz [Diagnostic Imaging Department, Medical University of Warsaw, Second Faculty of Medicine with English and Physiotherapy Divisions, Warsaw (Poland); Otto, Maciej [Department of General, Vascular and Transplant Surgery, Medical University of Warsaw, First Faculty of Medicine, Warsaw (Poland); Jakubowski, Wiesław S. [Diagnostic Imaging Department, Medical University of Warsaw, Second Faculty of Medicine with English and Physiotherapy Divisions, Warsaw (Poland)

    2015-08-15

    Highlights: • Adrenal masses may differ on parametric perfusion ultrasound. • Hyperplastic nodules present distinctive patterns on CEUS in regard to adenomas. • Adrenal lesions perfusion should be further investigated with different modalities. - Abstract: Objectives: To evaluate the possibilities of differentiation of non-malignant adrenal masses with the application of the new technique for the evaluation of enhancement after administration of an ultrasound contrast agent: parametric imaging. Patients and Methods: 34 non-malignant adrenal masses in 29 patients were evaluated in a dynamic examination after the administration of ultrasound contrast agent with parametric imaging. Patterns on parametric imaging of arrival time were evaluated. The final diagnosis was based on CT, MRI, biochemical studies, follow up and/or histopathology examination. Results: The study included: 12 adenomas, 10 hyperplastic nodules, 7 myelolipomas, 3 pheochromocytomas, hemangioma with hemorrhage and cyst. The pattern of peripheral laminar inflow of Sonovue on parametric images of arrival time of was 100% sensitive for hyperplastic nodules and 83% specific in regard to adenomas. Conclusions: Parametric contrast enhanced ultrasound may accurately differentiate hyperplastic adrenal nodules from adenomas and could be complementary to CT or MRI. Incorporation of perfusion studies to CT or MRI could possibly enable one-shop complete characterization of adrenal masses. This could deliver additional information in diagnostics of patients with Conn Syndrome and warrants further studies in this cohort of patients.

  11. Application of parametric ultrasound contrast agent perfusion studies for differentiation of hyperplastic adrenal nodules from adenomas—Initial study

    International Nuclear Information System (INIS)

    Slapa, Rafal Z.; Kasperlik–Zaluska, Anna A.; Migda, Bartosz; Otto, Maciej; Jakubowski, Wiesław S.

    2015-01-01

    Highlights: • Adrenal masses may differ on parametric perfusion ultrasound. • Hyperplastic nodules present distinctive patterns on CEUS in regard to adenomas. • Adrenal lesions perfusion should be further investigated with different modalities. - Abstract: Objectives: To evaluate the possibilities of differentiation of non-malignant adrenal masses with the application of the new technique for the evaluation of enhancement after administration of an ultrasound contrast agent: parametric imaging. Patients and Methods: 34 non-malignant adrenal masses in 29 patients were evaluated in a dynamic examination after the administration of ultrasound contrast agent with parametric imaging. Patterns on parametric imaging of arrival time were evaluated. The final diagnosis was based on CT, MRI, biochemical studies, follow up and/or histopathology examination. Results: The study included: 12 adenomas, 10 hyperplastic nodules, 7 myelolipomas, 3 pheochromocytomas, hemangioma with hemorrhage and cyst. The pattern of peripheral laminar inflow of Sonovue on parametric images of arrival time of was 100% sensitive for hyperplastic nodules and 83% specific in regard to adenomas. Conclusions: Parametric contrast enhanced ultrasound may accurately differentiate hyperplastic adrenal nodules from adenomas and could be complementary to CT or MRI. Incorporation of perfusion studies to CT or MRI could possibly enable one-shop complete characterization of adrenal masses. This could deliver additional information in diagnostics of patients with Conn Syndrome and warrants further studies in this cohort of patients

  12. Effect of microbubble ligation to cells on ultrasound signal enhancement: implications for targeted imaging.

    Science.gov (United States)

    Lankford, Miles; Behm, Carolyn Z; Yeh, James; Klibanov, Alexander L; Robinson, Peter; Lindner, Jonathan R

    2006-10-01

    Molecular imaging with contrast-enhanced ultrasound (CEU) relies on the detection of microbubbles retained in regions of disease. The aim of this study was to determine whether microbubble attachment to cells influences their acoustic signal generation and stability. Biotinylated microbubbles were attached to streptavidin-coated plates to derive density versus intensity relations during low- and high-power imaging. To assess damping from microbubble attachment to solid or cell surfaces, in vitro imaging was performed for microbubbles charge-coupled to methacrylate spheres and for vascular cell adhesion molecule-1-targeted microbubbles attached to endothelial cells. Signal enhancement on plates increased according to acoustic power and microbubble site density up to 300 mm. Microbubble signal was reduced by attachment to solid spheres during high- and low-power imaging but was minimally reduced by attachment to endothelial cells and only at low power. Attachment of targeted microbubbles to rigid surfaces results in damping and a reduction of their acoustic signal, which is not seen when microbubbles are attached to cells. A reliable concentration versus intensity relationship can be expected from microbubble attachment to 2-dimensional surfaces until a very high site density is reached.

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

    Science.gov (United States)

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

    2012-06-01

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

  14. Contrast enhanced ultrasound in the evaluation and percutaneous treatment of hepatic and renal tumors

    International Nuclear Information System (INIS)

    Meloni, Maria Franca; Smolock, Amanda; Cantisani, Vito; Bezzi, Mario; D'Ambrosio, Ferdinando; Proiti, Maria; Lee, Fred; Aiani, Luca; Calliada, Fabrizio; Ferraioli, Giovanna

    2015-01-01

    Highlights: • Image-guided percutaneous ablation techniques are increasingly being used for the treatment of malignant tumors of the liver and kidney when surgery is not indicated. • Percutaneous ablation relies on imaging at every step of the process in order to detect, guide, and confirm complete tumor coagulation. • CEUS is a real-time dynamic imaging technique that plays an important role in the management of patients treated with ablation for malignant tumors. • This review focuses on the role of CEUS in the evaluation of patients undergoing percutaneous treatments for hepatic and renal tumors. - Abstract: Image-guided percutaneous ablation techniques are increasingly being used for the treatment of malignant tumors of the liver and kidney. Contrast enhanced ultrasound (CEUS) is a real-time dynamic imaging technique that plays an important role in the pre-, intra-, and post-procedural management of these patients. This review will focus on the role of CEUS in the evaluation of patients undergoing treatment with percutaneous ablation for hepatic or renal tumors

  15. Evaluation of breast lesions by contrast enhanced ultrasound: Qualitative and quantitative analysis

    International Nuclear Information System (INIS)

    Wan Caifeng; Du Jing; Fang Hua; Li Fenghua; Wang Lin

    2012-01-01

    Objective: To evaluate and compare the diagnostic performance of qualitative, quantitative and combined analysis for characterization of breast lesions in contrast enhanced ultrasound (CEUS), with histological results used as the reference standard. Methods: Ninety-one patients with 91 breast lesions BI-RADS 3–5 at US or mammography underwent CEUS. All lesions underwent qualitative and quantitative enhancement evaluation. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of different analytical method for discrimination between benign and malignant breast lesions. Results: Histopathologic analysis of the 91 lesions revealed 44 benign and 47 malignant. For qualitative analysis, benign and malignant lesions differ significantly in enhancement patterns (p z1 ), 0.768 (A z2 ) and 0.926(A z3 ) respectively. The values of A z1 and A z3 were significantly higher than that for A z2 (p = 0.024 and p = 0.008, respectively). But there was no significant difference between the values of A z1 and A z3 (p = 0.625). Conclusions: The diagnostic performance of qualitative and combined analysis was significantly higher than that for quantitative analysis. Although quantitative analysis has the potential to differentiate benign from malignant lesions, it has not yet improved the final diagnostic accuracy.

  16. Contrast-enhanced ultrasound of focal nodular hyperplasia: a matter of size

    Energy Technology Data Exchange (ETDEWEB)

    Bertin, Caroline [Hopital Beaujon APHP, Radiology Department, Clichy (France); Egels, Sophie; Huynh-Charlier, Isabelle [Hopital Pitie-Salpetriere APHP, Radiology Department, Paris (France); Wagner, Mathilde [Hopital Pitie-Salpetriere APHP, Radiology Department, Paris (France); Universite Paris Diderot, INSERM, UMR 1149, Laboratoire IPMA, Centre de Recherche sur l' Inflammation, Faculte de Medecine X Bichat, Paris (France); Vilgrain, Valerie [Hopital Beaujon APHP, Radiology Department, Clichy (France); Universite Paris Diderot, INSERM, UMR 1149, Laboratoire IPMA, Centre de Recherche sur l' Inflammation, Faculte de Medecine X Bichat, Paris (France); Lucidarme, Olivier [Hopital Pitie-Salpetriere APHP, Radiology Department, Paris (France); Sorbonne Universites, UPMC Univ Paris 06, CNRS UMR 7371, INSERM UMRS 1146, Laboratoire d' Imagerie Biomedicale, Paris (France); Groupe Hospitalier Pitie-Salpetriere - Charles Foix, Service de Radiologie Polyvalente et Oncologique, Paris (France)

    2014-10-15

    To assess the contrast-enhanced ultrasound (CEUS) frequencies of centrifugal enhancement, spoke-wheel sign and central scar in focal nodular hyperplasia (FNH) as a function of lesion size. Ninety-four FNHs were retrospectively reviewed to assess their largest diameter and enhancement pattern, including centrifugal enhancement from one central artery, spoke-wheel sign, diffuse or centripetal enhancement, central scar and late-phase washout. Mean FNH-lesion size was 3.7 ± 2.1 cm. Only 43.6 % of FNHs had centrifugal enhancement, with a spoke-wheel pattern (23.4 %) or without (20.2 %), while 56.4 % showed diffuse or centripetal enhancement. Centrifugal enhancement was observed in 73.9 % of FNHs ≤3.1 cm and 14.6 % of FNHs >3.1 cm (P < 10{sup -4}). Size and frequency of centrifugal enhancement were negatively correlated (r = -0.57, P < 10{sup -4}). The spoke-wheel pattern was also seen more frequently in smaller (37 %) than in larger FNHs (10.4 %) (P < 10{sup -3}). Late-phase washout was described in 5.3 % of FNHs and was not size-dependent. Lesions with a central scar were larger than those without, respectively, 5.7 ± 1.7 and 3.6 ± 2.0 cm (P = 0.012). Typical centrifugal enhancement yielding a confident FNH diagnosis is seen significantly more frequently when the lesion is ≤3.1 cm. (orig.)

  17. Differential diagnosis of gastric cancer and gastritis: the role of contrast-enhanced ultrasound (CEUS).

    Science.gov (United States)

    Xue, Heng; Ge, Hui-Yu; Miao, Li-Ying; Wang, Shu-Min; Zhao, Bo; Wang, Jin-Rui; Cui, Li-Gang

    2017-03-01

    To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in differential diagnosis of gastric cancer and gastritis, with histological results as reference standard. From September 2011 to August 2014, 82 patients (50 males and 32 females; mean age ± SD, 59.5 ± 15.0 years; range 19-91 years) with gastric cancer or gastritis were included in this Ethics Committee-approved prospective study. Conventional ultrasonography (US) and CEUS were applied to distinguish the two lesions, and both qualitative and quantitative features were evaluated. Of the 82 histopathologic-proven lesions, 58 were cancer and 24 were gastritis. For US, the gastric wall stratification was not preserved in about one-third of cancer (21/58, 36.2%) compared with gastritis (0/24, 0%) (p gastritis (19/24, 79.2%, p gastritis. CEUS has the potential to make the diagnosis more accurate.

  18. Hepatic contrast-enhance ultrasound: impact of its introduction in the Australian context

    International Nuclear Information System (INIS)

    Won, So Yeun; Singh, Neha; Lim, Beng Ghee; Stella, Damien; Gibson, Robert

    2014-01-01

    Contrast-enhanced ultrasound (CEUS) is a relatively new imaging modality in Australia. We discuss our early experience with CEUS at Royal Melbourne Hospital in assessment of focal liver lesions and its clinical impact. Radiology department and hospital computerised information systems were used to identify and collate information regarding the indication, previous and follow-up imaging, CEUS findings and subsequent final diagnoses of patients who underwent hepatic CEUS from 12/12/2007 to 20/4/2012. A total of 388 hepatic CEUS were performed, examining 409 lesions. The cases were grouped as either 'initial study' or 'follow-up' group, with main focus on the former group. Of the 367 lesions in the 'initial study' group, CEUS was able to distinguish benign from malignant pathology in 344 cases (93.8%). This was especially beneficial in setting of known malignancy with indeterminate liver lesions found on CT to confidently exclude metastatic disease. For 124 of 162 patients who had an incidentally detected indeterminate liver lesion, CEUS was the final imaging investigation required to make a diagnosis. CEUS is a valuable tool in assessment of focal liver lesions in conjunction with other conventional modalities in a variety of clinical settings. In particular, it provided definitive diagnosis in a significant proportion of incidentally identified liver lesions many of which are benign, saving patient anxiety and further unnecessary follow-up.

  19. Influence of ageing on quantitative contrast-enhanced ultrasound of the kidneys in healthy cats.

    Science.gov (United States)

    Stock, Emmelie; Paepe, Dominique; Daminet, Sylvie; Duchateau, Luc; Saunders, Jimmy H; Vanderperren, Katrien

    2018-05-05

    The degenerative effects of ageing on the kidneys have been extensively studied in humans. However, only recently interest has been focused on renal ageing in veterinary medicine. Contrast-enhanced ultrasound allows non-invasive evaluation of renal perfusion in conscious cats. Renal perfusion parameters were obtained in 43 healthy cats aged 1-16 years old, and the cats were divided in four age categories: 1-3 years, 3-6 years, 6-10 years and over 10 years. Routine renal parameters as serum creatinine, serum urea, urine-specific gravity, urinary protein:creatinine ratio and systolic blood pressure were also measured. No significant differences in any of the perfusion parameters were observed among the different age categories. A trend towards a lower peak enhancement and wash-in area under the curve with increasing age, suggestive for a lower blood volume, was detected when comparing the cats over 10 years old with the cats of 1-3 years old. Additionally, no significant age-effect was observed for the serum and urine parameters, whereas a higher blood pressure was observed in healthy cats over 10 years old. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Quantitative contrast enhanced ultrasound of the liver for time intensity curves-Reliability and potential sources of errors.

    Science.gov (United States)

    Ignee, Andre; Jedrejczyk, Maciej; Schuessler, Gudrun; Jakubowski, Wieslaw; Dietrich, Christoph F

    2010-01-01

    Time intensity curves for real-time contrast enhanced low MI ultrasound is a promising technique since it adds objective data to the more subjective conventional contrast enhanced technique. Current developments showed that the amount of uptake in modern targeted therapy strategies correlates with therapy response. Nevertheless no basic research has been done concerning the reliability and validity of the method. Videos sequences of 31 consecutive patients for at least 60s were recorded. Parameters analysed: area under the curve, maximum intensity, mean transit time, perfusion index, time to peak, rise time. The influence of depth, lateral shift as well as size and shape of the region of interest was analysed. The parameters time to peak and rise time showed a good stability in different depths. Overall there was a variation >50% for all other parameters. Mean transit time, time to peak and rise time were stable from 3 to 10cm depths, whereas all other parameters showed only satisfying results at 4-6cm. Time to peak and rise time were stable as well against lateral shifting whereas all other parameters had again variations over 50%. Size and shape of the region of interest did not influence the results. (1) It is important to compare regions of interest, e.g. in a tumour vs. representative parenchyma in the same depths. (2) Time intensity curves should not be analysed in a depth of less than 4cm. (3) The parameters area under the curve, perfusion index and maximum intensity should not be analysed in a depth more than 6cm. (4) Size and shape of a region of interest in liver parenchyma do not affect time intensity curves. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  1. Quantitative contrast enhanced ultrasound of the liver for time intensity curves-Reliability and potential sources of errors

    Energy Technology Data Exchange (ETDEWEB)

    Ignee, Andre [Department of Internal Medicine and Diagnostic Imaging, Caritas Hospital, Uhlandstr. 7, 97990 Bad Mergentheim (Germany)], E-mail: andre.ignee@gmx.de; Jedrejczyk, Maciej [Department of Diagnostic Imaging, 2nd Division of Medical Faculty, Medical University, Ul. Kondratowicza 8, 03-242 Warsaw (Poland)], E-mail: mjedrzejczyk@interia.pl; Schuessler, Gudrun [Department of Internal Medicine and Diagnostic Imaging, Caritas Hospital, Uhlandstr. 7, 97990 Bad Mergentheim (Germany)], E-mail: gudrunschuessler@gmx.de; Jakubowski, Wieslaw [Department of Diagnostic Imaging, 2nd Division of Medical Faculty, Medical University, Ul. Kondratowicza 8, 03-242 Warsaw (Poland)], E-mail: ewajbmd@go2.pl; Dietrich, Christoph F. [Department of Internal Medicine and Diagnostic Imaging, Caritas Hospital, Uhlandstr. 7, 97990 Bad Mergentheim (Germany)], E-mail: christoph.dietrich@ckbm.de

    2010-01-15

    Introduction: Time intensity curves for real-time contrast enhanced low MI ultrasound is a promising technique since it adds objective data to the more subjective conventional contrast enhanced technique. Current developments showed that the amount of uptake in modern targeted therapy strategies correlates with therapy response. Nevertheless no basic research has been done concerning the reliability and validity of the method. Patients and methods: Videos sequences of 31 consecutive patients for at least 60 s were recorded. Parameters analysed: area under the curve, maximum intensity, mean transit time, perfusion index, time to peak, rise time. The influence of depth, lateral shift as well as size and shape of the region of interest was analysed. Results: The parameters time to peak and rise time showed a good stability in different depths. Overall there was a variation >50% for all other parameters. Mean transit time, time to peak and rise time were stable from 3 to 10 cm depths, whereas all other parameters showed only satisfying results at 4-6 cm. Time to peak and rise time were stable as well against lateral shifting whereas all other parameters had again variations over 50%. Size and shape of the region of interest did not influence the results. Discussion: (1) It is important to compare regions of interest, e.g. in a tumour vs. representative parenchyma in the same depths. (2) Time intensity curves should not be analysed in a depth of less than 4 cm. (3) The parameters area under the curve, perfusion index and maximum intensity should not be analysed in a depth more than 6 cm. (4) Size and shape of a region of interest in liver parenchyma do not affect time intensity curves.

  2. Quantitative contrast enhanced ultrasound of the liver for time intensity curves-Reliability and potential sources of errors

    International Nuclear Information System (INIS)

    Ignee, Andre; Jedrejczyk, Maciej; Schuessler, Gudrun; Jakubowski, Wieslaw; Dietrich, Christoph F.

    2010-01-01

    Introduction: Time intensity curves for real-time contrast enhanced low MI ultrasound is a promising technique since it adds objective data to the more subjective conventional contrast enhanced technique. Current developments showed that the amount of uptake in modern targeted therapy strategies correlates with therapy response. Nevertheless no basic research has been done concerning the reliability and validity of the method. Patients and methods: Videos sequences of 31 consecutive patients for at least 60 s were recorded. Parameters analysed: area under the curve, maximum intensity, mean transit time, perfusion index, time to peak, rise time. The influence of depth, lateral shift as well as size and shape of the region of interest was analysed. Results: The parameters time to peak and rise time showed a good stability in different depths. Overall there was a variation >50% for all other parameters. Mean transit time, time to peak and rise time were stable from 3 to 10 cm depths, whereas all other parameters showed only satisfying results at 4-6 cm. Time to peak and rise time were stable as well against lateral shifting whereas all other parameters had again variations over 50%. Size and shape of the region of interest did not influence the results. Discussion: (1) It is important to compare regions of interest, e.g. in a tumour vs. representative parenchyma in the same depths. (2) Time intensity curves should not be analysed in a depth of less than 4 cm. (3) The parameters area under the curve, perfusion index and maximum intensity should not be analysed in a depth more than 6 cm. (4) Size and shape of a region of interest in liver parenchyma do not affect time intensity curves.

  3. Advances in ultrasound-targeted microbubble-mediated gene therapy for liver fibrosis.

    Science.gov (United States)

    Huang, Cuiyuan; Zhang, Hong; Bai, Ruidan

    2017-07-01

    Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM) and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble-mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.

  4. Advances in ultrasound-targeted microbubble-mediated gene therapy for liver fibrosis

    Directory of Open Access Journals (Sweden)

    Cuiyuan Huang

    2017-07-01

    Full Text Available Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble–mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.

  5. The Use of Enteric Contrast Media for Diagnostic CT, MRI, and Ultrasound in Infants and Children: A Practical Approach.

    Science.gov (United States)

    Callahan, Michael J; Talmadge, Jennifer M; MacDougall, Robert; Buonomo, Carlo; Taylor, George A

    2016-05-01

    Enteric contrast media are commonly administered for diagnostic cross-sectional imaging studies in the pediatric population. The purpose of this manuscript is to review the use of enteric contrast media for CT, MRI, and ultrasound in infants, children, and adolescents and to share our experiences at a large tertiary care pediatric teaching hospital. The use of enteric contrast material for diagnostic imaging in infants and children continues to evolve with advances in imaging technology and available enteric contrast media. Many principles of enteric contrast use in pediatric imaging are similar to those in adult imaging, but important differences must be kept in mind when imaging the gastrointestinal tract in infants and children, and practical ways to optimize the imaging examination and the patient experience should be employed where possible.

  6. Contrast-enhanced Ultrasound for Detection of Crohn's Disease Activity: Systematic Review and Meta-analysis.

    Science.gov (United States)

    Serafin, Zbigniew; Białecki, Marcin; Białecka, Agnieszka; Sconfienza, Luca Maria; Kłopocka, Maria

    2016-03-01

    Reports on imaging of active Crohn's disease (aCD) using contrast-enhanced ultrasound (CEUS) are encouraging. However, the statistical power of most published papers is limited due to the small size of the patient groups included. This study was performed to verify the diagnostic value of CEUS in detecting aCD. A systematic literature search was performed by two independent reviewers for articles on the test characteristics of CEUS for the identification of aCD. The quality of the analysed studies was evaluated using a quality assessment tool for diagnostic accuracy studies (QUADAS-2). Pooling was performed using a diagnostic random-effect model and bivariate analysis. Eight articles were included in the final analysis, with a total of 332 patients. There was no significant publication bias. Significant heterogeneity was found regarding CEUS methodology and sonographic definitions of aCD. In a bivariate analysis, pooled sensitivity was 0.94 (95% CI 0.87-0.97) and pooled specificity was 0.79 (95% CI 0.67-0.88). Spearman correlation statistics presented no significant diagnostic threshold effect (r = 0.12, p > 0.9). Subgroup analysis showed that relative intestine wall enhancement had the highest diagnostic value (area under the curve 94%), while the presence of enhancement and analysis of the slope were less useful (area under the curve 91 and 90%, respectively). CEUS presents good sensitivity and moderate specificity in the detection of the aCD. Large-scale randomized trials with quantitative evaluation of CEUS images are necessary to promote this technique in clinical practice. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  7. Small nodules (1-2 cm) in liver cirrhosis: Characterization with contrast-enhanced ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Hyun-Jung [Department of Medical Imaging, Toronto General Hospital, University of Toronto, 585 University Avenue, Toronto, Ontario M5G 2N2 (Canada); Kim, Tae Kyoung [Department of Medical Imaging, Toronto General Hospital, University of Toronto, 585 University Avenue, Toronto, Ontario M5G 2N2 (Canada)], E-mail: taekyoung.kim@uhn.on.ca; Wilson, Stephanie R. [Department of Medical Imaging, Toronto General Hospital, University of Toronto, 585 University Avenue, Toronto, Ontario M5G 2N2 (Canada)

    2009-12-15

    Objective: To determine the diagnostic efficacy of arterial phase contrast-enhanced ultrasound (CEUS) for characterizing small hepatic nodules (1-2 cm) in patients with high-risk for hepatocellular carcinoma (HCC). Materials and methods: Over 12 months, CEUS was performed in 59 patients at high-risk for HCC with small hepatic nodules (1-2 cm; mean, 1.5 cm). Based only on arterial phase (<45 s) vascular intensity and pattern, lesions were prospectively diagnosed as HCC if there was hypervascularity without known features of hemangioma. The diagnosis of HCC was made regardless of the presence or absence of washout. Verification of diagnosis was made by liver transplantation (n = 13), biopsy (n = 12), resection (n = 3) or clinical and imaging follow-up for at least 12 months (n = 31). Results: At of the time of CEUS, the 59 nodules were diagnosed as HCC in 26 and benign lesions in 33, including 20 regenerative/dysplastic nodules (RN/DN), 11 hemangiomas, and 2 focal fat sparing. All 26 nodules with arterial phase hypervascularity without hemangioma-like features were HCC. However, CEUS misdiagnosed HCC as RN/DN in 4 cases with arterial iso- (n = 3) or hypovascularity (n = 1). CEUS correctly diagnosed all 11 hemangiomas. The sensitivity, specificity, and accuracy of CEUS for diagnosing HCC were 86.7, 100, and 93.2%. Conclusions: Arterial phase vascular intensity and pattern of CEUS are highly accurate for the diagnosis of small (1-2 cm) HCC and hemangioma in liver cirrhosis. On CEUS, arterial phase hypervascularity without a hemangioma-pattern alone may be sufficient for diagnosis of small HCC. Infrequent iso/hypovascular HCC may erroneously suggest RN/DN necessitating biopsy or close follow-up.

  8. Quantitative measurement of total cerebral blood flow using 2D phase-contrast MRI and doppler ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Keum Soo; Choi, Sun Seob; Lee, Young Il [Dong-A Univ., College of Medicine, Busan (Korea, Republic of)

    2001-12-01

    To compare of quantitative measurement of the total cerebral blood flow using two-dimensional phase-contrast MR imaging and Doppler ultrasound. In 16 volunteers (mean age, 26 years; mean body weight, 66 kg) without abnormal medical histories, two-dimensional phase-contrast MR imaging was performed at the level of the C2-3 inter vertebral disc for flow measurement of the internal carotid arteries and the vertebral arteries. Volume flow measurements using Doppler ultrasound were also performed at the internal carotid arteries 2cm above the carotid bifurcation, and at the vertebral arteries at the level of the upper pole of the thyroid gland. Flows in the four vessels measured by the two methods were compared using Wilcoxon's correlation analysis and the median score. Total cerebral blood flows were calculated by summing these four vessel flows, and mean values for the 16 volunteers were calculated. Cerebral blood flows measured by 2-D phase-contrast MR imaging and Doppler ultrasounds were 233 and 239 ml/min in the right internal carotid artery, 250 and 248 ml/min in the left internal carotid artery, 62 and 56 ml/min in the right vertebral artery, and 83 and 68 ml/min in the left vertebral artery. Correlation coefficients of the blood flows determined by the two methods were 0.48, 0.54, 0.49, and 0.62 in each vessel, while total cerebral blood flows were 628{+-}68 (range, 517 to 779) ml/min and 612{+-}79 (range, 482 to 804)ml/min, respectively. Total cerebral blood flow was easily measured using 2-D phase-contrast MR imaging and Doppler ultrasound, and the two noninvasive methods can therefore be used clinically for the measurement of total cerebral blood flow.

  9. Correlation of contrast-enhanced ultrasound parameters with oncogene expression and cell proliferation activity in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Ce Zhang

    2017-01-01

    Objective: To study the correlation of contrast-enhanced ultrasound parameters with oncogene expression and cell proliferation activity in breast cancer. Methods: Breast cancer lesions and benign breast lesions surgically removed in Zigong Third People's Hospital between May 2014 and February 2017 were selected, contrast-enhanced ultrasound was done before operation to draw the time-intensity curve and calculate the area under the curve (AUC), and the expression of proliferation molecules and tumor suppressor genes were detected after operation. Results:The contrast-enhanced ultrasound parameter AUC of the breast cancer lesion was greatly higher than that of the benign breast lesion; ECT2, ZKSCAN3, USP39 and EphA2 mRNA expression in breast cancer lesions were obviously higher than those in benign breast lesions whereas HPK1, TCEAL17, CCN5, ATG2B and ATG4D mRNA expression were greatly lower than those in benign breast lesions; ECT2, ZKSCAN3, USP39 and EphA2 mRNA expression in breast cancer lesions with high AUC were greatly higher than those in breast cancer lesions with low AUC whereas HPK1, TCEAL17, CCN5, ATG2B and ATG4D mRNA expression were greatly lower than those in breast cancer lesions with low AUC. Conclusion: The contrast-enhanced ultrasound parameter AUC of breast cancer lesion significantly increases and is closely related to the higher expression of pro-proliferation molecules and the lower expression of tumor suppressor genes.

  10. Abdominal ultrasound-scanning versus non-contrast computed tomography as screening method for abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Liisberg, Mads; Diederichsen, Axel C.; Lindholt, Jes S.

    2017-01-01

    Background: Validating non-contrast-enhanced computed tomography (nCT) compared to ultrasound sonography (US) as screening method for abdominal aortic aneurysm (AAA) screening. Methods: Consecutively attending men (n = 566) from the pilot study of the randomized Danish CardioVascular Screening......CT seems superior to US concerning sensitivity, and is able to detect aneurysmal lesions not detectable with US. Finally, the prevalence of AAA in Denmark seems to remain relatively high, in this small pilot study group....

  11. Contrast-enhanced ultrasound and computed tomography findings of granulomatosis with polyangiitis presenting with multiple intrarenal microaneurysms: A case report.

    Science.gov (United States)

    Kim, Youe Ree; Lee, Young Hwan; Lee, Jong-Ho; Yoon, Kwon-Ha

    Granulomatosis with polyangiitis (GPA) is a systemic disorder that affects small- and medium- sized vessels in many organs. Although the kidneys are the second most commonly involved organ in patients with GPA, its manifestation as multiple intrarenal aneurysms is rare. We report an unusual manifestation of GPA with multiple intrarenal microaneurysms, as demonstrated by contrast-enhanced ultrasound and computed tomography. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. High-Resolution Ultrasound-Switchable Fluorescence Imaging in Centimeter-Deep Tissue Phantoms with High Signal-To-Noise Ratio and High Sensitivity via Novel Contrast Agents.

    Science.gov (United States)

    Cheng, Bingbing; Bandi, Venugopal; Wei, Ming-Yuan; Pei, Yanbo; D'Souza, Francis; Nguyen, Kytai T; Hong, Yi; Yuan, Baohong

    2016-01-01

    For many years, investigators have sought after high-resolution fluorescence imaging in centimeter-deep tissue because many interesting in vivo phenomena-such as the presence of immune system cells, tumor angiogenesis, and metastasis-may be located deep in tissue. Previously, we developed a new imaging technique to achieve high spatial resolution in sub-centimeter deep tissue phantoms named continuous-wave ultrasound-switchable fluorescence (CW-USF). The principle is to use a focused ultrasound wave to externally and locally switch on and off the fluorophore emission from a small volume (close to ultrasound focal volume). By making improvements in three aspects of this technique: excellent near-infrared USF contrast agents, a sensitive frequency-domain USF imaging system, and an effective signal processing algorithm, for the first time this study has achieved high spatial resolution (~ 900 μm) in 3-centimeter-deep tissue phantoms with high signal-to-noise ratio (SNR) and high sensitivity (3.4 picomoles of fluorophore in a volume of 68 nanoliters can be detected). We have achieved these results in both tissue-mimic phantoms and porcine muscle tissues. We have also demonstrated multi-color USF to image and distinguish two fluorophores with different wavelengths, which might be very useful for simultaneously imaging of multiple targets and observing their interactions in the future. This work has opened the door for future studies of high-resolution centimeter-deep tissue fluorescence imaging.

  13. Targeted gene delivery to the synovial pannus in antigen-induced arthritis by ultrasound-targeted microbubble destruction in vivo.

    Science.gov (United States)

    Xiang, Xi; Tang, Yuanjiao; Leng, Qianying; Zhang, Lingyan; Qiu, Li

    2016-02-01

    The purpose of this study was to optimize an ultrasound-targeted microbubble destruction (UTMD) technique to improve the in vivo transfection efficiency of the gene encoding enhanced green fluorescent protein (EGFP) in the synovial pannus in an antigen-induced arthritis rabbit model. A mixture of microbubbles and plasmids was locally injected into the knee joints of an antigen-induced arthritis (AIA) rabbits. The plasmid concentrations and ultrasound conditions were varied in the experiments. We also tested local articular and intravenous injections. The rabbits were divided into five groups: (1) ultrasound+microbubbles+plasmid; (2) ultrasound+plasmid; (3) microbubble+plasmid; (4) plasmid only; (5) untreated controls. EGFP expression was observed by fluorescent microscope and immunohistochemical staining in the synovial pannus of each group. The optimal plasmid dosage and ultrasound parameter were determined based on the results of EGFP expression and the present and absent of tissue damage under light microscopy. The irradiation procedure was performed to observe the duration of the EGFP expression in the synovial pannus and other tissues and organs, as well as the damage to the normal cells. The optimal condition was determined to be a 1-MHz ultrasound pulse applied for 5 min with a power output of 2 W/cm(2) and a 20% duty cycle along with 300 μg of plasmid. Under these conditions, the synovial pannus showed significant EGFP expression without significant damage to the surrounding normal tissue. The EGFP expression induced by the local intra-articular injection was significantly more increased than that induced by the intravenous injection. The EGFP expression in the synovial pannus of the ultrasound+microbubbles+plasmid group was significantly higher than that of the other four groups (Ppannus of an AIA model. Thus, this could become a safe and effective non-viral gene transfection procedure for arthritis therapy. Copyright © 2015 Elsevier B.V. All rights

  14. Does ultrasound contrast agent improve the diagnostic value of colour and power Doppler sonography in superficial lymph node enlargement?

    International Nuclear Information System (INIS)

    Schulte-Altedorneburg, Gernot; Demharter, Johannes; Linne, Renate; Droste, Dirk W.; Bohndorf, Klaus; Buecklein, Wolfgang

    2003-01-01

    Objective: to analyse whether ultrasound contrast agent (UCA) improves the diagnostic accuracy to differentiate between benign and malignant superficial lymph node enlargement by using colour-coded duplex sonography (CCDS) and power Doppler (PD). Methods: 32 patients with suspected malignant superficial lymph node enlargement prospectively underwent standardised ultrasound examinations using B-mode sonography and native and contrast-enhanced CCDS and PD immediately before biopsy. Solbiati-Index (longitudinal-transverse diameter ratio) and intranodal flow patterns by using different vascularisation types were assessed. Histological and sonographical findings were correlated. Results: 27 malignant and 5 benign lymph nodes were found. Solbiati-Index was lower in malignant lymph nodes than in benign nodes (mean 1.5 vs. 2.4, P<0.045). More intranodal flow patterns could be detected after UCA (53 vs. 43) but the number of correctly identified malignant nodes decreased after UCA (26 vs. 24) and the number of correctly identified benign nodes remained constant compared with native CCDS and PD. In 31% of the colour-mode studies, PD was considered to visualise more clearly intranodal vascular flow patterns than CCDS. Conclusion: despite depicting more intranodal vascular patterns, the use of an ultrasound contrast agent seems not to improve the diagnostic value of CCDS and PD compared with native colour-mode studies in superficial lymph node enlargement

  15. Evaluation of high frequency ultrasound methods and contrast agents for characterising tumor response to anti-angiogenic treatment

    Energy Technology Data Exchange (ETDEWEB)

    Rix, Anne, E-mail: arix@ukaachen.de [Department of Experimental Molecular Imaging, Pauwelsstrasse 30, 52074 Aachen, RWTH-Aachen University, Aachen (Germany); Lederle, Wiltrud, E-mail: wlederle@ukaachen.de [Department of Experimental Molecular Imaging, Pauwelsstrasse 30, 52074 Aachen, RWTH-Aachen University, Aachen (Germany); Siepmann, Monica, E-mail: monica.siepmann@rub.de [Department of Medical Engineering, Universitätstraße 150, 44780 Bochum, Ruhr-University Bochum, Bochum (Germany); Fokong, Stanley, E-mail: sfokong@ukaachen.de [Department of Experimental Molecular Imaging, Pauwelsstrasse 30, 52074 Aachen, RWTH-Aachen University, Aachen (Germany); Behrendt, Florian F., E-mail: fbehrendt@ukaachen.de [Department of Nuclear Medicine, Pauwelsstrasse 30, 52074 Aachen, RWTH-Aachen University, Aachen (Germany); Bzyl, Jessica, E-mail: jbzyl@ukaachen.de [Department of Experimental Molecular Imaging, Pauwelsstrasse 30, 52074 Aachen, RWTH-Aachen University, Aachen (Germany); Grouls, Christoph, E-mail: cgrouls@ukaachen.de [Department of Experimental Molecular Imaging, Pauwelsstrasse 30, 52074 Aachen, RWTH-Aachen University, Aachen (Germany); Kiessling, Fabian, E-mail: fkiessling@ukaachen.de [Department of Experimental Molecular Imaging, Pauwelsstrasse 30, 52074 Aachen, RWTH-Aachen University, Aachen (Germany); Palmowski, Moritz, E-mail: mpalmowski@ukaachen.de [Department of Experimental Molecular Imaging, Pauwelsstrasse 30, 52074 Aachen, RWTH-Aachen University, Aachen (Germany); Department of Nuclear Medicine, Pauwelsstrasse 30, 52074 Aachen, RWTH-Aachen University, Aachen (Germany)

    2012-10-15

    Purpose: To compare non-enhanced and contrast-enhanced high-frequency 3D Doppler ultrasound with contrast-enhanced 2D and 3D B-mode imaging for assessing tumor vascularity during antiangiogenic treatment using soft-shell and hard-shell microbubbles. Materials and methods: Antiangiogenic therapy effects (SU11248) on vascularity of subcutaneous epidermoid-carcinoma xenografts (A431) in female CD1 nude mice were investigated longitudinally using non-enhanced and contrast-enhanced 3D Doppler at 25 MHz. Additionally, contrast-enhanced 2D and 3D B-mode scans were performed by injecting hard-shell (poly-butyl-cyanoacrylate-based) and soft-shell (phospholipid-based) microbubbles. Suitability of both contrast agents for high frequency imaging and the sensitivity of the different ultrasound methods to assess early antiangiogenic therapy effects were investigated. Ultrasound data were validated by immunohistology. Results: Hard-shell microbubbles induced higher signal intensity changes in tumors than soft-shell microbubbles in 2D B-mode measurements (424 ± 7 vs. 169 ± 8 A.U.; p < 0.01). In 3D measurements, signals of soft-shell microbubbles were hardly above the background (5.48 ± 4.57 vs. 3.86 ± 2.92 A.U.), while signals from hard-shell microbubbles were sufficiently high (30.5 ± 8.06 A.U). Using hard-shell microbubbles 2D and 3D B-mode imaging depicted a significant decrease in tumor vascularity during antiangiogenic therapy from day 1 on. Using soft-shell microbubbles significant therapy effects were observed at day 4 after therapy in 2D B-mode imaging but could not be detected in the 3D mode. With non-enhanced and contrast-enhanced Doppler imaging significant differences between treated and untreated tumors were found from day 2 on. Conclusion: Hard-shell microbubble-enhanced 2D and 3D B-mode ultrasound achieved highest sensitivity for assessing therapy effects on tumor vascularisation and were superior to B-mode ultrasound with soft-shell microbubbles and to Doppler

  16. Data on consistency among different methods to assess atherosclerotic plaque echogenicity on standard ultrasound and intraplaque neovascularization on contrast-enhanced ultrasound imaging in human carotid artery

    Directory of Open Access Journals (Sweden)

    Mattia Cattaneo

    2016-12-01

    Full Text Available Here we provide the correlation among different carotid ultrasound (US variables to assess echogenicity n standard carotid US and to assess intraplaque neovascularization on contrast enhanced US. We recruited 45 consecutive subjects with an asymptomatic≥50% carotid artery stenosis. Carotid plaque echogenicity at standard US was visually graded according to Gray–Weale classification (GW and measured by the greyscale median (GSM, a semi-automated computerized measurement performed by Adobe Photoshop®. On CEUS imaging IPNV was graded according to the visual appearance of contrast within the plaque according to three different methods: CEUS_A (1=absent; 2=present; CEUS_B a three-point scale (increasing IPNV from 1 to 3; CEUS_C a four-point scale (increasing IPNV from 0 to 3. We have also implemented a new simple quantification method derived from region of interest (ROI signal intensity ratio as assessed by QLAB software. Further information is available in “Contrast-enhanced ultrasound imaging of intraplaque neovascularization and its correlation to plaque echogenicity in human carotid arteries atherosclerosis (M. Cattaneo, D. Staub, A.P. Porretta, J.M. Gallino, P. Santini, C. Limoni et al., 2016 [1].

  17. Clinical utility of three-dimensional contrast-enhanced ultrasound in the differentiation between noninvasive and invasive neoplasms of urinary bladder.

    Science.gov (United States)

    Li, Qiu-yang; Tang, Jie; He, En-hui; Li, Yan-mi; Zhou, Yun; Zhang, Xu; Chen, Guangfu

    2012-11-01

    The purpose of this study was to evaluate the effectiveness of three-dimensional contrast-enhanced ultrasound in differentiating invasive and noninvasive neoplasms of urinary bladder. A total of 60 lesions in 60 consecutive patients with bladder tumors received three dimensional ultrasonography, low acoustic power contrast enhanced ultrasonography and low acoustic power three-dimensional contrast-enhanced ultrasound examination. The IU22 ultrasound scanner and a volume transducer were used and the ultrasound contrast agent was SonoVue. The contrast-specific sonographic imaging modes were PI (pulse inversion) and PM (power modulation). The three dimensional ultrasonography, contrast enhanced ultrasonography, and three-dimensional contrast-enhanced ultrasound images were independently reviewed by two readers who were not in the images acquisition. Images were analyzed off-site. A level of confidence in the diagnosis of tumor invasion of the muscle layer was assigned on a 5° scale. Receiver operating characteristic analysis was used to assess overall confidence in the diagnosis of muscle invasion by tumor. Kappa values were used to assess inter-readers agreement. Histologic diagnosis was obtained for all patients. Final pathologic staging revealed 44 noninvasive tumors and 16 invasive tumors. Three-dimensional contrast-enhanced ultrasound depicted all 16 muscle-invasive tumors. The diagnostic performance of three-dimensional contrast-enhanced ultrasound was better than those of three dimensional ultrasonography and contrast enhanced ultrasonography. The receiver operating characteristic curves were 0.976 and 0.967 for three-dimensional contrast-enhanced ultrasound, those for three dimensional ultrasonography were 0.881 and 0.869, those for contrast enhanced ultrasonography were 0.927 and 0.929. The kappa values in the three dimensional ultrasonography, contrast enhanced ultrasonography and three-dimensional contrast-enhanced ultrasound for inter-reader agreements

  18. Clinical utility of three-dimensional contrast-enhanced ultrasound in the differentiation between noninvasive and invasive neoplasms of urinary bladder

    International Nuclear Information System (INIS)

    Li, Qiu-yang; Tang, Jie; He, En-hui; Li, Yan-mi; Zhou, Yun; Zhang, Xu; Chen, Guangfu

    2012-01-01

    Objectives: The purpose of this study was to evaluate the effectiveness of three-dimensional contrast-enhanced ultrasound in differentiating invasive and noninvasive neoplasms of urinary bladder. Methods: A total of 60 lesions in 60 consecutive patients with bladder tumors received three dimensional ultrasonography, low acoustic power contrast enhanced ultrasonography and low acoustic power three-dimensional contrast-enhanced ultrasound examination. The IU22 ultrasound scanner and a volume transducer were used and the ultrasound contrast agent was SonoVue. The contrast-specific sonographic imaging modes were PI (pulse inversion) and PM (power modulation). The three dimensional ultrasonography, contrast enhanced ultrasonography, and three-dimensional contrast-enhanced ultrasound images were independently reviewed by two readers who were not in the images acquisition. Images were analyzed off-site. A level of confidence in the diagnosis of tumor invasion of the muscle layer was assigned on a 5° scale. Receiver operating characteristic analysis was used to assess overall confidence in the diagnosis of muscle invasion by tumor. Kappa values were used to assess inter-readers agreement. Histologic diagnosis was obtained for all patients. Results: Final pathologic staging revealed 44 noninvasive tumors and 16 invasive tumors. Three-dimensional contrast-enhanced ultrasound depicted all 16 muscle-invasive tumors. The diagnostic performance of three-dimensional contrast-enhanced ultrasound was better than those of three dimensional ultrasonography and contrast enhanced ultrasonography. The receiver operating characteristic curves were 0.976 and 0.967 for three-dimensional contrast-enhanced ultrasound, those for three dimensional ultrasonography were 0.881 and 0.869, those for contrast enhanced ultrasonography were 0.927 and 0.929. The kappa values in the three dimensional ultrasonography, contrast enhanced ultrasonography and three-dimensional contrast-enhanced ultrasound

  19. Contrast generation in the nuclear-spin tomography by pulsed ultrasound

    International Nuclear Information System (INIS)

    Oehms, Ole Benjamin

    2009-01-01

    In the framework of this thesis a combined method of ultrasound and nuclear-spin tomography is presented. Via ultrasound pulses by the sound-radiation force in liquids and tissue phantoms motions are generated, which depend on ther viscoelastic properties. This motions are made visible by a motion-sensitive tomograph sequence in the phase image of the tomograph in form of a phase change. The first measurements on simple phantoms and liquids are presented. [de

  20. Detection of the Single-Session Complete Ablation Rate by Contrast-Enhanced Ultrasound during Ultrasound-Guided Laser Ablation for Benign Thyroid Nodules: A Prospective Study

    Directory of Open Access Journals (Sweden)

    Shuhua Ma

    2016-01-01

    Full Text Available This study aimed to investigate the single-session complete ablation rate of ultrasound-guided percutaneous laser ablation (LA for benign thyroid nodules. LA was performed in 90 patients with 118 benign thyroid nodules. Contrast-enhanced ultrasound (CEUS was used to evaluate complete nodule ablation one day after ablation. Thyroid nodule volumes, thyroid functions, clinical symptoms and complications were evaluated 1, 3, 6, 12, and 18 months after ablation. Results showed that all benign thyroid nodules successfully underwent LA. The single-session complete ablation rates for nodules with maximum diameters ≤2 cm, 2-3 cm and ≥3 cm were 93.4%, 70.3% and 61.1%, respectively. All nodule volumes significantly decreased than that one day after ablation (P0.05. Three patients had obvious pain during ablation; one (1.1% had recurrent laryngeal nerve injury, but the voice returned to normal within 6 months after treatment. Thus, ultrasound-guided LA can effectively inactivate benign thyroid nodules. LA is a potentially viable minimally invasive treatment that offers good cosmetic effects.

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

    Science.gov (United States)

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

    2018-05-01

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

  2. Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction.

    Science.gov (United States)

    Xu, Yali; Cui, Hai; Zhu, Qiong; Hua, Xing; Xia, Hongmei; Tan, Kaibin; Gao, Yunhua; Zhao, Jing; Liu, Zheng

    2016-01-01

    Objective. Blood-brain barrier (BBB) is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p ultrasound-exposed hemisphere (4 ± 1, grade 2) while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery.

  3. Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction

    Directory of Open Access Journals (Sweden)

    Yali Xu

    2016-01-01

    Full Text Available Objective. Blood-brain barrier (BBB is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p<0.01. Erythrocytes extravasations were demonstrated in the ultrasound-exposed hemisphere (4±1, grade 2 while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery.

  4. Ultrasound

    Science.gov (United States)

    ... completed. Young children may need additional preparation. When scheduling an ultrasound for yourself or your child, ask ... of Privacy Practices Notice of Nondiscrimination Manage Cookies Advertising Mayo Clinic is a not-for-profit organization ...

  5. Ultrasound

    Science.gov (United States)

    ... reflect off body structures. A computer receives the waves and uses them to create a picture. Unlike with an x-ray or CT scan, this test does not use ionizing radiation. The test is done in the ultrasound ...

  6. Comparative analysis of contrast between hepatic vein and hepatic parenchyma with controlled velocity of ultrasound in normal and fatty liver

    International Nuclear Information System (INIS)

    Yun, Eun Joo; Choi, Byung Jin; Han, Joon Koo; Cha, Joo Hee; Kim, Seung Hyup; Lee, Dong Hyuk

    2000-01-01

    To evaluate the contrast between hepatic vein and hepatic parenchyma with controlled velocities of ultrasound in normal and fatty liver. 31 patient with normal liver and 39 patients with moderate degree of fatty liver were studies with sonography with controlled velocities of ultrasound (1,580 m/sec, 1,540 m/sec, 1,500 m/sec, 1,460 m/sec). Sonographic images were captured with picture grabbing (Sono-PACS) and were recalled with visual C++(Microsoft Redmond. WA, USA). The contrast between hepatic vein and parenchyma was measured and analyzed on each sonographic image. The number of patients with the highest contrast between hepatic vein and hepatic parenchyma among the 31 patients with normal liver were 5 (16.1%) with 1,580 m/sec, 12 (38.8%) with 1,540 m/sec, 9 (29.0%) with 1,500 m/sec, and 5 (16.1%) with 1,460 m/sec. The number of patients with highest contrast between hepatic vein and hepatic parenchyma among the 39 patients with fatty liver were 3 (7.7%) with 1,580 m/sec, 7 (17.9%) with 1,540 m/sec, 12 (30.8%) with 1,500 m/sec and 17 (43.6%) with 1,460 m/sec. The velocity of ultrasound for the highest contrast between hepatic vein and hepatic parenchyma in normal liver was 1,540 m/sec, and 1,460 m/sec in fatty liver.

  7. Pharmacokinetic changes induced by focused ultrasound in glioma-bearing rats as measured by dynamic contrast-enhanced MRI.

    Directory of Open Access Journals (Sweden)

    Feng-Yi Yang

    Full Text Available Focused ultrasound (FUS combined with microbubbles has been shown to be a noninvasive and targeted drug delivery technique for brain tumor treatment. The purpose of this study was to measure the kinetics of Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA in glioma-bearing rats in the presence of FUS-induced blood-brain barrier disruption (BBB-D by magnetic resonance imaging (MRI. A total of ten glioma-bearing rats (9-12 weeks, 290-340 g were used in this study. Using dynamic contrast-enhanced (DCE-MRI, the spatial permeability of FUS-induced BBB-D was evaluated and the kinetic parameters were calculated by a general kinetic model (GKM. The results demonstrate that the mean Ktrans of the sonicated tumor (0.128±0.019 at 20 min and 0.103±0.023 at 24 h after sonication, respectively was significantly higher than (2.46-fold at 20 min and 1.78-fold at 24 h that of the contralateral (non-sonicated tumor (0.052±0.019 at 20 min and 0.058±0.012 at 24 h after sonication, respectively. In addition, the transfer constant Ktrans in the sonicated tumor correlated strongly with tissue EB extravasation (R = 0.95, which suggests that DCE-MRI may reflect drug accumulation in the brain. Histological observations showed no macroscopic damage except for a few small erythrocyte extravasations. The current study demonstrates that DCE-MRI can monitor the dynamics of the FUS-induced BBB-D process and constitutes a useful tool for quantifying BBB permeability in tumors.

  8. Post-operative monitoring of tissue transfers: advantages using contrast enhanced ultrasound (CEUS) and contrast enhanced MRI (ceMRI) with dynamic perfusion analysis?

    Science.gov (United States)

    Lamby, P; Prantl, L; Fellner, C; Geis, S; Jung, E M

    2011-01-01

    The immediate evaluation of microvascular tissue flaps with respect to microcirculation after transplantation is crucial for optimal monitoring and outcome. The purpose of our investigation was to evaluate the clinical value of contrast-enhanced ultrasound (CEUS) and contrast-enhanced MRI (ceMRI) for monitoring the integrity of tissue flaps in plastic surgery. To this end, we investigated 10 patients (47 ± 16 a) between postoperative day 7 and 14 who underwent flap surgery in order to cover tissue defects in various body regions. For CEUS we utilized the GE LOGIQ E9 equipped with a linear transducer (6-9 MHz). After application of 2.4 ml SonoVue, the tissue perfusion was detected in Low MI-Technique (MI present, both technologies provide an optimal assessment of perfusion in cutaneous, subcutaneous and muscle tissue layers, whereby the detection of fatty tissue perfusion is currently more easily detected using CEUS compared to ceMRI.

  9. Targeted Ultrasound-Guided Perineural Hydrodissection of the Sciatic Nerve for the Treatment of Piriformis Syndrome.

    Science.gov (United States)

    Burke, Christopher J; Walter, William R; Adler, Ronald S

    2018-05-01

    Piriformis syndrome is a common cause of lumbar, gluteal, and thigh pain, frequently associated with sciatic nerve symptoms. Potential etiologies include muscle injury or chronic muscle stretching associated with gait disturbances. There is a common pathological end pathway involving hypertrophy, spasm, contracture, inflammation, and scarring of the piriformis muscle, leading to impingement of the sciatic nerve. Ultrasound-guided piriformis injections are frequently used in the treatment of these pain syndromes, with most of the published literature describing injection of the muscle. We describe a safe, effective ultrasound-guided injection technique for the treatment of piriformis syndrome using targeted sciatic perineural hydrodissection followed by therapeutic corticosteroid injection.

  10. Lower extremity revascularization without preoperative contrast arteriography: experience with duplex ultrasound arterial mapping in 485 cases.

    Science.gov (United States)

    Ascher, Enrico; Hingorani, Anil; Markevich, Natalia; Costa, Tatiana; Kallakuri, Shreedhar; Khanimoy, Yuri

    2002-01-01

    This study reviews our experience with duplex ultrasound arterial mapping (DUAM) for preoperative evaluation in 466 patients (262 men) who underwent 485 lower extremity revascularization procedures from January 1, 1998 to May 30, 2001. Preoperative imaging consisted of DUAM alone in 449 procedures and DUAM and contrast angiography (CA) in 36. An attempt to image from the distal aorta to the pedal arteries was made in all the patients. The selection of optimal inflow and outflow bypasses anastomotic sites was based on a schematic drawing following DUAM examination. Inflow disease was also assessed by intraoperative pressure gradient (IPG) between the distal anastomosis and radial arteries, and completion arteriography of the runoff vessels was obtained, which was correlated with the preoperative findings. Indications for surgery were severe claudication in 91 (19%) limbs, tissue loss in 197 (40%), rest pain in 113 (23%), acute ischemia in 46 (10%), popliteal aneurysm in 18 (4%), superficial femoral artery aneurysm in 1, abdominal aortic aneurysm with claudication in 1, and failing graft in 18 (4%). Age ranged from 30 to 97 years (mean 72 +/- 12 (SD) years) and risk factors such as diabetes, hypertension, use of tobacco, coronary artery disease, and end-stage renal disease were present in 45%, 45%, 44%, 44%, and 13% of the patients, respectively. One hundred twenty-one (25%) limbs had at least 1 previous ipsilateral revascularization. The mean DUAM time was 66 +/- 20 (SD) min (30-150 min). Additional preoperative imaging was deemed necessary in 36 cases due to extensive ulcers, edema, severe arterial wall calcification, and very poor runoff. The distal anastomosis was to the popliteal artery in 173 cases and to the tibial and pedal arteries in 255. Inflow procedures to the femoral arteries, embolectomy, thrombectomy, balloon angioplasty, and patch angioplasty accounted for the remaining 57 cases. Overall, 6-, 12-, and -24- month secondary patency rates were 86%, 80

  11. Contrast-enhanced ultrasound for quantitative assessment of portal pressure in canine liver fibrosis.

    Science.gov (United States)

    Zhai, Lin; Qiu, Lan-Yan; Zu, Yuan; Yan, Yan; Ren, Xiao-Zhuan; Zhao, Jun-Feng; Liu, Yu-Jiang; Liu, Ji-Bin; Qian, Lin-Xue

    2015-04-21

    To explore the feasibility of non-invasive quantitative estimation of portal venous pressure by contrast-enhanced ultrasound (CEUS) in a canine model. Liver fibrosis was established in adult canines (Beagles; n = 14) by subcutaneous injection of carbon tetrachloride (CCl4). CEUS parameters, including the area under the time-intensity curve and intensity at portal/arterial phases (Qp/Qa and Ip/Ia, respectively), were used to quantitatively assess the blood flow ratio of the portal vein/hepatic artery at multiple time points. The free portal venous pressures (FPP) were measured by a multi-channel baroreceptor using a percutaneous approach at baseline and 8, 16, and 24 wk after CCl4 injections in each canine. Liver biopsies were obtained at the end of 8, 16, and 24 wk from each animal, and the stage of the fibrosis was assessed according to the Metavir scoring system. A Pearson correlation test was performed to compare the FPP with Qp/Qa and Ip/Ia. Pathologic examination of 42 biopsies from the 14 canines at weeks 8, 16, and 24 revealed that liver fibrosis was induced by CCl4 and represented various stages of liver fibrosis, including F0 (n = 3), F1 (n = 12), F2 (n = 14), F3 (n = 11), and F4 (n = 2). There were significant differences in the measurements of Qp/Qa (19.85 ± 3.30 vs 10.43 ± 1.21, 9.63 ± 1.03, and 8.77 ± 0.96) and Ip/Ia (1.77 ± 0.37 vs 1.03 ± 0.12, 0.83 ± 0.10, and 0.69 ± 0.13) between control and canine fibrosis at 8, 16, and 24 wk, respectively (all P fibrosis model. Prediction of elevated FPP based on Qp/Qa and Ip/Ia was highly sensitive, as assessed by the area under the receiver operating curve (0.866 and 0.895, respectively). CEUS is a potential method to accurately, but non-invasively, estimate portal venous pressure through measurement of Qp/Qa and Ip/Ia parameters.

  12. Real-time non-rigid target tracking for ultrasound-guided clinical interventions

    Science.gov (United States)

    Zachiu, C.; Ries, M.; Ramaekers, P.; Guey, J.-L.; Moonen, C. T. W.; de Senneville, B. Denis

    2017-10-01

    Biological motion is a problem for non- or mini-invasive interventions when conducted in mobile/deformable organs due to the targeted pathology moving/deforming with the organ. This may lead to high miss rates and/or incomplete treatment of the pathology. Therefore, real-time tracking of the target anatomy during the intervention would be beneficial for such applications. Since the aforementioned interventions are often conducted under B-mode ultrasound (US) guidance, target tracking can be achieved via image registration, by comparing the acquired US images to a separate image established as positional reference. However, such US images are intrinsically altered by speckle noise, introducing incoherent gray-level intensity variations. This may prove problematic for existing intensity-based registration methods. In the current study we address US-based target tracking by employing the recently proposed EVolution registration algorithm. The method is, by construction, robust to transient gray-level intensities. Instead of directly matching image intensities, EVolution aligns similar contrast patterns in the images. Moreover, the displacement is computed by evaluating a matching criterion for image sub-regions rather than on a point-by-point basis, which typically provides more robust motion estimates. However, unlike similar previously published approaches, which assume rigid displacements in the image sub-regions, the EVolution algorithm integrates the matching criterion in a global functional, allowing the estimation of an elastic dense deformation. The approach was validated for soft tissue tracking under free-breathing conditions on the abdomen of seven healthy volunteers. Contact echography was performed on all volunteers, while three of the volunteers also underwent standoff echography. Each of the two modalities is predominantly specific to a particular type of non- or mini-invasive clinical intervention. The method demonstrated on average an accuracy of

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

    Directory of Open Access Journals (Sweden)

    Liyi Mai

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

  14. Therapeutic response assessment of high intensity focused ultrasound therapy for uterine fibroid: Utility of contrast-enhanced ultrasonography

    International Nuclear Information System (INIS)

    Zhou Xiaodong; Ren Xiaolong; Zhang Jun; He Guangbin; Zheng Minjuan; Tian Xue; Li Li; Zhu Ting; Zhang Min; Wang Lei; Luo Wen

    2007-01-01

    Purpose: To assess the utility of contrast-enhanced ultrasonography (ceUS) in the assessment of the therapeutic response to high intensity focused ultrasound (HIFU) ablation in patients with uterine fibroid. Materials and methods: Sixty-four patients with a total of 64 uterine fibroids (mean: 5.3 ± 1.2 cm; range: 3.2-8.9 cm) treated with HIFU ablation under the ultrasound guidance were evaluated with ceUS after receiving an intravenous bolus injection of a microbubble contrast agent (SonoVue) within 1 week after intervention. We obtained serial ceUS images during the time period from beginning to 5 min after the initiation of the bolus contrast injection. All of the patients underwent a contrast enhanced MRI (ceMRI) and ultrasound guided needle puncture biopsy within 1 week after HIFU ablation. And as a follow-up, all of the patients underwent US at 1, 3, 6 and 12 months after HIFU treatment. The volume change was observed and compared to pre- and post-HIFU ablation. The results of the ceUS were compared with those of the ceMRI in terms of the presence or absence of residual unablated tumor and pathologic change in the treated lesions. Results: On ceUS, diagnostic accuracy was 100%, while residual unablated tumors were found in three uterine fibroids (4.7%) and failed treatment was found in eight uterine fibroids (12.5%). All the 11 fibroids were subjected to additional HIFU ablation. Of the 58 ablated fibroids without residual tumors on both the ceUS and ceMRI after the HIFU ablation, the volumes of all the fibroids decreased in different degrees during the 1 year follow-up USs. And histologic examinations confirmed findings of necrotic and viable tumor tissue, respectively. Conclusion: CEUS is potentially useful for evaluating the early therapeutic effect of percutaneous HIFU ablation for uterine fibroids

  15. The use of Acoustic Radiation Force decorrelation-weighted pulse inversion (ADW-PI) for enhanced ultrasound contrast imaging

    Science.gov (United States)

    Herbst, Elizabeth; Unnikrishnan, Sunil; Wang, Shiying; Klibanov, Alexander L.; Hossack, John A.; Mauldin, F. William

    2016-01-01

    Objectives The use of ultrasound imaging for cancer diagnosis and screening can be enhanced with the use of molecularly targeted microbubbles. Nonlinear imaging strategies such as pulse inversion (PI) and “contrast pulse sequences” (CPS) can be used to differentiate microbubble signal, but often fail to suppress highly echogenic tissue interfaces. This failure results in false positive detection and potential misdiagnosis. In this study, a novel Acoustic Radiation Force (ARF) based approach was developed for superior microbubble signal detection. The feasibility of this technique, termed ARF-decorrelation-weighted PI (ADW-PI), was demonstrated in vivo using a subcutaneous mouse tumor model. Materials and Methods Tumors were implanted in the hindlimb of C57BL/6 mice by subcutaneous injection of MC38 cells. Lipid-shelled microbubbles were conjugated to anti-VEGFR2 antibody and administered via bolus injection. An image sequence using ARF pulses to generate microbubble motion was combined with PI imaging on a Verasonics Vantage programmable scanner. ADW-PI images were generated by combining PI images with inter-frame signal decorrelation data. For comparison, CPS images of the same mouse tumor were acquired using a Siemens Sequoia clinical scanner. Results Microbubble-bound regions in the tumor interior exhibited significantly higher signal decorrelation than static tissue (n = 9, p < 0.001). The application of ARF significantly increased microbubble signal decorrelation (n = 9, p < 0.01). Using these decorrelation measurements, ADW-PI imaging demonstrated significantly improved microbubble contrast-to-tissue ratio (CTR) when compared to corresponding CPS or PI images (n = 9, p < 0.001). CTR improved with ADW-PI by approximately 3 dB compared to PI images and 2 dB compared to CPS images. Conclusions Acoustic radiation force can be used to generate adherent microbubble signal decorrelation without microbubble bursting. When combined with pulse inversion

  16. Intra-biliary contrast-enhanced ultrasound for evaluating biliary obstruction during percutaneous transhepatic biliary drainage: A preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Er-jiao [Department of Medical Ultrasonics, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630 (China); Zheng, Rong-qin, E-mail: zhengrq@mail.sysu.edu.cn [Department of Medical Ultrasonics, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630 (China); Su, Zhong-zhen; Li, Kai; Ren, Jie; Guo, Huan-yi [Department of Medical Ultrasonics, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630 (China)

    2012-12-15

    Objectives: The aimed of this study was to investigate the value of intra-biliary contrast-enhanced ultrasound (IB-CEUS) for evaluating biliary obstruction during percutaneous transhepatic biliary drainage (PTBD). Materials and methods: 80 patients with obstructive jaundice who underwent IB-CEUS during PTBD were enrolled. The diluted ultrasound contrast agent was injected via the drainage catheter to perform IB-CEUS. Both conventional ultrasound and IB-CEUS were used to detect the tips of the drainage catheters and to compare the detection rates of the tips. The obstructive level and degree of biliary tract were evaluated by IB-CEUS. Fluoroscopic cholangiography (FC) and computer tomography cholangiography (CTC) were taken as standard reference for comparison. Results: Conventional ultrasound displayed only 43 tips (43/80, 53.8%) of the drainage catheters within the bile ducts while IB-CEUS identified all 80 tips (80/80, 100%) of the drainage catheters including 4 of them out of the bile duct (P < 0.001). IB-CEUS made correct diagnosis in 44 patients with intrahepatic and 36 patients with extrahepatic biliary obstructions. IB-CEUS accurately demonstrated complete obstruction in 56 patients and incomplete obstruction in 21 patients. There were 3 patients with incomplete obstruction misdiagnosed to be complete obstruction by IB-CEUS. The diagnostic accuracy of biliary obstruction degree was 96.3% (77/80). Conclusion: IB-CEUS could improve the visualization of the drainage catheters and evaluate the biliary obstructive level and degree during PTBD. IB-CEUS may be the potential substitute to FC in the PTBD procedure.

  17. Ultrasound-targeted microbubble destruction enhances naked plasmid DNA transfection in rabbit Achilles tendons in vivo.

    Science.gov (United States)

    Qiu, L; Zhang, L; Wang, L; Jiang, Y; Luo, Y; Peng, Y; Lin, L

    2012-07-01

    The study was to investigate the probability of increasing the transfection of the gene in tendons by ultrasound-targeted microbubble destruction (UTMD), and to search for the most suitable transfection conditions. A mixture of microbubbles and enhanced green fluorescent protein (EGFP) plasmids was injected into rabbit Achilles tendons by different administration routes and the tendons were ultrasound pulse by different ultrasonic conditions in order to determine the most appropriate conditions. Then, the rabbits were divided into four groups: (1) ultrasound + microbubbles + plasmid; (2) ultrasound+ plasmid; (3) microbubble + plasmid; (4) plasmid only. EGFP expression in the tendons and other tissues, and the damage to tendon and paratenon were all observed. The results showed that EGFP expression in the tendon was higher by ultrasound pulse with 2 W cm(-2) of output intensity and a 20% duty cycle for 10 min. Local injection was determined to be the better administration route. Among the four groups, EGFP expression in Group 1 was higher than that in other groups. EGFP expression was highest on seventh day, then it gradually decrease over time, and lasted more than 56 days. EGFP expression was not found in other tissues. There was no obvious injury caused by UTMD. Under suitable conditions, it is feasible to use UTMD as a safe and effective gene transfection therapy for tendon injuries.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  19. Molecular ultrasound imaging: current status and future directions

    International Nuclear Information System (INIS)

    Deshpande, N.; Needles, A.; Willmann, J.K.

    2010-01-01

    Targeted contrast-enhanced ultrasound (molecular ultrasound) is an emerging imaging strategy that combines ultrasound technology with novel molecularly-targeted ultrasound contrast agents for assessing biological processes at the molecular level. Molecular ultrasound contrast agents are nano- or micro-sized particles that are targeted to specific molecular markers by adding high-affinity binding ligands onto the surface of the particles. Following intravenous administration, these targeted ultrasound contrast agents accumulate at tissue sites overexpressing specific molecular markers, thereby enhancing the ultrasound imaging signal. High spatial and temporal resolution, real-time imaging, non-invasiveness, relatively low costs, lack of ionising irradiation and wide availability of ultrasound systems are advantages compared to other molecular imaging modalities. In this article we review current concepts and future directions of molecular ultrasound imaging, including different classes of molecular ultrasound contrast agents, ongoing technical developments of pre-clinical and clinical ultrasound systems, the potential of molecular ultrasound for imaging different diseases at the molecular level, and the translation of molecular ultrasound into the clinic.

  20. Microbubbles in macrocysts - Contrast-enhanced ultrasound assisted sclerosant therapy of a congenital macrocystic lymphangioma: a case report.

    Science.gov (United States)

    Menendez-Castro, Carlos; Zapke, Maren; Fahlbusch, Fabian; von Goessel, Heiko; Rascher, Wolfgang; Jüngert, Jörg

    2017-07-06

    Congenital cystic lymphangiomas are benign malformations due to a developmental disorder of lymphatic vessels. Besides surgical excision, sclerosant therapy of these lesions by intracavitary injection of OK-432 (Picibanil®), a lyophilized mixture of group A Streptococcus pyogenes, is a common therapeutical option. For an appropriate application of OK-432, a detailed knowledge about the structure and composition of the congenital cystic lymphangioma is essential. SonoVue® is a commercially available contrast agent commonly used in sonography by intravenous and intracavitary application. Here we report the case of 2 month old male patient with a large thoracic congenital cystic lymphangioma. Preinterventional imaging of the malformation was performed by contrast-enhanced ultrasound after intracavitary application of SonoVue® immediately followed by a successful sclerotherapy with OK-432. Contrast agent-enhanced ultrasound imaging offers a valuable option to preinterventionally clarify the anatomic specifications of a congenital cystic lymphangioma in more detail than by single conventional sonography. By the exact knowledge about the composition and especially about the intercystic communications of the lymphangioma sclerosant therapy becomes safer and more efficient.

  1. Optimization of Contrast-to-Tissue Ratio by Adaptation of Transmitted Ternary Signal in Ultrasound Pulse Inversion Imaging

    Directory of Open Access Journals (Sweden)

    Sébastien Ménigot

    2013-01-01

    Full Text Available Ultrasound contrast imaging has provided more accurate medical diagnoses thanks to the development of innovating modalities like the pulse inversion imaging. However, this latter modality that improves the contrast-to-tissue ratio (CTR is not optimal, since the frequency is manually chosen jointly with the probe. However, an optimal choice of this command is possible, but it requires precise information about the transducer and the medium which can be experimentally difficult to obtain, even inaccessible. It turns out that the optimization can become more complex by taking into account the kind of generators, since the generators of electrical signals in a conventional ultrasound scanner can be unipolar, bipolar, or tripolar. Our aim was to seek the ternary command which maximized the CTR. By combining a genetic algorithm and a closed loop, the system automatically proposed the optimal ternary command. In simulation, the gain compared with the usual ternary signal could reach about 3.9 dB. Another interesting finding was that, in contrast to what is generally accepted, the optimal command was not a fixed-frequency signal but had harmonic components.

  2. Do Anesthetic Techniques Influence the Threshold for Glomerular Capillary Hemorrhage Induced in Rats by Contrast-Enhanced Diagnostic Ultrasound?

    Science.gov (United States)

    Miller, Douglas L; Lu, Xiaofang; Fabiilli, Mario; Dou, Chunyan

    2016-02-01

    Glomerular capillary hemorrhage can be induced by ultrasonic cavitation during contrast-enhanced diagnostic ultrasound (US) exposure, an important nonthermal US bioeffect. Recent studies of pulmonary US exposure have shown that thresholds for another nonthermal bioeffect of US, pulmonary capillary hemorrhage, is strongly influenced by whether xylazine is included in the specific anesthetic technique. The objective of this study was to determine the influence of xylazine on contrast-enhanced diagnostic US-induced glomerular capillary hemorrhage. In this study, anesthesia with ketamine only was compared to ketamine plus xylazine for induction of glomerular capillary hemorrhage in rats by 1.6-MHz intermittent diagnostic US with a microsphere contrast agent (similar to Definity; Lantheus Medical Imaging, Inc, North Billerica, MA). Glomerular capillary hemorrhage was measured as a percentage of glomeruli with hemorrhage found in histologic sections for groups of rats scanned at different peak rarefactional pressure amplitudes. There was a significant difference between the magnitude of the glomerular capillary hemorrhage between the anesthetics at 2.3 MPa, with 45.6% hemorrhage for ketamine only, increasing to 63.2% hemorrhage for ketamine plus xylazine (P Ultrasound in Medicine.

  3. Perfusion quantification in contrast-enhanced ultrasound (CEUS)--ready for research projects and routine clinical use.

    Science.gov (United States)

    Tranquart, F; Mercier, L; Frinking, P; Gaud, E; Arditi, M

    2012-07-01

    With contrast-enhanced ultrasound (CEUS) now established as a valuable imaging modality for many applications, a more specific demand has recently emerged for quantifying perfusion and using measured parameters as objective indicators for various disease states. However, CEUS perfusion quantification remains challenging and is not well integrated in daily clinical practice. The development of VueBox™ alleviates existing limitations and enables quantification in a standardized way. VueBox™ operates as an off-line software application, after dynamic contrast-enhanced ultrasound (DCE-US) is performed. It enables linearization of DICOM clips, assessment of perfusion using patented curve-fitting models, and generation of parametric images by synthesizing perfusion information at the pixel level using color coding. VueBox™ is compatible with most of the available ultrasound platforms (nonlinear contrast-enabled), has the ability to process both bolus and disruption-replenishment kinetics loops, allows analysis results and their context to be saved, and generates analysis reports automatically. Specific features have been added to VueBox™, such as fully automatic in-plane motion compensation and an easy-to-use clip editor. Processing time has been reduced as a result of parallel programming optimized for multi-core processors. A long list of perfusion parameters is available for each of the two administration modes to address all possible demands currently reported in the literature for diagnosis or treatment monitoring. In conclusion, VueBox™ is a valid and robust quantification tool to be used for standardizing perfusion quantification and to improve the reproducibility of results across centers. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Clinical Applications of Contrast-Enhanced Ultrasound in the Pediatric Work-Up of Focal Liver Lesions and Blunt Abdominal Trauma

    DEFF Research Database (Denmark)

    Laugesen, Nicolaj Grønbæk; Nolsoe, Christian Pallson; Rosenberg, Jacob

    2017-01-01

    of CEUS is indeed promising. However, no ultrasound contrast agent manufactured today is registered for pediatric use in Europe. The contrast agent SonoVue(®) has recently been approved by the FDA under the name of Lumason(®) to be used in hepatic investigations in adults and children. This article...... help reduce radiation exposure and use of iodinated contrast agents in pediatrics, thereby potentially reducing complications in routine imaging.......In pediatrics ultrasound has long been viewed more favorably than imaging that exposes patients to radiation and iodinated contrast or requires sedation. It is child-friendly and diagnostic capabilities have been improved with the advent of contrast-enhanced ultrasound (CEUS). The application...

  5. Contrast ultrasound-guided photothermal therapy using gold nanoshelled microcapsules in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shumin [Department of Ultrasonography, Peking University Third Hospital, Beijing 100083 (China); Ordos Center Hospital, Ordos, Inner Mongolia 017000 (China); Dai, Zhifei [Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871 (China); Ke, Hengte [Nanomedicine and Biosensor Laboratory, School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001 (China); Qu, Enze [Department of Ultrasonography, Peking University Third Hospital, Beijing 100083 (China); Qi, Xiaoxu; Zhang, Kuo [Department of Laboratory Animal Science, Peking University Health Science Center, Beijing 100019 (China); Wang, Jinrui, E-mail: jinrui_wang@sina.com [Department of Ultrasonography, Peking University Third Hospital, Beijing 100083 (China)

    2014-01-15

    Objectives: The purpose of this study was to test whether dual functional gold nano-shelled microcapsules (GNS-MCs) can be used as an ultrasound imaging enhancer and as an optical absorber for photothermal therapy (PTT) in a rodent model of breast cancer. Methods: GNS-MCs were fabricated with an inner air and outer gold nanoshell spherical structure. Photothermal cytotoxicity of GNS-MCs was tested with BT474 cancer cells in vitro and non-obese diabetes-SCID (NOD/SCID) mice with breast cancer. GNS-MCs were injected into the tumor under ultrasound guidance and treated with near-infrared (NIR) laser irradiation. The photothermal ablative effectiveness of GNS-MCs was evaluated by measuring the surface and internal temperature of the tumor as well as the size of the tumor using histological confirmation. Results: NIR laser irradiation resulted in significant tumor cell death in GNS-MCs-treated BT474 cells in vitro. GNS-MCs were able to serve as an ultrasound enhancer to guide the intratumoral injection of GNS-MCs and ensure their uniform distribution. In vivo studies revealed that NIR laser irradiation increased the intratumoral temperature to nearly 70 °C for 8 min in GNS-MCs-treated mice. Tumor volumes decreased gradually and tumors were completely ablated in 6 out of 7 mice treated with GNS-MCs and laser irradiation by 17 days after treatment. Conclusion: This study demonstrates that ultrasound-guided PTT with theranostic GNS-MCs is a promising technique for in situ treatment of breast cancer.

  6. Lung Surfactant Microbubbles Increase Lipophilic Drug Payload for Ultrasound-Targeted Delivery

    OpenAIRE

    Sirsi, Shashank R.; Fung, Chinpong; Garg, Sumit; Tianning, Mary Y.; Mountford, Paul A.; Borden, Mark A.

    2013-01-01

    The cavitation response of circulating microbubbles to targeted ultrasound can be used for noninvasive, site-specific delivery of shell-loaded materials. One challenge for microbubble-mediated delivery of lipophilic compounds is the limitation of drug loading into the microbubble shell, which is commonly a single phospholipid monolayer. In this study, we investigated the use of natural lung surfactant extract (Survanta?, Abbott Nutrition) as a microbubble shell material in order to improve dr...

  7. HematoPorphyrin Monomethyl Ether polymer contrast agent for ultrasound/photoacoustic dual-modality imaging-guided synergistic high intensity focused ultrasound (HIFU) therapy.

    Science.gov (United States)

    Yan, Sijing; Lu, Min; Ding, Xiaoya; Chen, Fei; He, Xuemei; Xu, Chunyan; Zhou, Hang; Wang, Qi; Hao, Lan; Zou, Jianzhong

    2016-08-18

    This study is to prepare a hematoporphyrin monomethyl ether (HMME)-loaded poly(lactic-co-glycolic acid) (PLGA) microcapsules (HMME/PLGA), which could not only function as efficient contrast agent for ultrasound (US)/photoacoustic (PA) imaging, but also as a synergistic agent for high intensity focused ultrasound (HIFU) ablation. Sonosensitizer HMME nanoparticles were integrated into PLGA microcapsules with the double emulsion evaporation method. After characterization, the cell-killing and cell proliferation-inhibiting effects of HMME/PLGA microcapsules on ovarian cancer SKOV3 cells were assessed. The US/PA imaging-enhancing effects and synergistic effects on HIFU were evaluated both in vitro and in vivo. HMME/PLGA microcapsules were highly dispersed with well-defined spherical morphology (357 ± 0.72 nm in diameter, PDI = 0.932). Encapsulation efficiency and drug-loading efficiency were 58.33 ± 0.95% and 4.73 ± 0.15%, respectively. The HMME/PLGA microcapsules remarkably killed the SKOV3 cells and inhibited the cell proliferation, significantly enhanced the US/PA imaging results and greatly enhanced the HIFU ablation effects on ovarian cancer in nude mice by the HMME-mediated sono-dynamic chemistry therapy (SDT). HMME/PLGA microcapsules represent a potential multifunctional contrast agent for HIFU diagnosis and treatment, which might provide a novel strategy for the highly efficient imaging-guided non-invasive HIFU synergistic therapy for cancers by SDT in clinic.

  8. Dynamic Contrast-Enhanced Ultrasound of Colorectal Liver Metastases as an Imaging Modality for Early Response Prediction to Chemotherapy

    DEFF Research Database (Denmark)

    Mogensen, Marie Benzon; Hansen, Martin Lundsgaard; Henriksen, Birthe Merete

    2017-01-01

    Our aim was to investigate whether dynamic contrast-enhanced ultrasound (DCE-US) can detect early changes in perfusion of colorectal liver metastases after initiation of chemotherapy. Newly diagnosed patients with colorectal cancer with liver metastases were enrolled in this explorative prospective...... study. Patients were treated with capecitabine or 5-fluorouracil-based chemotherapy with or without bevacizumab. DCE-US was performed before therapy (baseline) and again 10 days after initiation of treatment. Change in contrast-enhancement in one liver metastasis (indicator lesion) was measured....... Treatment response was evaluated with a computed tomography (CT) scan after three cycles of treatment and the initially observed DCE-US change of the indicator lesion was related to the observed CT response. Eighteen patients were included. Six did not complete three series of chemotherapy...

  9. Effects of high-fat diet and losartan on renal cortical blood flow using contrast ultrasound imaging.

    Science.gov (United States)

    Declèves, Anne-Emilie; Rychak, Joshua J; Smith, Dan J; Sharma, Kumar

    2013-11-01

    Obesity-related kidney disease occurs as a result of complex interactions between metabolic and hemodynamic effects. Changes in microvascular perfusion may play a major role in kidney disease; however, these changes are difficult to assess in vivo. Here, we used perfusion ultrasound imaging to evaluate cortical blood flow in a mouse model of high-fat diet-induced kidney disease. C57BL/6J mice were randomized to a standard diet (STD) or a high-fat diet (HFD) for 30 wk and then treated either with losartan or a placebo for an additional 6 wk. Noninvasive ultrasound perfusion imaging of the kidney was performed during infusion of a microbubble contrast agent. Blood flow within the microvasculature of the renal cortex and medulla was derived from imaging data. An increase in the time required to achieve full cortical perfusion was observed for HFD mice relative to STD. This was reversed following treatment with losartan. These data were concurrent with an increased glomerular filtration rate in HFD mice compared with STD- or HFD-losartan-treated mice. Losartan treatment also abrogated fibro-inflammatory disease, assessed by markers at the protein and messenger level. Finally, a reduction in capillary density was found in HFD mice, and this was reversed upon losartan treatment. This suggests that alterations in vascular density may be responsible for the elevated perfusion time observed by imaging. These data demonstrate that ultrasound contrast imaging is a robust and sensitive method for evaluating changes in renal microvascular perfusion and that cortical perfusion time may be a useful parameter for evaluating obesity-related renal disease.

  10. Applicator for in-vitro ultrasound-activated targeted drug delivery

    Science.gov (United States)

    Gerold, B.; Gourevich, D.; Volovick, A.; Xu, D.; Arditti, F.; Prentice, P.; Cochran, S.; Gnaim, J.; Medan, Y.; Wang, L.; Melzer, A.

    2012-10-01

    Reducing toxicity and improving uptake of cancer drugs in tumors are important goals of targeted drug delivery (TDD). Ultrasonic drug release from various encapsulants has been a focus of many research groups. However, a single standard ultrasonic device, viable for use by biologists, is not currently present in the market. The device reported here is designed to allow investigation of the impact of ultrasound on cellular uptake and cell viability in-vitro. In it, single-element transducers with different operating frequencies are mounted below a standard 96-well plate. The plate is moved above the transducers, such that each line of wells can be sonicated at a different frequency. To assess the device, 96-well plates were seeded with cells and sonicated using different ultrasonic parameters, with and without doxorubicin. Cell viability was measured by colorimetric MTT assay and the uptake of doxorubicin by cells was also determined. The device proved to be highly viable in preliminary tests; it demonstrated that change in ultrasonic parameters produces different effect on cells. For example, increase in uptake of doxorubicin was demonstrated following ultrasound application. The growing interest in ultrasound-activated TDD emphasizes the need for standardization of the ultrasound device and the one reported here may offer some indications of how that may be achieved. It is planned to further improve the prototype by increasing the number of ultrasonic frequencies and degrees of freedom for each transducer.

  11. Targeted Ultrasound of an Indeterminate Breast Lesion on Mammography: When Does It Influence Management?

    Science.gov (United States)

    Sohail, Saba; Masroor, Imrana; Afzal, Shaista

    2015-08-01

    To determine the change over mammographic diagnosis, BI-RADS category and management following targeted ultrasound of an indeterminate lesion seen on mammography and associated factors, if any. Descriptive, analytical study. Radiology Department, The Aga Khan University Hospital and Clifton Medical Services, Karachi, from April 2010 to May 2011. Patients referred for targeted breast ultrasound following X-ray mammography were selected regardless of age. Targeted Ultrasound (TUS) was defined as a limited ultrasound of a specific lesion or breast part as indicated by the referring source. Comparison was made between the post mammography and post TUS lesion characterization, diagnosis and BI-RADS category (0-5) which was taken as a measure of management change. Those were evaluated to determine significance of age, marital status, parity, breast parenchymal pattern ( dense, fatty, heterogeneous), referring source for the TUS (radiology resident, radiologist or surgeon), lesion characteristics (density, echogenecity, shape, location, margins, size, depth-to-width ratio, enhancement or shadowing), presenting symptoms or signs and reason for TUS. Ap-value of 0.05 or less was taken as significant. There were a total of 342 patients with mean age of 49.7 ±13.5 years. It assigned a definite category in 232 patients with an indefinite category (0) on mammography requiring further investigation. It decreased the suspicion for malignancy in 180 (77.58%) by assigning a low BI-RADS category and increased the suspicion in 52 (22.41%). The factors significantly associated with this changes included clinical indication being diagnostic (p management of an indeterminate breast lesion in a high number of patients, particularly when there was a lump as indication for imaging in the presence of risk factors in a patient with otherwise heterogeneously dense breast parenchyma.

  12. Applicability of contrast-enhanced ultrasound in the diagnosis of plantar fasciitis

    DEFF Research Database (Denmark)

    Broholm, Rikke; Pingel, Jessica; Simonsen, Lene

    2017-01-01

    -mode ultrasound (US) in patients with plantar fasciitis (PF). 20 patients with unilateral PF were included and were divided by US in insertional thickening (10), midsubstance thickening (5) and no US changes (5). The MV was measured simultaneously in both heels. Four areas in the plantar fascia and plantar fat...... pad were measured independently by two observers. Inter- and intra-observer correlation analyses were performed. The asymptomatic heels showed a constantly low MV, and for the whole group of patients a significantly higher MV was found in the symptomatic plantar fascia and plantar fat pad. Inter...

  13. Diagnosis of urachal anomalies in infancy and childhood by contrast fistulography, ultrasound and CT

    International Nuclear Information System (INIS)

    Nagasaki, A.; Handa, N.; Kawanami, T.

    1991-01-01

    From 1981 to 1989 seventeen cases of pediatric patients with urachal remnants have been treated at the Fukuoka Municipal Children's Hospital (2 patent urachus, 5 urachal cyst, 9 urachal sinus, 1 urachal diverticulum). The cases of patent urachus were discovered in the neonates due to a urine discharge from the umbilicus; in the older children, cysts or sinuses accompanied by an infection led to the diagnosis of the urachal anomaly. In 8 of 11 cases, fistulography established the diagnosis. In 9 of 12 cases, ultrasound imaging was diagnostically successful, as was CT in all 3 cases that were given scans. (orig.)

  14. Diagnostic accuracy of contrast-enhanced ultrasound for the differential diagnosis of hepatocellular carcinoma: ESCULAP versus CEUS-LI-RADS.

    Science.gov (United States)

    Schellhaas, Barbara; Görtz, Ruediger S; Pfeifer, Lukas; Kielisch, Christian; Neurath, Markus F; Strobel, Deike

    2017-09-01

    A comparison is made of two contrast-enhanced ultrasound (CEUS) algorithms for the diagnosis of hepatocellular carcinoma (HCC) in high-risk patients: Erlanger Synopsis of Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at Risk (ESCULAP) and American College of Radiology Contrast-Enhanced Ultrasound-Liver Imaging Reporting and Data System (ACR-CEUS-LI-RADSv.2016). Focal liver lesions in 100 high-risk patients were assessed using both CEUS algorithms (ESCULAP and CEUS-LI-RADSv.2016) for a direct comparison. Lesions were categorized according to size and contrast enhancement in the arterial, portal venous and late phases.For the definite diagnosis of HCC, categories ESCULAP-4, ESCULAP-Tr and ESCULAP-V and CEUS-LI-RADS-LR-5, LR-Tr and LR-5-V were compared. In addition, CEUS-LI-RADS-category LR-M (definitely/probably malignant, but not specific for HCC) and ESCULAP-category C [intrahepatic cholangiocellular carcinoma (ICC)] were compared.Histology, CE-computed tomography and CE-MRI served as reference standards. The reference standard among 100 lesions included 87 HCCs, six ICCs and seven non-HCC-non-ICC-lesions. For the diagnosis of HCC, the diagnostic accuracy of CEUS was significantly higher with ESCULAP versus CEUS-LI-RADS (94.3%/72.4%; pdiagnostic accuracy for ICC (LR-M/ESCULAP-C) was identical with both algorithms (50%), with higher PPV for ESCULAP-C versus LR-M (75 vs. 50%). CEUS-based algorithms contribute toward standardized assessment and reporting of HCC-suspect lesions in high-risk patients. ESCULAP shows significantly higher diagnostic accuracy, sensitivity and negative predictive value with no loss of specificity compared with CEUS-LI-RADS. Both algorithms have an excellent PPV. Arterial hyperenhancement is the key feature for the diagnosis of HCC with CEUS. Washout should not be a necessary prerequisite for the diagnosis of definite HCC. CEUS-LI-RADS in its current version is inferior to ESCULAP for the noninvasive diagnosis of HCC

  15. In vivo Photoacoustic Imaging of Prostate Cancer Using Targeted Contrast Agent

    Science.gov (United States)

    2016-11-01

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

  16. Standardization of dynamic contrast-enhanced ultrasound for the evaluation of antiangiogenic therapies: the French multicenter Support for Innovative and Expensive Techniques Study.

    Science.gov (United States)

    Lassau, Nathalie; Chapotot, Louis; Benatsou, Baya; Vilgrain, Valérie; Kind, Michèle; Lacroix, Joëlle; Cuinet, Marie; Taieb, Sophie; Aziza, Richard; Sarran, Antony; Labbe, Catherine; Gallix, Benoît; Lucidarme, Olivier; Ptak, Yvette; Rocher, Laurence; Caquot, Louis Michel; Chagnon, Sophie; Marion, Denis; Luciani, Alain; Uzan-Augui, Joëlle; Koscielny, Serge

    2012-12-01

    The objectives of this study are to describe the standardization and dissemination of dynamic contrast-enhanced ultrasound (DCE-US) for the evaluation of antiangiogenic treatments in solid tumors across 19 oncology centers in France and to define a quality score to account for the variability of the evaluation criteria used to collect DCE-US data. This prospective Soutien aux Techniques Innovantes Coûteuses (Support for Innovative and Expensive Techniques) DCE-US study included patients with metastatic breast cancer, melanoma, colon cancer, gastrointestinal stromal tumors, renal cell carcinoma and patients with primary hepatocellular carcinoma tumors treated with antiangiogenic therapy. The DCE-US method was made available across 19 oncology centers in France. Overall, 2339 DCE-US examinations were performed by 65 radiologists in 539 patients.One target site per patient was studied. Standardized DCE-US examinations were performed before treatment (day 0) and at days 7, 15, 30, and 60. Dynamic contrast-enhanced ultrasound data were transferred from the different sites to the main study center at the Institut Gustave-Roussy for analysis. Quantitative analyses were performed with a mathematical model to determine 7 DCE-US functional parameters using raw linear data. Radiologists had to evaluate 6 criteria that were potentially linked to the precision of the evaluation of these parameters: lesion size, target motion, loss of target, clear borders, total acquisition of wash-in, and vascular recognition imaging window adapted to the lesion size.Eighteen DCE-US examinations were randomly selected from the Soutien aux Techniques Innovantes Coûteuses (Support for Innovative and Expensive Techniques) database. Each examination was quantified twice by 8 engineers/radiologists trained to evaluate the perfusion parameters. The intraobserver variability was estimated on the basis of differences between examinations performed by the same radiologist. The mean coefficient of

  17. Effect of contrast-enhanced ultrasound on differential diagnosis of intrahepatic cholangiocarcinoma and arterial phase enhanced hepatic inflammatory lesions

    Institute of Scientific and Technical Information of China (English)

    Shanshan Yin; Qiuli Cui; Kun Yan; Wei Yang; Wei Wu; Liping Bao; Minhua Chen

    2017-01-01

    Objective:To investigate differential diagnosis between intrahepatic cholangiocarcinoma (ICC) and arterial phase enhanced hepatic inflammatory lesions in patients without liver cirrhosis using contrast-enhanced ultrasound (CEUS).Methods:ICC and hepatic inflammatory lesions cases with CEUS and pathological diagnosis between Sep 2013 and Oct 2016 were investigated retrospectively.Imaging features of conventional ultrasound and CEUS were analyzed.The parameters of time intensity curve (TIC),including the arrival time,peak intensity (PI) in the lesions,the starting time for washout,and the intensity difference at 3 min (△I3) after contrast agent infection between the lesion and the liver parenchyma,were compared between ICC and hepatic inflammatory lesions.Results:Twenty-five ICC and fifteen inflammatory patients were included in this study.Seventeen ICC (68.0%) and two inflammatory cases (13.3%) showed bile duct dilatation on conventional ultrasound.Using CEUS,three ICC cases (12.0%) were misdiagnosed as inflammatory lesions and three inflammatory lesions (20.0%) as ICC;two ICC (8.0%) and one inflammatory case (6.7%) could not be made definite diagnosis.Washout started at 34.5±3.5 s and 61.5± 12.9 s for ICC and inflammatory lesions respectively (P<0.001).The intensity difference between lesion and liver parenchyma at 3 min after contrast agent injection was 10.8±3.1 dB in ICC and 4.2±2.3 dB in inflammatory group (P<0.00 1).The sensitivity and specificity differentiating ICC and inflammatory lesions were 76% and 87% if the cut-offvalue of the intensity difference was 7.7 dB.Conclusions:Combined with TIC analysis,and particularly with the characteristic of the early-starting and obvious washout in ICC,CEUS can be useful in differential diagnosis between hepatic inflammatory lesions and ICC.

  18. Targeted drug delivery with focused ultrasound-induced blood-brain barrier opening using acoustically-activated nanodroplets.

    Science.gov (United States)

    Chen, Cherry C; Sheeran, Paul S; Wu, Shih-Ying; Olumolade, Oluyemi O; Dayton, Paul A; Konofagou, Elisa E

    2013-12-28

    Focused ultrasound (FUS) in the presence of systemically administered microbubbles has been shown to locally, transiently and reversibly increase the permeability of the blood-brain barrier (BBB), thus allowing targeted delivery of therapeutic agents in the brain for the treatment of central nervous system diseases. Currently, microbubbles are the only agents that have been used to facilitate the FUS-induced BBB opening. However, they are constrained within the intravascular space due to their micron-size diameters, limiting the delivery effect at or near the microvessels. In the present study, acoustically-activated nanodroplets were used as a new class of contrast agents to mediate FUS-induced BBB opening in order to study the feasibility of utilizing these nanoscale phase-shift particles for targeted drug delivery in the brain. Significant dextran delivery was achieved in the mouse hippocampus using nanodroplets at clinically relevant pressures. Passive cavitation detection was used in the attempt to establish a correlation between the amount of dextran delivered in the brain and the acoustic emission recorded during sonication. Conventional microbubbles with the same lipid shell composition and perfluorobutane core as the nanodroplets were also used to compare the efficiency of an FUS-induced dextran delivery. It was found that nanodroplets had a higher BBB opening pressure threshold but a lower stable cavitation threshold than microbubbles, suggesting that contrast agent-dependent acoustic emission monitoring was needed. A more homogeneous dextran delivery within the targeted hippocampus was achieved using nanodroplets without inducing inertial cavitation or compromising safety. Our results offered a new means of developing the FUS-induced BBB opening technology for potential extravascular targeted drug delivery in the brain, extending the potential drug delivery region beyond the cerebral vasculature. © 2013.

  19. A comparison of prostate tumor targeting strategies using magnetic resonance imaging-targeted, transrectal ultrasound-guided fusion biopsy.

    Science.gov (United States)

    Martin, Peter R; Cool, Derek W; Fenster, Aaron; Ward, Aaron D

    2018-03-01

    Magnetic resonance imaging (MRI)-targeted, three-dimensional (3D) transrectal ultrasound (TRUS)-guided prostate biopsy aims to reduce the 21-47% false-negative rate of clinical two-dimensional (2D) TRUS-guided systematic biopsy, but continues to yield false-negative results. This may be improved via needle target optimization, accounting for guidance system errors and image registration errors. As an initial step toward the goal of optimized prostate biopsy targeting, we investigated how needle delivery error impacts tumor sampling probability for two targeting strategies. We obtained MRI and 3D TRUS images from 49 patients. A radiologist and radiology resident assessed these MR images and contoured 81 suspicious regions, yielding tumor surfaces that were registered to 3D TRUS. The biopsy system's root-mean-squared needle delivery error (RMSE) and systematic error were modeled using an isotropic 3D Gaussian distribution. We investigated two different prostate tumor-targeting strategies using (a) the tumor's centroid and (b) a ring in the lateral-elevational plane. For each simulation, targets were spaced at equal arc lengths on a ring with radius equal to the systematic error magnitude. A total of 1000 biopsy simulations were conducted for each tumor, with RMSE and systematic error magnitudes ranging from 1 to 6 mm. The difference in median tumor sampling probability and probability of obtaining a 50% core involvement was determined for ring vs centroid targeting. Our simulation results indicate that ring targeting outperformed centroid targeting in situations where systematic error exceeds RMSE. In these instances, we observed statistically significant differences showing 1-32% improvement in sampling probability due to ring targeting. Likewise, we observed statistically significant differences showing 1-39% improvement in 50% core involvement probability due to ring targeting. Our results suggest that the optimal targeting scheme for prostate biopsy depends on

  20. The value of ultrasound contrast for assessing cancer cell proliferation and invasion function as well as angiogenesis in lesions of in patients with gastric cancer

    Directory of Open Access Journals (Sweden)

    Qin Yang

    2017-06-01

    Full Text Available Objective: To study the value of ultrasound contrast for assessing cancer cell proliferation and invasion as well as angiogenesis in lesions of in patients with gastric cancer. Methods: A total of 39 patients with gastric cancer and 48 patients with gastric ulcer who were treated in our hospital between August 2012 and May 2016 were included in gastric cancer group and gastric ulcer group respectively, and 50 healthy subjects who accepted gastroscopy in our hospital during the same period were included in normal control group. The day after admission, color Doppler diasonograph was used to test the gastric ultrasound contrast parameters; fluorescence quantitative PCR method was used to detect the proliferation and invasion gene mRNA expression in stomach tissue; enzyme-linked immunosorbent assay (ELISA was used to detect the serum angiogenesis index levels. Results: Ultrasound contrast parameters ET and TTP levels of gastric cancer group and gastric ulcer group were significantly lower than those of normal control group, and ultrasound contrast parameters ET and TTP levels of gastric cancer group were significantly lower than those of gastric ulcer group; Stat3, Survivin, Bcl-2, 毬-catenin, eIF4E, CD44, UHRF1 and c-met mRNA expression in tissue as well as VEGF, EGFR, HIF-毩 and Ang-2 levels in serum of gastric cancer group were higher than those of gastric ulcer group and normal control group while E-cadherin mRNA expression in tissue was lower than those of gastric ulcer group and normal control group; Spearman correlation analysis showed that ultrasound contrast parameters ET and TTP levels were correlated with the cancer cell proliferation and invasion function as well as angiogenesis indexes in lesions. Conclusion: Ultrasound contrast parameters can accurately assess the malignant degree of gastric cancer, and is expected to become the reliable means for early diagnosis and treatment guidance of gastric cancer in the future.

  1. [Value of contrast-enhanced ultrasound (CEUS) in the differential diagnosis between benign and malignant renal neoplasms].

    Science.gov (United States)

    Zhang, Sheng; Wang, Xiao-qing; Xin, Xiao-jie; Xu, Yong

    2013-05-01

    To investigate the value of contrast enhanced ultrasound (CEUS) imaging in the differential diagnosis between benign and malignant renal neoplasms. Two hundred and forty-five cases of renal space-occupying lesions confirmed by biopsy or surgical pathology were included in this study. The CEUS features of the renal space-occupying lesions, i.e., the enhancement degree, homogeneity of enhancement, washing-in and washing-out time and enhancement pattern, were retrospectively analyzed. There were 210 cases of malignant renal tumors and 35 cases of benign lesions. The CEUS modes of the malignant renal tumors included "quick in and quick out" 82 cases, "quick in and slow out" 64 cases, "slow in and quick out" 18 cases and "slow in and slow out" 46 cases; good enhancement 150 cases (71.4%) and inhomogeneous enhancement 180 cases (85.7%).Both the contrast agent filling defect area and solid component enhancement of solid-cystic tumors were important features of malignant renal tumors. In the 35 cases of benign lesions,the CEUS modes included "quick in and quick out" 4 cases, "quick in and slow out" 8 cases, "slow in and quick out" 10 cases and "slow in and slow out" 13 cases. Most of the benign tumors showed low enhancement 51.4% (18/35) and inhomogeneous enhancement 54.3% (19/35). There were significant differences between the malignant and benign renal neoplasms in CEUS mode, degree of enhancement and homogeneity of enhancement (P benign and malignant tumors were 77.1% and 83.8%, respectively, while the two-dimensional ultrasound diagnosis of benign and malignant tumors were 68.6% and 76.7%, respectively, with a significant difference (P benign and malignant renal lesions.

  2. Contrast-enhanced harmonic endoscopic ultrasound in solid lesions of the pancreas: results of a pilot study.

    Science.gov (United States)

    Napoleon, B; Alvarez-Sanchez, M V; Gincoul, R; Pujol, B; Lefort, C; Lepilliez, V; Labadie, M; Souquet, J C; Queneau, P E; Scoazec, J Y; Chayvialle, J A; Ponchon, T

    2010-07-01

    Distinguishing pancreatic adenocarcinoma from other pancreatic masses remains challenging with current imaging techniques. This prospective study aimed to evaluate the accuracy of a new procedure, imaging the microcirculation pattern of the pancreas by contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) with a new Olympus prototype echo endoscope. 35 patients presenting with solid pancreatic lesions were prospectively enrolled. All patients had conventional B mode and power Doppler EUS. After an intravenous bolus injection of 2.4 ml of a second-generation ultrasound contrast agent (SonoVue) CEH-EUS was then performed with a new Olympus prototype echo endoscope (xGF-UCT 180). The microvascular pattern was compared with the final diagnosis based on the pathological examination of specimens from surgery or EUS-guided fine-needle aspiration (EUS-FNA) or on follow-up for at least 12 months. The final diagnoses were: 18 adenocarcinomas, 9 neuroendocrine tumors, 7 chronic pancreatitis, and 1 stromal tumor. Power Doppler failed to display microcirculation, whereas harmonic imaging demonstrated it in all cases. Out of 18 lesions with a hypointense signal on CEH-EUS, 16 were adenocarcinomas. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy of hypointensity for diagnosing pancreatic adenocarcinoma were 89 %, 88 %, 88 %, 89 %, and 88.5 %, compared with corresponding values of 72 %, 100 %, 77 %, 100 %, and 86 % for EUS-FNA. Of five adenocarcinomas with false-negative results at EUS-FNA, four had a hypointense echo signal at CEH-EUS. CEH-EUS with the new Olympus prototype device successfully visualizes the microvascular pattern in pancreatic solid lesions, and may be useful for distinguishing adenocarcinomas from other pancreatic masses.

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

    DEFF Research Database (Denmark)

    Andersen, Klaus Scheldrup; Jensen, Jørgen Arendt

    2009-01-01

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

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

    DEFF Research Database (Denmark)

    Andersen, Klaus Scheldrup; Jensen, Jørgen Arendt

    2010-01-01

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

  5. New mechanisms for non-porative ultrasound stimulation of cargo delivery to cell cytosol with targeted perfluorocarbon nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Soman, N R; Marsh, J N; Lanza, G M; Wickline, S A [Washington University School of Medicine, Consortium for Translational Research in Advanced Imaging and Nanomedicine, CTRAIN, Campus Box 8215, St Louis, MO 63110 (United States)], E-mail: saw@wuphys.wustl.edu

    2008-05-07

    The cell membrane constitutes a major barrier for non-endocytotic intracellular delivery of therapeutic molecules from drug delivery vehicles. Existing approaches to breaching the cell membrane include cavitational ultrasound (with microbubbles), electroporation and cell-penetrating peptides. We report the use of diagnostic ultrasound for intracellular delivery of therapeutic bulky cargo with the use of molecularly targeted liquid perfluorocarbon (PFC) nanoparticles. To demonstrate the concept, we used a lipid with a surrogate polar head group, nanogold-DPPE, incorporated into the nanoparticle lipid monolayer. Melanoma cells were incubated with nanogold particles and this was followed by insonication with continuous wave ultrasound (2.25 MHz, 5 min, 0.6 MPa). Cells not exposed to ultrasound showed gold particles partitioned only in the outer bilayer of the cell membrane with no evidence of the intracellular transit of nanogold. However, the cells exposed to ultrasound exhibited numerous nanogold-DPPE components inside the cell that appeared polarized inside intracellular vesicles demonstrating cellular uptake and trafficking. Further, ultrasound-exposed cells manifested no incorporation of calcein or the release of lactate dehydrogenase. These observations are consistent with a mechanism that suggests that ultrasound is capable of stimulating the intracellular delivery of therapeutic molecules via non-porative mechanisms. Therefore, non-cavitational adjunctive ultrasound offers a novel paradigm in intracellular cargo delivery from PFC nanoparticles.

  6. New mechanisms for non-porative ultrasound stimulation of cargo delivery to cell cytosol with targeted perfluorocarbon nanoparticles

    International Nuclear Information System (INIS)

    Soman, N R; Marsh, J N; Lanza, G M; Wickline, S A

    2008-01-01

    The cell membrane constitutes a major barrier for non-endocytotic intracellular delivery of therapeutic molecules from drug delivery vehicles. Existing approaches to breaching the cell membrane include cavitational ultrasound (with microbubbles), electroporation and cell-penetrating peptides. We report the use of diagnostic ultrasound for intracellular delivery of therapeutic bulky cargo with the use of molecularly targeted liquid perfluorocarbon (PFC) nanoparticles. To demonstrate the concept, we used a lipid with a surrogate polar head group, nanogold-DPPE, incorporated into the nanoparticle lipid monolayer. Melanoma cells were incubated with nanogold particles and this was followed by insonication with continuous wave ultrasound (2.25 MHz, 5 min, 0.6 MPa). Cells not exposed to ultrasound showed gold particles partitioned only in the outer bilayer of the cell membrane with no evidence of the intracellular transit of nanogold. However, the cells exposed to ultrasound exhibited numerous nanogold-DPPE components inside the cell that appeared polarized inside intracellular vesicles demonstrating cellular uptake and trafficking. Further, ultrasound-exposed cells manifested no incorporation of calcein or the release of lactate dehydrogenase. These observations are consistent with a mechanism that suggests that ultrasound is capable of stimulating the intracellular delivery of therapeutic molecules via non-porative mechanisms. Therefore, non-cavitational adjunctive ultrasound offers a novel paradigm in intracellular cargo delivery from PFC nanoparticles

  7. New mechanisms for non-porative ultrasound stimulation of cargo delivery to cell cytosol with targeted perfluorocarbon nanoparticles

    Science.gov (United States)

    Soman, N. R.; Marsh, J. N.; Lanza, G. M.; Wickline, S. A.

    2008-05-01

    The cell membrane constitutes a major barrier for non-endocytotic intracellular delivery of therapeutic molecules from drug delivery vehicles. Existing approaches to breaching the cell membrane include cavitational ultrasound (with microbubbles), electroporation and cell-penetrating peptides. We report the use of diagnostic ultrasound for intracellular delivery of therapeutic bulky cargo with the use of molecularly targeted liquid perfluorocarbon (PFC) nanoparticles. To demonstrate the concept, we used a lipid with a surrogate polar head group, nanogold-DPPE, incorporated into the nanoparticle lipid monolayer. Melanoma cells were incubated with nanogold particles and this was followed by insonication with continuous wave ultrasound (2.25 MHz, 5 min, 0.6 MPa). Cells not exposed to ultrasound showed gold particles partitioned only in the outer bilayer of the cell membrane with no evidence of the intracellular transit of nanogold. However, the cells exposed to ultrasound exhibited numerous nanogold-DPPE components inside the cell that appeared polarized inside intracellular vesicles demonstrating cellular uptake and trafficking. Further, ultrasound-exposed cells manifested no incorporation of calcein or the release of lactate dehydrogenase. These observations are consistent with a mechanism that suggests that ultrasound is capable of stimulating the intracellular delivery of therapeutic molecules via non-porative mechanisms. Therefore, non-cavitational adjunctive ultrasound offers a novel paradigm in intracellular cargo delivery from PFC nanoparticles.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  9. Ultrasound effects on brain-targeting mannosylated liposomes: in vitro and blood-brain barrier transport investigations.

    Science.gov (United States)

    Zidan, Ahmed S; Aldawsari, Hibah

    2015-01-01

    Delivering drugs to intracerebral regions can be accomplished by improving the capacity of transport through blood-brain barrier. Using sertraline as model drug for brain targeting, the current study aimed at modifying its liposomal vesicles with mannopyranoside. Box-Behnken design was employed to statistically optimize the ultrasound parameters, namely ultrasound amplitude, time, and temperature, for maximum mannosylation capacity, sertraline entrapment, and surface charge while minimizing vesicular size. Moreover, in vitro blood-brain barrier transport model was established to assess the transendothelial capacity of the optimized mannosylated vesicles. Results showed a dependence of vesicular size, mannosylation capacity, and sertraline entrapment on cavitation and bubble implosion events that were related to ultrasound power amplitude, temperature. However, short ultrasound duration was required to achieve >90% mannosylation with nanosized vesicles (ultrasound parameters of 65°C, 27%, and 59 seconds for ultrasound temperature, amplitude, and time were elucidated to produce 81.1%, 46.6 nm, and 77.6% sertraline entrapment, vesicular size, and mannosylation capacity, respectively. Moreover, the transendothelial ability was significantly increased by 2.5-fold by mannosylation through binding with glucose transporters. Hence, mannosylated liposomes processed by ultrasound could be a promising approach for manufacturing and scale-up of brain-targeting liposomes.

  10. Investigations of internal noise levels for different target sizes, contrasts, and noise structures

    Science.gov (United States)

    Han, Minah; Choi, Shinkook; Baek, Jongduk

    2014-03-01

    To describe internal noise levels for different target sizes, contrasts, and noise structures, Gaussian targets with four different sizes (i.e., standard deviation of 2,4,6 and 8) and three different noise structures(i.e., white, low-pass, and highpass) were generated. The generated noise images were scaled to have standard deviation of 0.15. For each noise type, target contrasts were adjusted to have the same detectability based on NPW, and the detectability of CHO was calculated accordingly. For human observer study, 3 trained observers performed 2AFC detection tasks, and correction rate, Pc, was calculated for each task. By adding proper internal noise level to numerical observer (i.e., NPW and CHO), detectability of human observer was matched with that of numerical observers. Even though target contrasts were adjusted to have the same detectability of NPW observer, detectability of human observer decreases as the target size increases. The internal noise level varies for different target sizes, contrasts, and noise structures, demonstrating different internal noise levels should be considered in numerical observer to predict the detection performance of human observer.

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

    Directory of Open Access Journals (Sweden)

    F. Salaffi

    2011-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-04-09

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2010-04-01

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

  15. Diagnostic accuracy of magnetic resonance, computed tomography and contrast enhanced ultrasound in radiological multimodality assessment of peribiliary liver metastases.

    Directory of Open Access Journals (Sweden)

    Vincenza Granata

    Full Text Available We compared diagnostic performance of Magnetic Resonance (MR, Computed Tomography (CT and Ultrasound (US with (CEUS and without contrast medium to identify peribiliary metastasis.We identified 35 subjects with histological proven peribiliary metastases who underwent CEUS, CT and MR study. Four radiologists evaluated the presence of peribiliary lesions, using a 4-point confidence scale. Echogenicity, density and T1-Weigthed (T1-W, T2-W and Diffusion Weighted Imaging (DWI signal intensity as well as the enhancement pattern during contrast studies on CEUS, CT and MR so as hepatobiliary-phase on MRI was assessed.All lesions were detected by MR. CT detected 8 lesions, while US/CEUS detected one lesion. According to the site of the lesion, respect to the bile duct and hepatic parenchyma: 19 (54.3% were periductal, 15 (42.8% were intra-periductal and 1 (2.8% was periductal-intrahepatic. According to the confidence scale MRI had the best diagnostic performance to assess the lesion. CT obtained lower diagnostic performance. There was no significant difference in MR signal intensity and contrast enhancement among all metastases (p>0.05. There was no significant difference in CT density and contrast enhancement among all metastases (p>0.05.MRI is the method of choice for biliary tract tumors but it does not allow a correct differential diagnosis among different histological types of metastasis. The presence of biliary tree dilatation without hepatic lesions on CT and US/CEUS study may be an indirect sign of peribiliary metastases and for this reason the patient should be evaluated by MRI.

  16. Diagnostic Accuracy of Ultrasound, Contrast-enhanced CT, and Conventional MRI for Differentiating Leiomyoma From Leiomyosarcoma.

    Science.gov (United States)

    Gaetke-Udager, Kara; McLean, Karen; Sciallis, Andrew P; Alves, Timothy; Maturen, Katherine E; Mervak, Benjamin M; Moore, Andreea G; Wasnik, Ashish P; Erba, Jake; Davenport, Matthew S

    2016-10-01

    This study aimed to determine whether uterine leiomyoma can be distinguished from uterine leiomyosarcoma on ultrasound (US), computed tomography (CT), and/or magnetic resonance imaging (MRI) without diffusion-weighted imaging. Institutional review board approval was obtained and informed consent was waived for this Health Insurance Portability and Accountability Act-compliant retrospective case-control diagnostic accuracy study. All subjects with resected uterine leiomyosarcoma diagnosed over a 17-year period (1998-2014) at a single institution for whom pre-resection US (n = 10), CT (n = 11), or MRI (n = 7) was available were matched by tumor size and imaging modality with 28 subjects with resected uterine leiomyoma. Six blinded radiologists (three attendings, three residents) assigned 5-point Likert scores for the following features: (1) margins, (2) necrosis, (3) hemorrhage, (4) vascularity, (5) calcifications, (6) heterogeneity, and (7) likelihood of malignancy (primary end point). Mean suspicion scores were calculated and receiver operating characteristic curves were generated. The ability of individual morphologic features to predict malignancy was assessed with logistic regression. Mean suspicion scores were 2.5 ± 1.2 (attendings) and 2.4 ± 1.3 (residents) for leiomyoma, and 2.7 ± 1.3 (attendings) and 2.7 ± 1.4 (residents) for leiomyosarcoma. The areas under the receiver operating characteristic curves (range: 0.330-0.685) were not significantly different from chance, either overall (P = .36-.88) or by any modality (P = .28-.96), for any reader. Reader experience had no effect on diagnostic accuracy. No morphologic parameter was significantly predictive of malignancy (P = .10-.97). Uterine leiomyoma cannot be differentiated accurately from leiomyosarcoma on US, CT, or MRI without diffusion-weighted imaging. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  17. Quality Assurance of Ultrasound Imaging Systems for Target Localization and Online Setup Corrections

    International Nuclear Information System (INIS)

    Tome, Wolfgang A.; Orton, Nigel P.

    2008-01-01

    We describe quality assurance paradigms for ultrasound imaging systems for target localization (UISTL). To determine the absolute localization accuracy of a UISTL, an absolute coordinate system can be established in the treatment room and spherical targets at various depths can be localized. To test the ability of such a system to determine the magnitude of internal organ motion, a phantom that mimics the human male pelvic anatomy can be used to simulate different organ motion ranges. To assess the interuser variability of ultrasound (US) guidance, different experienced users can independently determine the daily organ shifts for the same patients for a number of consecutive fractions. The average accuracy for a UISTL for the localization of spherical targets at various depths has been found to be 0.57 ± 0.47 mm in each spatial dimension for various focal depths. For the phantom organ motion test it was found that the true organ motion could be determined to within 1.0 mm along each axis. The variability between different experienced users who localized the same 5 patients for five consecutive fractions was small in comparison to the indicated shifts. In addition to the quality assurance tests that address the ability of a UISTL to accurately localize a target, a thorough quality assurance program should also incorporate the following two aspects to ensure consistent and accurate localization in daily clinical use: (1) adequate training and performance monitoring of users of the US target localization system, and (2) prescreening of patients who may not be good candidates for US localization

  18. Role of laser contrast and foil thickness in target normal sheath acceleration

    Energy Technology Data Exchange (ETDEWEB)

    Gizzi, L.A. [ILIL, Istituto Nazionale di Ottica, CNR, Via G. Moruzzi 1, Pisa (Italy); INFN Sezione di Pisa, Largo Pontecorvo 3, 56127 Pisa (Italy); Altana, C. [Dipartimento di Fisica e Astronomia, Università degli Studi di Catania (Italy); Laboratori Nazionali del Sud, INFN, Via S. Sofia, Catania (Italy); Brandi, F. [ILIL, Istituto Nazionale di Ottica, CNR, Via G. Moruzzi 1, Pisa (Italy); Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genova (Italy); Cirrone, P. [Laboratori Nazionali del Sud, INFN, Via S. Sofia, Catania (Italy); Cristoforetti, G. [ILIL, Istituto Nazionale di Ottica, CNR, Via G. Moruzzi 1, Pisa (Italy); Fazzi, A. [Energy Department, Polytechnic of Milan, Milan (Italy); INFN, Milan (Italy); Ferrara, P.; Fulgentini, L. [ILIL, Istituto Nazionale di Ottica, CNR, Via G. Moruzzi 1, Pisa (Italy); Giove, D. [INFN-LASA, Via Fratelli Cervi 201, 20090 Segrate (Italy); Koester, P. [ILIL, Istituto Nazionale di Ottica, CNR, Via G. Moruzzi 1, Pisa (Italy); Labate, L. [ILIL, Istituto Nazionale di Ottica, CNR, Via G. Moruzzi 1, Pisa (Italy); INFN Sezione di Pisa, Largo Pontecorvo 3, 56127 Pisa (Italy); Lanzalone, G. [Laboratori Nazionali del Sud, INFN, Via S. Sofia, Catania (Italy); Università degli Studi di Enna Kore, Via delle Olimpiadi, 94100 Enna (Italy); Londrillo, P. [INAF–Osservatorio astronomico Bologna (Italy); Mascali, D.; Muoio, A. [Laboratori Nazionali del Sud, INFN, Via S. Sofia, Catania (Italy); Palla, D. [ILIL, Istituto Nazionale di Ottica, CNR, Via G. Moruzzi 1, Pisa (Italy); INFN Sezione di Pisa, Largo Pontecorvo 3, 56127 Pisa (Italy); Dipartimento di Fisica, Università di Pisa (Italy); Schillaci, F. [Laboratori Nazionali del Sud, INFN, Via S. Sofia, Catania (Italy); Sinigardi, S. [Dipartimento di Fisica e Astronomia, Università di Bologna, Bologna (Italy); INFN, Sez. di Bologna, Via Irnerio 46, 40126 Bologna (Italy); and others

    2016-09-01

    In this paper we present an experimental investigation of laser driven light-ion acceleration using the ILIL laser at an intensity of 2×10{sup 19} W/cm{sup 2}. In the experiment we focused our attention on the identification of the role of target thickness and resistivity in the fast electron transport and in the acceleration process. Here we describe the experimental results concerning the effect of laser contrast in the laser–target interaction regime. We also show preliminary results on ion acceleration which provide information about the role of bulk target ions and surface ions and target dielectric properties in the acceleration process.

  19. Contrast, size, and orientation-invariant target detection in infrared imagery

    Science.gov (United States)

    Zhou, Yi-Tong; Crawshaw, Richard D.

    1991-08-01

    Automatic target detection in IR imagery is a very difficult task due to variations in target brightness, shape, size, and orientation. In this paper, the authors present a contrast, size, and orientation invariant algorithm based on Gabor functions for detecting targets from a single IR image frame. The algorithms consists of three steps. First, it locates potential targets by using low-resolution Gabor functions which resist noise and background clutter effects, then, it removes false targets and eliminates redundant target points based on a similarity measure. These two steps mimic human vision processing but are different from Zeevi's Foveating Vision System. Finally, it uses both low- and high-resolution Gabor functions to verify target existence. This algorithm has been successfully tested on several IR images that contain multiple examples of military vehicles with different size and brightness in various background scenes and orientations.

  20. The role of contrast-enhanced ultrasound (CEUS) in visualizing atherosclerotic carotid plaque vulnerability: Which injection protocol? Which scanning technique?

    Energy Technology Data Exchange (ETDEWEB)

    Iezzi, Roberto, E-mail: roberto.iezzi@rm.unicatt.it [Department of Bioimaging and Radiological Sciences, Institute of Radiology, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168 Rome (Italy); Petrone, Gianluigi [Institute of Pathology, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168, Rome (Italy); Ferrante, Angela [Department of Vascular Surgery, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168 Rome (Italy); Lauriola, Libero [Institute of Pathology, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168, Rome (Italy); Vincenzoni, Claudio [Department of Vascular Surgery, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168 Rome (Italy); Torre, Michele Fabio la [Department of Bioimaging and Radiological Sciences, Institute of Radiology, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168 Rome (Italy); Snider, Francesco [Department of Vascular Surgery, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168 Rome (Italy); Rindi, Guido [Institute of Pathology, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168, Rome (Italy); Bonomo, Lorenzo [Department of Bioimaging and Radiological Sciences, Institute of Radiology, “A. Gemelli” Hospital—Catholic University, L.go A Gemelli 8, 00168 Rome (Italy)

    2015-05-15

    Highlights: • CEUS is a safe and efficacious technique for the identification and characterization of carotid plaque. • CEUS represents a diagnostic tool for the management of patients with carotid plaque, particularly in asymptomatic patients. • Improved diagnostic performance is achieved with the injection of 4 mL bolus of contrast-medium. • Improved diagnostic performance is achieved with the use of Dynamic Imaging rather than late-phase imaging. - Abstract: Purpose: To correlate the degree of plaque vulnerability as determined by contrast-enhanced ultrasound (CEUS) with histological findings. Secondary objectives were to optimize the CEUS acquisition technique and image evaluation methods. Materials and methods: Fifty consecutive patients, either symptomatic and asymptomatic referring to our department in order to perform carotid endarterectomy (TEA), were enrolled. Each patient provided informed consent before undergoing CEUS. Ultrasound examination was performed using high-frequency (8–14 MHz) linear probe and a non-linear pulse inversion technique (mechanical index: 0.09–1.3). A double contrast media injection (Sonovue, 2 mL and 4 mL; Bracco, Italy) was performed. Two videotapes were recorded for every injection: early “dynamic” phase and late “flash” phase, performed with 6 high mechanical index impulses. Movies were quantitatively and qualitatively evaluated. Qualitative and quantitative evaluation were statistically compared to immunohistological diagnosis of vulnerable plaque, considered as gold standard. Results: Qualitative CEUS evaluation obtained high statistical results when compared to immunohistological results, with values of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of 94%, 68%, 87%, 85% and 86%, respectively, which became higher if considering only asymptomatic patient, with a NPV of 91%. Nevertheless, quantitative software evaluation proved less

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

    Science.gov (United States)

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

    2015-07-01

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

  2. Contrast-Enhanced Ultrasound in the Diagnosis of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: Controversy over the ASSLD Guideline

    Directory of Open Access Journals (Sweden)

    Le-Hang Guo

    2015-01-01

    Full Text Available Hepatocellular carcinoma (HCC and intrahepatic cholangiocarcinoma (ICC are both regarded as primary liver cancers, having different biological behaviors and prognoses. Correct differentiation between them is essential for surgical planning and prognosis assessment. In 2005, the American Association for the Study of Liver Diseases (AASLD recommended that noninvasive diagnosis of HCC is achievable by a single dynamic technique (including contrast-enhanced ultrasound (CEUS showing intense arterial uptake followed by washout of contrast in the venous-delayed phases. However, CEUS has been dropped from the diagnostic techniques in the latest AASLD guideline according to the opinion of some authors from Europe that CEUS may offer false positive HCC diagnosis in patients with ICC. Since the update of AASLD guideline has been released, increased attention has been paid to this interesting topic. Remarkable controversy over this issue is present and this removal was not well received in Europe and Asia. This commentary summarized the opinions for the role of CUES in differentiation between HCC and ICC in recent years. It is concluded that prospective studies with strict design and large case series are mandatory to solve the controversies and stratification of ICC in terms of tumor size and liver background is also essential.

  3. Quantitative measurement of portal blood flow by magnetic resonance phase contrast. Comparative study of flow phantom and Doppler ultrasound in vivo

    International Nuclear Information System (INIS)

    Tsunoda, Masatoshi; Kimoto, Shin; Hamazaki, Keisuke; Takeda, Yoshihiro; Hiraki, Yoshio.

    1994-01-01

    A non-invasive method for measuring portal blood flow by magnetic resonance (MR) phase contrast was evaluated in a flow phantom and 20 healthy volunteers. In a flow phantom study, the flow volumes and mean flow velocities measured by MR phase contrast showed close correlations with those measured by electromagnetic flow-metry. In 20 healthy volunteers, the cross-sectional areas, flow volumes and mean flow velocities measured by MR phase contrast correlated well with those measured by the Doppler ultrasound method. Portal blood flow averaged during the imaging time could be measured under natural breathing conditions by using a large number of acquisitions without the limitations imposed on the Doppler ultrasound method. MR phase contrast is considered to be useful for the non-invasive measurement of portal blood flow. (author)

  4. An Algorithm of Image Heterogeneity with Contrast-Enhanced Ultrasound in Differential Diagnosis of Solid Thyroid Nodules.

    Science.gov (United States)

    Jin, Lifang; Xu, Changsong; Xie, Xueqian; Li, Fan; Lv, Xiuhong; Du, Lianfang

    2017-01-01

    Enhancement heterogeneity on contrast-enhanced ultrasonography (CEUS) is used to differentiate between benign and malignant thyroid nodules. In this study, we used an algorithm to quantify enhancement heterogeneity of solid thyroid nodules on CEUS. The heterogeneity value (HV) is calculated as standard deviation/mean intensity × 100 (using Adobe Photoshop). The heterogeneity ratio (HR) is calculated as the ratio of the HV of the nodule to that of the surrounding parenchyma. Three phases-ascending, peak and descending phases-were studied. HV values at ascending (HV a ) and peak (HV p ) phases were significantly higher in malignant nodules than in benign nodules (95.57 ± 43.87 vs. 73.06 ± 44.04, p = 0.009, and 32.53 ± 10.73 vs. 26.44 ± 8.25, p = 0.002, respectively). HR a , HR p and HR d were significantly higher in malignant nodules than in benign nodules (1.93 ± 1.03 vs. 1.00 ± 0.47, p = 0.000, 1.43 ± 0.51 vs. 1.09 ± 0.28, p = 0.000, and 1.33 ± 0.40 vs. 1.08 ± 0.33, p = 0.001, respectively). HR a achieved optimal diagnostic performance on receiver operating characteristic curve analysis. The algorithm used for assessment of image heterogeneity on CEUS examination may be a useful adjunct to conventional ultrasound for differential diagnosis of solid thyroid nodules. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  5. The contribution of contrast enhanced ultrasound for the characterization of benign liver lesions in clinical practice - a monocentric experience.

    Science.gov (United States)

    Martie, Alina; Bota, Simona; Sporea, Ioan; Sirli, Roxana; Popescu, Alina; Danila, Mirela

    2012-12-01

    Contrast-enhanced ultrasound (CEUS) uses second generation microbubble contrast agents and is considered to be a useful imaging method for focal liver lesions (FLLs) characterization. To observe if CEUS increases the diagnostic performance of benign FLLs as compared with standard ultrasonography examination (US). This is a single centre study developed during September 2009- December 2011 in the Department of Gastroenterology and Hepatology, in Timisoara. We evaluated 386 benign FLLs diagnosed by means of CEUS. Before performing CEUS, all FLLs were examined by US and Power Doppler techniques. At CEUS, the benign nature of a lesion was established by the absence of washout in the portal and late phase. The typical features observed using contrast, allowed their classification in a particular type of pathology, according to the 2008 EFSUMB Guidelines. From 386 benign FLLs, 81 (20.9%) of them were diagnosed in patients with chronic liver disease, while 305 (79.1%) were in patients without chronic hepatopathy. In 355 (92%) cases CEUS established a particular type of pathology. The most frequent lesions were: hemangiomas (37.5%), focal fatty alterations (24.8%), complex cysts (10.7%) and regenerative nodules (11.8%). Based on US we correctly estimated the positive diagnosis in 55.7% cases and using CEUS, the diagnostic performance increased up to 92%. In our study, by means of US the estimate positive diagnosis was made in 55.7% of cases. CEUS properly characterized 92% of benign FLLs and increased the diagnostic performance of these lesions, as compared with US.

  6. Contrast-enhanced voiding urosonography (ceVUS) with the intravesical administration of the ultrasound contrast agent Optison™ for vesicoureteral reflux detection in children: a prospective clinical trial.

    Science.gov (United States)

    Ntoulia, Aikaterini; Back, Susan J; Shellikeri, Sphoorti; Poznick, Laura; Morgan, Trudy; Kerwood, Joanne; Christopher Edgar, J; Bellah, Richard D; Reid, Janet R; Jaramillo, Diego; Canning, Douglas A; Darge, Kassa

    2018-02-01

    Contrast-enhanced voiding urosonography (ceVUS) is widely used outside the United States to diagnose vesicoureteral reflux (VUR) in children and is highly sensitive while avoiding exposure to ionizing radiation. At the onset of this study, two ultrasound (US) contrast agents were available in the United States. Pediatric safety data for intravenous administration was published for one, Optison™. This study aimed to evaluate the diagnostic performance and safety of ceVUS using Optison™ and compare its diagnostic efficacy with voiding cystourethrogram (VCUG) for VUR detection and grading in children. The United States Food and Drug Administration and institutional Investigational New Drug authorizations were obtained to conduct a prospective comparative study of ceVUS with Optison™ and VCUG. CeVUS was performed with intravesical administration of 0.2% Optison™/normal saline solution. A standard VCUG followed. Safety assessment included physical examination, and heart rate, pulse oximetry and adverse reactions monitoring before, during and immediately after the examinations. A follow-up questionnaire was completed by telephone 48-h after the studies. Sixty-two pelviureteric units were studied in 30 patients with a mean age of 3.5 years (range: 0.1-17 years) including 21 girls and 9 boys. No severe adverse events occurred. All patients had normal heart rate and blood oxygenation saturation prior to, during and after the studies. At the 48-h follow-up, one patient (3.3%) reported transient dysuria. Taking the VCUG as the reference standard, ceVUS had a sensitivity of 91.7% (95%; confidence interval [CI]: 61.5%-99.8%) and specificity of 98% (95%; CI: 89.4%-99.9%). The concordance between ceVUS and VCUG for VUR detection and grading was 84.3% and 81.8%, respectively. VUR grades were discrepant in 4/11 refluxing pelviureteric units, with VCUG upgrading VUR in 2. Detection of VUR with Optison™ ceVUS was comparable to VCUG without exposure to ionizing radiation

  7. A speeded-up saliency region-based contrast detection method for small targets

    Science.gov (United States)

    Li, Zhengjie; Zhang, Haiying; Bai, Jiaojiao; Zhou, Zhongjun; Zheng, Huihuang

    2018-04-01

    To cope with the rapid development of the real applications for infrared small targets, the researchers have tried their best to pursue more robust detection methods. At present, the contrast measure-based method has become a promising research branch. Following the framework, in this paper, a speeded-up contrast measure scheme is proposed based on the saliency detection and density clustering. First, the saliency region is segmented by saliency detection method, and then, the Multi-scale contrast calculation is carried out on it instead of traversing the whole image. Second, the target with a certain "integrity" property in spatial is exploited to distinguish the target from the isolated noises by density clustering. Finally, the targets are detected by a self-adaptation threshold. Compared with time-consuming MPCM (Multiscale Patch Contrast Map), the time cost of the speeded-up version is within a few seconds. Additional, due to the use of "clustering segmentation", the false alarm caused by heavy noises can be restrained to a lower level. The experiments show that our method has a satisfied FASR (False alarm suppression ratio) and real-time performance compared with the state-of-art algorithms no matter in cloudy sky or sea-sky background.

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

    Science.gov (United States)

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

    2010-01-21

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

  9. High-intensity interstitial ultrasound for thermal ablation of focal cancer targets in prostate

    Science.gov (United States)

    Salgaonkar, Vasant A.; Scott, Serena; Kurhanewicz, John; Diederich, Chris J.

    2017-03-01

    Recent advances in image based techniques such as multi-parametric MRI (MP-MRI) can provide precise targeting of focal disease in the prostate. Thermal ablation of such cancer targets while avoiding rectum, urethra, neurovascular bundles (NVB) and sphincter is clinically challenging. The approach described here employs multi-element ultrasound linear arrays designed for transperineal placement within prostate. They consist of independently powered sectored tubular transducers (6.5 - 8.0 MHz) that provide spatial control of energy deposition in angle and length. Volumetric ablation strategies were investigated through patient-specific biothermal models based on Pennes bioheat transfer equation. The acoustic and heat transfer models used here have been validated in several previous simulation and experimental studies. Focal disease sites in prostate were identified through multi-parametric MR images of representative patient cases (n=3). Focal cancer lesions and critical anatomy (prostate, urethra, rectum, bladder, seminal vesicles) were manually segmented (Mimics, Materialise) and converted to 3D finite element meshes (3-Matic, Materialise). The chosen test cases consisted of patients with medium and large sized glands and models of bulk tissue ablation covered volumes in a single quadrant in posterior prostate, hemi-gland targets and "hockey-stick" targets (lesions in three quadrants). Ultrasound applicator placement was determined such that devices were positioned along the prostate periphery while avoiding surrounding anatomy. Transducer sector angles were chosen based on applicator location within limits of fabrication practicability. Thermal models were numerically solved using finite element methods (FEM) in COMSOL Multiphysics. Temperature and thermal dose distributions were calculated to determine treated volumes (> 240 CEM43C, >52 °C) and safety profiles (<10 CEM43C, <45 °C) for nerve, rectal and urethral sparing. Modeling studies indicated that focal

  10. Imaging of the Achilles tendon in spondyloarthritis: a comparison of ultrasound and conventional, short and ultrashort echo time MRI with and without intravenous contrast

    International Nuclear Information System (INIS)

    Hodgson, R.J.; Emery, P.; Grainger, A.J.; O'Connor, P.J.; Evans, R.; Coates, L.; Marzo-Ortega, H.; Helliwell, P.; McGonagle, D.; Robson, M.D.

    2011-01-01

    To compare conventional MRI, ultrashort echo time MRI and ultrasound for assessing the extent of tendon abnormalities in spondyloarthritis. 25 patients with spondyloarthritis and Achilles symptoms were studied with MRI and ultrasound. MR images of the Achilles tendon were acquired using T1-weighted spin echo, gradient echo and ultrashort echo time (UTE) sequences with echo times (TE) between 0.07 and 16 ms, before and after intravenous contrast medium. Greyscale and power Doppler ultrasound were also performed. The craniocaudal extent of imaging abnormalities measured by a consultant musculoskeletal radiologist was compared between the different techniques. Abnormalities were most extensive on spoiled gradient echo images with TE=2 ms. Contrast enhancement after intravenous gadolinium was greatest on the UTE images (TE=0.07 ms). Fewer abnormalities were demonstrated using unenhanced UTE. Abnormalities were more extensive on MRI than ultrasound. Contrast enhancement was more extensive than power Doppler signal. 3D spoiled gradient echo images with an echo time of 2 ms demonstrate more extensive tendon abnormalities than the other techniques in spondyloarthritis. Abnormalities of vascularity are best demonstrated on enhanced ultrashort echo time images. (orig.)

  11. An ex vivo feasibility experimental study on targeted cell surgery by high intensity focused ultrasound

    Science.gov (United States)

    Wang, Zhi Biao; Wu, Junru; Fang, Liao Qiong; Wang, Hua; Li, Fa Qi; Tian, Yun Bo; Gong, Xiao Bo; Zhang, Hong; Zhang, Lian; Feng, Ruo

    2012-10-01

    High intensity focused ultrasound (HIFU) has become a new noninvasive surgical modality in medicine. A portion of tissue seated inside a patient's body may experience coagulative necrosis after a few seconds of insonification by high intensity focused ultrasound (US) generated by an extracorporeal focusing US transducer. The region of tissue affected by coagulative necrosis (CN) usually has an ellipsoidal shape when the thermal effect due to US absorption plays the dominant role. Its long and short axes are parallel and perpendicular to the US propagation direction respectively. It was shown by ex vivo experiments that the dimension of the short and long axes of the tissue which experiences CN can be as small as 50 μm and 250 μm respectively after one second exposure of US pulse (the spatial and pulse average acoustic power is on the order of tens of Watts and the local acoustic spatial and temporal pulse averaged intensity is on the order of 3 × 104 W/cm2) generated by a 1.6 MHz HIFU transducer of 12 cm diameter and 11 cm geometric focal length (f-number = 0.92). The numbers of cells which suffered CN were estimated to be on the order of 40. This result suggests that HIFU is able to interact with tens of cells at/near its focal zone while keeping the neighboring cells minimally affected, and thus the targeted cell surgery may be achievable.

  12. Targeted therapy of animal eyes with tumors by laser-generated focused ultrasound (Conference Presentation)

    Science.gov (United States)

    Lee, Taehwa; Luo, Wei; Demirci, Hakan; Guo, L. Jay

    2016-03-01

    Cavitation therapy based on high-amplitude focused ultrasound (e.g., Histotripsy) has shown great promise in clinical trials. The technique realizes localized treatments of tissues and diseased cells by controlling cavitation zones, which can be even smaller than its acoustic spot sizes. Also, the short pressure pulse used in the technique can minimize the unwanted heat accumulation, which the conventional piezoelectric transducers suffer from due to low operating frequencies and relatively long acoustic pulses. However, this modality requires bulky system composed of array of piezoelectric elements and electric amplifiers in order to obtain high pressure amplitude. Moreover, especially when treating an area much smaller than the acoustic spot size, this approach may be vulnerable to nucleation sites within the focal volume, which can potentially induce cavitation and thus enlarge the total treatment area. Here, we show targeted cell-level therapy by using laser generated ultrasound. By employing a concave lens coated by a carbon nanotube (CNT)-polymer composite, high-amplitude acoustic pressure can be obtained at a tight focal spot (small focal spot, comparable to cavitation zone, lead to controlled cavitation treatment. Such feature can be exploited for treating intraocular tumors but without harming other parts of the eye (e.g. healthy retina and choroid) and therefore preserve the vision of the patients. We demonstrate that the localized disruption effects can be used for cell-level surgery to remove cells and to kill cells. Some experimental examples are shown using animal eyeballs.

  13. Contrast-enhanced ultrasound evaluation of hepatic microvascular changes in liver diseases.

    Science.gov (United States)

    Ridolfi, Francesco; Abbattista, Teresa; Busilacchi, Paolo; Brunelli, Eugenio

    2012-10-07

    To assess if software assisted-contrast-enhanced ultrasonography (CEUS) provides reproducible perfusion parameters of hepatic parenchyma in patients affected by chronic liver disease. Forty patients with chronic viral liver disease, with (n = 20) or without (n = 20) cirrhosis, and 10 healthy subjects underwent CEUS and video recordings of each examination were then analysed with Esaote's Qontrast software. CEUS dedicated software Qontrast was used to determine peak (the maximum signal intensity), time to peak (TTP), region of blood value (RBV) proportional to the area under the time-intensity curve, mean transit time (MTT) measured in seconds and region of blood flow (RBF). Qontrast-assisted CEUS parameters displayed high inter-observer reproducibility (κ coefficients of 0.87 for MTT and 0.90 TTP). When the region of interest included a main hepatic vein, Qontrast-calculated TTP was significantly shorter in cirrhotic patients (vs non-cirrhotics and healthy subjects) (71.0 ± 11.3 s vs. 82.4 ± 15.6 s, 86.3 ± 20.3 s, P < 0.05). MTTs in the patients with liver cirrhosis were significantly shorter than those of controls (111.9 ± 22.0 s vs. 139.4 ± 39.8 s, P < 0.05), but there was no significant difference between the cirrhotic and non-cirrhotic groups (111.9 ± 22.0 s vs. 110.3 ± 14.6 s). Peak enhancement in the patients with liver cirrhosis was also higher than that observed in controls (23.9 ± 5.9 vs. 18.9 ± 7.1, P = 0.05). There were no significant intergroup differences in the RBVs and RBFs. Qontrast-assisted CEUS revealed reproducible differences in liver perfusion parameters during the development of hepatic fibrogenesis.

  14. Correction of Non-Linear Propagation Artifact in Contrast-Enhanced Ultrasound Imaging of Carotid Arteries: Methods and in Vitro Evaluation.

    Science.gov (United States)

    Yildiz, Yesna O; Eckersley, Robert J; Senior, Roxy; Lim, Adrian K P; Cosgrove, David; Tang, Meng-Xing

    2015-07-01

    Non-linear propagation of ultrasound creates artifacts in contrast-enhanced ultrasound images that significantly affect both qualitative and quantitative assessments of tissue perfusion. This article describes the development and evaluation of a new algorithm to correct for this artifact. The correction is a post-processing method that estimates and removes non-linear artifact in the contrast-specific image using the simultaneously acquired B-mode image data. The method is evaluated on carotid artery flow phantoms with large and small vessels containing microbubbles of various concentrations at different acoustic pressures. The algorithm significantly reduces non-linear artifacts while maintaining the contrast signal from bubbles to increase the contrast-to-tissue ratio by up to 11 dB. Contrast signal from a small vessel 600 μm in diameter buried in tissue artifacts before correction was recovered after the correction. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  15. Stereotactic ultrasound for target volume definition in a patient with prostate cancer and bilateral total hip replacement.

    Science.gov (United States)

    Boda-Heggemann, Judit; Haneder, Stefan; Ehmann, Michael; Sihono, Dwi Seno Kuncoro; Wertz, Hansjörg; Mai, Sabine; Kegel, Stefan; Heitmann, Sigrun; von Swietochowski, Sandra; Lohr, Frank; Wenz, Frederik

    2015-01-01

    Target-volume definition for prostate cancer in patients with bilateral metal total hip replacements (THRs) is a challenge because of metal artifacts in the planning computed tomography (CT) scans. Magnetic resonance imaging (MRI) can be used for matching and prostate delineation; however, at a spatial and temporal distance from the planning CT, identical rectal and vesical filling is difficult to achieve. In addition, MRI may also be impaired by metal artifacts, even resulting in spatial image distortion. Here, we present a method to define prostate target volumes based on ultrasound images acquired during CT simulation and online-matched to the CT data set directly at the planning CT. A 78-year-old patient with cT2cNxM0 prostate cancer with bilateral metal THRs was referred to external beam radiation therapy. T2-weighted MRI was performed on the day of the planning CT with preparation according to a protocol for reproducible bladder and rectal filling. The planning CT was obtained with the immediate acquisition of a 3-dimensional ultrasound data set with a dedicated stereotactic ultrasound system for online intermodality image matching referenced to the isocenter by ceiling-mounted infrared cameras. MRI (offline) and ultrasound images (online) were thus both matched to the CT images for planning. Daily image guided radiation therapy (IGRT) was performed with transabdominal ultrasound and compared with cone beam CT. Because of variations in bladder and rectal filling and metal-induced image distortion in MRI, soft-tissue-based matching of the MRI to CT was not sufficient for unequivocal prostate target definition. Ultrasound-based images could be matched, and prostate, seminal vesicles, and target volumes were reliably defined. Daily IGRT could be successfully completed with transabdominal ultrasound with good accordance between cone beam CT and ultrasound. For prostate cancer patients with bilateral THRs causing artifacts in planning CTs, ultrasound referenced to

  16. Dynamic contrast-enhanced ultrasound and transient arterial occlusion for quantification of arterial perfusion reserve in peripheral arterial disease

    International Nuclear Information System (INIS)

    Amarteifio, E.; Wormsbecher, S.; Krix, M.; Demirel, S.; Braun, S.; Delorme, S.; Böckler, D.; Kauczor, H.-U.; Weber, M.-A.

    2012-01-01

    Objective: To quantify muscular micro-perfusion and arterial perfusion reserve in peripheral arterial disease (PAD) with dynamic contrast-enhanced ultrasound (CEUS) and transient arterial occlusion. Materials and methods: This study had local institutional review board approval and written informed consent was obtained from all subjects. We examined the dominant lower leg of 40 PAD Fontaine stage IIb patients (mean age, 65 years) and 40 healthy volunteers (mean age, 54 years) with CEUS (7 MHz; MI, 0.28) during continuous intravenous infusion of 4.8 mL microbubbles. Transient arterial occlusion at mid-thigh level simulated physical exercise. With time–CEUS–intensity curves obtained from regions of interest within calf muscles, we derived the maximum CEUS signal after occlusion (max) and its time (t max ), slope to maximum (m), vascular response after occlusion (AUC post ), and analysed accuracy, receiver operating characteristic (ROC) curves, and correlations with ankle-brachial index (ABI) and walking distance. Results: All parameters differed in PAD and volunteers (p max was delayed (31.2 ± 13.6 vs. 16.7 ± 8.5 s, p post as optimal parameter combination for diagnosing PAD and therefore impaired arterial perfusion reserve. Conclusions: Dynamic CEUS with transient arterial occlusion quantifies muscular micro-perfusion and arterial perfusion reserve. The technique is accurate to diagnose PAD.

  17. Assessment of skeletal muscle microcirculation in type 2 diabetes mellitus using dynamic contrast-enhanced ultrasound: a pilot study.

    Science.gov (United States)

    Amarteifio, Erick; Wormsbecher, Stephanie; Demirel, Serdar; Krix, Martin; Braun, Simone; Rehnitz, Christoph; Delorme, Stefan; Kauczor, Hans-Ulrich; Weber, Marc-André

    2013-09-01

    To investigate muscular micro-perfusion by employing dynamic contrast-enhanced ultrasound (CEUS) and performing transient arterial occlusion in patients with type 2 diabetes mellitus (DM-2). Twenty DM-2 patients (mean age, 58 ± 8.6 years; duration of diabetes, 15.4 ± 12.1 years) and 20 healthy volunteers (mean age, 54 ± 5.4 years) participated. CEUS was applied to the calf, while 4.8 mL of SonoVue(®) was injected intravenously. At the thigh level, arterial occlusion (60 s) was performed. CEUS parameters (tmax, max, AUCpost and m) were evaluated and Pearson-product-moment correlation coefficients were computed. A moderate negative correlation of HbA1c and max was established (-0.53). Max in patients with DM-2 >10 years was 79.89 ± 37.4. Max in patients with DM-2 duration 10 years was 3924.01 ± 1630.52. AUCpost in patients with DM-2 duration <10 years was 6453.59 ± 3206.23 (p = 0.04). Patients with long history of DM-2 present with impaired muscular perfusion. CEUS and transient arterial occlusion may provide appropriate methods for semi-quantitative evaluation of muscular micro-perfusion in patients with DM-2.

  18. Radiofrequency ablation of renal tumours: diagnostic accuracy of contrast-enhanced ultrasound for early detection of residual tumour

    International Nuclear Information System (INIS)

    Hoeffel, Christine; Pousset, Maud; Elie, Caroline; Timsit, Marc-Olivier; Mejean, Arnaud; Merran, Samuel; Tranquart, Francois; Khairoune, Ahmed; Helenon, Olivier; Correas, Jean-Michel; Joly, Dominique; Richard, Stephane

    2010-01-01

    To evaluate the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) in the early detection of residual tumour after radiofrequency ablation (RFA) of renal tumours. Patients referred to our institution for RFA of renal tumours prospectively underwent CEUS and computed tomography (CT) or magnetic resonance imaging (MRI) before, within 1 day and 6 weeks after treatment. Identification of residual tumour was assessed by three blinded radiologists. Reference standard was CT/MRI performed at least 1 year after RFA. A total of 66 renal tumours in 43 patients (median age 62 years; range 44-71.5) were studied. Inter-reader agreement (κ value) was 0.84 for CEUS. Prevalence of residual disease was 19%. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), respectively, were as follows: 64% [confidence interval (CI) 39-84], 98% [CI 91-100], 82% [CI 52-95] and 92% [CI 83-97] on 24-h CEUS; 79% [CI 52-92], 100% [CI 94-100], 100% [CI 74-100] and 95% [CI 87-100] on 6-week CEUS; 79% [CI 52-92], 95% [CI 86-98], 79% [CI 52-92] and 95% [CI 86-98] on 24-h CT/MRI; and 100% [CI 72-100], 98% [CI 90-100], 91% [CI 62-98] and 100% [CI 93-100] on 6-week CT/MRI. CEUS has high specificity for the early diagnosis of residual tumour after renal RFA. (orig.)

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

    Science.gov (United States)

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

    2017-01-01

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

  20. Targeted Vessel Ablation for More Efficient Magnetic Resonance-Guided High-Intensity Focused Ultrasound Ablation of Uterine Fibroids

    Energy Technology Data Exchange (ETDEWEB)

    Voogt, Marianne J., E-mail: m.voogt@umcutrecht.nl [University Medical Center Utrecht, Department of Radiology (Netherlands); Stralen, Marijn van [University Medical Center Utrecht, Image Sciences Institute (Netherlands); Ikink, Marlijne E. [University Medical Center Utrecht, Department of Radiology (Netherlands); Deckers, Roel; Vincken, Koen L.; Bartels, Lambertus W. [University Medical Center Utrecht, Image Sciences Institute (Netherlands); Mali, Willem P. Th. M.; Bosch, Maurice A. A. J. van den [University Medical Center Utrecht, Department of Radiology (Netherlands)

    2012-10-15

    Purpose: To report the first clinical experience with targeted vessel ablation during magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) treatment of symptomatic uterine fibroids. Methods: Pretreatment T1-weighted contrast-enhanced magnetic resonance angiography was used to create a detailed map of the uterine arteries and feeding branches to the fibroids. A three-dimensional overlay of the magnetic resonance angiography images was registered on 3D T2-weighted pretreatment imaging data. Treatment was focused primarily on locations where supplying vessels entered the fibroid. Patients were followed 6 months after treatment with a questionnaire to assess symptoms and quality of life (Uterine Fibroid Symptom and Quality of Life) and magnetic resonance imaging to quantify shrinkage of fibroid volumes. Results: In two patients, three fibroids were treated with targeted vessel ablation during MR-HIFU. The treatments resulted in almost total fibroid devascularization with nonperfused volume to total fibroid volume ratios of 84, 68, and 86%, respectively, of treated fibroids. The predicted ablated volumes during MR-HIFU in patients 1 and 2 were 45, 40, and 82 ml, respectively, while the nonperfused volumes determined immediately after treatment were 195, 92, and 190 ml respectively, which is 4.3 (patient 1) and 2.3 (patient 2) times higher than expected based on the thermal dose distribution. Fibroid-related symptoms reduced after treatment, and quality of life improved. Fibroid volume reduction ranged 31-59% at 6 months after treatment. Conclusion: Targeted vessel ablation during MR-HIFU allowed nearly complete fibroid ablation in both patients. This technique may enhance the use of MR-HIFU for fibroid treatment in clinical practice.

  1. Multi-frequency accelerating strategy for the contrast source inversion method of ultrasound waveform tomography using pulse data

    Science.gov (United States)

    Lin, Hongxiang; Azuma, Takashi; Qu, Xiaolei; Takagi, Shu

    2017-03-01

    In this work, we construct a multi-frequency accelerating strategy for the contrast source inversion (CSI) method using pulse data in the time domain. CSI is a frequency-domain inversion method for ultrasound waveform tomography that does not require the forward solver through the process of reconstruction. Several prior researches show that the CSI method has a good performance of convergence and accuracy in the low-center-frequency situation. In contrast, utilizing the high-center-frequency data leads to a high-resolution reconstruction but slow convergence on large numbers of grid. Our objective is to take full advantage of all low frequency components from pulse data with the high-center-frequency data measured by the diagnostic device. First we process the raw data in the frequency domain. Then multi-frequency accelerating strategy helps restart CSI in the current frequency using the last iteration result obtained from the lower frequency component. The merit of multi- frequency accelerating strategy is that computational burden decreases at the first few iterations. Because the low frequency component of dataset computes on the coarse grid with assuming a fixed number of points per wavelength. In the numerical test, the pulse data were generated by the K-wave simulator and have been processed to meet the computation of the CSI method. We investigate the performance of the multi-frequency and single-frequency reconstructions and conclude that the multi-frequency accelerating strategy significantly enhances the quality of the reconstructed image and simultaneously reduces the average computational time for any iteration step.

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

    Science.gov (United States)

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

    2017-02-01

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

  3. Real-time contrast ultrasound muscle perfusion imaging with intermediate-power imaging coupled with acoustically durable microbubbles.

    Science.gov (United States)

    Seol, Sang-Hoon; Davidson, Brian P; Belcik, J Todd; Mott, Brian H; Goodman, Reid M; Ammi, Azzdine; Lindner, Jonathan R

    2015-06-01

    There is growing interest in limb contrast-enhanced ultrasound (CEU) perfusion imaging for the evaluation of peripheral artery disease. Because of low resting microvascular blood flow in skeletal muscle, signal enhancement during limb CEU is prohibitively low for real-time imaging. The aim of this study was to test the hypothesis that this obstacle can be overcome by intermediate- rather than low-power CEU when performed with an acoustically resilient microbubble agent. Viscoelastic properties of Definity and Sonazoid were assessed by measuring bulk modulus during incremental increases in ambient pressure to 200 mm Hg. Comparison of in vivo microbubble destruction and signal enhancement at a mechanical index (MI) of 0.1 to 0.4 was performed by sequential reduction in pulsing interval from 10 to 0.05 sec during limb CEU at 7 MHz in mice and 1.8 MHz in dogs. Destruction was also assessed by broadband signal generation during passive cavitation detection. Real-time CEU perfusion imaging with destruction-replenishment was then performed at 1.8 MHz in dogs using an MI of 0.1, 0.2, or 0.3. Sonazoid had a higher bulk modulus than Definity (66 ± 12 vs 29 ± 2 kPa, P = .02) and exhibited less inertial cavitation (destruction) at MIs ≥ 0.2. On in vivo CEU, maximal signal intensity increased incrementally with MI for both agents and was equivalent between agents except at an MI of 0.1 (60% and 85% lower for Sonazoid at 7 and 1.8 MHz, respectively, P power imaging coupled with a durable microbubble contrast agent. Copyright © 2015 American Society of Echocardiography. All rights reserved.

  4. Luminance and chromatic contributions to a hyperacuity task: isolation by contrast polarity and target separation.

    Science.gov (United States)

    Sun, Hao; Cooper, Bonnie; Lee, Barry B

    2012-03-01

    Vernier thresholds are known to be elevated when a target pair has opposite contrast polarity. Polarity reversal is used to assess the role of luminance and chromatic pathways in hyperacuity performance. Psychophysical hyperacuity thresholds were measured for pairs of gratings of various combinations of luminance (Lum) and chromatic (Chr) contrast polarities, at different ratios of luminance to chromatic contrast. With two red-green gratings of matched luminance and chromatic polarity (+Lum+Chr), there was an elevation of threshold at isoluminance. When both luminance and chromatic polarity were mismatched (-Lum-Chr), thresholds were substantially elevated under all conditions. With the same luminance contrast polarity and opposite chromatic polarity (+Lum-Chr) thresholds were only elevated close to isoluminance; in the reverse condition (-Lum+Chr), thresholds were elevated as in the -Lum-Chr condition except close to equiluminance. Similar data were obtained for gratings isolating the short-wavelength cone mechanism. Further psychophysical measurements assessed the role of target separation with matched or mismatched contrast polarity; similar results were found for luminance and chromatic gratings. Comparison physiological data were collected from parafoveal ganglion cells of the macaque retina. Positional precision of ganglion cell signals was assessed under conditions related to the psychophysical measurements. On the basis of these combined observations, it is argued that both magnocellular, parvocellular, and koniocellular pathways have access to cortical positional mechanisms associated with vernier acuity. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2016-01-01

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

  6. In situ targeted activation of an anticancer agent using ultrasound-triggered release of composite droplets.

    Science.gov (United States)

    Bezagu, Marine; Clarhaut, Jonathan; Renoux, Brigitte; Monti, Fabrice; Tanter, Mickael; Tabeling, Patrick; Cossy, Janine; Couture, Olivier; Papot, Sebastien; Arseniyadis, Stellios

    2017-12-15

    The efficiency of a drug is usually highly dependent on the way it is administered or delivered. As such, targeted-therapy, which requires conceiving drug-delivery vehicles that will change their state from a relatively stable structure with a very slow leak-rate to an unstable structure with a fast release, clearly improves the pharmacokinetics, the absorption, the distribution, the metabolism and the therapeutic index of a given drug. In this context, we have developed a particularly effective double stimuli-responsive drug-delivery method allowing an ultrasound-induced release of a monomethylauristatin E-glucuronide prodrug and its subsequent activation by a β-glucuronidase. This led to an increase of cytotoxicity of about 80% on cancer cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Early Detection of Ovarian Cancer by Contrast-Enhanced Ultrasound-Targeted Imaging

    Science.gov (United States)

    2013-09-01

    minutes in a microwave oven . Endogenous peroxidase in the Figure 1. Gross morphology of normal ovaries and ovaries with tumor in laying hens. ( A ) Normal...J Immunol 175, 385–393. [24] Dennis G Jr, Kubagawa H, and Cooper MD (2000). Paired Ig-like receptor homologs in birds and mammals share a common...other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

  9. Targeted Ultrasound for MR-Detected Lesions in Breast Cancer Patients

    International Nuclear Information System (INIS)

    Shin, Jung Hee; Han, Boo Kyung; Choe, Yeon Hyeon; Ko, Kyung Ran; Choi, Nami

    2007-01-01

    To investigate the usefulness of targeted ultrasound (US) in the identification of additional suspicious lesions found by magnetic resonance (MR) imaging in breast cancer patients and the changes in treatment based on the identification of the lesions by the use of targeted US. One-hundred forty nine patients who underwent breast MR imaging for a preoperative evaluation of breast cancer between January 2002 and July 2004 were included in the study. We searched all cases for any additional lesions that were found initially by MR imaging and investigated the performance of targeted US in identifying the lesions. We also investigated their pathological outcomes and changes in treatment as a result of lesion identification. Of the 149 patients with breast cancer, additional suspicious lesions were detected with MR imaging in 62 patients (42%). Of the 69 additional lesions found in those 62 patients, 26 (38%) were confirmed as cancers by histology. Thirty-eight lesions in 31 patients were examined with targeted US and were histologically revealed as cancers in 18 (47%), high risk lesions in two (5%), benign lesions in 15 (39%), and unidentified lesions in three (8%). The cancer rate was statistically higher in lesions with a US correlate than in lesions without a US correlate (p = 0.028). Of 31 patients, the surgical plan was altered in 27 (87%). The use of targeted US justified a change in treatment for 22 patients (81%) and misled five patients (19%) into having an unnecessary surgical excision. Targeted US can play a useful role in the evaluation of additional suspicious lesions detected by MR imaging in breast cancer patients, but is limited in lesions without a US correlate

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

    Directory of Open Access Journals (Sweden)

    Scott D Swanson

    2008-06-01

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

  11. Ultrasound effects on brain-targeting mannosylated liposomes: in vitro and blood–brain barrier transport investigations

    Directory of Open Access Journals (Sweden)

    Zidan AS

    2015-07-01

    Full Text Available Ahmed S Zidan,1,2 Hibah Aldawsari1 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt Abstract: Delivering drugs to intracerebral regions can be accomplished by improving the capacity of transport through blood–brain barrier. Using sertraline as model drug for brain targeting, the current study aimed at modifying its liposomal vesicles with mannopyranoside. Box-Behnken design was employed to statistically optimize the ultrasound parameters, namely ultrasound amplitude, time, and temperature, for maximum mannosylation capacity, sertraline entrapment, and surface charge while minimizing vesicular size. Moreover, in vitro blood–brain barrier transport model was established to assess the transendothelial capacity of the optimized mannosylated vesicles. Results showed a dependence of vesicular size, mannosylation capacity, and sertraline entrapment on cavitation and bubble implosion events that were related to ultrasound power amplitude, temperature. However, short ultrasound duration was required to achieve >90% mannosylation with nanosized vesicles (<200 nm of narrow size distribution. Optimized ultrasound parameters of 65°C, 27%, and 59 seconds for ultrasound temperature, amplitude, and time were elucidated to produce 81.1%, 46.6 nm, and 77.6% sertraline entrapment, vesicular size, and mannosylation capacity, respectively. Moreover, the transendothelial ability was significantly increased by 2.5-fold by mannosylation through binding with glucose transporters. Hence, mannosylated liposomes processed by ultrasound could be a promising approach for manufacturing and scale-up of brain-targeting liposomes. Keywords: CNS delivery, sizing, lipid based formulations, quality by design, sertraline hydrochloride

  12. Enhancement characteristics of benign and malignant focal peripheral nodules in the peripheral zone of the prostate gland studied using contrast-enhanced transrectal ultrasound

    International Nuclear Information System (INIS)

    Tang, J.; Yang, J.-C.; Luo, Y.; Li, J.; Li, Y.; Shi, H.

    2008-01-01

    Aim: To assess the value of contrast-enhanced grey-scale transrectal ultrasound (CETRUS) in predicting the nature of peripheral zone hypoechoic lesions of the prostate. Materials and Methods: Ninety-one patients with peripheral zone hypoechoic lesions on ultrasound were evaluated with CETRUS followed by lesion-specific and sextant transrectal ultrasound-guided biopsies. The enhancement patterns of the lesions were observed and graded subjectively using adjacent peripheral zone tissue as the reference. Time to enhancement (AT), time to peak intensity (TTP) and peak intensity (PI) were quantified within each nodule. Ultrasound findings were correlated with biopsy findings. Results: Transrectal ultrasound-guided biopsy of the hypoechoic lesions revealed prostate cancer in 44 patients and benign prostatic diseases in 47. The intensity of enhancement within the lesions were graded as no enhancement, increased, equal, or decreased compared with adjacent peripheral zone tissue in two, 30, five and seven in the prostate cancer group and 14, 15, four and 14 in the benign group, respectively. The difference was statistically significant (p < 0.05). The peak enhancement intensity was found to be the most optimal discriminatory parameter (area under curve AUC 0.70; 95% CI: 0.58, 0.82). Conclusion: Malignant hypoechoic nodules in the peripheral zone of the prostate are more likely to enhance early and more intensely on CETRUS. A non-enhanced hypoechoic peripheral zone lesion was more likely to be benign

  13. Ultrasound-targeted microbubble destruction improves the low density lipoprotein receptor gene expression in HepG2 cells

    International Nuclear Information System (INIS)

    Guo Dongping; Li Xiaoyu; Sun, Ping; Tang Yibo; Chen Xiuying; Chen Qi; Fan Leming; Zang Bin; Shao Lizheng; Li Xiaorong

    2006-01-01

    Ultrasound-targeted microbubble destruction had been employed in gene delivery and promised great potential. Liver has unique features that make it attractive for gene therapy. However, it poses formidable obstacles to hepatocyte-specific gene delivery. This study was designed to test the efficiency of therapeutic gene transfer and expression mediated by ultrasound/microbubble strategy in HepG 2 cell line. Air-filled albumin microbubbles were prepared and mixed with plasmid DNA encoding low density lipoprotein receptor (LDLR) and green fluorescent protein. The mixture of the DNA and microbubbles was administer to cultured HepG 2 cells under variable ultrasound conditions. Transfection rate of the transferred gene and cell viability were assessed by FACS analysis, confocal laser scanning microscopy, Western blot analysis and Trypan blue staining. The result demonstrated that microbubbles with ultrasound irradiation can significantly elevate exogenous LDLR gene expression and the expressed LDLRs were functional and active to uptake their ligands. We conclude that ultrasound-targeted microbubble destruction has the potential to promote safe and efficient LDLR gene transfer into hepatocytes. With further refinement, it may represent an effective nonviral avenue of gene therapy for liver-involved genetic diseases

  14. Diagnostic performance of power doppler and ultrasound contrast agents in early imaging-based diagnosis of organ-confined prostate cancer: Is it possible to spare cores with contrast-guided biopsy?

    Energy Technology Data Exchange (ETDEWEB)

    Delgado Oliva, F., E-mail: frandelgol@hotmail.com; Arlandis Guzman, S.; Bonillo García, M.; Broseta Rico, E.; Boronat Tormo, F.

    2016-10-15

    Objectives: To evaluate the diagnostic performance of gray scale transrectal ultrasound-B-mode US (BMUS), power Doppler (PDUS), and sonographic contrast (CEUS) in early imaging-based diagnosis of localized prostate cancer (PCa) and to compare the diagnostic profitability of randomized biopsy (RB), US-targeted prostate biopsy by means of PDUS and CEUS. Material and methods: A single-center, prospective, transversal, epidemiological study was conducted from January 2010 to January 2014. We consecutively included patients who an imaging study of the prostate with BMUS, PDUS, and CEUS was performed, followed by prostate biopsy due to clinical suspicion of prostate cancer (PSA 4–20 ng/mL and/or rectal exam suggestive of malignancy). The diagnostic performance of BMUS, PDUS, and CEUS was determined by calculating the Sensitivity (S), Specificity (Sp), Predictive values (PV), and diagnostic odds ratio (OR) of the diagnosis tests and, for these variables, in the population general and based on their clinical stage according to rectal exam (cT1 and cT2). PCa detection rates determined by means of a randomized 10-core biopsy scheme were compared with detection rates of CEUS-targeted (SonoVue) 2-core biopsies. Results: Of the initial 984 patients, US contrast SonoVue was administered to 179 (18.2%). The PCa detection rate by organ of BMUS/PDUS in the global population was 38% versus 43% in the subpopulation with CEUS. The mean age of the patients was 64.3 ± 7.01 years (95% CI, 63.75–64.70); mean total PSA was 8.9 ± 3.61 ng/mL (95% CI, 8.67–9.13) and the mean prostate volume was 56.2 ± 29 cc (95% CI, 54.2–58.1). The detection rate by organ of targeted biopsy with BMUS, PDUS, and CEUS were as follows: Global population (10.6, 8.2, 24.5%), stage cT1 (5.6, 4.2, 16.4%), and stage cT2 (32.4, 22.3, 43.5%). Comparing the detection rates of the CEUS-targeted biopsy and randomized biopsy, the following results were obtained: Global population (24.5% vs. 41.8%), stage cT1 (16

  15. Diagnostic performance of power doppler and ultrasound contrast agents in early imaging-based diagnosis of organ-confined prostate cancer: Is it possible to spare cores with contrast-guided biopsy?

    International Nuclear Information System (INIS)

    Delgado Oliva, F.; Arlandis Guzman, S.; Bonillo García, M.; Broseta Rico, E.; Boronat Tormo, F.

    2016-01-01

    Objectives: To evaluate the diagnostic performance of gray scale transrectal ultrasound-B-mode US (BMUS), power Doppler (PDUS), and sonographic contrast (CEUS) in early imaging-based diagnosis of localized prostate cancer (PCa) and to compare the diagnostic profitability of randomized biopsy (RB), US-targeted prostate biopsy by means of PDUS and CEUS. Material and methods: A single-center, prospective, transversal, epidemiological study was conducted from January 2010 to January 2014. We consecutively included patients who an imaging study of the prostate with BMUS, PDUS, and CEUS was performed, followed by prostate biopsy due to clinical suspicion of prostate cancer (PSA 4–20 ng/mL and/or rectal exam suggestive of malignancy). The diagnostic performance of BMUS, PDUS, and CEUS was determined by calculating the Sensitivity (S), Specificity (Sp), Predictive values (PV), and diagnostic odds ratio (OR) of the diagnosis tests and, for these variables, in the population general and based on their clinical stage according to rectal exam (cT1 and cT2). PCa detection rates determined by means of a randomized 10-core biopsy scheme were compared with detection rates of CEUS-targeted (SonoVue) 2-core biopsies. Results: Of the initial 984 patients, US contrast SonoVue was administered to 179 (18.2%). The PCa detection rate by organ of BMUS/PDUS in the global population was 38% versus 43% in the subpopulation with CEUS. The mean age of the patients was 64.3 ± 7.01 years (95% CI, 63.75–64.70); mean total PSA was 8.9 ± 3.61 ng/mL (95% CI, 8.67–9.13) and the mean prostate volume was 56.2 ± 29 cc (95% CI, 54.2–58.1). The detection rate by organ of targeted biopsy with BMUS, PDUS, and CEUS were as follows: Global population (10.6, 8.2, 24.5%), stage cT1 (5.6, 4.2, 16.4%), and stage cT2 (32.4, 22.3, 43.5%). Comparing the detection rates of the CEUS-targeted biopsy and randomized biopsy, the following results were obtained: Global population (24.5% vs. 41.8%), stage cT1 (16

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

    Science.gov (United States)

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

    2015-03-01

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

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

    International Nuclear Information System (INIS)

    Yazdani, Farshad; Fattahi, Bahare; Azizi, Najmodin

    2016-01-01

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

  18. Diagnostic performance of power doppler and ultrasound contrast agents in early imaging-based diagnosis of organ-confined prostate cancer: Is it possible to spare cores with contrast-guided biopsy?

    Science.gov (United States)

    Delgado Oliva, F; Arlandis Guzman, S; Bonillo García, M; Broseta Rico, E; Boronat Tormo, F

    2016-10-01

    To evaluate the diagnostic performance of gray scale transrectal ultrasound-B-mode US (BMUS), power Doppler (PDUS), and sonographic contrast (CEUS) in early imaging-based diagnosis of localized prostate cancer (PCa) and to compare the diagnostic profitability of randomized biopsy (RB), US-targeted prostate biopsy by means of PDUS and CEUS. A single-center, prospective, transversal, epidemiological study was conducted from January 2010 to January 2014. We consecutively included patients who an imaging study of the prostate with BMUS, PDUS, and CEUS was performed, followed by prostate biopsy due to clinical suspicion of prostate cancer (PSA 4-20ng/mL and/or rectal exam suggestive of malignancy). The diagnostic performance of BMUS, PDUS, and CEUS was determined by calculating the Sensitivity (S), Specificity (Sp), Predictive values (PV), and diagnostic odds ratio (OR) of the diagnosis tests and, for these variables, in the population general and based on their clinical stage according to rectal exam (cT1 and cT2). PCa detection rates determined by means of a randomized 10-core biopsy scheme were compared with detection rates of CEUS-targeted (SonoVue) 2-core biopsies. Of the initial 984 patients, US contrast SonoVue was administered to 179 (18.2%). The PCa detection rate by organ of BMUS/PDUS in the global population was 38% versus 43% in the subpopulation with CEUS. The mean age of the patients was 64.3±7.01years (95% CI, 63.75-64.70); mean total PSA was 8.9±3.61ng/mL (95% CI, 8.67-9.13) and the mean prostate volume was 56.2±29cc (95% CI, 54.2-58.1). The detection rate by organ of targeted biopsy with BMUS, PDUS, and CEUS were as follows: Global population (10.6, 8.2, 24.5%), stage cT1 (5.6, 4.2, 16.4%), and stage cT2 (32.4, 22.3, 43.5%). Comparing the detection rates of the CEUS-targeted biopsy and randomized biopsy, the following results were obtained: Global population (24.5% vs. 41.8%), stage cT1 (16% vs. 35%), and stage cT2 (43.5% vs. 66.6%), with a p value0

  19. Characterization of hepatic lesions (≤30 mm) with liver-specific contrast agents: A comparison between ultrasound and magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Masanori, E-mail: machat1215@yahoo.co.jp [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Maruyama, Hitoshi, E-mail: maru-cib@umin.ac.jp [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Shimada, Taro, E-mail: bobtaro51@yahoo.co.jp [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Kamezaki, Hidehiro, E-mail: ugn29814@yahoo.co.jp [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Sekimoto, Tadashi, E-mail: tad_sekimoto@yahoo.co.jp [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Kanai, Fumihiko, E-mail: kanaif@faculty.chiba-u.jp [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Yokosuka, Osamu, E-mail: yokosukao@faculty.chiba-u.jp [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan)

    2013-01-15

    Purpose: Imaging-based differentiation of hepatic lesions (≤30 mm) between well-differentiated hepatocellular carcinomas (w-HCC) and regenerative nodules (RN) presents difficulties. The aim was to compare the diagnostic abilities to differentiate w-HCC from RN using contrast-enhanced ultrasound and magnetic resonance imaging (MRI) both with liver-specific contrast agents. Materials and methods: This prospective study included 67 pathologically proven hepatic lesions (17.5 ± 5.4 mm, 54 w-HCCs, 13 RNs) in 56 patients with chronic hepatitis/cirrhosis (male 40, female 16; 29–79y). Hepatic-arterial/liver-specific phase enhancements were assessed quantitatively by ultrasound with perflubutane microbubble agent and MRI with gadolinium-ethoxybenzyl-diethylenetriamine with respect to the histological findings. Results: Sensitivity, specificity and accuracy of hepatic-arterial phase hyper-enhancement for w-HCC were 59.3%, 100% and 67.2% by ultrasound and 46.3%, 100% and 56.7% by MRI without significant difference. Meanwhile, those of liver-specific-phase hypo-enhancement for w-HCC were 44.4%, 100% and 55.2% by ultrasound and 87.0% (p < 0.0001), 46.2% (p = 0.0052) and 79.1% (p = 0.0032) by MRI. Diagnostic accuracies for w-HCC by area under the receiver operating characteristic curves were higher in the hepatic-arterial phase in ultrasound (0.8316) than MRI (0.6659, p = 0.0101) and similar in the liver-specific phase in ultrasound (0.7225) and MRI (0.7347, p = 0.8814). Conclusions: Hypervascularity is a significant feature which distinguishes w-HCC from RN, and ultrasound exerts a beneficial impact better than MRI for such characterization. However, both imaging have comparable abilities in the characterization of non-hypervascular lesions, compensating mutually for the poor sensitivity of ultrasound and the poor specificity of MRI in the liver-specific phase.

  20. Ultrasound-targeted hepatic delivery of factor IX in hemophiliac mice.

    Science.gov (United States)

    Anderson, C D; Moisyadi, S; Avelar, A; Walton, C B; Shohet, R V

    2016-06-01

    Ultrasound-targeted microbubble destruction (UTMD) was used to direct the delivery of plasmid and transposase-based vectors encoding human factor IX (hFIX) to the livers of hemophilia B (FIX-/-) mice. The DNA vectors were incorporated into cationic lipid microbubbles, injected intravenously, and transfected into hepatocytes by acoustic cavitation of the bubbles as they transited the liver. Ultrasound parameters were identified that produced transfection of hepatocytes in vivo without substantial damage or bleeding in the livers of the FIX-deficient mice. These mice were treated with a conventional expression plasmid, or one containing a piggyBac transposon construct, and hFIX levels in the plasma and liver were evaluated at multiple time points after UTMD. We detected hFIX in the plasma by western blotting from mice treated with either plasmid during the 12 days after UTMD, and in the hepatocytes of treated livers by immunofluorescence. Reductions in clotting time and improvements in the percentage of FIX activity were observed for both plasmids, conventional (4.15±1.98%), and transposon based (2.70±.75%), 4 to 5 days after UTMD compared with untreated FIX (-/-) control mice (0.92±0.78%) (P=0.001 and P=0.012, respectively). Reduced clotting times persisted for both plasmids 12 days after treatment (reflecting percentage FIX activity of 3.12±1.56%, P=0.02 and 3.08±0.10%, P=0.001, respectively). Clotting times from an additional set of mice treated with pmGENIE3-hFIX were evaluated for long-term effects and demonstrated a persistent reduction in average clotting time 160 days after a single treatment. These data suggest that UTMD could be a minimally invasive, nonviral approach to enhance hepatic FIX expression in patients with hemophilia.

  1. Assessing tumor extent on contrast-enhanced spectral mammography versus full-field digital mammography and ultrasound.

    Science.gov (United States)

    Patel, Bhavika K; Garza, Sandra Alheli; Eversman, Sarah; Lopez-Alvarez, Yania; Kosiorek, Heidi; Pockaj, Barbara A

    To compare breast cancer size measurements on full-field digital mammography (FFDM), contrast-enhanced spectral mammography (CEDM), and ultrasound (US), with histologic tumor size used as the reference standard. Material and methods The HIPAA complaint, IRB approved study comprised 88 women with newly diagnosed breast cancer who underwent FFDM and CEDM;74 also had US. Breast density, histologic subtype, and maximum tumor measurements were recorded. Pearson correlation coefficients for FFDM, US, and CEDM vs histopathology were 0.598, 0.639, and 0.859, respectively (P<0.001). The following correlation coefficients were calculated for dense breasts (n=48): histopathology vs FFDM (0.555), US (0.633), and CEDM (0.843) (P<0.001); for nondense breasts (n=40), they were FFDM (0.618), US (0.512), and CEDM (0.885) (P<0.001). For size difference, the mean (SD) for histopathology vs FFDM, US, and CEDM was -1.3 (11.9) mm, -2.8 (11.1) mm, and 2.9 (9.5) mm, respectively. Limits of agreement were -24.8 to 22.0mm, -24.5 to 18.8mm, and -15.6 to 21.4mm, respectively. In patients with biopsy-proven malignancy, size measurements correlated well with histopathologic size, and were higher on CEDM than those for FFDM and US in patients with dense or nondense breasts. The added value of CEDM as a supplement to FFDM in determining tumor size, however, was greater in patients with dense breasts. CEDM may be a promising alternative preoperative measurement tool for breast cancer patients with dense breasts and/or limited access or contraindications to MRI. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Diagnostic accuracy of contrast-enhanced ultrasound in differentiating benign and malignant focal liver lesions: a retrospective study

    International Nuclear Information System (INIS)

    Ooi, Chin-Chin; Low, Su-Chong Albert; Lim, Sze-Ying; Bakar, Rafidah Abu; Lo, Richard Hoau-Gong; Schneider-Kolsky, Michal; Lombardo, Paul

    2010-01-01

    Full text: Purpose: The purpose of this study was to access the diagnostic accuracy of our early experience with contrast-enhanced ultrasound (CEUS) in the characterisation of focal liver lesions (FLLs) using histopathology, contrastenhanced computed tomography (CT), magnetic resonance imaging (MRI) or other imaging follow-up as the standard of reference. Materials and Methods: Seventy-three patients with 82 FLLs who underwent liver CEUS from January 2006 to December 2008 were retrospectively reviewed. CEUS was performed with up to 4.8 mL of SonoVue (Bracco, Milan, Italy) using a low mechanical index mode. The CEUS findings were compared with histopathology, or where histopathology was not available, clinical and imaging follow-up over at least 12 months was used as the standard of reference. Results: Of the 82 FLLs, 50 were malignant and 32 were benign at final diagnosis. CEUS correctly identified 43 malignant FLLs, with final diagnosis confirmed by histopathology in 13 lesions and clinico-radiological follow-up in 30 lesions. Twenty-nine lesions were correctly identified as benign on CEUS, with all these lesions confirmed on c1inico-radiological follow-up. CEUS demonstrated a sensitivity of 86.0% and a specificity of 90.6% in the characterisation of liver lesions as malignant, with an overall accuracy of 87.8% (P< 0.05). Conclusion: Our early experience has shown that CEUS can be accurate in differentiating malignant from benign FLLs and may become a useful first-line imaging tool where CT or MRI are not available or contra-indicated.

  3. Quantitative contrast-enhanced ultrasound evaluation of pathological complete response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy.

    Science.gov (United States)

    Wan, Cai-Feng; Liu, Xue-Song; Wang, Lin; Zhang, Jie; Lu, Jin-Song; Li, Feng-Hua

    2018-06-01

    To clarify whether the quantitative parameters of contrast-enhanced ultrasound (CEUS) can be used to predict pathological complete response (pCR) in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NAC). Fifty-one patients with histologically proved locally advanced breast cancer scheduled for NAC were enrolled. The quantitative data for CEUS and the tumor diameter were collected at baseline and before surgery, and compared with the pathological response. Multiple logistic regression analysis was performed to examine quantitative parameters at CEUS and the tumor diameter to predict the pCR, and receiver operating characteristic (ROC) curve analysis was used as a summary statistic. Multiple logistic regression analysis revealed that PEAK (the maximum intensity of the time-intensity curve during bolus transit), PEAK%, TTP% (time to peak), and diameter% were significant independent predictors of pCR, and the area under the ROC curve was 0.932(Az 1 ), and the sensitivity and specificity to predict pCR were 93.7% and 80.0%. The area under the ROC curve for the quantitative parameters was 0.927(Az 2 ), and the sensitivity and specificity to predict pCR were 81.2% and 94.3%. For diameter%, the area under the ROC curve was 0.786 (Az 3 ), and the sensitivity and specificity to predict pCR were 93.8% and 54.3%. The values of Az 1 and Az 2 were significantly higher than that of Az 3 (P = 0.027 and P = 0.034, respectively). However, there was no significant difference between the values of Az 1 and Az 2 (P = 0.825). Quantitative analysis of tumor blood perfusion with CEUS is superior to diameter% to predict pCR, and can be used as a functional technique to evaluate tumor response to NAC. Copyright © 2018. Published by Elsevier B.V.

  4. Diagnostic Performance and Confidence of Contrast-Enhanced Ultrasound in the Differential Diagnosis of Cystic and Cysticlike Liver Lesions.

    Science.gov (United States)

    Corvino, Antonio; Catalano, Orlando; Corvino, Fabio; Sandomenico, Fabio; Petrillo, Antonella

    2017-09-01

    The aims of this study were to assess the diagnostic performance of contrast-enhanced ultrasound (CEUS) in the characterization of atypical cystic and cysticlike focal liver lesions in comparison with conventional US and to determine whether the use of CEUS can reduce the need for further diagnostic workup. In a 3-year period 48 patients with 50 atypical cystic and cysticlike lesions found at conventional US underwent CEUS. Diagnostic confirmation was obtained in cytohistopathologic examinations, with other imaging modalities, and in follow-up. Overall, there were 24 cystic lesions and 26 cysticlike solid lesions, specifically 32 benign and 18 malignant lesions. The conventional US and CEUS images and cine loops were reviewed by two blinded readers independently. Sensitivity, specificity, area under the ROC curve (A z ), and interobserver agreement were calculated. Diagnostic performance improved after review of CEUS examinations by both readers (conventional US A z = 0.781 vs 0.972; CEUS A z = 0.734 vs 0.957). Interreader agreement increased, although slightly (conventional US weighted κ = 0.894; CEUS weighted κ = 0.953). In terms of differential diagnosis, the occurrence of correctly characterized lesions increased after CEUS for both readers (reader 1, 62% to 98%; reader 2, 56% to 96%). The development of low-acoustic-power CEUS has made it possible to identify several imaging features of cystic and cysticlike focal liver lesions that, in association with history and clinical findings, may help to correctly characterize them. Our data indicate the usefulness of CEUS in the evaluation of patients with these lesions.

  5. Changes in the micro-circulation of skeletal muscle due to varied isometric exercise assessed by contrast-enhanced ultrasound

    International Nuclear Information System (INIS)

    Krix, Martin; Weber, Marc-Andre; Kauczor, Hans-Ulrich; Delorme, Stefan; Krakowski-Roosen, Holger

    2010-01-01

    Purpose: To quantitatively assess local muscle micro-circulation with real-time contrast-enhanced ultrasound (CEUS) during different exercises and compare the results with performed muscle work and global blood flow. Materials and methods: Sixteen low mechanical index CEUS examinations of the right lower leg flexors of healthy volunteers were performed using a continuous infusion of SonoVue (4.8 mL/300 s). Several muscle perfusion parameters were extracted from derived CEUS signal intensity time curves during different isometric exercises (10-50% of maximum individual strength for 20-30 s) and then correlated with the performed muscle work or force, and the whole lower leg blood flow which we measured simultaneously by venous occlusion plethysmography (VOP). Results: The shapes of the CEUS curve during and after exercise differed individually depending on the performed muscle work. The maximum blood volume MAX was observed only after exercise cessation and was significantly correlated with the performed muscle force (r = 0.77, p < 0.0001). The blood volume over exercise time was inversely correlated with the spent muscle work (r = -0.60, p = 0.006). CEUS and VOP measurements correlated only at rest and after the exercise. During exercise, mean CEUS local blood volume decreased (from 3.48 to 2.19 (∼mL)), while mean VOP global blood flow increased (mean, from 3.96 to 7.71 mL/100 mg/min). Conclusion: Real-time low-MI CEUS provides complementary information about the local muscle micro-circulation compared to established blood flow measures. CEUS may be used for a better understanding of muscle perfusion physiology and in the diagnosis of micro-circulation alterations such as in peripheral arterial occlusive disease or diabetic angiopathy.

  6. Detection of urinary leakage after radical retropubic prostatectomy by contrast enhanced ultrasound - do we still need conventional retrograde cystography?

    Science.gov (United States)

    Schoeppler, Gita M; Buchner, Alexander; Zaak, Dirk; Khoder, Wael; Staehler, Michael; Stief, Christian G; Reiser, Maximilian F; Clevert, Dirk-Andre

    2010-12-01

    To prospectively evaluate the accuracy of transvesical contrast-enhanced ultrasound (CEUS) as an alternative method for the detection of anastomotic leakage after radical retropubic prostatectomy (RRP) in comparison with the current standard method of conventional retrograde cystography (CG). Forty-three patients underwent RRP for histologically proven localized prostate cancer. The vesico-urethral anastomosis was evaluated 8 days after RRP by CG and CEUS. Any peri-anastomotic leakage was assessed and determined in CG and CEUS as follows: no extravasation (EV), small leakage (≤0.5 cm), moderate leakage (>0.5 cm to ≤2 cm), large leakage (>2 cm diameter of EV seen). In total, 21 (49%) patients showed a watertight anastomosis. Ten (23%), two (4.7%) and ten (23%) patients showed a small, intermediate and large EV, respectively. In 31 cases (72%) there was 100% agreement of CG and CEUS for detection of no, moderate and large EV, respectively. In nine cases a small and in two cases a moderate EV was categorized as watertight anastomosis by CEUS. Only in one case did CG detect a small EV where a large EV was detected in CEUS. The agreement between both methods was 95% for detecting absence or large leakages. CEUS is a promising imaging modality that seems to be equivalent to CG for detecting the presence of a large anastomotic leakage that is clinically relevant for postoperative persistence of the indwelling catheter. CEUS could be a cheap and time-saving alternative to the CG without exposure of the patient to radiation. © 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.

  7. A local contrast based approach to threshold segmentation for PET target volume delineation

    International Nuclear Information System (INIS)

    Drever, Laura; Robinson, Don M.; McEwan, Alexander; Roa, Wilson

    2006-01-01

    Current radiation therapy techniques, such as intensity modulated radiation therapy and three-dimensional conformal radiotherapy rely on the precise delivery of high doses of radiation to well-defined volumes. CT, the imaging modality that is most commonly used to determine treatment volumes cannot, however, easily distinguish between cancerous and normal tissue. The ability of positron emission tomography (PET) to more readily differentiate between malignant and healthy tissues has generated great interest in using PET images to delineate target volumes for radiation treatment planning. At present the accurate geometric delineation of tumor volumes is a subject open to considerable interpretation. The possibility of using a local contrast based approach to threshold segmentation to accurately delineate PET target cross sections is investigated using well-defined cylindrical and spherical volumes. Contrast levels which yield correct volumetric quantification are found to be a function of the activity concentration ratio between target and background, target size, and slice location. Possibilities for clinical implementation are explored along with the limits posed by this form of segmentation

  8. Application of Ultrasound to Selectively Localize Nanodroplets for Targeted Imaging and Therapy

    Directory of Open Access Journals (Sweden)

    Paul A. Dayton

    2006-07-01

    Full Text Available Lipid-coated perfluorocarbon nanodroplets are submicrometer-diameter liquid-filled droplets with proposed applications in molecularly targeted therapeutics and ultrasound (US imaging. Ultrasonic molecular imaging is unique in that the optimal application of these agents depends not only on the surface chemistry, but also on the applied US field, which can increase receptor-ligand binding and membrane fusion. Theory and experiments are combined to demonstrate the displacement of perfluorocarbon nanoparticles in the direction of US propagation, where a traveling US wave with a peak pressure on the order of megapascals and frequency in the megahertz range produces a particle translational velocity that is proportional to acoustic intensity and increases with increasing center frequency. Within a vessel with a diameter on the order of hundreds of micrometers or larger, particle velocity on the order of hundreds of micrometers per second is produced and the dominant mechanism for droplet displacement is shown to be bulk fluid streaming. A model for radiation force displacement of particles is developed and demonstrates that effective particle displacement should be feasible in the microvasculature. In a flowing system, acoustic manipulation of targeted droplets increases droplet retention. Additionally, we demonstrate the feasibility of US-enhanced particle internalization and therapeutic delivery.

  9. Adding temporally localized noise can enhance the contribution of target knowledge on contrast detection.

    Science.gov (United States)

    Silvestre, Daphné; Cavanagh, Patrick; Arleo, Angelo; Allard, Rémy

    2017-02-01

    External noise paradigms are widely used to characterize sensitivity by comparing the effect of a variable on contrast threshold when it is limited by internal versus external noise. A basic assumption of external noise paradigms is that the processing properties are the same in low and high noise. However, recent studies (e.g., Allard & Cavanagh, 2011; Allard & Faubert, 2014b) suggest that this assumption could be violated when using spatiotemporally localized noise (i.e., appearing simultaneously and at the same location as the target) but not when using spatiotemporally extended noise (i.e., continuously displayed, full-screen, dynamic noise). These previous findings may have been specific to the crowding and 0D noise paradigms that were used, so the purpose of the current study is to test if this violation of noise-invariant processing also occurs in a standard contrast detection task in white noise. The rationale of the current study is that local external noise triggers the use of recognition rather than detection and that a recognition process should be more affected by uncertainty about the shape of the target than one involving detection. To investigate the contribution of target knowledge on contrast detection, the effect of orientation uncertainty was evaluated for a contrast detection task in the absence of noise and in the presence of spatiotemporally localized or extended noise. A larger orientation uncertainty effect was observed with temporally localized noise than with temporally extended noise or with no external noise, indicating a change in the nature of the processing for temporally localized noise. We conclude that the use of temporally localized noise in external noise paradigms risks triggering a shift in process, invalidating the noise-invariant processing required for the paradigm. If, instead, temporally extended external noise is used to match the properties of internal noise, no such processing change occurs.

  10. Age-related differences in skeletal muscle microvascular response to exercise as detected by contrast-enhanced ultrasound (CEUS).

    Science.gov (United States)

    Hildebrandt, Wulf; Schwarzbach, Hans; Pardun, Anita; Hannemann, Lena; Bogs, Björn; König, Alexander M; Mahnken, Andreas H; Hildebrandt, Olaf; Koehler, Ulrich; Kinscherf, Ralf

    2017-01-01

    Aging involves reductions in exercise total limb blood flow and exercise capacity. We hypothesized that this may involve early age-related impairments of skeletal muscle microvascular responsiveness as previously reported for insulin but not for exercise stimuli in humans. Using an isometric exercise model, we studied the effect of age on contrast-enhanced ultrasound (CEUS) parameters, i.e. microvascular blood volume (MBV), flow velocity (MFV) and blood flow (MBF) calculated from replenishment of Sonovue contrast-agent microbubbles after their destruction. CEUS was applied to the vastus lateralis (VLat) and intermedius (VInt) muscle in 15 middle-aged (MA, 43.6±1.5 years) and 11 young (YG, 24.1±0.6 years) healthy males before, during, and after 2 min of isometric knee extension at 15% of peak torque (PT). In addition, total leg blood flow as recorded by femoral artery Doppler-flow. Moreover, fiber-type-specific and overall capillarisation as well as fiber composition were additionally assessed in Vlat biopsies obtained from CEUS site. MA and YG had similar quadriceps muscle MRT-volume or PT and maximal oxygen uptake as well as a normal cardiovascular risk factors and intima-media-thickness. During isometric exercise MA compared to YG reached significantly lower levels in MFV (0.123±0.016 vs. 0.208±0.036 a.u.) and MBF (0.007±0.001 vs. 0.012±0.002 a.u.). In the VInt the (post-occlusive hyperemia) post-exercise peaks in MBV and MBF were significantly lower in MA vs. YG. Capillary density, capillary fiber contacts and femoral artery Doppler were similar between MA and YG. In the absence of significant age-related reductions in capillarisation, total leg blood flow or muscle mass, healthy middle-aged males reveal impaired skeletal muscle microcirculatory responses to isometric exercise. Whether this limits isometric muscle performance remains to be assessed.

  11. Age-related differences in skeletal muscle microvascular response to exercise as detected by contrast-enhanced ultrasound (CEUS.

    Directory of Open Access Journals (Sweden)

    Wulf Hildebrandt

    Full Text Available Aging involves reductions in exercise total limb blood flow and exercise capacity. We hypothesized that this may involve early age-related impairments of skeletal muscle microvascular responsiveness as previously reported for insulin but not for exercise stimuli in humans.Using an isometric exercise model, we studied the effect of age on contrast-enhanced ultrasound (CEUS parameters, i.e. microvascular blood volume (MBV, flow velocity (MFV and blood flow (MBF calculated from replenishment of Sonovue contrast-agent microbubbles after their destruction. CEUS was applied to the vastus lateralis (VLat and intermedius (VInt muscle in 15 middle-aged (MA, 43.6±1.5 years and 11 young (YG, 24.1±0.6 years healthy males before, during, and after 2 min of isometric knee extension at 15% of peak torque (PT. In addition, total leg blood flow as recorded by femoral artery Doppler-flow. Moreover, fiber-type-specific and overall capillarisation as well as fiber composition were additionally assessed in Vlat biopsies obtained from CEUS site. MA and YG had similar quadriceps muscle MRT-volume or PT and maximal oxygen uptake as well as a normal cardiovascular risk factors and intima-media-thickness.During isometric exercise MA compared to YG reached significantly lower levels in MFV (0.123±0.016 vs. 0.208±0.036 a.u. and MBF (0.007±0.001 vs. 0.012±0.002 a.u.. In the VInt the (post-occlusive hyperemia post-exercise peaks in MBV and MBF were significantly lower in MA vs. YG. Capillary density, capillary fiber contacts and femoral artery Doppler were similar between MA and YG.In the absence of significant age-related reductions in capillarisation, total leg blood flow or muscle mass, healthy middle-aged males reveal impaired skeletal muscle microcirculatory responses to isometric exercise. Whether this limits isometric muscle performance remains to be assessed.

  12. Use of Contrast-Enhanced Ultrasound to Study Relationship between Serum Uric Acid and Renal Microvascular Perfusion in Diabetic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Ling Wang

    2015-01-01

    Full Text Available Purpose. To investigate the relationship between uric acid and renal microvascular perfusion in diabetic kidney disease (DKD using contrast-enhanced ultrasound (CEUS method. Materials and Methods. 79 DKD patients and 26 healthy volunteers were enrolled. Renal function and urine protein markers were tested. DKD patients were subdivided into two groups including a normal serum uric acid (SUA group and a high SUA group. Contrast-enhanced ultrasound (CEUS was performed, and low acoustic power contrast-specific imaging was used for quantitative analysis. Results. Normal controls (NCs had the highest levels of AUC, AUC1, and AUC2. Compared to the normal SUA DKD group, high SUA DKD patients had significantly higher IMAX, AUC, and AUC1 (P<0.05. DKD patients with low urinary uric acid (UUA excretion had significantly higher AUC2 compared to DKD patients with normal UUA (P<0.05. Conclusion. Hyperuricemia in DKD patients was associated with a renal ultrasound image suggestive of microvascular hyperperfusion. The CEUS parameter AUC1 holds promise as an indicator for renal microvascular hyperperfusion, while AUC2 might be a useful indicator of declining glomerular filtration rate in DKD patients with decreased excretion of uric acid.

  13. Preparation and in vitro evaluation of poly(D,L-lactide-co-glycolide) air-filled nanocapsules as a contrast agent for ultrasound imaging.

    Science.gov (United States)

    Néstor, Mendoza-Muñoz; Kei, Noriega-Peláez Eddy; Guadalupe, Nava-Arzaluz María; Elisa, Mendoza-Elvira Susana; Adriana, Ganem-Quintanar; David, Quintanar-Guerrero

    2011-10-01

    The aim of this study was to prepare air-filled nanocapsules intended ultrasound contrast agents (UCAs) with a biodegradable polymeric shell composed of poly(d,l-lactide-co-glycolide) (PLGA). Because of their size, current commercial UCAs are not capable of penetrating the irregular vasculature that feeds growing tumors. The new generation of UCAs should be designed on the nanoscale to enhance tumor detection, in addition, the polymeric shell in contrast with monomolecular stabilized UCAs improves the mechanical properties against ultrasound pressure and lack of stability. The preparation method of air-filled nanocapsules was based on a modification of the double-emulsion solvent evaporation technique. Air-filled nanocapsules with a mean diameter of 370±96nm were obtained. Electronic microscopies revealed spherical-shaped particles with smooth surfaces and a capsular morphology, with a shell thickness of ∼50nm. Air-filled nanocapsules showed echogenic power in vitro, providing an enhancement of up to 15dB at a concentration of 0.045mg/mL at a frequency of 10MHz. Loss of signal for air-filled nanocapsules was 2dB after 30min, suggesting high stability. The prepared contrast agent in this work has the potential to be used in ultrasound imaging. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2016-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Hou L

    2015-07-01

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

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

    Science.gov (United States)

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

    2011-09-01

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

  17. Ultra-High-Contrast Laser Acceleration of Relativistic Electrons in Solid Targets

    Energy Technology Data Exchange (ETDEWEB)

    Higginson, Drew Pitney [Univ. of California, San Diego, CA (United States)

    2013-01-01

    The cone-guided fast ignition approach to Inertial Con nement Fusion requires laser-accelerated relativistic electrons to deposit kilojoules of energy within an imploded fuel core to initiate fusion burn. One obstacle to coupling electron energy into the core is the ablation of material, known as preplasma, by laser energy proceeding nanoseconds prior to the main pulse. This causes the laser-absorption surface to be pushed back hundreds of microns from the initial target surface; thus increasing the distance that electrons must travel to reach the imploded core. Previous experiments have shown an order of magnitude decrease in coupling into surrogate targets when intentionally increasing the amount of preplasma. Additionally, for electrons to deposit energy within the core, they should have kinetic energies on the order of a few MeV, as less energetic electrons will be stopped prior to the core and more energetic electrons will pass through the core without depositing much energy. Thus a quantitative understanding of the electron energy spectrum and how it responds to varied laser parameters is paramount for fast ignition. For the rst time, this dissertation quantitatively investigates the acceleration of electrons using an ultra-high-contrast laser. Ultra-high-contrast lasers reduce the laser energy that reaches the target prior to the main pulse; drastically reducing the amount of preplasma. Experiments were performed in a cone-wire geometry relevant to fast ignition. These experiments irradiated the inner-tip of a Au cone with the laser and observed electrons that passed through a Cu wire attached to the outer-tip of the cone. The total emission of K x-rays is used as a diagnostic to infer the electron energy coupled into the wire. Imaging the x-ray emission allowed an e ective path-length of electrons within the wire to be determined, which constrained the electron energy spectrum. Experiments were carried out on the ultra-high-contrast Trident laser at Los

  18. The Attentional Blink is Modulated by First Target Contrast: Implications of an Attention Capture Hypothesis

    DEFF Research Database (Denmark)

    Nielsen, Simon; Andersen, Tobias

    2011-01-01

    When two targets (T1 & T2) are presented in rapid succession, observers often fail to report T2 if they attend to T1. The bottleneck theory proposes that this attentional blink (AB) is due to T1 occupying a slow processing stage when T2 is presented. Accordingly, if increasing T1 difficulty...... increases T1 processing time, this should cause a greater AB. The attention capture hypothesis suggests that T1 captures attention, which cannot be reallocated to T2 in time. Accordingly, if increasing T1 difficulty decreases T1 saliency, this should cause a smaller AB. In two experiments we find support...... for an attention capture hypothesis. In Experiment 1 we find that AB magnitude increases with T1 contrast – but only when T1 is unmasked. In Experiment 2 we add Gaussian noise to targets and vary T1 contrast but keep T1 ‘s SNR constant. Again we find that AB magnitude increases with T1 contrast....

  19. The attentional blink is modulated by first target contrast: Implications of an attention capture hypothesis

    DEFF Research Database (Denmark)

    Nielsen, Simon; Andersen, Tobias S

    2011-01-01

    When two targets (T1 & T2) are presented in rapid succession, observers often fail to report T2 if they attend to T1. The bottleneck theory proposes that this attentional blink (AB) is due to T1 occupying a slow processing stage when T2 is presented. Accordingly, if increasing T1 difficulty...... increases T1 processing time, this should cause a greater AB. The attention capture hypothesis suggests that T1 captures attention, which cannot be reallocated to T2 in time. Accordingly, if increasing T1 difficulty decreases T1 saliency, this should cause a smaller AB. In two experiments we find support...... for an attention capture hypothesis. In Experiment 1 we find that AB magnitude increases with T1 contrast – but only when T1 is unmasked. In Experiment 2 we add Gaussian noise to targets and vary T1 contrast but keep T1 ‘s SNR constant. Again we find that AB magnitude increases with T1 contrast....

  20. Systematic Compared With Targeted Staging with Endobronchial Ultrasound in Patients with Lung Cancer.

    Science.gov (United States)

    Sanz-Santos, José; Serra, Pere; Torky, Mohamed; Andreo, Felipe; Centeno, Carmen; Mendiluce, Leire; Martínez-Barenys, Carlos; López de Castro, Pedro; Ruiz-Manzano, Juan

    2018-04-06

    To evaluate the accuracy of systematic mediastinal staging by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) (sampling of all visible nodes measuring ≥5mm from stations N3 to N1 regardless of their positron emission tomography/computed tomography (PET/CT) features) and compare this staging approach with targeted EBUS-TBNA staging (sampling only 18F-fluorodeoxyglucose (FDG)-avid nodes) in patients with N2 non-small cell lung cancer (NSCLC) on PET/CT. Retrospective study of 107 patients who underwent systematic EBUS-TBNA mediastinal staging. The results were compared with those of a hypothetical scenario where only FDG-avid nodes on PET/CT would be sampled. Systematic EBUS-TBNA sampling demonstrated N3 disease in 3 patients, N2 disease in 60 (42 single-station or N2a, 18 multiple-station or N2b) and N0/N1 disease in 44. Of these 44, seven underwent mediastinoscopy, which did not show mediastinal disease; six of the seven proceeded to lung resection, which also showed no mediastinal disease. Thirty-four N0/N1 patients after EBUS-TBNA underwent lung resection directly: N0/N1 was found in 30 and N2 in four (one N2b with a PET/CT showing N2a disease, three N2a). Sensitivity, specificity, negative predictive value, positive predictive value, and overall accuracy of systematic EBUS-TBNA were 94%, 100%, 90%, 100% and 96%, respectively. Compared to targeted EBUS-TBNA, systematic EBUS-TBNA sampling provided additional important clinical information in 14 cases (13%): three N3 cases would have passed unnoticed, and 11 N2b cases would have been staged as N2a. In clinical practice, systematic sampling of the mediastinum by EBUS-TBNA, regardless of PET/CT features, is to be recommended over targeted sampling. Copyright © 2018. Published by Elsevier Inc.

  1. Target vessel detection by epicardial ultrasound in off-pump coronary bypass surgery.

    Science.gov (United States)

    Hayakawa, Masato; Asai, Tohru; Kinoshita, Takeshi; Suzuki, Tomoaki; Shiraishi, Shoichiro

    2013-01-01

    The detection of embedded coronary arteries is difficult especially in off-pump coronary bypass surgery. From June 2010, we introduced high-frequency epicardial ultrasound (ECUS) to assess and evaluate embedded arteries during off-pump coronary bypass surgery. Between June 2010 and June 2011, a total of 89 consecutive patients underwent isolated coronary bypass surgery at our institution. The patients consisted of 72 men and 17 women with a mean age of 67.9 years. We routinely use the VeriQC system (MediStim, Oslo, Norway) to detect the target vessels in the operation. The patients were assigned to one of two groups, depending on whether ECUS was used in the operation (n = 10, ECUS group) or not (n = 79, non-ECUS group). We analyzed the impact of introducing the ECUS in terms of operative outcome. All patients underwent revascularization using the off-pump technique without emergent conversion to cardiopulmonary bypass during surgery. The total number of distal anastomoses was 299, and 12 target vessels could not be identified either visually or on palpation. Thus, the frequency of the embedded coronary arteries was 4.01% (12/299 cases). The preoperative profiles of the two groups were not significantly different. Operation time was significantly longer in the ECUS group (P = 0.02). There were no significant differences in postoperative outcome between the two groups. In the present study, in which the target coronary arteries could not be detected either visually or on palpation in 12 (4.01%) of 299 cases, the use of high-frequency ECUS allowed all patients to undergo off-pump coronary bypass surgery without conversion to cardiopulmonary bypass during the operation. High-frequency ECUS is therefore useful in off-pump coronary bypass surgery.

  2. Ultrasound pregnancy

    Science.gov (United States)

    Pregnancy sonogram; Obstetric ultrasonography; Obstetric sonogram; Ultrasound - pregnancy; IUGR - ultrasound; Intrauterine growth - ultrasound; Polyhydramnios - ultrasound; Oligohydramnios - ultrasound; ...

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

    Directory of Open Access Journals (Sweden)

    Qian DONG

    2017-06-01

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

  4. Ultrafast 2-dimensional image monitoring and array-based passive cavitation detection for ultrasound contrast agent destruction in a variably sized region.

    Science.gov (United States)

    Xu, Shanshan; Hu, Hong; Jiang, Hujie; Xu, Zhi'an; Wan, Mingxi

    2014-11-01

    A combined approach was proposed, based on programmable ultrasound equipment, to simultaneously monitor surviving microbubbles and detect cavitation activity during microbubble destruction in a variably sized region for use in ultrasound contrast agent (UCA)-enhanced therapeutic ultrasound applications. A variably sized focal region wherein the acoustic pressure was above the UCA fragmentation threshold was synthesized at frequencies of 3, 4, 5, and 6 MHz with a linear broadband imaging probe. The UCAs' temporal and spatial distribution during the microbubbles' destruction was monitored in a 2-dimensional imaging plane at 5 MHz and a frame rate of 400 Hz, and simultaneously, broadband noise emissions during the microbubbles' fragmentation were extracted by using the backscattered signals produced by the focused release bursts (ie, destruction pulses) themselves. Afterward, the temporal evolution of broadband noise emission, the surviving microbubbles in a region of interest (ROI), and the destruction area in a static UCA suspension were computed. Then the inertial cavitation dose, destruction rate of microbubbles in the ROI, and area of the destruction region were determined. It was found that an increasing pulse length and a decreasing transmit aperture and excitation frequency were correlated with an increased inertial cavitation dose, microbubble destruction rate, and destruction area. Furthermore, it was obvious that the microbubble destruction rate was significantly correlated with the inertial cavitation dose (P cavitation dose could be regulated by manipulating the transmission parameters. © 2014 by the American Institute of Ultrasound in Medicine.

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

    Science.gov (United States)

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

    2016-05-01

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

  6. Ultrasound Targeted Microbubble Destruction Stimulates Cellular Endocytosis in Facilitation of Adeno-Associated Virus Delivery

    Directory of Open Access Journals (Sweden)

    Lian-Fang Du

    2013-05-01

    Full Text Available The generally accepted mechanism for ultrasound targeted microbubble destruction (UTMD to enhance drug and gene delivery is through sonoporation. However, passive uptake of adeno-associated virus (AAV into cells following sonoporation does not adequately explain observations of enhanced transduction by UTMD. This study investigated alternative mechanisms of UTMD enhancement in AAV delivery. UTMD significantly enhanced transduction efficiency of AAV in a dose-dependent manner. UTMD stimulated a persistent uptake of AAV into the cytoplasm and nucleus. This phenomenon occurred over several hours, suggesting that some viral particles are endocytosed by cells rather than exclusively passing through pores created by sonoporation. Additionally, UTMD enhanced clathrin expression and accumulation at the plasma membrane suggesting greater clathrin-mediated endocytosis following UTMD. Transmission electron microscopy (TEM revealed that UTMD stimulated formation of clathrin-coated pits (CPs and uncoated pits (nCPs. Furthermore, inhibition of clathrin-mediated endocytosis partially blocked the enhancement of AAV uptake following UTMD. The results of this study implicate endocytosis as a mechanism that contributes to UTMD-enhanced AAV delivery.

  7. Ultra-High-Contrast Laser Acceleration of Relativistic Electrons in Solid Targets

    Science.gov (United States)

    Higginson, Drew Pitney

    The cone-guided fast ignition approach to Inertial Confinement Fusion requires laser-accelerated relativistic electrons to deposit kilojoules of energy within an imploded fuel core to initiate fusion burn. One obstacle to coupling electron energy into the core is the ablation of material, known as preplasma, by laser energy proceeding nanoseconds prior to the main pulse. This causes the laser-absorption surface to be pushed back hundreds of microns from the initial target surface; thus increasing the distance that electrons must travel to reach the imploded core. Previous experiments have shown an order of magnitude decrease in coupling into surrogate targets when intentionally increasing the amount of preplasma. Additionally, for electrons to deposit energy within the core, they should have kinetic energies on the order of a few MeV, as less energetic electrons will be stopped prior to the core and more energetic electrons will pass through the core without depositing much energy. Thus a quantitative understanding of the electron energy spectrum and how it responds to varied laser parameters is paramount for fast ignition. For the first time, this dissertation quantitatively investigates the acceleration of electrons using an ultra-high-contrast laser. Ultra-high-contrast lasers reduce the laser energy that reaches the target prior to the main pulse; drastically reducing the amount of preplasma. Experiments were performed in a cone-wire geometry relevant to fast ignition. These experiments irradiated the inner-tip of a Au cone with the laser and observed electrons that passed through a Cu wire attached to the outer-tip of the cone. The total emission of Kalpha x-rays is used as a diagnostic to infer the electron energy coupled into the wire. Imaging the x-ray emission allowed an effective path-length of electrons within the wire to be determined, which constrained the electron energy spectrum. Experiments were carried out on the ultra-high-contrast Trident laser

  8. Focused Ultrasound-Induced Blood-Brain Barrier Opening: Association with Mechanical Index and Cavitation Index Analyzed by Dynamic Contrast-Enhanced Magnetic-Resonance Imaging.

    Science.gov (United States)

    Chu, Po-Chun; Chai, Wen-Yen; Tsai, Chih-Hung; Kang, Shih-Tsung; Yeh, Chih-Kuang; Liu, Hao-Li

    2016-09-15

    Focused ultrasound (FUS) with microbubbles can temporally open the blood-brain barrier (BBB), and the cavitation activities of microbubbles play a key role in the BBB-opening process. Previous attempts used contrast-enhanced magnetic resonance imaging (CE-MRI) to correlate the mechanical index (MI) with the scale of BBB-opening, but MI only partially gauged acoustic activities, and CE-MRI did not fully explore correlations of pharmacodynamic/pharmacokinetic behaviors. Recently, the cavitation index (CI) has been derived to serve as an indicator of microbubble-ultrasound stable cavitation, and may also serve as a valid indicator to gauge the level of FUS-induced BBB opening. This study investigates the feasibility of gauging FUS-induced BBB opened level via the two indexes, MI and CI, through dynamic contrast-enhanced (DCE)-MRI analysis as well as passive cavitation detection (PCD) analysis. Pharmacodynamic/pharmacokinetic parameters derived from DCE-MRI were characterized to identify the scale of FUS-induced BBB opening. Our results demonstrated that DCE-MRI can successfully access pharmacodynamic/pharmacokinetic BBB-opened behavior, and was highly correlated both with MI and CI, implying the feasibility in using these two indices to gauge the scale of FUS-induced BBB opening. The proposed finding may facilitate the design toward using focused ultrasound as a safe and reliable noninvasive CNS drug delivery.

  9. Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models

    Energy Technology Data Exchange (ETDEWEB)

    Thorek, Daniel L.J., E-mail: dthorek1@jhmi.edu [Division of Nuclear Medicine, The Russell H. Morgan Department of Radiology and Radiological Sciences, The Johns Hopkins School of Medicine, Baltimore, MD (United States); Kramer, Robin M. [Tri-Institutional Training Program in Laboratory Animal Medicine and Science, Memorial Sloan-Kettering Cancer Center (MSKCC), Weill Cornell Medical College, The Rockefeller University, New York, NY (United States); Chen, Qing; Jeong, Jeho; Lupu, Mihaela E. [Department of Medical Physics, MSKCC, New York, NY (United States); Lee, Alycia M.; Moynahan, Mary E.; Lowery, Maeve [Department of Medicine, MSKCC, New York, NY (United States); Ulmert, David [Molecular Pharmacology and Chemistry Program, MSKCC, New York, NY (United States); Department of Surgery (Urology), Skåne University Hospital, Malmö (Sweden); Zanzonico, Pat; Deasy, Joseph O.; Humm, John L. [Department of Medical Physics, MSKCC, New York, NY (United States); Russell, James, E-mail: russellj@mskcc.org [Department of Medical Physics, MSKCC, New York, NY (United States)

    2015-10-01

    Purpose: To evaluate the feasibility of delivering experimental radiation therapy to tumors in the mouse pancreas. Imaging and treatment were performed using combined CT (computed tomography)/orthovoltage treatment with a rotating gantry. Methods and Materials: After intraperitoneal administration of radiopaque iodinated contrast, abdominal organ delineation was performed by x-ray CT. With this technique we delineated the pancreas and both orthotopic xenografts and genetically engineered disease. Computed tomographic imaging was validated by comparison with magnetic resonance imaging. Therapeutic radiation was delivered via a 1-cm diameter field. Selective x-ray radiation therapy of the noninvasively defined orthotopic mass was confirmed using γH2AX staining. Mice could tolerate a dose of 15 Gy when the field was centered on the pancreas tail, and treatment was delivered as a continuous 360° arc. This strategy was then used for radiation therapy planning for selective delivery of therapeutic x-ray radiation therapy to orthotopic tumors. Results: Tumor growth delay after 15 Gy was monitored, using CT and ultrasound to determine the tumor volume at various times after treatment. Our strategy enables the use of clinical radiation oncology approaches to treat experimental tumors in the pancreas of small animals for the first time. We demonstrate that delivery of 15 Gy from a rotating gantry minimizes background healthy tissue damage and significantly retards tumor growth. Conclusions: This advance permits evaluation of radiation planning and dosing parameters. Accurate noninvasive longitudinal imaging and monitoring of tumor progression and therapeutic response in preclinical models is now possible and can be expected to more effectively evaluate pancreatic cancer disease and therapeutic response.

  10. Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models

    International Nuclear Information System (INIS)

    Thorek, Daniel L.J.; Kramer, Robin M.; Chen, Qing; Jeong, Jeho; Lupu, Mihaela E.; Lee, Alycia M.; Moynahan, Mary E.; Lowery, Maeve; Ulmert, David; Zanzonico, Pat; Deasy, Joseph O.; Humm, John L.; Russell, James

    2015-01-01

    Purpose: To evaluate the feasibility of delivering experimental radiation therapy to tumors in the mouse pancreas. Imaging and treatment were performed using combined CT (computed tomography)/orthovoltage treatment with a rotating gantry. Methods and Materials: After intraperitoneal administration of radiopaque iodinated contrast, abdominal organ delineation was performed by x-ray CT. With this technique we delineated the pancreas and both orthotopic xenografts and genetically engineered disease. Computed tomographic imaging was validated by comparison with magnetic resonance imaging. Therapeutic radiation was delivered via a 1-cm diameter field. Selective x-ray radiation therapy of the noninvasively defined orthotopic mass was confirmed using γH2AX staining. Mice could tolerate a dose of 15 Gy when the field was centered on the pancreas tail, and treatment was delivered as a continuous 360° arc. This strategy was then used for radiation therapy planning for selective delivery of therapeutic x-ray radiation therapy to orthotopic tumors. Results: Tumor growth delay after 15 Gy was monitored, using CT and ultrasound to determine the tumor volume at various times after treatment. Our strategy enables the use of clinical radiation oncology approaches to treat experimental tumors in the pancreas of small animals for the first time. We demonstrate that delivery of 15 Gy from a rotating gantry minimizes background healthy tissue damage and significantly retards tumor growth. Conclusions: This advance permits evaluation of radiation planning and dosing parameters. Accurate noninvasive longitudinal imaging and monitoring of tumor progression and therapeutic response in preclinical models is now possible and can be expected to more effectively evaluate pancreatic cancer disease and therapeutic response

  11. Method comparison of ultrasound and kilovoltage x-ray fiducial marker imaging for prostate radiotherapy targeting

    International Nuclear Information System (INIS)

    Fuller, Clifton David; Jr, Charles R Thomas; Schwartz, Scott; Golden, Nanalei; Ting, Joe; Wong, Adrian; Erdogmus, Deniz; Scarbrough, Todd J

    2006-01-01

    Several measurement techniques have been developed to address the capability for target volume reduction via target localization in image-guided radiotherapy; among these have been ultrasound (US) and fiducial marker (FM) software-assisted localization. In order to assess interchangeability between methods, US and FM localization were compared using established techniques for determination of agreement between measurement methods when a 'gold-standard' comparator does not exist, after performing both techniques daily on a sequential series of patients. At least 3 days prior to CT simulation, four gold seeds were placed within the prostate. FM software-assisted localization utilized the ExacTrac X-Ray 6D (BrainLab AG, Germany) kVp x-ray image acquisition system to determine prostate position; US prostate targeting was performed on each patient using the SonArray (Varian, Palo Alto, CA). Patients were aligned daily using laser alignment of skin marks. Directional shifts were then calculated by each respective system in the X, Y and Z dimensions before each daily treatment fraction, previous to any treatment or couch adjustment, as well as a composite vector of displacement. Directional shift agreement in each axis was compared using Altman-Bland limits of agreement, Lin's concordance coefficient with Partik's grading schema, and Deming orthogonal bias-weighted correlation methodology. 1019 software-assisted shifts were suggested by US and FM in 39 patients. The 95% limits of agreement in X, Y and Z axes were ±9.4 mm, ±11.3 mm and ±13.4, respectively. Three-dimensionally, measurements agreed within 13.4 mm in 95% of all paired measures. In all axes, concordance was graded as 'poor' or 'unacceptable'. Deming regression detected proportional bias in both directional axes and three-dimensional vectors. Our data suggest substantial differences between US and FM image-guided measures and subsequent suggested directional shifts. Analysis reveals that the vast majority of

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  13. Added Value of Contrast-Enhanced Ultrasound on Biopsies of Focal Hepatic Lesions Invisible on Fusion Imaging Guidance.

    Science.gov (United States)

    Kang, Tae Wook; Lee, Min Woo; Song, Kyoung Doo; Kim, Mimi; Kim, Seung Soo; Kim, Seong Hyun; Ha, Sang Yun

    2017-01-01

    To assess whether contrast-enhanced ultrasonography (CEUS) with Sonazoid can improve the lesion conspicuity and feasibility of percutaneous biopsies for focal hepatic lesions invisible on fusion imaging of real-time ultrasonography (US) with computed tomography/magnetic resonance images, and evaluate its impact on clinical decision making. The Institutional Review Board approved this retrospective study. Between June 2013 and January 2015, 711 US-guided percutaneous biopsies were performed for focal hepatic lesions. Biopsies were performed using CEUS for guidance if lesions were invisible on fusion imaging. We retrospectively evaluated the number of target lesions initially invisible on fusion imaging that became visible after applying CEUS, using a 4-point scale. Technical success rates of biopsies were evaluated based on histopathological results. In addition, the occurrence of changes in clinical decision making was assessed. Among 711 patients, 16 patients (2.3%) were included in the study. The median size of target lesions was 1.1 cm (range, 0.5-1.9 cm) in pre-procedural imaging. After CEUS, 15 of 16 (93.8%) focal hepatic lesions were visualized. The conspicuity score was significantly increased after adding CEUS, as compared to that on fusion imaging (p making for 11 of 16 patients (68.8%). The addition of CEUS could improve the conspicuity of focal hepatic lesions invisible on fusion imaging. This dual guidance using CEUS and fusion imaging may affect patient management via changes in clinical decision-making.

  14. Targeted Nanodiamonds as Phenotype Specific Photoacoustic Contrast Agents for Breast Cancer

    Science.gov (United States)

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

    2015-01-01

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

  15. Real-time contrast-enhanced ultrasound determination of microvascular blood volume in abdominal subcutaneous adipose tissue in man. Evidence for adipose tissue capillary recruitment

    DEFF Research Database (Denmark)

    Tobin, L; Simonsen, L; Bülow, J

    2010-01-01

    The adipose tissue metabolism is dependent on its blood perfusion. During lipid mobilization e.g. during exercise and during lipid deposition e.g. postprandial, adipose tissue blood flow is increased. This increase in blood flow may involve capillary recruitment in the tissue. We investigated...... of ultrasound contrast agent to establish the reproducibility of the technique. In nine subjects, the effect of an oral glucose load on blood flow and microvascular volume was measured in abdominal subcutaneous adipose tissue and forearm skeletal muscle. ¹³³Xe washout and venous occlusion strain......-gauge plethysmography was used to measure the adipose tissue and forearm blood flow, respectively. Ultrasound signal intensity of the first plateau phases was 27 ± dB in the abdominal subcutaneous adipose tissue and 18 ± 2 dB (P

  16. Contrast agent based on nano-emulsion for targeted biomedical imaging

    International Nuclear Information System (INIS)

    Attia, Mohamed

    2016-01-01

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

  17. Randomized trial of tourniquet vs blood pressure cuff for target vein dilation in ultrasound-guided peripheral intravenous access.

    Science.gov (United States)

    Nelson, Drew; Jeanmonod, Rebecca; Jeanmonod, Donald

    2014-07-01

    Ten percent of the time, peripheral intravenous access (PIV) is not obtained in 2 attempts in the emergency department. Typically, a tourniquet is used to dilate the target vein; but recent research showed that a blood pressure (BP) cuff improves dilation, which may translate to increased PIV success. We sought to determine if there is improved success in obtaining ultrasound-guided PIV using a BP cuff vs a tourniquet in "difficult stick" patients. This is a prospective, randomized, single-blinded trial. Adult patients requiring PIV with at least 2 prior failed attempts were enrolled. Patients were assigned to tourniquet or BP cuff for target vein dilation randomly. Nurses prepared the patient for PIV attempt by either placing a BP cuff inflated to 150 mm Hg or placing a tourniquet on the chosen extremity. The extremity was draped to blind the physician to assignment. Physicians then attempted ultrasound-guided PIV. Failures were defined as IVs requiring greater than 3 ultrasound-guided attempts or 30 minutes, or patient intolerance. If failure occurred, the physician was unblinded; and the patient could be crossed over and reattempted. Thirty-eight patients were enrolled. The success rate for the tourniquet group (n = 17) and BP cuff group (n = 21) was 82.4% and 47.6%, respectively (P = .04). There were no differences between groups for vessel depth, diameter, or procedure time. Six in the BP cuff group were crossed over and had successful PIV obtained with tourniquet. Tourniquet is superior to BP cuff for target vein dilation in ultrasound-guided PIV. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Myocardial regeneration in adriamycin cardiomyopathy by nuclear expression of GLP1 using ultrasound targeted microbubble destruction

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shuyuan [Baylor Research Institute, Baylor University Medical Center, 3812 Elm Street, Dallas, TX (United States); Chen, Jiaxi [The University of Texas Southwestern Medical Center at Dallas, Medical School, 5235 Harry Hine Blvd., Dallas, TX (United States); Huang, Pintong [Department of Ultrasonography, The 2nd Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, Zhejiang Province (China); Meng, Xing-Li; Clayton, Sandra; Shen, Jin-Song [Baylor Research Institute, Baylor University Medical Center, 3812 Elm Street, Dallas, TX (United States); Grayburn, Paul A., E-mail: paulgr@baylorhealth.edu [Baylor Research Institute, Baylor University Medical Center, 3812 Elm Street, Dallas, TX (United States); Department of Internal Medicine, Division of Cardiology, Baylor Heart and Vascular Institute, Baylor University Medical Center, 621 N. Hall St, Suite H030, Dallas, TX (United States)

    2015-03-20

    Recently GLP-1 was found to have cardioprotective effects independent of those attributable to tight glycemic control. Methods and results: We employed ultrasound targeted microbubble destruction (UTMD) to deliver piggybac transposon plasmids encoding the GLP-1 gene with a nuclear localizing signal to rat hearts with adriamycin cardiomyopathy. After a single UTMD treatment, overexpression of transgenic GLP-1 was found in nuclei of rat heart cells with evidence that transfected cardiac cells had undergone proliferation. UTMD-GLP-1 gene therapy restored LV mass, fractional shortening index, and LV posterior wall diameter to nearly normal. Nuclear overexpression of GLP-1 by inducing phosphorylation of FoxO1-S256 and translocation of FoxO1 from the nucleus to the cytoplasm significantly inactivated FoxO1 and activated the expression of cyclin D1 in nuclei of cardiac muscle cells. Reversal of adriamycin cardiomyopathy appeared to be mediated by dedifferentiation and proliferation of nuclear FoxO1-positive cardiac muscle cells with evidence of embryonic stem cell markers (OCT4, Nanog, SOX2 and c-kit), cardiac early differentiation markers (NKX2.5 and ISL-1) and cellular proliferation markers (BrdU and PHH3) after UTMD with GLP-1 gene therapy. Conclusions: Intranuclear myocardial delivery of the GLP-1gene can reverse established adriamycin cardiomyopathy by stimulating myocardial regeneration. - Highlights: • The activation of nuclear FoxO1 in cardiac muscle cells associated with adriamycin cardiomyopathy. • Myocardial nuclear GLP-1 stimulates myocardial regeneration and reverses adriamycin cardiomyopathy. • The process of myocardial regeneration associated with dedifferentiation and proliferation.

  19. Myocardial regeneration in adriamycin cardiomyopathy by nuclear expression of GLP1 using ultrasound targeted microbubble destruction

    International Nuclear Information System (INIS)

    Chen, Shuyuan; Chen, Jiaxi; Huang, Pintong; Meng, Xing-Li; Clayton, Sandra; Shen, Jin-Song; Grayburn, Paul A.

    2015-01-01

    Recently GLP-1 was found to have cardioprotective effects independent of those attributable to tight glycemic control. Methods and results: We employed ultrasound targeted microbubble destruction (UTMD) to deliver piggybac transposon plasmids encoding the GLP-1 gene with a nuclear localizing signal to rat hearts with adriamycin cardiomyopathy. After a single UTMD treatment, overexpression of transgenic GLP-1 was found in nuclei of rat heart cells with evidence that transfected cardiac cells had undergone proliferation. UTMD-GLP-1 gene therapy restored LV mass, fractional shortening index, and LV posterior wall diameter to nearly normal. Nuclear overexpression of GLP-1 by inducing phosphorylation of FoxO1-S256 and translocation of FoxO1 from the nucleus to the cytoplasm significantly inactivated FoxO1 and activated the expression of cyclin D1 in nuclei of cardiac muscle cells. Reversal of adriamycin cardiomyopathy appeared to be mediated by dedifferentiation and proliferation of nuclear FoxO1-positive cardiac muscle cells with evidence of embryonic stem cell markers (OCT4, Nanog, SOX2 and c-kit), cardiac early differentiation markers (NKX2.5 and ISL-1) and cellular proliferation markers (BrdU and PHH3) after UTMD with GLP-1 gene therapy. Conclusions: Intranuclear myocardial delivery of the GLP-1gene can reverse established adriamycin cardiomyopathy by stimulating myocardial regeneration. - Highlights: • The activation of nuclear FoxO1 in cardiac muscle cells associated with adriamycin cardiomyopathy. • Myocardial nuclear GLP-1 stimulates myocardial regeneration and reverses adriamycin cardiomyopathy. • The process of myocardial regeneration associated with dedifferentiation and proliferation

  20. Added value of contrast-enhanced ultrasound on biopsies of focal hepatic lesions invisible on fusion imaging guidance

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Tae Wook; Lee, Min Woo; Song, Kyoung Doo; Kim, Mimi; Kim, Seung Soo; Kim, Seong Hyun; Ha, Sang Yun [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2017-01-15

    To assess whether contrast-enhanced ultrasonography (CEUS) with Sonazoid can improve the lesion conspicuity and feasibility of percutaneous biopsies for focal hepatic lesions invisible on fusion imaging of real-time ultrasonography (US) with computed tomography/magnetic resonance images, and evaluate its impact on clinical decision making. The Institutional Review Board approved this retrospective study. Between June 2013 and January 2015, 711 US-guided percutaneous biopsies were performed for focal hepatic lesions. Biopsies were performed using CEUS for guidance if lesions were invisible on fusion imaging. We retrospectively evaluated the number of target lesions initially invisible on fusion imaging that became visible after applying CEUS, using a 4-point scale. Technical success rates of biopsies were evaluated based on histopathological results. In addition, the occurrence of changes in clinical decision making was assessed. Among 711 patients, 16 patients (2.3%) were included in the study. The median size of target lesions was 1.1 cm (range, 0.5–1.9 cm) in pre-procedural imaging. After CEUS, 15 of 16 (93.8%) focal hepatic lesions were visualized. The conspicuity score was significantly increased after adding CEUS, as compared to that on fusion imaging (p < 0.001). The technical success rate of biopsy was 87.6% (14/16). After biopsy, there were changes in clinical decision making for 11 of 16 patients (68.8%). The addition of CEUS could improve the conspicuity of focal hepatic lesions invisible on fusion imaging. This dual guidance using CEUS and fusion imaging may affect patient management via changes in clinical decision-making.

  1. Added value of contrast-enhanced ultrasound on biopsies of focal hepatic lesions invisible on fusion imaging guidance

    International Nuclear Information System (INIS)

    Kang, Tae Wook; Lee, Min Woo; Song, Kyoung Doo; Kim, Mimi; Kim, Seung Soo; Kim, Seong Hyun; Ha, Sang Yun

    2017-01-01

    To assess whether contrast-enhanced ultrasonography (CEUS) with Sonazoid can improve the lesion conspicuity and feasibility of percutaneous biopsies for focal hepatic lesions invisible on fusion imaging of real-time ultrasonography (US) with computed tomography/magnetic resonance images, and evaluate its impact on clinical decision making. The Institutional Review Board approved this retrospective study. Between June 2013 and January 2015, 711 US-guided percutaneous biopsies were performed for focal hepatic lesions. Biopsies were performed using CEUS for guidance if lesions were invisible on fusion imaging. We retrospectively evaluated the number of target lesions initially invisible on fusion imaging that became visible after applying CEUS, using a 4-point scale. Technical success rates of biopsies were evaluated based on histopathological results. In addition, the occurrence of changes in clinical decision making was assessed. Among 711 patients, 16 patients (2.3%) were included in the study. The median size of target lesions was 1.1 cm (range, 0.5–1.9 cm) in pre-procedural imaging. After CEUS, 15 of 16 (93.8%) focal hepatic lesions were visualized. The conspicuity score was significantly increased after adding CEUS, as compared to that on fusion imaging (p < 0.001). The technical success rate of biopsy was 87.6% (14/16). After biopsy, there were changes in clinical decision making for 11 of 16 patients (68.8%). The addition of CEUS could improve the conspicuity of focal hepatic lesions invisible on fusion imaging. This dual guidance using CEUS and fusion imaging may affect patient management via changes in clinical decision-making

  2. Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood-brain barrier opening.

    Science.gov (United States)

    Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel; Konofagou, Elisa E

    2017-04-01

    Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood-brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood-brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo.

  3. Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood–brain barrier opening

    Science.gov (United States)

    Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel

    2016-01-01

    Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood–brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood–brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo. PMID:27278929

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-01-15

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

  5. High-contrast laser acceleration of relativistic electrons in solid cone-wire targets

    Energy Technology Data Exchange (ETDEWEB)

    Higginson, D. P. [Univ. of California-San Diego, La Jolla, CA (United States); Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Link, A. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Sawada, H. [Univ. of California-San Diego, La Jolla, CA (United States); Wilks, S. C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Chawla, S. R. [Univ. of California-San Diego, La Jolla, CA (United States); Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Chen, C. D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Jarrott, L. C. [Univ. of California-San Diego, La Jolla, CA (United States); Flippo, K. A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); McLean, H. S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Patel, P. K. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Perez, F. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Beg, F. N. [Univ. of California-San Diego, La Jolla, CA (United States); Bartal, T. [Univ. of California-San Diego, La Jolla, CA (United States); Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Wei, M. S. [General Atomics, San Diego, CA (United States)

    2015-12-31

    Optimization of electron coupling into small solid angles is of extreme importance to applications, such as Fast Ignition, that require maximum electron energy deposition within a small volume. To optimize this coupling, we use the ultra-high-contrast Trident laser, which remains below intensity of 1011 W/cm2 until < 0.1 ns before the main pulse, while still attaining high-energy, 75 J, and peak intensity of 5 x 1019 W/cm2. Using a cone-wire target, we find that the coupling into the 40 μm diameter wire is increased by a factor of 2.7x over the low-contrast Titan laser at similar peak intensity. Full-scale simulations are used to model the laser interaction and quantitatively reproduce the experimental results. These show that increase in coupling is due to both a closer interaction, as well as the reduction of laser filamentation and self-focusing.

  6. Ultrasound guidance to perform intra-articular injection of gadolinium-based contrast material for magnetic resonance arthrography as an alternative to fluoroscopy: the time is now

    Energy Technology Data Exchange (ETDEWEB)

    Messina, Carmelo [Universita degli Studi di Milano, Scuola di Specializzazione in Radiodiagnostica, Milano (Italy); Banfi, Giuseppe [IRCCS Istituto Ortopedico Galeazzi, Milano (Italy); Universita Vita-Salute San Raffaele, Milano (Italy); Aliprandi, Alberto [Universita degli Studi di Milano, Dipartimento di Scienze Biomediche per la Salute, Milano (Italy); Mauri, Giovanni [Universita degli Studi di Milano, Dipartimento di Scienze Biomediche per la Salute, Milano (Italy); Istituto Europeo di Oncologia, Unita di Radiologia Interventistica, Milano (Italy); Secchi, Francesco; Sardanelli, Francesco; Sconfienza, Luca Maria [Universita degli Studi di Milano, Dipartimento di Scienze Biomediche per la Salute, Milano (Italy); IRCCS Policlinico San Donato, Servizio di Radiologia, San Donato, Milanese (Italy)

    2016-05-15

    Magnetic resonance (MR) imaging has been definitively established as the reference standard in the evaluation of joints in the body. Similarly, magnetic resonance arthrography has emerged as a technique that has been proven to increase significantly the diagnostic performance if compared with conventional MR imaging, especially when dealing with fibrocartilage and articular cartilage abnormalities. Diluted gadolinium can be injected in the joint space using different approaches: under palpation using anatomic landmarks or using an imaging guidance, such as fluoroscopy, computed tomography, or ultrasound. Fluoroscopy has been traditionally used, but the involvement of ionizing radiation should represent a remarkable limitation of this modality. Conversely, ultrasound has emerged as a feasible, cheap, quick, and radiation-free modality that can be used to inject joints, with comparable accuracy of fluoroscopy. In the present paper, we discuss the advantages and disadvantages of using fluoroscopy or ultrasound in injecting gadolinium-based contrast agents in joints to perform magnetic resonance arthrography, also in view of the new EuroSAFE Imaging initiative promoted by the European Society of Radiology and the recent updates to the European Atomic Energy Community 2013/59 directive on the medical use of ionizing radiation. (orig.)

  7. MRI screening-detected breast lesions in high-risk young women: the value of targeted second-look ultrasound and imaging-guided biopsy.

    Science.gov (United States)

    Peter, P; Dhillon, R; Bose, S; Bourke, A

    2016-10-01

    To analyse the value of targeted second-look ultrasound and imaging-guided biopsy in high-risk young women eligible for screening magnetic resonance imaging (MRI) in a tertiary referral centre in Perth, Western Australia. A retrospective analysis of eligible high-risk young women who underwent screening breast MRI and targeted second-look ultrasound between June 2012 and June 2014 was performed with review of data. Over a 2-year period, 139 women underwent high-risk screening MRI. Of these, 30 women (with a total of 45 lesions) were recalled for targeted second-look ultrasound. Thirty-four MRI-detected lesions were identified on targeted ultrasound with 19 of them proceeding to ultrasound-guided biopsy, while the remaining 15 lesions were considered benign on ultrasound, were not biopsied, and were stable on follow-up imaging 12 months later. One lesion proceeded to an MRI-guided biopsy to confirm a benign result. Of the 11 lesions not seen on ultrasound, nine underwent MRI biopsy, one proceeded directly to hook wire localisation and excision, and one did not return for biopsy and was lost to follow-up. The overall biopsy rate was 14.4%. The cancer detection rate was 1.4%. The results of this study indicate that targeted second-look ultrasound and ultrasound-guided biopsy is a cost-effective and time-efficient approach for MRI-detected lesions in young women at high risk of developing breast cancer. MRI-guided biopsy should be considered for ultrasonographically occult suspicious lesions as there is a low, but definite, risk of cancer. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  8. Contrast generation in the nuclear-spin tomography by pulsed ultrasound; Kontrasterzeugung in der Kernspintomographie durch gepulsten Ultraschall

    Energy Technology Data Exchange (ETDEWEB)

    Oehms, Ole Benjamin

    2009-07-10

    In the framework of this thesis a combined method of ultrasound and nuclear-spin tomography is presented. Via ultrasound pulses by the sound-radiation force in liquids and tissue phantoms motions are generated, which depend on ther viscoelastic properties. This motions are made visible by a motion-sensitive tomograph sequence in the phase image of the tomograph in form of a phase change. The first measurements on simple phantoms and liquids are presented. [German] Im Rahmen dieser Arbeit wird eine kombinierte Methode aus Ultraschall und Kernspintomographie vorgestellt. Ueber Ultraschallpulse werden durch die Schallstrahlungskraft in Fluessigkeiten und Gewebephantomen Bewegungen erzeugt, die von den viskoelastischen Eigenschaften abhaengen. Diese Bewegungen werden mit einer bewegungssensitiven Tomographensequenz im Phasenbild des Tomographen in Form einer Phasenaenderung sichtbar gemacht. Die ersten Messungen an einfachen Phantomen und Fluessigkeiten werden praesentiert. (orig.)

  9. Piezoelectric Composite Micromachined Multifrequency Transducers for High-Resolution, High-Contrast Ultrasound Imaging for Improved Prostate Cancer Assessment

    Science.gov (United States)

    2016-10-01

    imaging system ( Verasonics Vantage , Kirkland, WA) was used to drive the array and acquire echoes. For this work, 19 TX elements were fired as a group...imaging was conducted with the Verasonics programmable ultrasound system ( Verasonics Vantage , Redmond, WA). The Verasonics sampling frequency...multi-channel research imaging system ( Verasonics Vantage , Kirkland, WA) was used to drive the array and acquire echoes. For this work, 19 TX elements

  10. Intravascular ultrasound guidance to minimize the use of iodine contrast in percutaneous coronary intervention: the MOZART (Minimizing cOntrast utiliZation With IVUS Guidance in coRonary angioplasTy) randomized controlled trial.

    Science.gov (United States)

    Mariani, José; Guedes, Cristiano; Soares, Paulo; Zalc, Silvio; Campos, Carlos M; Lopes, Augusto C; Spadaro, André G; Perin, Marco A; Filho, Antonio Esteves; Takimura, Celso K; Ribeiro, Expedito; Kalil-Filho, Roberto; Edelman, Elazer R; Serruys, Patrick W; Lemos, Pedro A

    2014-11-01

    The aim of this study was to evaluate the impact of intravascular ultrasound (IVUS) guidance on the final volume of contrast agent used in patients undergoing percutaneous coronary intervention (PCI). To date, few approaches have been described to reduce the final dose of contrast agent in PCIs. We hypothesized that IVUS might serve as an alternative imaging tool to angiography in many steps during PCI, thereby reducing the use of iodine contrast. A total of 83 patients were randomized to angiography-guided PCI or IVUS-guided PCI; both groups were treated according to a pre-defined meticulous procedural strategy. The primary endpoint was the total volume contrast agent used during PCI. Patients were followed clinically for an average of 4 months. The median total volume of contrast was 64.5 ml (interquartile range [IQR]: 42.8 to 97.0 ml; minimum, 19 ml; maximum, 170 ml) in the angiography-guided group versus 20.0 ml (IQR: 12.5 to 30.0 ml; minimum, 3 ml; maximum, 54 ml) in the IVUS-guided group (p MOZART]; NCT01947335). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  11. Method comparison of ultrasound and kilovoltage x-ray fiducial marker imaging for prostate radiotherapy targeting

    Science.gov (United States)

    Fuller, Clifton David; Thomas, Charles R., Jr.; Schwartz, Scott; Golden, Nanalei; Ting, Joe; Wong, Adrian; Erdogmus, Deniz; Scarbrough, Todd J.

    2006-10-01

    Several measurement techniques have been developed to address the capability for target volume reduction via target localization in image-guided radiotherapy; among these have been ultrasound (US) and fiducial marker (FM) software-assisted localization. In order to assess interchangeability between methods, US and FM localization were compared using established techniques for determination of agreement between measurement methods when a 'gold-standard' comparator does not exist, after performing both techniques daily on a sequential series of patients. At least 3 days prior to CT simulation, four gold seeds were placed within the prostate. FM software-assisted localization utilized the ExacTrac X-Ray 6D (BrainLab AG, Germany) kVp x-ray image acquisition system to determine prostate position; US prostate targeting was performed on each patient using the SonArray (Varian, Palo Alto, CA). Patients were aligned daily using laser alignment of skin marks. Directional shifts were then calculated by each respective system in the X, Y and Z dimensions before each daily treatment fraction, previous to any treatment or couch adjustment, as well as a composite vector of displacement. Directional shift agreement in each axis was compared using Altman-Bland limits of agreement, Lin's concordance coefficient with Partik's grading schema, and Deming orthogonal bias-weighted correlation methodology. 1019 software-assisted shifts were suggested by US and FM in 39 patients. The 95% limits of agreement in X, Y and Z axes were ±9.4 mm, ±11.3 mm and ±13.4, respectively. Three-dimensionally, measurements agreed within 13.4 mm in 95% of all paired measures. In all axes, concordance was graded as 'poor' or 'unacceptable'. Deming regression detected proportional bias in both directional axes and three-dimensional vectors. Our data suggest substantial differences between US and FM image-guided measures and subsequent suggested directional shifts. Analysis reveals that the vast majority of

  12. WE-D-210-04: Radiation-Induced Polymerization of Ultrasound Contrast Agents in View of Non-Invasive Dosimetry in External Beam Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Callens, M; Verboven, E; Van Den Abeele, K [Department of Physics, Wave Propagation and Signal Processing, KU Leuven KULAK, Kortrijk (Belgium); D’Agostino, E [DoseVue NV, Hasselt (Belgium); Pfeiffer, H [Department of Materials Engineering, KU Leuven, Leuven (Belgium); D’hooge, J [Department of Cardiovascular Sciences, Bio-Medical Science Group, KU Leuven, Leuven (Belgium)

    2015-06-15

    Purpose: Ultrasound contrast agents (UCA’s) based on gas-filled microbubbles encapsulated by an amphiphilic shell are well established as safe and effective echo-enhancers in diagnostic imaging. In view of an alternative application of UCA’s, we investigated the use of targeted microbubbles as radiation sensors for external beam radiation therapy. As radiation induces permanent changes in the microbubble’s physico-chemical properties, a robust measure of these changes can provide a direct or indirect estimate of the applied radiation dose. For instance, by analyzing the ultrasonic dispersion characteristics of microbubble distributions before and after radiation treatment, an estimate of the radiation dose at the location of the irradiated volume can be made. To increase the radiation sensitivity of microbubbles, polymerizable diacetylene molecules can be incorporated into the shell. This study focuses on characterizing the acoustic response and quantifying the chemical modifications as a function of radiation dose. Methods: Lipid/diacetylene microbubbles were irradiated with a 6 MV photon beam using dose levels in the range of 0–150 Gy. The acoustic response of the microbubbles was monitored by ultrasonic through-transmission measurements in the range of 500 kHz to 20 MHz, thereby providing the dispersion relations of the phase velocity, attenuation and nonlinear coefficient. In addition, the radiation-induced chemical modifications were quantified using UV-VIS spectroscopy. Results: UV-VIS spectroscopy measurements indicate that ionizing radiation induces the polymerization of diacetylenes incorporated in the microbubble shell. The polymer yield strongly depends on the shell composition and the radiation-dose. The acoustic response is inherently related to the visco-elastic properties of the shell and is strongly influenced by the shell composition and the physico-chemical changes in the environment. Conclusion: Diacetylene-containing microbubbles are

  13. Comparison of trans-perineal ultrasound-guided pressure augmented saline colostomy distension study and conventional contrast radiographic colostography in children with anorectal malformation.

    Science.gov (United States)

    Ekwunife, Okechukwu Hyginus; Umeh, Eric Okechukwu; Ugwu, Jideofor Okechukwu; Ebubedike, Uzoamaka Rufina; Okoli, Chinedu Christian; Modekwe, Victor Ifeanyichukwu; Elendu, Kelechi Collins

    2016-01-01

    In children with high and intermediate anorectal malformation, distal colostography is an important investigation done to determine the relationship between the position of the rectal pouch and the probable site of the neo-anus as well as the presence or absence of a fistula. Conventionally, this is done using contrast with fluoroscopy or still X-ray imaging. This, however, has the challenges of irradiation, availability and affordability, especially in developing countries. This study compared the accuracy of trans-perineal ultrasound-guided pressure augmented saline colostomy distension study (SCDS) with conventional contrast distal colostography (CCDC) in the determination of the precise location of the distal rectal pouch and in detecting the presence and site of fistulous communication between the rectum and the urogenital tract was studied. Trans-perineal ultrasound-guided pressure augmented SCDS, CCDC and intra-operative measurements were done sequentially for qualified infants with anorectal malformation and colostomy. Pouch skin distance and presence or absence of recto urinary or genital fistula was measured prospectively in each case. Statistical significance was inferred at P-value of 0.01. On its ability to detect presence or absence of a fistula: SCDS had a sensitivity of 50.0%, specificity of 100.0%, accuracy of 69.2%, negative predictive value of fistulas of 55.6% and a positive predictive value of fistulas of 100.0%. Ultrasound-guided pressure augmented SCDS can safely and reliably be used to assess the distal colonic anatomy and the presence of fistula in infants with Anorectal malformation who are on colostomy.

  14. Evaluation of the therapeutic efficacy of high-intensity focused ultrasound ablation of hepatocellular carcinoma by three-dimensional sonography with a perflubutane-based contrast agent

    International Nuclear Information System (INIS)

    Numata, Kazushi; Fukuda, Hiroyuki; Ohto, Masao; Itou, Ryu; Nozaki, Akito; Kondou, Masaaki; Morimoto, Manabu; Karasawa, Eii; Tanaka, Katsuaki

    2010-01-01

    Objective: We performed contrast-enhanced three-dimensional sonography (CE 3D US) with a perflubutane-based contrast agent to immediately evaluate the completeness of ablation of small hepatocellular carcinoma (HCC) lesions by extracorporeal high-intensity focused ultrasound (HIFU). Subjects and methods: Twenty-one HCC lesions were treated by a single ultrasound-guided HIFU ablation session, and CE 3D US was performed before, immediately after, and 1 week, and 1 month after HIFU, and contrast-enhanced CT (CE CT) or contrast-enhanced MRI (CE MRI) was performed before HIFU, 1 week and 1 month after HIFU, and during the follow-up period. Results: Immediately and 1 month after HIFU, 17 lesions were evaluated as adequately ablated by CE 3D US, and the other 4 lesions as residual tumors. One month after HIFU, 18 were evaluated as adequately ablated by CE CT or CE MRI, and the other 3 as residual tumors. The evaluation by CE 3D US immediately after HIFU and by CE CT or CE MRI 1 month after HIFU was concordant with 20 lesions. The kappa value for agreement between the findings of CE 3D US and other modalities by two blinded observers was 0.83. When the 1-month CE CT or CE MRI findings were used as the reference standard, the sensitivity, specificity, and accuracy of CE 3D US immediately after HIFU for the diagnosis of the adequate ablation were 100%, 75%, and 95%, respectively. Conclusion: CE 3D US appears to be a useful method for immediate evaluation of therapeutic efficacy of HIFU ablation of HCC lesions.

  15. Evaluation of the therapeutic efficacy of high-intensity focused ultrasound ablation of hepatocellular carcinoma by three-dimensional sonography with a perflubutane-based contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Numata, Kazushi, E-mail: kz-numa@urahp.yokohama-cu.ac.j [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan); Fukuda, Hiroyuki; Ohto, Masao; Itou, Ryu [Department of Internal Medicine, Naruto General Hospital, 167 Naruto, Sanbu, Chiba 289-1326 (Japan); Nozaki, Akito; Kondou, Masaaki; Morimoto, Manabu [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan); Karasawa, Eii [Department of Gastroenterology, International University of Health and Welfare Atami Hospital, 13-1 Higashi Kaigan-cho, Atami, Shizuoka 413-0012 (Japan); Tanaka, Katsuaki [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan)

    2010-08-15

    Objective: We performed contrast-enhanced three-dimensional sonography (CE 3D US) with a perflubutane-based contrast agent to immediately evaluate the completeness of ablation of small hepatocellular carcinoma (HCC) lesions by extracorporeal high-intensity focused ultrasound (HIFU). Subjects and methods: Twenty-one HCC lesions were treated by a single ultrasound-guided HIFU ablation session, and CE 3D US was performed before, immediately after, and 1 week, and 1 month after HIFU, and contrast-enhanced CT (CE CT) or contrast-enhanced MRI (CE MRI) was performed before HIFU, 1 week and 1 month after HIFU, and during the follow-up period. Results: Immediately and 1 month after HIFU, 17 lesions were evaluated as adequately ablated by CE 3D US, and the other 4 lesions as residual tumors. One month after HIFU, 18 were evaluated as adequately ablated by CE CT or CE MRI, and the other 3 as residual tumors. The evaluation by CE 3D US immediately after HIFU and by CE CT or CE MRI 1 month after HIFU was concordant with 20 lesions. The kappa value for agreement between the findings of CE 3D US and other modalities by two blinded observers was 0.83. When the 1-month CE CT or CE MRI findings were used as the reference standard, the sensitivity, specificity, and accuracy of CE 3D US immediately after HIFU for the diagnosis of the adequate ablation were 100%, 75%, and 95%, respectively. Conclusion: CE 3D US appears to be a useful method for immediate evaluation of therapeutic efficacy of HIFU ablation of HCC lesions.

  16. PLGA/PFC particles loaded with gold nanoparticles as dual contrast agents for photoacoustic and ultrasound imaging

    Science.gov (United States)

    Wang, Yan J.; Strohm, Eric M.; Sun, Yang; Niu, Chengcheng; Zheng, Yuanyi; Wang, Zhigang; Kolios, Michael C.

    2014-03-01

    Phase-change contrast agents consisting of a perfluorocarbon (PFC) liquid core stabilized by a lipid, protein, or polymer shell have been proposed for a variety of clinical applications. Previous work has demonstrated that vaporization can be induced by laser irradiation through optical absorbers incorporated inside the droplet. In this study, Poly-lactide-coglycolic acid (PLGA) particles loaded with PFC liquid and silica-coated gold nanoparticles (GNPs) were developed and characterized using photoacoustic (PA) methods. Microsized PLGA particles were loaded with PFC liquid and GNPs (14, 35, 55nm each with a 20nm silica shell) using a double emulsion method. The PA signal intensity and optical vaporization threshold were investigated using a 375 MHz transducer and a focused 532-nm laser (up to 450-nJ per pulse). The laser-induced vaporization threshold energy decreased with increasing GNP size. The vaporization threshold was 850, 690 and 420 mJ/cm2 for 5μm-sized PLGA particles loaded with 14, 35 and 55 nm GNPs, respectively. The PA signal intensity increased as the laser fluence increased prior to the vaporization event. This trend was observed for all particles sizes. PLGA particles were then incubated with MDA-MB-231 breast cancer cells for 6 hours to investigate passive targeting, and the vaporization of the PLGA particles that were internalized within cells. The PLGA particles passively internalized by MDA cells were visualized via confocal fluorescence imaging. Upon PLGA particle vaporization, bubbles formed inside the cells resulting in cell destruction. This work demonstrates that GNPs-loaded PLGA/PFC particles have potential as PA theranostic agents in PA imaging and optically-triggered drug delivery systems.

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

    Science.gov (United States)

    Zhou, Zhuxian; Han, Zhen; Lu, Zheng-Rong

    2016-04-01

    The clinical application of nanoparticular Gd(III) based contrast agents for tumor molecular MRI has been hindered by safety concerns associated with prolonged tissue retention, although they can produce strong tumor enhancement. In this study, a targeted well-defined cyclodextrin-based nanoglobular contrast agent was developed through self-assembly driven by host-guest interactions for safe and effective cancer molecular MRI. Multiple β-cyclodextrins attached POSS (polyhedral oligomeric silsesquioxane) nanoglobule was used as host molecule. Adamantane-modified macrocyclic Gd(III) contrast agent, cRGD (cyclic RGDfK peptide) targeting ligand and fluorescent probe was used as guest molecules. The targeted host-guest nanoglobular contrast agent cRGD-POSS-βCD-(DOTA-Gd) specifically bond to αvβ3 integrin in malignant 4T1 breast tumor and provided greater contrast enhancement than the corresponding non-targeted agent. The agent also provided significant fluorescence signal in tumor tissue. The histological analysis of the tumor tissue confirmed its specific and effective targeting to αvβ3 integrin. The targeted imaging agent has a potential for specific cancer molecular MR and fluorescent imaging. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2013-03-01

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

  19. Light localization with low-contrast targets in a patient implanted with a suprachoroidal-transretinal stimulation retinal prosthesis.

    Science.gov (United States)

    Endo, Takao; Fujikado, Takashi; Hirota, Masakazu; Kanda, Hiroyuki; Morimoto, Takeshi; Nishida, Kohji

    2018-04-20

    To evaluate the improvement in targeted reaching movements toward targets of various contrasts in a patient implanted with a suprachoroidal-transretinal stimulation (STS) retinal prosthesis. An STS retinal prosthesis was implanted in the right eye of a 42-year-old man with advanced Stargardt disease (visual acuity: right eye, light perception; left eye, hand motion). In localization tests during the 1-year follow-up period, the patient attempted to touch the center of a white square target (visual angle, 10°; contrast, 96, 85, or 74%) displayed at a random position on a monitor. The distance between the touched point and the center of the target (the absolute deviation) was averaged over 20 trials with the STS system on or off. With the left eye occluded, the absolute deviation was not consistently lower with the system on than off for high-contrast (96%) targets, but was consistently lower with the system on for low-contrast (74%) targets. With both eyes open, the absolute deviation was consistently lower with the system on than off for 85%-contrast targets. With the system on and 96%-contrast targets, we detected a shorter response time while covering the right eye, which was being implanted with the STS, compared to covering the left eye (2.41 ± 2.52 vs 8.45 ± 3.78 s, p trial: Feb. 20, 2014 Date of registration: Jan. 4, 2014 Trial registration number: UMIN000012754 Registration site: UMIN Clinical Trials Registry (UMIN-CTR) http://www.umin.ac.jp/ctr/index.htm.

  20. Validation of dynamic contrast-enhanced ultrasound in predicting outcomes of antiangiogenic therapy for solid tumors: the French multicenter support for innovative and expensive techniques study.

    Science.gov (United States)

    Lassau, Nathalie; Bonastre, Julia; Kind, Michèle; Vilgrain, Valérie; Lacroix, Joëlle; Cuinet, Marie; Taieb, Sophie; Aziza, Richard; Sarran, Antony; Labbe-Devilliers, Catherine; Gallix, Benoit; Lucidarme, Olivier; Ptak, Yvette; Rocher, Laurence; Caquot, Louis-Michel; Chagnon, Sophie; Marion, Denis; Luciani, Alain; Feutray, Sylvaine; Uzan-Augui, Joëlle; Coiffier, Benedicte; Benastou, Baya; Koscielny, Serge

    2014-12-01

    Dynamic contrast-enhanced ultrasound (DCE-US) has been used in single-center studies to evaluate tumor response to antiangiogenic treatments: the change of area under the perfusion curve (AUC), a criterion linked to blood volume, was consistently correlated with the Response Evaluation Criteria in Solid Tumors response. The main objective here was to do a multicentric validation of the use of DCE-US to evaluate tumor response in different solid tumor types treated by several antiangiogenic agents. A secondary objective was to evaluate the costs of the procedure. This prospective study included patients from 2007 to 2010 in 19 centers (8 teaching hospitals and 11 comprehensive cancer centers). All patients treated with antiangiogenic therapy were eligible. Dynamic contrast-enhanced ultrasound examinations were performed at baseline as well as on days 7, 15, 30, and 60. For each examination, a perfusion curve was recorded during 3 minutes after injection of a contrast agent. Change from baseline at each time point was estimated for each of 7 fitted criteria. The main end point was freedom from progression (FFP). Criterion/time-point combinations with the strongest correlation with FFP were analyzed further to estimate an optimal cutoff point. A total of 1968 DCE-US examinations in 539 patients were analyzed. The median follow-up was 1.65 years. Variations from baseline were significant at day 30 for several criteria, with AUC having the most significant association with FFP (P = 0.00002). Patients with a greater than 40% decrease in AUC at day 30 had better FFP (P = 0.005) and overall survival (P = 0.05). The mean cost of each DCE-US was 180&OV0556;, which corresponds to $250 using the current exchange rate. Dynamic contrast-enhanced ultrasound is a new functional imaging technique that provides a validated criterion, namely, the change of AUC from baseline to day 30, which is predictive of tumor progression in a large multicenter cohort. Because of its low cost, it

  1. Ultrasound-mediated blood-brain barrier disruption for targeted drug delivery in the central nervous system

    Science.gov (United States)

    Aryal, Muna; Arvanitis, Costas D.; Alexander, Phillip M.; McDannold, Nathan

    2014-01-01

    The physiology of the vasculature in the central nervous system (CNS), which includes the blood-brain barrier (BBB) and other factors, complicates the delivery of most drugs to the brain. Different methods have been used to bypass the BBB, but they have limitations such as being invasive, non-targeted or requiring the formulation of new drugs. Focused ultrasound (FUS), when combined with circulating microbubbles, is a noninvasive method to locally and transiently disrupt the BBB at discrete targets. This review provides insight on the current status of this unique drug delivery technique, experience in preclinical models, and potential for clinical translation. If translated to humans, this method would offer a flexible means to target therapeutics to desired points or volumes in the brain, and enable the whole arsenal of drugs in the CNS that are currently prevented by the BBB. PMID:24462453

  2. Effect of different ultrasound contrast materials and temperatures on patient comfort during intrauterine and tubal assessment for infertility

    International Nuclear Information System (INIS)

    Fenzl, Vanja

    2012-01-01

    Hysterosalpingo-contrast sonography (HyCoSy) is safe and easy to perform outpatient method in the evaluation of female infertility. During this procedure a certain level of discomfort and pain are experienced by patients. On the basis of reducing avoidable pain inductors the aim of this study was to compare pain sensation due to different warmth of applied contrasts (sterile saline and Echovist ® ). Prospective and randomized study was performed on patients requiring tubal and uterine assessment during standard infertility work up. One group of patients was examined using both contrasts at room temperature and the other group using preheated contrasts at body temperature. Pain experience of the procedure was rated by patients for each contrast by numerical scale (0–10) immediately after the procedure. There was significant statistical difference between pain scores during application of two contrasts in each group; Echovist induces significantly less pain in comparison to sterile saline at the same temperature (P = 0.002, 0.001). Between two groups there is also statistically significant difference in pain during introduction of the same contrast at different temperature (P < 0.001). The most tolerable for the patient is body temperature of the applied contrasts although their structure and concentrations can be another factor associated with tolerability of the procedure.

  3. Effect of different ultrasound contrast materials and temperatures on patient comfort during intrauterine and tubal assessment for infertility

    Energy Technology Data Exchange (ETDEWEB)

    Fenzl, Vanja, E-mail: vanja.radic@inet.hr [Department of Gynecology and Obstetrics, University Hospital “Merkur”, Zajčeva 19 (Croatia); University of Applied Health Studies, Mlinarska Cesta 38, 10000 Zagreb (Croatia)

    2012-12-15

    Hysterosalpingo-contrast sonography (HyCoSy) is safe and easy to perform outpatient method in the evaluation of female infertility. During this procedure a certain level of discomfort and pain are experienced by patients. On the basis of reducing avoidable pain inductors the aim of this study was to compare pain sensation due to different warmth of applied contrasts (sterile saline and Echovist{sup ®}). Prospective and randomized study was performed on patients requiring tubal and uterine assessment during standard infertility work up. One group of patients was examined using both contrasts at room temperature and the other group using preheated contrasts at body temperature. Pain experience of the procedure was rated by patients for each contrast by numerical scale (0–10) immediately after the procedure. There was significant statistical difference between pain scores during application of two contrasts in each group; Echovist induces significantly less pain in comparison to sterile saline at the same temperature (P = 0.002, 0.001). Between two groups there is also statistically significant difference in pain during introduction of the same contrast at different temperature (P < 0.001). The most tolerable for the patient is body temperature of the applied contrasts although their structure and concentrations can be another factor associated with tolerability of the procedure.

  4. The partitioning of nanoparticles to endothelium or interstitium during ultrasound-microbubble-targeted delivery depends on peak-negative pressure

    International Nuclear Information System (INIS)

    Hsiang, Y.-H.; Song, J.; Price, R. J.

    2015-01-01

    Patients diagnosed with advanced peripheral arterial disease often face poor prognoses and have limited treatment options. For some patient populations, the therapeutic growth of collateral arteries (i.e. arteriogenesis) that bypass regions affected by vascular disease may become a viable treatment option. Our group and others are developing therapeutic approaches centered on the ability of ultrasound-activated microbubbles to permeabilize skeletal muscle capillaries and facilitate the targeted delivery of pro-arteriogenic growth factor-bearing nanoparticles. The development of such approaches would benefit significantly from a better understanding of how nanoparticle diameter and ultrasound peak-negative pressure affect both total nanoparticle delivery and the partitioning of nanoparticles to endothelial or interstitial compartments. Toward this goal, using Balb/C mice that had undergone unilateral femoral artery ligation, we intra-arterially co-injected nanoparticles (50 and 100 nm) with microbubbles, applied 1 MHz ultrasound to the gracilis adductor muscle at peak-negative pressures of 0.7, 0.55, 0.4, and 0.2 MPa, and analyzed nanoparticle delivery and distribution. As expected, total nanoparticle (50 and 100 nm) delivery increased with increasing peak-negative pressure, with 50 nm nanoparticles exhibiting greater tissue coverage than 100 nm nanoparticles. Of particular interest, increasing peak-negative pressure resulted in increased delivery to the interstitium for both nanoparticle sizes, but had little influence on nanoparticle delivery to the endothelium. Thus, we conclude that alterations to peak-negative pressure may be used to adjust the fraction of nanoparticles delivered to the interstitial compartment. This information will be useful when designing ultrasound protocols for delivering pro-arteriogenic nanoparticles to skeletal muscle

  5. The partitioning of nanoparticles to endothelium or interstitium during ultrasound-microbubble-targeted delivery depends on peak-negative pressure

    Energy Technology Data Exchange (ETDEWEB)

    Hsiang, Y.-H.; Song, J.; Price, R. J., E-mail: rprice@virginia.edu [University of Virginia, Department of Biomedical Engineering (United States)

    2015-08-15

    Patients diagnosed with advanced peripheral arterial disease often face poor prognoses and have limited treatment options. For some patient populations, the therapeutic growth of collateral arteries (i.e. arteriogenesis) that bypass regions affected by vascular disease may become a viable treatment option. Our group and others are developing therapeutic approaches centered on the ability of ultrasound-activated microbubbles to permeabilize skeletal muscle capillaries and facilitate the targeted delivery of pro-arteriogenic growth factor-bearing nanoparticles. The development of such approaches would benefit significantly from a better understanding of how nanoparticle diameter and ultrasound peak-negative pressure affect both total nanoparticle delivery and the partitioning of nanoparticles to endothelial or interstitial compartments. Toward this goal, using Balb/C mice that had undergone unilateral femoral artery ligation, we intra-arterially co-injected nanoparticles (50 and 100 nm) with microbubbles, applied 1 MHz ultrasound to the gracilis adductor muscle at peak-negative pressures of 0.7, 0.55, 0.4, and 0.2 MPa, and analyzed nanoparticle delivery and distribution. As expected, total nanoparticle (50 and 100 nm) delivery increased with increasing peak-negative pressure, with 50 nm nanoparticles exhibiting greater tissue coverage than 100 nm nanoparticles. Of particular interest, increasing peak-negative pressure resulted in increased delivery to the interstitium for both nanoparticle sizes, but had little influence on nanoparticle delivery to the endothelium. Thus, we conclude that alterations to peak-negative pressure may be used to adjust the fraction of nanoparticles delivered to the interstitial compartment. This information will be useful when designing ultrasound protocols for delivering pro-arteriogenic nanoparticles to skeletal muscle.

  6. Color Doppler ultrasound evaluation of asphyxial neonatal left ventricular function and its correlation with target organ damage

    Directory of Open Access Journals (Sweden)

    Cheng-Cai Chen

    2017-01-01

    Full Text Available Objective: To study the color Doppler ultrasound parameters of asphyxial neonatal left ventricular function and the correlation with target organ damage. Methods: Normal neonates, mildly asphyxial neonates and severely asphyxial neonates born in our hospital between January 2014 and December 2015 were selected as the control group (n = 46, mild asphyxia group (n = 37 and severe asphyxia group (n = 23 respectively. On the 1st day after birth, color Doppler ultrasound was used to evaluate left ventricular function, and serum was collected to determine myocardial tissue injury, brain tissue injury and brain tissue metabolism indexes. Results: Color Doppler ultrasound parameters cardiac output (CO, ejection fraction (EF and left ventricular fraction shortening (FS as well as serum folate and vitamin B12 content of mild asphyxia group and severe asphyxia group were significantly lower than those of control group (P<0.05 while serum creatine kinase isoenzyme (CK-MB, troponin I (cTnI, troponin T (cTnT, S100B, neuron-specific enolase (NSE, creatine kinase BB (CK-BB, glycogen phosphorylase BB (GPBB, and homocysteine (Hcy content were significantly higher than those of control group (P<0.05; CO, FS and EF as well as serum folate and vitamin B12 content of severe asphyxia group were significantly lower than those of mild asphyxia group (P<0.05 while serum CK-MB, cTnT, cTnI, S100B, NSE, CK-BB, GPBB and Hcy content were significantly higher than those of mild asphyxia group (P<0.05. Conclusions: Color Doppler ultrasound can accurately assess asphyxial neonatal left ventricular function damage degree and is closely related to myocardial tissue injury and brain tissue injury degree.

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  8. Clinical utility of a microbubble-enhancing contrast (“SonoVue”) in treatment of uterine fibroids with high intensity focused ultrasound: A retrospective study

    International Nuclear Information System (INIS)

    Peng, Song; Xiong, Yu; Li, Kequan; He, Min; Deng, Yongbin; Chen, Li; Zou, Min; Chen, Wenzhi; Wang, Zhibiao; He, Jia

    2012-01-01

    Purpose: To evaluate the clinical value of the contrast agent SonoVue in the treatment of uterine fibroids with ultrasound-guided high intensity focused ultrasound (HIFU) therapeutic ablation. Materials and Methods: A total of 291 patients with solitary uterine fibroid from three centers were treated with ultrasound-guided HIFU. Among them, 129 patients from Suining Central Hospital of Sichuan were treated without using SonoVue. 162 patients from the First Hospital of Chongqing Medical University and Chongqing Haifu Hospital were treated with using SonoVue before, during and after HIFU procedure to assess the extent of HIFU. Results: The non-perfused volume (indicative of successful ablation) was observed in all treated uterine fibroids immediately after HIFU ablation; median fractional ablation, defined as non-perfused volume divided by the fibroid volume immediately after HIFU treatment, was 86.0% (range, 28.8–100.0%) in the group with using SonoVue, and 83.0% (8.7–100.0%) without SonoVue. The rate of massive gray scale changes was higher with SonoVue than without the agent. The sonication time to achieve massive gray scale changes was shorter with SonoVue than without. The sonication time for ablating 1 cm 3 of fibroid volume was significantly shorter with using SonoVue than without. No major complications were observed in any patients. Conclusions: Based on our results, SonoVue may enhance the outcome of HIFU ablation and can be used to assess the extent of treatment.

  9. The use of contrast-enhanced color doppler ultrasound in the differentiation of retinal detachment from vitreous membrane

    International Nuclear Information System (INIS)

    Han, Sang Suk; Chang, Seung Kook; Yoon, Jung Hee; Lee, Young Joon

    2001-01-01

    To compare the clinical utility of contrast-enhanced color Doppler US in the differentiation of retinal detachment (RD) from vitreous membrane (VM) with that of various conventional US modalities, and to analyze the enhancement patterns in cases showing an enhancement effect. In 32 eyes examined over a recent two-year period, RD (n=14) and VM (n=18) were confirmed by surgery (n=28) or clinical follow-up (n=4). In all cases, gray-scale, color Doppler, and power Doppler US were performed prior to contrast injection, and after the intravenous injection of Levovist (Schering, Berlin) by hand for 30 seconds at a dose of 2.5 g and a concentration of 300 mg/mL via an antecubital vein, contrast-enhanced color Doppler US was performed. At Doppler US, the diagnostic criterion for RD and VM was whether or not color signals were visualized in membranous structures. Diagnostic accuracy was 78% at gray-scale US, 81% at color Doppler US, 59% at power Doppler US, and 97% at contrast-enhanced color Doppler US. The sensitivity of color Doppler US to color signals in RD increased from 57% to 93% after contrast enhancement. The enhancement patterns observed were signal accentuation (n=3), signal extension (n=2), signal addition (n=3), and new signal visualization (n=5). Contrast-enhanced color Doppler US was the most accurate US modality for differentiating RD from VM, showing a significantly increased signal detection rate in RD

  10. Indeterminate solid hepatic lesions identified on non-diagnostic contrast-enhanced computed tomography: Assessment of the additional diagnostic value of contrast-enhanced ultrasound in the non-cirrhotic liver

    International Nuclear Information System (INIS)

    Quaia, Emilio; De Paoli, Luca; Angileri, Roberta; Cabibbo, Biagio; Cova, Maria Assunta

    2014-01-01

    Objective: To assess the additional diagnostic value of contrast-enhanced ultrasound (CEUS) in the characterization of indeterminate solid hepatic lesions identified on non-diagnostic contrast-enhanced computed tomography (CT). Methods: Fifty-five solid hepatic lesions (1–4 cm in diameter) in 46 non-cirrhotic patients (26 female, 20 male; age ± SD, 55 ± 10 years) underwent CEUS after being detected on contrast-enhanced CT which was considered as non-diagnostic after on-site analysis. Two blinded independent readers assessed CT and CEUS scans and were asked to classify retrospectively each lesion as a malignant or benign based on reference diagnostic criteria for the different hepatic lesion histotypes. Diagnostic accuracy and confidence (area – A z – under ROC curve) were assessed by using gadobenate dimeglumine-enhanced magnetic resonance (MR) imaging (n = 30 lesions), histology (n = 7 lesions), or US follow-up (n = 18 lesions) as the reference standards. Results: Final diagnoses included 29 hemangiomas, 3 focal nodular hyperplasias, 1 hepatocellular adenoma, and 22 metastases. The additional review of CEUS after CT images improved significantly (P < .05) the diagnostic accuracy (before vs after CEUS review = 49% [20/55] vs 89% [49/55] – reader 1 and 43% [24/55] vs 92% [51/55] – reader 2) and confidence (A z , 95% Confidence Intervals before vs after CEUS review = .773 [.652–.895] vs .997 [.987–1] – reader 1 and .831 [.724–.938] vs .998 [.992–1] – reader 2). Conclusions: CEUS improved the characterization of indeterminate solid hepatic lesions identified on non-diagnostic contrast-enhanced CT by identifying some specific contrast enhancement patterns.

  11. Quantitative analysis of thyroid tumors vascularity: A comparison between 3-D contrast-enhanced ultrasound and 3-D Power Doppler on benign and malignant thyroid nodules.

    Science.gov (United States)

    Caresio, Cristina; Caballo, Marco; Deandrea, Maurilio; Garberoglio, Roberto; Mormile, Alberto; Rossetto, Ruth; Limone, Paolo; Molinari, Filippo

    2018-05-15

    To perform a comparative quantitative analysis of Power Doppler ultrasound (PDUS) and Contrast-Enhancement ultrasound (CEUS) for the quantification of thyroid nodules vascularity patterns, with the goal of identifying biomarkers correlated with the malignancy of the nodule with both imaging techniques. We propose a novel method to reconstruct the vascular architecture from 3-D PDUS and CEUS images of thyroid nodules, and to automatically extract seven quantitative features related to the morphology and distribution of vascular network. Features include three tortuosity metrics, the number of vascular trees and branches, the vascular volume density, and the main spatial vascularity pattern. Feature extraction was performed on 20 thyroid lesions (ten benign and ten malignant), of which we acquired both PDUS and CEUS. MANOVA (multivariate analysis of variance) was used to differentiate benign and malignant lesions based on the most significant features. The analysis of the extracted features showed a significant difference between the benign and malignant nodules for both PDUS and CEUS techniques for all the features. Furthermore, by using a linear classifier on the significant features identified by the MANOVA, benign nodules could be entirely separated from the malignant ones. Our early results confirm the correlation between the morphology and distribution of blood vessels and the malignancy of the lesion, and also show (at least for the dataset used in this study) a considerable similarity in terms of findings of PDUS and CEUS imaging for thyroid nodules diagnosis and classification. © 2018 American Association of Physicists in Medicine.

  12. Contrast-Enhanced Ultrasound and Near-Infrared Spectroscopy of the Neonatal Bowel: Novel, Bedside, Noninvasive, and Radiation-Free Imaging for Early Detection of Necrotizing Enterocolitis.

    Science.gov (United States)

    Al-Hamad, Suzanne; Hackam, David J; Goldstein, Seth D; Huisman, Thierry A G M; Darge, Kassa; Hwang, Misun

    2018-05-31

    Despite extensive research and improvements in the field of neonatal care, the morbidity and mortality associated with necrotizing enterocolitis (NEC) have remained unchanged over the past three decades. Early detection of ischemia and necrotic bowel is vital in improving morbidity and mortality associated with NEC; however, strategies for predicting and preventing NEC are lacking. Contrast-enhanced ultrasound (CEUS) and near-infrared spectroscopy (NIRS) are novel techniques in pediatrics that have been proven as safe modalities. CEUS has benefits over conventional ultrasound (US) by its improved real-time evaluation of the micro- and macrovascularities of normally and abnormally perfused tissue. US has been implemented as a useful adjunct to X-ray for earlier evaluation of NEC. NIRS is another noninvasive technique that has shown promise in improving early detection of NEC. The purpose of this article is to review the current understanding of changes in bowel perfusion in NEC, discuss the accuracy of abdominal US in detecting NEC, and explain how the use of CEUS and NIRS will enhance the precise and early detection of altered/pathological bowel wall perfusion in the initial development and course of NEC. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

    Science.gov (United States)

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

    2015-06-01

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-12-12

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

  16. Rest-Stress Limb Perfusion Imaging in Humans with Contrast Ultrasound Using Intermediate-Power Imaging and Microbubbles Resistant to Inertial Cavitation.

    Science.gov (United States)

    Davidson, Brian P; Hodovan, James; Belcik, J Todd; Moccetti, Federico; Xie, Aris; Ammi, Azzdine Y; Lindner, Jonathan R

    2017-05-01

    Contrast-enhanced ultrasound (CEU) limb perfusion imaging is a promising approach for evaluating peripheral artery disease (PAD). However, low signal enhancement in skeletal muscle has necessitated high-power intermittent imaging algorithms, which are not clinically feasible. We hypothesized that CEU using a combination of intermediate power and a contrast agent resistant to inertial cavitation would allow real-time limb stress perfusion imaging. In normal volunteers, CEU of the calf skeletal muscle was performed on separate days with Sonazoid, Optison, or Definity. Progressive reduction in the ultrasound pulsing interval was used to assess the balance between signal enhancement and agent destruction at escalating mechanical indices (MI, 0.1-0.4). Real-time perfusion imaging at MI 0.1-0.4 using postdestructive replenishment kinetics was performed at rest and during 25 W plantar flexion contractile exercise. For Optison, limb perfusion imaging was unreliable at rest due to very low signal enhancement generated at all MIs and was possible during exercise-induced hyperemia only at MI 0.1 due to agent destruction at higher MIs. For Definity, signal intensity progressively increased with MI but was offset by microbubble destruction, which resulted in modest signal enhancement during CEU perfusion imaging and distortion of replenishment curves at MI ≥ 0.2. For Sonazoid, there strong signal enhancement at MI ≥ 0.2, with little destruction detected only at MI 0.4. Accordingly, high signal intensity and nondistorted perfusion imaging was possible at MI 0.2-0.3 and detected an 8.0- ± 5.7-fold flow reserve. Rest-stress limb perfusion imaging in humans with real-time CEU, which requires only seconds to perform, is possible using microbubbles with viscoelastic properties that produce strong nonlinear signal generation without destruction at intermediate acoustic pressures. Copyright © 2016 American Society of Echocardiography. All rights reserved.

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

    Science.gov (United States)

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

    2009-05-01

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

  18. The value of contrast-enhanced laparoscopic ultrasound during robotic-assisted surgery for primary colorectal cancer

    DEFF Research Database (Denmark)

    Ellebaek, Signe Bremholm; Fristrup, Claus Wilki; Pless, Torsten

    2018-01-01

    AIM: The aim of this study was to assess the potential clinical value of contrast enhanced laparoscopic ultrasonography (CE-LUS) as a screening modality for liver metastases during robotic assisted surgery for primary colorectal cancer (CRC). METHOD: A prospective, descriptive (feasibility) study...... including 50 consecutive patients scheduled for robotic assisted surgery for primary CRC. CE-LUS was performed by 2 experienced specialists. Only patients without metastatic disease were included. Follow-up was obtained with contrast-enhanced CT imaging at 3 and 12 months postoperatively. RESULTS: Fifty......-up revealed no liver metastasis in any of the patients. CONCLUSION: CE-LUS did not increase the detection rate of occult liver metastasis during robotic assisted primary CRC surgery. The use of CE-LUS as a screening modality for detection of liver metastasis cannot be recommended based on this study...

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

    Science.gov (United States)

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

    2017-08-01

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

  20. WE-DE-BRA-08: A Linear Accelerator Target Allowing Rapid Switching Between Treatment and High-Contrast Imaging Modes

    Energy Technology Data Exchange (ETDEWEB)

    Yewondwossen, M; Robar, J; Parsons, D [Dalhousie University, Halifax, NS (Canada)

    2016-06-15

    Purpose: During radiotherapy treatment, lung tumors can display substantial respiratory motion. This motion usually necessitates enlarged treatment margins to provide full tumour coverage. Unfortunately, these margins limit the dose that can be prescribed for tumour control and cause complications to normal tissue. Options for real-time methods of direct detection of tumour position, and particularly those that obviate the need for inserted fiducial markers, are limited. We propose a method of tumor tracking without implanted fiducial markers using a novel fast switching-target that toggles between a FFF copper/tungsten therapy mode and a FFF low-Z target mode for imaging. In this work we demonstrate proof-of-concept of this new technology. Methods: The prototype includes two targets: i) a FFF copper/tungsten target equivalent to that in the Varian 2100 EX 6 MV, and ii) a low-Z (carbon) target with a thickness of 110% of continuous slowing down approximation range (CSDA) at 7 MeV. The two targets can be exchanged with a custom made linear slide and motor-driven actuator. The usefulness of the switching-target concept is demonstrated through experimental BEV Planar images acquired with continual treatment and imaging at a user-defined period. Results: The prototype switching-target demonstrates that two recent advances in linac technology (FFF target for therapy and low-Z target) can be combined with synergy. The switching-target approach offers the capacity for rapid switching between treatment and high-contrast imaging modes, allowing intrafractional tracking, as demonstrated in this work with dynamic breathing phantom. By using a single beam-line, the design is streamlined and may obviate the need for an auxiliary imaging system (e.g., kV OBI.) Conclusion: This switching-target approach is a feasible combination of two current advances in linac technology (FFF target for therapy and a FFF low-Z target) allowing new options in on-line IGRT.

  1. Clinical value of elasticity imaging and contrast-enhanced ultrasound in the diagnosis of papillary thyroid microcarcinoma.

    Science.gov (United States)

    Li, Fengsheng; Zhang, Jianlei; Wang, Yunmei; Liu, Liwen

    2015-09-01

    The present study aimed to evaluate the value of elasticity imaging and contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of papillary thyroid microcarcinoma (TMC). In total, 73 patients exhibiting a total of 80 small thyroid nodules, which were difficult to diagnose using conventional ultrasonography, underwent elasticity imaging and CEUS. The diagnostic findings were subsequently clarified by intraoperative and pathological examination, and the accuracy of the 2 diagnostic methods was compared. The correct diagnostic rate of CEUS was 85% (68/80 nodules), of which 6 cases of TMC were misdiagnosed as benign lesions and 6 benign nodules were misdiagnosed as TMC. By contrast, the accuracy rate of the elasticity imaging, based on the 5-point diagnostic method, was 92.5% (74/80 nodules), of which 3 cases of TMC were misdiagnosed as benign nodules and 3 benign nodules were misdiagnosed as TMC. Furthermore, elasticity imaging in the diagnosis of TMC was determined to have sensitivity, specificity and accuracy rates of 94.0, 90.0 and 92.5%, respectively, whereas the corresponding rates for CEUS were 88.0, 80.0 and 85.0%, respectively. Thus, ultrasonographic elasticity imaging exhibited significant advantages in the diagnosis of TMC compared with CEUS (Padvantage in the diagnosis of TMC; however, an elasticity score of ≥3 is of high clinical value as a diagnostic criterion for TMC.

  2. An automatic respiratory gating method for the improvement of microcirculation evaluation: application to contrast-enhanced ultrasound studies of focal liver lesions

    Energy Technology Data Exchange (ETDEWEB)

    Mule, S; Kachenoura, N; Lucidarme, O; De Oliveira, A; Pellot-Barakat, C; Herment, A; Frouin, F, E-mail: Sebastien.Mule@gmail.com [INSERM UMR-S 678, 75634 Paris Cedex 13 (France)

    2011-08-21

    Contrast-enhanced ultrasound (CEUS), with the recent development of both contrast-specific imaging modalities and microbubble-based contrast agents, allows noninvasive quantification of microcirculation in vivo. Nevertheless, functional parameters obtained by modeling contrast uptake kinetics could be impaired by respiratory motion. Accordingly, we developed an automatic respiratory gating method and tested it on 35 CEUS hepatic datasets with focal lesions. Each dataset included fundamental mode and cadence contrast pulse sequencing (CPS) mode sequences acquired simultaneously. The developed method consisted in (1) the estimation of the respiratory kinetics as a linear combination of the first components provided by a principal components analysis constrained by a prior knowledge on the respiratory rate in the frequency domain, (2) the automated generation of two respiratory-gated subsequences from the CPS mode sequence by detecting end-of-inspiration and end-of-expiration phases from the respiratory kinetics. The fundamental mode enabled a more reliable estimation of the respiratory kinetics than the CPS mode. The k-means algorithm was applied on both the original CPS mode sequences and the respiratory-gated subsequences resulting in clustering maps and associated mean kinetics. Our respiratory gating process allowed better superimposition of manually drawn lesion contours on k-means clustering maps as well as substantial improvement of the quality of contrast uptake kinetics. While the quality of maps and kinetics was satisfactory in only 11/35 datasets before gating, it was satisfactory in 34/35 datasets after gating. Moreover, noise amplitude estimated within the delineated lesions was reduced from 62 {+-} 21 to 40 {+-} 10 (p < 0.01) after gating. These findings were supported by the low residual horizontal (0.44 {+-} 0.29 mm) and vertical (0.15 {+-} 0.16 mm) shifts found during manual motion correction of each respiratory-gated subsequence. The developed

  3. Evaluation of tumor response to intra-arterial chemoembolization of hepatocellular carcinoma: Comparison of contrast-enhanced ultrasound with multiphase computed tomography.

    Science.gov (United States)

    Paul, S B; Dhamija, E; Gamanagatti, S R; Sreenivas, V; Yadav, D P; Jain, S; Shalimar; Acharya, S K

    2017-03-01

    To compare the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) with that of multiphase computed tomography (CT) in the evaluation of tumor response to transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). Fifty patients (41 men, 9 women; mean age, 53 years±12.5 [SD]) with a total of 70 HCCs (mean size, 5cm±3 [SD]) were evaluated. Post-TACE therapeutic assessment of HCC was done at 4 weeks. Patients with TACE done earlier and reporting with suspicion for recurrence were also included. Patients with hepatic masses seen on ultrasound were enrolled and subjected to CEUS, multiphase CT and magnetic resonance imaging (MRI). Hyperenhancing area at the tumor site on arterial phase of CEUS/multiphase CT/MRI was termed as residual disease (RD), the patterns of which were described on CEUS. Diagnostic accuracies of CEUS and MPCT were compared to that of MRI that was used as the reference standard. CEUS detected RD in 43/70 HCCs (61%). RD had a heterogeneous pattern in 22/43 HCCs (51%). Sensitivities of CEUS and multiphase CT were 94% (34/36; 95% CI: 81-99%) and 50% (18/36; 95% CI: 33-67%) respectively. Significant difference in sensitivity was found between CEUS and multiphase CT (P=0.0001). CEUS and multiphase CT had 100% specificity (95% CI: 83-100%). CEUS is a useful technique for detecting RD in HCC after TACE. For long term surveillance, CEUS should be complemented with multiphase CT/MRI for a comprehensive evaluation. Copyright © 2016 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

  4. Relationship of thyroid ultrasound elasticity contrast index with serum autoantibody and Th1/Th2 cytokine levels in patients with Hashimoto's thyroiditis

    Directory of Open Access Journals (Sweden)

    Jian-Guo Sheng

    2016-10-01

    Full Text Available Objective: To study the relationship of thyroid ultrasound elasticity contrast index (ECI with serum autoantibody and Th1/Th2 cytokine levels in patients with Hashimoto's thyroiditis. Methods: A total of 68 patients diagnosed with Hashimoto's thyroiditis (HT in our hospitalas were selected as HT group, 60 healthy volunteers were selected as control group, ultrasound examination was performed to determine ECL, serum was collected to determine TPO-Ab, TG-Ab, IFN-γ, TNF-α, IL-2, IL-4 and IL-10 levels, and peripheral blood was collected to determine the positive expression rate of CD30 and CD195. Results: ECI of HT group was significantly higher than that of control group and the ECI of patients with small nodule type HT was significantly lower than that of patients with grid type HT; TPO-Ab, TG-Ab, IFN-γ, TNF-α and IL-2 levels in serum and positive expression rate of CD195 in peripheral blood of HT group were significantly higher than those of control group while IL-4 and IL-10 levels and positive expression rate of CD30 in peripheral blood were significantly lower than those of control group; TPO-Ab, TG-Ab, IFN-γ, TNF-α and IL-2 levels in serum and positive expression rate of CD195 in peripheral blood of patients with small nodule type HT were significantly lower than those of patients with grid type HT while IL-4 and IL-10 levels and positive expression rate of CD30 in peripheral blood were significantly higher than those of patients with grid type HT; ECI was positively correlated with TPO-Ab, TG-Ab, IFN-γ, TNF- α, IL-2b and CD195, and negatively correlated with IL-4, IL-10 and CD30. Conclusions: ECL significantly increases in patients with Hashimoto's thyroiditis and it can be used to evaluate the degree of immune dysfunction.

  5. Diagnostic accuracy of contrast-enhanced ultrasound in assessing the therapeutic response to radio frequency ablation for liver tumors: systematic review and meta-analysis.

    Science.gov (United States)

    Xuan, Min; Zhou, Fengsheng; Ding, Yan; Zhu, Qiaoying; Dong, Ji; Zhou, Hao; Cheng, Jun; Jiang, Xiao; Wu, Pengxi

    2018-04-01

    To review the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) used to detect residual or recurrent liver tumors after radiofrequency ablation (RFA). This technique uses contrast-enhanced computer tomography or/and contrast-enhanced magnetic resonance imaging as the gold standard of investigation. MEDLINE, EMBASE, and COCHRANE were systematically searched for all potentially eligible studies comparing CEUS with the reference standard that follows RFA. Risk of bias and applicability concerns were addressed by adopting the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Pooled point estimates for sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratios (DOR) with 95% CI were computed before plotting the sROC (summary receiver operating characteristic) curve. Meta-regression and subgroup analysis were used to identify the source of the heterogeneity that was detected. Publication bias was evaluated using Deeks' funnel plot asymmetry test. Ten eligible studies on 1162 lesions that occurred between 2001 and 2016 were included in the final analysis. The quality of the included studies assessed by the QUADAS-2 tool was considered reasonable. The pooled sensitivity and specificity of CEUS in detecting residual or recurrent liver tumors had the following values: 0.90 (95% CI 0.85-0.94) and 1.00 (95% CI 0.99-1.00), respectively. Overall DOR was 420.10 (95% CI 142.30-1240.20). The sources of heterogeneity could not be precisely identified by meta-regression or subgroup analysis. No evidence of publication bias was found. This study confirmed that CEUS exhibits high sensitivity and specificity in assessing therapeutic responses to RFA for liver tumors.

  6. Real-time non-rigid target tracking for ultrasound-guided clinical interventions

    NARCIS (Netherlands)

    Zachiu, Cornel; Ries, Mario G; Ramaekers, Pascal; Guey, Jean-Luc; Moonen, Chrit T W; de Senneville, Baudouin Denis

    2017-01-01

    Biological motion is a problem for non- or mini-invasive interventions when conducted in mobile/deformable organs due to the targeted pathology moving/deforming with the organ. This may lead to high miss rates and/or incomplete treatment of the pathology. Therefore, real-time tracking of the target

  7. Ultrasound -- Pelvis

    Medline Plus

    Full Text Available ... Ultrasound - Abdomen Obstetric Ultrasound Ultrasound - Prostate Kidney and Bladder Stones Abnormal Vaginal Bleeding Ovarian Cancer Images related to Ultrasound - Pelvis Sponsored by Please ...

  8. Ultrasound -- Pelvis

    Medline Plus

    Full Text Available ... Children's (Pediatric) Ultrasound - Abdomen Obstetric Ultrasound Ultrasound - Prostate Kidney and Bladder Stones Abnormal Vaginal Bleeding Ovarian Cancer Images related to Ultrasound - Pelvis Sponsored by Please ...

  9. Ultrasound -- Pelvis

    Medline Plus

    Full Text Available ... specific content. Related Articles and Media Sonohysterography Ultrasound - Abdomen Children's (Pediatric) Ultrasound - Abdomen Obstetric Ultrasound Ultrasound - Prostate Kidney and ...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-06-15

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

  11. Impact of analyzing fewer image frames per segment during offline volumetric radiofrequency based intravascular ultrasound measurements of target lesions prior to percutaneous coronary interventions

    NARCIS (Netherlands)

    Huisman, J.; Hartmann, M.; Hartmann, M.; Mintz, G.S.; van Houwelingen, G.K.; Stoel, M.G.; de Man, F.H.; Louwerenburg, H.; von Birgelen, Clemens

    2012-01-01

    In the present study, we evaluated the impact of a 50% reduction in number of image frames (every second frame) on the analysis time and variability of offline volumetric radiofrequency-based intravascular ultrasound (RF-IVUS) measurements in target lesions prior to percutaneous coronary

  12. Predicting target vessel location on robot-assisted coronary artery bypass graft using CT to ultrasound registration

    International Nuclear Information System (INIS)

    Cho, Daniel S.; Linte, Cristian; Chen, Elvis C. S.; Bainbridge, Daniel; Wedlake, Chris; Moore, John; Barron, John; Patel, Rajni; Peters, Terry

    2012-01-01

    Purpose: Although robot-assisted coronary artery bypass grafting (RA-CABG) has gained more acceptance worldwide, its success still depends on the surgeon's experience and expertise, and the conversion rate to full sternotomy is in the order of 15%-25%. One of the reasons for conversion is poor pre-operative planning, which is based solely on pre-operative computed tomography (CT) images. In this paper, the authors propose a technique to estimate the global peri-operative displacement of the heart and to predict the intra-operative target vessel location, validated via both an in vitro and a clinical study. Methods: As the peri-operative heart migration during RA-CABG has never been reported in the literatures, a simple in vitro validation study was conducted using a heart phantom. To mimic the clinical workflow, a pre-operative CT as well as peri-operative ultrasound images at three different stages in the procedure (Stage 0 --following intubation; Stage 1 --following lung deflation; and Stage 2 --following thoracic insufflation) were acquired during the experiment. Following image acquisition, a rigid-body registration using iterative closest point algorithm with the robust estimator was employed to map the pre-operative stage to each of the peri-operative ones, to estimate the heart migration and predict the peri-operative target vessel location. Moreover, a clinical validation of this technique was conducted using offline patient data, where a Monte Carlo simulation was used to overcome the limitations arising due to the invisibility of the target vessel in the peri-operative ultrasound images. Results: For the in vitro study, the computed target registration error (TRE) at Stage 0 , Stage 1 , and Stage 2 was 2.1, 3.3, and 2.6 mm, respectively. According to the offline clinical validation study, the maximum TRE at the left anterior descending (LAD) coronary artery was 4.1 mm at Stage 0 , 5.1 mm at Stage 1 , and 3.4 mm at Stage 2 . Conclusions: The authors

  13. Comparison of transient arterial occlusion and muscle exercise provocation for assessment of perfusion reserve in skeletal muscle with real-time contrast-enhanced ultrasound

    International Nuclear Information System (INIS)

    Krix, Martin; Krakowski-Roosen, Holger; Armarteifio, Erick; Fuerstenberger, Susanne; Delorme, Stefan; Kauczor, Hans-Ulrich; Weber, Marc-Andre

    2011-01-01

    Objective: Contrast-enhanced ultrasound (CEUS) is able to quantify muscle perfusion and changes in perfusion due to muscle exercise in real-time. However, reliable measurement of standardized muscle exercise is difficult to perform in clinical examinations. We compared perfusion reserve assessed by CEUS after transient arterial occlusion and exercise to find the most suitable measurement for clinical application. Methods: Contrast pulse sequencing (7 MHz) during continuous IV infusion of SonoVue (4.8 mL/300 s) was used in 8 healthy volunteers to monitor muscle perfusion of the gastrocnemius muscle during transient (1 min) arterial occlusion produced by a thigh cuff of a venous occlusion plethysmograph. Isometric muscle exercise (50% of individual maximum strength for 20 s) was subsequently performed during the same examination, and several CEUS parameters obtained from ultrasound-signal-intensity-time curves and its calculation errors were compared. Results: The mean maximum local blood volume after occlusion was 13.9 [∼mL] (range, 4.5-28.8 [∼mL]), and similar values were measured after sub-maximum exercise 13.8 [∼mL], (range, 4.6-22.2 [∼mL]. The areas under the curve during reperfusion vs. recovery were also similar (515.2 ± 257.5 compared to 482.2 ± 187.5 [∼mL s]) with a strong correlation (r = 0.65), as were the times to maximum (15.3 s vs. 15.9 s), with a significantly smaller variation for the occlusion method (±2.1 s vs. ±9.0 s, p = 0.03). The mean errors for all calculated CEUS parameters were lower for the occlusion method than for the exercise test. Conclusions: CEUS muscle perfusion measurements can be easily performed after transient arterial occlusion. It delivers data which are comparable to CEUS measurements after muscle exercise but with a higher robustness. This method can be easily applied in clinical examination of patients with e.g. PAOD or diabetic microvessel diseases to assess perfusion reserve.

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

    Science.gov (United States)

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

    2015-07-01

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

  15. Contrast ultrasound using SonoVue for pelvic radiation with concurrent chemotherapy monitoring in stage I B-II cervical cancer; Apport de l'echographie Doppler avec injection de contraste pour la prise en charge des cancers du col de l'uterus de stades IB et II par chimioradiotherapie concomitante

    Energy Technology Data Exchange (ETDEWEB)

    Marret, H. [Hopital Bretonneau, Service de Gynecologie, 37 - Tours (France); Barillot, I. [Hopital Bretonneau, Service de Radiotherapie, 37 - Tours (France); Rolland, Y. [CRLCC Eugene-Marquis, 35 - Rennes (France); Leveque, J. [Hopital Anne-de-Bretagne, 35 - Rennes (France)

    2009-10-15

    The aim of the present study was to evaluate whether angiogenic parameters as assessed by trans vaginal color Doppler ultrasound and by enhanced cervix ultrasound may predict prognostic factors of stage I B greater than 4 cm and II cervical cancer treated by radio chemotherapy. A total of 40 patients with histologically proven advanced stage invasive cervical cancer will be evaluated by color Doppler, contrast ultrasound, and MRI before radiotherapy, after the second chemotherapy cycle and prior to surgery. Subjective assessment of the amount of vessels within the tumor (scanty-moderate or abundant) and resistance index (R.I.) will be recorded for Doppler, enhancement and washout period will be studied after injection of SonoVue for contrast ultrasound. All patients will have radical hysterectomy and pelvic lymph node dissection. Comparison with MRI results will be done. The main parameter studied will be persistence of tumor cells in the analysis of the radical hysterectomy. We expected to correlate contrast parameters with persistent disease in order to confirm ultrasound parameters that will be useful to monitor radio chemotherapy and to predict therapeutic answer of such treatment. (authors)

  16. Ultrasound-targeted stromal cell-derived factor-1-loaded microbubble destruction promotes mesenchymal stem cell homing to kidneys in diabetic nephropathy rats

    Directory of Open Access Journals (Sweden)

    Wu S

    2014-12-01

    Full Text Available Shengzheng Wu,1 Lu Li,1 Gong Wang,1 Weiwei Shen,2 Yali Xu,1 Zheng Liu,1 Zhongxiong Zhuo,1 Hongmei Xia,1 Yunhua Gao,1 Kaibin Tan1 1Department of Ultrasound, 2Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China Abstract: Mesenchymal stem cell (MSC therapy has been considered a promising strategy to cure diabetic nephropathy (DN. However, insufficient MSCs can settle in injured kidneys, which constitute one of the major barriers to the effective implementation of MSC therapy. Stromal cell-derived factor-1 (SDF-1 plays a vital role in MSC migration and involves activation, mobilization, homing, and retention, which are presumably related to the poor homing in DN therapy. Ultrasound-targeted microbubble destruction has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve MSC homing to DN kidneys, we present a strategy to increase SDF-1 via ultrasound-targeted microbubble destruction. In this study, we developed SDF-1-loaded microbubbles (MBSDF-1 via covalent conjugation. The characterization and bioactivity of MBSDF-1 were assessed in vitro. Target release in the targeted kidneys was triggered with diagnostic ultrasound in combination with MBSDF-1. The related bioeffects were also elucidated. Early DN was induced in rats with streptozotocin. Green fluorescent protein-labeled MSCs were transplanted intravenously following the target release of SDF-1 in the kidneys of normal and DN rats. The homing efficacy was assessed by detecting the implanted exogenous MSCs at 24 hours. The in vitro results showed an impressive SDF-1 loading efficacy of 79% and a loading content of 15.8 µg/mL. MBSDF-1 remained bioactive as a chemoattractant. In the in vivo study, SDF-1 was successfully released in the targeted kidneys. The homing efficacy of MSCs to DN kidneys after the target release of SDF-1 was remarkably ameliorated at 24 hours compared with

  17. Cone beam CT with zonal filters for simultaneous dose reduction, improved target contrast and automated set-up in radiotherapy

    International Nuclear Information System (INIS)

    Moore, C J; Marchant, T E; Amer, A M

    2006-01-01

    Cone beam CT (CBCT) using a zonal filter is introduced. The aims are reduced concomitant imaging dose to the patient, simultaneous control of body scatter for improved image quality in the tumour target zone and preserved set-up detail for radiotherapy. Aluminium transmission diaphragms added to the CBCT x-ray tube of the Elekta Synergy TM linear accelerator produced an unattenuated beam for a central 'target zone' and a partially attenuated beam for an outer 'set-up zone'. Imaging doses and contrast noise ratios (CNR) were measured in a test phantom for transmission diaphragms 12 and 24 mm thick, for 5 and 10 cm long target zones. The effect on automatic registration of zonal CBCT to conventional CT was assessed relative to full-field and lead-collimated images of an anthropomorphic phantom. Doses along the axis of rotation were reduced by up to 50% in both target and set-up zones, and weighted dose (two thirds surface dose plus one third central dose) was reduced by 10-20% for a 10 cm long target zone. CNR increased by up to 15% in zonally filtered CBCT images compared to full-field images. Automatic image registration remained as robust as that with full-field images and was superior to CBCT coned down using lead-collimation. Zonal CBCT significantly reduces imaging dose and is expected to benefit radiotherapy through improved target contrast, required to assess target coverage, and wide-field edge detail, needed for robust automatic measurement of patient set-up error

  18. Logistic regression analysis of conventional ultrasonography, strain elastosonography, and contrast-enhanced ultrasound characteristics for the differentiation of benign and malignant thyroid nodules.

    Science.gov (United States)

    Pang, Tiantian; Huang, Leidan; Deng, Yingyuan; Wang, Tianfu; Chen, Siping; Gong, Xuehao; Liu, Weixiang

    2017-01-01

    The aim of the study is to screen the significant sonographic features by logistic regression analysis and fit a model to diagnose thyroid nodules. A total of 525 pathological thyroid nodules were retrospectively analyzed. All the nodules underwent conventional ultrasonography (US), strain elastosonography (SE), and contrast -enhanced ultrasound (CEUS). Those nodules' 12 suspicious sonographic features were used to assess thyroid nodules. The significant features of diagnosing thyroid nodules were picked out by logistic regression analysis. All variables that were statistically related to diagnosis of thyroid nodules, at a level of p regression analysis model. The significant features in the logistic regression model of diagnosing thyroid nodules were calcification, suspected cervical lymph node metastasis, hypoenhancement pattern, margin, shape, vascularity, posterior acoustic, echogenicity, and elastography score. According to the results of logistic regression analysis, the formula that could predict whether or not thyroid nodules are malignant was established. The area under the receiver operating curve (ROC) was 0.930 and the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 83.77%, 89.56%, 87.05%, 86.04%, and 87.79% respectively.

  19. Diagnostic accuracy of contrast enhanced ultrasound in patients with blunt abdominal trauma presenting to the emergency department: a systematic review and meta-analysis.

    Science.gov (United States)

    Zhang, Zhongheng; Hong, Yucai; Liu, Ning; Chen, Yuhao

    2017-06-30

    We aimed to investigate the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) in evaluating blunt abdominal trauma for patients presenting to the emergency department. Electronic search of Scopus and Pubmed was performed from inception to September 2016. Human studies investigating the diagnostic accuracy of CEUS in identifying abdominal solid organ injuries were included. Risk of bias was assessed using the QUADAS tool. A total of 10 studies were included in the study and 9 of them were included for meta-analysis. The log(DOR) values ranged from 3.80 (95% CI: 2.81-4.79) to 8.52 (95% CI: 4.58-12.47) in component studies. The combined log(DOR) was 6.56 (95% CI: 5.66-7.45). The Cochran's Q was 11.265 (p = 0.793 with 16 degrees of freedom), and the Higgins' I 2 was 0%. The CEUS had a sensitivity of 0.981 (95% CI: 0.868-0.950) and a false positive rate of 0.018 (95% CI: 0.010-0.032) for identifying parenchymal injuries, with an AUC of 0.984. CEUS performed at emergency department had good diagnostic accuracy in identifying abdominal solid organ injuries. CEUS can be recommended in monitoring solid organ injuries, especially for patients managed with non-operative strategy.

  20. Contrast-enhanced transrectal ultrasound for prediction of prostate cancer aggressiveness: The role of normal peripheral zone time-intensity curves.

    Science.gov (United States)

    Huang, Hui; Zhu, Zheng-Qiu; Zhou, Zheng-Guo; Chen, Ling-Shan; Zhao, Ming; Zhang, Yang; Li, Hong-Bo; Yin, Li-Ping

    2016-12-08

    To assess the role of time-intensity curves (TICs) of the normal peripheral zone (PZ) in the identification of biopsy-proven prostate nodules using contrast-enhanced transrectal ultrasound (CETRUS). This study included 132 patients with 134 prostate PZ nodules. Arrival time (AT), peak intensity (PI), mean transit time (MTT), area under the curve (AUC), time from peak to one half (TPH), wash in slope (WIS) and time to peak (TTP) were analyzed using multivariate linear logistic regression and receiver operating characteristic (ROC) curves to assess whether combining nodule TICs with normal PZ TICs improved the prediction of prostate cancer (PCa) aggressiveness. The PI, AUC (p < 0.001 for both), MTT and TPH (p = 0.011 and 0.040 respectively) values of the malignant nodules were significantly higher than those of the benign nodules. Incorporating the PI and AUC values (both, p < 0.001) of the normal PZ TIC, but not the MTT and TPH values (p = 0.076 and 0.159 respectively), significantly improved the AUC for prediction of malignancy (PI: 0.784-0.923; AUC: 0.758-0.891) and assessment of cancer aggressiveness (p < 0.001). Thus, all these findings indicate that incorporating normal PZ TICs with nodule TICs in CETRUS readings can improve the diagnostic accuracy for PCa and cancer aggressiveness assessment.