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Sample records for gas-carrier ultrasound contrast

  1. Section 6—Mechanical Bioeffects in the Presence of Gas-Carrier Ultrasound Contrast Agents

    PubMed Central

    2007-01-01

    This review addresses the issue of mechanical ultrasound-induced bioeffects in the presence of gas carrier contrast agents (GCAs). Here, the term “contrast agent” refers to those agents that provide ultrasound contrast by being composed of microbubbles, encapsulated or not, containing one or more gases. Provided in this section are summaries on how contrast agents work, some of their current uses, and the potential for bio-effects associated with their presence in an ultrasonic field. PMID:10680618

  2. Section 6--mechanical bioeffects in the presence of gas-carrier ultrasound contrast agents. American Institute of Ultrasound in Medicine.

    PubMed

    2000-02-01

    This review addresses the issue of mechanical ultrasound-induced bioeffects in the presence of gas carrier contrast agents (GCAs). Here, the term "contrast agent" refers to those agents that provide ultrasound contrast by being composed of microbubbles, encapsulated or not, containing one or more gases. Provided in this section are summaries on how contrast agents work, some of their current uses, and the potential for bioeffects associated with their presence in an ultrasonic field.

  3. Ultrasound Contrast Agents

    NASA Astrophysics Data System (ADS)

    Cachard, Christian; Basset, Olivier

    While the use of contrast agents in other imaging modalities (X ray, MRI, PET, …) has been routinely accepted for many years, the development and commercialization of contrast agents designed specifically for ultrasound imaging has occurred only very recently. As in the other imaging modalities, the injection of contrast agents during an ultrasound examination is intended to facilitate the detection and diagnosis of specific pathologies. Contrast agents efficiency is based on the backscattering of ultrasound by microbubbles. These microparticules are intravenously injected in the blood flow. After an introduction and generalities on ultrasound contrast agents (UCA) the microbubble physics in an acoustic field will be developed. Second, physics characteristics of contrast agents will be compared (bubbles with or without shell, gas nature, size distribution). Influence of acoustic pressure on the behaviour of the microparticules (linear, non linear and destruction) will be discussed. Finally, a review of specific imaging adapted to contrast agent properties as harmonic imaging, pulse inversion imaging will be presented.

  4. Ultrasound contrast agents

    PubMed Central

    Ignee, Andre; Atkinson, Nathan S. S.; Schuessler, Gudrun; Dietrich, Christoph F.

    2016-01-01

    Endoscopic ultrasound (EUS) plays an important role in imaging of the mediastinum and abdominal organs. Since the introduction of US contrast agents (UCA) for transabdominal US, attempts have been made to apply contrast-enhanced US techniques also to EUS. Since 2003, specific contrast-enhanced imaging was possible using EUS. Important studies have been published regarding contrast-enhanced EUS and the characterization of focal pancreatic lesions, lymph nodes, and subepithelial tumors. In this manuscript, we describe the relevant UCA, their application, and specific image acquisition as well as the principles of image tissue characterization using contrast-enhanced EUS. Safety issues, potential future developments, and EUS-specific issues are reviewed. PMID:27824024

  5. Ultrasound Despeckling for Contrast Enhancement

    PubMed Central

    Tay, Peter C.; Garson, Christopher D.; Acton, Scott T.; Hossack, John A.

    2010-01-01

    Images produced by ultrasound systems are adversely hampered by a stochastic process known as speckle. A despeckling method based upon removing outlier is proposed. The method is developed to contrast enhance B-mode ultrasound images. The contrast enhancement is with respect to decreasing pixel variations in homogeneous regions while maintaining or improving differences in mean values of distinct regions. A comparison of the proposed despeckling filter is compared with the other well known despeckling filters. The evaluations of despeckling performance are based upon improvements to contrast enhancement, structural similarity, and segmentation results on a Field II simulated image and actual B-mode cardiac ultrasound images captured in vivo. PMID:20227984

  6. Ultrasound contrast agents for ultrasound molecular imaging.

    PubMed

    Tranquart, F; Arditi, M; Bettinger, T; Frinking, P; Hyvelin, J M; Nunn, A; Pochon, S; Tardy, I

    2014-11-01

    Ultrasound is a real-time imaging technique which is widely used in many clinical applications for its capacity to provide anatomic information with high spatial and temporal resolution. The advent of ultrasound contrast agents in combination with contrast-specific imaging modes has given access to perfusion assessments at an organ level, leading to an improved diagnostic accuracy. More recently, the development of biologically-targeted ultrasound contrast agents has expanded the role of ultrasound even further into molecular imaging applications. Ultrasound molecular imaging can be used to visualize the expression of intravascular markers, and to assess their local presence over time and/or during therapeutic treatment. Major applications are in the field of inflammation and neoangiogenesis due to the strictly intravascular presence of microbubbles. Various technologies have been investigated for attaching the targeting moiety to the shell from simple biotin-avidin constructs to more elaborated insertion within the shell through attachment to PEG residues. This important improvement has allowed a clinical translation of initial pre-clinical investigations, opening the way for an early detection and an accurate characterization of lesions in patients. The combination of anatomic, functional and molecular information/data provided by contrast ultrasound is a powerful tool which is still in its infancy due to the lack of agents suitable for clinical use. The advantages of ultrasound techniques combined with the molecular signature of lesions will represent a significant advance in imaging in the field of personalized medicine. © Georg Thieme Verlag KG Stuttgart · New York.

  7. Contrast-specific ultrasound techniques.

    PubMed

    Quaia, E

    2007-06-01

    The advent of microbubble contrast agents has determined an important evolution of ultrasound (US) technology due to the introduction of contrast-specific US techniques. This was due to the fact that neither colour or power Doppler are suitable for correct management of the signals produced by microbubble insonation, as they are limited by the heavy presence of artefacts. Microbubbles may be insonated by a characteristic frequency named resonance or fundamental frequency (f (0)) by using a high or low transmit power. If insonated by a high transmit power, microbubbles produce a wideband harmonic signal due to microbubble destruction. If insonated by a low transmit power, microbubbles produce harmonic frequencies (2f, 3f, 4f) due to their nonlinear physical behaviour. Contrast-specific US techniques have recently undergone an important technical development with the introduction of innovative algorithms able to register selectively the harmonic signals produced by microbubbles and to suppress the signal produced by stationary tissues. The different contrast-specific US techniques may be distinguished by their basic principle into pseudo-Doppler, harmonic, phase-modulation, amplitude-modulation and phase-and amplitude-modulation techniques.

  8. Towards Dynamic Contrast Specific Ultrasound Tomography

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

    We report on the first study demonstrating the ability of a recently-developed, contrast-enhanced, ultrasound imaging method, referred to as cumulative phase delay imaging (CPDI), to image and quantify ultrasound contrast agent (UCA) kinetics. Unlike standard ultrasound tomography, which exploits changes in speed of sound and attenuation, CPDI is based on a marker specific to UCAs, thus enabling dynamic contrast-specific ultrasound tomography (DCS-UST). For breast imaging, DCS-UST will lead to a more practical, faster, and less operator-dependent imaging procedure compared to standard echo-contrast, while preserving accurate imaging of contrast kinetics. Moreover, a linear relation between CPD values and ultrasound second-harmonic intensity was measured (coefficient of determination = 0.87). DCS-UST can find clinical applications as a diagnostic method for breast cancer localization, adding important features to multi-parametric ultrasound tomography of the breast.

  9. Towards Dynamic Contrast Specific Ultrasound Tomography

    PubMed Central

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

    2016-01-01

    We report on the first study demonstrating the ability of a recently-developed, contrast-enhanced, ultrasound imaging method, referred to as cumulative phase delay imaging (CPDI), to image and quantify ultrasound contrast agent (UCA) kinetics. Unlike standard ultrasound tomography, which exploits changes in speed of sound and attenuation, CPDI is based on a marker specific to UCAs, thus enabling dynamic contrast-specific ultrasound tomography (DCS-UST). For breast imaging, DCS-UST will lead to a more practical, faster, and less operator-dependent imaging procedure compared to standard echo-contrast, while preserving accurate imaging of contrast kinetics. Moreover, a linear relation between CPD values and ultrasound second-harmonic intensity was measured (coefficient of determination = 0.87). DCS-UST can find clinical applications as a diagnostic method for breast cancer localization, adding important features to multi-parametric ultrasound tomography of the breast. PMID:27703251

  10. Ultrasound microbubble contrast and current clinical applications.

    PubMed

    Dindyal, Shiva; Kyriakides, Constantinos

    2011-01-01

    Ultrasound imaging is widely used worldwide principally because it is cheap, easily available and contains no exposure to ionizing radiation. The advent of microbubble ultrasound contrast has further increased the diagnostic sensitivity and specificity of this technique thus widening its clinical applications. The third generation of ultrasound contrast agents consist of sulphur hexafluoride microbubbles encased in a phospholipid shell. This review will elaborate on the pharmacology, safety profile and method of action of these agents. We also aim to discuss the ever expanding uses for contrast enhanced ultrasound in a number of clinical specialities which include the liver, kidney, prostate, sentinel node detection, vascular tree and endovascular stent surveillance. We will also discuss some of the recent patents regarding the future uses of ultrasound microbubble contrast and recent technological advances in clinical applications.

  11. Contrast enhanced ultrasound of breast cancer

    PubMed Central

    Cassano, E; Rizzo, S; Bozzini, A; Menna, S; Bellomi, M

    2006-01-01

    The importance of ultrasound examination in the diagnosis of breast cancer has been widely demonstrated. During the last few years, the introduction of ultrasound contrast media has been considered a promising tool for studying the vascular pattern of focal lesions within the breast. Our purpose was to assess whether contrast-enhanced (CE) ultrasound examination, performed using specific contrast imaging modes, can be helpful for detection and characterization of breast lesions, and for prediction of the response of breast cancer to therapy. PMID:16478698

  12. Contrast enhanced ultrasound of sentinel lymph nodes.

    PubMed

    Cui, XinWu; Ignee, Andre; Nielsen, Michael Bachmann; Schreiber-Dietrich, Dagmar; De Molo, Chiara; Pirri, Clara; Jedrzejczyk, Maciej; Christoph, Dietrich F

    2013-03-01

    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.

  13. Microbubble ultrasound contrast agents: a review.

    PubMed

    Stride, E; Saffari, N

    2003-01-01

    The superior scattering properties of gas bubbles compared with blood cells have made microbubble ultrasound contrast agents important tools in ultrasound diagnosis. Over the past 2 years they have become the focus of a wide and rapidly expanding field of research, with their benefits being repeatedly demonstrated, both in ultrasound image enhancement, and more recently in drug and gene delivery applications. However, despite considerable investigation, their behaviour is by no means fully understood and, while no definite evidence of harmful effects has been obtained, there remain some concerns as to their safety. In this review the existing theoretical and experimental evidence is examined in order to clarify the extent to which contrast agents are currently understood and to identify areas for future research. In particular the disparity between the conditions considered in theoretical models and those encountered both in vitro, and more importantly in vivo is discussed, together with the controversy regarding the risk of harmful bio-effects.

  14. Contrast-enhanced and targeted ultrasound

    PubMed Central

    Postema, Michiel; Gilja, Odd Helge

    2011-01-01

    Ultrasonic imaging is becoming the most popular medical imaging modality, owing to the low price per examination and its safety. However, blood is a poor scatterer of ultrasound waves at clinical diagnostic transmit frequencies. For perfusion imaging, markers have been designed to enhance the contrast in B-mode imaging. These so-called ultrasound contrast agents consist of microscopically small gas bubbles encapsulated in biodegradable shells. In this review, the physical principles of ultrasound contrast agent microbubble behavior and their adjustment for drug delivery including sonoporation are described. Furthermore, an outline of clinical imaging applications of contrast-enhanced ultrasound is given. It is a challenging task to quantify and predict which bubble phenomenon occurs under which acoustic condition, and how these phenomena may be utilized in ultrasonic imaging. Aided by high-speed photography, our improved understanding of encapsulated microbubble behavior will lead to more sophisticated detection and delivery techniques. More sophisticated methods use quantitative approaches to measure the amount and the time course of bolus or reperfusion curves, and have shown great promise in revealing effective tumor responses to anti-angiogenic drugs in humans before tumor shrinkage occurs. These are beginning to be accepted into clinical practice. In the long term, targeted microbubbles for molecular imaging and eventually for directed anti-tumor therapy are expected to be tested. PMID:21218081

  15. Contrast-enhanced and targeted ultrasound.

    PubMed

    Postema, Michiel; Gilja, Odd Helge

    2011-01-07

    Ultrasonic imaging is becoming the most popular medical imaging modality, owing to the low price per examination and its safety. However, blood is a poor scatterer of ultrasound waves at clinical diagnostic transmit frequencies. For perfusion imaging, markers have been designed to enhance the contrast in B-mode imaging. These so-called ultrasound contrast agents consist of microscopically small gas bubbles encapsulated in biodegradable shells. In this review, the physical principles of ultrasound contrast agent microbubble behavior and their adjustment for drug delivery including sonoporation are described. Furthermore, an outline of clinical imaging applications of contrast-enhanced ultrasound is given. It is a challenging task to quantify and predict which bubble phenomenon occurs under which acoustic condition, and how these phenomena may be utilized in ultrasonic imaging. Aided by high-speed photography, our improved understanding of encapsulated microbubble behavior will lead to more sophisticated detection and delivery techniques. More sophisticated methods use quantitative approaches to measure the amount and the time course of bolus or reperfusion curves, and have shown great promise in revealing effective tumor responses to anti-angiogenic drugs in humans before tumor shrinkage occurs. These are beginning to be accepted into clinical practice. In the long term, targeted microbubbles for molecular imaging and eventually for directed anti-tumor therapy are expected to be tested.

  16. Molecular imaging with targeted contrast ultrasound.

    PubMed

    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.

  17. Superhydrophobic silica nanoparticles as ultrasound contrast agents.

    PubMed

    Jin, Qiaofeng; Lin, Chih-Yu; Kang, Shih-Tsung; Chang, Yuan-Chih; Zheng, Hairong; Yang, Chia-Min; Yeh, Chih-Kuang

    2017-05-01

    Microbubbles have been widely studied as ultrasound contrast agents for diagnosis and as drug/gene carriers for therapy. However, their size and stability (lifetime of 5-12min) limited their applications. The development of stable nanoscale ultrasound contrast agents would therefore benefit both. Generating bubbles persistently in situ would be one of the promising solutions to the problem of short lifetime. We hypothesized that bubbles could be generated in situ by providing stable air nuclei since it has been found that the interfacial nanobubbles on a hydrophobic surface have a much longer lifetime (orders of days). Mesoporous silica nanoparticles (MSNs) with large surface areas and different levels of hydrophobicity were prepared to test our hypothesis. It is clear that the superhydrophobic and porous nanoparticles exhibited a significant and strong contrast intensity compared with other nanoparticles. The bubbles generated from superhydrophobic nanoparticles sustained for at least 30min at a MI of 1.0, while lipid microbubble lasted for about 5min at the same settings. In summary MSNs have been transformed into reliable bubble precursors by making simple superhydrophobic modification, and made into a promising contrast agent with the potentials to serve as theranostic agents that are sensitive to ultrasound stimulation.

  18. Synthesis of laboratory Ultrasound Contrast Agents.

    PubMed

    Park, Jingam; Park, Donghee; Shin, Unchul; Moon, Sanghyub; Kim, Chihyun; Kim, Han Sung; Park, Hyunjin; Choi, Kiju; Jung, Bongkwang; Oh, Jaemin; Seo, Jongbum

    2013-10-21

    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.

  19. Model of Therapeutic Ultrasound Contrast Agent Dynamics

    NASA Astrophysics Data System (ADS)

    Hsiao, Chao-Tsung; Lu, Xiaozhen; Chahine, Georges

    2007-11-01

    Targeted drug and gene delivery are rapidly emerging applications for ultrasound contrast agents since this could reduce potential deleterious side effects to healthy tissue and minimize the overall dose needed. Therapeutic ultrasound contrast agents are encapsulated microbubbles usually composed of a high molecular weight gas core and a highly viscous thick liquid shell. Development of new contrast agents requires a good understanding of the stability and breakup mechanisms of the liquid shell when subjected to ultrasonic acoustic waves. A novel numerical code, which enables one to investigate the dynamics of thick-shelled contrast agents and the interaction between multiple agents and with nearby boundaries has been developed by coupling a Boundary Element Method solver and a finite-volume Navier-Stokes solver. We have applied the coupled code to examine shell breakup mechanisms for contrast agents near a solid wall. We found that the shell thickness varies significantly from location to location due to non-spherical deformations and that the contrast agent may break up due to local shell thinning and stretching as the non-spherical deformation is significant.

  20. Nano/microparticles and ultrasound contrast agents.

    PubMed

    Zheng, Shu-Guang; Xu, Hui-Xiong; Chen, Hang-Rong

    2013-12-28

    Microbubbles have been used for many years now in clinical practice as contrast agents in ultrasound imaging. Recently, their therapeutic applications have also attracted more attention. However, the short circulation time (minutes) and relatively large size (two to ten micrometers) of currently used commercial microbubbles do not allow effective extravasation into tumor tissue, preventing efficient tumor targeting. Fortunately, more multifunctional and theranostic nanoparticles with some special advantages over the traditional microbubbles have been widely investigated and explored for biomedical applications. The way to synthesize an ideal ultrasound contrast agent based on nanoparticles in order to achieve an expected effect on contrast imaging is a key technique. Currently a number of nanomaterials, including liposomes, polymers, micelles, dendrimers, emulsions, quantum dots, solid nanoparticles etc., have already been applied to pre or clinical trials. Multifunctional and theranostic nanoparticles with some special advantages, such as the tumor-targeted (passive or active), multi-mode contrast agents (magnetic resonance imaging, ultrasonography or fluorescence), carrier or enhancer of drug delivery, and combined chemo or thermal therapy etc., are rapidly gaining popularity and have shown a promising application in the field of cancer treatment. In this mini review, the trends and the advances of multifunctional and theranostic nanoparticles are briefly discussed.

  1. Imaging microvasculature with contrast-enhanced ultraharmonic ultrasound.

    PubMed

    Maresca, David; Skachkov, Ilya; Renaud, Guillaume; Jansen, Krista; van Soest, Gijs; de Jong, Nico; van der Steen, Antonius F W

    2014-06-01

    Atherosclerotic plaque neovascularization was shown to be one of the strongest predictors of future cardiovascular events. Yet, the clinical tools for coronary wall microvasculature detection in vivo are lacking. Here we report an ultrasound pulse sequence capable of detecting microvasculature invisible in conventional intracoronary imaging. The method combines intravascular ultrasound with an ultrasound contrast agent, i.e., a suspension of microscopic vascular acoustic resonators that are small enough to penetrate the capillary bed after intravenous administration. The pulse sequence relies on brief chirp excitations to extract ultraharmonic echoes specific to the ultrasound contrast agent. We implemented the pulse sequence on an intravascular ultrasound probe and successfully imaged the microvasculature of a 6 days old chicken embryo respiratory organ. The feasibility of microvasculature imaging with intravascular ultrasound sets the stage for a translation of the method to studies of intra-plaque neovascularization detection in humans. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  2. Covert contrast in velar fronting: An acoustic and ultrasound study

    PubMed Central

    Byun, Tara McAllister; Buchwald, Adam; Mizoguchi, Ai

    2016-01-01

    There is growing evidence that speech sound acquisition is a gradual process, with instrumental measures frequently revealing covert contrast in errors perceived to involve phonemic substitution. Ultrasound imaging has the potential to expand our understanding of covert contrast by showing whether a child uses different tongue shapes while producing sounds that are perceived as neutralized. This study used an ultrasound measure (Dorsum Excursion Index) and acoustic measures (VOT and spectral moments of the burst) to investigate overt and covert contrast between velar and alveolar stops in child speech. Participants were two children who produced a perceptually overt velar-alveolar contrast and two children who neutralized the contrast via velar fronting. Both acoustic and ultrasound measures revealed significant differences between perceptually distinct velar and alveolar targets. One child with velar fronting demonstrated covert contrast in one acoustic and one ultrasound measure; the other showed no evidence of contrast. Clinical implications are discussed. PMID:26325303

  3. Temperature dependent behavior of ultrasound contrast agents.

    PubMed

    Mulvana, Helen; Stride, Eleanor; Hajnal, Jo V; Eckersley, Robert J

    2010-06-01

    Recent interest in ultrasound contrast agents (UCAs) as tools for quantitative imaging and therapy has increased the need for accurate characterization. Laboratory investigations are frequently undertaken in a water bath at room temperature; however, implications for in vivo applications are not presented. Acoustic investigation of a bulk suspension of SonoVue (Bracco Research, Geneva, Switzerland) was made in a water bath at temperatures of 20-45 degrees C. UCA characteristics were significantly affected by temperature, particularly between 20 and 40 degrees C, leading to an increase in attenuation from 1.7-2.5 dB, respectively (p = 0.002) and a 2-dB increase in scattered signal over the same range (p = 0.05) at an insonation pressure of 100 kPa. Optical data supported the hypothesis that a temperature-mediated increase in diameter was the dominant cause, and revealed a decrease in bubble stability. In conclusion, measurements made at room temperature require careful interpretation with regard to behavior in vivo.

  4. Intravascular Targets for Molecular Contrast-Enhanced Ultrasound Imaging

    PubMed Central

    Moestue, Siver A.; Gribbestad, Ingrid S.; Hansen, Rune

    2012-01-01

    Molecular targeting of contrast agents for ultrasound imaging is emerging as a new medical imaging modality. It combines advances in ultrasound technology with principles of molecular imaging, thereby allowing non-invasive assessment of biological processes in vivo. Preclinical studies have shown that microbubbles, which provide contrast during ultrasound imaging, can be targeted to specific molecular markers. These microbubbles accumulate in tissue with target (over) expression, thereby significantly increasing the ultrasound signal. This concept offers safe and low-cost imaging with high spatial resolution and sensitivity. It is therefore considered to have great potential in cancer imaging, and early-phase clinical trials are ongoing. In this review, we summarize the current literature on targets that have been successfully imaged in preclinical models using molecularly targeted ultrasound contrast agents. Based on preclinical experience, we discuss the potential clinical utility of targeted microbubbles. PMID:22837657

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

    PubMed

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

    2015-12-01

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

  6. Functionalized multiwalled carbon nanotubes as ultrasound contrast agents

    PubMed Central

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

    2012-01-01

    Ultrasonography is a fundamental diagnostic imaging tool in everyday clinical practice. Here, we are unique in describing the use of functionalized multiwalled carbon nanotubes (MWCNTs) as hyperechogenic material, suggesting their potential application as ultrasound contrast agents. Initially, we carried out a thorough investigation to assess the echogenic property of the nanotubes in vitro. We demonstrated their long-lasting ultrasound contrast properties. We also showed that ultrasound signal of functionalized MWCNTs is higher than graphene oxide, pristine MWCNTs, and functionalized single-walled CNTs. Qualitatively, the ultrasound signal of CNTs was equal to that of sulfur hexafluoride (SonoVue), a commercially available contrast agent. Then, we found that MWCNTs were highly echogenic in liver and heart through ex vivo experiments using pig as an animal model. In contrast to the majority of ultrasound contrast agents, we observed in a phantom bladder that the tubes can be visualized within a wide variety of frequencies (i.e., 5.5–10 MHz) and 12.5 MHz using tissue harmonic imaging modality. Finally, we demonstrated in vivo in the pig bladder that MWCNTs can be observed at low frequencies, which are appropriate for abdominal organs. Importantly, we did not report any toxicity of CNTs after 7 d from the injection by animal autopsy, organ histology and immunostaining, blood count, and chemical profile. Our results reveal the enormous potential of CNTs as ultrasound contrast agents, giving support for their future applications as theranostic nanoparticles, combining diagnostic and therapeutic modalities. PMID:23012426

  7. Contrast-enhanced ultrasound for imaging of adrenal masses.

    PubMed

    Dietrich, C F; Ignee, A; Barreiros, A P; Schreiber-Dietrich, D; Sienz, M; Bojunga, J; Braden, B

    2010-04-01

    The number of incidentally discovered adrenal masses is growing due to the increased use of modern high-resolution imaging techniques. However, the characterization and differentiation of benign and malignant adrenal lesions is challenging. This study aimed to evaluate contrast-enhanced ultrasound for the characterization of adrenal masses. We studied 58 patients with adrenal masses detected with computed tomography, magnetic resonance imaging, or ultrasound. 7 patients had bilateral adrenal lesions. Contrast-enhanced ultrasound was performed using high-resolution ultrasound (3.5 - 7 MHz) and intravenous injection of 2.4 ml SonoVue. The contrast enhancement pattern of all adrenal lesions was documented. The 18 malignant adrenal tumors were significantly larger at the time of diagnosis compared to the 40 benign lesions (p < 0.03). The majority of benign adrenal lesions (37 / 40) had a nonspecific type of contrast enhancement (24 / 40) or a peripheral to central contrast filling (13 / 40) described as the iris phenomenon. Similar findings were observed in malignant adrenal tumors: most malignant lesions also showed nonspecific (6 / 18) or peripheral to central contrast filling (9 / 18). Peripheral to central contrast filling had 50 % sensitivity (26 - 74 %) and 68 % specificity (51 - 81 %) for indicating malignancy. Contrast-enhanced ultrasound facilitates the visualization of vascularization even in small adrenal masses, but it does not help to distinguish malignant and benign lesions. Georg Thieme Verlag KG Stuttgart . New York.

  8. Collapse dynamics of ultrasound contrast agent microbubbles

    NASA Astrophysics Data System (ADS)

    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

  9. Perfusion imaging with non-contrast ultrasound

    NASA Astrophysics Data System (ADS)

    Tierney, Jaime E.; Dumont, Douglas M.; Byram, Brett C.

    2016-04-01

    A Doppler ultrasound clutter filter that enables estimation of low velocity blood flow could considerably improve ultrasound as a tool for clinical diagnosis and monitoring, including for the evaluation of vascular diseases and tumor perfusion. Conventional Doppler ultrasound is currently used for visualizing and estimating blood flow. However, conventional Doppler is limited by frame rate and tissue clutter caused by involuntary movement of the patient or sonographer. Spectral broadening of the clutter due to tissue motion limits ultrasound's ability to detect blood flow less than about 5mm/s at an 8MHz center frequency. We propose a clutter filtering technique that may increase the sensitivity of Doppler measurements to at least as low as 0.41mm/s. The proposed filter uses an adaptive demodulation scheme that decreases the bandwidth of the clutter. To test the performance of the adaptive demodulation method at removing sonographer hand motion, six volunteer subjects acquired data from a basic quality assurance phantom. Additionally, to test initial in vivo feasibility, an arterial occlusion reactive hyperemia study was performed to assess the efficiency of the proposed filter at preserving signals from blood velocities 2mm/s or greater. The hand motion study resulted in initial average bandwidths of 577Hz (28.5mm/s), which were decreased to 7.28Hz (0.36mm/s) at -60 dB at 3cm using our approach. The in vivo power Doppler study resulted in 15.2dB and 0.15dB dynamic ranges between the lowest and highest blood flow time points for the proposed filter and conventional 50Hz high pass filter, respectively.

  10. Assessment of subclinical atherosclerosis using contrast-enhanced ultrasound.

    PubMed

    van den Oord, Stijn C H; ten Kate, Gerrit L; Akkus, Zeynettin; Renaud, Guillaume; Sijbrands, Eric J G; ten Cate, Folkert J; van der Lugt, Aad; Bosch, Johan G; de Jong, Nico; van der Steen, Antonius F W; Schinkel, Arend F L

    2013-01-01

    The sensitivity of standard carotid ultrasound and colour Doppler for the detection of subclinical atherosclerotic plaques is suboptimal. The aim of this study is to assess whether contrast-enhanced ultrasound (CEUS) added to standard carotid ultrasound improves the detection of subclinical atherosclerosis. Carotid intima-media thickness (CIMT) measurement, standard carotid ultrasound including colour Doppler imaging, and CEUS were performed in 100 asymptomatic patients with one or more risk factors for atherosclerosis. CEUS was performed using intravenous administration of SonoVue™ contrast agent (Bracco S.p.A., Milan, Italy). CIMT, standard ultrasound, colour Doppler, and CEUS were reviewed by two independent observers. Standard ultrasound, colour Doppler, and CEUS were scored for the presence of atherosclerotic plaques. Subclinical atherosclerosis was diagnosed if patients had a CIMT above their age-corrected threshold value or if atherosclerotic plaques were present on standard carotid ultrasound clips or CEUS clips. McNemar's test was performed to compare between groups. Twenty-one patients (21%) had a thickened CIMT value and were considered to have subclinical atherosclerosis. Standard carotid ultrasound including colour Doppler demonstrated atherosclerotic plaques in 77 patients (77%). The addition of CEUS to the standard ultrasound protocol demonstrated atherosclerotic plaques in 88 patients (88%). The incorporation of CEUS into the standard carotid ultrasound protocol resulted in a significantly improved detection of patients with subclinical atherosclerosis (P < 0.01). CEUS has an incremental value for the detection of subclinical atherosclerosis in the carotid arteries. Atherosclerotic plaques which were only detected with CEUS and not with standard carotid ultrasound and colour Doppler imaging were predominantly hypoechoic.

  11. Cardiac arrhythmias produced by ultrasound and contrast agents

    NASA Astrophysics Data System (ADS)

    Rota, Claudio

    Ultrasound is used widely in medicine for both diagnostic and therapeutic applications. Ultrasound contrast agents are suspensions of gas-filled microbubbles used to enhance diagnostic imaging. Microbubble contrast agents can increase the likelihood of bioeffects of ultrasound associated with acoustic cavitation. Under certain exposure conditions, the interaction of ultrasound with cardiac tissues can produce cardiac arrhythmias. The general objective of this thesis was to develop a greater understanding of ultrasound-induced premature cardiac beats. The hypothesis guiding this work was that acoustic cavitation is the physical mechanism for the production of arrhythmias with ultrasound. This hypothesis was tested through a series of experiments with mice in vivo and theoretical investigations. Results of this research supported the acoustic cavitation hypothesis. The acoustic pressure threshold for premature beats was significantly lower with microbubble contrast agents present in the blood than without. With microbubbles, the threshold for premature beats was below the current output limits of diagnostic devices. The threshold was not significantly dependent upon contrast agent type and was not influenced by contrast agent dose over three orders of magnitude. Furthermore, the dependence of the threshold on acoustic frequency was consistent with the frequency dependence of acoustic cavitation. Experimentally determined thresholds for premature beats in vivo were in excellent agreement with theoretically estimated thresholds for inertial cavitation. A passive cavitation detector (PCD) was used to measure the acoustic emissions produced by cavitating microbubbles in vivo. A direct correlation between the amplitude of the PCD and the percentage of ultrasound pulses producing a premature beat was consistent with cavitation as a mechanism for this bioeffect. Although this thesis focused on the mechanistic understanding of ultrasound-induced arrhythmias, more persistent

  12. [Management of salivary gland diseases with contrast-enhanced ultrasound].

    PubMed

    Zengel, P; Schrötzlmair, F; Kramer, M; Paprottka, P; Clevert, D-A

    2011-06-01

    Obstructive diseases of the salivary glands are a common problem in otorhinolaryngology. They are mostly due to sialolithiasis followed by duct stenosis and other rarer causes. Several diagnostic modalities exist which allow classification of the disease; however, in 5-10% of all cases ultrasound and conventional radiological imaging do not provide a clear diagnosis. Ultrasound examination with contrast material injected into the duct (IA-CEUS, intraductal administered contrast-enhanced ultrasound) enables improved evaluation of obstructive diseases of the salivary glands and at the same time an evaluation of the parenchyma of the glands is possible. As a complementary method to conventional investigation techniques IA-CEUS is an economic and rapid method with low side-effects which improves the diagnostic assessment of ultrasound and results in a better treatment for patients.

  13. Acoustic bubble sorting for ultrasound contrast agent enrichment.

    PubMed

    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.

  14. Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  16. Ultrasound imaging beyond the vasculature with new generation contrast agents.

    PubMed

    Perera, Reshani H; Hernandez, Christopher; Zhou, Haoyan; Kota, Pavan; Burke, Alan; Exner, Agata A

    2015-01-01

    Current commercially available ultrasound contrast agents are gas-filled, lipid- or protein-stabilized microbubbles larger than 1 µm in diameter. Because the signal generated by these agents is highly dependent on their size, small yet highly echogenic particles have been historically difficult to produce. This has limited the molecular imaging applications of ultrasound to the blood pool. In the area of cancer imaging, microbubble applications have been constrained to imaging molecular signatures of tumor vasculature and drug delivery enabled by ultrasound-modulated bubble destruction. Recently, with the rise of sophisticated advancements in nanomedicine, ultrasound contrast agents, which are an order of magnitude smaller (100-500 nm) than their currently utilized counterparts, have been undergoing rapid development. These agents are poised to greatly expand the capabilities of ultrasound in the field of targeted cancer detection and therapy by taking advantage of the enhanced permeability and retention phenomenon of many tumors and can extravasate beyond the leaky tumor vasculature. Agent extravasation facilitates highly sensitive detection of cell surface or microenvironment biomarkers, which could advance early cancer detection. Likewise, when combined with appropriate therapeutic agents and ultrasound-mediated deployment on demand, directly at the tumor site, these nanoparticles have been shown to contribute to improved therapeutic outcomes. Ultrasound's safety profile, broad accessibility and relatively low cost make it an ideal modality for the changing face of healthcare today. Aided by the multifaceted nano-sized contrast agents and targeted theranostic moieties described herein, ultrasound can considerably broaden its reach in future applications focused on the diagnosis and staging of cancer. © 2015 Wiley Periodicals, Inc.

  17. Ultrasound Imaging Beyond the Vasculature with New Generation Contrast Agents

    PubMed Central

    Perera, Reshani H.; Hernandez, Christopher; Zhou, Haoyan; Kota, Pavan; Burke, Alan

    2015-01-01

    Current commercially available ultrasound contrast agents are gas-filled, lipid- or protein-stabilized microbubbles larger than 1 μm in diameter. Because the signal generated by these agents is highly dependent on their size, small yet highly echogenic particles have been historically difficult to produce. This has limited the molecular imaging applications of ultrasound to the blood pool. In the area of cancer imaging, microbubble applications have been constrained to imaging molecular signatures of tumor vasculature and drug delivery enabled by ultrasound-modulated bubble destruction. Recently, with the rise of sophisticated advancements in nanomedicine, ultrasound contrast agents, which are an order of magnitude smaller (100-500 nm) than their currently utilized counterparts, have been undergoing rapid development. These agents are poised to greatly expand the capabilities of ultrasound in the field of targeted cancer detection and therapy by taking advantage of the enhanced permeability and retention phenomenon of many tumors and can extravasate beyond the leaky tumor vasculature. Agent extravasation facilitates highly sensitive detection of cell surface or microenvironment biomarkers, which could advance early cancer detection. Likewise, when combined with appropriate therapeutic agents and ultrasound-mediated deployment on demand, directly at the tumor site, these nanoparticles have been shown to contribute to improved therapeutic outcomes. Ultrasound's safety profile, broad accessibility and relatively low cost make it an ideal modality for the changing face of healthcare today. Aided by the multifaceted nano-sized contrast agents and targeted theranostic moieties described herein, ultrasound can considerably broaden its reach in future applications focused on the diagnosis and staging of cancer. PMID:25580914

  18. Microbubble contrast agents: targeted ultrasound imaging and ultrasound-assisted drug-delivery applications.

    PubMed

    Klibanov, Alexander L

    2006-03-01

    The use of microbubble contrast agents for general tissue delineation and perfusion enjoys steady interest in ultrasound imaging. Microbubbles as contrast materials require a small dosage and show excellent detection sensitivity. Targeting ligands on the surface of microbubbles permit the selective accumulation of these particles in the areas of interest, which show an up-regulated level of receptor molecules on vascular endothelium. Selective contrast imaging of inflammation, ischemia-reperfusion injury, angiogenesis, and thrombosis has been achieved in animal models. Ultrasound-assisted drug delivery and activation, performed by combining microbubble agent containing drug substances or coadministered with pharmaceutical agents (including plasmid DNA for transfection), has been achieved in multiple model systems in vitro and in vivo. Ultrasound and microbubbles-based targeted acceleration of the thrombolytic enzyme action already have reached clinical trials. Overall, microbubble targeting and ultrasound-assisted microbubble-based drug-delivery systems will offer a step toward the application of targeted personalized diagnostics and therapy.

  19. Methods for blood flow measurements using ultrasound contrast agents

    NASA Astrophysics Data System (ADS)

    Fowlkes, J. Brian

    2003-10-01

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

  20. Ultrasound Activated Contrast Imaging for Prostate Cancer Detection

    DTIC Science & Technology

    2007-03-01

    Goldberg. Nonlinear imaging with a new contrast agent. Ultrasound Med Biol, vol. 29, pp. S97, 2003. R. J. Ro, F. Forsberg, M. Knauer, W. T. Shi, P. A ... Lewin , R. Bernardi. On the temperature and concentration dependency of excitation-enhanced imaging. Proc Biomed Eng Soc Ann Fall Meetg, abstract no

  1. Contrast Imaging in Mouse Embryos Using High-frequency Ultrasound

    PubMed Central

    Denbeigh, Janet M.; Nixon, Brian A.; Puri, Mira C.; Foster, F. Stuart

    2015-01-01

    Ultrasound contrast-enhanced imaging can convey essential quantitative information regarding tissue vascularity and perfusion and, in targeted applications, facilitate the detection and measure of vascular biomarkers at the molecular level. Within the mouse embryo, this noninvasive technique may be used to uncover basic mechanisms underlying vascular development in the early mouse circulatory system and in genetic models of cardiovascular disease. The mouse embryo also presents as an excellent model for studying the adhesion of microbubbles to angiogenic targets (including vascular endothelial growth factor receptor 2 (VEGFR2) or αvβ3) and for assessing the quantitative nature of molecular ultrasound. We therefore developed a method to introduce ultrasound contrast agents into the vasculature of living, isolated embryos. This allows freedom in terms of injection control and positioning, reproducibility of the imaging plane without obstruction and motion, and simplified image analysis and quantification. Late gestational stage (embryonic day (E)16.6 and E17.5) murine embryos were isolated from the uterus, gently exteriorized from the yolk sac and microbubble contrast agents were injected into veins accessible on the chorionic surface of the placental disc. Nonlinear contrast ultrasound imaging was then employed to collect a number of basic perfusion parameters (peak enhancement, wash-in rate and time to peak) and quantify targeted microbubble binding in an endoglin mouse model. We show the successful circulation of microbubbles within living embryos and the utility of this approach in characterizing embryonic vasculature and microbubble behavior. PMID:25867243

  2. Contrast imaging in mouse embryos using high-frequency ultrasound.

    PubMed

    Denbeigh, Janet M; Nixon, Brian A; Puri, Mira C; Foster, F Stuart

    2015-03-04

    Ultrasound contrast-enhanced imaging can convey essential quantitative information regarding tissue vascularity and perfusion and, in targeted applications, facilitate the detection and measure of vascular biomarkers at the molecular level. Within the mouse embryo, this noninvasive technique may be used to uncover basic mechanisms underlying vascular development in the early mouse circulatory system and in genetic models of cardiovascular disease. The mouse embryo also presents as an excellent model for studying the adhesion of microbubbles to angiogenic targets (including vascular endothelial growth factor receptor 2 (VEGFR2) or αvβ3) and for assessing the quantitative nature of molecular ultrasound. We therefore developed a method to introduce ultrasound contrast agents into the vasculature of living, isolated embryos. This allows freedom in terms of injection control and positioning, reproducibility of the imaging plane without obstruction and motion, and simplified image analysis and quantification. Late gestational stage (embryonic day (E)16.6 and E17.5) murine embryos were isolated from the uterus, gently exteriorized from the yolk sac and microbubble contrast agents were injected into veins accessible on the chorionic surface of the placental disc. Nonlinear contrast ultrasound imaging was then employed to collect a number of basic perfusion parameters (peak enhancement, wash-in rate and time to peak) and quantify targeted microbubble binding in an endoglin mouse model. We show the successful circulation of microbubbles within living embryos and the utility of this approach in characterizing embryonic vasculature and microbubble behavior.

  3. Cumulative phase delay imaging - A new contrast enhanced ultrasound modality

    SciTech Connect

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

    2015-10-28

    Recently, a new acoustic marker for ultrasound contrast agents (UCAs) has been introduced. A cumulative phase delay (CPD) between the second harmonic and fundamental pressure wave field components is in fact observable for ultrasound propagating through UCAs. This phenomenon is absent in the case of tissue nonlinearity and is dependent on insonating pressure and frequency, UCA concentration, and propagation path length through UCAs. In this paper, ultrasound images based on this marker are presented. The ULA-OP research platform, in combination with a LA332 linear array probe (Esaote, Firenze Italy), were used to image a gelatin phantom containing a PVC plate (used as a reflector) and a cylindrical cavity measuring 7 mm in diameter (placed in between the observation point and the PVC plate). The cavity contained a 240 µL/L SonoVueO{sup ®} UCA concentration. Two insonating frequencies (3 MHz and 2.5 MHz) were used to scan the gelatine phantom. A mechanical index MI = 0.07, measured in water at the cavity location with a HGL-0400 hydrophone (Onda, Sunnyvale, CA), was utilized. Processing the ultrasound signals backscattered from the plate, ultrasound images were generated in a tomographic fashion using the filtered back-projection method. As already observed in previous studies, significantly higher CPD values are measured when imaging at a frequency of 2.5 MHz, as compared to imaging at 3 MHz. In conclusion, these results confirm the applicability of the discussed CPD as a marker for contrast imaging. Comparison with standard contrast-enhanced ultrasound imaging modalities will be the focus of future work.

  4. Cumulative phase delay imaging - A new contrast enhanced ultrasound modality

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

    Recently, a new acoustic marker for ultrasound contrast agents (UCAs) has been introduced. A cumulative phase delay (CPD) between the second harmonic and fundamental pressure wave field components is in fact observable for ultrasound propagating through UCAs. This phenomenon is absent in the case of tissue nonlinearity and is dependent on insonating pressure and frequency, UCA concentration, and propagation path length through UCAs. In this paper, ultrasound images based on this marker are presented. The ULA-OP research platform, in combination with a LA332 linear array probe (Esaote, Firenze Italy), were used to image a gelatin phantom containing a PVC plate (used as a reflector) and a cylindrical cavity measuring 7 mm in diameter (placed in between the observation point and the PVC plate). The cavity contained a 240 µL/L SonoVueO® UCA concentration. Two insonating frequencies (3 MHz and 2.5 MHz) were used to scan the gelatine phantom. A mechanical index MI = 0.07, measured in water at the cavity location with a HGL-0400 hydrophone (Onda, Sunnyvale, CA), was utilized. Processing the ultrasound signals backscattered from the plate, ultrasound images were generated in a tomographic fashion using the filtered back-projection method. As already observed in previous studies, significantly higher CPD values are measured when imaging at a frequency of 2.5 MHz, as compared to imaging at 3 MHz. In conclusion, these results confirm the applicability of the discussed CPD as a marker for contrast imaging. Comparison with standard contrast-enhanced ultrasound imaging modalities will be the focus of future work.

  5. How to Develop a Contrast-Enhanced Ultrasound Program.

    PubMed

    Barr, Richard G

    2017-02-02

    With the recent Food and Drug Administration approval of Lumason (sulfur hexafluoride lipid-type A microsphere, Bracco Diagnostics Inc, Monroe Township, NJ) for contrast-enhanced ultrasound (CEUS) to characterize focal liver lesions in both adult and pediatric patients, widespread use of CEUS is expected in the United States. This paper provides guidance in setting up a CEUS program, and reviews the practical details that will need to be instituted in a standard ultrasound department to provide both safe and efficient use of CEUS. A review of the indications, contraindications, adverse events, instructions for performing the exam, and image interpretation are discussed.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

    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.

  8. [Contrast-enhanced ultrasound findings of breast cancer].

    PubMed

    Zhang, Jian-xing; Shen, Qiang; Cai, Li-shan; Gao, Lei; Song, Guang-hui; Xie, Xiao-yan; Huang, Jie-xin

    2009-04-01

    To study the manifestation of breast cancers of different sizes in contrast-enhanced sonography. Eighty-four patients with breast cancers were examined by contrast-enhanced ultrasound. Among them, the tumor diameter was beyond 2.0 cm in 50 cases, and no greater than 2.0 cm in the rest cases. The time-intensity curve (TIC) on the enhanced images was analyzed quantitatively, and the relations between the type of TIC and the enhancement patterns of the tumors were analyzed. The enhancement patterns of the breast cancers showed significant difference between patients with tumor diameter beyond 2.0 cm and those with smaller tumors (P<0.01), but the other parameters were comparable between the two groups (P>0.05). The enhancement patterns of breast cancers differ between tumors with sizes over 2.0 cm and smaller tumors, and differential analysis is suggested in the diagnosis of breast cancer using contrast-enhanced ultrasound.

  9. Contrast ultrasound molecular imaging of inflammation in cardiovascular disease.

    PubMed

    Lindner, Jonathan R

    2009-11-01

    The cellular immune response plays an important role in almost every major form of cardiovascular disease. The ability to image the key aspects of the immune response in the clinical setting could be used to improve diagnostic information, to provide important prognostic or risk information, and to customize therapy according to disease phenotype. Accordingly, targeted imaging probes for assessing inflammation have been developed for essentially all forms of medical imaging. Molecular imaging of inflammation with contrast ultrasound relies on the detection of targeted microbubble or other gas-filled particle contrast agents. These agents are confined to the vascular space and, hence, have been targeted to either activated leucocytes or endothelial cell adhesion molecules that are upregulated in inflammation and mediate leucocyte recruitment and adhesion. This review focuses on the inflammation-targeting strategies for ultrasound contrast agents and how they have been matched to cardiovascular disease states such as myocardial ischaemia, infarction, atherosclerosis, transplant rejection, and arteriogenesis.

  10. Vascular applications of contrast-enhanced ultrasound imaging.

    PubMed

    Mehta, Kunal S; Lee, Jake J; Taha, Ashraf A; Avgerinos, Efthymios; Chaer, Rabih A

    2017-07-01

    Contrast-enhanced ultrasound (CEUS) imaging is a powerful noninvasive modality offering numerous potential diagnostic and therapeutic applications in vascular medicine. CEUS imaging uses microbubble contrast agents composed of an encapsulating shell surrounding a gaseous core. These microbubbles act as nearly perfect intravascular reflectors of ultrasound energy and may be used to enhance the overall contrast and quality of ultrasound images. The purpose of this narrative review is to survey the current literature regarding CEUS imaging and discuss its diagnostic and therapeutic roles in current vascular and selected nonvascular applications. The PubMed, MEDLINE, and Embase databases were searched until July 2016 using the PubMed and Ovid Web-based search engines. The search terms used included contrast-enhanced, microbubble, ultrasound, carotid, aneurysm, and arterial. The diagnostic and therapeutic utility of CEUS imaging has grown exponentially, particularly in the realms of extracranial carotid arterial disease, aortic disease, and peripheral arterial disease. Studies have demonstrated that CEUS imaging is diagnostically superior to conventional ultrasound imaging in identifying vessel irregularities and measuring neovascularization to assess plaque vulnerability and end-muscle perfusion. Groups have begun to use microbubbles as agents in therapeutic applications for targeted drug and gene therapy delivery as well as for the enhancement of sonothrombolysis. The emerging technology of microbubbles and CEUS imaging holds considerable promise for cardiovascular medicine and cancer therapy given its diagnostic and therapeutic utility. Overall, with proper training and credentialing of technicians, the clinical implications are innumerable as microbubble technology is rapidly bursting onto the scene of cardiovascular medicine. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  11. Multifunctional ultrasound contrast agents for imaging guided photothermal therapy.

    PubMed

    Guo, Caixin; Jin, Yushen; Dai, Zhifei

    2014-05-21

    Among all the imaging techniques, ultrasound imaging has a unique advantage due to its features of real-time, low cost, high safety, and portability. Ultrasound contrast agents (UCAs) have been widely used to enhance ultrasonic signals. One of the most exciting features of UCAs for use in biomedicine is the possibility of easily putting new combinations of functional molecules into microbubbles (MBs), which are the most routinely used UCAs. Various therapeutic agents and medical nanoparticles (quantum dots, gold, Fe3O4, etc.) can be loaded into ultrasound-responsive MBs. Hence, UCAs can be developed as multifunctional agents that integrate capabilities for early detection and diagnosis and for imaging guided therapy of various diseases. The current review will focus on such state-of-the-art UCA platforms that have been exploited for multimodal imaging and for imaging guided photothermal therapy.

  12. 3D imaging options and ultrasound contrast agents for the ultrasound assessment of pediatric rheumatic patients.

    PubMed

    Madej, Tomasz

    2013-12-01

    The application of 3D imaging in pediatric rheumatology helps to make the assessment of inflammatory changes more objective and to estimate accurately their volume and the actual response to treatment in the course of follow-up examinations. Additional interesting opportunities are opened up by the vascularity analysis with the help of power Doppler and color Doppler in 3D imaging. Contrast-enhanced ultrasound examinations enable a more sensitive assessment of the vascularity of inflamed structures of the locomotor system, and a more accurate analysis of treatment's effect on changes in vascularity, and thereby the inflammation process activity, as compared to the classical options of power and color Doppler. The equipment required, time limitations, as well as the high price in the case of contrast-enhanced ultrasound, contribute to the fact that the 3D analysis of inflammatory changes and contrast-enhanced ultrasound examinations are not routinely applied for pediatric patients.

  13. Dual-Frequency Piezoelectric Transducers for Contrast Enhanced Ultrasound Imaging

    PubMed Central

    Martin, K. Heath; Lindsey, Brooks D.; Ma, Jianguo; Lee, Mike; Li, Sibo; Foster, F. Stuart; Jiang, Xiaoning; Dayton, Paul A.

    2014-01-01

    For many years, ultrasound has provided clinicians with an affordable and effective imaging tool for applications ranging from cardiology to obstetrics. Development of microbubble contrast agents over the past several decades has enabled ultrasound to distinguish between blood flow and surrounding tissue. Current clinical practices using microbubble contrast agents rely heavily on user training to evaluate degree of localized perfusion. Advances in separating the signals produced from contrast agents versus surrounding tissue backscatter provide unique opportunities for specialized sensors designed to image microbubbles with higher signal to noise and resolution than previously possible. In this review article, we describe the background principles and recent developments of ultrasound transducer technology for receiving signals produced by contrast agents while rejecting signals arising from soft tissue. This approach relies on transmitting at a low-frequency and receiving microbubble harmonic signals at frequencies many times higher than the transmitted frequency. Design and fabrication of dual-frequency transducers and the extension of recent developments in transducer technology for dual-frequency harmonic imaging are discussed. PMID:25375755

  14. Dual-frequency piezoelectric transducers for contrast enhanced ultrasound imaging.

    PubMed

    Martin, K Heath; Lindsey, Brooks D; Ma, Jianguo; Lee, Mike; Li, Sibo; Foster, F Stuart; Jiang, Xiaoning; Dayton, Paul A

    2014-11-04

    For many years, ultrasound has provided clinicians with an affordable and effective imaging tool for applications ranging from cardiology to obstetrics. Development of microbubble contrast agents over the past several decades has enabled ultrasound to distinguish between blood flow and surrounding tissue. Current clinical practices using microbubble contrast agents rely heavily on user training to evaluate degree of localized perfusion. Advances in separating the signals produced from contrast agents versus surrounding tissue backscatter provide unique opportunities for specialized sensors designed to image microbubbles with higher signal to noise and resolution than previously possible. In this review article, we describe the background principles and recent developments of ultrasound transducer technology for receiving signals produced by contrast agents while rejecting signals arising from soft tissue. This approach relies on transmitting at a low-frequency and receiving microbubble harmonic signals at frequencies many times higher than the transmitted frequency. Design and fabrication of dual-frequency transducers and the extension of recent developments in transducer technology for dual-frequency harmonic imaging are discussed.

  15. Contrast-enhanced ultrasound (CEUS) in blunt abdominal trauma

    PubMed Central

    Piccolo, Claudia Lucia; Galluzzo, Michele; Ianniello, Stefania; Sessa, Barbara; Trinci, Margherita

    2016-01-01

    Baseline ultrasound is essential in the early assessment of patients with a huge haemoperitoneum undergoing an immediate abdominal surgery; nevertheless, even with a highly experienced operator, it is not sufficient to exclude parenchymal injuries. More recently, a new ultrasound technique using second generation contrast agents, named contrast-enhanced ultrasound (CEUS) has been developed. This technique allows all the vascular phase to be performed in real time, increasing ultrasound capability to detect parenchymal injuries, enhancing some qualitative findings, such as lesion extension, margins and its relationship with capsule and vessels. CEUS has been demonstrated to be almost as sensitive as contrast-enhanced CT in the detection of traumatic injuries in patients with low-energy isolated abdominal trauma, with levels of sensitivity and specificity up to 95%. Several studies demonstrated its ability to detect lesions occurring in the liver, spleen, pancreas and kidneys and also to recognize active bleeding as hyperechoic bands appearing as round or oval spots of variable size. Its role seems to be really relevant in paediatric patients, thus avoiding a routine exposure to ionizing radiation. Nevertheless, CEUS is strongly operator dependent, and it has some limitations, such as the cost of contrast media, lack of panoramicity, the difficulty to explore some deep regions and the poor ability to detect injuries to the urinary tract. On the other hand, it is timesaving, and it has several advantages, such as its portability, the safety of contrast agent, the lack to ionizing radiation exposure and therefore its repeatability, which allows follow-up of those traumas managed conservatively, especially in cases of fertile females and paediatric patients. PMID:26607647

  16. Ultrasound contrast agents for bleeding detection and acoustic hemostasis

    NASA Astrophysics Data System (ADS)

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

    2005-04-01

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

  17. Characterization and Ultrasound-Pulse Mediated Destruction of Ultrasound Contrast Microbubbles

    NASA Astrophysics Data System (ADS)

    Sarkar, Kausik; Jain, Pankaj; Chatterjee, Dhiman

    2006-05-01

    Intravenously injected encapsulated microbubbles improve the contrast of an ultrasound image. Their destruction is used in measuring blood flow, stimulating arteriogenesis, and drug delivery. We measure attenuation and scattering of ultrasound through solution of commercial contrast agents such as Sonazoid and Definity. We have developed a number of different interfacial rheology models for the encapsulation of such microbubbles. By matching with experimentally measured attenuation, we obtain the characteristic rheological parameters. We compare model predictions with measured subharmonic responses. We also investigate microbubble destruction under acoustic excitation by measuring time-varying attenuation data.

  18. A theoretical investigation of chirp insonification of ultrasound contrast agents.

    PubMed

    Barlow, Euan; Mulholland, Anthony J; Gachagan, Anthony; Nordon, Alison

    2011-08-01

    A theoretical investigation of second harmonic imaging of an Ultrasound Contrast Agent (UCA) under chirp insonification is considered. By solving the UCA's dynamical equation analytically, the effect that the chirp signal parameters and the UCA shell parameters have on the amplitude of the second harmonic frequency are examined. This allows optimal parameter values to be identified which maximise the UCA's second harmonic response. A relationship is found for the chirp parameters which ensures that a signal can be designed to resonate a UCA for a given set of shell parameters. It is also shown that the shell thickness, shell viscosity and shell elasticity parameter should be as small as realistically possible in order to maximise the second harmonic amplitude. Keller-Herring, Second Harmonic, Chirp, Ultrasound Contrast Agent.

  19. Ultrasound Activated Contrast Imaging for Prostate Cancer Detection

    DTIC Science & Technology

    2006-03-01

    539-550, 2005. F. Forsberg, W. T. Shi, M. M. Knauer, A. L. Hall, C. Vecchio, R. Bernardi . Real time excitation enhanced ultrasound contrast...simulations. Ultrasonics, 32:447-453, 1994. 5. Shi WT, Forsberg F, Bautista R, Vecchio C, Bernardi R, Goldberg BB. Image enhancement by acoustic...Phys. Fluids, 17:100603 – 100603-8, 2005. 10. Forsberg F, Shi WT, Knauer MM, Hall AL, Vecchio C, Bernardi R. Real time excitation enhanced

  20. Contrast-enhanced ultrasound: clinical applications in patients with atherosclerosis.

    PubMed

    Schinkel, Arend F L; Kaspar, Mathias; Staub, Daniel

    2016-01-01

    Contrast-enhanced ultrasound (CEUS) is increasingly being used to evaluate patients with known or suspected atherosclerosis. The administration of a microbubble contrast agent in conjunction with ultrasound results in an improved image quality and provides information that cannot be assessed with standard B-mode ultrasound. CEUS is a high-resolution, noninvasive imaging modality, which is safe and may benefit patients with coronary, carotid, or aortic atherosclerosis. CEUS allows a reliable assessment of endocardial borders, left ventricular function, intracardiac thrombus and myocardial perfusion. CEUS results in an improved detection of carotid atherosclerosis, and allows assessment of high-risk plaque characteristics including intraplaque vascularization, and ulceration. CEUS provides real-time bedside information in patients with a suspected or known abdominal aortic aneurysm or aortic dissection. The absence of ionizing radiation and safety of the contrast agent allow repetitive imaging which is particularly useful in the follow-up of patients after endovascular aneurysm repair. New developments in CEUS-based molecular imaging will improve the understanding of the pathophysiology of atherosclerosis and may in the future allow to image and directly treat cardiovascular diseases (theragnostic CEUS). Familiarity with the strengths and limitations of CEUS may have a major impact on the management of patients with atherosclerosis.

  1. Zero Contrast Coronary Intervention Using Intravascular Ultrasound Guidance in a Patient with Allergy to Contrast Medium.

    PubMed

    Nagaoka, Masakazu; Tsumuraya, Naoko; Nie, Masaki; Ikari, Yuji

    2016-09-20

    The occurrence of allergy to iodinated contrast in certain patients may prevent the use of percutaneous coronary intervention (PCI) in such cases. We present a 53-year-old male with a history of allergic reaction to iodinated contrast who successfully underwent intravascular ultrasound (IVUS) guided PCI. Stent size was determined based on IVUS. After PCI, stent expansion and a lack of edge dissection or incomplete apposition were confirmed by IVUS. Thus, PCI without contrast injection under IVUS may be feasible in selected patients with allergy to iodinated contrast.

  2. Value of contrast-enhanced ultrasound in rheumatic disease.

    PubMed

    Klauser, Andrea Sabine

    2005-12-01

    Ultrasound (US) is a useful tool in the assessment of rheumatic disease. It permits assessment of early erosive changes and vascularity detection in synovial proliferation, caused by inflammatory activity by using colour/power Doppler US (CDUS/PDUS). In the detection of slow flow and flow in small vessels, the CDUS/PDUS technique is limited. Contrast enhanced US can improve the detection of inflammatory vascularity but is not yet included in routine diagnosis of this condition. However, contrast enhanced US shows promising results in diagnosis, assessment of disease activity and follow up of inflammatory rheumatic diseases.

  3. Dynamic contrast-enhanced endoscopic ultrasound: A quantification method

    PubMed Central

    Dietrich, Christoph F.; Dong, Yi; Froehlich, Eckhart; Hocke, Michael

    2017-01-01

    Dynamic contrast-enhanced ultrasound (DCE-US) has been recently standardized by guidelines and recommendations. The European Federation of Societies for US in Medicine and Biology position paper describes the use for DCE-US. Comparatively, little is known about the use of contrast-enhanced endoscopic US (CE-EUS). This current paper reviews and discusses the clinical use of CE-EUS and DCE-US. The most important clinical use of DCE-US is the prediction of tumor response to new drugs against vascular angioneogenesis. PMID:28218195

  4. Feasibility of ultrasound phase contrast for heating localization.

    PubMed

    Farny, Caleb H; Clement, Greg T

    2008-03-01

    Ultrasound-based methods for temperature monitoring could greatly assist focused ultrasound visualization and treatment planning based on sound speed-induced change in phase as a function of temperature. A method is presented that uses reflex transmission integration, planar projection, and tomographic reconstruction techniques to visualize phase contrast by measuring the sound field before and after heat deposition. Results from experiments and numerical simulations employing a through-transmission setup are presented to demonstrate feasibility of using phase contrast methods for identifying temperature change. A 1.088-MHz focused transducer was used to interrogate a medium with a phase contrast feature, following measurement of the baseline reference field with a hydrophone. A thermal plume in water and a tissue phantom with multiple water columns was used in separate experiments to produce a phase contrast. The reference and phase contrast field scans were numerically backprojected and the phase difference correctly identified the position and orientation of the features. The peak temperature reconstructed from the phase shift was within 0.2 degrees C of the measured temperature in the plume. Simulated results were in good agreement with experimental results. Finally, employment of reflex transmission imaging techniques for adopting a pulse-echo arrangement was simulated, and its future experimental application is discussed.

  5. Diagnosis of liver cirrhosis with contrast-enhanced ultrasound

    PubMed Central

    Liu, Guang-Jian; Lu, Ming-De

    2010-01-01

    The assessment of the extent of liver fibrosis is very important for the prognosis and clinical management of chronic liver diseases. Although liver biopsy is the gold standard for the assessment of liver fibrosis, new non-invasive diagnostic methods are urgently needed in clinical work due to certain limitations and complications of biopsy. Noninvasive imaging studies play an important role in the diagnosis of focal liver disease and diffuse liver diseases. Among them, ultrasonography is the first choice for study of the liver in clinical work. With the development of ultrasound contrast agents and contrast specific imaging techniques, contrast-enhanced ultrasound (CEUS) shows good performance and great potential in the evaluation of liver fibrosis. Researchers have tried different kinds of contrast agent and imaging method, such as arrival time of contrast agent in the hepatic vein, and quantitative analysis of the enhancement level of liver parenchyma, to evaluate the degree of liver fibrosis during the past 10 years. This review mainly summarizes the clinical studies concerning the assessment of liver fibrosis using CEUS. PMID:21160737

  6. Interfacial rheology of encapsulated microbubble contrast agents for medical ultrasound

    NASA Astrophysics Data System (ADS)

    Sarkar, Kausik

    2002-11-01

    Intravenous encapsulated microbubble contrast agents (1-10 mu) have become an established clinical tool for enhancing ultrasound sensitivity. Bubbles enhance contrast due to their high scattering cross-sections relative to those of rigid particles. The high values result from the large difference in density and compressibility. Furthermore, they act as damped mass-spring systems with enhanced resonant signal near their natural frequency. Most contrast agents are made with an encapsulating shell that prevents their premature dissolution. Free bubbles can last only a fraction of a second, whereas persistence requirements for a bubble to successfully reach from peripheral veins, where they are injected, to end-organs via heart is 12-27 seconds. Different contrast agents differ in the materials, structure and properties of their shells. We will present a model of the surface rheology of the shell. It will be compared with the currently available models of the shell. Preliminary results of the encapsulated bubble dynamics will be provided.

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

    PubMed

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

    2010-03-01

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

  8. Ultrasound contrast agent fabricated from microbubbles containing instant adhesives, and its ultrasound imaging ability

    NASA Astrophysics Data System (ADS)

    Makuta, T.; Tamakawa, Y.

    2012-04-01

    Non-invasive surgery techniques and drug delivery system with acoustic characteristics of ultrasound contrast agent have been studied intensively in recent years. Ultrasound contrast agent collapses easily under the blood circulating and the ultrasound irradiating because it is just a stabilized bubble without solid-shell by surface adsorption of surfactant or lipid. For improving the imaging stability, we proposed the fabrication method of the hollow microcapsule with polymer shell, which can be fabricated just blowing vapor of commonly-used instant adhesive (Cyanoacrylate monomer) into water as microbubbles. Therefore, the cyanoacrylate vapor contained inside microbubble initiates polymerization on the gasliquid interface soon after microbubbles are generated in water. Consequently, hollow microspheres coated by cyanoacrylate thin film are generated. In this report, we revealed that diameter distributions of microbubbles and microcapsules were approximately same and most of them were less than 10 μm, that is, smaller than blood capillary. In addition, we also revealed that hollow microcapsules enhanced the acoustic signal especially in the harmonic contrast imaging and were broken or agglomerated under the ultrasound field. As for the yield of hollow microcapsules, we revealed that sodium dodecyl sulfate addition to water phase instead of deoxycolic acid made the fabrication yield increased.

  9. Contrast harmonic endoscopic ultrasound: Instrumentation, echoprocessors, and echoendoscopes

    PubMed Central

    Iglesias-Garcia, Julio; Lariño-Noia, Jose; Domínguez-Muñoz, J. Enrique

    2017-01-01

    Endoscopic ultrasound (EUS) has become as one the best diagnostic and therapeutic methods for the management of several intraintestinal and extraintestinal diseases, among them to highlight pancreaticobiliary indications, mediastinal evaluation, and the analysis of gastrointestinal lesions. Over the years, there has been an enormous evolution in the systems available to perform EUS. Newer processors and echoendoscopes are available nowadays, with the ability to perform new imaging analysis, such as elastography and contrast enhancement. In the present article, we will review which systems are available nowadays, focusing also in the technical advances associated. PMID:28218199

  10. Ultrasound Induced Fluorescence of Nanoscale Liposome Contrast Agents

    PubMed Central

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

    2016-01-01

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

  11. Second harmonic inversion for ultrasound contrast harmonic imaging.

    PubMed

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

    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(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.

  12. Usefulness of ultrasound contrast for image enhancement during stress echocardiography.

    PubMed

    Ten Cate, Folkert J

    2002-10-01

    Although stress echocardiography has been established as a diagnostic technique for the detection and assessment of ischemia, there are still a number of limitations to the technique. These are related to suboptimal image quality with poor visualization of endocardial borders. Because assessment of wall motion is fundamental to the diagnostic value of stress echocardiography (both pharmacologic and exercise), endocardial border visualization is of utmost importance. Furthermore, interinstitutional observer agreement of 100% in highest image quality patients to a cumbersome 43% in low image quality patients is present. Therefore, improvements of image quality during stress are essential. One of the recent improvements is harmonic imaging, which improves visualization of endocardial borders at rest and during dobutamine stress. However, there is room for improvement. Since the introduction of ultrasound contrast agents, contrast has been increasingly used for better endocardial border visualization. Data from centers with a large number of stress echocardiography tests have shown that the addition of contrast agents decreases the number of more redundant diagnostic testing. Data obtained in our center in a subset of patients administered with SonoVue, a new generation contrast agent made of stabilized microbubbles containing sulfur hexafluoride, an inert gas, showed an improvement in the number of evaluable segments with fundamental and harmonic imaging and in the endocardial border detection during dobutamine stress echocardiography. Contrast also enables future quantitative analysis using acoustic quantification (AQ), and color kinesis. These studies should be carried out now that contrast has been approved for introduction to the market.

  13. Nanobubble-Affibody: Novel ultrasound contrast agents for targeted molecular ultrasound imaging of tumor.

    PubMed

    Yang, Hengli; Cai, Wenbin; Xu, Lei; Lv, Xiuhua; Qiao, Youbei; Li, Pan; Wu, Hong; Yang, Yilin; Zhang, Li; Duan, Yunyou

    2015-01-01

    Nanobubbles (NBs), as novel ultrasound contrast agents (UCAs), have attracted increasing attention in the field of molecular ultrasound imaging for tumors. However, the preparation of uniform-sized NBs is considered to be controversial, and poor tumor selectivity in in vivo imaging has been reported. In this study, we fabricated uniform nano-sized NBs (478.2 ± 29.7 nm with polydispersity index of 0.164 ± 0.044, n = 3) using a thin-film hydration method by controlling the thickness of phospholipid films; we then conjugated the NBs with Affibody molecules to produce nano-sized UCAs referred to as NB-Affibody with specific affinity to human epidermal growth factor receptor type 2 (HER2)-overexpressing tumors. NB-Affibody presented good ultrasound enhancement, demonstrating a peak intensity of 104.5 ± 2.1 dB under ultrasound contrast scanning. Ex vivo experiments further confirmed that the NB-Affibody conjugates were capable of targeting HER2-expressing tumor cells in vivo with high affinity. The newly prepared nano-sized NB-Affibody conjugates were observed to be novel targeted UCAs for efficient and safe specific molecular imaging and may have potential applications in early cancer quantitative diagnosis and targeted therapy in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Feasibility of quantitative contrast ultrasound imaging of bladder tumors in dogs.

    PubMed

    Pollard, Rachel E; Watson, Katherine D; Hu, Xiaowen; Ingham, Elizabeth; Ferrara, Katherine W

    2017-01-01

    The purpose of this pilot study was to assess the feasibility of Cadence contrast pulse sequencing ultrasound to predict clinical and angiogenic tumor response in dogs undergoing chemotherapy. Contrast ultrasound facilitated visualization of bladder tumors but failed to identify a straightforward relationship between ultrasound measures and clinical outcome.

  15. Current topics in ultrasound contrast agent application and design

    NASA Astrophysics Data System (ADS)

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

    2001-05-01

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

  16. High-frequency dynamics of ultrasound contrast agents.

    PubMed

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

    2005-11-01

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

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

    PubMed

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

    2015-07-08

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2005-03-01

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

  20. High-Frequency Dynamics of Ultrasound Contrast Agents

    PubMed Central

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

    2006-01-01

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

  1. Contrast-enhanced ultrasound for liver imaging: recent advances.

    PubMed

    Salvatore, Veronica; Borghi, Alberto; Piscaglia, Fabio

    2012-01-01

    Contrast-enhanced ultrasonography (CEUS), providing relevant informations not available with non-enhanced ultrasonography, greatly impacted the practice of liver imaging. The characterization of focal liver lesions (FLLs), is obtained in a rapid, accurate and safe way and is considered the main hepatic indication; however CEUS offers other established or emergent relevant applications. Metastases detection and assessment of response to locoregional tumor treatment are accepted applications with specific indications. Needle guidance in case of poorly or non visible target lesions at conventional ultrasound is also accepted. The early assessment of response to systemic treatment, and in particular to antiangiogenic ones, by quantification software is an emergent application. The manageability of CEUS determined also its use in the operating theatre, improving the accuracy of intraoperatory US with a significant impact on final surgical strategy. In cirrhotic patients, the role of CEUS was proven highly accurate and sensitive in the characterization of portal vein thrombosis, by identification of contrast arterial enhancement inside the thrombus, that occurs only in case of neoplastic origin. In recent years microbubbles taken up by Kupffer cells, thus possessing a "postvascular" phase, were registered as ultrasound contrast agent in Japan (Sonazoid). During the post-vascular phase tumoral tissue tend to appear as a contrast defect image due to the lack of Kupffer cells, strongly contributing to tumor staging beside characterization. Newly developed techniques, such as fusion imaging or real-time three dimensional US, in addition to other applications of CEUS, in terms of post-transplantation or cholecystitis-related complications, have been recently proposed and will be discussed.

  2. [Transabdominal ultrasound examination, contrast-enhanced ultrasound examination and endoscopic ultrasound scanning in the determination of the aetiology and the degree of severity in acute pancreatitis].

    PubMed

    Møller Andersen, Anders; Malmstrøm, Marie Louise; Novovic, Srdan; Jørgensen, Lars Nannestad; Nissen, Flemming Helge; Hansen, Mark Berner

    2013-05-20

    A transabdominal ultrasound examination is part of the standard work-up for patients with acute pancreatitis. Transabdominal ultrasound examination displays a high sensitivity for the detection of gallbladder stones. With the recent introduction of contrast enhancement in ultrasound it has become possible to determine the severity of acute pancreatitis. Endoscopic ultrasound has shown a high sensitivity in the diagnosis of stones in the common bile duct and is an important peroperative surgical tool in endoscopic transgastric necrosectomi as well.

  3. Contrast enhanced ultrasound (CEUS) in blunt abdominal trauma.

    PubMed

    Cagini, Lucio; Gravante, Sabrina; Malaspina, Corrado Maria; Cesarano, Elviro; Giganti, Melchiorre; Rebonato, Alberto; Fonio, Paolo; Scialpi, Michele

    2013-07-15

    In the assessment of polytrauma patient, an accurate diagnostic study protocol with high sensitivity and specificity is necessary. Computed Tomography (CT) is the standard reference in the emergency for evaluating the patients with abdominal trauma. Ultrasonography (US) has a high sensitivity in detecting free fluid in the peritoneum, but it does not show as much sensitivity for traumatic parenchymal lesions. The use of Contrast-Enhanced Ultrasound (CEUS) improves the accuracy of the method in the diagnosis and assessment of the extent of parenchymal lesions. Although the CEUS is not feasible as a method of first level in the diagnosis and management of the polytrauma patient, it can be used in the follow-up of traumatic injuries of abdominal parenchymal organs (liver, spleen and kidneys), especially in young people or children.

  4. Contrast enhanced ultrasound (CEUS) in blunt abdominal trauma

    PubMed Central

    2013-01-01

    In the assessment of polytrauma patient, an accurate diagnostic study protocol with high sensitivity and specificity is necessary. Computed Tomography (CT) is the standard reference in the emergency for evaluating the patients with abdominal trauma. Ultrasonography (US) has a high sensitivity in detecting free fluid in the peritoneum, but it does not show as much sensitivity for traumatic parenchymal lesions. The use of Contrast-Enhanced Ultrasound (CEUS) improves the accuracy of the method in the diagnosis and assessment of the extent of parenchymal lesions. Although the CEUS is not feasible as a method of first level in the diagnosis and management of the polytrauma patient, it can be used in the follow-up of traumatic injuries of abdominal parenchymal organs (liver, spleen and kidneys), especially in young people or children. PMID:23902930

  5. Role of contrast-enhanced endoscopic ultrasound in lymph nodes

    PubMed Central

    Hocke, Michael; Ignee, Andre; Dietrich, Christoph

    2017-01-01

    Diagnosing unclear lymph node (LN) enlargements in the mediastinum and abdomen is the most important indication of endoscopic ultrasound (EUS)-fine needle aspiration (FNA) after the diagnosis and treatment of pancreatic diseases. Investigating LNs in these areas can happen in different clinical settings. Mostly, it is the first modality in general LN diseases without any peripheral LN enlargements. On the other hand, it can be the question of LN involvement in a known or suspected primary tumor. Due to EUS-FNA cytology, those questions can be answered highly, accurately. However, a primary discrimination of LNs might be helpful to increase the diagnostic value of the FNA cytology, especially in cases with multiple LN enlargements and hard to reach enlarged LNs for example by vessel interposition. Because of the unreliability of B-mode criteria, further diagnostic improvements such as elastography and contrast-enhanced EUS are investigated to increase the accuracy of the initial diagnosis. PMID:28218194

  6. Vascular flow and perfusion imaging with ultrasound contrast agents.

    PubMed

    Bruce, Matthew; Averkiou, Mike; Tiemann, Klaus; Lohmaier, Stefan; Powers, Jeff; Beach, Kirk

    2004-06-01

    Current techniques for imaging ultrasound (US) contrast agents (UCA) make no distinction between low-velocity microbubbles in the microcirculation and higher-velocity microbubbles in the larger vasculature. A combination of radiofrequency (RF) and Doppler filtering on a low mechanical index (MI) pulse inversion acquisition is presented that differentiates low-velocity microbubbles (on the order of mm/s) associated with perfusion, from the higher-velocity microbubbles (on the order of cm/s) in larger vessels. In vitro experiments demonstrate the ability to separate vascular flow using both harmonic and fundamental Doppler signals. Fundamental and harmonic Doppler signals from microbubbles using a low-MI pulse-inversion acquisition are compared with conventional color Doppler signals in vivo. Due to the lower transmit amplitude and enhanced backscatter from microbubbles, the in vivo signal to clutter ratios for both the fundamental (-11 dB) and harmonic (-4 dB) vascular flow signals were greater than with conventional power Doppler (-51 dB) without contrast agent. The processing investigated here, in parallel with conventional pulse-inversion processing, enables the simultaneous display of both perfusion and vascular flow. In vivo results demonstrating the feasibility and potential utility of the real-time display of both perfusion and vascular flow using US contrast agents are presented and discussed.

  7. Role of contrast-enhanced ultrasound (CEUS) in the diagnosis of endometrial pathology

    PubMed Central

    POP, CIPRIAN MIHAITA; MIHU, DAN; BADEA, RADU

    2015-01-01

    Ultrasound is the reference imaging procedure used for the exploration of endometrial pathology. As medical procedures improve and the requirements of modern medicine become more demanding, gray-scale ultrasound is insufficient in establishing gynecological diagnosis. Thus, more complex examination techniques are required: Doppler ultrasound, contrast-enhanced ultrasound (CEUS), 3D ultrasound, etc. Contrast-enhanced ultrasound is a special examination technique that gains more and more ground. This allows a detailed real-time evaluation of microcirculation in a certain territory, which is impossible to perform by Doppler ultrasound. The aim of this review is to synthesize current knowledge regarding CEUS applications in endometrial pathology, to detail the technical aspects of endometrial CEUS and the physical properties of the equipment and contrast agents used, as well as to identify the limitations of the method. PMID:26733740

  8. Harmonic chirp imaging method for ultrasound contrast agent.

    PubMed

    Borsboom, Jerome M G; Chin, Chien Ting; Bouakaz, Ayache; Versluis, Michel; de Jong, Nico

    2005-02-01

    Coded excitation is currently used in medical ultrasound to increase signal-to-noise ratio (SNR) and penetration depth. We propose a chirp excitation method for contrast agents using the second harmonic component of the response. This method is based on a compression filter that selectively compresses and extracts the second harmonic component from the received echo signal. Simulations have shown a clear increase in response for chirp excitation over pulse excitation with the same peak amplitude. This was confirmed by two-dimensional (2-D) optical observations of bubble response with a fast framing camera. To evaluate the harmonic compression method, we applied it to simulated bubble echoes, to measured propagation harmonics, and to B-mode scans of a flow phantom and compared it to regular pulse excitation imaging. An increase of approximately 10 dB in SNR was found for chirp excitation. The compression method was found to perform well in terms of resolution. Axial resolution was in all cases within 10% of the axial resolution from pulse excitation. Range side-lobe levels were 30 dB below the main lobe for the simulated bubble echoes and measured propagation harmonics. However, side-lobes were visible in the B-mode contrast images.

  9. Contrast-enhanced ultrasound of histologically proven hepatic epithelioid hemangioendothelioma

    PubMed Central

    Dong, Yi; Wang, Wen-Ping; Cantisani, Vito; D’Onofrio, Mirko; Ignee, Andre; Mulazzani, Lorenzo; Saftoiu, Adrian; Sparchez, Zeno; Sporea, Ioan; Dietrich, Christoph F

    2016-01-01

    AIM: To analyze contrast-enhanced ultrasound (CEUS) features of histologically proven hepatic epithelioid hemangioendothelioma (HEHE) in comparison to other multilocular benign focal liver lesions (FLL). METHODS: Twenty-five patients with histologically proven HEHE and 45 patients with histologically proven multilocular benign FLL were retrospectively reviewed. Four radiologists assessed the CEUS enhancement pattern in consensus. RESULTS: HEHE manifested as a single (n = 3) or multinodular (n = 22) FLL. On CEUS, HEHE showed rim-like (18/25, 72%) or heterogeneous hyperenhancement (7/25, 28%) in the arterial phase and hypoenhancement (25/25, 100%) in the portal venous and late phases (PVLP), a sign of malignancy. Eighteen patients showed central unenhanced areas (18/25, 72%); in seven patients (7/25, 28%), more lesions were detected in the PVLP. In contrast, all patients with hemangioma and focal nodular hyperplasia showed hyperenhancement as the most distinctive feature (P < 0.01). CONCLUSION: CEUS allows for characterization of unequivocal FLL. By analyzing the hypoenhancement in the PVLP, CEUS can determine the malignant nature of HEHE. PMID:27217705

  10. The angiogenic response is dependent on ultrasound contrast agent concentration

    PubMed Central

    2012-01-01

    Objective Ultrasound (US) and ultrasound contrast agents (UCAs) provide a way to noninvasively induce targeted angiogenesis. However, there exists a lack of understanding regarding the mechanisms of this process that has impeded progress. This study sought to characterize the angiogenic response, by both exploring the role of UCA concentration ([UCA]) in bioeffect induction at 0 days post exposure (DPE) and assessing the bioeffect as a possible potentiator of angiogenesis at 5 DPE. Methods A 1-MHz ultrasonic transducer was used to expose the gracilis muscles of Sprague Dawley rats for 5 min with a 10-μs pulse duration, 10-Hz pulse repetition frequency, and 0.7-MPa peak rarefactional acoustic pressure (pr). Four [UCA]s were tested: 0x (saline), 1×, 5×, and 10×, where 1× is 5% Definity by volume of solution. Evans blue dye (EBD) was used to quantify changes in acute vascular permeability (0 DPE), and VEGF expression was quantified at 5 DPE to support that angiogenesis had occurred. CD31 staining was used to assess capillary density at both time points. Results [UCA] was a significant parameter for determining EBD leakage (permeability) and VEGF expression (p < 0.001 for both). However, [UCA] was not a significant parameter for capillary density at 0 or 5 DPE. Multiple comparisons between 0 and 5 DPE showed that only 10× [UCA] at 5 DPE was significantly different than 0 DPE, suggesting a [UCA] dependence of the angiogenic response. Conclusions This study suggests that [UCA] was a significant parameter in the induction of an angiogenic response with US and UCAs. It also suggests that rather than damage from US and UCAs, as previously speculated, a nondestructive mechanical interaction between the UCAs and vascular endothelium induces bioeffects to potentiate the angiogenic response. PMID:22587914

  11. Ultrasound modulated optical tomography contrast enhancement with non-linear oscillation of microbubbles

    PubMed Central

    Ruan, Haowen; Mather, Melissa L.

    2015-01-01

    Background Ultrasound modulated optical tomography (USMOT) is an imaging technique used to provide optical functional information inside highly scattering biological tissue. One of the challenges facing this technique is the low image contrast. Methods A contrast enhancement imaging technique based on the non-linear oscillation of microbubbles is demonstrated to improve image contrast. The ultrasound modulated signal was detected using a laser pulse based speckle contrast detection system. Better understanding of the effects of microbubbles on the optical signals was achieved through simultaneous measurement of the ultrasound scattered by the microbubbles. Results The length of the laser pulse was found to affect the system response of the speckle contrast method with shorter pulses suppressing the fundamental ultrasound modulated optical signal. Using this property, image contrast can be enhanced by detection of the higher harmonic ultrasound modulated optical signals due to nonlinear oscillation and destruction of the microbubbles. Experimental investigations were carried out to demonstrate a doubling in contrast by imaging a scattering phantom containing an embedded silicone tube with microbubbles flowing through it. Conclusions The contrast enhancement in USMOT resulting from the use of ultrasound microbubbles has been demonstrated. Destruction of the microbubbles was shown to be the dominant effect leading to contrast improvement as shown by simultaneously detecting the ultrasound and speckle contrast signals. Line scans of a microbubble filled silicone tube embedded in a scattering phantom demonstrated experimentally the significant image contrast improvement that can be achieved using microbubbles and demonstrates the potential as a future clinical imaging tool. PMID:25694948

  12. Renal Masses With Equivocal Enhancement at CT: Characterization With Contrast-Enhanced Ultrasound.

    PubMed

    Bertolotto, Michele; Cicero, Calogero; Perrone, Rosaria; Degrassi, Ferruccio; Cacciato, Francesca; Cova, Maria A

    2015-05-01

    The purpose of this article is to retrospectively investigate in two radiology centers the role of contrast-enhanced ultrasound in the characterization of renal masses with equivocal enhancement at CT (i.e., with a density increase of 10-20 HU between unenhanced and contrast-enhanced scans) not characterized with conventional ultrasound modes. Forty-seven renal lesions (range, 0.8-7.7 cm; average, 2.6 cm) with equivocal enhancement at CT underwent contrast-enhanced ultrasound using sulfur hexafluoride-filled microbubbles. Examinations were digitally recorded for retrospective blinded evaluation by two radiologists with 20 and 10 years' experience in urologic imaging. Histologic results were available for 30 of 47 (64%) lesions (25 primary malignant tumors, two metastases, and three primary benign lesions). Two lesions increased in size and complexity during the follow-up and were considered malignant. One Bosniak category III and 14 category IIF cysts were stable after a follow-up of at least 3 years and were considered benign. ROC curve analysis was used to assess the capability of contrast-enhanced ultrasound to differentiate benign from malignant lesions. Twelve likely complex cystic lesions at gray-scale ultrasound were cystic also on contrast-enhanced ultrasound and reference procedures. Eleven of 34 lesions that appeared solid at gray-scale ultrasound were cystic on contrast-enhanced ultrasound and reference procedures. One lesion considered likely solid by one radiologist and possibly cystic by the other was a solid tumor at contrast-enhanced ultrasound and histologic analysis. The diagnostic performance of contrast-enhanced ultrasound to characterize the lesions as benign or malignant was high for both readers (AUC, 0.958 and 0.966, respectively). Contrast-enhanced ultrasound is effective for characterizing renal lesions presenting with equivocal enhancement at CT.

  13. Ultrasound Contrast Materials in Cardiovascular Medicine: from Perfusion Assessment to Molecular Imaging

    PubMed Central

    Klibanov, Alexander L

    2013-01-01

    Ultrasound imaging is widely used in cardiovascular diagnostics. Contrast agents expand the range of tasks that ultrasound can perform. In the clinic in US, endocardial border delineation and left ventricle opacification have been an approved indication for more than a decade. However, myocardial perfusion contrast ultrasound studies are still at the clinical trials stage. Blood pool contrast and perfusion in other tissues might be an easier indication to achieve: general blood pool ultrasound contrast is in wider use in Europe, Canada, Japan, and China. Targeted (molecular) contrast microbubbles will be the next generation of ultrasound imaging probes, capable of specific delineation of the areas of disease by adherence to molecular targets. The shell of targeted microbubbles (currently in the preclinical research and early stage clinical trials) is decorated with the ligands (antibodies, peptides or mimetics, hormones, carbohydrates) that ensure firm binding to the molecular markers of disease. PMID:23913363

  14. Degradation of X-ray contrast media compounds by combined ozone and ultrasound.

    PubMed

    Ning, Bo; Graham, Nigel J D; Lickiss, Paul D

    2007-11-01

    The aqueous degradation of iodinated X-ray contrast media (ICM) by the combination of ozone and ultrasound has been studied. Experiments were conducted at a constant ultrasound frequency of 20 kHz, at five power densities up to 0.235 W/mL, and various ozone centrations. In experiments involving dissolved ozone in solution, the addition of ultrasound significantly decreased the oxidation performance of the dissolved ozone, while the combination of dissolved oxygen and ultrasound gave a greater oxidation performance than ultrasound alone. However, the combination of gaseous ozone and ultrasound was found to give a higher degree of compound degradation than either ozone or ultrasound alone. In the experiments with final effluent, the degradation of ICM compounds by gaseous ozone and ultrasound was found to depend on the ozone dose applied. The degradation of ICM compounds in final effluent was modeled, which was found to moderately overestimate the observed compound degradation.

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

    NASA Astrophysics Data System (ADS)

    Bader, Kenneth B.; Holland, Christy K.

    2013-01-01

    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 ICAV = Pr/f (where Pr 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.

  16. Nanomaterials incorporated ultrasound contrast agents for cancer theranostics.

    PubMed

    Fu, Lei; Ke, Heng-Te

    2016-09-01

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

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

    PubMed

    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.

  18. Nanomaterials incorporated ultrasound contrast agents for cancer theranostics

    PubMed Central

    Fu, Lei; Ke, Heng-Te

    2016-01-01

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

  19. Contrast-enhanced ultrasound in ovarian tumors – diagnostic parameters: method presentation and initial experience

    PubMed Central

    MAXIM, ANITA-ROXANA; BADEA, RADU; TAMAS, ATILLA; TRAILA, ALEXANDRU

    2013-01-01

    The aim of this paper is to discuss and illustrate the use of contrast-enhanced ultrasound in evaluating ovarian tumors compared to conventional ultrasound, Doppler ultrasound and the histopathological analysis and suggest how this technique may best be used to distinguish benign from malignant ovarian masses. We present the method and initial experience of our center by analyzing the parameters used in contrast-enhanced ultrasound in 6 patients with ovarian tumors of uncertain etiology. For examination we used a Siemens ultrasound machine with dedicated contrast software and the contrast agent SonoVue, Bracco. The patients underwent conventional ultrasound, Doppler ultrasound and i.v. administration of the contrast agent. The parameters studied were: inflow of contrast (rise time), time to peak enhancement, mean transit time. The series of patients is part of an extensive prospective PhD study aimed at elaborating a differential diagnosis protocol for benign versus malignant ovarian tumors, by validating specific parameters for contrast-enhanced ultrasound. Although the method is currently used with great success in gastroenterology, urology and senology, its validation in gynecology is still in the early phases. Taking into consideration that the method is minimally invasive and much less costly that CT/MRI imaging, demonstrating its utility in oncologic gynecology would be a big step in preoperative evaluation of these cases. PMID:26527912

  20. [An adaptive ultrasound sound speed optimization based on image contrast analysis].

    PubMed

    Li, Xiaoying; Liu, Dongquan

    2011-12-01

    In order to get real time ultrasound images with clear structure and improved contrast, an adaptive ultrasound sound speed optimization method based on image contrast analysis was investigated. It firstly introduced the dynamic beamforming of ultrasound system, as well as the definition of assumed system's sound speed and the true sound speed propagated in tissues the degrade image quality due to their mismatch was also discussed. After given the pixel gray level value based ultrasound image contrast ratio, the basic idea to precisely estimate the true sound speed for real time system sound speed was proposed. Algorithms have been verified both in tissue-mimicking phantoms with known sound speeds and in vivo ultrasound images, compared with other existing method. The testing results showed that this new method not only produced accurate sound speed for ultrasound image optimization, but also finely met the critical computation requirement for real time applications.

  1. Acoustic response of compliable microvessels containing ultrasound contrast agents.

    PubMed

    Qin, Shengping; Ferrara, Katherine W

    2006-10-21

    The existing models of the dynamics of ultrasound contrast agents (UCAs) have largely been focused on an UCA surrounded by an infinite liquid. Preliminary investigations of a microbubble's oscillation in a rigid tube have been performed using linear perturbation, under the assumption that the tube diameter is significantly larger than the UCA diameter. In the potential application of drug and gene delivery, it may be desirable to fragment the agent shell within small blood vessels and in some cases to rupture the vessel wall, releasing drugs and genes at the site. The effect of a compliant small blood vessel on the UCA's oscillation and the microvessel's acoustic response are unknown. The aim of this work is to propose a lumped-parameter model to study the interaction of a microbubble oscillation and compliable microvessels. Numerical results demonstrate that in the presence of UCAs, the transmural pressure through the blood vessel substantially increases and thus the vascular permeability is predicted to be enhanced. For a microbubble within an 8 to 40 microm vessel with a peak negative pressure of 0.1 MPa and a centre frequency of 1 MHz, small changes in the microbubble oscillation frequency and maximum diameter are observed. When the ultrasound pressure increases, strong nonlinear oscillation occurs, with an increased circumferential stress on the vessel. For a compliable vessel with a diameter equal to or greater than 8 microm, 0.2 MPa PNP at 1 MHz is predicted to be sufficient for microbubble fragmentation regardless of the vessel diameter; however, for a rigid vessel 0.5 MPa PNP at 1 MHz may not be sufficient to fragment the bubbles. For a centre frequency of 1 MHz, a peak negative pressure of 0.5 MPa is predicted to be sufficient to exceed the stress threshold for vascular rupture in a small (diameter less than 15 microm) compliant vessel. As the vessel or surrounding tissue becomes more rigid, the UCA oscillation and vessel dilation decrease; however the

  2. Acoustic response of compliable microvessels containing ultrasound contrast agents

    NASA Astrophysics Data System (ADS)

    Qin, Shengping; Ferrara, Katherine W.

    2006-10-01

    The existing models of the dynamics of ultrasound contrast agents (UCAs) have largely been focused on an UCA surrounded by an infinite liquid. Preliminary investigations of a microbubble's oscillation in a rigid tube have been performed using linear perturbation, under the assumption that the tube diameter is significantly larger than the UCA diameter. In the potential application of drug and gene delivery, it may be desirable to fragment the agent shell within small blood vessels and in some cases to rupture the vessel wall, releasing drugs and genes at the site. The effect of a compliant small blood vessel on the UCA's oscillation and the microvessel's acoustic response are unknown. The aim of this work is to propose a lumped-parameter model to study the interaction of a microbubble oscillation and compliable microvessels. Numerical results demonstrate that in the presence of UCAs, the transmural pressure through the blood vessel substantially increases and thus the vascular permeability is predicted to be enhanced. For a microbubble within an 8 to 40 µm vessel with a peak negative pressure of 0.1 MPa and a centre frequency of 1 MHz, small changes in the microbubble oscillation frequency and maximum diameter are observed. When the ultrasound pressure increases, strong nonlinear oscillation occurs, with an increased circumferential stress on the vessel. For a compliable vessel with a diameter equal to or greater than 8 µm, 0.2 MPa PNP at 1 MHz is predicted to be sufficient for microbubble fragmentation regardless of the vessel diameter; however, for a rigid vessel 0.5 MPa PNP at 1 MHz may not be sufficient to fragment the bubbles. For a centre frequency of 1 MHz, a peak negative pressure of 0.5 MPa is predicted to be sufficient to exceed the stress threshold for vascular rupture in a small (diameter less than 15 µm) compliant vessel. As the vessel or surrounding tissue becomes more rigid, the UCA oscillation and vessel dilation decrease; however the

  3. Acoustic response of compliable microvessels containing ultrasound contrast agents

    PubMed Central

    Qin, Shengping; Ferrara, Katherine W.

    2010-01-01

    The existing models of the dynamics of ultrasound contrast agents (UCAs) have largely been focused on an UCA surrounded by an infinite liquid. Preliminary investigations of a microbubble’s oscillation in a rigid tube have been performed using linear perturbation, under the assumption that the tube diameter is significantly larger than UCA size. In the potential application of drug and gene delivery, it may be desirable to fragment the agent shell within small blood vessels and in some cases to rupture the vessel wall, releasing drugs and genes at the site. The effect of a compliant small blood vessel on the UCA’s oscillation and the microvessel’s acoustic response are unknown. The aim of this work is to propose a lumped-parameter model to study the interaction of a microbubble oscillation and compliable microvessels. Numerical results demonstrate that in the presence of UCAs, the transmural pressure through the blood vessel substantially increases and thus the vascular permeability is predicted to be enhanced. For a microbubble within an 8 to 40 micron vessel with a peak negative pressure of 0.1MPa and a center frequency of 1MHz, small changes in the microbubble oscillation frequency and maximum diameter are observed. When the ultrasound pressure increases, strong nonlinear oscillation occurs, with an increased circumferential stress on the vessel. For a compliable vessel with the range of diameters considered in this work, 0.2 MPa PNP at 1 MHz is predicted to be sufficient for microbubble fragmentation regardless the vessel diameter, however, for a rigid vessel 0.5 MPa PNP at 1 MHz may not be sufficient to fragment the bubbles. For a center frequency of 1MHz, a peak negative pressure of 0.5 MPa is predicted to be sufficient to exceed the stress threshold for vascular rupture in a small (diameter less than 15 μm) compliant vessel. As the vessel or surrounding tissue becomes more rigid, the UCA oscillation and vessel dilation decrease, however the

  4. A preliminary evaluation of self-made nanobubble in contrast-enhanced ultrasound imaging

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    Nanoscale bubbles (nanobubbles) have been reported to improve contrast in tumor-targeted ultrasound imaging due to the enhanced permeation and retention effects at tumor vascular leaks. In this work, a self-made nanobubble ultrasound contrast agent was preliminarily characterized and evaluated in-vitro and in-vivo. Fundamental properties such as morphology appearance, size distribution, zeta potential, bubble concentration (bubble numbers per milliliter contrast agent suspension) and the stability of nanobubbles were assessed by light microscope and particle sizing analysis. Then the concentration intensity curve and time intensity curves (TICs) were acquired by ultrasound imaging experiment in-vitro. Finally, the contrast-enhanced ultrasonography was performed on rat to investigate the procedure of liver perfusion. The results showed that the nanobubbles had good shape and uniform distribution with the average diameter of 507.9 nm, polydispersity index (PDI) of 0.527, and zeta potential of -19.17 mV. Significant contrast enhancement was observed in in-vitro ultrasound imaging, demonstrating that the self-made nanobubbles can enhance the contrast effect of ultrasound imaging efficiently in-vitro. Slightly contrast enhancement was observed in in-vivo ultrasound imaging, indicating that the nanobubbles are not stable enough in-vivo. Future work will be focused on improving the ultrasonic imaging performance, stability, and antibody binding of the nanoscale ultrasound contrast agent.

  5. Ultrasound guided site specific gene delivery system using adenoviral vectors and commercial ultrasound contrast agents.

    PubMed

    Howard, Candace M; Forsberg, Flemming; Minimo, Corrado; Liu, Ji-Bin; Merton, Daniel A; Claudio, Pier Paolo

    2006-11-01

    We have evaluated if ultrasound imaging (US) and various commercially available contrast microbubbles can serve as a non-invasive systemically administered delivery vehicle for site-specific adenoviral-mediated gene transfer in vitro and in vivo. The contrast agents were tested for their ability to enclose and to protect an adenoviral vector carrying the GFP marker gene (Ad-GFP) into the microbubbles. We have also evaluated the ability of the innate immune system to inactivate free adenoviruses as well as unenclosed viruses adsorbed on the surface of the contrast agents and in turn the ability of the microbubbles to enclose and to protect the viral vectors from such agents. In vitro as well as in vivo, innate components of the immune system were able to serve as inactivating agents to clear free viral particles and unenclosed adenoviruses adsorbed on the microbubbles' surface. Systemic delivery of Ad-GFP enclosed into microbubbles in the tail vein of nude mice resulted in specific targeting of the GFP transgene. Both fluorescence microscopy and GFP immunohistochemistry demonstrated US guided specific transduction in the targeted cells only, with no uptake in either heart, lungs or liver using complement-pretreated Ad-GFP microbubbles. This approach enhances target specificity of US microbubble destruction as a delivery vehicle for viral-mediated gene transfer.

  6. Contrast-enhanced (endoscopic) ultrasound and endoscopic ultrasound elastography in gastrointestinal stromal tumors

    PubMed Central

    Ignee, Andre; Jenssen, Christian; Hocke, Michael; Dong, Yi; Wang, Wen-Ping; Cui, Xin-Wu; Woenckhaus, Matthias; Iordache, Sevastita; Saftoiu, Adrian; Schuessler, Gudrun; Dietrich, Christoph F.

    2017-01-01

    Background and Objectives: Gastrointestinal stromal tumors (GISTs) represent the largest group of subepithelial tumors (SET) of the upper gastrointestinal (GI) tract. They may show malignant behavior, in contrast to other SET. Endoscopic ultrasound (EUS) is frequently used to characterize SET. With the introduction of contrast-enhanced ultrasound (CEUS) into EUS (CE-EUS), distinct enhancement patterns can be detected. In the presented study, the characteristic features of CE-EUS in GIST are analyzed and compared with those of other SET. Materials and Methods: Consecutive patients from four centers with SET of the upper and middle GI tract were included and received endoscopic or transcutaneous CEUS. The results were compared with EUS-guided tissue acquisition, forceps biopsy, or surgical resection. Results: Forty-two out of 62 (68%) patients had SET of the stomach, 17/62 (27%) of the small intestine, 2/62 (3%) of the esophagus, and 1/62 (2%) extraintestinal. Eighty-one percent underwent surgery. Leiomyoma was found in 5/62 (8%) and GIST in 57/62 patients (92%). Thirty-nine out of 57 (68%) patients had GIST lesions in the stomach, 17/57 (30%) had GIST of the small intestine, and 1/57 (2%) patients had extraintestinal GISTs. GIST size was 62.6 ± 42.1 (16–200) mm. Hyperenhancement had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 98%, 100%, 100%, 93%, and 98% for the diagnosis of GIST. Fifty out of 57 patients with GIST (88%) showed avascular areas in the center of the lesions. Conclusion: CE-EUS and CEUS show hyperenhancement and avascular areas in a high percentage of GIST but not in leiomyoma. Thus, GIST and leiomyoma can be discriminated accurately. PMID:28218202

  7. Experimental characterization, comparison and image quality assessment of two ultrasound contrast agents: Optison and Definity

    NASA Astrophysics Data System (ADS)

    Hughes, Amy C.; Day, Steven W.; Linte, Cristian A.; Schwarz, Karl Q.

    2016-04-01

    Microbubble-based contrast agents are commonly used in ultrasound imaging to help differentiate the blood pool from the endocardial wall. It is essential to use an agent which produces high image intensity relative to the surrounding tissue, commonly referred to contrast effect. When exposed to ultrasound waves, microbubbles produce an intense backscatter signal in addition to the contrast produced by the fluctuating size of the microbubbles. However, over time, the microbubble concentration depletes, leading to reduced visual enhancement. The retention time associated with contrast effect varies according to the frequency and power level of the ultrasound wave, as well as the contrast agent used. The primary objective of this study was to investigate and identify the most appropriate image acquisition parameters that render optimal contrast effect for two intravenous contrast agents, Optison™ and Definity™. Several controlled in vitro experiments were conducted using an experimental apparatus that featured a perfused tissue-emulating phantom. A continuous flow of contrast agent was imaged using ultrasound at different frequencies and power levels, while a pulse wave Doppler device was used to monitor the concentration of the contrast agent solution. The contrast effect was determined based on the image intensity inside the flow pipe mimicking the blood-pool relative to the intensity of the surrounding phantom material mimicking cardiac tissue. To identify the combination of parameters that yielded optimal visualization for each contrast agent tested, the contrast effect was assessed at different microbubble concentrations and different ultrasound imaging frequencies and transmission power levels.

  8. Contrast-enhanced Ultrasound Imaging of Antiangiogenic Tumor Therapy.

    PubMed

    Klotz, Laura V; Clevert, Dirk-Andre; Scheckinger, Siiri; Strieth, Sebastian; Eichhorn, Martin E

    2015-05-01

    Anti-angiogenic treatment is a promising strategy for cancer therapy and is currently evaluated in clinical trials. The aim of the present study was to further investigate the effects of an anti-angiogenic therapy, inhibiting vascular endothelial growth factor (VEGF) and endothelial growth factor (EGF) using a tyrosine kinase inhibitor for blocking tumor angiogenesis and tumor progression in vivo. Experiments were performed using C57/Bl6 mice (25 ± 5 g of body weight (b.w.)) implanted with subcutaneous Lewis lung carcinoma (LLC-1). From day 7 till 21 after tumor cell implantation, animals (n=7 per group) were treated by monotherapy using ZD6474 (50 mg/kg b.w. per os (p.o.)) daily. A control group received only the solvent polysorbate 80. Using contrast enhanced ultrasound (CE-US) parameters of intra-tumoral microcirculation animals were examined 24 h after the last application of ZD6474. Moreover, subcutaneous tumor growth was measured over the whole therapy period. Finally, histological analyses were performed to analyze the functional vessel density in the tumor tissue. ZD6474 reduced tumor growth of LLC-1 in C57/Bl6 mice significantly. A significant difference of maximal signal intensity (ΔSImax) and area below the intensity time curve (AUC) after antiangiogenic therapy was recorded in the tumor center by CE-US. Vessel density after hematoxyline and eosin, as well as CD31, staining showed no significant difference in both groups. Anti-angiogenic effects can be quantitatively demonstrated using CE-US imaging, which represents the spreading of efficient vessels in the tumor tissue, especially in the tumor center. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. Application of ultrasound contrast in identification and diagnosis of ocular spaceoccupying lesions

    PubMed Central

    Yuan, Jia-Ying; Zhang, Jian-Hua; Tang, Chong; Zhao, Jing-Zhi; Pang, Chao; Ren, Xin-Chun; Zhu, Hong; Zhang, Yun-Tao

    2011-01-01

    AIM To analyze the application significance of ultrasound contrast agent in identification and diagnosis of ocular spaceoccupying lesions, and mainly analyze its advantages and problems. METHODS Thirty-two representative literatures about the application of ultrasound contrast agent in diagnosis of spaceoccupying lesions at home and abroad were collected after focused on sorting the literature reporting the application of ultrasound contrast diagnostic technology in the diagnosis and identification of ocular spaceoccupying lesions in recent years. Its advantages and problems were retrospectively analyzed, and reasonable assessment on existing problems was made and possible solutions to the problems were proposed. RESULTS As a new imaging diagnostic technique, the contrast-enhanced ultrasound, which can enhance the display of tumor microcirculation vessels and improve the tumor's ultrasound diagnostic capability, was analyzed. Through sorting and comprehensively analyzing the collected literatures, the positive rate of ocular spaceoccupying lesion diagnosis could be significantly improved with ultrasound contrast technology. Thus, the vascular perfusion in normal tissues and lesions was reflected objectively. According to the lesion's perfusion characteristics of the contrast agent plus with the performance features of two-dimensional ultrasound, the ocular spaceoccupying lesions can be accurately diagnosed, and this could provide clinicians with reliable research basis in this field. CONCLUSION Ultrasound contrast examination is a new testing method, and ultrasound contrast agent can significantly enhance the ultrasonic detection signal, clearly show the blood perfusion in vessels and tissues, increase the image contrast resolution, and improve the lesion's detection capability in the microcirculation perfusion level, especially its important value in the diagnosis of ocular tumor. PMID:22553676

  10. Fusion imaging of contrast-enhanced ultrasound and contrast-enhanced CT or MRI before radiofrequency ablation for liver cancers.

    PubMed

    Bo, Xiao-Wan; Xu, Hui-Xiong; Wang, Dan; Guo, Le-Hang; Sun, Li-Ping; Li, Xiao-Long; Zhao, Chong-Ke; He, Ya-Ping; Liu, Bo-Ji; Li, Dan-Dan; Zhang, Kun

    2016-11-01

    To investigate the usefulness of fusion imaging of contrast-enhanced ultrasound (CEUS) and CECT/CEMRI before percutaneous ultrasound-guided radiofrequency ablation (RFA) for liver cancers. 45 consecutive patients with 70 liver lesions were included between March 2013 and October 2015, and all the lesions were identified on CEMRI/CECT prior to inclusion in the study. Planning ultrasound for percutaneous RFA was performed using conventional ultrasound, ultrasound-CECT/CEMRI and CEUS and CECT/CEMRI fusion imaging during the same session. The numbers of the conspicuous lesions on ultrasound and fusion imaging were recorded. RFA was performed according to the results of fusion imaging. Complete response (CR) rate was calculated and the complications were recorded. On conventional ultrasound, 25 (35.7%) of the 70 lesions were conspicuous, whereas 45 (64.3%) were inconspicuous. Ultrasound-CECT/CEMRI fusion imaging detected additional 24 lesions thus increased the number of the conspicuous lesions to 49 (70.0%) (70.0% vs 35.7%; p < 0.001 in comparison with conventional ultrasound). With the use of CEUS and CECT/CEMRI fusion imaging, the number of the conspicuous lesions further increased to 67 (95.7%, 67/70) (95.7% vs 70.0%, 95.7% vs 35.7%; both p < 0.001 in comparison with ultrasound and ultrasound-CECT/CEMRI fusion imaging, respectively). With the assistance of CEUS and CECT/CEMRI fusion imaging, the confidence level of the operator for performing RFA improved significantly with regard to visualization of the target lesions (p = 0.001). The CR rate for RFA was 97.0% (64/66) in accordance to the CECT/CEMRI results 1 month later. No procedure-related deaths and major complications occurred during and after RFA. Fusion of CEUS and CECT/CEMRI improves the visualization of those inconspicuous lesions on conventional ultrasound. It also facilitates improvement in the RFA operators' confidence and CR of RFA. Advances in knowledge: CEUS and CECT/CEMRI fusion imaging

  11. Contrast-Enhanced Ultrasound Imaging for the Detection of Focused Ultrasound-Induced Blood-Brain Barrier Opening

    PubMed Central

    Fan, Ching-Hsiang; Lin, Wun-Hao; Ting, Chien-Yu; Chai, Wen-Yen; Yen, Tzu-Chen; Liu, Hao-Li; Yeh, Chih-Kuang

    2014-01-01

    The blood-brain barrier (BBB) can be transiently and locally opened by focused ultrasound (FUS) in the presence of microbubbles (MBs). Various imaging modalities and contrast agents have been used to monitor this process. Unfortunately, direct ultrasound imaging of BBB opening with MBs as contrast agent is not feasible, due to the inability of MBs to penetrate brain parenchyma. However, FUS-induced BBB opening is accompanied by changes in blood flow and perfusion, suggesting the possibility of perfusion-based ultrasound imaging. Here we evaluated the use of MB destruction-replenishment, which was originally developed for analysis of ultrasound perfusion kinetics, for verifying and quantifying FUS-induced BBB opening. MBs were intravenously injected and the BBB was disrupted by 2 MHz FUS with burst-tone exposure at 0.5-0.7 MPa. A perfusion kinetic map was estimated by MB destruction-replenishment time-intensity curve analysis. Our results showed that the scale and distribution of FUS-induced BBB opening could be determined at high resolution by ultrasound perfusion kinetic analysis. The accuracy and sensitivity of this approach was validated by dynamic contrast-enhanced MRI. Our successful demonstration of ultrasound imaging to monitor FUS-induced BBB opening provides a new approach to assess FUS-dependent brain drug delivery, with the benefit of high temporal resolution and convenient integration with the FUS device. PMID:25161701

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

    PubMed

    Paefgen, Vera; Doleschel, Dennis; Kiessling, Fabian

    2015-01-01

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

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

    PubMed Central

    Paefgen, Vera; Doleschel, Dennis; Kiessling, Fabian

    2015-01-01

    Ultrasound (US) is one of the most frequently used diagnostic methods. It is a non-invasive, comparably inexpensive imaging method with a broad spectrum of applications, which can be increased even more by using bubbles as contrast agents (CAs). There are various different types of bubbles: filled with different gases, composed of soft- or hard-shell materials, and ranging in size from nano- to micrometers. These intravascular CAs enable functional analyses, e.g., to acquire organ perfusion in real-time. Molecular analyses are achieved by coupling specific ligands to the bubbles’ shell, which bind to marker molecules in the area of interest. Bubbles can also be loaded with or attached to drugs, peptides or genes and can be destroyed by US pulses to locally release the entrapped agent. Recent studies show that US CAs are also valuable tools in hyperthermia-induced ablation therapy of tumors, or can increase cellular uptake of locally released drugs by enhancing membrane permeability. This review summarizes important steps in the development of US CAs and introduces the current clinical applications of contrast-enhanced US. Additionally, an overview of the recent developments in US probe design for functional and molecular diagnosis as well as for drug delivery is given. PMID:26441654

  14. Voiding urosonography: Contrast-enhanced ultrasound cystography to diagnose vesico-ureteric reflux: A pilot study.

    PubMed

    Babu, Ramesh; Gopinath, Vinu; Sai, Venkata

    2015-01-01

    We report two children with hydronephrosis, in whom we have utilized voiding urosonography (VUS) in the evaluation of vesico-ureteric reflux. With wider availability of ultrasound contrast agents and high-end ultrasound machines, VUS is likely to become a popular tool to diagnose or exclude VUR.

  15. Stochastic explanation of speckle contrast detection in ultrasound-modulated optical tomography.

    PubMed

    Zemp, Roger; Sakadzić, Sava; Wang, Lihong V

    2006-06-01

    Ultrasound-modulated optical tomography is an imaging technique that detects ultrasonically tagged light in optically turbid media to obtain images with optical contrast and ultrasonic spatial resolution. A CCD-camera-based speckle contrast detection scheme has been introduced previously to detect modulated light emerging from the ultrasonic sample volume. Differences in speckle contrast were experimentally observed when ultrasound was applied compared to when it was not. In this paper we provide an analytic explanation for this phenomenon and connect speckle statistics with ultrasonic field parameters. The theory predicts that speckle contrast changes linearly with applied acoustic intensity. This prediction is experimentally validated for both 1 and ultrasound. Signal dependence on ultrasound frequency is discussed.

  16. Quantitative measurement of ultrasound pressure field by optical phase contrast method and acoustic holography

    NASA Astrophysics Data System (ADS)

    Oyama, Seiji; Yasuda, Jun; Hanayama, Hiroki; Yoshizawa, Shin; Umemura, Shin-ichiro

    2016-07-01

    A fast and accurate measurement of an ultrasound field with various exposure sequences is necessary to ensure the efficacy and safety of various ultrasound applications in medicine. The most common method used to measure an ultrasound pressure field, that is, hydrophone scanning, requires a long scanning time and potentially disturbs the field. This may limit the efficiency of developing applications of ultrasound. In this study, an optical phase contrast method enabling fast and noninterfering measurements is proposed. In this method, the modulated phase of light caused by the focused ultrasound pressure field is measured. Then, a computed tomography (CT) algorithm used to quantitatively reconstruct a three-dimensional (3D) pressure field is applied. For a high-intensity focused ultrasound field, a new approach that combines the optical phase contrast method and acoustic holography was attempted. First, the optical measurement of focused ultrasound was rapidly performed over the field near a transducer. Second, the nonlinear propagation of the measured ultrasound was simulated. The result of the new approach agreed well with that of the measurement using a hydrophone and was improved from that of the phase contrast method alone with phase unwrapping.

  17. Ultrasound molecular imaging of ovarian cancer with CA-125 targeted nanobubble contrast agents.

    PubMed

    Gao, Yong; Hernandez, Christopher; Yuan, Hai-Xia; Lilly, Jacob; Kota, Pavan; Zhou, Haoyan; Wu, Hanping; Exner, Agata A

    2017-06-09

    Ultrasound is frequently utilized in diagnosis of gynecologic malignancies such as ovarian cancer. Because epithelial ovarian cancer (EOC) is often characterized by overexpression of cancer antigen 125 (CA-125), ultrasound contrast agents able to target this molecular signature could be a promising complementary strategy. In this work, we demonstrate application of CA-125-targeted echogenic lipid and surfactant-stabilized nanobubbles imaged with standard clinical contrast harmonic ultrasound for imaging of CA-125 positive OVCAR-3 tumors in mice. Surface functionalization of the nanobubbles with a CA-125 antibody achieved rapid significantly (P < 0.05) enhanced tumor accumulation, higher peak ultrasound signal intensity and slower wash out rates in OVCAR-3 tumors compared to CA-125 negative SKOV-3 tumors. Targeted nanobubbles also exhibited increased tumor retention and prolonged echogenicity compared to untargeted nanobubbles. Data suggest that ultrasound molecular imaging using CA-125 antibody-conjugated nanobubbles may contribute to improved diagnosis of EOC. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Constrained Adaptive Beamforming for Improved Contrast in Breast Ultrasound

    DTIC Science & Technology

    2005-06-01

    led us to utilize a recently proposed method, Spatial Processing Optimized and Constrained ( SPOC ). In initial simulations this method not only...6 Review of the Adaptive Beamforming Literature ................... 7 SPOC Progress...given the parameters of in vivo ultrasound imaging. SPOC Progress: Most of the Adaptive Beamforming algorithms previously described fail when applied to

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  20. Insonation frequency selection may assist detection and therapeutic delivery of targeted ultrasound contrast agents.

    PubMed

    Payne, Edward; Ooi, Andrew; Manasseh, Richard

    2011-02-01

    Ultrasound-targeted drug delivery relies on the unique nature of ultrasound contrast agents--they are microbubbles that respond strongly to ultrasound. Intravenously injected microbubbles are smaller than a blood cell. By increasing the ultrasound power, the bubbles can be ruptured at the targeted endothelial wall, locally releasing any molecules in the bubble shell. Furthermore, ultrasound-activated microbubbles are known to cause sonoporation--the process by which ultrasound drives molecules through cellular membranes. However, techniques are required to selectively detect and rupture only those microbubbles on target walls. Experiments are presented on the behaviour of microbubbles on walls. For accuracy, imaging measurements are made on model microbubbles larger than contrast agents. Bubble size was varied and the resonant frequency peak determined. Microbubbles on walls have a shifted frequency in good agreement with theory: a 20-25% downshift from the frequency when far from walls. Effects other than the presence of the wall account for less than 5% of the shift. Theory predicts the frequency downshift should be sustained for actual contrast-agent sized bubbles. The effect of real, compliant cell walls requires investigation. An appropriate downshift in the applied ultrasound frequency could selectively tune gene or drug delivery. To make this feasible, it may be necessary to manufacture monodispersed microbubbles.

  1. Application of contrast-enhanced ultrasound after liver transplantation: Current status and perspectives

    PubMed Central

    Ren, Jie; Wu, Tao; Zheng, Bo-Wen; Tan, Ying-Yi; Zheng, Rong-Qin; Chen, Gui-Hua

    2016-01-01

    Liver transplantation is an effective treatment for patients with end-stage liver disease. Accurate imaging evaluation of the transplanted patient is critical for ensuring that the limited donor liver is functioning appropriately. Ultrasound contrast agents (UCAs), in combination with contrast-specific imaging techniques, are increasingly accepted in clinical use for the assessment of the hepatic vasculature, bile ducts and liver parenchyma in pre-, intra- and post-transplant patients. We describe UCAs, their technical requirements, the recommended clinical indications, image interpretation and the limitations for contrast-enhanced ultrasound applications in liver transplantation. PMID:26819526

  2. Effects of dissolved gases and an echo contrast agent on ultrasound mediated in vitro gene transfection.

    PubMed

    Ogawa, Ryohei; Kondo, Takashi; Honda, Hidemi; Zhao, Qing Li; Fukuda, Shigekazu; Riesz, Peter

    2002-09-01

    The effects of acoustic cavitation on in vitro transfection by ultrasound were investigated. HeLa cells were exposed to 1.0 MHz continuous ultrasound in culture media containing the luciferase gene. Transfection efficiency was elevated when an echo contrast agent, Levovist was added or air was dissolved in the medium. When cells were sonicated in medium saturated with Ar, N2 or N2O which have different gamma values (Cp/Cv), or were saturated with He, Ar or Ne with different thermal conductivities, the effectiveness for the dissolved gases in the ultrasound mediated transfection was Ar > N2 > N2O or Ar > Ne > He, respectively. When free radical formation in water by ultrasound was monitored as a measure of inertial cavitation, it was similarly affected by dissolved gases. These results indicate that the efficiency of ultrasound mediated transfection was significantly affected either by occurrence of or by modification of inertial cavitation due to various gases.

  3. Encapsulated microbubbles and echogenic liposomes for contrast ultrasound imaging and targeted drug delivery

    PubMed Central

    Paul, Shirshendu; Nahire, Rahul; Mallik, Sanku; Sarkar, Kausik

    2014-01-01

    Micron- to nanometer-sized ultrasound agents, like encapsulated microbubbles and echogenic liposomes, are being developed for diagnostic imaging and ultrasound mediated drug/gene delivery. This review provides an overview of the current state of the art of the mathematical models of the acoustic behavior of ultrasound contrast microbubbles. We also present a review of the in vitro experimental characterization of the acoustic properties of microbubble based contrast agents undertaken in our laboratory. The hierarchical two-pronged approach of modeling contrast agents we developed is demonstrated for a lipid coated (Sonazoid™) and a polymer shelled (poly D-L-lactic acid) contrast microbubbles. The acoustic and drug release properties of the newly developed echogenic liposomes are discussed for their use as simultaneous imaging and drug/gene delivery agents. Although echogenicity is conclusively demonstrated in experiments, its physical mechanisms remain uncertain. Addressing questions raised here will accelerate further development and eventual clinical approval of these novel technologies. PMID:26097272

  4. Adaptive Clutter Demodulation for Non-Contrast Ultrasound Perfusion Imaging.

    PubMed

    Tierney, Jaime; Coolbaugh, Crystal; Towse, Theodore; Byram, Brett

    2017-09-01

    Conventional Doppler ultrasound is useful for visualizing fast blood flow in large resolvable vessels. However, frame rate and tissue clutter caused by movement of the patient or sonographer make visualizing slow flow with ultrasound difficult. Patient and sonographer motion causes spectral broadening of the clutter signal, which limits ultrasound's sensitivity to velocities greater than 5-10 mm/s for typical clinical imaging frequencies. To address this, we propose a clutter filtering technique that may increase the sensitivity of Doppler measurements to at least as low as 0.52 mm/s. The proposed technique uses plane wave imaging and an adaptive frequency and amplitude demodulation scheme to decrease the bandwidth of tissue clutter. To test the performance of the adaptive demodulation method at suppressing tissue clutter bandwidths due to sonographer hand motion alone, six volunteer subjects acquired data from a stationary phantom. Additionally, to test in vivo feasibility, arterial occlusion and muscle contraction studies were performed to assess the efficiency of the proposed filter at preserving signals from blood velocities 2 mm/s or greater at a 7.8 MHz center frequency. The hand motion study resulted in initial average bandwidths of 175 Hz (8.60mm/s), which were decreased to 10.5 Hz (0.52 mm/s) at -60 dB using our approach. The in vivo power Doppler studies resulted in 4.73 dB and 4.80 dB dynamic ranges of the blood flow with the proposed filter and 0.15 dB and 0.16 dB dynamic ranges of the blood flow with a conventional 50 Hz high-pass filter for the occlusion and contraction studies, respectively.

  5. Breast contrast-enhanced ultrasound: is a scoring system feasible? A preliminary study in China.

    PubMed

    Xiao, Xiaoyun; Ou, Bing; Yang, Haiyun; Wu, Huan; Luo, Baoming

    2014-01-01

    Although many studies about breast contrast-enhanced ultrasound had been conducted, clear diagnostic criteria for evaluating enhancement patterns are still lacking. This study aims to identify significant indicators for breast contrast-enhanced ultrasound and to establish an initial scoring system. Totally 839 patients were included in the study. This study was divided into two parts. 364 patients were included in part 1 while 475 in part 2. Conventional ultrasound and contrast-enhanced ultrasound were used to examine each lesion. Only the cases in part 2 were also examined by elastography. In part 1, Logistic regression analysis was performed to predict significant variables. A 5-point scoring system was developed based on the results. In part 2, the scoring system was used to evaluate all the breast lesions. To evaluate the diagnostic efficacy of the new scoring system, it was compared with the system established for elastography and conventional ultrasound (BI-RADS). Three independent variables, namely, lesion scope, margin, and shape were selected in the final step of the logistic regression analysis in part 1. In part 2, the area under the ROC (receiver operating characteristic) curve for the contrast-enhanced scoring system was 0.912. The difference in the diagnostic capabilities of the contrast-enhanced scoring system and elastography was not statistically significant (P = 0.17). The difference in the diagnostic capabilities of the contrast-enhanced scoring system and BI-RADS was statistically significant (P<0.001). The contrast-enhanced patterns of benign and malignant breast tumors are different. The application of a 5-point scoring system for contrast-enhanced ultrasound is clinically promising.

  6. Breast Contrast-Enhanced Ultrasound: Is a Scoring System Feasible? ----A Preliminary Study in China

    PubMed Central

    Xiao, Xiaoyun; Ou, Bing; Yang, Haiyun; Wu, Huan; Luo, Baoming

    2014-01-01

    Objectives Although many studies about breast contrast-enhanced ultrasound had been conducted, clear diagnostic criteria for evaluating enhancement patterns are still lacking. This study aims to identify significant indicators for breast contrast-enhanced ultrasound and to establish an initial scoring system. Materials and Methods Totally 839 patients were included in the study. This study was divided into two parts. 364 patients were included in part 1 while 475 in part 2. Conventional ultrasound and contrast-enhanced ultrasound were used to examine each lesion. Only the cases in part 2 were also examined by elastography. In part 1, Logistic regression analysis was performed to predict significant variables. A 5-point scoring system was developed based on the results. In part 2, the scoring system was used to evaluate all the breast lesions. To evaluate the diagnostic efficacy of the new scoring system, it was compared with the system established for elastography and conventional ultrasound (BI-RADS). Results Three independent variables, namely, lesion scope, margin, and shape were selected in the final step of the logistic regression analysis in part 1. In part 2, the area under the ROC (receiver operating characteristic) curve for the contrast-enhanced scoring system was 0.912. The difference in the diagnostic capabilities of the contrast-enhanced scoring system and elastography was not statistically significant (P = 0.17). The difference in the diagnostic capabilities of the contrast-enhanced scoring system and BI-RADS was statistically significant (P<0.001). Conclusions The contrast-enhanced patterns of benign and malignant breast tumors are different. The application of a 5-point scoring system for contrast-enhanced ultrasound is clinically promising. PMID:25133534

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

    PubMed

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

    2015-04-01

    The goal of the work described here was to assess the safety profile of intravenous second-generation ultrasound contrast agents (UCAs) containing sulfur hexafluoride in pediatric contrast-enhanced ultrasound. Between 2010 and 2013, a total of 167 examinations were performed in 137 children referred by the Oncology Department. Approval by an Independent Ethical Review Board on Scientific Research for the intravenous use of an UCA containing sulfur hexafluoride in children with oncologic diseases was obtained. Consent for UCA administration was acquired from the parents or legal guardians. Severe anaphylactic reaction was observed in 0.6% (n = 1). No other adverse events during or after intravenous administration of contrast were observed in the examined group (no changes in heart rate and rhythm, blood pressure, oxygen saturation or respiratory rate). There were no reports of subjective flushing, nausea, transient headaches or altered taste. Although second-generation ultrasound contrast agents are considered potentially safe, all investigators should be prepared for the development of adverse reactions and have provisions in place for all pediatric intravenous contrast-enhanced ultrasound examinations. More multicenter studies are essential to determination of an accurate UCA safety profile. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  8. Application of ultrasound microbubble contrast technology in ophthalmic targeted therapy: literature analysis.

    PubMed

    Yuan, Jia-Ying; Zhang, Jian-Hua; Tang, Chong; Zhu, Hong; Xie, Hua; Gao, Shuan-Jie

    2011-01-01

    To analyze the application of microbubble contrast technology in the treatment of ophthalmic diseases, mainly analyzing its advantages and existing problems. A total of 30 representative literatures about the application of ultrasound contrast agent in gene targeted therapy at home and abroad were collected, and focusing on sorting out the literature reporting the treatment of ophthalmic diseases with microbubble contrast technology in recent years, then recalling its advantages and problems, finally making reasonable assessment on existing problems and proposing possible solutions to the problems. DUE TO ITS UNIQUE SAFETY AND EFFICACY, THE TREATMENT OF OPHTHALMIC DISEASES WITH MICROBUBBLE CONTRAST TECHNOLOGY HAS INCREASINGLY DRAWN THE ATTENTION OF CLINICIANS, BUT TWO RELEVANT ISSUES SHOULD BE CONSIDERED: first, the nature of contrast agent and the choice of corresponding ultrasound parameters; second, relative incidence of tissue bleeding, intravascular hemolysis, moderate or severe allergy as well as other side effects. Microbubble may become the carrier of targeted therapy, and as a kind of new non-invasive delivery system, the ultrasound contrast agent has broad application prospects, but its application in ophthalmic research is still in its initial stage and the safety of contrast-enhanced ultrasound still needs further study.

  9. Quantitative Contrast-Enhanced Ultrasound Parameters in Crohn Disease: Their Role in Disease Activity Determination With Ultrasound.

    PubMed

    Medellin-Kowalewski, Alexandra; Wilkens, Rune; Wilson, Alexandra; Ruan, Ji; Wilson, Stephanie R

    2016-01-01

    The primary objective of our study was to examine the association between contrast-enhanced ultrasound (CEUS) parameters and established gray-scale ultrasound with color Doppler imaging (CDI) for the determination of disease activity in patients with Crohn disease. Our secondary objective was to develop quantitative time-signal intensity curve thresholds for disease activity. One hundred twenty-seven patients with Crohn disease underwent ultrasound with CDI and CEUS. Reviewers graded wall thickness, inflammatory fat, and mural blood flow as showing remission or inflammation (mild, moderate, or severe). If both gray-scale ultrasound and CDI predicted equal levels of disease activity, the studies were considered concordant. If ultrasound images suggested active disease not supported by CDI findings, the ultrasound results for disease activity were indeterminate. Time-signal intensity curves from CEUS were acquired with calculation of peak enhancement (PE), and AUCs. Interobserver variation and associations between PE and ultrasound parameters were examined. Multiclass ROC analysis was used to develop CEUS thresholds for activity. Ninety-six (76%) studies were concordant, 19 of which showed severe disease, and 31 (24%) studies were indeterminate. Kappa analyses revealed good interobserver agreement on grades for CDI (κ = 0.76) and ultrasound (κ = 0.80) assessments. PE values on CEUS and wall thickness showed good association with the Spearman rank correlation coefficient for the entire population (ρ = 0.62, p < 0.01) and for the concordant group (ρ = 0.70, p < 0.01). Multiclass ROC analyses of the concordant group using wall thickness alone as the reference standard showed cutoff points of 18.2 dB for differentiating mild versus moderate activity (sensitivity, 89.0% and specificity, 87.0%) and 23.0 dB for differentiating moderate versus severe (sensitivity, 90% and specificity, 86.8%). Almost identical cutoff points were observed when using ultrasound global

  10. Photoacoustic and ultrasound imaging using dual contrast perfluorocarbon nanodroplets triggered by laser pulses at 1064 nm.

    PubMed

    Hannah, Alexander S; VanderLaan, Donald; Chen, Yun-Sheng; Emelianov, Stanislav Y

    2014-09-01

    Recently, a dual photoacoustic and ultrasound contrast agent-named photoacoustic nanodroplet-has been introduced. Photoacoustic nanodroplets consist of a perfluorocarbon core, surfactant shell, and encapsulated photoabsorber. Upon pulsed laser irradiation the perfluorocarbon converts to gas, inducing a photoacoustic signal from vaporization and subsequent ultrasound contrast from the resulting gas microbubbles. In this work we synthesize nanodroplets which encapsulate gold nanorods with a peak absorption near 1064 nm. Such nanodroplets are optimal for extended photoacoustic imaging depth and contrast, safety and system cost. We characterized the nanodroplets for optical absorption, image contrast and vaporization threshold. We then imaged the particles in an ex vivo porcine tissue sample, reporting contrast enhancement in a biological environment. These 1064 nm triggerable photoacoustic nanodroplets are a robust biomedical tool to enhance image contrast at clinically relevant depths.

  11. Intraoperative high-resolution ultrasound and contrast-enhanced ultrasound of peripheral nerve tumors and tumorlike lesions.

    PubMed

    Pedro, Maria Teresa; Antoniadis, Gregor; Scheuerle, Angelika; Pham, Mirko; Wirtz, Christian Rainer; Koenig, Ralph W

    2015-09-01

    The diagnostic workup and surgical therapy for peripheral nerve tumors and tumorlike lesions are challenging. Magnetic resonance imaging is the standard diagnostic tool in the preoperative workup. However, even with advanced pulse sequences such as diffusion tensor imaging for MR neurography, the ability to differentiate tumor entities based on histological features remains limited. In particular, rare tumor entities different from schwannomas and neurofibromas are difficult to anticipate before surgical exploration and histological confirmation. High-resolution ultrasound (HRU) has become another important tool in the preoperative evaluation of peripheral nerves. Ongoing software and technical developments with transducers of up to 17-18 MHz enable high spatial resolution with tissue-differentiating properties. Unfortunately, high-frequency ultrasound provides low tissue penetration. The authors developed a setting in which intraoperative HRU was used and in which the direct sterile contact between the ultrasound transducer and the surgically exposed nerve pathology was enabled to increase structural resolution and contrast. In a case-guided fashion, the authors report the sonographic characteristics of rare tumor entities shown by intraoperative HRU and contrast-enhanced ultrasound.

  12. Contrast-enhanced endobronchial ultrasound: Potential value of a new method

    PubMed Central

    Dietrich, Christoph F.

    2017-01-01

    Endobronchial ultrasound (EBUS) has gained importance for mediastinal lymph node staging. Contrast-enhanced EBUS is so far not a discussed technique including contrast-enhanced high mechanical index (MI)-EBUS and potentially contrast-enhanced low MI-EBUS. Possible use could include characterization of mediastinal lymph nodes for better selection of biopsies, differential diagnosis of the primary tumor, and evaluation of thrombosis or tumor in vein infiltration. PMID:28218200

  13. The Expanding Role of Contrast-Enhanced Endoscopic Ultrasound in Pancreatobiliary Disease

    PubMed Central

    Choi, Jun-Ho; Seo, Dong Wan

    2015-01-01

    Since its introduction into clinical practice in the 1980s, endoscopic ultrasound (EUS) has been described as a good imaging modality for the diagnosis of pancreatobiliary diseases. However, differential diagnosis of certain lesions based only on B-mode ultrasound images can be challenging. Clinical use of ultrasound contrast agents has expanded the utility of EUS from that of detection to characterization of pancreatobiliary lesions based on the enhancement features of contrast-enhanced EUS (CE-EUS). Current low mechanical index techniques for CE-EUS using second-generation contrast agents have a number of distinct advantages over conventional diagnostic modalities in evaluating pancreatobiliary lesions, including real-time assessment of perfusion pattern, availability, and the absence of exposure to radiation. This article describes the technical aspects of CE-EUS and reviews the expanding indications in pancreatobiliary diseases and further development of this technique. PMID:26503571

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

    PubMed Central

    Ilunga-Mbuyamba, Elisee; Avina-Cervantes, Juan Gabriel; Lindner, Dirk; Cruz-Aceves, Ivan; Arlt, Felix; Chalopin, Claire

    2016-01-01

    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-iCEUSstart) and after (3D-iCEUSend) tumor resection. Based on rigid registration techniques, a preselected vascular segment in cT1MR is searched in 3D-iCEUSstart and 3D-iCEUSend 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. PMID:27070610

  15. Development and evaluation of a novel VEGFR2-targeted nanoscale ultrasound contrast agents

    NASA Astrophysics Data System (ADS)

    Yu, Houqiang; Li, Chunfang; He, Xiaoling; Zhou, Qibing; Ding, Mingyue

    2016-04-01

    Recent literatures have reported that the targeted nanoscale ultrasound contrast agents are becoming more and more important in medical application, like ultrasound imaging, detection of perfusion, drug delivery and molecular imaging and so on. In this study, we fabricated an uniform nanoscale bubbles (257 nm with the polydispersity index of 0.458) by incorporation of antibody targeted to vascular endothelial growth factor receptor 2 (VEGFR2) into the nanobubbles membrane by using avidin-biotin interaction. Some fundamental characterizations such as nanobubble suspension, surface morphology, particle size distribution and zeta potential were investigated. The concentration and time-intensity curves (TICs) were obtained with a self-made ultrasound experimental setup in vitro evaluation. In addition, in order to evaluate the contrast enhancement ability and the potential tumor-targeted ability in vivo, normal Wistar rats and nude female BALB/c mice were intravascular administration of the nanobubbles via tail vein injection, respectively. Significant contrast enhancement of ultrasound imaging within liver and tumor were visualized. These experiments demonstrated that the targeted nanobubbles is efficient in ultrasound molecular imaging by enhancement of the contrast effect and have potential capacity for targeted tumor diagnosis and therapy in the future.

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

    PubMed

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

    2013-05-01

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

  17. Attenuation Correction and Normalisation for Quantification of Contrast Enhancement in Ultrasound Images of Carotid Arteries.

    PubMed

    Cheung, Wing Keung; Gujral, Dorothy M; Shah, Benoy N; Chahal, Navtej S; Bhattacharyya, Sanjeev; Cosgrove, David O; Eckersley, Robert J; Harrington, Kevin J; Senior, Roxy; Nutting, Christopher M; Tang, Meng-Xing

    2015-07-01

    An automated attenuation correction and normalisation algorithm was developed to improve the quantification of contrast enhancement in ultrasound images of carotid arteries. The algorithm first corrects attenuation artefact and normalises intensity within the contrast agent-filled lumen and then extends the correction and normalisation to regions beyond the lumen. The algorithm was first validated on phantoms consisting of contrast agent-filled vessels embedded in tissue-mimicking materials of known attenuation. It was subsequently applied to in vivo contrast-enhanced ultrasound (CEUS) images of human carotid arteries. Both in vitro and in vivo results indicated significant reduction in the shadowing artefact and improved homogeneity within the carotid lumens after the correction. The error in quantification of microbubble contrast enhancement caused by attenuation on phantoms was reduced from 55% to 5% on average. In conclusion, the proposed method exhibited great potential in reducing attenuation artefact and improving quantification in contrast-enhanced ultrasound of carotid arteries. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  18. Intraoperative ultrasound with contrast medium in resective pancreatic surgery: a pilot study.

    PubMed

    Spinelli, Antonino; Del Fabbro, Daniele; Sacchi, Matteo; Zerbi, Alessandro; Torzilli, Guido; Lutman, Fabio R; Laghi, Luigi; Malesci, Alberto; Montorsi, Marco

    2011-11-01

    The introduction of contrast-enhanced ultrasound has been a major innovation in liver and pancreatic imaging. Previous studies have validated its intraoperative use during liver surgery, while there is a lack of data regarding its use during pancreatic surgery. The purpose of the present study was to prospectively evaluate the possible role of contrast-enhanced intraoperative ultrasound (CEIOUS) during resective pancreatic surgery for primary lesion characterization and intraoperative staging. Thirty-four patients (70% males, mean age 67.9 years) were selected for pancreatic surgery between October 2006 and July 2009. All patients underwent intraoperative ultrasound with intravenous injection of 4.8 mL sulfur-hexafluoride microbubbles. Location of the primary tumor, relation to the main vessels, contrast medium uptake modalities, presence of liver metastases, and multifocal pancreatic involvement were evaluated. The majority of operations were pancreatoduodenectomies (70.6%) performed for pancreatic ductal adenocarcinoma (64.7%). Additional lesions were detected by ultrasound in six patients (17.6%: liver metastases in four patients, a hemangioma in one patient, and a further pancreatic lesion in one patient). In five of these patients (5/34, 14.7%) surgical management was modified by these findings. All these new findings were diagnosed before injection of contrast medium, except for a metastasis from a neuroendocrine tumor; the characterization of the hemangioma was possible only after contrast injection. Intraoperative findings regarding location of primary tumor, relation to the main vessels, and lesion characterization did not differ from those obtained with preoperative imaging. In our experience intraoperative ultrasound is a valid technique for intraoperative staging prior to pancreatic resection; it is unclear whether, in pancreatic surgery, the addition of contrast enhancement adds any benefit to traditional intraoperative ultrasound.

  19. Quantitative assessment of placental perfusion by contrast-enhanced ultrasound in macaques and human subjects.

    PubMed

    Roberts, Victoria H J; Lo, Jamie O; Salati, Jennifer A; Lewandowski, Katherine S; Lindner, Jonathan R; Morgan, Terry K; Frias, Antonio E

    2016-03-01

    The uteroplacental vascular supply is a critical determinant of placental function and fetal growth. Current methods for the in vivo assessment of placental blood flow are limited. We demonstrate the feasibility of the use of contrast-enhanced ultrasound imaging to visualize and quantify perfusion kinetics in the intervillous space of the primate placenta. Pregnant Japanese macaques were studied at mid second trimester and in the early third trimester. Markers of injury were assessed in placenta samples from animals with or without contrast-enhanced ultrasound exposure (n = 6/group). Human subjects were recruited immediately before scheduled first-trimester pregnancy termination. All studies were performed with maternal intravenous infusion of lipid-shelled octofluoropropane microbubbles with image acquisition with a multipulse contrast-specific algorithm with destruction-replenishment analysis of signal intensity for assessment of perfusion. In macaques, the rate of perfusion in the intervillous space was increased with advancing gestation. No evidence of microvascular hemorrhage or acute inflammation was found in placental villous tissue and expression levels of caspase-3, nitrotyrosine and heat shock protein 70 as markers of apoptosis, nitrative, and oxidative stress, respectively, were unchanged by contrast-enhanced ultrasound exposure. In humans, placental perfusion was visualized at 11 weeks gestation, and preliminary data reveal regional differences in intervillous space perfusion within an individual placenta. By electron microscopy, we demonstrate no evidence of ultrastructure damage to the microvilli on the syncytiotrophoblast after first-trimester ultrasound studies. Use of contrast-enhanced ultrasound did not result in placental structural damage and was able to identify intervillous space perfusion rate differences within a placenta. Contrast-enhanced ultrasound imaging may offer a safe clinical tool for the identification of pregnancies that are at

  20. Stability analysis of ultrasound thick-shell contrast agents

    PubMed Central

    Lu, Xiaozhen; Chahine, Georges L.; Hsiao, Chao-Tsung

    2012-01-01

    The stability of thick shell encapsulated bubbles is studied analytically. 3-D small perturbations are introduced to the spherical oscillations of a contrast agent bubble in response to a sinusoidal acoustic field with different amplitudes of excitation. The equations of the perturbation amplitudes are derived using asymptotic expansions and linear stability analysis is then applied to the resulting differential equations. The stability of the encapsulated microbubbles to nonspherical small perturbations is examined by solving an eigenvalue problem. The approach then identifies the fastest growing perturbations which could lead to the breakup of the encapsulated microbubble or contrast agent. PMID:22280568

  1. Applications of contrast-enhanced harmonic endoscopic ultrasound on biliary, focal liver lesions and vascular diseases

    PubMed Central

    Choi, Jun-Ho; Seo, Dong-Wan

    2017-01-01

    Over the last decade, the clinical applications of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) have increased steadily. The development of second-generation ultrasound contrast agents has allowed superior visualization of the microvasculature and tissue perfusion of the target lesion. This methodology has proven useful in the differential diagnosis of solid pancreatic masses and lymph nodes. In addition, the applicability of CH-EUS has expanded to nonpancreas structures such as biliary, focal liver lesions, and vascular disease. This article focuses primarily on the novel applications of CH-EUS in biliary tract and visceral vascular diseases. PMID:28218196

  2. High correlation between microbubble contrast-enhanced ultrasound, magnetic resonance and histopathology in the evaluation of hepatocellular carcinoma

    PubMed Central

    de Queiroz, Marcos Roberto Gomes; Francisco, Miguel José; Garcia, Rodrigo Gobbo; Rahal, Antonio; Salvalaggio, Paolo; Funari, Marcelo Buarque de Gusmão

    2013-01-01

    ABSTRACT Objectives To evaluate the efficacy of microbubble contrast ultrasound in diagnosis of hepatocellular carcinoma and to compare its results with those of magnetic resonance and histopathology. Methods A total of 29 patients suffering from chronic liver diseases and awaiting liver transplants at Hospital Israelita Albert Einstein were subject to magnetic resonance, microbubble contrast ultrasound, and excision liver biopsies. Results Excellent agreement between magnetic resonance and microbubble contrast ultrasound was observed in this study. There was moderate agreement between both imaging methods and histopathology results. Conclusion Microbubble contrast ultrasound was as accurate as magnetic resonance to evaluate hepatocellular carcinoma. These results were confirmed by comparing both methods to histopathological diagnosis. PMID:24488392

  3. Application of nonlinear sliding mode control to ultrasound contrast agent microbubbles.

    PubMed

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

    2013-07-01

    A sliding mode control system is developed and applied to a spherical model of a contrast agent microbubble that simulates its radial response to ultrasound. The model uses a compressible form of the Rayleigh-Plesset equation combined with a thin-shell model. A nonlinear control law for the second-order model is derived and used to design and simulate the controller. The effect of the controller on the contrast agent response is investigated for various control scenarios. This work demonstrates the feasibility of using a nonlinear control system to modulate the dynamic response of ultrasound contrast agents, but highlights the need for improved feedback mechanisms and control input methods. Possible applications of the nonlinear control system to contrast agents illustrated in this work include radius stabilization in the presence of an acoustic wave, radial growth and subsequent collapse, and generation of periodic radial oscillations while a contrast agent is within an acoustic forcing regime known to cause a chaotic response.

  4. Porphyrin Nanodroplets: Sub-micrometer Ultrasound and Photoacoustic Contrast Imaging Agents.

    PubMed

    Paproski, Robert J; Forbrich, Alexander; Huynh, Elizabeth; Chen, Juan; Lewis, John D; Zheng, Gang; Zemp, Roger J

    2016-01-20

    A novel class of all-organic nanoscale porphyrin nanodroplet agents is presented which is suitable for multimodality ultrasound and photoacoustic molecular imaging. Previous multimodality photoacoustic-ultrasound agents are either not organic, or not yet demonstrated to exhibit enhanced accumulation in leaky tumor vasculature, perhaps because of large diameters. In the current study, porphyrin nanodroplets are created with a mean diameter of 185 nm which is small enough to exhibit the enhanced permeability and retention effect. Porphyrin within the nanodroplet shell has strong optical absorption at 705 nm with an estimated molar extinction coefficient >5 × 10(9) m(-1) cm(-1) , allowing both ultrasound and photoacoustic contrast in the same nanoparticle using all organic materials. The potential of nanodroplets is that they may be phase-changed into microbubbles using high pressure ultrasound, providing ultrasound contrast with single-bubble sensitivity. Multispectral photoacoustic imaging allows visualization of nanodroplets when injected intratumorally in an HT1080 tumor in the chorioallantoic membrane of a chicken embryo. Intravital microscopy imaging of Hep3-GFP and HT1080-GFP tumors in chicken embryos determines that nanodroplets accumulated throughout or at the periphery of tumors, suggesting that porphyrin nanodroplets may be useful for enhancing the visualization of tumors with ultrasound and/or photoacoustic imaging.

  5. [Contrast enhanced ultrasound in the liver using low mechanical index--what is the difference?].

    PubMed

    Becker, D

    2002-12-01

    Echo-enhancing agents (EEA), also known as ultrasound contrast media, have improved the diagnostic potential of gastroenterologic ultrasound within the last years. Initially used to increase color-Doppler signals the potential to use harmonic waves being generated by the use of EEAs was established later. The effect was based upon the distraction of the EEA bubbles and the resulting pseudo-Doppler signal, the exam was carried out with high ultrasound energy and intermittent switching on and off of the ultrasound beam. Using this effect in real-time during continuous scanning is possible since the introduction of new EEAs with a flexible shell. This flexible shell oscillates during the scan process emitting harmonic signals. This new technology opens new possibilities for the detection of liver tumors including the possible characterisation. The detection rate for liver metastases can be increased by app. 40 % with this new technology. Correct sonographic characterisation of liver tumors can be achieved in nearly 100 % more cases.

  6. Assessment and Monitoring Tumor Vascularity With Contrast-Enhanced Ultrasound Maximum Intensity Persistence Imaging

    PubMed Central

    Pysz, Marybeth A.; Foygel, Kira; Panje, Cedric M.; Needles, Andrew; Tian, Lu; Willmann, Jürgen K.

    2015-01-01

    Objectives Contrast-enhanced ultrasound imaging is increasingly being used in the clinic for assessment of tissue vascularity. The purpose of our study was to evaluate the effect of different contrast administration parameters on the in vivo ultrasound imaging signal in tumor-bearing mice using a maximum intensity persistence (MIP) algorithm and to evaluate the reliability of in vivo MIP imaging in assessing tumor vascularity. The potential of in vivo MIP imaging for monitoring tumor vascularity during antiangiogenic cancer treatment was further evaluated. Materials and Methods In intraindividual experiments, varying contrast microbubble concentrations (5 × 105, 5 × 106, 5 × 107, 5 × 108 microbubbles in 100 µL saline) and contrast injection rates (0.6, 1.2, and 2.4 mL/min) in subcutaneous tumor-bearing mice were applied and their effects on in vivo contrast-enhanced ultrasound MIP imaging plateau values were obtained using a dedicated small animal ultrasound imaging system (40 MHz). Reliability of MIP ultrasound imaging was tested following 2 injections of the same micro-bubble concentration (5 × 107 microbubbles at 1.2 mL/min) in the same tumors. In mice with subcutaneous human colon cancer xenografts, longitudinal contrast-enhanced ultrasound MIP imaging plateau values (baseline and at 48 hours) were compared between mice with and without antiangiogenic treatment (anti-vascular endothelial growth factor antibody). Ex vivo CD31 immunostaining of tumor tissue was used to correlate in vivo MIP imaging plateau values with microvessel density analysis. Results In vivo MIP imaging plateau values correlated significantly (P = 0.001) with contrast microbubble doses. At 3 different injection rates of 0.6, 1.2, and 2.4 mL/min, MIP imaging plateau values did not change significantly (P = 0.61). Following 2 injections with the same microbubble dose and injection rate, MIP imaging plateau values were obtained with high reliability with an intraclass correlation

  7. Real-Time 3D Contrast-Enhanced Transcranial Ultrasound and Aberration Correction

    PubMed Central

    Ivancevich, Nikolas M.; Pinton, Gianmarco F.; Nicoletto, Heather A.; Bennett, Ellen; Laskowitz, Daniel T.; Smith, Stephen W.

    2008-01-01

    Contrast-enhanced (CE) transcranial ultrasound (US) and reconstructed 3D transcranial ultrasound have shown advantages over traditional methods in a variety of cerebrovascular diseases. We present the results from a novel ultrasound technique, namely real-time 3D contrast-enhanced transcranial ultrasound. Using real-time 3D (RT3D) ultrasound and micro-bubble contrast agent, we scanned 17 healthy volunteers via a single temporal window and 9 via the sub-occipital window and report our detection rates for the major cerebral vessels. In 71% of subjects, both of our observers identified the ipsilateral circle of Willis from the temporal window, and in 59% we imaged the entire circle of Willis. From the sub-occipital window, both observers detected the entire vertebrobasilar circulation in 22% of subjects, and in 44% the basilar artery. After performing phase aberration correction on one subject, we were able to increase the diagnostic value of the scan, detecting a vessel not present in the uncorrected scan. These preliminary results suggest that RT3D CE transcranial US and RT3D CE transcranial US with phase aberration correction have the potential to greatly impact the field of neurosonology. PMID:18395321

  8. Ultrasound Activated Contrast Imaging for Prostate Cancer Detection

    DTIC Science & Technology

    2005-03-01

    Plesset type equation (as detailed in the previous report and in [7]): p(P+ 3 R2)= p -41R 2y 4KSR -IP+ sin mt 2 R R R R 2 The bubble radius is given by (r...viscous interfacial stresses are considered (see [6] for details) to develop a new simulation model of contrast bubbles based on a modified Rayleigh

  9. The role of contrast-enhanced ultrasound in imaging carotid arterial diseases.

    PubMed

    Clevert, Dirk A; Paprottka, Philipp; Sommer, Wieland H; Helck, Andreas; Reiser, Maximilian F; Zengel, Pamela

    2013-06-01

    The standard of care for the initial diagnosis of carotid artery bifurcation diseases is carotid duplex ultrasound. Carotid abnormalities or difficult examinations may represent a diagnostic challenge in patients with clinical symptoms as well as in the follow-up after carotid endarterectomy, carotid artery stenting or other interventions. A promising new method in the diagnosis and follow-up of pathologic carotid diseases is contrast-enhanced ultrasound (CEUS). In comparison with magnetic resonance imaging or computed tomography, the contrast agents used for CEUS remain within the vascular space and hence can be used to study vascular disease and could provide additional information on carotid arterial diseases. This review describes the current carotid duplex ultrasound examination and compares the pathologic findings with CEUS. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Acoustic cavitation of individual ultrasound contrast agent microbubbles confined in capillaries

    NASA Astrophysics Data System (ADS)

    Almaqwashi, Ali; McIntyre, David; Ammi, Azzdine

    2011-10-01

    Ultrasound targeted therapies mainly rely on the inertial cavitation of ultrasound contrast agent (UCA) microbubbles. Our objective is to determine the cavitation acoustic pressure threshold for the destruction of UCA microbubbles inside cellulose capillaries. Acoustic emission from individual Optison microbubbles confined inside a 200-μm diameter capillary was detected using a passive cavitation detection system. Excitation signals from a 2.25 MHz transmitter were applied to the microbubbles while their acoustic emission was detected by a broadband 15 MHz receiver. Time traces were recorded (100 MHz sampling, 12- bit), and frequency-domain analysis of the received signals was performed to characterize microbubble cavitation. The cavitation acoustic pressure threshold was found to be 1 MPa inside the capillary in comparison with ˜0.7 MPa previously reported for unconfined UCA microbubbles. This work provides a clearer understanding of the role of ultrasound contrast agent dynamics inside a capillary.

  11. Contrast-enhanced ultrasound (CEUS) in nephrology: Has the time come for its widespread use?

    PubMed

    Granata, Antonio; Zanoli, Luca; Insalaco, Monica; Valentino, Massimo; Pavlica, Pietro; Di Nicolò, Pier Paolo; Scuderi, Mario; Fiorini, Fulvio; Fatuzzo, Pasquale; Bertolotto, Michele

    2015-08-01

    Grey-scale ultrasound has an important diagnostic role in nephrology. The absence of ionizing radiations and nephrotoxicity, rapidity of execution, excellent repeatability, the possibility to perform the test at the patient's bed and the low cost represent important advantages of this technique. Paired with real-time sonography and colour-power-Doppler contrast-enhanced ultrasound (CEUS) reduces the diagnostic gap with computed tomography (CT) and magnetic resonance (MR) and represents a major step in the evolution of clinical ultrasound. Although there are several situations in which contrast-enhanced CT and MR are indicated (i.e. evaluation of cystic or ischemic lesions, traumatisms and ablative therapies of the native and transplanted kidney), the use of CT contrast media presents a high risk of contrast-induced nephropathy (i.e. in elderly people, subjects with comorbidities and those with renal dysfunction), while gadolinium-based RM contrast agents are contraindicated for the risk of nephrogenic systemic fibrosis (i.e. in patients with severe renal dysfunction). In these situations, CEUS may be a viable alternative, however, as any technique associated with the infusion of pharmacological substances, the potential advantages and risks of CEUS should be critically evaluated. In this regard, the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) has published the guidelines for the use of CEUS for the kidney imaging and the International Contrast Ultrasound Society (ICUS) has been recently founded. The aim of this review is to offer an updated overview of the potential applications of CEUS in nephrology, reporting some indications and possible risks associated to its use.

  12. Intravenous ultrasound contrast agents versus other imaging methods in pediatric patients with neoplastic diseases - a comparison.

    PubMed

    Piskunowicz, Maciej; Kosiak, Wojciech; Batko, Tomasz; Adamkiewicz-Drożyńska, Elżbieta; Szarmach, Arkadiusz

    2013-12-01

    The lack of registration of ultrasound contrast agents for use in patients below the age of 18 is a significant limitation of their usage. Despite this, examinations with the use of contrast agents are conducted in numerous centers, mainly as part of the diagnostic process of vesicoureteral reflux. Examinations after an intravenous administration of contrast agents are conducted rarely. The reason for this is not only the lack of registration, but also the lack of studies on their safety profile in paediatric patients or no guidelines concerning the dosage. It seems that imaging with the use of such agents could help solve certain clinical problems when other diagnostic methods fail. The paper presents selected cases of pediatric patients treated in oncological departments, in whom the examination with the use of ultrasound contrast agents had a considerable influence on the diagnostic and therapeutic process.

  13. Contrast-enhanced ultrasound for evaluation of high-intensity focused ultrasound treatment of benign uterine diseases: retrospective analysis of contrast safety.

    PubMed

    Cheng, Chong-Qing; Zhang, Rui-Tao; Xiong, Yu; Chen, Li; Wang, Jian; Huang, Guo-Hua; Li, Ke-Quan; Zhang, Lian; Bai, Jin

    2015-04-01

    As a noninvasive treatment technique, ultrasound-guided high-intensity focused ultrasound (HIFU) has been considered as a routine treatment for uterine fibroids and adenomyosis in China. Contrast-enhanced ultrasound (CEUS) has been proposed as another option to assess the treatment efficacy during HIFU treatment. The aim of this investigation is to evaluate the adverse effects of HIFU ablation for benign uterine diseases in a group of patients studied with ultrasound contrast agent (UCA), in comparison with a group of patients not exposed to UCA. From November 2010 to December 2013, 2604 patients with benign uterine diseases were treated with HIFU. Among them, 1300 patients were exposed to an UCA, whereas 1304 patients were not.During HIFU procedure, the incidences of leg pain, sacral/buttock pain, groin pain, treatment area pain, and the discomfort "hot" sensation on skin were higher in the patients who were exposed to SonoVue (Bracco, Milan, Italy) than those who were not (20.5% vs 11.7%, 52.5% vs 42.3%, 6.5% vs 4.5%, 68.9% vs 55.4%, and 48.1% vs 42.9%, respectively). Among the postoperative adverse effects, the incidence of lower abdominal pain was significantly higher in patients who were exposed to an UCA than those who were not (51.2% vs 39.9%, P < 0.05). Two patients who were exposed to an UCA had acute renal function failure.In conclusion, UCA may increase the incidences of some common HIFU-related adverse effects during HIFU treatment for benign uterine diseases, but most of which were acceptable and self-limited. After HIFU treatment, renal function should be monitored in patients with a history of hypertension or taking nonsteroidal anti-inflammatory drugs.

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

    PubMed

    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.

  15. Diagnostic value of contrast-enhanced ultrasound in thyroid nodules with calcification.

    PubMed

    Jiang, Jue; Shang, Xu; Wang, Hua; Xu, Yong-Bo; Gao, Ya; Zhou, Qi

    2015-03-01

    The aim of this study was to investigate the diagnostic values of conventional ultrasound and contrast-enhanced ultrasound (CEUS) in benign and malignant thyroid nodules with calcification. Conventional ultrasound and CEUS were performed in 122 patients with thyroid nodules with calcification. The thyroid nodules were characterized as benign or malignant by pathological diagnosis. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accordance rate of the two imaging methods were determined. The area under the receiver operating characteristics curve (AUC) was used to assess the diagnostic values of the two imaging methods. In 122 cases of thyroid nodules with calcification, 73 benign nodules and 49 malignant nodules were verified by pathological diagnosis. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accordance rate of conventional ultrasound were 50%, 77%, 59%, 69%, and 66%, respectively, and those of CEUS were 90%, 92%, 88%, 93%, and 91%, respectively. There were significant differences between the two imaging methods. AUCs of conventional ultrasound and CEUS were 0.628 ± 0.052 and 0.908 ± 0.031, suggesting low and high diagnostic values, respectively. CEUS has high diagnostic values, being significantly greater than those of conventional ultrasound, in differential diagnosis of benign and malignant thyroid nodules with calcification.

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

    PubMed

    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.

  17. Renal retention of lipid microbubbles: a potential mechanism for flank discomfort during ultrasound contrast administration.

    PubMed

    Liu, Ya Ni; Khangura, Jaspreet; Xie, Aris; Belcik, J Todd; Qi, Yue; Davidson, Brian P; Zhao, Yan; Kim, Sajeevani; Inaba, Yoichi; Lindner, Jonathan R

    2013-12-01

    The etiology of flank pain sometimes experienced during the administration of ultrasound contrast agents is unknown. The aim of this study was to investigate whether microbubble ultrasound contrast agents are retained within the renal microcirculation, which could lead to either flow disturbance or local release of vasoactive and pain mediators downstream from complement activation. Retention of lipid-shelled microbubbles in the renal microcirculation of mice was assessed by confocal fluorescent microscopy and contrast-enhanced ultrasound imaging with dose-escalating intravenous injection. Studies were performed with size-segregated microbubbles to investigate physical entrapment, after glycocalyx degradation and in wild-type and C3-deficient mice to investigate complement-mediated retention. Urinary bradykinin was measured before and after microbubble administrations. Renal contrast-enhanced ultrasound in human subjects (n = 13) was performed 7 to 10 min after the completion of lipid microbubble administration. In both mice and humans, microbubble retention was detected in the renal cortex by persistent contrast-enhanced ultrasound signal enhancement. Microbubble retention in mice was linearly related to dose and occurred almost exclusively in cortical glomerular microvessels. Microbubble retention did not affect microsphere-derived renal blood flow. Microbubble retention was not influenced by glycocalyx degradation or by microbubble size, thereby excluding lodging, but was reduced by 90% (P < .01) in C3-deficient mice. Urinary bradykinin increased by 65% 5 min after microbubble injection. Lipid-shelled microbubbles are retained in the renal cortex because of complement-mediated interactions with glomerular microvascular endothelium. Microbubble retention does not adversely affect renal perfusion but does generate complement-related intermediates that are known to mediate nociception and could be responsible for flank pain. Copyright © 2013 American Society of

  18. [Baseline and contrast-enhanced ultrasound of the liver in tumor patients].

    PubMed

    Oldenburg, A; Albrecht, T

    2008-10-01

    In patients with known malignancy, correct detection and characterization of liver lesions has important therapeutic consequences. Conventional sonography is the most commonly used modality for liver imaging in tumor patients. However, it has a lower sensitivity for the detection of liver metastases compared to contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI). The majority of liver metastases are hypoechoic and well defined in baseline ultrasound (US), while detection of isoechoic or small liver metastases <1 cm is difficult and the differentiation of liver metastases from benign liver lesions and other malignant liver tumors can be impossible with baseline US. The use of microbubble-based ultrasound contrast agents and contrast-specific imaging techniques advanced the accuracy of ultrasound in liver imaging. Levovist and SonoVue are the US contrast agents approved for liver imaging in Europe. Compared to Levovist, SonoVue allows continuous imaging of the liver in real-time over a period of up to 5 minutes. As a result, SonoVue became the preferred contrast agent for liver imaging in the recent years, while Levovist became less important. Important for the detection of liver metastases are the portal venous and late phases in which metastases show a wash-out and can be detected as hypoechoic lesions in homogeneous enhanced liver parenchyma. The detection of hepatic metastases is substantially improved by CEUS compared to conventional B-mode sonography. Several studies showed sensitivity in detecting liver metastases comparable to that of contrast-enhanced CT and MRI. Furthermore, the typical enhancement patterns of the different benign and malignant liver lesions allow reliable characterization and differentiation from liver metastases in the majority of cases. This paper provides information about the advantages and expedient application of contrast-enhanced ultrasound (CEUS) in tumor patients.

  19. Acoustic characterization of ultrasound contrast microbubbles and echogenic liposomes: Applications to imaging and drug-delivery

    NASA Astrophysics Data System (ADS)

    Paul, Shirshendu

    Micron- to nanometer - sized ultrasound agents, like encapsulated microbubbles and echogenic liposomes (ELIPs), are being actively developed for possible clinical implementations in diagnostic imaging and ultrasound mediated drug/gene delivery. The primary objective of this thesis is to characterize the acoustic behavior of and the ultrasound-mediated contents release from these contrast agents for developing multi-functional ultrasound contrast agents. Subharmonic imaging using contrast microbubbles can improve image quality by providing a higher signal to noise ratio. However, the design and development of contrast microbubbles with favorable subharmonic behavior requires accurate mathematical models capable of predicting their nonlinear dynamics. To this goal, 'strain-softening' viscoelastic interfacial models of the encapsulation were developed and subsequently utilized to simulate the dynamics of encapsulated microbubbles. A hierarchical two-pronged approach of modeling --- a model is applied to one set of experimental data to obtain the model parameters (material characterization), and then the model is validated against a second independent experiment --- is demonstrated in this thesis for two lipid coated (SonazoidRTM and DefinityRTM) and a few polymer (polylactide) encapsulated microbubbles. The proposed models were successful in predicting several experimentally observed behaviors e.g., low subharmonic thresholds and "compression-only" radial oscillations. Results indicate that neglecting the polydisperse size distribution of contrast agent suspensions, a common practice in the literature, can lead to inaccurate results. In vitro experimental investigation of the dependence of subharmonic response from these microbubbles on the ambient pressure is also in conformity with the recent numerical investigations, showing both increase or decrease under appropriate excitation conditions. Experimental characterization of the ELIPs and polymersomes was performed

  20. Ultrasound Findings of Intraductal Papillary Neoplasm in Bile Duct and the Added Value of Contrast-Enhanced Ultrasound.

    PubMed

    Liu, L N; Xu, H X; Zheng, S G; Sun, L P; Guo, L H; Zhang, Y F; Xu, J M; Liu, C; Xu, X H

    2015-12-01

    To investigate the imaging features of intraductal papillary neoplasm in bile duct (IPNB) on baseline ultrasound and contrast-enhanced ultrasound (CEUS). The imaging features on baseline ultrasound and CEUS in 16 pathologically proven IPNB lesions in 15 patients were retrospectively analyzed. Real-time contrast specific modes and contrast agent of SonoVue were used for CEUS. Bile duct dilation was present in all patients. The mean lengths for the intraductal papillary adenomas and adenocarcinomas were 2.5 ± 1.1 (range, 1.2 - 4.2 cm) and 5.6 ± 2.0 cm (range, 3.3 - 9.8 cm) (P = 0.004). Three imaging types of IPNB on ultrasound were depicted: bile duct dilation with intraductal mass (n = 8), bile duct dilation without intraductal mass (n = 3), and cystic-solid mixed type (n = 5). On CEUS, solid components of 13 lesions appeared hyper- (n = 12) or iso-enhancement (n = 1) in the arterial phase whereas all showed hypo-enhancement in the portal and late phases. For 3 lesions of bile duct dilation without intraductal mass, CEUS showed non-enhancement during all phases. Pre-surgical CEUS and conventional ultrasound made correct diagnoses in 12 (75.0 %) and 5(31.3 %) of 16 IPNBs respectively (P = 0.04). For CECT, correct diagnosis was also achieved in 12 (75.0 %) of 16 lesions (P = 1.00, in comparison with CEUS). IPNB should be taken into consideration when intraductal mass or cystic-solid mass with bile duct dilation, or remarkable bile duct dilation without intraductal mass, are found on US. Intraductal mass length > 3.0 cm is more commonly found in malignant IPNB. CEUS might facilitate the diagnosis of IPNB by easily excluding the possibility of commonly found sludge, nonshadowing stones, or blood clots. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Thresholds for visual detection of Young's modulus contrast in simulated ultrasound image movies.

    PubMed

    Miller, N R; Bamber, J C

    2000-08-01

    Elasticity imaging (EI) is being developed to allow the evaluation of the mechanical properties of soft tissue, but these properties are already assessed in routine ultrasound breast examination using a method that involves the subjective interpretation of tissue motion seen in real-time B-mode image movies during palpation. We refer to this method as relative motion assessment (RMA). The purpose of this study was to begin a process of learning about the usefulness and limitations of RMA relative to the emerging method of elasticity imaging. Perception experiments were performed to measure Young's modulus contrast thresholds for positive contrast lesions under controlled conditions that could subsequently be repeated to evaluate elasticity imaging for the same task. Observer ability to grade relative lesion contrast using RMA was also assessed. Simulated sequences of B-scans of tissue moving in response to an applied force were generated and used in a two-alternative forced-choice (2-AFC) experiment to measure contrast thresholds for the detection of disc-shaped elastic lesions by RMA in the absence of ultrasound echo contrast. Results were obtained for four observers at a lesion area of about 77 speckle cells and for five observers at lesion areas of about 42 and 139 speckle cells. Young's modulus contrast thresholds were found to decrease with increasing lesion size and were well within the range of contrast values that have been measured for breast tumours in vitro. It was also found that observers were quite skilled at using RMA to grade the relative strain contrast of lesions. The nonlinear relationship between the object contrast (Young's modulus contrast) and the image contrast (strain contrast) prevented observers from detecting very small lesions with 100% accuracy, no matter how high the object contrast. A preliminary comparison of the results for RMA with published thresholds for elastography indicated that elastography is likely to offer great benefit

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

    PubMed

    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 < 0.01), respectively. Thus, it was necessary to increase the mechanical index for better contrast visualization of the microbubbles with a higher transducer frequency. The lowest mechanical index for earliest visible microbubble destruction was 0

  3. DVP parametric imaging for characterizing ovarian masses in contrast-enhanced ultrasound.

    PubMed

    Sha-sha, H; Li, H; Jie, M; Gui, F; Wen-jun, G; Ming, H; Yang, Z; Qing, Y

    2015-01-01

    To evaluate whether parametric imaging with contrast-enhanced ultrasound is an approach capable of for the differential diagnosis of ovarian masses. The authors analysed 50 cases of ovarian masses by routine ultrasound and contrast-enhanced ultrasound with a new dedicated parametric image processing software-Sonoliver. The angiogenesis and blood perfusion mode on a digital video recorder were recorded and the morphological characteristics of time-intensity curve (TIC) and dynamic vascular pattern (DVP) curve were subsequently described. The quantity factor, including time to peak (TTP), maximum intensity (IMAX), rise time, (RT), mean transit time (mTT), generated by Sonoliver software were compared in both histological gradings. There were 24 cases (86%) displaying mainly hypo-enhanced with blue imaging in those with benign masses and 15 cases (68%) displaying mainly hyper-enhanced imaging with red in those with malignant masses. The difference was statistically significant (p < 0.05). DVP curves were unipolar below the baseline in 23 cases (82%) of benign masses and unipolar above the baseline in 15 cases (68%) of malignant masses. IMAX, TTP, and mTT were all significantly higher in those with malignant masses than those with benign ones (all p < 0.05), but, no statistical difference in the RT between the two groups was found (p > 0.05). According to the results, DVP parametric imaging is a new approach capable of differential diagnoses of overian masses with contrast-enhanced ultrasound.

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

    PubMed Central

    Săftoiu, Adrian; Vilmann, Peter; Bhutani, Manoop S.

    2016-01-01

    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 of intensity of the contrast signal through time-intensity curve analysis. Thus, contrast harmonic imaging-EUS has been used to differentiate pancreatic adenocarcinoma based on lower values of the peak enhancement. Future applications of CE-EUS in pancreatic adenocarcinoma include not only use of targeted 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 through sonoporation and ultrasound-induced release of the drugs locally. PMID:28000627

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

    PubMed

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

    2017-08-07

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  7. Soft-Tissue Tumor Contrast Enhancement Patterns: Diagnostic Value and Comparison Between Ultrasound and MRI.

    PubMed

    Gruber, Leonhard; Loizides, Alexander; Luger, Anna K; Glodny, Bernhard; Moser, Patrizia; Henninger, Benjamin; Gruber, Hannes

    2017-02-01

    The purpose of this study was to assess and compare contrast-enhanced ultrasound and MRI patterns in the diagnosis of soft-tissue masses. Two hundred fifty-five consecutively registered patients with histologically confirmed soft-tissue masses were included in this retrospective study. The diagnostic properties of four predefined contrast enhancement (CE) patterns were assessed, and logistic regression analysis was performed to determine the correlation between diagnosis and CE pattern, lesion size, and patient age and sex. The influence of lesion size on the occurrence of inhomogeneous CE patterns in malignancies was also determined. Homogeneous CE patterns were highly specific for benignity, and inhomogeneous CE was moderately specific for malignancy in both ultrasound and MRI. A combination of homogeneous and inhomogeneous CE patterns led to 88.3% and 88.7% sensitivity, 66.7% and 59.7% specificity, 73.4% and 68.2% correct classification, 54.6% and 47.8% positive predictive value, 92.6% and 92.7% negative predictive value, 2.65 and 2.20 positive likelihood ratio, and 0.18 and 0.19 negative likelihood ratio for contrast-enhanced ultrasound and contrast-enhanced MRI. Cases with homogeneous CE in either ultrasound or MRI also were predominantly benign. The occurrence of inhomogeneous CE in malignant lesions increased with size. CE patterns in ultrasound and MRI offer additional information about the differentiation of an unknown soft-tissue mass. The results of this study showed that homogeneous or absent CE was specific for benign differentiation and that heterogeneous CE was linked to malignancy. The routine analysis of CE patterns should increase diagnostic reliability in unclear soft-tissue masses.

  8. Usefulness of contrast-enhanced intraoperative ultrasound using Sonazoid in patients with hepatocellular carcinoma.

    PubMed

    Arita, Junichi; Takahashi, Michiro; Hata, Shojiro; Shindoh, Junichi; Beck, Yoshifumi; Sugawara, Yasuhiko; Hasegawa, Kiyoshi; Kokudo, Norihiro

    2011-12-01

    To assess the usefulness of contrast-enhanced intraoperative ultrasound (CE-IOUS) using Sonazoid (gaseous perflubutane) in patients with hepatocellular carcinoma (HCC). Contrast-enhanced intraoperative ultrasound using Sonazoid, a novel ultrasonic contrast agent enabling Kupffer imaging, may enable differentiation of HCC among new focal liver lesions found during fundamental intraoperative ultrasound (fundamental-NFLLs). Between February 2007 and February 2009, a total of 192 consecutive patients were enrolled. Fundamental intraoperative ultrasound and CE-IOUS were performed successively after laparotomy. The vascularity of 1 representative lesion was examined in harmonic mode for approximately 1 minute after the intravenous injection of Sonazoid (vascular phase). Approximately 15 minutes after the vascular phase, total liver scanning in the harmonic mode was commenced (Kupffer phase). One additional injection of Sonazoid was allowed to examine the vascularity of another lesion, if necessary. A tentative diagnosis of HCC was made when a lesion was either hypervascular during the vascular phase or hypoechoic during the Kupffer phase. A final diagnosis of HCC was made on the basis of the results of a histological examination or dynamic computed tomography findings obtained during the 12-month postoperative period. Seventy-nine fundamental-NFLLs were found in 50 patients (26%), 17 (22%) of which were finally diagnosed as HCC. The sensitivity, specificity, and accuracy of CE-IOUS for differentiating HCC among fundamental-NFLLs were 65%, 94%, and 87%, respectively. Contrast-enhanced intraoperative ultrasound identified 21 additional new hypoechoic lesions in 16 patients, of which 14 lesions (67%) in 11 patients were finally diagnosed as HCC. This prospective study protocol was approved by the institutional review board of the Tokyo University Hospital. An English-language summary of the protocol was submitted (registration ID: UMIN000003046) to the Clinical Trials

  9. Extravasation Risk Using Ultrasound-guided Peripheral Intravenous Catheters for Computed Tomography Contrast Administration.

    PubMed

    Rupp, Jordan D; Ferre, Robinson M; Boyd, Jeremy S; Dearing, Elizabeth; McNaughton, Candace D; Liu, Dandan; Jarrell, Kelli L; McWade, Conor M; Self, Wesley H

    2016-08-01

    Ultrasound-guided intravenous catheter (USGIV) insertion is increasingly being used for administration of intravenous (IV) contrast for computed tomography (CT) scans. The goal of this investigation was to evaluate the risk of contrast extravasation among patients receiving contrast through USGIV catheters. A retrospective observational study of adult patients who underwent a contrast-enhanced CT scan at a tertiary care emergency department during a recent 64-month period was conducted. The unadjusted prevalence of contrast extravasation was compared between patients with an USGIV and those with a standard peripheral IV inserted without ultrasound. Then, a two-stage sampling design was used to select a subset of the population for a multivariable logistic regression model evaluating USGIVs as a risk factor for extravasation while adjusting for potential confounders. In total, 40,143 patients underwent a contrasted CT scan, including 364 (0.9%) who had contrast administered through an USGIV. Unadjusted prevalence of extravasation was 3.6% for contrast administration through USGIVs and 0.3% for standard IVs (relative risk = 13.9, 95% confidence interval [CI] = 7.9 to 24.6). After potential confounders were adjusted for, CT contrast administered through USGIVs was associated with extravasation (adjusted odds ratio = 8.6, 95% CI = 4.6 to 16.2). No patients required surgical management for contrast extravasation; one patient in the standard IV group was admitted for observation due to extravasation. Patients who received contrast for a CT scan through an USGIV had a higher risk of extravasation than those who received contrast through a standard peripheral IV. Clinicians should consider this extravasation risk when weighing the risks and benefits of a contrast-enhanced CT scan in a patient with USGIV vascular access. © 2016 by the Society for Academic Emergency Medicine.

  10. Prospective comparison of use of contrast-enhanced ultrasound and contrast-enhanced computed tomography in the Bosniak classification of complex renal cysts

    PubMed Central

    Ragel, Matthew; Nedumaran, Anbu

    2016-01-01

    Aim To compare contrast-enhanced ultrasound and contrast-enhanced computed tomography in the evaluation of complex renal cysts using the Bosniak classification. Methods Forty-six patients with 51 complex renal cysts were prospectively examined using contrast-enhanced ultrasound and contrast-enhanced computed tomography and images analysed by two observers using the Bosniak classification. Adverse effects and patients’ preference were assessed for both modalities. Results There was complete agreement in Bosniak classification between both modalities and both observers in six cysts (11.8%). There was agreement of Bosniak classification on both modalities in 21 of 51 cysts (41.2%) for observer 1 and in 17 of 51 cysts (33.3%) for observer 2. Contrast-enhanced ultrasound gave a higher Bosniak classification than corresponding contrast-enhanced computed tomography in 31 % of cysts by both observers. Histological correlation was available in three lesions, all of which were malignant and classified as such simultaneously on both modalities by at least one observer, with remaining patients followed up with US or CT for 6–24 months. No adverse or side effects were reported following the use of US contrast, whilst 63.6% of patients suffered minor side effects following the use of CT contrast. 81.8% of the surveyed patients preferred contrast-enhanced ultrasound to contrast-enhanced computed tomography. Conclusion Contrast-enhanced ultrasound is a feasible tool in the evaluation of complex renal cysts in a non-specialist setting. Increased contrast-enhanced ultrasound sensitivity to enhancement compared to contrast-enhanced computed tomography, resulting in upgrading the Bosniak classification on contrast-enhanced ultrasound, has played a role in at best moderate agreement recorded by the observers with limited experience, but this would be overcome as the experience grows. To this end, we propose a standardised proforma for the contrast-enhanced ultrasound report. The

  11. Application of high-resolution ultrasound, real-time elastography, and contrast-enhanced ultrasound in differentiating solid thyroid nodules

    PubMed Central

    Zhang, Yu-Zhi; Xu, Ting; Gong, Hai-Yan; Li, Cui-Ying; Ye, Xin-Hua; Lin, Hong-Jun; Shen, Mei-Ping; Duan, Yu; Yang, Tao; Wu, Xiao-Hong

    2016-01-01

    Abstract High-resolution ultrasound (HRUS) is a sensitive tool for identifying thyroid nodules. Real-time elastography (RTE) and contrast-enhanced ultrasound (CEUS) are newly developed methods which could measure tissue elasticity and perfusion features. The aim of the present study was to evaluate and compare the diagnostic efficiency of HRUS, RTE, CEUS and their combined use in the differentiation of benign and malignant solid thyroid nodules. In total, 111 consecutive patients with 145 thyroid nodules who were scheduled for surgery were included in the study. All of them underwent HRUS, RTE, and CEUS examination. The independent ultrasound (US) predictors for malignancy were determined and quantified using logistic regression analysis, based on which a risk-scoring model was established for each method. The diagnostic efficiency of each method was assessed by receiver operating characteristic (ROC) curve analysis. HRUS showed the best diagnostic efficiency among the 3 US methods, with 74.6% sensitivity and 87.8% specificity. CEUS had higher sensitivity (85.7%), whereas RTE alone did not show much advantage. Combined use of RTE and HRUS increased the sensitivity (92.1%). The HRUS-RTE-CEUS combination could increase both the sensitivity and specificity (87.3%, 91.5%), with the best AUC (0.935) among all the methods. The overall diagnostic value of HRUS in predicting malignancy is the best among the 3 US methods. Combined use of RTE and CEUS and HRUS could improve the diagnostic efficiency for solid thyroid nodules. PMID:27828854

  12. Improving the contrast of breast cancer masses in ultrasound using an autoregressive model based filter.

    PubMed

    von Lavante, Etienne; Noble, J Alison

    2007-01-01

    The assessment and diagnosis of breast cancer with ultrasound is a challenging problem due to the low contrast between cancer masses and benign tissue. Due to this low contrast it has proven to be difficult to achieve reliable segmentation results on breast cancer masses. An autoregressive model has been employed to filter out of the backscattered RF-signal from a tissue harmonic image which is not degraded by harmonic leakage. Measurements on the filtered image have shown a significant (up to 45%) increase in contrast between cancer masses and benign tissue.

  13. Mesoporous silica nanoparticles as a breast cancer targeting contrast agent for ultrasound imaging

    NASA Astrophysics Data System (ADS)

    Milgroom, Andrew Carson

    Current clinical use of ultrasound for breast cancer diagnostics is strictly limited to a role as a supplementary detection method to other modalities, such as mammography or MRI. A major reason for ultrasound’s role as a secondary method is its inability to discern between cancerous and non-cancerous bodies of similar density, like dense calcifications or benign fibroadenomas. Its detection capabilities are further diminished by the variable density of the surrounding breast tissue with the progression of age. Preliminary studies suggest that mesoporous silica nanoparticles (MSNs) are a good candidate as an in situ contrast agent for ultrasound. By tagging the silica particle surface with the cancer-targeting antibody trastuzumab (Herceptin), suspect regions of interest can be better identified in real time with standard ultrasound equipment. Once the silica-antibody conjugate is injected into the bloodstream and enters the cancerous growth’s vasculature, the antibody arm will bind to HER2, a cell surface receptor known to be dysfunctional or overexpressed in certain types of breast cancer. As more particles aggregate at the cell surface, backscatter of the ultrasonic waves increases as a result of the higher porous silica concentration. This translates to an increased contrast around the lesion boundary. Tumor detection through ultrasound contrast enhancement provides a tremendous advantage over current cancer diagnostics because is it significantly cheaper and can be monitored in real time. Characterization of MCM-41 type MSNs suggests that these particles have sufficient stability and particle size distribution to penetrate through fenestrated tumor vasculature and accumulate in HER2+ breast cancer cells through the enhanced permeation and retention (EPR) effect. A study of acoustic properties showed that particle concentration is linearly correlated to image contrast in clinical frequency-range ultrasound, although less pronounced than typical microbubble

  14. Contrast-enhanced harmonic endoscopic ultrasound imaging: basic principles, present situation and future perspectives.

    PubMed

    Alvarez-Sánchez, María-Victoria; Napoléon, Bertrand

    2014-11-14

    Over the last decade, the development of stabilised microbubble contrast agents and improvements in available ultrasonic equipment, such as harmonic imaging, have enabled us to display microbubble enhancements on a greyscale with optimal contrast and spatial resolution. Recent technological advances made contrast harmonic technology available for endoscopic ultrasound (EUS) for the first time in 2008. Thus, the evaluation of microcirculation is now feasible with EUS, prompting the evolution of contrast-enhanced EUS from vascular imaging to images of the perfused tissue. Although the relevant experience is still preliminary, several reports have highlighted contrast-enhanced harmonic EUS (CH-EUS) as a promising noninvasive method to visualise and characterise lesions and to differentiate benign from malignant focal lesions. Even if histology remains the gold standard, the combination of CH-EUS and EUS fine needle aspiration (EUS-FNA) can not only render EUS more accurate but may also assist physicians in making decisions when EUS-FNA is inconclusive, increasing the yield of EUS-FNA by guiding the puncture with simultaneous imaging of the vascularity. The development of CH-EUS has also opened up exciting possibilities in other research areas, including monitoring responses to anticancer chemotherapy or to ethanol-induced pancreatic tissue ablation, anticancer therapies based on ultrasound-triggered drug and gene delivery, and therapeutic adjuvants by contrast ultrasound-induced apoptosis. Contrast harmonic imaging is gaining popularity because of its efficacy, simplicity and non-invasive nature, and many expectations are currently resting on this technique. If its potential is confirmed in the near future, contrast harmonic imaging will become a standard practice in EUS.

  15. Contrast-enhanced harmonic endoscopic ultrasound imaging: Basic principles, present situation and future perspectives

    PubMed Central

    Alvarez-Sánchez, María-Victoria; Napoléon, Bertrand

    2014-01-01

    Over the last decade, the development of stabilised microbubble contrast agents and improvements in available ultrasonic equipment, such as harmonic imaging, have enabled us to display microbubble enhancements on a greyscale with optimal contrast and spatial resolution. Recent technological advances made contrast harmonic technology available for endoscopic ultrasound (EUS) for the first time in 2008. Thus, the evaluation of microcirculation is now feasible with EUS, prompting the evolution of contrast-enhanced EUS from vascular imaging to images of the perfused tissue. Although the relevant experience is still preliminary, several reports have highlighted contrast-enhanced harmonic EUS (CH-EUS) as a promising noninvasive method to visualise and characterise lesions and to differentiate benign from malignant focal lesions. Even if histology remains the gold standard, the combination of CH-EUS and EUS fine needle aspiration (EUS-FNA) can not only render EUS more accurate but may also assist physicians in making decisions when EUS-FNA is inconclusive, increasing the yield of EUS-FNA by guiding the puncture with simultaneous imaging of the vascularity. The development of CH-EUS has also opened up exciting possibilities in other research areas, including monitoring responses to anticancer chemotherapy or to ethanol-induced pancreatic tissue ablation, anticancer therapies based on ultrasound-triggered drug and gene delivery, and therapeutic adjuvants by contrast ultrasound-induced apoptosis. Contrast harmonic imaging is gaining popularity because of its efficacy, simplicity and non-invasive nature, and many expectations are currently resting on this technique. If its potential is confirmed in the near future, contrast harmonic imaging will become a standard practice in EUS. PMID:25400439

  16. In vivo ultrasound visualization of non-occlusive blood clots with thrombin-sensitive contrast agents.

    PubMed

    Nakatsuka, Matthew A; Barback, Christopher V; Fitch, Kirsten R; Farwell, Alexander R; Esener, Sadik C; Mattrey, Robert F; Cha, Jennifer N; Goodwin, Andrew P

    2013-12-01

    The use of microbubbles as ultrasound contrast agents is one of the primary methods to diagnose deep venous thrombosis. However, current microbubble imaging strategies require either a clot sufficiently large to produce a circulation filling defect or a clot with sufficient vascularization to allow for targeted accumulation of contrast agents. Previously, we reported the design of a microbubble formulation that modulated its ability to generate ultrasound contrast from interaction with thrombin through incorporation of aptamer-containing DNA crosslinks in the encapsulating shell, enabling the measurement of a local chemical environment by changes in acoustic activity. However, this contrast agent lacked sufficient stability and lifetime in blood to be used as a diagnostic tool. Here we describe a PEG-stabilized, thrombin-activated microbubble (PSTA-MB) with sufficient stability to be used in vivo in circulation with no change in biomarker sensitivity. In the presence of actively clotting blood, PSTA-MBs showed a 5-fold increase in acoustic activity. Specificity for the presence of thrombin and stability under constant shear flow were demonstrated in a home-built in vitro model. Finally, PSTA-MBs were able to detect the presence of an active clot within the vena cava of a rabbit sufficiently small as to not be visible by current non-specific contrast agents. By activating in non-occlusive environments, these contrast agents will be able to detect clots not diagnosable by current contrast agents. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Measurement of the contrast agent intrinsic and native harmonic response with single transducer pulse waved ultrasound systems.

    PubMed

    Verbeek, X A; Willigers, J M; Brands, P J; Ledoux, L A; Hoeks, A P

    1999-01-01

    Ultrasound contrast agents, i.e., small gas filled microbubbles, enhance the echogenicity of blood and have the potential to be used for tissue perfusion assessment. The contrast agents scatter ultrasound in a nonlinear manner and thereby introduce harmonics in the ultrasound signal. This property is exploited in new ultrasound techniques like harmonic imaging, which aims to display only the contrast agent presence. Much attention has already been given to the physical properties of the contrast agent. The present study focuses on practical aspects of the measurement of the intrinsic harmonic response of ultrasound contrast agents with single transducer pulse waved ultrasound systems. Furthermore, the consequences of two other sources of harmonics are discussed. These sources are the nonlinear distortion of ultrasound in a medium generating native harmonics, and the emitted signal itself which might contain contaminating harmonics. It is demonstrated conceptually and by experiments that optimization of the contrast agent harmonic response measured with a single transducer is governed by the transducer spectral sensitivity distribution rather than the resonance properties of the contrast agent. Both native and contaminating harmonics may be of considerable strength and can be misinterpreted as intrinsic harmonics of the contrast agent. Practical difficulties to filter out the harmonic component selectively, without deteriorating the image, may cause misinterpretation of the fundamental as a harmonic.

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

    PubMed

    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.

  19. CONTRAST-ENHANCED INTRAVASCULAR ULTRASOUND PULSE SEQUENCES FOR BANDWIDTH-LIMITED TRANSDUCERS

    PubMed Central

    Maresca, David; Renaud, Guillaume; van Soest, Gijs; Li, Xiang; Zhou, Qifa; Shung, K. Kirk; de Jong, Nico; van der Steen, Antonius F. W.

    2013-01-01

    We demonstrate two methods for vasa vasorum imaging using contrast-enhanced intravascular ultrasound, which can be performed using commercial catheters. Plaque neovascularization was recognized as an independent marker of coronary artery plaque vulnerability. IVUS-based methods to image the microvessels available to date require high bandwidth (−6 dB relative frequency bandwidth >70%), which are not routinely available commercially. We explored the potential of ultraharmonic imaging and chirp reversal imaging for vasa vasorum imaging. In vitro recordings were performed on a tissue-mimicking phantom using a commercial ultrasound contrast agent and a transducer with a center frequency of 34 MHz and a −6 dB relative bandwidth of 56%. Acoustic peak pressures <500 kPa were used. A tissue-mimicking phantom with channels down to 200 μm in diameter was successfully imaged by the two contrast detection sequences while the smallest channel stayed invisible in conventional intravascular ultrasound images. Ultraharmonic imaging provided the best contrast agent detection. PMID:23384459

  20. Contrast-enhanced ultrasound using sulfur hexafluoride is safe in the pediatric setting.

    PubMed

    Torres, Alvaro; Koskinen, Seppo K; Gjertsen, Henrik; Fischler, Björn

    2017-11-01

    Background Contrast-enhanced ultrasound (CEUS) by using sulfur hexafluoride microbubbles is not licensed for use in children, but its off-label use is widespread. Purpose To outline our experience with the off-label use of CEUS in children, specifically with regards to safety. Material and Methods We retrieved all records of 10681 patients aged under 18 years who underwent abdominal ultrasound (US) January 2004 to December 2014. We then identified those who underwent an abdominal CEUS using sulfur hexafluoride microbubbles. Electronic patient charts were used to verify the indication for contrast agent, dose, possible adverse effects as well as information on patient height, weight, and age. Results We identified 173 patients (mean age, 11 years; range, 0.1-18 years) who underwent a total of 287 CEUS exams. Of all exams, 46% were performed on the native liver, 31% on a transplanted liver, and 23% on other organs. The indications were "circulatory status?" (40%), "characterization of lesion?" (40%), and miscellaneous (20%). Mean contrast dose was 2.3 mL (range, 0.1-8.1 mL). No immediate adverse effects were recorded. One patient experienced itching the day after, but this was considered to be a reaction to concomitantly administered fentanyl. Conclusion The use of intravenous ultrasound contrast seems safe in patients aged under 18 years and our results do not support the current practice to restrict the use of CEUS in children.

  1. Spatiotemporal correlation of ultrasound contrast agent dilution curves for angiogenesis localization by dispersion imaging.

    PubMed

    Kuenen, Maarten P J; Saidov, Tamerlan A; Wijkstra, Hessel; de la Rosette, Jean J M C H; Mischi, Massimo

    2013-12-01

    The major role of angiogenesis in cancer development has driven many researchers to investigate the prospects of noninvasive cancer imaging based on assessment of microvascular perfusion. The limited results so far may be caused by the complex and contradictory effects of angiogenesis on perfusion. Alternatively, assessment of ultrasound contrast agent dispersion kinetics, resulting from features such as density and tortuosity, has shown a promising potential to characterize angiogenic effects on the microvascular structure. This method, referred to as contrast-ultrasound dispersion imaging (CUDI), is based on contrast-enhanced ultrasound imaging after an intravenous contrast agent bolus injection. In this paper, we propose a new spatiotemporal correlation analysis to perform CUDI. We provide the rationale for indirect estimation of local dispersion by deriving the analytical relation between dispersion and the correlation coefficient among neighboring time-intensity curves obtained at each pixel. This robust analysis is inherently normalized and does not require curve-fitting. In a preliminary validation of the method for localization of prostate cancer, the results of this analysis show superior cancer localization performance (receiver operating characteristic curve area of 0.89) compared with those of previously reported CUDI implementations and perfusion estimation methods.

  2. Gray scale and contrast-enhanced ultrasound imaging of malignant liver tumors of vascular origin

    PubMed Central

    Schweitzer, Nora; Soudah, Bisharah; Gebel, Michael; Manns, Michael Peter

    2015-01-01

    Objectives Malignant vascular tumors of the liver are rare. The aim of this study was to investigate the applicability of gray scale and contrast-enhanced ultrasonography in patients with epithelioid hemangioendothelioma (EHE) of the liver and hepatic angiosarcoma (HA) and to describe the clinical presentation. Methods We retrospectively analyzed all patients with epithelioid hemangioendothelioma or hemangiosarcoma of the liver from 1998 to 2011, who underwent ultrasound investigation. We describe the findings in gray scale and contrast-enhanced ultrasound and the clinical course of the disease of seven patients with EHE and five patients with HA. Results Ultrasound investigation in EHE showed mostly multiple hypoechoic irregular lesions close to the liver capsule and with a halo in some cases. Contrast enhancement revealed inhomogeneously and through all contrast phases vascularized tumors with a rim enhancement in 50%, with or without early wash out. All tumors had avascular parts. HA presented as multiple and irregular hypo-, iso- or hyperechoic lesions. After contrast enhancement, hypervascularization with individual patterns was evident in all patients. Of five, three had liquid parts. Patients with HA were significantly older (58 vs. 37 years, p = 0.014) and presented with lower thrombocyte counts (84 vs. 264, p = 0.0025) and with higher CEA levels (4.6 vs. 1.5, p = 0.03). Conclusion EHE and HA are inhomogeneous tumors, explaining the high inter-individual variability and heterogeneity in ultrasound examination. The presence of multifocal lesions, heterogeneity and undefined margins may differentiate EHE or HA from hemangioma. A biopsy is essential in the diagnosis of vascular tumors. PMID:25653860

  3. Pitfalls of contrast-enhanced ultrasound (CEUS) in the diagnosis of splenic sarcoidosis.

    PubMed

    Tana, C; Iannetti, G; D'Alessandro, P; Tana, M; Mezzetti, A; Schiavone, C

    2013-01-01

    By observing the real-time behavior of focal liver lesions at three vascular phases (arterial, portal-venous, and late), contrast-enhanced ultrasound (CEUS) has been successfully applied to differentiate benign from malignant hepatic nodules. In recent years, numerous studies highlighted the usefulness of CEUS also for other applications such as abdominal trauma, renal, pancreatic, thyroid, and inflammatory bowel diseases, supporting its role even in differentiating benign from malignant splenic nodules. Therefore, the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) recently updated the guidelines for the use of ultrasound contrast agents in clinical practice, pointing out the indication to characterize splenic parenchymal inhomogeneity or suspected lesions found on conventional ultrasound (BUS). We describe the case of a patient with a history of colon cancer and finding, at BUS and CEUS, of hypoechoic lesions with a highly suggestive pattern for metastases, subsequently histologically proved to be splenic localizations of a benign and multisystemic granulomatous disease such as sarcoidosis. We therefore reviewed the current literature focusing on the role of CEUS in differentiating benign from malignant splenic lesions, emphasizing on the lack of data and numerical shortage of sarcoidosis derived-lesions in the available studies. We conclude that sarcoidosis remains a diagnosis of exclusion and new studies are needed before defining precise indications of CEUS in these patients.

  4. Contrast enhanced ultrasound by real-time spatiotemporal filtering of ultrafast images

    NASA Astrophysics Data System (ADS)

    Desailly, Yann; Tissier, Anne-Marie; Correas, Jean-Michel; Wintzenrieth, Frédéric; Tanter, Mickaël; Couture, Olivier

    2017-01-01

    Contrast enhanced ultrasound (CEUS) takes advantage of the nonlinear behaviour of injected microbubbles. If these contrast techniques yield good specificity between bubbles and tissues, they suffer some drawbacks, inherently linked to their dependence on nonlinear content. In recent years, plane-wave ultrasound reached frame rates of up to 20 000 fps. In this study we propose a linear technique for CEUS that takes advantage of these very high frame rates to separate bubbles from tissue without requiring nonlinearities. Data-driven spatiotemporal filtering operations are used to separate different features in the image on the basis of coherence both in space and time. Such filter recently proved to improve Doppler sensitivity (Demene et al 2015 IEEE Trans. Med. Imaging 34 2271-85). In contrast with bubbles, even slow moving ones, tissues are highly coherent both in space and time. Therefore, singular value decomposition (SVD) seems to be a powerful tool for the separation of contrast agents and tissues. In this paper, we apply SVD processing to linear ultrafast ultrasound images for CEUS Doppler. The contrast levels reached by this technique were compared to those of a nonlinear gold standard sequence (PMPI Doppler) through a flow phantom study. The SVD technique reached contrast-to-tissue ratios (CTR) up to 10 dB higher in vitro, and proved to be robust in terms of probe motion and slow flow. A trial was also conducted on a transplanted human kidney, already imaged by means of power Doppler (Claudon et al 1999 Am. J. Roentgenol. 173 41-6) and microbubbles (Kay et al 2009 Clin. Radiol. 64 1081-7). Contrast levels yielded by the SVD technique measured up to 13 dB higher than those of PMPI Doppler.

  5. Experimental Study of Ultrasound Contrast Agent Mediated Heat Transfer for Therapeutic Applications

    NASA Astrophysics Data System (ADS)

    Razansky, D.; Adam, D. R.; Einziger, P. D.

    2006-05-01

    Ultrasound Contrast Agents (UCA) have been recently suggested as efficient enhancers of ultrasonic power deposition in tissue. The ultrasonic energy absorption by UCA, considered as disadvantageous in diagnostic imaging, might be valuable in therapeutic applications such as targeted hyperthermia or ablation treatments. The current study, based on theoretical predictions, was designed to experimentally measure the dissipation and heating effects of encapsulated UCA (Optison™) in a well-controlled and calibrated environment.

  6. Contrast enhanced ultrasound imaging for assessment of spinal cord blood flow in experimental spinal cord injury.

    PubMed

    Dubory, Arnaud; Laemmel, Elisabeth; Badner, Anna; Duranteau, Jacques; Vicaut, Eric; Court, Charles; Soubeyrand, Marc

    2015-05-07

    Reduced spinal cord blood flow (SCBF) (i.e., ischemia) plays a key role in traumatic spinal cord injury (SCI) pathophysiology and is accordingly an important target for neuroprotective therapies. Although several techniques have been described to assess SCBF, they all have significant limitations. To overcome the latter, we propose the use of real-time contrast enhanced ultrasound imaging (CEU). Here we describe the application of this technique in a rat contusion model of SCI. A jugular catheter is first implanted for the repeated injection of contrast agent, a sodium chloride solution of sulphur hexafluoride encapsulated microbubbles. The spine is then stabilized with a custom-made 3D-frame and the spinal cord dura mater is exposed by a laminectomy at ThIX-ThXII. The ultrasound probe is then positioned at the posterior aspect of the dura mater (coated with ultrasound gel). To assess baseline SCBF, a single intravenous injection (400 µl) of contrast agent is applied to record its passage through the intact spinal cord microvasculature. A weight-drop device is subsequently used to generate a reproducible experimental contusion model of SCI. Contrast agent is re-injected 15 min following the injury to assess post-SCI SCBF changes. CEU allows for real time and in-vivo assessment of SCBF changes following SCI. In the uninjured animal, ultrasound imaging showed uneven blood flow along the intact spinal cord. Furthermore, 15 min post-SCI, there was critical ischemia at the level of the epicenter while SCBF remained preserved in the more remote intact areas. In the regions adjacent to the epicenter (both rostral and caudal), SCBF was significantly reduced. This corresponds to the previously described "ischemic penumbra zone". This tool is of major interest for assessing the effects of therapies aimed at limiting ischemia and the resulting tissue necrosis subsequent to SCI.

  7. Characteristics and Echogenicity of Clinical Ultrasound Contrast Agents: An In Vitro and In Vivo Comparison Study.

    PubMed

    Hyvelin, Jean-Marc; Gaud, Emmanuel; Costa, Maria; Helbert, Alexandre; Bussat, Philippe; Bettinger, Thierry; Frinking, Peter

    2017-05-01

    To compare physicochemical characteristics and in vitro and in vivo contrast-enhanced ultrasound imaging performance of 3 commercially available ultrasound contrast agents: SonoVue (Bracco Imaging SpA, Colleretto Giacosa, Italy; also marketed as Lumason in the USA), Definity (Lantheus Medical Imaging, North Billerica, MA) and Optison (GE Healthcare AS, Oslo, Norway). Physicochemical characteristics were measured with a Multisizer Coulter Counter (Beckman Coulter, Fullerton, CA). Two ultrasound systems (Aplio 500; Toshiba Medical Systems Corp, Tochigi-ken, Japan; and Logiq E9; GE Healthcare, Little Chalfont, England) were used with different transducers. Contrast enhancement was measured in vitro by dose-ranging measurements using a custom-built beaker setup; in vivo imaging performances were compared in pigs (heart and liver) and rabbits (liver). Quantitative analyses were performed with VueBox quantification software (Bracco Suisse SA, Plan-les-Ouates, Switzerland). Measured physicochemical characteristics were in agreement with those provided by the manufacturers. In vitro data demonstrated that the performance of SonoVue was similar to or better than that of Definity but superior to Optison (normalized scattered power 2- to 10-fold higher with SonoVue). Similar results were obtained in vivo, although the duration of enhancement in the pig heart was longer for SonoVue compared to Definity, and quantitative analysis revealed higher enhancement for SonoVue (1.5-fold increase). For liver imaging, SonoVue and Definity showed similar contrast enhancement and duration of enhancement, but compared to Optison, both peak enhancement and duration of enhancement were superior for SonoVue (up to 2-fold increase). Imaging performance of SonoVue was similar to or slightly better than that of Definity, but it was superior to Optison for the conditions used in this study. © 2017 by the American Institute of Ultrasound in Medicine.

  8. Injectable microbubbles as contrast agents for diagnostic ultrasound imaging: the key role of perfluorochemicals.

    PubMed

    Schutt, Ernest G; Klein, David H; Mattrey, Robert M; Riess, Jean G

    2003-07-21

    Ultrasonography has, until recently, lacked effective contrast-enhancing agents. Micrometer-sized gas bubbles that resonate at a diagnostic frequency are ideal reflectors for ultrasound. However, simple air bubbles, when injected into the blood stream, disappear within seconds through the combined effects of Laplace pressure, blood pressure, and exposure to ultrasound energy. Use of fluorocarbon vapor, by extending the persistence of microbubbles in vivo from seconds to minutes, propelled contrast ultrasonography into clinical practice. Imaging techniques that selectively suppress tissue, but not microbubble signal, further increase image contrast. Approved products consist of C3F8 or SF6 microbubbles, and N2 microbubbles osmotically stabilized with C6F14. These agents allow the detection and characterization of cardiovascular abnormalities and solid organ lesions, such as tumors. By providing higher quality images, they improve the accuracy and confidence of disease diagnosis, and can play a decisive role in clinical decision making. New objectives include agents that target specific cells for the molecular imaging of disease, and drug and gene delivery, including ultrasound-triggered delivery.

  9. The Subharmonic Behavior and Thresholds of High Frequency Ultrasound Contrast Agents

    NASA Astrophysics Data System (ADS)

    Allen, John

    2016-11-01

    Ultrasound contrast agents are encapsulated micro-bubbles used for diagnostic and therapeutic biomedical ultrasound. The agents oscillate nonlinearly about their equilibrium radii upon sufficient acoustic forcing and produce unique acoustic signatures that allow them to be distinguished from scattering from the surrounding tissue. The subharmonic response occurs below the fundamental and is associated with an acoustic pressure threshold. Subharmonic imaging using ultrasound contrast agents has been established for clinical applications at standard diagnostic frequencies typically below 20 MHz. However, for emerging applications of high frequency applications (above 20 MHz) subharmonic imaging is an area of on-going research. The effects of attenuation from tissue are more significant and the characterization of agents is not as well understood. Due to specificity and control production, polymer agents are useful for high frequency applications. In this study, we highlight novel measurement techniques to measure and characterize the mechanical properties of the shell of polymer contrast agents. The definition of the subharmonic threshold is investigated with respect to mono-frequency and chirp forcing waveforms which have been used to achieve optimal subharmonic content in the backscattered signal. Time frequency analysis using the Empirical Mode Decomposition (EMD) and the Hilbert-Huang transform facilitates a more sensitive and robust methodology for characterization of subharmonic content with respect to non-stationary forcing. A new definition of the subharmonic threshold is proposed with respect to the energy content of the associated adaptive basis decomposition. Additional studies with respect to targeted agent behavior and cardiovascular disease are discussed. NIH, ONR.

  10. The effect of the sample size and location on contrast ultrasound measurement of perfusion parameters.

    PubMed

    Leinonen, Merja R; Raekallio, Marja R; Vainio, Outi M; Ruohoniemi, Mirja O; O'Brien, Robert T

    2011-01-01

    Contrast-enhanced ultrasound can be used to quantify tissue perfusion based on region of interest (ROI) analysis. The effect of the location and size of the ROI on the obtained perfusion parameters has been described in phantom, ex vivo and in vivo studies. We assessed the effects of location and size of the ROI on perfusion parameters in the renal cortex of 10 healthy, anesthetized cats using Definity contrast-enhanced ultrasound to estimate the importance of the ROI on quantification of tissue perfusion with contrast-enhanced ultrasound. Three separate sets of ROIs were placed in the renal cortex, varying in location, size or depth. There was a significant inverse association between increased depth or increased size of the ROI and peak intensity (P < 0.05). There was no statistically significant difference in the peak intensity between the ROIs placed in a row in the near field cortex. There was no significant difference in the ROIs with regard to arrival time, time to peak intensity and wash-in rate. When comparing two different ROIs in a patient with focal lesions, such as suspected neoplasia or infarction, the ROIs should always be placed at same depth and be as similar in size as possible.

  11. Copper oxide nanoparticles as contrast agents for MRI and ultrasound dual-modality imaging.

    PubMed

    Perlman, Or; Weitz, Iris S; Azhari, Haim

    2015-08-07

    Multimodal medical imaging is gaining increased popularity in the clinic. This stems from the fact that data acquired from different physical phenomena may provide complementary information resulting in a more comprehensive picture of the pathological state. In this context, nano-sized contrast agents may augment the potential sensitivity of each imaging modality and allow targeted visualization of physiological points of interest (e.g. tumours). In this study, 7 nm copper oxide nanoparticles (CuO NPs) were synthesized and characterized. Then, in vitro and phantom specimens containing CuO NPs ranging from 2.4 to 320 μg · mL(-1) were scanned, using both 9.4 T MRI and through-transmission ultrasonic imaging. The results show that the CuO NPs induce shortening of the magnetic T1 relaxation time on the one hand, and increase the speed of sound and ultrasonic attenuation coefficient on the other. Moreover, these visible changes are NP concentration-dependent. The change in the physical properties resulted in a substantial increase in the contrast-to-noise ratio (3.4-6.8 in ultrasound and 1.2-19.3 in MRI). In conclusion, CuO NPs are excellent candidates for MRI-ultrasound dual imaging contrast agents. They offer radiation-free high spatial resolution scans by MRI, and cost-effective high temporal resolution scans by ultrasound.

  12. Nonspherical dynamics and shape mode stability of ultrasound contrast agent microbubbles

    NASA Astrophysics Data System (ADS)

    Calvisi, Michael

    2016-11-01

    Ultrasound contrast agents (UCAs) are shell encapsulated microbubbles developed originally for ultrasound imaging enhancement. UCAs are more recently being exploited for therapeutic applications, such as for drug delivery, gene therapy, and tissue ablation. Ultrasound transducer pulses can induce spherical (radial) UCA oscillations, translation, and nonspherical shape oscillations, the dynamics of which are highly coupled. If driven sufficiently strongly, the ultrasound can induce breakup of UCAs, which can facilitate drug or gene delivery but should be minimized for imaging purposes to increase residence time and maximize diagnostic effect. Therefore, an understanding of the interplay between the acoustic driving and nonspherical shape mode stability of UCAs is essential for both diagnostic and therapeutic applications. In this work, we use both analytical and numerical methods to analyze shape mode stability for cases of small and large nonspherical oscillations, respectively. To analyze shape mode stability in the limit of small nonspherical perturbations, we couple a radial model of a lipid-coated microbubble with a model for bubble translation and nonspherical shape oscillation. This hybrid model is used to predict shape mode stability for ultrasound driving frequencies and pressure amplitudes of clinical interest. In addition, calculations of the stability of individual shape modes, residence time, maximum radius, and translation are provided with respect to acoustic driving parameters and compared to an unshelled bubble. The effects of shell elasticity, shell viscosity, and initial radius on stability are investigated. Furthermore, the well-established boundary element method (BEM) is used to investigate the dynamics and shape stability of large amplitude nonspherical oscillations of an ultrasonically-forced, polymer-coated microbubble near a rigid boundary. Different instability modes are identified based on the degree of jetting and proximity to the

  13. Endoscopic ultrasound in the diagnosis of acinar cell carcinoma of the pancreas: contrast-enhanced endoscopic ultrasound, endoscopic ultrasound elastography, and pathological correlation.

    PubMed

    Chantarojanasiri, Tanyaporn; Hirooka, Yoshiki; Kawashima, Hiroki; Ohno, Eizaburo; Yamamura, Takeshi; Funasaka, Kohei; Nakamura, Masanao; Miyahara, Ryoji; Ishigami, Masatoshi; Watanabe, Osamu; Nakaguro, Masato; Shimoyama, Yoshie; Nakamura, Shigeo; Goto, Hidemi

    2016-11-01

    We report a case series of five patients with pancreatic acinar cell carcinoma who received surgical treatment and compared the preoperative contrast-enhanced endoscopic ultrasound (EUS) and EUS elastography patterns with the surgical specimens. The contrast-enhanced EUS indicated vascular tumors with gradual enhancement in four patients and a hypovascular tumor in one patient. The elastography indicated an elastic score of 3 (hard lesion with softer border) in two patients and a score of 5 (hard lesion, which included the surrounding area) in two patients. In tumors with an elastic score of 5, the pathology exhibited abundant hyalinizing fibrous stroma or massive tumor invasion to the surrounding tissue. We concluded that acinar cell carcinoma of the pancreas has various patterns of EUS contrast-enhancement and elastography, depending on the pathologic phenotype.

  14. Endoscopic ultrasound in the diagnosis of acinar cell carcinoma of the pancreas: contrast-enhanced endoscopic ultrasound, endoscopic ultrasound elastography, and pathological correlation

    PubMed Central

    Chantarojanasiri, Tanyaporn; Hirooka, Yoshiki; Kawashima, Hiroki; Ohno, Eizaburo; Yamamura, Takeshi; Funasaka, Kohei; Nakamura, Masanao; Miyahara, Ryoji; Ishigami, Masatoshi; Watanabe, Osamu; Nakaguro, Masato; Shimoyama, Yoshie; Nakamura, Shigeo; Goto, Hidemi

    2016-01-01

    We report a case series of five patients with pancreatic acinar cell carcinoma who received surgical treatment and compared the preoperative contrast-enhanced endoscopic ultrasound (EUS) and EUS elastography patterns with the surgical specimens. The contrast-enhanced EUS indicated vascular tumors with gradual enhancement in four patients and a hypovascular tumor in one patient. The elastography indicated an elastic score of 3 (hard lesion with softer border) in two patients and a score of 5 (hard lesion, which included the surrounding area) in two patients. In tumors with an elastic score of 5, the pathology exhibited abundant hyalinizing fibrous stroma or massive tumor invasion to the surrounding tissue. We concluded that acinar cell carcinoma of the pancreas has various patterns of EUS contrast-enhancement and elastography, depending on the pathologic phenotype. PMID:27853750

  15. Nonlinear contrast imaging with an array-based micro-ultrasound system.

    PubMed

    Needles, A; Arditi, M; Rognin, N G; Mehi, J; Coulthard, T; Bilan-Tracey, C; Gaud, E; Frinking, P; Hirson, D; Foster, F S

    2010-12-01

    The main goal of this study was to determine the optimal strategy for a real-time nonlinear contrast mode for small-animal imaging at high frequencies, on a new array-based micro-ultrasound system. Previously reported contrast imaging at frequencies above 15 MHz has primarily relied on subtraction schemes involving B-mode image data. These approaches provide insufficient contrast to tissue ratios under many imaging conditions. In this work, pulse inversion, amplitude modulation and combinations of these were systematically investigated for the detection of nonlinear fundamental and subharmonic signal components to maximize contrast-to-tissue ratio (CTR) in the 18-24 MHz range. From in vitro and in vivo measurements, nonlinear fundamental detection with amplitude modulation provided optimal results, allowing an improvement in CTR of 13 dB compared with fundamental imaging. Based on this detection scheme, in vivo parametric images of murine kidneys were generated using sequences of nonlinear contrast images after intravenous bolus injections of microbubble suspensions. Initial parametric images of peak enhancement (PE), wash-in rate (WiR) and rise time (RT) are presented. The parametric images are indicative of blood perfusion kinetics, which, in the context of preclinical imaging with small animals, are anticipated to provide valuable insights into the progression of human disease models, where blood perfusion plays a critical role in either the diagnosis or treatment of the disease. Copyright © 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  16. Contrast-Enhanced Ultrasound as a New Investigative Tool in Diagnostic Imaging of Muscle Injuries-A Pilot Study Evaluating Conventional Ultrasound, CEUS, and Findings in MRI.

    PubMed

    Hotfiel, Thilo; Heiss, Rafael; Swoboda, Bernd; Kellermann, Marion; Gelse, Kolja; Grim, Casper; Strobel, Deike; Wildner, Dane

    2017-07-11

    To emphasize the diagnostic value of contrast-enhanced ultrasound (CEUS) in the imaging of muscle injuries with different degrees of severity by comparing findings to established imaging modalities such as conventional ultrasound and magnetic resonance imaging (MRI). Case series. Institutional study. Conventional ultrasound and CEUS were performed in the Department of Internal Medicine. Magnetic resonance imaging was carried out in the Department of Radiology within the Magnetom Avanto 1.5T and Magnetom Skyra fit 3T (Siemens Healthineers, Erlangen, Germany) and in the Institution of Imaging Diagnostics and Therapy (Magnetom Avanto 1.5T; Siemens, Erlangen, Germany). Fifteen patients who underwent an acute muscle injury were recruited. The appearance and detectable size of muscle injuries were compared between each imaging modality. The injuries were assessed by 3 independent observers and blinded between imaging modalities. All 15 injuries were identified on MRI and CEUS, whereas 10 injuries showed abnormalities in conventional ultrasound. The determination and measurement revealed significant differences between conventional ultrasound and CEUS depending on injury severity. Contrast-enhanced ultrasound revealed an impairment of microcirculation in grade I lesions (corresponding to intramuscular edema observed in MRI), which was not detectable using conventional ultrasound. Our results indicate that performing CEUS seems to be a sensitive additional diagnostic modality in the early assessment of muscle injuries. Our results highlight the advantages of CEUS in the imaging of low-grade lesions when compared with conventional ultrasound, as this was the more accurate modality for identifying intramuscular edema.

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

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

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

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

    PubMed

    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.

  19. On-chip preparation of nanoscale contrast agents towards high-resolution ultrasound imaging.

    PubMed

    Peyman, Sally A; McLaughlan, James R; Abou-Saleh, Radwa H; Marston, Gemma; Johnson, Benjamin R G; Freear, Steven; Coletta, P Louise; Markham, Alexander F; Evans, Stephen D

    2016-02-21

    Micron-sized lipid-stabilised bubbles of heavy gas have been utilised as contrast agents for diagnostic ultrasound (US) imaging for many years. Typically bubbles between 1 and 8 μm in diameter are produced to enhance imaging in US by scattering sound waves more efficiently than surrounding tissue. A potential area of interest for Contrast Enhanced Ultrasound (CEUS) are bubbles with diameters <1 μm or 'nanobubbles.' As bubble diameter decreases, ultrasonic resonant frequency increases, which could lead to an improvement in resolution for high-frequency imaging applications when using nanobubbles. In addition, current US contrast agents are limited by their size to the vasculature in vivo. However, molecular-targeted nanobubbles could penetrate into the extra-vascular space of cancerous tissue providing contrast in regions inaccessible to traditional microbubbles. This paper reports a new microfluidic method for the generation of sub-micron sized lipid stabilised particles containing perfluorocarbon (PFC). The nanoparticles are produced in a unique atomisation-like flow regime at high production rates, in excess of 10(6) particles per s and at high concentration, typically >10(11) particles per mL. The average particle diameter appears to be around 100-200 nm. These particles, suspected of being a mix of liquid and gaseous C4F10 due to Laplace pressure, then phase convert into nanometer sized bubbles on the application of US. In vitro ultrasound characterisation from these nanoparticle populations showed strong backscattering compared to aqueous filled liposomes of a similar size. The nanoparticles were stable upon injection and gave excellent contrast enhancement when used for in vivo imaging, compared to microbubbles with an equivalent shell composition.

  20. An Integrated System for Superharmonic Contrast-Enhanced Ultrasound Imaging: Design and Intravascular Phantom Imaging Study.

    PubMed

    Li, Yang; Ma, Jianguo; Martin, K Heath; Yu, Mingyue; Ma, Teng; Dayton, Paul A; Jiang, Xiaoning; Shung, K Kirk; Zhou, Qifa

    2016-09-01

    Superharmonic contrast-enhanced ultrasound imaging, also called acoustic angiography, has previously been used for the imaging of microvasculature. This approach excites microbubble contrast agents near their resonance frequency and receives echoes at nonoverlapping superharmonic bandwidths. No integrated system currently exists could fully support this application. To fulfill this need, an integrated dual-channel transmit/receive system for superharmonic imaging was designed, built, and characterized experimentally. The system was uniquely designed for superharmonic imaging and high-resolution B-mode imaging. A complete ultrasound system including a pulse generator, a data acquisition unit, and a signal processing unit were integrated into a single package. The system was controlled by a field-programmable gate array, on which multiple user-defined modes were implemented. A 6-, 35-MHz dual-frequency dual-element intravascular ultrasound transducer was designed and used for imaging. The system successfully obtained high-resolution B-mode images of coronary artery ex vivo with 45-dB dynamic range. The system was capable of acquiring in vitro superharmonic images of a vasa vasorum mimicking phantom with 30-dB contrast. It could detect a contrast agent filled tissue mimicking tube of 200 μm diameter. For the first time, high-resolution B-mode images and superharmonic images were obtained in an intravascular phantom, made possible by the dedicated integrated system proposed. The system greatly reduced the cost and complexity of the superharmonic imaging intended for preclinical study. Significant: The system showed promise for high-contrast intravascular microvascular imaging, which may have significant importance in assessment of the vasa vasorum associated with atherosclerotic plaques.

  1. Logistic Regression Analysis of Contrast-Enhanced Ultrasound and Conventional Ultrasound Characteristics of Sub-centimeter Thyroid Nodules.

    PubMed

    Zhao, Rui-Na; Zhang, Bo; Yang, Xiao; Jiang, Yu-Xin; Lai, Xing-Jian; Zhang, Xiao-Yan

    2015-12-01

    The purpose of the study described here was to determine specific characteristics of thyroid microcarcinoma (TMC) and explore the value of contrast-enhanced ultrasound (CEUS) combined with conventional ultrasound (US) in the diagnosis of TMC. Characteristics of 63 patients with TMC and 39 with benign sub-centimeter thyroid nodules were retrospectively analyzed. Multivariate logistic regression analysis was performed to determine independent risk factors. Four variables were included in the logistic regression models: age, shape, blood flow distribution and enhancement pattern. The area under the receiver operating characteristic curve was 0.919. With 0.113 selected as the cutoff value, sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 90.5%, 82.1%, 89.1%, 84.2% and 87.3%, respectively. Independent risk factors for TMC determined with the combination of CEUS and conventional US were age, shape, blood flow distribution and enhancement pattern. Age was negatively correlated with malignancy, whereas shape, blood flow distribution and enhancement pattern were positively correlated. The logistic regression model involving CEUS and conventional US was found to be effective in the diagnosis of sub-centimeter thyroid nodules.

  2. Assessment of microcirculation by contrast-enhanced ultrasound: a new approach in vascular medicine.

    PubMed

    Kaspar, Mathias; Partovi, Sasan; Aschwanden, Markus; Imfeld, Stephan; Baldi, Thomas; Uthoff, Heiko; Staub, Daniel

    2015-01-01

    Contrast-enhanced ultrasound (CEUS) has emerged as a valuable imaging modality that complements and enhances standard vascular ultrasound imaging. Ultrasound contrast agents are gas-filled microbubbles that are injected intravenously and serve as intravascular tracers. Based on the properties to enhance and to quantify the macro- and microcirculation down to the capillary perfusion level in different vascular territories and organs, CEUS imaging has the potential to improve the diagnostic performance in the detection and characterisation of various vascular disorders reviewed in this article. In carotid atherosclerotic disease, CEUS imaging provides additional information on plaque vulnerability by illustrating the presence and extent of intraplaque neovascularisation. This new imaging modality may be helpful for further risk stratification of arteriosclerotic lesions and for detecting patients at risk for vascular events, eventually leading to more specific individually tailored therapeutic recommendations. CEUS imaging is also a helpful tool for the diagnosis and for monitoring of inflammatory vascular diseases. It increases the diagnostic performance of ultrasound in detecting inflammatory changes of the vessel wall such as hypervascularisation and hyperaemia. Changes in vessel wall enhancement may also reflect the response to anti-inflammatory therapy. Moreover, CEUS imaging is also a valuable tool for the assessment of the microcirculation and the tissue perfusion in solid organs including native and transplanted kidneys. The technique provides more accurate information on perfusion deficits of the parenchyma in patients with kidney infarction, necrosis or graft dysfunction. CEUS also has great potential in the assessment of the microcirculation of the skeletal muscle, particularly in patients with peripheral artery disease or diabetic microangiopathy. In the future, the use of targeted on site microbubbles could further enhance and expand the diagnostic

  3. Transdermal drug delivery aided by an ultrasound contrast agent: an in vitro experimental study.

    PubMed

    Park, Donghee; Yoon, Jinhee; Park, Jingam; Jung, Byungjo; Park, Hyunjin; Seo, Jongbum

    2010-02-11

    Sonophoresis temporarily increases skin permeability such that medicine can be delivered transdermally. Cavitation is believed to be the predominant mechanism in sonophoresis. In this study, an ultrasound contrast agent (UCA) strategy was adopted instead of low frequency ultrasound to assure that cavitation occurred, and the efficacy of sonophoresis with UCA was quantitatively analyzed by optical measurements. The target drug used in this study was 0.1 % Definity(R) in 70% glycerol, which was delivered into porcine skin samples. Glycerol was used because it is an optical clearing agent, and the efficiency of glycerol delivery could be analyzed with optical measurements. The applied acoustic pressure was approximately 600 kPa at 1 MHz ultrasound with a 10% duty cycle for 60 minutes. Experimental results indicated that the measured relative contrast (RC) after sonophoresis with UCA was approximately 80% higher than RC after sonophoresis without UCA. In addition, the variance of RC was also reduced by more than 50% with the addition of a UCA. The use of a UCA appeared to increase cavitation, demonstrating that the use of a UCA can be effective in transdermal drug delivery (TDD).

  4. Transdermal Drug Delivery Aided by an Ultrasound Contrast Agent: An In Vitro Experimental Study

    PubMed Central

    Park, Donghee; Yoon, Jinhee; Park, Jingam; Jung, Byungjo; Park, Hyunjin; Seo, Jongbum

    2010-01-01

    Sonophoresis temporarily increases skin permeability such that medicine can be delivered transdermally. Cavitation is believed to be the predominant mechanism in sonophoresis. In this study, an ultrasound contrast agent (UCA) strategy was adopted instead of low frequency ultrasound to assure that cavitation occurred, and the efficacy of sonophoresis with UCA was quantitatively analyzed by optical measurements. The target drug used in this study was 0.1 % Definity® in 70% glycerol, which was delivered into porcine skin samples. Glycerol was used because it is an optical clearing agent, and the efficiency of glycerol delivery could be analyzed with optical measurements. The applied acoustic pressure was approximately 600 kPa at 1 MHz ultrasound with a 10% duty cycle for 60 minutes. Experimental results indicated that the measured relative contrast (RC) after sonophoresis with UCA was approximately 80% higher than RC after sonophoresis without UCA. In addition, the variance of RC was also reduced by more than 50% with the addition of a UCA. The use of a UCA appeared to increase cavitation, demonstrating that the use of a UCA can be effective in transdermal drug delivery (TDD). PMID:20448793

  5. Time-resolved nanoseconds dynamics of ultrasound contrast agent microbubbles manipulated and controlled by optical tweezers

    NASA Astrophysics Data System (ADS)

    Garbin, Valeria; Cojoc, Dan; Ferrari, Enrico; Di Fabrizio, Enzo; Overvelde, Marlies L. J.; Versluis, Michel; van der Meer, Sander M.; de Jong, Nico; Lohse, Detlef

    2006-08-01

    Optical tweezers enable non-destructive, contact-free manipulation of ultrasound contrast agent (UCA) microbubbles, which are used in medical imaging for enhancing the echogenicity of the blood pool and to quantify organ perfusion. The understanding of the fundamental dynamics of ultrasound-driven contrast agent microbubbles is a first step for exploiting their acoustical properties and to develop new diagnostic and therapeutic applications. In this respect, optical tweezers can be used to study UCA microbubbles under controlled and repeatable conditions, by positioning them away from interfaces and from neighboring bubbles. In addition, a high-speed imaging system is required to record the dynamics of UCA microbubbles in ultrasound, as their oscillations occur on the nanoseconds timescale. In this work, we demonstrate the use of an optical tweezers system combined with a high-speed camera capable of 128-frame recordings at up to 25 million frames per second (Mfps), for the study of individual UCA microbubble dynamics as a function of the distance from solid interfaces.

  6. Contrast-ultrasound dispersion imaging for prostate cancer localization by improved spatiotemporal similarity analysis.

    PubMed

    Kuenen, M P J; Saidov, T A; Wijkstra, H; Mischi, M

    2013-09-01

    Angiogenesis plays a major role in prostate cancer growth. Despite extensive research on blood perfusion imaging aimed at angiogenesis detection, the diagnosis of prostate cancer still requires systematic biopsies. This may be due to the complex relationship between angiogenesis and microvascular perfusion. Analysis of ultrasound-contrast-agent dispersion kinetics, determined by multipath trajectories in the microcirculation, may provide better characterization of the microvascular architecture. We propose the physical rationale for dispersion estimation by an existing spatiotemporal similarity analysis. After an intravenous ultrasound-contrast-agent bolus injection, dispersion is estimated by coherence analysis among time-intensity curves measured at neighbor pixels. The accuracy of the method is increased by time-domain windowing and anisotropic spatial filtering for speckle regularization. The results in 12 patient data sets indicated superior agreement with histology (receiver operating characteristic curve area = 0.88) compared with those obtained by reported perfusion and dispersion analyses, providing a valuable contribution to prostate cancer localization. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  7. The performance of PEGylated nanocapsules of perfluorooctyl bromide as an ultrasound contrast agent.

    PubMed

    Díaz-López, Raquel; Tsapis, Nicolas; Santin, Mathieu; Bridal, Sharon Lori; Nicolas, Valérie; Jaillard, Danielle; Libong, Danielle; Chaminade, Pierre; Marsaud, Véronique; Vauthier, Christine; Fattal, Elias

    2010-03-01

    The surface of polymeric nanocapsules used as ultrasound contrast agents (UCAs) was modified with PEGylated phospholipids in order to escape recognition and clearance by the mononuclear phagocyte system and achieve passive tumor targeting. Nanocapsules consisted of a shell of poly(lactide-co-glycolide) (PLGA) encapsulating a liquid core of perfluorooctyl bromide (PFOB). They were decorated with poly(ethylene glycol-2000)-grafted distearoylphosphatidylethanolamine (DSPE-PEG) incorporated in the organic phase before the solvent emulsification-evaporation process. The influence of DSPE-PEG concentration on nanocapsule size, surface charge, morphology, hydrophobicity and complement activation was evaluated. Zeta potential measurements, Hydrophobic interaction chromatography and complement activation provide evidence of DSPE-PEG presence at nanocapsule surface. Electronic microscopy reveals that the core/shell structure is preserved up to 2.64 mg of DSPE-PEG for 100 mg PLGA. In vivo ultrasound imaging was performed in mice bearing xenograft tumor with MIA PaCa-2 cells, either after an intra-tumoral or intravenous injection of nanocapsules. Tumor was observed only after the intra-tumoral injection. Despite the absence of echogenic signal in the tumor after intravenous injection of nanocapsules, histological analysis reveals their accumulation within the tumor tissue demonstrating that tissue distribution is not the unique property required for ultrasound contrast agents to be efficient. (c) 2009 Elsevier Ltd. All rights reserved.

  8. [Duplex ultrasound detection of type II endoleaks by after endovascular aneurysm repair: interest of contrast enhancement].

    PubMed

    Costa, P; Bureau Du Colombier, P; Lermusiaux, P

    2013-12-01

    Type II endoleaks (EFII) are related to retrograde flow via aorta tributaries. They are the most frequent complication after endovascular aneurysm repair (EVAR). We hypothesized that the use of contrast-enhanced ultrasound (CEUS) by an experienced vascular physician could increase the sensitivity of detecting EFII compared with computed tomography angiography (CTA) taken as the gold standard. From November 2010 to February 2013, patients with EVAR were included prospectively. All patients had a color duplex ultrasound (CDU), CEUS and CTA. Sensitivity, specificity and kappa's coefficient were determined to estimate the performance of CDU and CEUS to assess EFII compared with CTA. Sixty CDU and 60 CEUS explorations were compared to 60 CTA explorations. Nineteen type EFII were detected by CTA, 14 by CDU and 15 by CEUS. CDU sensitivity was 74% (κ=0.75), and CEUS sensitivity was 78% (κ=0.8). Both tests exhibited 97% specificity. There was good agreement between CDU results (κ=0.75) and CEUS results (κ=0.8) compared with CTA. There was very good agreement between CDU and CEUS results for detection of EFII (κ=0.93). There was no statistically significant difference between the sensitivity of CDU and CEUS (P=0.32). Our results suggest that contrast enhancement does not increase yield for ultrasound detection of type II endoleaks when performed by an experienced vascular physician. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  9. [Method for Extracting Vascular Perfusion Region Based on Ultrasound Contrast Agent].

    PubMed

    Shan, Xin; Wen, Yingang; Lin, Tao; Zhu, Xinjian

    2015-10-01

    Vascular perfusion distribution in fibroids contrast-enhanced ultrasound images provides useful pathological and physiological information, because the extraction of the vascular perfusion area can be helpful to quantitative evaluation of uterine fibroids blood supply. The pixel gray scale in vascular perfusion area of fibroids contrast-enhanced ultrasound image sequences is different from that in other regions, and, based on this, we proposed a method of extracting vascular perfusion area of fibroids. Firstly, we denoised the image sequence, and then we used Brox optical flow method to estimate motion of two adjacent frames, based on the results of the displacement field for motion correction. Finally, we extracted vascular perfusion region from the surrounding background based on the differences in gray scale for the magnitude of the rich blood supply area and lack of blood supply area in ultrasound images sequence. The experimental results showed that the algorithm could accurately extract the vascular perfusion area, reach the precision of identification of clinical perfusion area, and only small amount of calculation was needed and the process was fairly simple.

  10. Surface modes and acoustic scattering of microspheres and ultrasound contrast agents.

    PubMed

    Falou, Omar; Jafari Sojahrood, Amin; Kumaradas, J Carl; Kolios, Michael C

    2012-09-01

    Surface modes of spherical objects subject to ultrasound excitation have been recently proposed to explain experimental measurements of scattering from microspheres and ultrasound contrast agents (UCAs). In this work, the relationship between surface modes and resonance frequencies of microspheres and UCAs is investigated. A finite-element model, built upon the fundamentals of wave propagation and structural mechanics, was introduced and validated against analytical solutions (error <5%). Numerical results showed the existence of a systematic relationship between resonance frequencies and surface modes of a 30 μm microsphere driven at 1-70 MHz. On the contrary, for a 100 nm shelled, 4 μm diameter UCA, no clear relationship between the resonance frequencies and the surface modes was found in the frequency range examined. Instead, the UCA exhibited a collection of complex oscillations, which appear to be a combination of various surface modes and displacements. A study of the effects of varying the shell properties on the backscatter showed the presence of peaks in the backscatter of thick-shelled UCAs, which are not predicted by previous models. In summary, this work presents a systematic effort to examine scattering and surface modes from ultrasound contrast agents using finite-element models.

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  13. Numerical Modeling of 3-D Dynamics of Ultrasound Contrast Agent Microbubbles Using the Boundary Integral Method

    NASA Astrophysics Data System (ADS)

    Calvisi, Michael; Manmi, Kawa; Wang, Qianxi

    2014-11-01

    Ultrasound contrast agents (UCAs) are microbubbles stabilized with a shell typically of lipid, polymer, or protein and are emerging as a unique tool for noninvasive therapies ranging from gene delivery to tumor ablation. The nonspherical dynamics of contrast agents are thought to play an important role in both diagnostic and therapeutic applications, for example, causing the emission of subharmonic frequency components and enhancing the uptake of therapeutic agents across cell membranes and tissue interfaces. A three-dimensional model for nonspherical contrast agent dynamics based on the boundary integral method is presented. The effects of the encapsulating shell are approximated by adapting Hoff's model for thin-shell, spherical contrast agents to the nonspherical case. A high-quality mesh of the bubble surface is maintained by implementing a hybrid approach of the Lagrangian method and elastic mesh technique. Numerical analyses for the dynamics of UCAs in an infinite liquid and near a rigid wall are performed in parameter regimes of clinical relevance. The results show that the presence of a coating significantly reduces the oscillation amplitude and period, increases the ultrasound pressure amplitude required to incite jetting, and reduces the jet width and velocity.

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

    NASA Astrophysics Data System (ADS)

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

    2016-12-01

    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. Projects supported by the National Natural Science Foundation of China (Grant Nos. 81127901, 81227004, 11374155, 11274170, 11274176, 11474001, 11474161, 11474166, and 11674173), the National High-Technology Research and Development Program, China (Grant No. 2012AA022702), and Qing Lan Project of Jiangsu Province, China.

  15. Preliminary Analysis of Clinical Situations Involved in Quantification of Contrast-Enhanced Ultrasound in Crohn's Disease.

    PubMed

    Cheng, Wenjie; Gao, Xiang; Wang, Weili; Zhi, Min; Tang, Jian; Wen, Yan-Ling; Yu, Junli; Chen, Yao; Liu, Xiaoyin; Yang, Chuan; Hu, Pinjin; Liu, Guangjian

    2016-08-01

    To assess influencing factors for quantitative analysis of contrast-enhanced ultrasound (CEUS) in Crohn's disease (CD), dynamic CEUS examinations from 77 consecutive CD patients were recorded. Peak intensity (PI) values were calculated using the pre-installed quantification software of the ultrasound scanner. The influence of depth, pressure from the ultrasound probe and intraluminal gas was analyzed. The PI value of the anterior wall was lower than that of the posterior wall when the depth was ≤3.4 cm (17.9 dB vs. 21.3 dB; p < 0.05) or evident pressure was exerted (19.1 dB vs. 22.5 dB; p < 0.01). In the presence of intraluminal gas, the PI of the anterior wall was higher than that of the posterior wall (20.7 dB vs. 18.8 dB; p < 0.05). Nevertheless, no significant difference was found between the PI value of anterior and posterior walls when the depth was >3.4 cm (19.8 dB vs. 20.3 dB), moderate pressure was exerted (20.5 dB vs. 21.1 dB) or luminal gas was excluded between the two bowel walls (18.9 dB vs. 21.2 dB; p ≥ 0.05). The factors of depth, pressure from the ultrasound probe and intraluminal gas can affect the quantification results of CEUS. It is preferable to place the region of interest in the posterior wall when luminal gas is absent and in the anterior wall when luminal gas is present. In the latter case, more attention should be paid to reducing pressure by the ultrasound probe.

  16. Investigations on the destruction of ultrasound contrast agents: Fragmentation thresholds, inertial cavitation, and bioeffects

    NASA Astrophysics Data System (ADS)

    Chen, Wen-Shiang

    Ultrasound contrast agents (UCA) have shown great potential in both diagnostic and therapeutic applications recently. To fully explore the possible applications and the safety concerns of using UCA, a complete understanding of the UCA responses to various acoustic fields is necessary. Therefore, we performed a series of experiments and simulations to investigate the various acoustic properties of UCA with different gases and shells. We also investigated the mechanisms of some UCA-enhanced bioeffects including thrombolysis, hemolysis and high-intensity focused ultrasound (HIFU) tumor ablation. Two pressure thresholds were found: the fragmentation threshold and continuous inertial cavitation (IC) threshold. At the fragmentation threshold, bubbles were destroyed and the released gas dissolved in the surrounding solution at a rate which depended on the bubble's initial size and type of gas. The continuous IC threshold occurred at a higher pressure, where fragments of destroyed UCA (derivative bubbles) underwent violent inertial collapse; the period of activity depending on acoustic parameters such as frequency, pressure, pulse length, and pulse repetition frequency (PRF). Different UCA had different threshold pressures and demonstrated different magnitudes of IC activity after destruction. The amount of derivative bubbles generated by IC was determined by several acoustic parameters including pressure, pulse length and PRE For the same acoustic energy delivered, longer pulses generated more bubbles. More IC could be induced if the derivative bubbles could survive through the 'off' period of the pulsed ultrasound waves, and served as nuclei for the subsequent IC. In therapeutic applications, evidences of IC activity were recorded during the hemolysis, thrombolysis, and the lesion-formation processes with UCA. Hemolysis and thrombolysis were highly correlated to the presence of ultrasound and UCA, and correlated well with the amount of the IC activity. Finally, the

  17. Hadamard-Encoded Multi-Pulses for Contrast-Enhanced Ultrasound Imaging.

    PubMed

    Gong, Ping; Song, Pengfei; Chen, Shigao

    2017-08-30

    The development of contrast-enhanced ultrasound (CEUS) imaging offers great opportunities for new ultrasound clinical applications such as myocardial perfusion imaging and abdominal lesion characterization. In CEUS imaging, the contrast agents (i.e., microbubbles) are utilized to improve the contrast between blood and tissue based on their high nonlinearity under low ultrasound pressure. In this paper, we propose a new CEUS pulse sequence by combining Hadamard-encoded multi-pulses (HEM) with fundamental frequency bandpass filter (i.e., filter centered on transmit frequency). HEM consecutively emits multi-pulses encoded by a second-order Hadamard matrix in each of the two transmission events (i.e., pulse-echo events), as opposed to conventional CEUS methods which emit individual pulses in two separate transmission events (i.e., pulse inversion, amplitude modulation, and pulse inversion amplitude modulation combined). In HEM imaging, the microbubble responses can be improved by the longer transmit pulse, and the tissue harmonics can be suppressed by the fundamental frequency filter, leading to significantly improved contrast-to-tissue ratio (CTR) and signal-to-noise ratio (SNR). In addition, the fast polarity change between consecutive coded pulse emissions excites strong nonlinear microbubble echoes, further enhancing the CEUS image quality. The spatial resolution of HEM image is compromised as compared to other microbubble imaging methods due to the longer transmit pulses and the lower imaging frequency (i.e., fundamental frequency). However, the resolution loss was shown to be negligible and could be offset by the significantly enhanced CTR, SNR and penetration depth. These properties of HEM can potentially facilitate robust CEUS imaging for a many clinical applications, especially for deep abdominal organs and heart.

  18. Application of contrast-enhanced ultrasound before inferior vena cava filter recovery.

    PubMed

    Yan, Ji-Ping; Li, Wei-Qin; Wang, Zhen-Feng; Guo, Bian-Lian

    2017-10-01

    This study aims to investigate the clinical value of contrast-enhanced ultrasound (CEU) before temporary inferior vena cava filter (IVCF) recovery in patients with deep venous thrombosis, in order to provide ultrasound signs for the recovery of IVCF in clinical practice. The CEU manifestations of patients with deep vein thrombosis before temporary IVCF recovery were retrospectively analyzed. With the manifestations of digital subtraction angiography (DSA) or results of the surgical recovery of IVCF as the standard, the detection rate of a thrombus in IVCF was compared between conventional ultrasound and CEU, and the role of CEU in detecting complications of IVCF was analyzed. In the 103 patients with IVCF, conventional ultrasound and CEU did not reveal any filter displacement and deformation, as well as infection. In 86 patients, filters were successfully recovered under DSA. In one patient, the filter was removed surgically. In 16 patients, recovery failed or was given up, and inferior vena cava (IVC) angiography was performed. The recovery rate of IVCF was 84.5%. Among all cases, thrombi were found within the filters or around the filter in 23 patients. The detection rate of thrombi was 47.8% (11/23) by conventional ultrasound and 82.6% (19/23) by CEU, and the difference between these two methods was statistically significant (P<0.05). CEU drew a misdiagnosis of thrombus within the filter in one patient, and the diagnosis was not confirmed after the recovery of the filter. The diagnostic coincidence rate of CEU for thrombus in the IVCF was 95.1%, and the positive predictive value was 95%. In another case, the foot of the IVCF pierced out of the wall of the IVC into the intestinal wall; and this was confirmed by DSA. Hence, recovery was given up. Thrombosis is the main complication after IVCF placement. CEU revealed typical manifestations of thrombi in the IVC, and has overcome the shortcoming of color Doppler ultrasound such as angular dependence. Its detection

  19. Current consensus and guidelines of contrast enhanced ultrasound for the characterization of focal liver lesions

    PubMed Central

    Jang, Jae Young; Kim, Moon Young; Jeong, Soung Won; Kim, Tae Yeob; Kim, Seung Up; Lee, Sae Hwan; Suk, Ki Tae; Park, Soo Young; Woo, Hyun Young; Kim, Sang Gyune; Heo, Jeong; Baik, Soon Koo; Kim, Hong Soo

    2013-01-01

    The application of ultrasound contrast agents (UCAs) is considered essential when evaluating focal liver lesions (FLLs) using ultrasonography (US). Microbubble UCAs are easy to use and robust; their use poses no risk of nephrotoxicity and requires no ionizing radiation. The unique features of contrast enhanced US (CEUS) are not only noninvasiveness but also real-time assessing of liver perfusion throughout the vascular phases. The later feature has led to dramatic improvement in the diagnostic accuracy of US for detection and characterization of FLLs as well as the guidance to therapeutic procedures and evaluation of response to treatment. This article describes the current consensus and guidelines for the use of UCAs for the FLLs that are commonly encountered in US. After a brief description of the bases of different CEUS techniques, contrast-enhancement patterns of different types of benign and malignant FLLs and other clinical applications are described and discussed on the basis of our experience and the literature data. PMID:23593604

  20. Subharmonic response from ultrasound contrast microbubbles for noninvasive blood pressure estimation

    NASA Astrophysics Data System (ADS)

    Katiyar, Amit; Sarkar, Kausik; Forsberg, Flemming

    2010-11-01

    Estimation of local organ-level blood pressure can help in diagnosing and monitoring heart and vascular diseases. Subharmonic signals from ultrasound contrast microbubbles have been proposed as a noninvasive alternative to the current practice of using manometer-tipped catheter. Approximately 10dB linear decrease in subharmonic component with 25 kPa pressure increase (typical blood pressure variation) has been reported for several contrast microbubbles. Here we report a theoretical investigation of the underlying phenomenon. We first study the well established model of a free microbubble to show that reduction of subharmonic with ambient pressure increase occurs only below a certain excitation frequency. Above this critical frequency, subharmonic signal increases with ambient pressure. Furthermore, where it decreases with ambient pressure, the relationship is linear only above certain excitation pressure. The dependence of the critical frequency on bubble radius and possibly bubble size distribution is discussed. We also report similar behavior for several models for encapsulated contrast microbubbles.

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

    NASA Astrophysics Data System (ADS)

    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.

  2. Acute segmental testicular infarction at contrast-enhanced ultrasound: early features and changes during follow-up.

    PubMed

    Bertolotto, Michele; Derchi, Lorenzo E; Sidhu, Paul S; Serafini, Giovanni; Valentino, Massimo; Grenier, Nicolas; Cova, Maria A

    2011-04-01

    The purpose of this retrospective study was to assess whether contrast-enhanced ultrasound is useful for characterization of acute segmental testicular infarction. Twenty men with acute scrotal pain and suspected segmental testicular infarction underwent contrast-enhanced ultrasound. Three patients underwent orchiectomy. For the other patients, the final diagnosis was based on the absence of tumor markers and a change in the size or shape of the tumor during follow-up. Forty-nine color Doppler ultrasound studies (16 within 24 hours of the onset of pain; 14, 2-17 days after pain onset; 19 after 1 month or more), and 38 contrast-enhanced ultrasound studies (13 within 24 hours after pain onset; nine, 2-17 days; 16 after 1 month or more) were performed. Fourteen of 16 lesions examined within 24 hours were oval, and two were wedge shaped. Eight lesions were isoechoic to the testis, six were hypoechoic, and two had mixed echogenicity. Twelve lesions were avascular and four were hypovascular at color Doppler examination. Contrast-enhanced ultrasound showed avascular parenchymal lobules in all cases and without perilesional rim enhancement in 12 of 13 studies. Two to 17 days after the symptoms appeared, contrast-enhanced ultrasound showed avascular lobules in all cases and perilesional rim enhancement in eight examinations. After 1 month or more, contrast-enhanced ultrasound depicted intralesional vascular spots in 12 of 14 infarcts. Perilesional enhancement was absent. Recognition of lobular morphologic characteristics and the presence of perilesional rim enhancement at contrast-enhanced ultrasound can increase confidence in the diagnosis of segmental testicular infarction compared with reliance on gray-scale and color Doppler findings. Changes in lesion features during follow-up confirm the differential diagnosis from other testicular lesions and allow conservative management.

  3. Accuracy of contrast-enhanced ultrasound compared with conventional ultrasound in acute pancreatitis: Diagnosis and complication monitoring.

    PubMed

    Cai, Diming; Parajuly, Shyam Sundar; Wang, Huiyao; Wang, Xiaoling; Ling, Wenwu; Song, Bin; Li, Yongzhong; Luo, Yan

    2016-11-01

    Contrast-enhanced ultrasound (CEUS) has been used for diagnosing acute pancreatitis (AP), particularly severe acute pancreatitis (SAP). However, the diagnostic difference between CEUS and conventional ultrasonography (CUS) for AP and SAP has not been reported. The aim of the present study was to investigate the diagnostic accuracy of CUS and CEUS for AP. A total of 196 patients clinically diagnosed with AP were selected. All patients underwent CUS, CEUS and contrast-enhanced computed tomography (CECT) within 72 h. CECT was considered the gold standard. Pancreatic size, peripancreatic fluid collection (PPFC) and splenic vessel complications were the variables observed by CUS and CEUS. The differences in the variables among the three methods were analyzed using the χ(2) test and statistical analysis software. Significant differences in pancreatic size, PPFC and splenic vessel complications in AP were observed between CEUS and CUS (P<0.05). χ(2) test results indicated that CEUS significantly differed from CUS in terms of having a higher diagnostic accuracy for AP and SAP (P<0.05). The results indicate that CEUS is a reliable method for the diagnosis and monitoring of AP and SAP, and may be substituted for CECT.

  4. Mesoporous silica nanoparticles as a breast-cancer targeting ultrasound contrast agent

    PubMed Central

    Milgroom, Andrew; Intrator, Miranda; Madhavan, Krishna; Mazzaro, Luciano; Shandas, Robin; Liu, Bolin; Park, Daewon

    2014-01-01

    Ultrasound (US) is used widely in the context of breast cancer. While it is advantageous for a number of reasons, it has low specificity and requires the use of a contrast agent. Its use as a standalone diagnostic and real-time imaging modality could be achieved by development of a tumor-targeted ultrasound contrast agent (UCA); functionalizing the UCA with a tumor-targeting agent would also allow the targeted administration of anti-cancer drugs at the tumor site. In this article, clinical US techniques are used to show that mesoporous silica nanoparticles (MSNs), functionalized with the monoclonal antibody Herceptin®, can be used as an effective UCA by increasing US image contrast. Furthermore, in vitro assays show the successful localization and binding of the MSN-Herceptin conjugate to HER2+ cancer cells, resulting in tumor-specific cytotoxicity. These results demonstrate the potential of MSNs as a stable, biocompatible, and effective therapeutic and diagnostic (“theranostic”) agent for US-based breast cancer imaging, diagnosis, and treatment. PMID:24269054

  5. Intravascular ultrasound-guided angioplasty of hemodialysis loop graft in a patient with contrast allergy.

    PubMed

    Casey, Patrick E; Miranda, Charles J; Al-Khaffaf, Haytham; Woodhead, Peter M

    2014-01-01

    A surveillance duplex scan detected a stenosis within a left groin hemodialysis loop graft in a 57-year-old woman who was allergic to both iohexol and gadolinium contrast agents. This precluded the use of standard angioplasty treatment techniques. Intravascular ultrasound (IVUS) uses a catheter mounted with a miniaturized ultrasound probe to produce detailed cross-sectional vessel images. Clinically, it has been used in the assessment of coronary artery disease but has also supplemented standard angiography techniques in the assessment of peripheral vascular and hemodialysis access lesions. IVUS was utilized as the solitary imaging modality to identify the graft stenosis and guide the placement of a 6 mm diameter angioplasty balloon. Two areas of stenosis were successfully dilated and subsequent IVUS re-examination showed abolition of the stenosis. Twelve-month follow-up surveillance scan showed that the graft remained functional with good flow rates. In the setting of contrast allergy, IVUS may provide a valid and safe tool in the localization and treatment of peripheral vessel stenosis, including arteriovenous fistula angioplasty. To our knowledge this is the first reported use of IVUS for hemodialysis graft salvage adopting a completely 'contrast-free' technique. More studies are required to establish the true role of IVUS in the management of hemodialysis access angioplasty, but this successful case contributes valuable information to the literature on its clinical application.

  6. Nanosized Ultrasound Enhanced-Contrast Agent for in Vivo Tumor Imaging via Intravenous Injection.

    PubMed

    Kim, Manse; Lee, Jong Hyun; Kim, Se Eun; Kang, Seong Soo; Tae, Giyoong

    2016-04-06

    To enhance the detection limit of ultrasound (US) imaging, ultrasound enhanced-contrast agents (UECAs) that can go preferentially to the target tissue such as a tumor and amplify the US signal have been developed. However, nanosized UECAs among various UECAs developed are very limited to clearly demonstrate proper ability for selective tumor detection by US imaging upon their intravenous injection. In this study, we prepared CaCO3 nanoparticles that were formed inside a flexible and biocompatible pluronic-based nanocarrier. This nanosized UECA was stable in serum-containing media and generated CO2, more preferentially at low pH; thus, it could be detected by US imaging. After intravenous injection into tumor-bearing mice, this nanosized UECA showed a significant US contrast enhancement at the tumor site in 1 h, in contrast to no change in the liver, followed by a rapid clearance from the body in 24 h. Therefore, the present nanosized UECA could be applied as an effective diagnostic modality for in vivo tumor imaging by ultrasonography.

  7. Contrast-enhanced ultrasound for blunt hepatic trauma: an animal experiment.

    PubMed

    Yekuo, Li; Shasha, Wang; Xiansheng, Zhu; Qi, Chen; Guoxin, Luo; Feng, Huo

    2010-09-01

    The aim of this study was to study the value of contrast-enhanced ultrasound (CEUS) in the diagnosis of active hemorrhage and intraparenchymal lesions in blunt hepatic trauma versus conventional ultrasound (US). Twenty heparinized and anesthetized domestic pigs have been created to animal models with blunt hepatic trauma by a special impacting device. Conventional US and CEUS were performed to determine if hepatic traumas were present. Active hemorrhage, the presence of intraparenchymal lesions, and sonographic pattern were evaluated for conventional US and CEUS, as compared with laparotomy and pathologic findings. Contrast-enhanced US detected active hemorrhage from the injured livers in all cases, but conventional US did not find that in any case. The sensitivity of CEUS and conventional US in diagnosing intraparenchymal lesions of blunt hepatic trauma were 100% and 60%, respectively. Contrast-enhanced US is more sensitive than conventional US in determining the active hemorrhage and intraparenchymal lesions in blunt hepatic trauma. Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.

  8. RENAL RETENTION OF LIPID MICROBUBBLES: A POTENTIAL MECHANISM FOR FLANK DISCOMFORT DURING ULTRASOUND CONTRAST ADMINISTRATION

    PubMed Central

    Liu, Ya Ni; Khangura, Jaspreet; Xie, Aris; Belcik, J. Todd; Qi, Yue; Davidson, Brian P.; Zhao, Yan; Kim, Sajeevani; Inaba, Yoichi; Lindner, Jonathan R.

    2013-01-01

    Background The etiology for flank pain sometimes experienced during administration of ultrasound contrast agents is unknown. We investigated whether microbubble ultrasound contrast agents are retained within the renal microcirculation which could lead to either flow disturbance or local release of vasoactive and pain mediators downstream from complement activation. Methods Retention of lipid-shelled microbubbles in the renal microcirculation of mice was assessed by confocal fluorescent microscopy and contrast-enhanced ultrasound (CEU) imaging with dose-escalating intravenous injection. Studies were performed with size-segregated microbubbles to investigate physical entrapment, after glycocalyx degradation, and in wild-type and C3-deficient mice to investigate complement-mediated retention. Urinary bradykinin was measured before and after microbubbles. Renal CEU in human subjects (n=13) was performed 7–10 min after completion of lipid microbubble administration. Results In both mice and humans, microbubble retention was detected in the renal cortex by persistent CEU signal enhancement. Microbubble retention in mice was linearly related to dose and occurred almost exclusively in cortical glomerular microvessels. Microbubble retention did not affect microsphere-derived renal blood flow. Microbubble retention was not influenced by glycocalyx degradation nor by microbubble size, thereby excluding lodging, but was reduced by 90% (p<0.01) in C3-deficient mice. Urinary bradykinin increased by 65% five minutes after microbubble injection. Conclusion Lipid-shelled microbubbles are retained in the renal cortex due to complement-mediated interactions with glomerular microvascular endothelium. Microbubble retention does not adversely affect renal perfusion but does generate complement-related intermediates that are known to mediate nociception and could be responsible for flank pain. PMID:24035699

  9. Stimulus-Responsive Ultrasound Contrast Agents for Clinical Imaging: Motivations, Demonstrations, and Future Directions

    PubMed Central

    Goodwin, Andrew P.; Nakatsuka, Matthew A.; Mattrey, Robert F.

    2014-01-01

    Microbubble ultrasound contrast agents allow imaging of the vasculature with excellent resolution and signal-to-noise ratios. Contrast in microbubbles derives from their interaction with an ultrasound wave to generate signal at harmonic frequencies of the stimulating pulse; subtracting the elastic echo caused by the surrounding tissue can enhance the specificity of these harmonic signals significantly. The nonlinear acoustic emission is caused by pressure-driven microbubble size fluctuations, which in both theoretical descriptions and empirical measurements was found to depend on the mechanical properties of the shell that encapsulates the microbubble as well as stabilizes it against the surrounding aqueous environment. Thus biochemically-induced switching between a rigid “off” state and a flexible “on” state provides a mechanism for sensing chemical markers for disease. In our research, we coupled DNA oligonucleotides to a stabilizing lipid monolayer to modulate stiffness of the shell and thereby induce stimulus-responsive behavior. In initial proof-of-principle studies, it was found that signal modulation came primarily from DNA crosslinks preventing the microbubble size oscillations rather than merely damping the signal. Next, these microbubbles were redesigned to include an aptamer sequence in the crosslinking strand, which not only allowed the sensing of the clotting enzyme thrombin but also provided a general strategy for sensing other soluble biomarkers in the bloodstream. Finally, the thrombin-sensitive microbubbles were validated in a rabbit model, presenting the first example of an ultrasound contrast agent that could differentiate between active and inactive clots for the diagnosis of Deep Venous Thrombosis. PMID:25195785

  10. Stimulus-responsive ultrasound contrast agents for clinical imaging: motivations, demonstrations, and future directions.

    PubMed

    Goodwin, Andrew P; Nakatsuka, Matthew A; Mattrey, Robert F

    2015-01-01

    Microbubble ultrasound contrast agents allow imaging of the vasculature with excellent resolution and signal-to-noise ratios. Contrast in microbubbles derives from their interaction with an ultrasound wave to generate signal at harmonic frequencies of the stimulating pulse; subtracting the elastic echo caused by the surrounding tissue can enhance the specificity of these harmonic signals significantly. The nonlinear acoustic emission is caused by pressure-driven microbubble size fluctuations, which in both theoretical descriptions and empirical measurements was found to depend on the mechanical properties of the shell that encapsulates the microbubble as well as stabilizes it against the surrounding aqueous environment. Thus biochemically induced switching between a rigid 'off' state and a flexible 'on' state provides a mechanism for sensing chemical markers for disease. In our research, we coupled DNA oligonucleotides to a stabilizing lipid monolayer to modulate stiffness of the shell and thereby induce stimulus-responsive behavior. In initial proof-of-principle studies, it was found that signal modulation came primarily from DNA crosslinks preventing the microbubble size oscillations rather than merely damping the signal. Next, these microbubbles were redesigned to include an aptamer sequence in the crosslinking strand, which not only allowed the sensing of the clotting enzyme thrombin but also provided a general strategy for sensing other soluble biomarkers in the bloodstream. Finally, the thrombin-sensitive microbubbles were validated in a rabbit model, presenting the first example of an ultrasound contrast agent that could differentiate between active and inactive clots for the diagnosis of deep venous thrombosis. © 2014 Wiley Periodicals, Inc.

  11. The Natural Frequency of Nonlinear Oscillation of Ultrasound Contrast Agents in Microvessels

    PubMed Central

    Qin, Shengping; Ferrara, Katherine W.

    2009-01-01

    Ultrasound Contrast Agent (UCAs) are under intensive investigation for their applications in physiological and molecular imaging and drug delivery. Prediction of the natural frequency of the oscillation of UCAs in microvessels has drawn increasing attention. To our knowledge, the existing models to predict the natural frequency of oscillation of UCAs in microvessels all apply the linear approximation and treat the blood vessel wall as a rigid boundary. In the potential applications of ultrasound imaging drug and gene delivery, the compliance of small vessels may play an important role in the bubble’s oscillation. The goal of this work is to provide a lumped-parameter model to study the natural frequency of nonlinear oscillation of UCAs in microvessels. Three types of the blood vessel conditions have been considered. i.e. rigid vessels, normal compliable vessels and vessels with increasing stiffness that could correspond to tumor vasculature. The corresponding bubble oscillation frequencies in the vessels with radius less than 100 μm are examined in detail. When a bubble with a radius of 4 μm is confined in a compliable vessel (inner radius 5 μm and length 100μm), the natural frequency of bubble oscillation increases by a factor of 1.7 as compared with a bubble in an unbounded field. The natural frequency of oscillation of a bubble in a compliable vessel increases with decreasing vessel size while decreasing with increasing values of vessel rigidity. This model suggests that contrast agent size, blood vessel size distribution and the type of vasculature should be comprehensively considered for choosing the transmitted frequency in ultrasound contrast imaging and drug delivery. PMID:17478030

  12. RGD-Targeted Ultrasound Contrast Agent for Longitudinal Assessment of Hep-2 Tumor Angiogenesis In Vivo

    PubMed Central

    Hu, Qiao; Wang, Xiao-Yan; Kang, Li-Ke; Wei, Hai-Ming; Xu, Chun-Mei; Wang, Tao; Wen, Zong-Hua

    2016-01-01

    Objective To prepare arginine-glycine-aspartate (RGD)-targeted ultrasound contrast microbubbles (MBs) and explore the feasibility of their use in assessing dynamic changes in αvβ3 integrin expression in a murine model of tumor angiogenesis. Methods RGD peptides were conjugated to the surfaces of microbubbles via biotin-avidin linkage. Microbubbles bearing RADfK peptides were prepared as controls. The RGD-MBs were characterized using an Accusizer 780 and optical microscopy. The binding specificity of the RGD-MBs for ανβ3-expressing endothelial cells (bEnd.3) was demonstrated in vitro by a competitive inhibition experiment. In an in vivo study, mice bearing tumors of three different stages were intravenously injected with RGD-MBs and subjected to targeted, contrast-enhanced, high-frequency ultrasound. Subsequently, tumors were harvested and sectioned for immunofluorescence analysis of ανβ3 expression. Results The mean size of the RGD-MBs was 2.36 ± 1.7 μm. The RGD-MBs showed significantly higher adhesion levels to bEnd.3 cells compared to control MBs (P < 0.01). There was rarely binding of RGD-MBs to αvβ3-negative MCF-7 cells. Adhesion of the RGD-MBs to the bEnd.3 cells was significantly inhibited following treatment with anti-alpha(v) antibodies. The quantitative acoustic video intensity for high-frequency, contrast-enhanced ultrasound imaging of subcutaneous human laryngeal carcinoma (Hep-2) tumor xenografts was significantly higher in small tumors (19.89 ± 2.49) than in medium tumors (11.25 ± 2.23) and large tumors (3.38 ± 0.67) (P < 0.01). Conclusions RGD-MBs enable noninvasive in vivo visualization of changes in tumor angiogenesis during tumor growth in subcutaneous cancer xenografts. PMID:26862757

  13. Acoustic angiography: a new high frequency contrast ultrasound technique for biomedical imaging

    NASA Astrophysics Data System (ADS)

    Shelton, Sarah E.; Lindsey, Brooks D.; Gessner, Ryan; Lee, Yueh; Aylward, Stephen; Lee, Hyunggyun; Cherin, Emmanuel; Foster, F. Stuart; Dayton, Paul A.

    2016-05-01

    Acoustic Angiography is a new approach to high-resolution contrast enhanced ultrasound imaging enabled by ultra-broadband transducer designs. The high frequency imaging technique provides signal separation from tissue which does not produce significant harmonics in the same frequency range, as well as high resolution. This approach enables imaging of microvasculature in-vivo with high resolution and signal to noise, producing images that resemble x-ray angiography. Data shows that acoustic angiography can provide important information about the presence of disease based on vascular patterns, and may enable a new paradigm in medical imaging.

  14. Sonographic imaging of extra-testicular focal lesions: comparison of grey-scale, colour Doppler and contrast-enhanced ultrasound

    PubMed Central

    Rafailidis, Vasileios; Robbie, Hasti; Konstantatou, Eleni; Huang, Dean Y; Deganello, Annamaria; Sellars, Maria E; Cantisani, Vito; Isidori, Andrea M

    2016-01-01

    Extra-testicular lesions are usually benign but present with nonspecific grey-scale sonography findings. This study assesses conventional sonographic characteristics in the differentiation of extra-testicular tumoural from inflammatory lesions and whether contrast-enhanced ultrasound has a role. A retrospective database analysis was performed. All patients were examined by experienced sonographers employing standard techniques combining grey-scale, colour Doppler sonography and contrast-enhanced ultrasound. Features recorded were: clinical symptoms, size, location, echogenicity, colour Doppler sonography and contrast-enhanced ultrasound enhancement. Vascularity on colour Doppler sonography and contrast-enhanced ultrasound was graded and compared. The lesions were classified as tumoural or inflammatory. The Chi-square test was used to analyse the sonographic patterns and kappa coefficient to measure the agreement between colour Doppler sonography and contrast-enhanced ultrasound. A total of 30 lesions were reviewed (median diameter 12 mm, range 5–80 mm, median age 52 years, range 18–86 years), including 13/30 tumoural and 17/30 inflammatory lesions. Lesions were hypoechoic (n = 12), isoechoic (n = 6), hyperechoic (n = 2) or mixed (n = 10). Grey-scale characteristics of tumoural vs. inflammatory lesions differed significantly (P = 0.026). On colour Doppler sonography, lesions had no vessels (n = 16), 2–3 vessels (n = 10) and ≥4 vessels (n = 4). On contrast-enhanced ultrasound, lesions showed no vascularity (n = 17), perfusion similar to testis (n = 7) and higher (n = 6). All abscesses identified (n = 9) showed no vascularity on both colour Doppler sonography and contrast-enhanced ultrasound. There was good agreement between these techniques in evaluating vascularity (κ = 0.719) and no significant difference between colour Doppler sonography and contrast-enhanced ultrasound of tumoural vs. inflammatory

  15. In vivo Pulsed Magneto-motive Ultrasound Imaging Using High-performance Magnetoactive Contrast Nanoagents

    PubMed Central

    Mehrmohammadi, Mohammad; Shin, Tae-Hyun; Qu, Min; Kruizinga, Pieter; Truby, Ryan L.; Lee, Jae-Hyun

    2014-01-01

    Previously, pulsed magneto-motive ultrasound (pMMUS) imaging has been introduced as a contrast-agent-assisted ultrasound-based imaging modality capable of visualizing biological events at the cellular and molecular level. In pMMUS imaging, a high intensity pulsed magnetic field is used to excite cells or tissue labeled with magnetic nanoparticles. Then, ultrasound (US) imaging is used to monitor the mechanical response of the tissue to an externally applied magnetic field (i.e., tissue displacement). Signal to noise ratio (SNR) in pMMUS imaging can be improved by using superparamagnetic nanoparticles with larger saturation magnetization. Metal-doped magnetic nanoparticles with enhanced tunable nanomagnetism are suitable candidates to improve the SNR and, therefore, sensitivity of pMMUS imaging, which is essential for in vivo pMMUS imaging. In this study, we demonstrate the capability of pMMUS imaging to identify the presence and distribution of zinc-doped iron oxide nanoparticles in live nude mice bearing A431 (human epithelial carcinoma) xenograft tumors. PMID:24080913

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

    NASA Astrophysics Data System (ADS)

    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).

  17. Ultrasound modulated fluorescence emission from Pyrene-labelled liposome contrast agents

    NASA Astrophysics Data System (ADS)

    Zhang, Qimei; Moles, Matthew D.; Mather, Melissa L.; Morgan, Stephen P.

    2014-09-01

    Ultrasound modulated fluorescence tomography (USMFT) has the potential to be a useful technique to obtain fluorescence images with optical contrast and ultrasound (US) resolution in deep tissue. However, due to the intrinsic incoherent properties of fluorescence and the low modulation depth, the signal-to-noise ratio (SNR) and image contrast are poor. In this paper, the feasibility of using pyrene-labelled nanosize liposomes as contrast agents to improve the modulation depth in USMFT is investigated by using a light-scattering technique. Compared with microbubbles (MBs), which have been applied to USMFT to improve the modulation depth, liposomes are more stable and they can be manufactured with good repeatability. Also liposomes have a lower US scattering coefficient due to their liquid core as compared to the gas core of MBs, which can be advantageous when switching on fluorescence in a region of interest is required. Pyrene can form excimer fluorescence when in close proximity to other pyrene molecules. The exposure of these liposomes to US can change the collision rate of the pyrene molecules and hence modulate the optical emission. In the current work, 100 nm sized liposomes composed of varying concentrations of pyrene-labelled phospholipids were investigated to identify a suitable liposome-based US contrast agent candidate. The fluorescence emission of the pyrene-labelled liposomes insonified by continuous US were studied. It has been observed that the excimer emission from 0.5 mol% pyrene-labelled liposome is US sensitive at pressures between 1.4 MPa and 2.7 MPa. Possible fluorescence modulation mechanisms and application of pyrene-labelled liposomes for high-resolution, high-contrast fluorescence imaging are also discussed.

  18. The nonlinear dynamics of microbubble contrast agents used in medical ultrasound

    NASA Astrophysics Data System (ADS)

    Reddy, Anil J.

    Microbubbles are used as contrast agents in diagnostic ultrasound, and as transport agents or to engender physical effects in therapeutic ultrasound. The distinguishing characteristic of bubbles is their small size, on the order of microns, which allows them to traverse the smallest capillaries in the human body. Furthermore, when subject to acoustic forcing (ultrasound), the oscillations of bubbles become highly nonlinear, leading to a unique echo characteristic. Bubble echo improves the clinician's ability to distinguish between blood carrying contrast agent from the surrounding tissue. Present ultrasound techniques, however, do not take full advantage of the nonlinear properties of oscillating microbubbles. In this work, a novel method to maximize the bubble echo, thereby improving image quality, is suggested. Pulse-inversion imaging is utilized as a means of filtering out the linear echo of surrounding tissue. A norm is defined for the nonlinear bubble echo and it is shown how the norm may be maximized, given a limit on ultrasound intensity, by optimizing the acoustic pulse shape using optimal control theory. The optimization is performed for a single bubble of a particular size. The optimal pulse yields a several-fold increase in the echo norm over conventional pulse driving. It is also shown that the optimal pulse effectively maximizes the echo of a bubble cloud with mean size equal to that of the single bubble. Increased bubble response comes as a result of severe radial collapse, which in turn drives the translation dynamics of the bubble. These motions have been observed by others in experiment, but have, up this point, been inadequately explained. The erratic translation of a bubble is found to be intimately coupled to the radial dynamics, especially in the case of violent oscillations. The assumption of spherical symmetry is relaxed and it is considered how bubble translation can be a mechanism for shape instability, thereby leading to bubble destruction

  19. Contrast-enhanced ultrasound in differentiating malignant from benign portal vein thrombosis in hepatocellular carcinoma

    PubMed Central

    Tarantino, Luciano; Ambrosino, Pasquale; Di Minno, Matteo Nicola Dario

    2015-01-01

    Portal vein thrombosis (PVT) may occur in liver cirrhosis patients. Malignant PVT is a common complication in cirrhotic patients with concomitant hepatocellular carcinoma (HCC) and, in some cases, it may be even the initial sign of an undetected HCC. Detection of malignant PVT in a patient with liver cirrhosis heavily affects the therapeutic strategy. Gray-scale ultrasound (US) is widely unreliable for differentiating benign and malignant thrombi. Although effective for this differential diagnosis, fine-needle biopsy remains an invasive technique. Sensitivity of color-doppler US in detection of malignant thrombi is highly dependent on the size of the thrombus. Contrast-enhanced computed tomography (CT) and contrast-enhanced magnetic resonance (MRI) can be useful to assess the nature of portal thrombus, while limited data are currently available about the role of positron emission tomography (PET) and PET-CT. In contrast with CT, MRI, PET, and PET-CT, contrast-enhanced ultrasound (CEUS) is a fast, effective, well tolerated and cheap technique, that can be performed even in the same session in which the thrombus has been detected. CEUS can be performed bedside and can be available also in transplanted patients. Moreover, CT and MRI only yield a snapshot analysis during contrast diffusion, while CEUS allows for a continuous real-time imaging of the microcirculation that lasts several minutes, so that the whole arterial phase and the late parenchymal phase of the contrast diffusion can be analyzed continuously by real-time US scanning. Continuous real-time monitoring of contrast diffusion entails an easy detection of thrombus maximum enhancement. Moreover, continuous quantitative analyses of enhancement (wash in - wash out studies) by CEUS during contrast diffusion is nowadays available in most CEUS machines, thus giving a more sophisticated and accurate evaluation of the contrast distribution and an increased confidence in diagnosis in difficult cases. In conclusion

  20. Enhanced Thermal Ablation by Combining Ultrasound Contrast Agents with a Miniature Flat Transducer

    NASA Astrophysics Data System (ADS)

    Murillo, A.; Goldendstedt, C.; Lafon, C.; Cathignol, D.; Chapelon, J.-Y.

    2007-05-01

    Miniature transducers can be used for performing interstitial thermal ablation. Increasing the frequency of non-focused transducers enhances energy deposition but limits the therapeutic range. In order to treat extended tumors, new therapeutic strategies must be explored. This work aimed to combine ultrasound contrast agents (UCA) with flat transducers for increasing the treatment depth. The idea consists in increasing attenuation away from the transducer to favor remote heat deposition. Thermal ablation is induced in three steps. 1- Attenuation raises by injecting UCA; 2- Destruction of bubbles next to the transducer by pulsed high intensity bursts, results in a gradient of attenuation; 3- Continuous ultrasound are applied for generating a localized thermal lesion. In vitro tests were performed on temperature-sensitive tissue phantoms in which the UCA BR14 (Bracco) was injected during the liquid phase. The feasibility of the idea was demonstrated in three stages. 1- The coefficient of attenuation was measured with the force balance as a function of the concentration of BR14. For 0.8 and 4.8% attenuation at 10MHz was found to be 0.35 and 1.33 Np/cm respectively. 2- Pulsed ultrasound was applied on phantoms to destroy UCA. Based on the echogenicity decay evidenced on ultrasound images, a 1MPa-pressure was required at 10MHz. 3- Heating beams were applied on phantoms presenting a gradient in attenuation. Lesions were 1.5 times larger than in phantoms with constant attenuation. This study demonstrates that UCA can be selectively destroyed in order to generate a gradient of attenuation and extended thermal lesions.

  1. Vascular imaging with ultrasound contrast agents: Characterization of pharmaceutical, physiological, and instrumentation parameters that influence clinical efficacy

    NASA Astrophysics Data System (ADS)

    Steinbach, Gregory Curtis

    Over the last decade, ultrasound contrast media have become important diagnostic tools. Their development lagged behind that of some of the other imaging modalities, even though ultrasound is used worldwide and is a technology that would benefit from an increased signal-to-noise ratio. Ultrasound contrast agents, used as a tool to improve signal, could have global diagnostic applications as well as the possibility of extending the diagnostic capabilities of outdated or inexpensive instruments, which often have poor sensitivity. Part of the lag in contrast agent development was due to the pharmaceutical challenge of creating a safe material that effectively scattered ultrasound. The challenge was further increased by the difficulty of reproducibly predicting and characterizing the properties of these materials in-vitro with results that correlated with clinical data. Additional significant problems included demonstrating the benefits of contrast agents and teaching the clinicians about the interactions between instrumentation and contrast materials so that they could use both tools synergistically to derive maximum diagnostic benefit. The purpose of this work is to reduce these challenges by characterizing the clinically relevant enhancement properties of two different classes of ultrasound contrast materials. The enhancement mechanisms of these agents differ considerably and will be discussed in detail. These differences provide a unique view of the variety of physical characteristics that can be utilized to design ultrasound contrast agents for a range of applications. The in-vitro characterization requirements of the agents differ, and the experimental model characteristics for each are described and demonstrated. The clinical enhancement characteristics are also described, as well as the differing impact of contrast- instrumentation interactions on the efficacy of the agents. Understanding these principles is important because ultrasound contrast agents are

  2. Quantitative assessment of tumor angiogenesis using real-time motion-compensated contrast-enhanced ultrasound imaging

    PubMed Central

    Pysz, Marybeth A.; Guracar, Ismayil; Foygel, Kira; Tian, Lu; Willmann, Jürgen K.

    2015-01-01

    Purpose To develop and test a real-time motion compensation algorithm for contrast-enhanced ultrasound imaging of tumor angiogenesis on a clinical ultrasound system. Materials and methods The Administrative Institutional Panel on Laboratory Animal Care approved all experiments. A new motion correction algorithm measuring the sum of absolute differences in pixel displacements within a designated tracking box was implemented in a clinical ultrasound machine. In vivo angiogenesis measurements (expressed as percent contrast area) with and without motion compensated maximum intensity persistence (MIP) ultrasound imaging were analyzed in human colon cancer xenografts (n = 64) in mice. Differences in MIP ultrasound imaging signal with and without motion compensation were compared and correlated with displacements in x- and y-directions. The algorithm was tested in an additional twelve colon cancer xenograft-bearing mice with (n = 6) and without (n = 6) anti-vascular therapy (ASA-404). In vivo MIP percent contrast area measurements were quantitatively correlated with ex vivo microvessel density (MVD) analysis. Results MIP percent contrast area was significantly different (P < 0.001) with and without motion compensation. Differences in percent contrast area correlated significantly (P < 0.001) with x- and y-displacements. MIP percent contrast area measurements were more reproducible with motion compensation (ICC = 0.69) than without (ICC = 0.51) on two consecutive ultrasound scans. Following anti-vascular therapy, motion-compensated MIP percent contrast area significantly (P = 0.03) decreased by 39.4 ± 14.6 % compared to non-treated mice and correlated well with ex vivo MVD analysis (Rho = 0.70; P = 0.05). Conclusion Real-time motion-compensated MIP ultrasound imaging allows reliable and accurate quantification and monitoring of angiogenesis in tumors exposed to breathing-induced motion artifacts. PMID:22535383

  3. Contrast-enhanced ultrasound after endovascular aortic repair—current status and future perspectives

    PubMed Central

    Partovi, Sasan; Kaspar, Mathias; Aschwanden, Markus; Lopresti, Charles; Madan, Shivanshu; Uthoff, Heiko; Imfeld, Stephan

    2015-01-01

    An increasing number of patients with abdominal aortic aneurysms (AAAs) are undergoing endovascular aortic repair (EVAR) instead of open surgery. These patients require lifelong surveillance, and the follow-up imaging modality of choice has been traditionally computed tomography angiography (CTA). Repetitive CTA imaging is associated with cumulative radiation exposure and requires the administration of multiple doses of nephrotoxic contrast agents. Contrast-enhanced ultrasound (CEUS) has emerged as an alternative strategy in the follow-up of patients with EVAR and demonstrates high sensitivity and specificity for detection of endoleaks. In fact, a series of studies have shown that CEUS is at least performing equal to computed tomography for the detection and classification of endoleaks. This article summarizes current evidence of CEUS after EVAR and demonstrates its usefulness via various patient cases. PMID:26673398

  4. Role of contrast harmonic-endoscopic ultrasound in pancreatic cystic lesions

    PubMed Central

    Serrani, Marta; Lisotti, Andrea; Caletti, Giancarlo; Fusaroli, Pietro

    2017-01-01

    Incidental pancreatic cysts (PCs) are frequently encountered in the general population often in asymptomatic patients who undergo imaging tests to investigate unrelated conditions. The detection of a PC poses a significant clinical dilemma, as the differential diagnosis is quite broad ranging from benign to malignant conditions. Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) has been reported to be an accurate tool in the differential diagnosis; however, its sensitivity is suboptimal and false negative results do occur. Contrast harmonic EUS (CH-EUS) was demonstrated to be a useful tool to investigate pancreatic solid lesions to differentiate between benign and malignant ones. In the setting of PCs, CH-EUS could help identify areas of malignant growth inside the cystic cavities. Several studies have reported promising results showing malignant areas in PCs as hyperenhanced lesions. Confirmation of malignancy can then be obtained by FNA, which should be precisely targeted according to the findings of the contrast harmonic study. PMID:28218197

  5. Contrast-enhanced ultrasound: A promising method for renal microvascular perfusion evaluation.

    PubMed

    Wang, Ling; Mohan, Chandra

    2016-09-01

    This article reviews the application of contrast-enhanced ultrasound (CEUS) in gauging renal microvascular perfusion in diverse renal diseases. The unique nature of the contrast agents used in CEUS provides real-time and quantitative imaging of the vasculature. In addition to the traditional use of CEUS for evaluation of kidney masses, it also emerges as a safe and effective imaging approach to assess microvascular perfusion in diffuse renal lesions, non-invasively. Although the precise CEUS parameters that may best predict disease still warrant systematic evaluation, animal models and limited clinical trials in humans raise hopes that CEUS could outcompete competing modalities as a first-line tool for assessing renal perfusion non-invasively, even in ailments such as acute kidney injury and chronic kidney disease.

  6. Contrast-enhanced ultrasound: A promising method for renal microvascular perfusion evaluation

    PubMed Central

    2016-01-01

    Abstract This article reviews the application of contrast-enhanced ultrasound (CEUS) in gauging renal microvascular perfusion in diverse renal diseases. The unique nature of the contrast agents used in CEUS provides real-time and quantitative imaging of the vasculature. In addition to the traditional use of CEUS for evaluation of kidney masses, it also emerges as a safe and effective imaging approach to assess microvascular perfusion in diffuse renal lesions, non-invasively. Although the precise CEUS parameters that may best predict disease still warrant systematic evaluation, animal models and limited clinical trials in humans raise hopes that CEUS could outcompete competing modalities as a first-line tool for assessing renal perfusion non-invasively, even in ailments such as acute kidney injury and chronic kidney disease. PMID:28191530

  7. Contrast enhanced transabdominal ultrasound in the characterisation of pancreatic lesions with cystic appearance.

    PubMed

    Beyer-Enke, Stefan A; Hocke, Michael; Ignee, Andre; Braden, Barbara; Dietrich, Christoph F

    2010-09-06

    Contrast enhanced ultrasound (CEUS) has been established for detection and characterisation of liver tumours and differential diagnosis of solid pancreatic lesions. The role of transabdominal CEUS in cystic pancreatic disease is less obvious. We prospectively evaluated CEUS for characterization of undetermined cystic pancreatic lesions with respect to the differential diagnosis of pseudocysts and cystic neoplasia and differentiation between benign and malignant disease (gold standard: histology or cytology). One-hundred and fourteen patients (63 males, 51 females; median age: 62 years, range: 33-87 years) were prospectively examined. Conventional B-mode and transabdominal CEUS. Conventional B-mode (criteria: solid nodules, septae), and contrast enhancing features of cystic pancreatic lesions (microperfusion of solid nodules) were analysed. Final diagnoses were made by surgery (47 patients) or histology/cytology and follow-up of at least one year (67 patients). Fifty patients proved to have neoplastic lesions (37 malignant, 13 of benign origin). Sixty-four patients had pseudocysts caused by acute (27 patients) or chronic pancreatitis (37 patients). Conventional B-mode had a sensitivity of 94% and a low specificity of 44% in the differentiation of pseudocysts versus neoplasia. CEUS had a higher specificity of 77% with the same sensitivity of conventional B-mode ultrasound. The combination of conventional ultrasound and CEUS improved the specificity even more to 97% with an unchanged sensitivity. CEUS was not reliable in the differentiation of benign and malignant neoplasia. CEUS improves the differentiation between pseudocysts and pancreatic neoplasia in comparison to the conventional B-mode imaging. The microvascularisation visualised using CEUS even in small nodules (with or without septae) associated with cystic lesions is an indicator for cystic pancreatic neoplasia.

  8. Update on the safety and efficacy of commercial ultrasound contrast agents in cardiac applications.

    PubMed

    Appis, Andrew W; Tracy, Melissa J; Feinstein, Steven B

    2015-06-01

    Ultrasound contrast agents (UCAs) are currently used throughout the world in both clinical and research settings. The concept of contrast-enhanced ultrasound imaging originated in the late 1960s, and the first commercially available agents were initially developed in the 1980s. Today's microbubbles are designed for greater utility and are used for both approved and off-label indications. In October 2007, the US Food and Drug Administration (FDA) imposed additional product label warnings that included serious cardiopulmonary reactions, several new disease-state contraindications, and a mandated 30 min post-procedure monitoring period for the agents Optison and Definity. These additional warnings were prompted by reports of cardiopulmonary reactions that were temporally related but were not clearly attributable to these UCAs. Subsequent published reports over the following months established not only the safety but also the improved efficacy of clinical ultrasound applications with UCAs. The FDA consequently updated the product labeling in June 2008 and reduced contraindications, although it continued to monitor select patients. In addition, a post-marketing program was proposed to the sponsors for a series of safety studies to further assess the risk of UCAs. Then in October 2011, the FDA leadership further downgraded the warnings after hearing the results of the post-marketing data, which revealed continued safety and improved efficacy. The present review focuses on the use of UCAs in today's clinical practice, including the approved indications, a variety of off-label uses, and the most recent data, which affirms the safety and efficacy of UCAs.

  9. Update on the safety and efficacy of commercial ultrasound contrast agents in cardiac applications

    PubMed Central

    Tracy, Melissa J; Feinstein, Steven B

    2015-01-01

    Ultrasound contrast agents (UCAs) are currently used throughout the world in both clinical and research settings. The concept of contrast-enhanced ultrasound imaging originated in the late 1960s, and the first commercially available agents were initially developed in the 1980s. Today's microbubbles are designed for greater utility and are used for both approved and off-label indications. In October 2007, the US Food and Drug Administration (FDA) imposed additional product label warnings that included serious cardiopulmonary reactions, several new disease-state contraindications, and a mandated 30 min post-procedure monitoring period for the agents Optison and Definity. These additional warnings were prompted by reports of cardiopulmonary reactions that were temporally related but were not clearly attributable to these UCAs. Subsequent published reports over the following months established not only the safety but also the improved efficacy of clinical ultrasound applications with UCAs. The FDA consequently updated the product labeling in June 2008 and reduced contraindications, although it continued to monitor select patients. In addition, a post-marketing program was proposed to the sponsors for a series of safety studies to further assess the risk of UCAs. Then in October 2011, the FDA leadership further downgraded the warnings after hearing the results of the post-marketing data, which revealed continued safety and improved efficacy. The present review focuses on the use of UCAs in today's clinical practice, including the approved indications, a variety of off-label uses, and the most recent data, which affirms the safety and efficacy of UCAs. PMID:26693339

  10. Quantitative contrast-enhanced ultrasound imaging: a review of sources of variability

    PubMed Central

    Tang, M.-X.; Mulvana, H.; Gauthier, T.; Lim, A. K. P.; Cosgrove, D. O.; Eckersley, R. J.; Stride, E.

    2011-01-01

    Ultrasound provides a valuable tool for medical diagnosis offering real-time imaging with excellent spatial resolution and low cost. The advent of microbubble contrast agents has provided the additional ability to obtain essential quantitative information relating to tissue vascularity, tissue perfusion and even endothelial wall function. This technique has shown great promise for diagnosis and monitoring in a wide range of clinical conditions such as cardiovascular diseases and cancer, with considerable potential benefits in terms of patient care. A key challenge of this technique, however, is the existence of significant variations in the imaging results, and the lack of understanding regarding their origin. The aim of this paper is to review the potential sources of variability in the quantification of tissue perfusion based on microbubble contrast-enhanced ultrasound images. These are divided into the following three categories: (i) factors relating to the scanner setting, which include transmission power, transmission focal depth, dynamic range, signal gain and transmission frequency, (ii) factors relating to the patient, which include body physical differences, physiological interaction of body with bubbles, propagation and attenuation through tissue, and tissue motion, and (iii) factors relating to the microbubbles, which include the type of bubbles and their stability, preparation and injection and dosage. It has been shown that the factors in all the three categories can significantly affect the imaging results and contribute to the variations observed. How these factors influence quantitative imaging is explained and possible methods for reducing such variations are discussed. PMID:22866229

  11. TOPICAL REVIEW: Ultrasound contrast microbubbles in imaging and therapy: physical principles and engineering

    NASA Astrophysics Data System (ADS)

    Qin, Shengping; Caskey, Charles F.; Ferrara, Katherine W.

    2009-03-01

    Microbubble contrast agents and the associated imaging systems have developed over the past 25 years, originating with manually-agitated fluids introduced for intra-coronary injection. Over this period, stabilizing shells and low diffusivity gas materials have been incorporated in microbubbles, extending stability in vitro and in vivo. Simultaneously, the interaction of these small gas bubbles with ultrasonic waves has been extensively studied, resulting in models for oscillation and increasingly sophisticated imaging strategies. Early studies recognized that echoes from microbubbles contained frequencies that are multiples of the microbubble resonance frequency. Although individual microbubble contrast agents cannot be resolved—given that their diameter is on the order of microns—nonlinear echoes from these agents are used to map regions of perfused tissue and to estimate the local microvascular flow rate. Such strategies overcome a fundamental limitation of previous ultrasound blood flow strategies; the previous Doppler-based strategies are insensitive to capillary flow. Further, the insonation of resonant bubbles results in interesting physical phenomena that have been widely studied for use in drug and gene delivery. Ultrasound pressure can enhance gas diffusion, rapidly fragment the agent into a set of smaller bubbles or displace the microbubble to a blood vessel wall. Insonation of a microbubble can also produce liquid jets and local shear stress that alter biological membranes and facilitate transport. In this review, we focus on the physical aspects of these agents, exploring microbubble imaging modes, models for microbubble oscillation and the interaction of the microbubble with the endothelium.

  12. Destruction of contrast microbubbles used for ultrasound imaging and drug delivery

    NASA Astrophysics Data System (ADS)

    Jain, Pankaj; Sarkar, Kausik; Chatterjee, Dhiman

    2005-09-01

    Microbubble contrast agent destruction by ultrasound pulse is useful in real-time blood-flow velocity measurement, stimulating arteriogenesis, or targeted drug delivery. We investigated in vitro destruction of contrast agent Definity (Bristol Meyer-Squibb Imaging, North Billerica, MA) by measuring attenuation of ultrasound through it. The measurement is performed with single-cycle bursts for varying pressure amplitudes at 50-, 100-, and 200-Hz pulse repetition frequencies (PRF). At low excitation levels, the attenuation increases with time, indicating an increase in bubble size due to ingress of dissolved air from the surrounding liquid. With increased excitation levels, the attenuation level decreases with time, indicating destruction of microbubbles. A critical pressure amplitude (1.2 MPa) was found for all three PRFs, below which there is no significant bubble destruction. Above the critical excitation level, the rate of destruction depends on excitation levels. But, at high pressure amplitudes destruction becomes independent of excitation pressure amplitude. The results are interpreted to identify two different mechanisms of bubble destruction by its signature in attenuation, namely, slow dissolution by diffusion at intermediate pressure amplitudes and catastrophic shell rupture at high amplitudes.

  13. Ultrasound contrast microbubbles in imaging and therapy: physical principles and engineering.

    PubMed

    Qin, Shengping; Caskey, Charles F; Ferrara, Katherine W

    2009-03-21

    Microbubble contrast agents and the associated imaging systems have developed over the past 25 years, originating with manually-agitated fluids introduced for intra-coronary injection. Over this period, stabilizing shells and low diffusivity gas materials have been incorporated in microbubbles, extending stability in vitro and in vivo. Simultaneously, the interaction of these small gas bubbles with ultrasonic waves has been extensively studied, resulting in models for oscillation and increasingly sophisticated imaging strategies. Early studies recognized that echoes from microbubbles contained frequencies that are multiples of the microbubble resonance frequency. Although individual microbubble contrast agents cannot be resolved-given that their diameter is on the order of microns-nonlinear echoes from these agents are used to map regions of perfused tissue and to estimate the local microvascular flow rate. Such strategies overcome a fundamental limitation of previous ultrasound blood flow strategies; the previous Doppler-based strategies are insensitive to capillary flow. Further, the insonation of resonant bubbles results in interesting physical phenomena that have been widely studied for use in drug and gene delivery. Ultrasound pressure can enhance gas diffusion, rapidly fragment the agent into a set of smaller bubbles or displace the microbubble to a blood vessel wall. Insonation of a microbubble can also produce liquid jets and local shear stress that alter biological membranes and facilitate transport. In this review, we focus on the physical aspects of these agents, exploring microbubble imaging modes, models for microbubble oscillation and the interaction of the microbubble with the endothelium.

  14. Robust contrast source inversion method with automatic choice rule of regularization parameters for ultrasound waveform tomography

    NASA Astrophysics Data System (ADS)

    Lin, Hongxiang; Azuma, Takashi; Qu, Xiaolei; Takagi, Shu

    2016-07-01

    We consider ultrasound waveform tomography using an ultrasound prototype equipped with the ring-array transducers. For this purpose, we use robust contrast source inversion (robust CSI), viz extended contrast source inversion, to reconstruct the sound-speed image from the wave-field data. The robust CSI method is implemented by the alternating minimization method. An automatic choice rule is employed into the alternating minimization method in order to heuristically determine a suitable regularization parameter while iterating. We prove the convergence of this algorithm. The numerical examples show that the robust CSI method with the automatic choice rule improves the spatial resolution of medical images and enhances the robustness, even when the wave-field data of a wavelength of 6.16 mm contaminated by 5% noise are used. The numerical results also show that the images reconstructed by the proposed method yield a spatial resolution of approximately half the wavelength that may be adequate for imaging a breast tumor at Stage I.

  15. Material characterization of poly-lactic acid shelled ultrasound contrast agent and their dynamics

    NASA Astrophysics Data System (ADS)

    Paul, Shirshendu; Russakow, Daniel; Rodgers, Tyler; Sarkar, Kausik; Cochran, Michael; Wheatley, Margaret

    2011-11-01

    Micron-size gas bubbles encapsulated with lipids and proteins are used as contrast enhancing agents for ultrasound imaging. Biodegradable polymer poly-lactic acid (PLA) has recently been suggested as a possible means of encapsulation. Here, we report in vitro measurement of attenuation and scattering of ultrasound through an emulsion of PLA agent as well as theoretical modeling of the encapsulated bubble dynamics. The attenuation measured with three different transducers of central frequencies 2.25, 3.5 and 5 MHz, shows a peak around 2-3 MHz. These bubbles also show themselves to possess excellent scattering characteristics including strong non-linear response that can be used for harmonic and sub-harmonic contrast imaging. Our recently developed interfacial rheological models are applied to describe the dynamics of these bubbles; rheological model properties are estimated using measured attenuation data. The model is then applied to predict nonlinear scattered response, and the prediction is compared against experimental observation. Partially supported by NSF and NIH.

  16. Effectiveness of contrast-enhanced ultrasound in the classification and emergency management of abdominal trauma.

    PubMed

    Lv, Faqin; Ning, Yanting; Zhou, Xuan; Luo, Yukun; Liang, Tong; Nie, Yongkang; Li, Tanshi; Tang, Jie

    2014-10-01

    To analyse the correlation between contrast-enhanced ultrasound (CEUS)-based classification of the severity of abdominal parenchymal organ trauma and clinical outcomes, and to explore CEUS in classifying patients with such trauma, expecting that the use of CEUS will potentially enhance the quality and speed of the emergency management of abdominal trauma. Three hundred six consecutive patients with blunt abdominal parenchymal organ trauma who received CEUS examination were retrospectively analysed. Two CEUS radiologists (identified as Reader A and Reader B in this study) who were not involved in the CEUS examinations of the patients were then asked to classify the patients independently according to their CEUS results. The classification results were later compared with patients' clinical outcomes using Spearman's rank correlation. The final clinical outcomes showed that 25.5 % (78/306) of patients received conservative treatment, 52.0 % (159/306) received minimally invasive treatment, and 22.5 % (69/306) received surgery. Spearman's rank correlation coefficients between the CEUS-based classification and clinical outcome were 0.952 from Reader A and 0.960 from Reader B. CEUS can play an important role in the emergency management of abdominal trauma through the classification of patients for different treatment methods. • The severity of abdominal trauma was classified by contrast-enhanced ultrasound (CEUS) • There was a high correlation between CEUS-based classification and clinical outcomes • CEUS-based classification is helpful for surgeons in the emergency management of abdominal trauma.

  17. Quantitative guidelines for the prediction of ultrasound contrast agent destruction during injection.

    PubMed

    Threlfall, Greg; Wu, Hong Juan; Li, Katherine; Aldham, Ben; Scoble, Judith; Sutalo, Ilija D; Raicevic, Anna; Pontes-Braz, Luisa; Lee, Brian; Schneider-Kolsky, Michal; Ooi, Andrew; Coia, Greg; Manasseh, Richard

    2013-10-01

    Experiments and theory were undertaken on the destruction of ultrasound contrast agent microbubbles on needle injection, with the aim of predicting agent loss during in vivo studies. Agents were expelled through a variety of syringe and needle combinations, subjecting the microbubbles to a range of pressure drops. Imaging of the bubbles identified cases where bubbles were destroyed and the extent of destruction. Fluid-dynamic calculations determined the pressure drop for each syringe and needle combination. It was found that agent destruction occurred at a critical pressure drop that depended only on the type of microbubble. Protein-shelled microbubbles (sonicated bovine serum albumin) were virtually all destroyed above their critical pressure drop of 109 ± 7 kPa Two types of lipid-shelled microbubbles were found to have a pressure drop threshold above which more than 50% of the microbubbles were destroyed. The commercial lipid-shelled agent Definity was found to have a critical pressure drop for destruction of 230 ± 10 kPa; for a previously published lipid-shelled agent, this value was 150 ± 40 kPa. It is recommended that attention to the predictions of a simple formula could preclude unnecessary destruction of microbubble contrast agent during in vivo injections. This approach may also preclude undesirable release of drug or gene payloads in targeted microbubble therapies. Example values of appropriate injection rates for various agents and conditions are given. 2013 World Federation for Ultrasound in Medicine & Biology. All rights reserved

  18. Ultrasound contrast microbubbles in imaging and therapy: physical principles and engineering

    PubMed Central

    Qin, Shengping; Caskey, Charles F; Ferrara, Katherine W

    2010-01-01

    Microbubble contrast agents and the associated imaging systems have developed over the past twenty-five years, originating with manually-agitated fluids introduced for intra-coronary injection. Over this period, stabilizing shells and low diffusivity gas materials have been incorporated in microbubbles, extending stability in vitro and in vivo. Simultaneously, the interaction of these small gas bubbles with ultrasonic waves has been extensively studied, resulting in models for oscillation and increasingly sophisticated imaging strategies. Early studies recognized that echoes from microbubbles contained frequencies that are multiples of the microbubble resonance frequency. Although individual microbubble contrast agents cannot be resolved—given that their diameter is on the order of microns—nonlinear echoes from these agents are used to map regions of perfused tissue and to estimate the local microvascular flow rate. Such strategies overcome a fundamental limitation of previous ultrasound blood flow strategies; the previous Doppler-based strategies are insensitive to capillary flow. Further, the insonation of resonant bubbles results in interesting physical phenomena that have been widely studied for use in drug and gene delivery. Ultrasound pressure can enhance gas diffusion, rapidly fragment the agent into a set of smaller bubbles or displace the microbubble to a blood vessel wall. Insonation of a microbubble can also produce liquid jets and local shear stress that alter biological membranes and facilitate transport. In this review, we focus on the physical aspects of these agents, exploring microbubble imaging modes, models for microbubble oscillation and the interaction of the microbubble with the endothelium. PMID:19229096

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

    PubMed

    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).

  20. Computation of nonlinear ultrasound fields using a linearized contrast source method.

    PubMed

    Verweij, Martin D; Demi, Libertario; van Dongen, Koen W A

    2013-08-01

    Nonlinear ultrasound is important in medical diagnostics because imaging of the higher harmonics improves resolution and reduces scattering artifacts. Second harmonic imaging is currently standard, and higher harmonic imaging is under investigation. The efficient development of novel imaging modalities and equipment requires accurate simulations of nonlinear wave fields in large volumes of realistic (lossy, inhomogeneous) media. The Iterative Nonlinear Contrast Source (INCS) method has been developed to deal with spatiotemporal domains measuring hundreds of wavelengths and periods. This full wave method considers the nonlinear term of the Westervelt equation as a nonlinear contrast source, and solves the equivalent integral equation via the Neumann iterative solution. Recently, the method has been extended with a contrast source that accounts for spatially varying attenuation. The current paper addresses the problem that the Neumann iterative solution converges badly for strong contrast sources. The remedy is linearization of the nonlinear contrast source, combined with application of more advanced methods for solving the resulting integral equation. Numerical results show that linearization in combination with a Bi-Conjugate Gradient Stabilized method allows the INCS method to deal with fairly strong, inhomogeneous attenuation, while the error due to the linearization can be eliminated by restarting the iterative scheme.

  1. Ultrasound exposure (mechanical index 1.8) with acoustic radiation force impulse evokes extrasystolic waves in rabbit heart under concomitant administration of an ultrasound contrast agent.

    PubMed

    Ishiguro, Yasunao; Nitta, Naotaka; Taniguchi, Nobuyuki; Akai, Kazuki; Takakayama, Noriya; Sasanuma, Hideki; Ogata, Yukiyo; Yasuda, Yoshikazu; Akiyama, Iwaki

    2016-01-01

    Acoustic radiation force impulse (ARFI) is a modality for elasticity imaging of various organs using shear waves. In some situations, the heart is a candidate for elasticity evaluation with ARFI. Additionally, an ultrasound contrast agent (UCA) provides information on the blood flow conditions of the cardiac muscle. This study aimed to evaluate ARFI's effect on the heart concomitantly with UCA administration (i.e., perfluorobutane). Ultrasound with ARFI was applied to the hearts of male Japanese white rabbits (n = 3) using a single-element focused transducer with or without UCA administration. They were exposed to ultrasound for 0.3 ms with a mechanical index (MI) of 1.8. UCA was administered in two ways: a single (bolus) injection or drip infusion. Electrocardiograms were recorded to identify arrhythmias during ultrasound exposure. Extrasystolic waves were observed following ultrasound exposure with drip infusion of UCA. Life-threatening arrhythmia was not observed. The frequency of the extra waves ranged from 4.2 to 59.6 %. With bolus infusion, extra waves were not observed. Arrhythmogenicity was observed during ultrasound (MI 1.8) with ARFI and concomitant administration of UCA in rabbits. Although the bolus administration of UCA was similar to its clinical use, which may not cause extra cardiac excitation, cardiac ultrasound examinations with ARFI should be carefully performed, particularly with concomitant use of UCA.

  2. The ultrasound contrast imaging properties of lipid microbubbles loaded with urokinase in dog livers and their thrombolytic effects when combined with low-frequency ultrasound in vitro.

    PubMed

    Ren, Shu-Ting; Kang, Xiao-Ning; Liao, Yi-Ran; Wang, Wei; Ai, Hong; Chen, Li-Na; Luo, Hui-Ting; Fu, Rong-Guo; Tan, Li-Fang; Shen, Xin-Liang; Wang, Bing

    2014-04-01

    A new microbubble loaded with urokinase (uPA-MB) was explored in a previous study. However, its zeta potential and ultrasound contrast imaging properties and its thrombolytic effects when combined with low-frequency ultrasound (LFUS) were unclear. The zeta potential and ultrasound contrast imaging property of 5 uPA-MBs loading with 50,000 IU uPA was respectively detected using a Malvern laser particle analyzer and a Logiq 9 digital premium ultrasound system. Its ultrasound contrast imaging property was performed on the livers of two healthy dogs to compare with SonoVue. And the clot mass loss rate, D-dimer concentration and surface morphology of the clot residues were measured to evaluate the thrombolytic effect after treatment with three doses of 5 uPA-MBs combined with LFUS in vitro. The zeta potential of 5 uPA-MBs (-27.0 ± 2.40 mV) was higher than that of normal microbubbles (-36.95 ± 1.77 mV). Contrast-enhanced imaging of the hepatic vessels using 5 uPA-MBs was similar to SonoVue, while the imaging duration of 5 uPA-MBs (10 min) was longer than SonoVue (6 min). The thrombolytic effect of three doses of uPA-MBs combined with LFUS was significantly better than that of the control group and showed dose dependence. The 5 uPA-MBs have a negative charge on their surface and good echogenicity as ultrasound contrast agents. The 5 uPA-MBs combined with LFUS can promote thrombolysis in a dose-dependent manner.

  3. Intravenous contrast ultrasound examination using contrast-tuned imaging (CnTI) and the contrast medium SonoVue for discrimination between benign and malignant adnexal masses with solid components.

    PubMed

    Testa, A C; Timmerman, D; Van Belle, V; Fruscella, E; Van Holsbeke, C; Savelli, L; Ferrazzi, E; Leone, F P G; Marret, H; Tranquart, F; Exacoustos, C; Nazzaro, G; Bokor, D; Magri, F; Van Huffel, S; Ferrandina, G; Valentin, L

    2009-12-01

    To determine whether intravenous contrast ultrasound examination is superior to gray-scale or power Doppler ultrasound for discrimination between benign and malignant adnexal masses with complex ultrasound morphology. In an international multicenter study, 134 patients with an ovarian mass with solid components or a multilocular cyst with more than 10 cyst locules, underwent a standardized transvaginal ultrasound examination followed by contrast examination using the contrast-tuned imaging technique and intravenous injection of the contrast medium SonoVue(R). Time intensity curves were constructed, and peak intensity, area under the intensity curve, time to peak, sharpness and half wash-out time were calculated. The sensitivity and specificity with regard to malignancy were calculated and receiver-operating characteristics (ROC) curves were drawn for gray-scale, power Doppler and contrast variables and for pattern recognition (subjective assignment of a certainly benign, probably benign, uncertain or malignant diagnosis, using gray-scale and power Doppler ultrasound findings). The gold standard was the histological diagnosis of the surgically removed tumors. After exclusions (surgical removal of the mass > 3 months after the ultrasound examination, technical problems), 72 adnexal masses with solid components were used in our statistical analyses. The values for peak contrast signal intensity and area under the contrast signal intensity curve in malignant tumors were significantly higher than those in borderline tumors and benign tumors, while those for the benign and borderline tumors were similar. The area under the ROC curve of the best contrast variable with regard to diagnosing borderline or invasive malignancy (0.84) was larger than that of the best gray-scale (0.75) and power Doppler ultrasound variable (0.79) but smaller than that of pattern recognition (0.93). Findings on ultrasound contrast examination differed between benign and malignant tumors but there

  4. Correlation of Rupture Dynamics to the Nonlinear Backscatter Response From Polymer-Shelled Ultrasound Contrast Agents

    PubMed Central

    Koppolu, Sujeethraj; Chitnis, Parag V.; Mamou, Jonathan; Allen, John S.; Ketterling, Jeffrey A.

    2016-01-01

    Polymer-shelled ultrasound contrast agents (UCAs) may expel their encapsulated gas subject to ultrasound-induced shell buckling or rupture. Nonlinear oscillations of this gas bubble can produce a subharmonic component in the ultrasound backscatter. This study investigated the relationship between this gas-release mechanism and shell-thickness–to–radius ratios (STRRs) of polymer-shelled UCAs. Three types of polylactide-shelled UCAs with STRRs of 7.5, 40, and 100 nm/µm were studied. Each UCA population had a nominal mean diameter of 2 µm. UCAs were subjected to increasing static overpressure ranging from 2 to 330 kPa over a duration of 2 h in a custom-designed test chamber while being imaged using a 200× magnification video microscope at a frame rate of 5 frames/s. Digitized video images were binarized and processed to obtain the cross-sectional area of individual UCAs. Integration of the normalized cross-sectional area over normalized time, defined as buckling factor (Bf), provided a dimensionless parameter for quantifying and comparing the degree of pre-rupture buckling exhibited by the UCAs of different STRRs in response to overpressure. The UCAs with an STRR of 7.5 nm/µm exhibited a distinct shell-buckling phase before shell rupture (Bf < 1), whereas the UCAs with higher STRRs (40 and 100 nm/µm) did not undergo significant pre-rupture buckling (Bf ≈ 1). The difference in the overpressure response was correlated with the subharmonic response produced by these UCAs. When excited using 20-MHz ultrasound, individual UCAs (N = 3000) in populations that did not exhibit a buckling phase produced a subharmonic response that was an order of magnitude greater than the UCA population with a prominent pre-rupture buckling phase. These results indicate the mechanism of gas expulsion from these UCAs might be a relevant factor in determining the level of subharmonic response in response to high-frequency ultrasound. PMID:25935932

  5. Ultrasound

    MedlinePlus

    Ultrasound is a type of imaging. It uses high-frequency sound waves to look at organs and ... liver, and other organs. During pregnancy, doctors use ultrasound to view the fetus. Unlike x-rays, ultrasound ...

  6. Perfusion estimation using contrast enhanced three-dimensional subharmonic ultrasound imaging: an in vivo study

    PubMed Central

    Sridharan, Anush; Eisenbrey, John R.; Liu, Ji-Bin; Machado, Priscilla; Halldorsdottir, Valgerdur G.; Dave, Jaydev K.; Zhao, Hongjia; He, Yu; Park, Suhyun; Dianis, Scott; Wallace, Kirk; Thomenius, Kai E.; Forsberg, Flemming

    2013-01-01

    Objectives The ability to estimate tissue perfusion (in mL/min/g) in vivo using contrast-enhanced three-dimensional (3D) harmonic and subharmonic ultrasound imaging was investigated. Materials and Methods A Logiq 9 scanner (GE Healthcare, Milwaukee, WI) equipped with a 4D10L probe was modified to perform 3D harmonic imaging (HI; ftransmit = 5 MHz and freceive = 10 MHz) and subharmonic imaging (SHI; ftransmit= 5.8 MHz and freceive= 2.9 MHz). In vivo imaging was performed in the lower pole of both kidneys in five open-abdomen canines after injection of the ultrasound contrast agent (UCA) Definity (Lantheus Medical Imaging, N Billerica, MA). The canines received a 5 μL/kg bolus injection of Definity for HI and a 20 μL/kg bolus for SHI in triplicate for each kidney. Ultrasound data acquisition was started just prior to injection of UCA (in order to capture the wash-in) and continued until washout. A microvascular staining technique based on stable (non-radioactive) isotope-labeled microspheres (Biophysics Assay Laboratory Inc, Worcester, MA) was used to quantify the degree of perfusion in each kidney (the reference standard). Ligating a surgically exposed branch of the renal arteries induced lower perfusion rates. This was followed by additional contrast-enhanced imaging and microsphere injections to measure post-ligation perfusion. Slice data were extracted from the 3D ultrasound volumes and used to generate time-intensity curves off-line in the regions corresponding to the tissue samples used for microvascular staining. The mid-line plane was also selected from the 3D volume (as a quasi-2D image) and compared to the 3D imaging modes. Perfusion was estimated from the initial slope of the fractional blood volume uptake (for both HI and SHI) and compared to the reference standard using linear regression analysis. Results Both 3D HI and SHI were able to provide visualization of flow and, thus, perfusion in the kidneys. However, SHI provided near complete tissue

  7. Ultrasound Molecular Imaging of Tumor Angiogenesis with an Integrin Targeted Microbubble Contrast Agent

    PubMed Central

    Anderson, Christopher R.; Hu, Xiaowen; Tlaxca, Jose; Decleves, Anne-Emilie; Houghtaling, Robert; Sharma, Kumar; Lawrence, Michael; Ferrara, Katherine; Rychak, Joshua J.

    2010-01-01

    Rationale and Objectives Ultrasound molecular imaging is an emerging technique for sensitive detection of intravascular targets. Molecular imaging of angiogenesis has strong potential for both clinical use and as a research tool in tumor biology and the development of anti-angiogenic therapies. Our objective is to develop a robust microbubble (MB) ultrasound contrast agent platform to which targeting ligands can be conjugated by biocompatible, covalent conjugation chemistry, and to develop a pure low mechanical index imaging processing method and corresponding quantifying method. The microbubbles and the imaging methods were evaluated in a mouse model of breast cancer in vivo. Materials and Methods We utilized a cyclic RGD (cRGD) pentapeptide containing a terminal cysteine group conjugated to the surface of MB bearing pyridyldithio-propionate (PDP) for targeting αvβ3 integrins. As negative controls, MB without a ligand or MB bearing a scrambled sequence (cRAD) were prepared. To enable characterization of peptides bound to MB surfaces, the cRGD peptide was labeled with FITC and detected by plate fluorometry, flow cytometry, and fluorescence microscopy. Targeted adhesion of cRGD-MB was demonstrated in an in vitro flow adhesion assay against recombinant murine αvβ3 integrin protein and αvβ3 integrin-expressing endothelial cells (bEnd.3). The specificity of cRGD-MB for αvβ3 integrin was demonstrated by treating bEnd.3 EC with a blocking antibody. A murine model of mammary carcinoma was used to assess targeted adhesion and ultrasound molecular imaging in vivo. The targeted microbubbles were visualized using a low mechanical index contrast imaging pulse sequence, and quantified by intensity normalization and two-dimensional Fourier transform analysis, Results The cRGD ligand concentration on the MB surface was ~8.2 × 106 molecules/MB. At a wall shear stress of 1.0 dynes/cm2, cRGD-MB exhibited 5-fold higher adhesion to immobilized recombinant αvβ3 integrin

  8. Feasibility of Dual Optics/Ultrasound Imaging and Contrast Media for the Detection and Characterization of Prostate Cancer

    DTIC Science & Technology

    2009-03-01

    acousto - optic effect will be used to only modulate light (at the ultrasound frequency) which propagates through a small ultrasound focal zone. This...DOD Idea Development Award is concerned with the development of a novel acousto - optic detection idea based on quadrature measurements with a gain...perform acousto - optic molecular imaging of prostate cancer with incoherent photons using endogenous contrast, e.g. hypoxia, and with fluorescent probes and microbubbles for increased specificity and signal enhancement.

  9. Successful stent implantation guided by intravascular ultrasound and a Doppler guidewire without contrast injection in a patient with allergy to iodinated contrast media.

    PubMed

    Okura, Hiroyuki; Nezuo, Shintaro; Yoshida, Kiyoshi

    2011-07-01

    Presence of allergy to iodinated contrast may prevent percutaneous coronary intervention (PCI) to be performed. We present a 76-year-old male with a history of allergic reaction to iodinated contrast who successfully underwent intravascular ultrasound (IVUS) and a Doppler guidewire-guided PCI. Stent size was determined based on IVUS. After PCI, stent expansion and a lack of edge dissection or incomplete apposition were confirmed by IVUS and a good antegrade coronary flow was confirmed by a Doppler guidewire. Thus, PCI without contrast injection under IVUS and a Doppler guidewire-guidance may be feasible in selected patients with allergy to iodinated contrast.

  10. Quantitative analysis of ultrasound contrast flow behavior in carotid plaque neovasculature.

    PubMed

    Hoogi, Assaf; Akkus, Zeynettin; van den Oord, Stijn C H; ten Kate, Gerrit L; Schinkel, Arend F L; Bosch, Johan G; de Jong, Nico; Adam, Dan; van der Steen, Antonius F W

    2012-12-01

    Intraplaque neovascularization is considered as an important indication for plaque vulnerability. We propose a semiautomatic algorithm for quantification of neovasculature, thus, enabling assessment of plaque vulnerability. The algorithm detects and tracks contrast spots using multidimensional dynamic programming. Classification of contrast tracks into blood vessels and artifacts was performed. The results were compared with manual tracking, visual classification and maximal intensity projection. In 28 plaques, 97% of the contrast spots were detected. In 89% of the objects, the automatic tracking determined the contrast motion with an average distance of less than 0.5 mm from the manual marking. Furthermore, 75% were correctly classified into artifacts and vessels. The automated neovascularization grading agreed within 1 grade with visual analysis in 91% of the cases, which was comparable to the interobserver variability of visual grading. These results show that the method can successfully quantify features that are linked to vulnerability of the carotid plaque. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  12. Optimization of contrast resolution by genetic algorithm in ultrasound tissue harmonic imaging.

    PubMed

    Ménigot, Sébastien; Girault, Jean-Marc

    2016-09-01

    The development of ultrasound imaging techniques such as pulse inversion has improved tissue harmonic imaging. Nevertheless, no recommendation has been made to date for the design of the waveform transmitted through the medium being explored. Our aim was therefore to find automatically the optimal "imaging" wave which maximized the contrast resolution without a priori information. To overcome assumption regarding the waveform, a genetic algorithm investigated the medium thanks to the transmission of stochastic "explorer" waves. Moreover, these stochastic signals could be constrained by the type of generator available (bipolar or arbitrary). To implement it, we changed the current pulse inversion imaging system by including feedback. Thus the method optimized the contrast resolution by adaptively selecting the samples of the excitation. In simulation, we benchmarked the contrast effectiveness of the best found transmitted stochastic commands and the usual fixed-frequency command. The optimization method converged quickly after around 300 iterations in the same optimal area. These results were confirmed experimentally. In the experimental case, the contrast resolution measured on a radiofrequency line could be improved by 6% with a bipolar generator and it could still increase by 15% with an arbitrary waveform generator. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Three-dimensional modeling of the dynamics of therapeutic ultrasound contrast agents.

    PubMed

    Hsiao, Chao-Tsung; Lu, Xiaozhen; Chahine, Georges

    2010-12-01

    A 3-D thick-shell contrast agent dynamics model was developed by coupling a finite volume Navier-Stokes solver and a potential boundary element method flow solver to simulate the dynamics of thick-shelled contrast agents subjected to pressure waves. The 3-D model was validated using a spherical thick-shell model validated by experimental observations. We then used this model to study shell break-up during nonspherical deformations resulting from multiple contrast agent interaction or the presence of a nearby solid wall. Our simulations indicate that the thick viscous shell resists the contrast agent from forming a re-entrant jet, as normally observed for an air bubble oscillating near a solid wall. Instead, the shell thickness varies significantly from location to location during the dynamics, and this could lead to shell break-up caused by local shell thinning and stretching. Copyright © 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  14. An in vitro system for the study of ultrasound contrast agents using a commercial imaging system.

    PubMed

    Sboros, V; Moran, C M; Anderson, T; Gatzoulis, L; Criton, A; Averkiou, M; Pye, S D; McDicken, W N

    2001-12-01

    An in vitro system for the investigation of the behaviour of contrast microbubbles in an ultrasound field, that provides a full diagnostic range of settings, is yet to be presented in the literature. The evaluation of a good compromise of such a system is presented in this paper. It is based on (a) an HD13000 ATL scanner (Bothell, WA, USA) externally controlled by a PC and (b) on the use of well-defined reference materials. The suspensions of the reference ultrasonic scattering material are placed in an anechoic tank. The pulse length ranges from 2 to 10 cycles, the acoustic pressure from 0.08 to 1.8 MPa, the transmit frequency from 1 to 4.3 MHz, and the receive frequency from 1 to 8 MHz. The collection of 256 samples of RF data, at an offset distance from the transducer face, was performed at 20 MHz digitization rate, which corresponds to approximately 1 cm depth in water. Two particle suspensions are also presented for use as reference scatterers for contrast studies: (a) a suspension of Orgasol (ELF Atochem, Paris, France) particles (approximately 5 microm mean diameter) and (b) a suspension of Eccosphere (New Metals & Chemicals Ltd, Essex, UK) particles (approximately 50 microm mean diameter). A preliminary experiment with the contrast agent Definity (DuPont Pharmaceutical Co, Waltham, MA) showed that the above two materials are suitable for use as a reference for contrast backscatter.

  15. Kupffer-phase findings of hepatic hemangiomas in contrast-enhanced ultrasound with sonazoid.

    PubMed

    Sugimoto, Katsutoshi; Moriyasu, Fuminori; Saito, Kazuhiro; Yoshiara, Hiroki; Imai, Yasuharu

    2014-06-01

    The aim of this study was to assess quantitatively the Kupffer-phase enhancement patterns of hepatic hemangiomas in contrast-enhanced ultrasound (CEUS) with Sonazoid. A total of 46 patients with 46 hepatic hemangiomas (17.1 ± 6.2 mm in diameter, 34 typical type and 12 high-flow type) underwent CEUS in the Kupffer phase. The lesion-to-liver contrast ratio in the Kupffer phase was quantitatively assessed for both types of hemangioma. Most of the hepatic hemangiomas, whether or not they were the high-flow type, were iso- to hypo-echoic relative to the surrounding liver parenchyma. The contrast ratio was -5.33 ± 6.70 dB for the high-flow hemangiomas and -4.54 ± 6.28 dB for the typical hemangiomas. There was no significant difference in contrast ratio between the two types of lesions (p = 0.73). All of the hemangiomas, whether of typical or high-flow type, are iso- to hypo-echoic relative to the surrounding liver parenchyma on Kupffer-phase imaging.

  16. Predictive Value of Conventional Ultrasound and Contrast-Enhanced Ultrasound in Early Recurrence of Hepatocellular Carcinoma after Surgical Resection.

    PubMed

    Wang, Yibin; Liao, Jintang; Qi, Wenjun; Xie, Lulu; Li, Yueyi

    2016-05-01

    The goals of the work described here were to study the pre-operative risk factors associated with early recurrence (ER) of hepatocellular carcinoma (HCC) after surgical resection and discuss the value of conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) in predicting ER of HCC, so as to provide more information for optimizing clinical treatment and improving prognosis. A retrospective analysis was conducted on 59 patients who underwent both US and CEUS examinations pre-operatively and surgical resection for HCC between December 2010 and January 2014 in our hospital. The patients' clinical data, laboratory examination data and ultrasonic imaging diagnostic data were collected. Univariate analysis and logistic regression analysis were performed to determine the independent risk factors for ER of HCC after surgical resection. Diagnostic values of independent risk factors in predicting ER were further evaluated. The 59 patients were divided into the ER group (27 cases) and ER-free group (32 cases). There were no significant differences in age and sex between the two groups (p > 0.05). Univariate analysis revealed that differences in pre-operative serum α-fetoprotein level ≥400 ng/mL (p = 0.008), tumor diameter ≥5 cm (p = 0.012), macroscopic vascular invasion (p = 0.040), "fast wash-out" enhancement pattern (p = 0.006) and inhomogeneous distribution of contrast agent (p = 0.031) statistically significantly differed between the two groups. Logistic regression analysis indicated that pre-operative serum AFP level ≥400 ng/mL (p = 0.024), tumor diameter ≥5 cm (p = 0.042) and "fast wash-out" enhancement pattern (p = 0.009) were independent risk factors for ER of HCC; macrovascular invasion (p = 0.095) and inhomogeneous distribution of contrast agent (p = 0.628) did not statistically significantly differ between two groups (p = 0.628). Predictive values of the independent risk factors were further evaluated. The sensitivity of a "fast wash

  17. Optically and acoustically triggerable sub-micron phase-change contrast agents for enhanced photoacoustic and ultrasound imaging.

    PubMed

    Lin, Shengtao; Shah, Anant; Hernández-Gil, Javier; Stanziola, Antonio; Harriss, Bethany I; Matsunaga, Terry O; Long, Nicholas; Bamber, Jeffrey; Tang, Meng-Xing

    2017-06-01

    We demonstrate a versatile phase-change sub-micron contrast agent providing three modes of contrast enhancement: 1) photoacoustic imaging contrast, 2) ultrasound contrast with optical activation, and 3) ultrasound contrast with acoustic activation. This agent, which we name 'Cy-droplet', has the following novel features. It comprises a highly volatile perfluorocarbon for easy versatile activation, and a near-infrared optically absorbing dye chosen to absorb light at a wavelength with good tissue penetration. It is manufactured via a 'microbubble condensation' method. The phase-transition of Cy-droplets can be optically triggered by pulsed-laser illumination, inducing photoacoustic signal and forming stable gas bubbles that are visible with echo-ultrasound in situ. Alternatively, Cy-droplets can be converted to microbubble contrast agents upon acoustic activation with clinical ultrasound. Potentially all modes offer extravascular contrast enhancement because of the sub-micron initial size. Such versatility of acoustic and optical 'triggerability' can potentially improve multi-modality imaging, molecularly targeted imaging and controlled drug release.

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

    PubMed

    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 (<1 MHz) and low amplitudes (<0.5 MPa). The objective of this study was to determine 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.

  19. Acoustic characterization and pharmacokinetic analyses of new nanobubble ultrasound contrast agents.

    PubMed

    Wu, Hanping; Rognin, Nicolas G; Krupka, Tianyi M; Solorio, Luis; Yoshiara, Hiroki; Guenette, Gilles; Sanders, Christopher; Kamiyama, Naohisa; Exner, Agata A

    2013-11-01

    In contrast to the clinically used microbubble ultrasound contrast agents, nanoscale bubbles (or nanobubbles) may potentially extravasate into tumors that exhibit more permeable vasculature, facilitating targeted molecular imaging and drug delivery. Our group recently presented a simple strategy using the non-ionic surfactant Pluronic as a size control excipient to produce nanobubbles with a mean diameter of 200 nm that exhibited stability and echogenicity on par with microbubbles. The objective of this study was to carry out an in-depth characterization of nanobubble properties as compared with Definity microbubbles, both in vitro and in vivo. Through use of a tissue-mimicking phantom, in vitro experiments measured the echogenicity of the contrast agent solutions and the contrast agent dissolution rate over time. Nanobubbles were found to be more echogenic than Definity microbubbles at three different harmonic frequencies (8, 6.2 and 3.5 MHz). Definity microbubbles also dissolved 1.67 times faster than nanobubbles. Pharmacokinetic studies were then performed in vivo in a subcutaneous human colorectal adenocarcinoma (LS174T) in mice. The peak enhancement and decay rates of contrast agents after bolus injection in the liver, kidney and tumor were analyzed. No significant differences were observed in peak enhancement between the nanobubble and Definity groups in the three tested regions (tumor, liver and kidney). However, the decay rates of nanobubbles in tumor and kidney were significantly slower than those of Definity in the first 200-s fast initial phase. There were no significant differences in the decay rates in the liver in the initial phase or in three regions of interest in the terminal phase. Our results suggest that the stability and acoustic properties of the new nanobubble contrast agents are superior to those of the clinically used Definity microbubbles. The slower washout of nanobubbles in tumors suggests potential entrapment of the bubbles within

  20. Quantitative ultrasound molecular imaging by modeling the binding kinetics of targeted contrast agent

    NASA Astrophysics Data System (ADS)

    Turco, Simona; Tardy, Isabelle; Frinking, Peter; Wijkstra, Hessel; Mischi, Massimo

    2017-03-01

    Ultrasound molecular imaging (USMI) is an emerging technique to monitor diseases at the molecular level by the use of novel targeted ultrasound contrast agents (tUCA). These consist of microbubbles functionalized with targeting ligands with high-affinity for molecular markers of specific disease processes, such as cancer-related angiogenesis. Among the molecular markers of angiogenesis, the vascular endothelial growth factor receptor 2 (VEGFR2) is recognized to play a major role. In response, the clinical-grade tUCA BR55 was recently developed, consisting of VEGFR2-targeting microbubbles which can flow through the entire circulation and accumulate where VEGFR2 is over-expressed, thus causing selective enhancement in areas of active angiogenesis. Discrimination between bound and free microbubbles is crucial to assess cancer angiogenesis. Currently, this is done non-quantitatively by looking at the late enhancement, about 10 min after injection, or by calculation of the differential targeted enhancement, requiring the application of a high-pressure ultrasound (US) burst to destroy all the microbubbles in the acoustic field and isolate the signal coming only from bound microbubbles. In this work, we propose a novel method based on mathematical modeling of the binding kinetics during the tUCA first pass, thus reducing the acquisition time and with no need for a destructive US burst. Fitting time-intensity curves measured with USMI by the proposed model enables the assessment of cancer angiogenesis at both the vascular and molecular levels. This is achieved by estimation of quantitative parameters related to the microvascular architecture and microbubble binding. The proposed method was tested in 11 prostate-tumor bearing rats by performing USMI after injection of BR55, and showed good agreement with current USMI methods. The novel information provided by the proposed method, possibly combined with the current non-quantitative methods, may bring deeper insight into

  1. Contrast-enhanced ultrasound improves accurate identification of appendiceal mucinous adenocarcinoma in an old patient

    PubMed Central

    Shang, Jing; Ruan, Li-tao; Dang, Ying; Wang, Yun-yue; Song, Yan; Lian, Jie

    2016-01-01

    Abstract Background: Adenocarcinoma of appendiceal origin is far rarer than other colorectal carcinomas and its preoperative diagnosis is challenging. To our knowledge, utility of contrast-enhanced ultrasound (CEUS) to diagnose it is much less. Method: A 61-year-old man presented with abdominal pain in the right lower quadrant for 20 days. In order to fulfill an accurately preoperative diagnosis, he received laboratory and imaging tests such as carcinoembryonic antigen (CEA), computer tomography (CT), CEUS and endoscope. Diagnosis and Intervention: He was initially suspected of suffering appendicitis, while his white blood cell count was normal and carcinoembryonic antigen (CEA) in serum was remarkably increased. Both routine ultrasound and computer tomography (CT) examinations supported suppurative appendicitis. The overall data, however, failed to excluded neoplastic pathology thoroughly. Therefore, CEUS was carried out and showed an inhomogeneous enhancement intra the lesion located in the body of the appendix, which made our consideration of neoplasm. The result of the follow-up biopsy guided by endoscope was consistent with appendiceal tumor. The patient received laparoscopic right hemicolectomy. Histopathology confirmed as well differentiated mucinous adenocarcinoma of appendix origin. His postoperative course was uneventful, and he had a regular diet again without any complaint. Result: Serum CEA was remarkably increased (12.00 ng/mL). Both routine ultrasound and CT examinations supported suppurative appendicitis. However, CEUS examination showed an inhomogeneous enhancement intra the lesion located in the body of the appendix, which made our consideration of neoplasm. The follow-up biopsy guided by endoscope and surgical specimens confirmed as well differentiated mucinous adenocarcinoma of appendix origin. Conclusion: Most mucinous adenocarcinoma mimicking appendicitis results in difficult diagnosis preoperatively. Clinician and radiologist should be

  2. Respiratory motion correction of liver contrast-enhanced ultrasound sequences by selecting reference image automatically

    NASA Astrophysics Data System (ADS)

    Zhang, Ji; Zhang, Yan-Rong; Chen, Juan; Chen, Xiao-Hui; Zhong, Xiao-Li

    2017-03-01

    Objective: Respiratory motion correction is necessary to quantitative analysis of liver contrast-enhance ultrasound (CEUS) image sequences. However, traditionally manual selecting reference image would affect the accuracy of the respiratory motion correction. Methods First, the original high-dimensional ultrasound gray-level image data was mapped into a two-dimensional space by using Laplacian Eigenmaps (LE). Then, the cluster analysis was adopted using K-means, and the optimal ultrasound reference image could be gotten for respiratory motion correction. Finally, this proposed method was validated on 18 CEUS cases of VX2 tumor in rabbit liver, and the effectiveness of this method was demonstrated. Results After correction, the time-intensity curves extracted from the region of interest of CEUS image sequences became smoother. Before correction, the average of total mean structural similarity (TMSSIM) and the average of mean correlation coefficient (MCC) from image sequences were 0.45+/-0.11 and 0.67+/-0.16, respectively. After correction, the two parameters were increased obviously P<0.001), and were 0.59+/-0.11 and 0.81+/-0.11, respectively. The average of deviation valve (DV) from image sequences before correction was 92.16+/-18.12. After correction, the average was reduced to one-third of the original value. Conclusions: The proposed respiratory motion method could improve the accuracy of the quantitative analysis of CEUS by using the reference image based on the traditionally manual selection. This method is operated simply and has a potential in clinical application.

  3. Quantitative ultrasound molecular imaging by modeling the binding kinetics of targeted contrast agent.

    PubMed

    Turco, Simona; Tardy, Isabelle; Frinking, Peter; Wijkstra, Hessel; Mischi, Massimo

    2017-03-21

    Ultrasound molecular imaging (USMI) is an emerging technique to monitor diseases at the molecular level by the use of novel targeted ultrasound contrast agents (tUCA). These consist of microbubbles functionalized with targeting ligands with high-affinity for molecular markers of specific disease processes, such as cancer-related angiogenesis. Among the molecular markers of angiogenesis, the vascular endothelial growth factor receptor 2 (VEGFR2) is recognized to play a major role. In response, the clinical-grade tUCA BR55 was recently developed, consisting of VEGFR2-targeting microbubbles which can flow through the entire circulation and accumulate where VEGFR2 is over-expressed, thus causing selective enhancement in areas of active angiogenesis. Discrimination between bound and free microbubbles is crucial to assess cancer angiogenesis. Currently, this is done non-quantitatively by looking at the late enhancement, about 10 min after injection, or by calculation of the differential targeted enhancement, requiring the application of a high-pressure ultrasound (US) burst to destroy all the microbubbles in the acoustic field and isolate the signal coming only from bound microbubbles. In this work, we propose a novel method based on mathematical modeling of the binding kinetics during the tUCA first pass, thus reducing the acquisition time and with no need for a destructive US burst. Fitting time-intensity curves measured with USMI by the proposed model enables the assessment of cancer angiogenesis at both the vascular and molecular levels. This is achieved by estimation of quantitative parameters related to the microvascular architecture and microbubble binding. The proposed method was tested in 11 prostate-tumor bearing rats by performing USMI after injection of BR55, and showed good agreement with current USMI methods. The novel information provided by the proposed method, possibly combined with the current non-quantitative methods, may bring deeper insight into

  4. Volume Navigation with Contrast Enhanced Ultrasound and Image Fusion for Percutaneous Interventions: First Results

    PubMed Central

    Hoffstetter, Patrick; Dendl, Lena Marie; Klebl, Frank; Agha, Ayman; Wiggermann, Phillipp; Stroszcynski, Christian; Schreyer, Andreas Georg

    2012-01-01

    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. PMID:22448281

  5. Efficacy of contrast-enhanced ultrasound washout rate in predicting hepatocellular carcinoma differentiation.

    PubMed

    Feng, Yan; Qin, Xia-Chuan; Luo, Yan; Li, Yong-Zhong; Zhou, Xiang

    2015-06-01

    The aim of this retrospective study was to evaluate the efficacy of contrast-enhanced ultrasound (CEUS) washout rate in predicting hepatocellular carcinoma (HCC) differentiation. Two hundred seventy-one patients underwent liver resection for HCC between April 2008 and December 2012 after being examined by CEUS using the contrast agent SonoVue with a low mechanical index (<0.1) in a routine procedure. Contrast agent washout rates obtained from video images were divided into four categories from slow to fast: WR1 = no washout in all phases (slowest); WR2 = washout after 120 s from contrast injection (late-phase washout); WR3 = washout between 41 and 120 s from contrast injection (portal venous washout); WR4 = washout before 40 s from contrast injection (fastest washout rate). HCC nodules were graded as well, moderately and poorly differentiated. Spearman rank correlation and χ(2)-tests were used to assess group relationships and differences. Receiver operating characteristic curve analysis was used to determine the diagnostic predictive value of CEUS. Among the 271 patients, 18 (6.6%) had well differentiated, 150 (55.4%) had moderately differentiated and 103 (38.0%) had poorly differentiated HCC. Statistical tests indicated that washout rate was significantly correlated with tumor differentiation (p < 0.05), and the poorly differentiated HCCs had earlier washout. At the cutoff point of WR4, CEUS based on washout rate performed poorly in distinguishing poorly differentiated from moderately and well-differentiated HCCs, with a sensitivity, specificity and accuracy (area under the curve) of 24%, 97% and 0.68, respectively. However, at the cutoff point of WR2, the sensitivity, specificity and accuracy of CEUS in differentiating well-differentiated HCC from other HCCs were significantly better: 98%, 78% and 0.96, respectively. Thus, CEUS washout rate may have a role in identifying patients with well-differentiated HCC.

  6. Contrast-enhanced ultrasound for evaluation of renal trauma during acute hemorrhagic shock: a canine model.

    PubMed

    Lin, Qian; Lv, Faqin; Luo, Yukun; Song, Qing; Xu, Qinghua; Su, Yihua; Tang, Yu; Tang, Jie

    2015-04-01

    Contrast-enhanced ultrasound (CEUS) is a highly specific and sensitive method for assessing hemodynamically stable patients with blunt abdominal trauma. We evaluated the efficacy of CEUS in assessing renal trauma in different states of hemodynamic instability or shock. Hemorrhagic renal lesions reflecting grade III-IV trauma were established in the kidneys of 25 mongrel dogs. Mild, moderate, and severe systemic hypotension was induced by controlled exsanguination. The features of renal trauma in CEUS and contrast-enhanced computed tomography (CECT) were assessed and compared before shock and during shock progression. Gross pathology showed that with trauma, the kidneys gradually shrank and became soft, and the active bleeding in the area of the renal trauma gradually reduced and stopped. No significant differences were observed in the trauma detection rates between CEUS and CECT at any stage of shock. During the baseline and mild shock stage, sonograms obtained after intravenous injection of contrast agent showed marked contrast medium extravasation and pooling at the site of active bleeding. With shock progression, the difference in enhancement between trauma areas and the surrounding renal tissue decreased: the trauma areas became indistinct and the abnormal enhancement associated with active bleeding diminished. Further, CEUS enabled visualization of changes in renal perfusion associated with shock progression. Changes in contrast agent arrival time and the time to peaking were observed earliest in the mild shock model. The contrast agent peak intensity reduced, while the washout time increased as shock progressed from moderate to severe. In our canine model, CEUS was found to be as accurate as CECT in assessing hemorrhagic renal lesions. Thus, CEUS seems a promising tool for monitoring hemodynamic changes and predicting early shock to enable the conservative treatment of severe renal trauma.

  7. Ultrasound molecular imaging contrast agent binding to both E- and P-selectin in different species.

    PubMed

    Bettinger, Thierry; Bussat, Philippe; Tardy, Isabelle; Pochon, Sibylle; Hyvelin, Jean-Marc; Emmel, Patricia; Henrioud, Sylvie; Biolluz, Nathalie; Willmann, Jürgen K; Schneider, Michel; Tranquart, François

    2012-09-01

    Ultrasound molecular imaging is increasingly used in preclinical studies to measure the expression of vascular markers during inflammation process. In this context, a new ultrasound contrast agent functionalized with a recombinant P-selectin glycoprotein ligand-1 analogue (rPSGL-Ig) was developed (MBrPSGL-Ig). This agent was assayed in vitro and in vivo to evaluate its binding performance and potential to image expression of inflammatory markers E- and P-selectin. Performance of this newly developed agent was compared with that of antibody (MBAb) or sialyl Lewis X (MBsLe) containing microbubbles and with control microbubbles (MBC). The targeted ultrasound contrast agents were prepared by coupling biotin-conjugated ligands onto streptavidin-functionalized microbubbles. First, in vitro experiments were performed to measure the adhesion efficiency of these microbubble constructs under static or flow conditions (114 sec), on cell monolayer (human umbilical vein endothelial cells and bEnd.5), or coatings of E- or P-selectin of various animal species, respectively. Second, molecular imaging studies were performed in a rat inflammatory model 24 hours after intramuscular injection of lipopolysaccharide in the hind limb. Finally, immunohistochemistry staining of rat inflamed muscle tissue was performed to assess expression of E- and P-selectin. Microbubbles functionalized with rPSGL-Ig (MBrPSGL-Ig) displayed firm in vitro binding on the coating of both recombinant E- or P-selectin, with an efficiency similar to microbubbles comprising antibody specific for E-selectin (MBE) or P-selectin (MBP). In contrast, lower binding capacity was measured with MBsLe. At the surface of inflamed endothelial cells, MBrPSGL-Ig were able to interact specifically with E- and P-selectin. Binding specificity was demonstrated by performing blocking experiments with target-specific antibodies, resulting in an 80% to 95% decrease in binding. Ten minutes after microbubble injection, echo signal

  8. Development and characterization of hollow polymeric microcapsules for use as contrast agents for diagnostic ultrasound

    NASA Astrophysics Data System (ADS)

    Narayan, Padma Jyothi

    1999-09-01

    This thesis concerns the development and characterization of a new type of rigid-shelled ultrasound contrast agent. A novel method was devised for producing hollow, gas- filled, polymer microcapsules, sized to less than 10 μm in diameter for contrast imaging. This method involved the encapsulation of a solid, volatile core material, and its subsequent evacuation by sublimation. The biodegradable polymer, 50/50 poly(D,L-lactide-co- glycolide), was the main focus of this study. Polymer- based contrast agents have many advantages, such as their applicability for concomitant imaging and drug delivery. Three encapsulation techniques were evaluated: solvent evaporation, coacervation, and spray drying. The polymer molecular weight and polydispersity in the solvent evaporation and coacervation techniques strongly affected microcapsule size and morphology. Efficient mechanical agitation and shear were crucial for obtaining high yields in the desired size range (less than 6 μm). In spray drying, a factorial design approach was used to optimize conditions to produce microcapsules. The main factors affecting spray drying were found to be the temperature driving force for drying and initial polymer concentration. The smallest microcapsule mean diameters were produced by spray drying (3-4 μm) and solvent evaporation (5-6 μm). Zeta potential (ζ) studies for all microcapsule types indicated that the encapsulation technique affected their surface properties due to the orientation of the polymer chains within nascent polymer droplets. Microcapsules with the most hydrophilic tendency were produced with solvent evaporation (ζ ~ -50 mV). In vitro acoustic testing revealed that the 20-41 μm size fractions of coacervate microcapsules were the most echogenic. In vivo ultrasound studies with both solvent evaporation and coacervate microcapsules showed visible enhancement of the color Doppler image in the rabbit kidney for the samples less than 10 μm in diameter. A mathematical

  9. In vitro evaluation of the impact of ultrasound scanner settings and contrast bolus volume on time-intensity curves.

    PubMed

    Gauthier, Thomas P; Chebil, Mohamed; Peronneau, Pierre; Lassau, Nathalie

    2012-01-01

    The objective of this study was to assess in vitro the impact of ultrasound scanner settings and contrast bolus volume on time-intensity curves formed from dynamic contrast-enhanced ultrasound image loops. An indicator-dilution experiment was developed with an in vitro flow phantom setup used with SonoVue contrast agent (Bracco SpA, Milan, Italy). Imaging was performed with a Philips iU22 scanner and two transducers (L9-3 linear and C5-1 curvilinear). The following ultrasound scanner settings were investigated, along with contrast bolus volume: contrast-specific nonlinear pulse sequence, gain, mechanical index, focal zone depth, acoustic pulse center frequency and bandwidth. Four parameters (rise time, mean transit time, peak intensity, and area under the curve) were derived from time-intensity curves which were obtained after pixel by pixel linearization of log-compressed data (also referred to as video data) included in a region of interest. Rise time was found to be the parameter least impacted by changes to ultrasound scanner settings and contrast bolus volume; the associated coefficient of variation varied between 0.7% and 6.9% while it varied between 0.8% and 19%, 12% and 71%, and 9.2% and 66%, for mean transit time, peak intensity, and area under the curve, respectively. The present study assessed the impact of ultrasound scanner settings and contrast bolus volume on time-intensity curve analysis. One should be aware of these issues to standardize their technique in each specific organ of interest and to achieve accurate, sensitive, and reproducible data using dynamic contrast-enhanced ultrasound. One way to mitigate the impact of ultrasound scanner settings in longitudinal, multi-center quantitative dynamic contrast-enhanced ultrasound studies may be to prohibit any adjustments to those settings throughout a given study. Further clinical studies are warranted to confirm the reproducibility and diagnostic or prognostic value of time-intensity curve

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

    PubMed

    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.

  11. Sonophoresis using ultrasound contrast agents for transdermal drug delivery: an in vivo experimental study.

    PubMed

    Park, Donghee; Ryu, Heungil; Kim, Han Sung; Kim, Young-Sun; Choi, Kyu-Sil; Park, Hyunjin; Seo, Jongbum

    2012-04-01

    Sonophoresis temporally increases skin permeability such that various medications can be delivered noninvasively. Previous sonophoresis studies have suggested that cavitation plays an important role in enhancing transdermal drug delivery (TDD). In this study, the feasibility of controlled cavitation using ultrasound contrast agents (UCAs) at high frequency was explored through in vivo experiments in a rat model. Two commercially available UCAs, SonoVue® and Definity®, were used at 2.47 MHz and 1.12 MHz, respectively. Fluorescein isothiocyanate (FITC)-dextran with 0.1% UCA was used as the drug to be delivered through the skin. Ultrasound with a 10 ms pulse and a 1% duty cycle at 1 MPa acoustic pressure for 30 min was applied in all sonication sessions. The efficacy of sonophoresis with UCAs was quantitatively analyzed using an optical imaging system that was used to count photons emitted from fluorescein. The results showed that the proposed sonophoresis method significantly improved drug penetration compared with the traditional sonophoresis method with 4 kD, 20 kD and 150 kD FITC-dextrans at 1.12 MHz, and with 4 kD and 20 kD FITC-dextrans at 2.47 MHz. Sonophoresis for TDD was performed more effectively with the aid of UCAs. Sonophoresis with UCAs has excellent potential for broad applications in drug delivery for diseases requiring the chronic administration of medications such as diabetes.

  12. The diagnostic value of contrast-enhanced ultrasound in differentiating small renal carcinoma and angiomyolipoma.

    PubMed

    Chen, Lin; Wang, Ling; Diao, Xuehong; Qian, Weiqing; Fang, Liang; Pang, Yun; Zhan, Jia; Chen, Yue

    2015-08-01

    The aim of this study was to explore the value of contrast-enhanced ultrasound (CEUS) in differentiating small renal masses. A total of 102 small renal masses (≤ 3 cm) in 99 patients were examined using conventional ultrasound (CUS) and CEUS, and the findings were reviewed and evaluated in comparison to pathology. Significant differences between renal cell carcinomas (RCCs) and angiomyolipomas (AMLs) were noted in terms of the orientation and echogenicity on CUS (p < 0.05 for both), but the location, shape, margins, homogeneity, and blood flow signals of RCCs on color Doppler flow imaging (CDFI) were similar to those of AMLs (p > 0.05 for all). On CEUS, however, the enhancement intensity, washout in the late phase, and perilesional rim-like enhancement differed significantly for RCCs and AMLs (p = 0.000 for all). Significant differences between CEUS and CUS in terms of sensitivity (88.9% vs. 55.6%), the negative predictive value (68.0% vs. 29.5%), the false negative rate (9.9% vs. 44.5%), and accuracy (88.3% vs. 58.9%) were noted (p < 0.05 for all). CEUS, with its unique features, has value in diagnosing small RCCs and AMLs and outperforms CUS in differentiation of small RCCs and AMLs.

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

    PubMed

    Broholm, Rikke; Pingel, Jessica; Simonsen, Lene; Bülow, Jens; Johannsen, Finn

    2017-02-27

    Contrast-enhanced ultrasound (CEUS) is used to visualize the microvascularisation 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). 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-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. This article is protected by copyright. All rights reserved.

  14. Rupture threshold characterization of polymer-shelled ultrasound contrast agents subjected to static overpressure

    PubMed Central

    Chitnis, Parag V.; Lee, Paul; Mamou, Jonathan; Allen, John S.; Böhmer, Marcel; Ketterling, Jeffrey A.

    2011-01-01

    Polymer-shelled micro-bubbles are employed as ultrasound contrast agents (UCAs) and vesicles for targeted drug delivery. UCA-based delivery of the therapeutic payload relies on ultrasound-induced shell rupture. The fragility of two polymer-shelled UCAs manufactured by Point Biomedical or Philips Research was investigated by characterizing their response to static overpressure. The nominal diameters of Point and Philips UCAs were 3 μm and 2 μm, respectively. The UCAs were subjected to static overpressure in a glycerol-filled test chamber with a microscope-reticule lid. UCAs were reconstituted in 0.1 mL of water and added over the glycerol surface in contact with the reticule. A video-microscope imaged UCAs as glycerol was injected (5 mL∕h) to vary the pressure from 2 to 180 kPa over 1 h. Neither UCA population responded to overpressure until the rupture threshold was exceeded, which resulted in abrupt destruction. The rupture data for both UCAs indicated three subclasses that exhibited different rupture behavior, although their mean diameters were not statistically different. The rupture pressures provided a measure of UCA fragility; the Philips UCAs were more resilient than Point UCAs. Results were compared to theoretical models of spherical shells under compression. Observed variations in rupture pressures are attributed to shell imperfections. These results may provide means to optimize polymeric UCAs for drug delivery and elucidate associated mechanisms. PMID:21580800

  15. Rupture threshold characterization of polymer-shelled ultrasound contrast agents subjected to static overpressure.

    PubMed

    Chitnis, Parag V; Lee, Paul; Mamou, Jonathan; Allen, John S; Böhmer, Marcel; Ketterling, Jeffrey A

    2011-04-15

    Polymer-shelled micro-bubbles are employed as ultrasound contrast agents (UCAs) and vesicles for targeted drug delivery. UCA-based delivery of the therapeutic payload relies on ultrasound-induced shell rupture. The fragility of two polymer-shelled UCAs manufactured by Point Biomedical or Philips Research was investigated by characterizing their response to static overpressure. The nominal diameters of Point and Philips UCAs were 3 μm and 2 μm, respectively. The UCAs were subjected to static overpressure in a glycerol-filled test chamber with a microscope-reticule lid. UCAs were reconstituted in 0.1 mL of water and added over the glycerol surface in contact with the reticule. A video-microscope imaged UCAs as glycerol was injected (5 mL∕h) to vary the pressure from 2 to 180 kPa over 1 h. Neither UCA population responded to overpressure until the rupture threshold was exceeded, which resulted in abrupt destruction. The rupture data for both UCAs indicated three subclasses that exhibited different rupture behavior, although their mean diameters were not statistically different. The rupture pressures provided a measure of UCA fragility; the Philips UCAs were more resilient than Point UCAs. Results were compared to theoretical models of spherical shells under compression. Observed variations in rupture pressures are attributed to shell imperfections. These results may provide means to optimize polymeric UCAs for drug delivery and elucidate associated mechanisms.

  16. Ultrasound contrast agent loaded with nitric oxide as a theranostic microdevice.

    PubMed

    Grishenkov, Dmitry; Gonon, Adrian; Weitzberg, Eddie; Lundberg, Jon O; Harmark, Johan; Cerroni, Barbara; Paradossi, Gaio; Janerot-Sjoberg, Birgitta

    2015-01-01

    The current study describes novel multifunctional polymer-shelled microbubbles (MBs) loaded with nitric oxide (NO) for integrated therapeutic and diagnostic applications (ie, theranostics) of myocardial ischemia. We used gas-filled MBs with an average diameter of 4 μm stabilized by a biocompatible shell of polyvinyl alcohol. In vitro acoustic tests showed sufficient enhancement of the backscattered power (20 dB) acquired from the MBs' suspension. The values of attenuation coefficient (0.8 dB/cm MHz) and phase velocities (1,517 m/s) were comparable with those reported for the soft tissue. Moreover, polymer MBs demonstrate increased stability compared with clinically approved contrast agents with a fracture threshold of about 900 kPa. In vitro chemiluminescence measurements demonstrated that dry powder of NO-loaded MBs releases its gas content in about 2 hours following an exponential decay profile with an exponential time constant equal to 36 minutes. The application of high-power ultrasound pulse (mechanical index =1.2) on the MBs resuspended in saline decreases the exponential time constant from 55 to 4 minutes in air-saturated solution and from 17 to 10 minutes in degassed solution. Thus, ultrasound-triggered release of NO is achieved. Cytotoxicity tests indicate that phagocytosis of the MBs by macrophages starts within 6-8 hours. This is a suitable time for initial diagnostics, treatment, and monitoring of the therapeutic effect using a single injection of the proposed multifunctional MBs.

  17. Ultrasound contrast agent loaded with nitric oxide as a theranostic microdevice

    PubMed Central

    Grishenkov, Dmitry; Gonon, Adrian; Weitzberg, Eddie; Lundberg, Jon O; Harmark, Johan; Cerroni, Barbara; Paradossi, Gaio; Janerot-Sjoberg, Birgitta

    2015-01-01

    The current study describes novel multifunctional polymer-shelled microbubbles (MBs) loaded with nitric oxide (NO) for integrated therapeutic and diagnostic applications (ie, theranostics) of myocardial ischemia. We used gas-filled MBs with an average diameter of 4 μm stabilized by a biocompatible shell of polyvinyl alcohol. In vitro acoustic tests showed sufficient enhancement of the backscattered power (20 dB) acquired from the MBs’ suspension. The values of attenuation coefficient (0.8 dB/cm MHz) and phase velocities (1,517 m/s) were comparable with those reported for the soft tissue. Moreover, polymer MBs demonstrate increased stability compared with clinically approved contrast agents with a fracture threshold of about 900 kPa. In vitro chemiluminescence measurements demonstrated that dry powder of NO-loaded MBs releases its gas content in about 2 hours following an exponential decay profile with an exponential time constant equal to 36 minutes. The application of high-power ultrasound pulse (mechanical index =1.2) on the MBs resuspended in saline decreases the exponential time constant from 55 to 4 minutes in air-saturated solution and from 17 to 10 minutes in degassed solution. Thus, ultrasound-triggered release of NO is achieved. Cytotoxicity tests indicate that phagocytosis of the MBs by macrophages starts within 6–8 hours. This is a suitable time for initial diagnostics, treatment, and monitoring of the therapeutic effect using a single injection of the proposed multifunctional MBs. PMID:25995614

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

    PubMed Central

    Mao, Feng; Dong, Yi; Ji, Zhengbiao; Cao, Jiaying

    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. PMID:28133613

  19. Rupture threshold characterization of polymer-shelled ultrasound contrast agents subjected to static overpressure

    NASA Astrophysics Data System (ADS)

    Chitnis, Parag V.; Lee, Paul; Mamou, Jonathan; Allen, John S.; Böhmer, Marcel; Ketterling, Jeffrey A.

    2011-04-01

    Polymer-shelled micro-bubbles are employed as ultrasound contrast agents (UCAs) and vesicles for targeted drug delivery. UCA-based delivery of the therapeutic payload relies on ultrasound-induced shell rupture. The fragility of two polymer-shelled UCAs manufactured by Point Biomedical or Philips Research was investigated by characterizing their response to static overpressure. The nominal diameters of Point and Philips UCAs were 3 μm and 2 μm, respectively. The UCAs were subjected to static overpressure in a glycerol-filled test chamber with a microscope-reticule lid. UCAs were reconstituted in 0.1 mL of water and added over the glycerol surface in contact with the reticule. A video-microscope imaged UCAs as glycerol was injected (5 mL/h) to vary the pressure from 2 to 180 kPa over 1 h. Neither UCA population responded to overpressure until the rupture threshold was exceeded, which resulted in abrupt destruction. The rupture data for both UCAs indicated three subclasses that exhibited different rupture behavior, although their mean diameters were not statistically different. The rupture pressures provided a measure of UCA fragility; the Philips UCAs were more resilient than Point UCAs. Results were compared to theoretical models of spherical shells under compression. Observed variations in rupture pressures are attributed to shell imperfections. These results may provide means to optimize polymeric UCAs for drug delivery and elucidate associated mechanisms.

  20. Accuracy of Contrast-Enhanced Ultrasound in the Diagnosis of Bile Duct Obstruction

    PubMed Central

    Fontán, F. J. P.; Reboredo, Á. R.; Siso, A. R.

    2015-01-01

    Purpose: To investigate the ability of contrast-enhanced ultrasound (CEUS) to differentiate benign from malignant lesions causing biliary duct obstruction. Materials and Methods: Between November 2006 and December 2013, 59 patients with bile duct obstruction of undetermined cause in baseline ultrasound underwent CEUS study. The enhancement and posterior washout were analyzed in real time all along the study duration (5′). The final diagnosis suggested by CEUS was compared with histologic diagnosis (47.5%) or with radiologic follow-up with TC, RM or ERCP. Results: Final diagnoses included 42 malignant lesions (cholangiocarcinoma n=22, metastases n=6, pancreatic carcinoma n=6, hepatocarcinoma n=4, gallbladder carcinoma n=2, ampullary carcinoma n=1 and lymphoma n=1) and 17 benign lesions (lithiasis or biliary sludge n=15, xanthogranulomatous cholecystitis n=1 and indeterminate n=1). CEUS accuracy compared with final diagnoses based on combined reference standard was 86.4%. CEUS correctly identified 36 of 42 malignant lesions (sensibility 85.7%) and 15 of 17 benign lesions (specificity 88.2%). The positive predictive value of CEUS for malignancy was 94.7%, while the negative predictive value was 71.4%. Conclusion: CEUS is useful to differentiate between benign and malignant causes of obstructive jaundice. This technique improves the detection of bile duct invasion in hepatic neoplasms and permits better evaluation of intra- and extraductal extension of hilar hepatobiliary tumors. PMID:27689143

  1. A model for the dynamics of ultrasound contrast agents in vivo

    PubMed Central

    Qin, Shengping; Ferrara, Katherine W.

    2010-01-01

    The Rayleigh-Plesset (RP) equation for a clean gas bubble in an incompressible and infinite liquid has previously been applied to approximately simulate the behavior of ultrasound contrast agents (UCA) in vivo, and extended RP equations have been proposed to account for the effects of the UCA shell or surrounding soft tissue. These models produce results that are consistent with experimental measurements for low acoustic pressure scenarios. For applications of UCAs in therapeutic medicine, the transmitted acoustic pulse can have a peak negative pressure (PNP) up to a few megapascals, resulting in discrepancies between measurements and predictions using these extended RP equations. Here, a model was developed to describe the dynamics of UCAs in vivo while taking account of the effects of liquid compressibility, the shell and the surrounding tissue. Liquid compressibility is approximated to first order and the shell is treated either as a Voigt viscoelastic solid or a Newtonian viscous liquid. Finite deformation of the shell and tissue is derived. Dynamics of UCAs with a shell of lipid, polymer, albumin and liquid are investigated for typical therapeutic ultrasound pulses. The effects of liquid compressibility and shell and tissue parameters are analyzed. PMID:20815486

  2. Application of Contrast-Enhanced Ultrasound in Cystic Pancreatic Lesions Using a Simplified Classification Diagnostic Criterion

    PubMed Central

    Fan, Zhihui; Yan, Kun; Wang, Yanjie; Qiu, Jianxing; Wu, Wei; Yang, Lei; Chen, Minhua

    2015-01-01

    Objective. Classification diagnosis was performed for cystic pancreatic lesions using ultrasound (US) and contrast-enhanced ultrasound (CEUS) to explore the diagnostic value of CEUS by comparison with enhanced CT. Methods. Sixty-four cases with cystic pancreatic lesions were included in this study. The cystic lesions of pancreas were classified into four types by US, CEUS, and CT: type I unilocular cysts; type II microcystic lesions; type III macrocystic lesions; and type IV cystic lesions with solid components or irregular thickening of the cystic wall or septa. Results. Eighteen type I, 7 type II, 10 type III, and 29 type IV cases were diagnosed by CT. The classification results by US were as follows: 6 type I; 5 type II; 4 type III; and 49 type IV cases. Compared with the results by enhanced CT, the kappa value was 0.36. Using CEUS, 15, 6, 12, and 31 cases were diagnosed as types I–IV, respectively. The kappa value was 0.77. Conclusion. CEUS has obvious superiority over US in the classification diagnostic accuracy in cystic pancreatic lesions and CEUS results showed substantial agreement with enhanced CT. CEUS could contribute to the differential diagnosis of cystic pancreatic diseases. PMID:26090467

  3. Contrast ultrasound in hepatocellular carcinoma at a tertiary liver center: First Indian experience.

    PubMed

    Laroia, Shalini Thapar; Bawa, Simranjeet Singh; Jain, Deepak; Mukund, Amar; Sarin, Shiv

    2013-06-28

    To assess the role of contrast enhanced ultrasonography in evaluation of hepatocellular carcinoma (HCC) at the first Indian tertiary liver center. Retrospective analysis of contrast enhanced ultrasound (CEUS) examinations over 24 mo for diagnosis, surveillance, characterization and follow up of 50 patients in the context of HCC was performed. The source and indication of referrals, change in referral rate, accuracy and usefulness of CEUS in a tertiary liver center equipped with a 64 slice dual energy computer tomography (CT) and 3 tesla magnetic resonance imaging (MRI) were studied. Sonovue (BR1, Bracco, Italy, a second generation contrast agent) was used for contrast US studies. Contrast enhanced CT/MRI or both were performed in all patients. The findings were taken as a baseline reference and correlation was done with respect to contrast US. Contrast enhanced MRI was performed using hepatocyte specific gadobenate dimeglumine (Gd-BOPTA). Iomeron (400 mg; w/v) was used for dynamic CT examinations. About 20 (40%) of the examinations were referred from clinicians for characterization of a mass from previous imaging. About 15 (30%) were performed for surveillance in chronic liver disease; 5 (10%) examinations were performed for monitoring lesions after radiofrequency ablation (RFA); 3 (6%) were post trans-arterial chemo-embolization (TACE) assessments and 3 (6%) were patients with h/o iodinated contrast allergy. About 2 (4%) were performed on hemodynamically unstable patients in the intensive care with raised alpha fetoprotein and 2 (4%) patients were claustrophobic. The number of patients referred from clinicians steadily increased from 12 in the first 12 mo of the study to 38 in the last 12 mo. CEUS was able to diagnose 88% of positive cases of HCC as per reference standards. In the surveillance group, specificity was 53.3% vs 100% by CT/MRI. Post RFA and TACE specificity of lesion characterization by CEUS was 100% in single/large mass assessment, similar to CT

  4. International guidelines for contrast-enhanced ultrasonography: ultrasound imaging in the new millennium

    PubMed Central

    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. PMID:26867761

  5. Intravenous application of second-generation ultrasound contrast agents in children: a review of the literature.

    PubMed

    Piskunowicz, M; Kosiak, W; Batko, T

    2012-04-01

    CEUS examinations using second-generation ultrasound contrast agents (UCA) are conducted in children, despite not being registered for individuals less than 18 years of age. We searched the Medline® database through Pubmed® and Scopus database, in order to find articles in which UCA were administered intravenously in patients under the age of 18. We analyzed in detail 9 papers (7 case reports, 2 original research studies), describing the examinations with intravenous administration of the UCA in children, and 23 original papers, in which the study group included at least one individual under the age of 18. Neither of the analyzed studies included any reports of adverse effects after UCA administration. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Contrast enhanced ultrasound in urothelial carcinoma of urinary bladder: An underutilized staging and grading modality

    PubMed Central

    Gupta, Vijayant Govinda; Singh, Shrawan Kumar; Lal, Anupam; Kakkar, Nandita

    2016-01-01

    Introduction To evaluate contrast enhanced ultrasound (CEUS) as a modality to predict T stage of cancer of urinary bladder (CAUB) and to predict the grade of the tumor preoperatively. Material and methods 110 patients with CAUB presenting to the Department of Urology at our institution between July 2014 and December 2015 underwent CEUS prior to endoscopic resection and the CEUS findings were compared with histopathology results. Results CEUS had a sensitivity of 75, 65 and 90% and specificity of 95, 85 and 92% in detecting Ta, T1 and muscle invasion respectively. CEUS had a sensitivity of 78% and specificity of 85% in detecting the grade of the lesion. Conclusions CEUS is a good alternative for T staging and grading of CAUB preoperatively. It is uniquely advantageous in detecting clots or necrosis and in patients with low eGFR where other imaging modalities are contraindicated. PMID:28127451

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

    PubMed Central

    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. PMID:21302993

  8. New generation ICG-based contrast agents for ultrasound-switchable fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Yu, Shuai; Cheng, Bingbing; Yao, Tingfeng; Xu, Cancan; Nguyen, Kytai T.; Hong, Yi; Yuan, Baohong

    2016-10-01

    Recently, we developed a new technology, ultrasound-switchable fluorescence (USF), for high-resolution imaging in centimeter-deep tissues via fluorescence contrast. The success of USF imaging highly relies on excellent contrast agents. ICG-encapsulated poly(N-isopropylacrylamide) nanoparticles (ICG-NPs) are one of the families of the most successful near-infrared (NIR) USF contrast agents. However, the first-generation ICG-NPs have a short shelf life (<1 month). This work significantly increases the shelf life of the new-generation ICG-NPs (>6 months). In addition, we have conjugated hydroxyl or carboxyl function groups on the ICG-NPs for future molecular targeting. Finally, we have demonstrated the effect of temperature-switching threshold (Tth) and the background temperature (TBG) on the quality of USF images. We estimated that the Tth of the ICG-NPs should be controlled at ~38-40 °C (slightly above the body temperature of 37 °C) for future in vivo USF imaging. Addressing these challenges further reduces the application barriers of USF imaging.

  9. Accuracy of core-needle biopsy after contrast-enhanced ultrasound in soft-tissue tumours.

    PubMed

    De Marchi, Armanda; Brach del Prever, Elena Maria; Linari, Alessandra; Pozza, Simona; Verga, Lucia; Albertini, Ugo; Forni, Marco; Gino, Gian Carlo; Comandone, Alessandro; Brach del Prever, Adalberto Maria; Piana, Raimondo; Faletti, Carlo

    2010-11-01

    Percutaneous biopsies are gaining acceptance in the diagnosis of soft-tissue tumours. Sampling in the most representative area is not easy in sarcomas of huge dimension. We hypothesised that ultrasound (US) contrast medium could identify the representative area for focus core-needle biopsy (CNB) METHODS: This is a retrospective cohort series of 115 soft-tissue masses treated from January 2007 to November 2008. Accuracy of US-guided CNB after contrast-enhanced US (CEUS) was determined by comparing the histology of the biopsy with the definitive diagnosis in 105 surgically excised samples (42 benign, 63 malignant) and with the expected outcome in the remaining ten malignant cases not surgically treated. A myxoid component was present in 21 sarcomas (34.4%). Of samples, 94.8% were adequate for diagnosis with 97.1% sensitivity and 92.5% specificity. Sensitivity and specificity in specific histopathological subgroupings were 100%, and in grading definition they were 100% and 96.8%. US-guided CNB is safe and effective. US contrast medium depicts tumour vascular supply and identifies the representative area(s) for sampling. Sensitivity and specificity are also high in subgrouping and grading, including myxoid types. Discussion about biopsy is part of the essential multidisciplinary strategy for these tumours.

  10. Magnetic resonance and ultrasound contrast imaging of polymer-shelled microbubbles loaded with iron oxide nanoparticles

    PubMed Central

    Sciallero, Claudia; Balbi, Luca; Paradossi, Gaio; Trucco, Andrea

    2016-01-01

    Dual-mode contrast agents (CAs) have great potential for improving diagnostics. However, the effectiveness of CAs is strictly related to both the solution adopted to merge the two agents into a single probe unit, and the ratio between the two agents. In this study, two dual-mode CAs for simultaneous magnetic resonance imaging (MRI) and ultrasound imaging (UI) were assessed. For this purpose, different densities of superparamagnetic iron oxide nanoparticles (SPIONs) were anchored to the external surface of polymer-shelled microbubbles (MBs) or were physically entrapped into the shell. In vitro static and dynamic experiments were carried out with a limited concentration of modified MBs (106 bubbles ml−1) by avoiding destruction during UI (performed at a peak pressure lower than 320 kPa) and by using a low-field MRI system (with a magnetic flux density equal to 0.25 T). Under these conditions, different imaging techniques, set-up parameters and SPION densities were used to achieve satisfactory detection of the CAs by using both UI and MRI. However, when the SPION density was increased, the MRI contrast improved, whereas the UI contrast worsened due to the reduced elasticity of the MB shell. For both UI and MRI, MBs with externally anchored SPIONs provided better performance than MBs with SPIONs entrapped into the shell. In particular, a SPION density of 29% with respect to the mass of the MBs was successfully tested. PMID:27853587

  11. Self-assembled microbubbles as contrast agents for ultrasound/magnetic resonance dual-modality imaging.

    PubMed

    Song, Sheng; Guo, Heze; Jiang, Zequan; Jin, Yuqing; Wu, Ying; An, Xiao; Zhang, Zhaofeng; Sun, Kang; Dou, Hongjing

    2015-09-01

    In this work, superparamagnetic self-assembled microbubbles (SAMBs) consisting of "Poly(acrylic acid)-Iron oxide nanoparticles-Polyamine" sandwich-like shells and tetradecafluorohexane cores were fabricated by a template-free self-assembly approach. The SAMBs exhibit not only magnetic resonance (MR) T2 imaging functionality, but also ultrasound (US) image contrast, showing great potential as US/MR dual contrast agents. The diameters of the SAMBs can be tuned easily from 450nm to 1300nm by changing the precursor ratio, and this size variation directly affects their in vitro MRI and US signals. The SAMBs also exhibit in vivo contrast enhancement capabilities in rat liver with injection through portal vein, for both MR and US imaging. Additionally, the biodistribution of SAMBs over time suggests normal systemic metabolic activity through the spleen. The results show that the Fe content in rat liver reduces to a level of which Fe cannot be detected in 45days. The SAMBs exhibit no obvious damage to the primary organs of rat during the metabolic process, indicating their good biocompatibility in vivo. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  12. New generation ICG-based contrast agents for ultrasound-switchable fluorescence imaging

    PubMed Central

    Yu, Shuai; Cheng, Bingbing; Yao, Tingfeng; Xu, Cancan; Nguyen, Kytai T.; Hong, Yi; Yuan, Baohong

    2016-01-01

    Recently, we developed a new technology, ultrasound-switchable fluorescence (USF), for high-resolution imaging in centimeter-deep tissues via fluorescence contrast. The success of USF imaging highly relies on excellent contrast agents. ICG-encapsulated poly(N-isopropylacrylamide) nanoparticles (ICG-NPs) are one of the families of the most successful near-infrared (NIR) USF contrast agents. However, the first-generation ICG-NPs have a short shelf life (<1 month). This work significantly increases the shelf life of the new-generation ICG-NPs (>6 months). In addition, we have conjugated hydroxyl or carboxyl function groups on the ICG-NPs for future molecular targeting. Finally, we have demonstrated the effect of temperature-switching threshold (Tth) and the background temperature (TBG) on the quality of USF images. We estimated that the Tth of the ICG-NPs should be controlled at ~38–40 °C (slightly above the body temperature of 37 °C) for future in vivo USF imaging. Addressing these challenges further reduces the application barriers of USF imaging. PMID:27775014

  13. Radial Modulation Contrast Imaging Using a 20-MHz Single-Element Intravascular Ultrasound Catheter

    PubMed Central

    Yu, Francois T. H.; Villanueva, Flordeliza S.; Chen, Xucai

    2014-01-01

    Contrast-enhanced intravascular ultrasound imaging is a promising tool for the characterization of coronary vasa vasorum proliferation, which has been identified as a marker of, and possible etiologic factor in, the development of high-risk atherosclerotic plaques. Resonance-based nonlinear detection methods have required the development of prototype catheters which are not commercially available, thus limiting clinical translation. In this study, we investigated the performances of a radial modulation imaging approach (25/3 MHz combination) using simulations, implemented it on a clinical 20-MHz rotating catheter, and tested it in a wall-less tissue-mimicking flow phantom perfused with lipid-encapsulated microbubbles (MBs). The effects of the phase lag, low-frequency pressure, and MB concentration on the envelope subtracted radial modulation signals were investigated as a function of depth. Our dual-pulse dual-frequency approach produced contrast-specific images with contrast-to-tissue improvements over B-mode of 15.1 ± 2.1 dB at 2 mm and 6.8 ± 0.1 dB at 4 mm depths. Using this imaging strategy, 200-μm-diameter cellulose tubing perfused with MBs could be resolved while surrounding tissue scattering was suppressed. These results raise promise for the detection of coronary vasa vasorum and may ultimately facilitate the detection of plaque at risk for rupture. PMID:24803134

  14. Development of Ultrasound-switchable Fluorescence Imaging Contrast Agents based on Thermosensitive Polymers and Nanoparticles

    PubMed Central

    Cheng, Bingbing; Wei, Ming-Yuan; Liu, Yuan; Pitta, Harish; Xie, Zhiwei; Hong, Yi; Nguyen, Kytai T.; Yuan, Baohong

    2015-01-01

    In this work we first introduced a recently developed high-resolution, deep-tissue imaging technique, ultrasound-switchable fluorescence (USF). The imaging principles based on two types of USF contrast agents were reviewed. To improve USF imaging techniques further, excellent USF contrast agents were developed based on high-performance thermoresponsive polymers and environment-sensitive fluorophores. Herein, such contrast agents were synthesized and characterized with five key parameters: (1) peak excitation and emission wavelengths (λex and λem), (2) the fluorescence intensity ratio between on and off states (IOn/IOff), (3) the fluorescence lifetime ratio between on and off states (τOn/τOff), (4) the temperature threshold to switch on fluorophores (Tth), and (5) the temperature transition bandwidth (TBW). We mainly investigated fluorescence intensity and lifetime changes of four environment-sensitive dyes [7-(2-Aminoethylamino)-N,N-dimethyl-4-benzofurazansulfonamide (DBD-ED), St633, Sq660, and St700] as a function of temperature, while the dye was attached to poly(N-isopropylacrylamide) linear polymers or encapsulated in nanoparticles. Six fluorescence resonance energy transfer systems were invented in which both the donor (DBD-ED or ST425) and the acceptor (Sq660) were adopted. Our results indicate that three Förster resonance energy transfer systems, where both IOn/IOff and τOn/τOff are larger than 2.5, are promising for application in future surface tissue bioimaging by USF technique. PMID:26052192

  15. Attenuation correction in ultrasound contrast agent imaging: elementary theory and preliminary experimental evaluation.

    PubMed

    Tang, Meng-Xing; Mari, Jean-Martial; Wells, Peter N T; Eckersley, Robert J

    2008-12-01

    Progress in imaging and quantification of tissue perfusion using ultrasound (US) and microbubble contrast agents has been undermined by the lack of an effective automatic attenuation correction technique. In this article, an elementary model of the US attenuation processes for microbubble contrast enhanced imaging is developed. In the model, factors such as nonlinear bubble scattering, nonlinear attenuation, attenuation to both fundamental and harmonic and the US beam profile are considered. Methods are proposed for fast formation of images with automatic attenuation correction based on the model. In the proposed method, linear tissue echoes are extracted and filtered and then used to compensate for the attenuation in nonlinear bubble echoes at the same location to produce quantities that are a truer representation of bubble concentration. The technique does not require additional measurements and can be implemented in real time. Preliminary experiments on laboratory phantoms consisting of bubbles and tissue-mimicking materials are presented and the effectiveness of the proposed method is supported by improvements in image quality compared with unprocessed data. This development is an important step towards real-time quantitative contrast US imaging.

  16. Analysis of muscle microcirculation in advanced diabetes mellitus by contrast enhanced ultrasound.

    PubMed

    Duerschmied, D; Maletzki, P; Freund, G; Olschewski, M; Seufert, J; Bode, C; Hehrlein, C

    2008-07-01

    Contrast enhanced ultrasound (CEUS) was recently established to quantify perfusion deficits in peripheral arterial disease (PAD). However, this approach was not suitable to assess microangiopathy of skeletal muscle, a major contributor to PAD in diabetic patients. We hypothesized that an optimized methodology would detect impaired microcirculation. Ten patients with advanced diabetes mellitus (mean diabetes duration 21 years), 10 PAD patients, and 10 control subjects were enrolled consecutively. The arrival times of the contrast agent Sonovue after intravenous injection were assessed selectively in a small artery, muscle tissue and a muscle vein of the calf muscle. Contrast transit times (CTTs) were calculated as the differences between arrival times. The median CTT for artery-vein was significantly higher in the diabetes group (43 s) than in the PAD (22 s, p=0.007) and control groups (11 s, p<0.001, no value overlap). CTTs for artery-muscle and muscle-vein were shorter with highest median values in the diabetes group. We validated improved CEUS as consistent method to detect changes in the microvascular bed. This method may become a valuable tool to quantify impaired microcirculation in diabetes and help to improve patient care.

  17. Molecular imaging using contrast-enhanced ultrasound: evaluation of angiogenesis and cell therapy.

    PubMed

    Leong-Poi, Howard

    2009-11-01

    The field of regenerative medicine and its applications for cardiovascular diseases continues to grow rapidly, fuelled by the increasing numbers of symptomatic patients who are not candidates for conventional revascularization procedures and remain refractory to maximal medical therapy. Therapeutic angiogenesis, initially in the form of the administration of growth factor protein or gene therapy and, more recently, in the form of adult progenitor cell therapy, has emerged as a promising new method of treatment for patients with ischaemic heart disease and peripheral arterial disease. There is a growing interest in non-invasive imaging techniques to evaluate the response to angiogenic gene-and cell-based therapies. Contrast-enhanced ultrasound (CEU) techniques using site-specific microbubbles have recently been developed for the molecular imaging of the vascular phenotype that characterizes angiogenesis. These methods have now been modified to allow the imaging of progenitor cell engraftment into neovessels. These molecular imaging techniques using contrast ultrasound and targeted microbubbles have the potential to further characterize the angiogenic response, aid in the optimization of gene- and cell-based strategies of therapeutic neovascularization, and ultimately serve to monitor the therapeutic effects in patients enrolled in clinical trials of regenerative therapies. This review will focus specifically on CEU molecular imaging techniques for the evaluation of angiogenesis and cell therapies in cardiovascular diseases, including: (i) an overview of the techniques and results of pre-clinical studies; (ii) a comparison of CEU molecular imaging techniques with other available molecular imaging modalities; and (iii) a discussion of the future role of CEU molecular imaging in the field of regenerative medicine.

  18. Diagnostic Accuracy of Contrast-Enhanced Ultrasound Enhancement Patterns for Thyroid Nodules

    PubMed Central

    Zhang, Yan; Luo, Yu-kun; Zhang, Ming-bo; Li, Jie; Li, Junlai; Tang, Jie

    2016-01-01

    Background The aim of this study was to investigate the accuracy of contrast-enhanced ultrasound (CEUS) enhancement patterns in the assessment of thyroid nodules. Material/Methods A total of 158 patients with suspected thyroid cancer underwent conventional ultrasound (US) and CEUS examinations. The contrast enhancement patterns of the lesions, including the peripheries of the lesions, were assessed by CEUS scans. The relationship between the size of the lesions and the degree of enhancement was also studied. US- and/or CEUS-guided biopsy was used to obtain specimens for histopathological diagnosis. Results The final data included 148 patients with 157 lesions. Seventy-five patients had 82 malignant lesions and 73 patients had 75 benign lesions. Peripheral ring enhancement was seen in 40 lesions. The differences of enhancement patterns and peripheral rings between benign and malignant nodules were significant (p=0.000, 0.000). The diagnostic sensitivity, specificity, and accuracy for malignant were 88%, 65.33%, and 88.32%, respectively, for CEUS, whereas they were 98.33%, 42.67%, and 71.97%, respectively, for TC by conventional US. The misdiagnosis rate by conventional US was 57.33% and 34.67% by CEUS (p=0.005). With regard to the size of lesions, a significant difference was found between low-enhancement, iso-enhancement, high-enhancement, iso-enhancement with no-enhancement area and no-enhancement (p=0.000). Conclusions In patients with suspicious US characteristics, CEUS had high specificity and contributed to establishing the diagnosis. Therefore, CEUS could avoid unnecessary biopsy. PMID:27916971

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

    PubMed

    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. Changes of area under curve (AUC), derived peak intensity (DPI) were statistically significant (P <  0.05). DPI less than 12 and AUC greater than 1400 had high utility in DN, with 71.7% and 67.3% sensitivity, 77.8% and 80.0% specificity. These results were significantly better than those obtained with RI and PSV which had no significant difference in early stage of DN (P > 0.05). CEUS might be helpful to improve early diagnosis of DN by quantitative analyses. AUC and DPI might be valuable quantitative indexes.

  20. Ultrasound-assisted extraction of Achyrocline satureioides prevents contrast-induced nephropathy in mice.

    PubMed

    Guss, Ketheley L; Pavanni, Stefano; Prati, Bruno; Dazzi, Lucas; de Oliveira, Jairo P; Nogueira, Breno V; Pereira, Thiago M C; Fronza, Marcio; Endringer, Denise C; Scherer, Rodrigo

    2017-07-01

    Achyrocline satureioides or Macela, has been largely used in traditional folk medicine in Brazil as an anti-inflammatory agent and to treat various digestive disorders. The aim of the present study was to evaluate the preventive action of the extracts of A. satureioides obtained by maceration and ultrasound-assisted extraction, quercetin and N-acetylcysteine against contrast-induced nephropathy in mice. The antioxidant activity, cytotoxicity and inhibition of nitric oxide (NO) production in macrophages were evaluated. Also, chemical analyses of phenolic compounds, total flavonoids, and quercetin by LC-MS/MS present in various extracts of A. satureioides were performed. Thirty six mice were divided into six groups: control group (C), Contrast-Induced Nephropathy group (CIN), Group N-acetylcysteine 200mg/kg (NAC); Group quercetin 10mg/kg (Q), Group Macela 10mg/kg (M10), and Group Macela 50mg/kg (M50). The serum levels of urea and creatinine, advanced oxidation protein products (AOPP) and renal ultrastructure were evaluated by electron microscopy scanning. Ultrasound-assisted extraction improved the quality of extract (with 100% ethanol), since did not show toxicity to fibroblasts, and showed potent antioxidant activity and a high content of phenolic compounds, flavonoids, and quercetin, in addition to being able to reduce the production of NO in dose-dependent effect in macrophages. Results showed that animals treated with Macela extracts maintained normal levels of urea, creatinine, and AOPP, while preserving ultrastructure of the renal cells. The obtained results were more promising than NAC and Q groups in protecting against renal failure caused by CIN, showing that the plant can be a promising drug for preventing this disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Contrast-enhanced endoscopic ultrasound in discrimination between benign and malignant mediastinal and abdominal lymph nodes.

    PubMed

    Hocke, Michael; Menges, Markus; Topalidis, Theodor; Dietrich, Christoph F; Stallmach, Andreas

    2008-04-01

    Enlarged lymph nodes in the mediastinum reflect neoplastic, infectious or other diseases. The classification of these nodes is crucial in the management of the patient. Currently, only invasive measures obtaining tissue samples reach satisfying specificity. Contrast-enhanced endoscopic ultrasound (EUS) may offer a non-invasive alternative. A total of 122 patients (age: 63 +/- 15 years, 92 males, 30 females) with enlarged mediastinal and/or paraaortic lymph nodes diagnosed by CT scan were included in the study. EUS-guided fine needle aspiration was performed and cytologic specimens were diagnosed as representing a malignant or benign process in case of Papanicolau IV and V, or Papanicolau I and II, respectively. Based on cytology results, the investigated lymph nodes were classified as neoplastic (n = 48) or non-neoplastic lymph nodes. Using the B-mode criteria the preliminary diagnosis was confirmed in 64 out of 74 benign lymph nodes (specificity 86%). Regarding malignant lymph nodes 33 of 48 were confirmed (sensitivity 68%). Using the advanced contrast-enhanced EUS criteria the diagnosis was confirmed in 68 of 74 benign lymph nodes (specificity 91%). However, in case of malignant lymph nodes the number of correct diagnoses dropped to 29 of 48 lymph nodes (sensitivity 60%). The contrast-enhanced EUS criteria to identify benign lymph nodes and node enlargement in malignant lymphoma do not differ. If those ten patients with malignant lymphoma are excluded, the sensitivity of the contrast enhanced EUS for malignant lymph nodes rises to 73%. Contrast-enhanced EUS improves the specificity in diagnosing benign lymph nodes as compared to B-mode EUS. It does not improve the correct identification of malignant lymph nodes and cannot replace EUS-guided fine-needle aspiration.

  2. FEASIBILITY AND SAFETY OF CONTRAST-ENHANCED ULTRASOUND IN THE DISTAL LIMB OF SIX HORSES.

    PubMed

    Seiler, Gabriela S; Campbell, Nigel; Nixon, Britton; Tsuruta, James K; Dayton, Paul A; Jennings, Samuel; Redding, W Rich; Lustgarten, Meghann

    2016-05-01

    Vascular alterations play important roles in many orthopedic diseases such as osteoarthritis, tendonitis, and synovitis in both human and equine athletes. Understanding these alterations could enhance diagnosis, prognosis, and treatment. Contrast-enhanced ultrasound (CEUS) could be a valuable method for evaluation of blood flow and perfusion of these processes in the equine distal limb, however no reports were found describing feasibility or safety of the technique. The goal of this prospective, experimental study was to describe the feasibility and safety of distal limb CEUS in a sample of six horses. For each horse, CEUS of the distal limb was performed after intravenous injections of 5 and 10 ml, as well as intra-arterial injections of 0.5 and 1 ml contrast medium. Vital parameters were monitored and CEUS images were assessed qualitatively and quantitatively for degree of contrast enhancement. None of the horses had clinically significant changes in their vital parameters after contrast medium injection. One horse had a transient increase in respiratory rate, and several horses had mild increases of systolic blood pressure of short duration after intravenous, but not after intra-arterial injections. Intra-arterial injection was possible in all horses and resulted in significantly improved contrast enhancement both quantitatively (P = 0.027) and qualitatively (P = 0.019). Findings from this study indicated that CEUS is a feasible and safe diagnostic test for evaluation of the equine distal limb. Future studies are needed to assess the clinical utility of this test for horses with musculoskeletal diseases. © 2016 American College of Veterinary Radiology.

  3. Visualization of multimodal polymer-shelled contrast agents using ultrasound contrast sequences: an experimental study in a tissue mimicking flow phantom.

    PubMed

    Larsson, Malin; Larsson, Matilda; Oddo, Letizia; Margheritelli, Silvia; Paradossi, Gaio; Nowak, Jacek; Brodin, Lars-Åke; Caidahl, Kenneth; Bjällmark, Anna

    2013-08-29

    A multimodal polymer-shelled contrast agent (CA) with target specific potential was recently developed and tested for its acoustic properties in a single element transducer setup. Since the developed polymeric CA has different chemical composition than the commercially available CAs, there is an interest to study its acoustic response when using clinical ultrasound systems. The aim of this study was therefore to investigate the acoustic response by studying the visualization capability and shadowing effect of three polymer-shelled CAs when using optimized sequences for contrast imaging. The acoustic response of three types of the multimodal CA was evaluated in a tissue mimicking flow phantom setup by measuring contrast to tissue ratio (CTR) and acoustic shadowing using five image sequences optimized for contrast imaging. The measurements were performed over a mechanical index (MI) range of 0.2-1.2 at three CA concentrations (106, 105, 104 microbubbles/ml). The CTR-values were found to vary with the applied contrast sequence, MI and CA. The highest CTR-values were obtained when a contrast sequence optimized for higher MI imaging was used. At a CA concentration of 106 microbubbles/ml, acoustic shadowing was observed for all contrast sequences and CAs. The CAs showed the potential to enhance ultrasound images generated by available contrast sequences. A CA concentration of 106 MBs/ml implies a non-linear relation between MB concentration and image intensity.

  4. [Contrast-enhanced Ultrasound in Diagnostic Imaging of Muscle Injuries: Perfusion Imaging in the Early Arterial Phase].

    PubMed

    Hotfiel, T; Carl, H D; Swoboda, B; Engelhardt, M; Heinrich, M; Strobel, D; Wildner, D

    2016-03-01

    Ultrasound is a standard procedure widely used in the diagnostic investigation of muscle injuries and widely described in the literature. Its advantages include rapid availability, cost effectiveness and the possibility to perform a real-time dynamic examination with the highest possible spatial resolution. In the diagnostic work-up of minor lesions (muscle stiffness, muscle strain), plain ultrasound has so far been inferior to MRI. The case presented by us is an example of the possibilities offered by contrast-enhanced ultrasound (CEUS) in the imaging of muscle injuries compared with plain B-mode image ultrasound and MRI imaging of the affected region. This case report is about a high-performance football player who sustained a muscle injury. He underwent an ultrasound examination (S 2000, 9L4 Probe, Siemens, Germany), which was performed simultaneously in the conventional and contrast-enhanced mode at the level of the lesion. An intravenous bolus injection of 4.8 ml of intravascular contrast agent (SonoVue(®), Bracco, Italy) was given via a cubital intravenous line. After that, the distribution of contrast agent was visualised in the early arterial phase. In addition, a plain magnetic resonance imaging scan of both thighs was performed for reference. On conventional ultrasound, the lesion was not clearly distinguishable from neighbouring tissue, whereas contrast-enhanced ultrasound demonstrated a well delineated, circumscribed area of impaired perfusion with hypoenhancement compared with the surrounding muscles at the clinical level of the lesion in the arterial wash-in phase (0-30 sec, after intravenous administration). The MRI scan revealed an edema signal with perifascial fluid accumulation in the corresponding site. The use of intravascular contrast agent enabled the sensitive detection of a minor injury by ultrasound for the first time. An intramuscular edema seen in the MRI scan showed a functional arterial perfusion impairment on ultrasound, which was

  5. In Vivo Quantification of Flow Dynamics in Intracranial Aneurysms Using Intra-Operative Contrast-Specific Ultrasound and PIV Techniques

    NASA Astrophysics Data System (ADS)

    CantÓN, G.Á.}Dor

    2005-11-01

    The goal of this study is to assess in vivo the hemodynamics of intracranial aneurysms using ultrasound and Digital Particle Imaging Velocimetry (DPIV) techniques. An ultrasound machine, equipped with an intra-operative transducer, was used to visualize the flow features inside an aneurysm with the aid of microbubbles as ultrasound contrast agent. The ultrasound studies were done using a Phase Inversion technique. Operating in the Doppler mode, the flow velocities in the afferent and the downstream vascular segments as well as inside the aneurysm were recorded and assessed. We analyzed the ultrasound data sets with a DPIV technique using backscattered signals from the microbubbles. The spatial and temporal distribution of velocity, vorticity, and stress fields was measured. These quantities were also measured in an in vitro aneurysmal model using the DPIV system. Our study shows that an advanced contrast-specific ultrasound technique in combination with a DPIV technique can be used to quantify in real time the flow-mechanical patterns inside the aneurysm.

  6. Detection of acoustic cavitation in the heart with microbubble contrast agents in vivo: a mechanism for ultrasound-induced arrhythmias.

    PubMed

    Rota, Claudio; Raeman, Carol H; Child, Sally Z; Dalecki, Diane

    2006-11-01

    Ultrasound fields can produce premature cardiac contractions under appropriate exposure conditions. The pressure threshold for ultrasound-induced premature contractions is significantly lowered when microbubble contrast agents are present in the vasculature. The objective of this study was to measure directly ultrasound-induced cavitation in the murine heart in vivo and correlate the occurrence of cavitation with the production of premature cardiac contractions. A passive cavitation detection technique was used to quantify cavitation activity in the heart. Experiments were performed with anesthetized, adult mice given intravenous injections of either a contrast agent (Optison) or saline. Murine hearts were exposed to ultrasound pulses (200 kHz, 1 ms, 0.1-0.25 MPa). Premature beats were produced in mice injected with Optison and the likelihood of producing a premature beat increased with increasing pressure amplitude. Similarly, cavitation was detected in mice injected with Optison and the amplitude of the passive cavitation detector signal increased with increasing exposure amplitude. Furthermore, there was a direct correlation between the extent of cavitation and the likelihood of ultrasound producing a premature beat. Neither premature beats nor cavitation activity were observed in animals injected with saline and exposed to ultrasound. These results are consistent with acoustic cavitation as a mechanism for this bioeffect.

  7. A comparison of ultrasound-based advanced oxidation processes for the removal of X-ray contrast media.

    PubMed

    Ning, B; Graham, N J D; Lickiss, P D

    2009-01-01

    The degradation of specific iodinated X-ray contrast media (ICM) compounds (viz: diatrizoate, iomeprol, iopromide, and iopamidol) by ultrasound irradiation in aqueous solution, with and without the presence of hydrogen peroxide or ozone, has been studied. Experiments were carried out at a constant ultrasound frequency of 20 kHz, at two power intensity values of 17.6 and 200.1 W cm(-2), and at five power densities up to 0.235 W ml(-1). Zero-order kinetic rate constants for the ICM degradation by ultrasound alone were calculated under certain sonication conditions. Pyrolysis appeared to contribute approximately 30%, and radical attack 70%, of the overall ICM degradation performance. The effect of ultrasound intensity on compound degradation (at a given power density) was found to play a negligible role, whereas ultrasound power density was found to be a major factor controlling the overall oxidation process under these conditions. The compound degradation by ultrasound alone was relatively minor, but the addition of hydrogen peroxide in the sonication process gave some improvement with a doubling in the degradation performance at the greatest applied peroxide concentration. The combination of gaseous ozone and ultrasound was found to be very effective in degrading ICM compounds and an almost complete compound removal could be achieved.

  8. Biodegradable double-targeted PTX-mPEG-PLGA nanoparticles for ultrasound contrast enhanced imaging and antitumor therapy in vitro

    PubMed Central

    Sun, Ying; Duan, You Rong; Du, Lian Fang

    2016-01-01

    A porous-structure nano-scale ultrasound contrast agent (UCA) was made of monomethoxypoly (ethylene glycol)-poly (lactic-co-glycolic acid) (mPEG-PLGA), and modified by double-targeted antibody: anti-carcinoembryonic antigen (CEA) and anti-carbohydrate antigen 19-9 (CA19-9), as a double-targeted nanoparticles (NPs). Anti-tumor drug paclitaxel (PTX) was encapsulated in the double-targeted nanoparticles (NPs). The morphor and release curve were characterized. We verified a certain anticancer effect of PTX-NPs through cytotoxicity experiments. The cell uptake result showed much more NPs may be facilitated to ingress the cells or tissues with ultrasound (US) or ultrasound targeted microbubble destruction (UTMD) transient sonoporation in vitro. Ultrasound contrast-enhanced images in vitro and in vivo were investigated. Compared with SonoVue, the NPs prolonged imaging time in rabbit kidneys and tumor of nude mice, which make it possible to further enhance anti-tumor effects by extending retention time in the tumor region. The novel double-targeted NPs with the function of ultrasound contrast enhanced imaging and anti-tumor therapy can be a promising way in clinic. PMID:27835907

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

    NASA Astrophysics Data System (ADS)

    Peruzzini, D.; Viti, J.; Tortoli, P.; Verweij, M. D.; de Jong, N.; Vos, H. J.

    2015-10-01

    Currently, in medical ultrasound contrast agent (UCA) imaging the second harmonic scattering of the microbubbles is regularly used. This scattering is in competition with the signal that is caused by nonlinear wave propagation in tissue. It was reported that UCA imaging based on the third or higher harmonics, i.e. "superharmonic" imaging, shows better contrast. However, the superharmonic scattering has a lower signal level compared to e.g. second harmonic signals. This study investigates the contrast-to-tissue ratio (CTR) and signal to noise ratio (SNR) of superharmonic UCA scattering in a tissue/vessel mimicking phantom using a real-time clinical scanner. Numerical simulations were performed to estimate the level of harmonics generated by the microbubbles. Data were acquired with a custom built dual-frequency cardiac phased array probe. Fundamental real-time images were produced while beam formed radiofrequency (RF) data was stored for further offline processing. The phantom consisted of a cavity filled with UCA surrounded by tissue mimicking material. The acoustic pressure in the cavity of the phantom was 110 kPa (MI = 0.11) ensuring non-destructivity of UCA. After processing of the acquired data from the phantom, the UCA-filled cavity could be clearly observed in the images, while tissue signals were suppressed at or below the noise floor. The measured CTR values were 36 dB, >38 dB, and >32 dB, for the second, third, and fourth harmonic respectively, which were in agreement with those reported earlier for preliminary contrast superharmonic imaging. The single frame SNR values (in which `signal' denotes the signal level from the UCA area) were 23 dB, 18 dB, and 11 dB, respectively. This indicates that noise, and not the tissue signal, is the limiting factor for the UCA detection when using the superharmonics in nondestructive mode.

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

    SciTech Connect

    Peruzzini, D.; Viti, J.; Tortoli, P.; Verweij, M. D.; Jong, N. de; Vos, H. J.

    2015-10-28

    Currently, in medical ultrasound contrast agent (UCA) imaging the second harmonic scattering of the microbubbles is regularly used. This scattering is in competition with the signal that is caused by nonlinear wave propagation in tissue. It was reported that UCA imaging based on the third or higher harmonics, i.e. “superharmonic” imaging, shows better contrast. However, the superharmonic scattering has a lower signal level compared to e.g. second harmonic signals. This study investigates the contrast-to-tissue ratio (CTR) and signal to noise ratio (SNR) of superharmonic UCA scattering in a tissue/vessel mimicking phantom using a real-time clinical scanner. Numerical simulations were performed to estimate the level of harmonics generated by the microbubbles. Data were acquired with a custom built dual-frequency cardiac phased array probe. Fundamental real-time images were produced while beam formed radiofrequency (RF) data was stored for further offline processing. The phantom consisted of a cavity filled with UCA surrounded by tissue mimicking material. The acoustic pressure in the cavity of the phantom was 110 kPa (MI = 0.11) ensuring non-destructivity of UCA. After processing of the acquired data from the phantom, the UCA-filled cavity could be clearly observed in the images, while tissue signals were suppressed at or below the noise floor. The measured CTR values were 36 dB, >38 dB, and >32 dB, for the second, third, and fourth harmonic respectively, which were in agreement with those reported earlier for preliminary contrast superharmonic imaging. The single frame SNR values (in which ‘signal’ denotes the signal level from the UCA area) were 23 dB, 18 dB, and 11 dB, respectively. This indicates that noise, and not the tissue signal, is the limiting factor for the UCA detection when using the superharmonics in nondestructive mode.

  11. A novel coded excitation scheme to improve spatial and contrast resolution of quantitative ultrasound imaging.

    PubMed

    Sanchez, Jose R; Pocci, Darren; Oelze, Michael L

    2009-10-01

    Quantitative ultrasound (QUS) imaging techniques based on ultrasonic backscatter have been used successfully to diagnose and monitor disease. A method for improving the contrast and axial resolution of QUS parametric images by using the resolution enhancement compression (REC) technique is proposed. Resolution enhancement compression is a coded excitation and pulse compression technique that enhances the -6-dB bandwidth of an ultrasonic imaging system. The objective of this study was to combine REC with QUS (REC-QUS) and evaluate and compare improvements in scatterer diameter estimates obtained using the REC technique to conventional pulsing methods. Simulations and experimental measurements were conducted with a single-element transducer (f/4) having a center frequency of 10 MHz and a -6-dB bandwidth of 80%. Using REC, the -6-dB bandwidth was enhanced to 155%. Images for both simulation and experimental measurements contained a signal-to-noise ratio of 28 dB. In simulations, to monitor the improvements in contrast a software phantom with a cylindrical lesion was evaluated. In experimental measurements, tissue-mimicking phantoms that contained glass spheres with different scatterer diameters were evaluated. Estimates of average scatterer diameter in the simulations and experiments were obtained by comparing the normalized backscattered power spectra to theory over the -6-dB bandwidth for both conventional pulsing and REC. Improvements in REC-QUS over conventional QUS were quantified through estimate bias and standard deviation, contrast-to-noise ratio, and histogram analysis of QUS parametric images. Overall, a 51% increase in contrast and a 60% decrease in the standard deviation of average scatterer diameter estimates were obtained during simulations, while a reduction of 34% to 71% was obtained in the standard deviation of average scatterer diameter for the experimental results.

  12. Intraprocedure contrast enhanced ultrasound: the value in assessing the effect of ultrasound-guided high intensity focused ultrasound ablation for uterine fibroids.

    PubMed

    Peng, Song; Hu, Liang; Chen, Wenzhi; Chen, Jinyun; Yang, Caiyong; Wang, Xi; Zhang, Rong; Wang, Zhibiao; Zhang, Lian

    2015-04-01

    To investigate the value of microbubble contrast-enhanced ultrasound (CEUS) in evaluating the treatment response of uterine fibroids to HIFU ablation. Sixty-eight patients with a solitary uterine fibroid from the First Affiliated Hospital of Chongqing Medical University were included and analyzed. All patients underwent pre- and post-treatment magnetic resonance imaging (MRI) with a standardized protocol, as well as pre-evaluation, intraprocedure, and immediate post-treatment CEUS. CEUS and MRI were compared by different radiologists. In comparison with MRI, CEUS showed that the size of fibroids, volume of fibroids, size of non-perfused regions, non-perfused volume (NPV) or fractional ablation (NPV ratio) was similar to that of MRI. In terms of CEUS examination results, the median volume of fibroids was 75.2 (interquartile range, 34.2-127.3) cm(3), the median non-perfused volume was 54.9 (interquartile range, 28.0-98.1) cm(3), the mean fractional ablation was 83.7±13.6 (range, 30.0-100.0)%. In terms of MRI examination results, the median volume of fibroids was 74.1 (interquartile range, 33.4-116.2) cm(3). On the basis of contrast-enhanced T1-weighted images immediately after HIFU treatment, the median non-perfused volume was 58.5 (interquartile range, 27.7-100.0) cm(3), the average fractional ablation was 84.2±14.2 (range, 40.0-100.0)%. CEUS clearly showed the size of fibroids and the non-perfused areas of the fibroid. Results from CEUS correlated well with results obtained from MRI. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

    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

  14. Contrast-enhanced imaging of SPIO-labeled platelets using magnetomotive ultrasound

    PubMed Central

    Pope, Ava G.; Wu, Gongting; McWhorter, Frances Y.; Merricks, Elizabeth C.; Nichols, Timothy C.; Czernuszewicz, Tomasz J.; Gallippi, Caterina M.; Oldenburg, Amy L.

    2013-01-01

    The ability to image platelets in vivo can provide insight into blood clotting processes and coagulopathies, and aid in identifying sites of vascular endothelial damage related to trauma or cardiovascular disease. Toward this end, we have developed a magnetomotive ultrasound (MMUS) system that provides contrast-enhanced imaging of superparamagnetic iron oxide (SPIO) labeled platelets via magnetically-induced vibration. Platelets are a promising platform for functional imaging contrast because they readily take up SPIOs and are easily harvested from blood. Here we report a novel MMUS system that accommodates an arbitrarily thick sample while maintaining portability. We employed a frequency- and phase-locked motion detection algorithm based on bandpass filtering of the differential RF phase, which allows for the detection of sub-resolution vibration amplitudes on the order of several nanometers. We then demonstrated MMUS in homogenous tissue phantoms at SPIO concentrations as low as 0.09 mg/ml Fe (p < 0.0001, n = 6, t-test). Finally, we showed that our system is capable of 3-dimensional imaging of a 185 μL simulated clot containing SPIO-platelets. This highlights the potential utility for non-invasive imaging of platelet-rich clots, which would constitute a fundamental advance in technology for the study of hemostasis and detection of clinically relevant thrombi. PMID:24077004

  15. Ultrasound contrast imaging: influence of scatterer motion in multi-pulse techniques.

    PubMed

    Lin, Fanglue; Cachard, Christian; Mori, Riccardo; Varray, Francois; Guidi, Francesco; Basset, Olivier

    2013-10-01

    In ultrasound contrast imaging, many techniques based on multiple transmissions have been proposed to increase the contrast-to-tissue ratio (CTR). They are generally based on the response of static scatterers inside the imaged region. However, scatterer motion, for example in blood vessels, has an inevitable influence on multi-pulse techniques, which can either enhance or degrade the technique involved. This paper investigates the response of static nonlinear media insonated by multi-pulses with various phase shifts, and the influence of scatterer motion on multi-pulse techniques. Simulations and experimental results from a single bubble and clouds of bubbles show that the phase shift of the echoes backscattered from bubbles is dependent on the transmissions' phase shift, and that the bubble motion influences the efficiency of multi-pulse techniques: fundamental and second-harmonic amplitudes of the processed signal change periodically, exhibiting maximum or minimum values, according to scatterer motion. Furthermore, experimental results based on the second-harmonic inversion (SHI) technique reveal that bubble motion can be taken into account to regulate the pulse repetition frequency (PRF). With the optimal PRF, the CTR of SHI images can be improved by about 12 dB compared with second-harmonic images.

  16. Case Report of Contrast-Enhanced Ultrasound Features of Primary Hepatic Neuroendocrine Tumor

    PubMed Central

    Li, Wei; Zhuang, Bo-wen; Wang, Zhu; Liao, Bing; Hong, Ling-yao; Xu, Ming; Lin, Xiao-na; Xie, Xiao-yan; Lu, Ming-de; Chen, Li-da; Wang, Wei

    2016-01-01

    Abstract Primary hepatic neuroendocrine tumors (PHNETs) are very rare and their clinical features and treatment outcomes are not well understood. It is difficult to reach a proper diagnosis before biopsy or resection. The aim of this study was to analyze the imaging features of PHNETs on contrast-enhanced ultrasound (CEUS). The clinical characteristics, CEUS findings, pathological features, treatment and prognosis of 6 patients with PHNET treated in our hospital were retrospectively analyzed. Most PHNETs occurred in middle-aged patients, and the most common clinical manifestation was right upper quadrant palpable mass and abdominal pain. Multiple small anechoic intralesional cavities occurred frequently in PHNET. Multilocular cystic with internal septation or monolocular with wall nodule could also be detected. On contrast-enhanced ultrasonography (CEUS), heterogeneous hyperenhancement in the arterial phase and wash-out hypoenhancement were observed in most patients, while computed tomography scanning yielded similar results. Diagnosis of PHNET was confirmed by immunohistochemical result and follow-up with the absence of extrahepatic primary sites. Five patients received surgical resection and 2 cases exhibited recurrence. Transcatheter arterial chemoembolization was performed in 1 patient with recurrence. Only 1 patient received conservative care. The median overall survival in 5 patients who underwent surgical treatment was 27 months (18–36 months). PHNET is a rare tumor, and its diagnosis is difficult. The CEUS features reported in this series may enrich the knowledge base for characterization of PHNET. PMID:27227910

  17. An in vitro study of a microbubble contrast agent using a clinical ultrasound imaging system

    NASA Astrophysics Data System (ADS)

    Sboros, V.; Moran, C. M.; Pye, S. D.; McDicken, W. N.

    2004-01-01

    Optimal insonation settings for contrast imaging are yet to be specified, mainly due to the lack of good understanding of the behaviour of the microbubbles. A satisfactory model that explains the behaviour of individual contrast agent scatterers has not yet been reported in the literature. An in vitro system based on a commercial scanner (ATL HDI3000) has been developed to investigate the backscatter of such agents. Suspensions of Definity® were introduced in an anechoic tank. The frequency of transmitted ultrasound varied from 1 to 5 MHz, pulse period from 2 to 10 periods and peak negative acoustic pressure from 0.08 to 1.7 MPa. The backscatter at the fundamental and second harmonic frequency windows from the agent was normalized in terms of the corresponding components of backscatter from a blood mimicking fluid suspension. The agent provided a dominant resonance effect at 1.6 MHz transmit frequency. Second harmonic normalized backscatter averaged around 9 dB higher than the fundamental. The normalized fundamental backscatter intensity was linear with peak negative pressure. The second harmonic at resonance peaked at 0.5 MPa suggestive of bubble disruption above such pressure. The system proved capable of illustrating the ultrasonic behaviour of Definity® in vitro, and the investigation suggested particular insonation conditions for optimal image enhancement using Definity®.

  18. Contrast-enhanced imaging of SPIO-labeled platelets using magnetomotive ultrasound

    NASA Astrophysics Data System (ADS)

    Pope, Ava G.; Wu, Gongting; McWhorter, Frances Y.; Merricks, Elizabeth P.; Nichols, Timothy C.; Czernuszewicz, Tomasz J.; Gallippi, Caterina M.; Oldenburg, Amy L.

    2013-10-01

    The ability to image platelets in vivo can provide insight into blood clotting processes and coagulopathies, and aid in identifying sites of vascular endothelial damage related to trauma or cardiovascular disease. Toward this end, we have developed a magnetomotive ultrasound (MMUS) system that provides contrast-enhanced imaging of superparamagnetic iron oxide (SPIO) labeled platelets via magnetically-induced vibration. Platelets are a promising platform for functional imaging contrast because they readily take up SPIOs and are easily harvested from blood. Here we report a novel MMUS system that accommodates an arbitrarily thick sample while maintaining portability. We employed a frequency- and phase-locked motion detection algorithm based on bandpass filtering of the differential RF phase, which allows for the detection of sub-resolution vibration amplitudes on the order of several nanometers. We then demonstrated MMUS in homogenous tissue phantoms at SPIO concentrations as low as 0.09 mg ml-1 Fe (p < 0.0001, n = 6, t-test). Finally, we showed that our system is capable of three-dimensional imaging of a 185 µL simulated clot containing SPIO-platelets. This highlights the potential utility for non-invasive imaging of platelet-rich clots, which would constitute a fundamental advance in technology for the study of hemostasis and detection of clinically relevant thrombi.

  19. Real-time contrast enhanced ultrasound imaging of focal splenic lesions.

    PubMed

    Li, Wei; Liu, Guangjian; Wang, Wei; Wang, Zhu; Huang, Yang; Xu, ZuoFeng; Xie, XiaoYan; Lu, MingDe

    2014-04-01

    To investigate the imaging features of focal splenic lesions (FSLs) on contrast-enhanced ultrasound (CEUS). Thirty two patients with FSLs proved by pathology were retrospectively analyzed. CEUS was performed using intravenous bolus injection of 2.4 ml sulfur hexafluoride-filled microbubble contrast agent and real time scanning. There were hemangioma (n=7), lymphoma (n=8), true cyst (n=3), infarction (n=4), hematolymphangioma (n=2), metastasis tumor (n=2), and one for each of the following entities extramedullary hemopoiesis, hamartoma, tuberculosis, Langerhans' cell histiocytosis, inflammatory pseudotumor and myxofibrosarcoma. Among 21 benign lesions, 4 infarctions and 3 cysts presented non-enhancement throughout CEUS scanning, and the other 14 lesions displayed various enhancement levels with 6 (42.9%) hyper-enhancement, 2 (14.3%) iso-enhancement and 6 (42.9%) hypo-enhancement in arterial phase and 11 (78.6%) hypo-enhancement, 1 (7.1%) iso-enhancement and 2 (14.3%) hyper-enhancement in late phase, respectively. The enhancement pattern included 9 (64.3%) homogeneous, 4 (28.6%) heterogeneous and 1 (7.1%) rim-like enhancement. As for the malignant FSLs, all the lesions became completely or extensively hypo-enhancement during the late phase no matter their vascularity during arterial phase. The CEUS features reported in this series may enrich the knowledge for CEUS characterization of FSLs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Analysis of flash echo from contrast agent for designing optimal ultrasound diagnostic systems.

    PubMed

    Kamiyama, N; Moriyasu, F; Mine, Y; Goto, Y

    1999-03-01

    Microbubble-based contrast agents can enhance echoes in areas of low blood flow, but the bubbles are extremely sensitive and collapse easily when exposed to ultrasound (US) irradiation. An experimental study of bubble collapse was carried out to design new functions for US diagnostic systems to detect echoes from microbubbles more efficiently. For contrast agent (Levovist) solution, a high-intensity, but momentary, echo (flash echo), was observed in the first frame image after a several-second suspension of transmission, but was not seen in the second frame image. These "flash echo" signals were analyzed and categorized based on microscopic observation, and the results showed that the longevity of the microbubbles was reduced by conditions such as B-mode imaging. Next, a numerical simulation of the bubbles in liquid was performed under the same conditions as in the in vitro experiment. The results showed that even bubbles less than 1 microm in diameter expand and collapse within one pulse drive, which would generate flash echoes. The flash echo imaging system described here permits flexible intermittent scanning with variable intervals, with a variable number of frames at the trigger, and with simultaneous monitoring at low power output. Animal experiments were also conducted to evaluate the system. As the interval between frames was increased, the flash echoes gradually increased, and perfusion in the parenchyma was clearly observed with an interval of 4 s.

  1. A New Imaging Strategy Using Wideband Transient Response of Ultrasound Contrast Agents

    PubMed Central

    Kruse, Dustin E.; Ferrara, Katherine W.

    2006-01-01

    High-resolution clinical systems operating near 15 MHz are becoming more available; however, they lack sensitive harmonic imaging modes for ultrasound contrast agent (UCA) detection, primarily due to limited bandwidth. When an UCA is driven to nonlinear oscillation, a very wideband acoustic transient response is produced that extends beyond 15 MHz. We propose a novel strategy using two separate transducers at widely separated frequencies and arranged confocally to simultaneously excite and receive acoustic transients from UCAs. Experiments were performed to demonstrate that this new mode shows similar resolution, higher echo amplitudes, and greatly reduced attenuation compared to transmission at a higher frequency, and superior resolution compared to transmission and reception at a lower frequency. The proposed method is shown to resolve two 200 μm tubes with centers separated by 400 μm. Strong acoustic transients were detected for rarefaction-first 1-cycle pulses with peak-negative pressures above 300 kPa. The results of this work may lead to uses in flow and/or targeted imaging in applications requiring very high sensitivity to contrast agents. PMID:16245601

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

    NASA Astrophysics Data System (ADS)

    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.

  3. Quantitative contrast-enhanced ultrasound of intraplaque neovascularization in patients with carotid atherosclerosis.

    PubMed

    van den Oord, S C H; Akkus, Z; Bosch, J G; Hoogi, A; ten Kate, G L; Renaud, G; Sijbrands, E J G; Verhagen, H J; van der Lugt, A; Adam, D; de Jong, N; van der Steen, A F W; Schinkel, A F L

    2015-04-01

    Intraplaque neovascularization (IPN) is an increasingly studied marker of the vulnerable atherosclerotic plaque, and contrast-enhanced ultrasound (CEUS) is an in vivo imaging technique for the assessment of IPN. The purpose of this study was to test novel quantification methods for the detection of carotid IPN using CEUS. 25 patients with established carotid atherosclerosis underwent bilateral carotid CEUS using a Philips iU-22 ultrasound system with an L9 - 3 transducer. Visual scoring of IPN was performed using a 3-point score. Quantification of IPN was performed using novel custom developed software. In short, regions of interest were drawn over the atherosclerotic plaques. After motion compensation, several IPN features were calculated. Statistical analysis was performed using Spearman's rho. Reproducibility of the quantification features was calculated using intra-class correlation coefficients and mean differences between calculations. 45 carotid arteries were available for the quantification of IPN. The quantification of IPN was feasible in all 45 carotid plaques. The IPN area, IPN area ratio and neovessel count had a good correlation with the visual IPN score (respectively ρ = 0.719, ρ = 0.538, ρ = 0.474 all p < 0.01). The intra-observer and inter-observer agreement was good to excellent (p < 0.01). The intra-observer and inter-observer variability was low. The quantification of carotid IPN on CEUS is feasible and provides multiple features on carotid IPN. Accurate quantitative assessment of IPN may be important to recognize and to monitor changes during therapy in vulnerable atherosclerotic plaques. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Plasma Sterilization of Poly Lactic Acid Ultrasound Contrast Agents: Surface Modification and Implications for Drug Delivery

    PubMed Central

    Eisenbrey, John R.; Hsu, Jennifer; Wheatley, Margaret A.

    2013-01-01

    Poly lactic acid (PLA) ultrasound contrast agents (CA) have been previously developed in our laboratory for ultrasound (US) imaging, as well as surface coated with doxorubicin to create a potential targeted platform of chemotherapeutic delivery using focused US. However, we have previously found it impossible to sterilize these agents while at the same time maintaining their acoustic properties, a task that would probably require fabrication within a clean facility. The purpose of this paper is to investigate the feasibility of using plasma to sterilize these CA while maintaining maximum echogenicity, a step that would greatly facilitate in vivo investigations. Effects of plasma exposure time (1, 3 and 6 minutes) and intensity (low- 10 mA, 6.8 W; medium- 15 mA, 10.5 W; and high- 25 mA, 18W) on the CA’s acoustic properties, surface morphology, zeta potential, capacity to carry chemotherapeutics, and overall sterility are described. Both increases in plasma intensity and exposure time increased CA zeta potential and also significantly increased drug payload. High intensity plasma exposure for three minutes was found to be an optimal sterilization protocol for maximal (100%) preservation of CA echogenicity. Plasma exposure resulted in sterile samples and maintained original CA enhancement of 20 dB and acoustic half-life over 75 minutes, while increasing CA zeta potential by 11 mV and doxorubicin loading efficiency by 10%. This study not only shows how a highly temperature and pressure sensitive agent can be sterilized using plasma, but also that surface modification can be used to increase surface binding of drug. PMID:19766380

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

    NASA Astrophysics Data System (ADS)

    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

  6. Imaging features of hepatic angiomyolipomas on real-time contrast-enhanced ultrasound

    PubMed Central

    Wang, Z; Xu, H-X; Xie, X-Y; Xie, X-H; Kuang, M; Xu, Z-F; Liu, G-J; Chen, L-D; Lin, M-X; Lu, M-D

    2010-01-01

    The aim of this study was to evaluate the imaging features of hepatic angiomyolipoma (AML) on contrast-enhanced ultrasound (CEUS). The imaging features of 12 pathologically proven hepatic AML lesions in 10 patients who had undergone baseline ultrasound (BUS) and CEUS examinations were evaluated retrospectively. The enhancement extent, pattern and dynamic change, along with the enhancement process, on CEUS were analysed. The diagnostic results of BUS and CEUS before pathological examination were also recorded. The results showed that 75% (9/12) of the AML lesions exhibited mixed echogenicity on BUS and most showed remarkable hyperechogenicity in combination with a hypoechoic or anechoic portion. Arterial flow signals were detected in 75% (9/12) of the lesions on colour Doppler imaging. On CEUS, 66.7% (n = 8) of the 12 lesions exhibited hyperenhancement in the arterial phase, slight hyperenhancement (n = 2) or isoenhancement (n = 6) in the portal phase, and slight hyperenhancement (n = 1) or isoenhancement (n = 7) in the late phase. Three (25%) lesions exhibited hyperenhancement in the arterial phase and hypoenhancement in both portal and late phases. One (8.3%) lesion exhibited hypoenhancement throughout the CEUS process. Before pathological examination with BUS, only 3 (25%) lesions were correctly diagnosed as hepatic AML. Conversely, on CEUS, correct diagnoses were made for 66.8% (8/12) of hepatic AMLs. Therefore, arterial hyperenhancement and subsequent sustained enhancement on CEUS were found in the majority of hepatic AMLs. The combination of BUS and CEUS leads to the correct diagnosis in the majority of hepatic AMLs, and is higher than the success rate achieved by BUS alone. PMID:19723766

  7. Diagnostic and prognostic values of contrast-enhanced ultrasound in breast cancer: a retrospective study

    PubMed Central

    Zhao, Yi-Xuan; Liu, Shuang; Hu, Yan-Bing; Ge, Yan-Yan; Lv, Dong-Mei

    2017-01-01

    This study aimed to explore the diagnostic and prognostic values of contrast-enhanced ultrasound (CEUS) in breast cancer. Between September 2009 and October 2011, a total of 143 breast cancer patients and 161 healthy people were selected as case group and control group, respectively. After the identification of lesions by conventional ultrasound, all patients underwent CEUS. The CEUS images were analyzed, and time–intensity curves (TICs) were obtained. Hematoxylin–eosin and immunohistochemistry staining was performed on tissue specimens, according to which the expressions of estrogen receptor (ER), c-erb-B2, p53, and Ki-67 were measured. Multivariate logistic regression analysis was used to compare CEUS and TIC parameters between the two groups. Compared with the control group, cancer patients showed high enhancement, heterogeneous enhancement or defects in the central region, expansion of lesion diameter after enhancement and crab-like blur lesion edges. The peak intensity (PI), relative start time of enhancement, relative PI, and relative area under the curve in the case group were significantly higher than those in the control group. Logistic analysis showed that the uniformity of enhancement, expansion of lesion diameter, and relative PI were significant diagnostic parameters of breast cancer, with area under the curve being 0.798, 0.776, and 0.919, respectively. There were strong associations between CEUS characteristics and expressions of prognostic factors in breast cancer: the heterogeneous enhancement was common in c-erb-B2-positive tumors; the centripetal enhancement occurred more in ER-negative tumors; perforator vessels were often seen in tumors at high histological grade; perfusion defects were common in ER-negative, c-erb-B2-positive, and Ki-67-positive tumors. CEUS is a useful tool for the early diagnosis and prognosis of breast cancer. PMID:28260926

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

    PubMed Central

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

    2014-01-01

    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 on-screen 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

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

    PubMed

    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.

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

    PubMed

    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

  11. A General Framework for Modeling Sub- and Ultraharmonics of Ultrasound Contrast Agent Signals with MISO Volterra Series

    PubMed Central

    Charara, Jamal; Girault, Jean-Marc

    2013-01-01

    Sub- and ultraharmonics generation by ultrasound contrast agents makes possible sub- and ultraharmonics imaging to enhance the contrast of ultrasound images and overcome the limitations of harmonic imaging. In order to separate different frequency components of ultrasound contrast agents signals, nonlinear models like single-input single-output (SISO) Volterra model are used. One important limitation of this model is its incapacity to model sub- and ultraharmonic components. Many attempts are made to model sub- and ultraharmonics using Volterra model. It led to the design of mutiple-input singe-output (MISO) Volterra model instead of SISO Volterra model. The key idea of MISO modeling was to decompose the input signal of the nonlinear system into periodic subsignals at the subharmonic frequency. In this paper, sub- and ultraharmonics modeling with MISO Volterra model is presented in a general framework that details and explains the required conditions to optimally model sub- and ultraharmonics. A new decomposition of the input signal in periodic orthogonal basis functions is presented. Results of application of different MISO Volterra methods to model simulated ultrasound contrast agents signals show its efficiency in sub- and ultraharmonics imaging. PMID:23554840

  12. Contrast-enhanced ultrasound (CEUS) appearances of an adrenal phaeochromocytoma in a child with Von Hippel-Lindau disease.

    PubMed

    Al Bunni, Faise; Deganello, Annamaria; Sellars, Maria E; Schulte, Klaus-Martin; Al-Adnani, Mudher; Sidhu, Paul S

    2014-12-01

    A phaeochromocytoma is a rare catecholamine-secreting tumour arising from the chromaffin cells. We describe a case of a child with Von Hippel-Lindau disease, with an adrenal phaeochromocytoma who presented with severe dilated cardiomyopathy driven by secondary hypertension. Contrast-enhanced ultrasound findings are described and compared with both magnetic resonance imaging and computed tomography imaging.

  13. Role of intra-operative contrast-enhanced ultrasound (CEUS) in robotic-assisted nephron-sparing surgery.

    PubMed

    Alenezi, Ahmad N; Karim, Omer

    2015-03-01

    This review examines studies of intra-operative contrast-enhanced ultrasound (CEUS) and its emerging role and advantages in robotic-assisted nephron-sparing surgery. Contrast-enhanced ultrasound is a technology that combines the use of second-generation contrast agents consisting of microbubbles with existent ultrasound techniques. Until now, this novel technology has aided surgeons with procedures involving the liver. However, with recent advances in the CEUS technique and the introduction of robotics in nephron-sparing surgery, CEUS has proven to be efficacious in answering several clinical questions with respect to the kidneys. In addition, the introduction of the microbubble-based contrast agents has increased the image quality and signal uptake by the ultrasound probe. This has led to better, enhanced scanning of the macro and microvasculature of the kidneys, making CEUS a powerful diagnostic modality. This imaging method is capable of further lowering the learning curve and warm ischemia time (WIT) during robotic-assisted nephron-sparing surgery, with its increased level of capillary perfusion and imaging. CEUS has the potential to increase the sensitivity and specificity of intra-operative images, and can significantly improve the outcome of robotic-assisted nephron-sparing surgery by increasing the precision and diagnostic insight of the surgeon. The purpose of this article is to review the practical and potential uses of CEUS as an intra-operative imaging technique during robotic-assisted nephron-sparing surgery.

  14. Demonstration of an occult biliary-arterial fistula using percutaneous contrast-enhanced ultrasound cholangiography in a transplanted liver.

    PubMed

    Daneshi, Mohammad; Rajayogeswaran, Brathaban; Peddu, Praveen; Sidhu, Paul S

    2014-02-01

    We present a case of a biliary-arterial communication as a consequence of the placement of an internal-external biliary drainage catheter in a liver transplant patient diagnosed on contrast-enhanced ultrasound using a novel application by injecting microbubble contrast into the catheter tube. We postulate that this method may be sensitive in identifying occult communications between the biliary tree and the vascular compartment when a catheter drain is positioned, and there is hemobilia or unexplained sepsis.

  15. Improved Linear Contrast-Enhanced Ultrasound Imaging via Analysis of First-Order Speckle Statistics.

    PubMed

    Lowerison, Matthew R; Hague, M Nicole; Chambers, Ann F; Lacefield, James C

    2016-09-01

    The linear subtraction methods commonly used for preclinical contrast-enhanced imaging are susceptible to registration errors and motion artifacts that lead to reduced contrast-to-tissue ratios. To address this limitation, a new approach to linear contrast-enhanced ultrasound (CEUS) is proposed based on the analysis of the temporal dynamics of the speckle statistics during wash-in of a bolus injection of microbubbles. In the proposed method, the speckle signal is approximated as a mixture of temporally varying random processes, representing the microbubble signal, superimposed onto spatially heterogeneous tissue backscatter in multiple subvolumes within the region of interest. A wash-in curve is constructed by plotting the effective degrees of freedom (EDoFs) of the histogram of the speckle signal as a function of time. The proposed method is, therefore, named the EDoF method. The EDoF parameter is proportional to the shape parameter of the Nakagami distribution. Images acquired at 18 MHz from a murine mammary fat pad breast cancer xenograft model were processed using gold-standard nonlinear amplitude modulation, conventional linear subtraction, and the proposed statistical method. The EDoF method shows promise for improving the robustness of linear CEUS based on reduced frame-to-frame variability compared with the conventional linear subtraction time-intensity curves. Wash-in curve parameters estimated using the EDoF method also demonstrate higher correlation to nonlinear CEUS than the conventional linear method. The conceptual basis of the statistical method implies that EDoF wash-in curves may carry information about vascular complexity that could provide valuable new imaging biomarkers for cancer research.

  16. Parametric imaging using subharmonic signals from ultrasound contrast agents in patients with breast lesions.

    PubMed

    Eisenbrey, John R; Dave, Jaydev K; Merton, Daniel A; Palazzo, Juan P; Hall, Anne L; Forsberg, Flemming

    2011-01-01

    Parametric maps showing perfusion of contrast media can be useful tools for characterizing lesions in breast tissue. In this study we show the feasibility of parametric subharmonic imaging (SHI), which allows imaging of a vascular marker (the ultrasound contrast agent) while providing near complete tissue suppression. Digital SHI clips of 16 breast lesions from 14 women were acquired. Patients were scanned using a modified LOGIQ 9 scanner (GE Healthcare, Waukesha, WI) transmitting/receiving at 4.4/2.2 MHz. Using motion-compensated cumulative maximum intensity (CMI) sequences, parametric maps were generated for each lesion showing the time to peak (TTP), estimated perfusion (EP), and area under the time-intensity curve (AUC). Findings were grouped and compared according to biopsy results as benign lesions (n = 12, including 5 fibroadenomas and 3 cysts) and carcinomas (n = 4). For each lesion CMI, TTP, EP, and AUC parametric images were generated. No significant variations were detected with CMI (P = .80), TTP (P = .35), or AUC (P = .65). A statistically significant variation was detected for the average pixel EP (P = .002). Especially, differences were seen between carcinoma and benign lesions (mean ± SD, 0.10 ± 0.03 versus 0.05 ± 0.02 intensity units [IU]/s; P = .0014) and between carcinoma and fibroadenoma (0.10 ± 0.03 versus 0.04 ± 0.01 IU/s; P = .0044), whereas differences between carcinomas and cysts were found to be nonsignificant. In conclusion, a parametric imaging method for characterization of breast lesions using the high contrast to tissue signal provided by SHI has been developed. While the preliminary sample size was limited, results show potential for breast lesion characterization based on perfusion flow parameters.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

    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.

  19. Dynamic contrast-enhanced ultrasound parametric maps to evaluate intratumoral vascularization.

    PubMed

    Pitre-Champagnat, Stephanie; Leguerney, Ingrid; Bosq, Jacques; Peronneau, Pierre; Kiessling, Fabian; Calmels, Lucie; Coulot, Jeremy; Lassau, Nathalie

    2015-04-01

    The purposes of this study were to assess the reliability of parametric maps from dynamic contrast-enhanced ultrasound (DCE-US) to reflect the heterogeneous distribution of intratumoral vascularization and to predict the tissue features linked to vasculature. This study was designed to compare DCE-US parametric maps with histologic vascularity measurements. Dynamic contrast-enhanced ultrasound was performed on 17 melanoma-bearing nude mice after a 0.1-mL bolus injection of SonoVue (Bracco SPA, Milan, Italy). The parametric maps were developed from raw linear data to extract pixelwise 2 semiquantitative parameters related to perfusion and blood volume, namely, area under the curve (AUC) and peak intensity (PI). The mathematical method to fit the time-intensity curve for each pixel was a polynomial model used in clinical routine and patented by the team. Regions of interest (ROIs) were drawn on DCE-US parametric maps for whole tumors and for several local areas of 15 mm within each tumor (iROI), the latter reflecting the heterogeneity of intratumoral blood volume. As the criterion standard correlation, microvessel densities (MVDs) were determined for both ROI categories. In detail, for all iROI of 15 mm, MVD and maturity were divided separately for vessels of 0 to 10 μm, 10 to 40 μm, and greater than 40 μm in diameter, and the results were correlated with the ultrasound findings. Among the 17 studied mice, a total of 64 iROIs were analyzed. For the whole-tumor ROI set, AUC and PI values significantly correlated with MVD (rAUC = 0.52 [P = 0.0408] and rPI = 0.70 [P = 0.0026]). In the case of multiple iROI, a strong linear correlation was observed between the DCE-US parameters and the density of vessels ranging in their diameter from 0 to 10 μm (rAUC = 0.68 [P < 0.0001]; rPI = 0.63 [P < 0.0001]), 10 to 40 μm (rAUC = 0.98 [P = 0.0003]; rPI = 0.98 [P = 0.0004]), and greater than 40 μm (rAUC = 0.86 [P = 0.0120]; rPI = 0.92 [P = 0.0034]), respectively. However, the

  20. Do Anesthetic Techniques Influence the Threshold for Glomerular Capillary Hemorrhage induced in Rats by Contrast Enhanced Diagnostic Ultrasound?

    PubMed Central

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

    2016-01-01

    Objectives Glomerular capillary hemorrhage (GCH) can be induced by ultrasonic cavitation during contrast enhanced diagnostic ultrasound (CEDUS), an important nonthermal ultrasound bioeffect. Recent studies of pulmonary ultrasound exposure have shown that thresholds for another nonthermal bioeffect of ultrasound, pulmonary capillary hemorrhage, is strongly influenced by whether or not xylazine is included in the specific anesthetic technique. Methods In this study, anesthesia with ketamine only was compared to ketamine plus xylazine for the induction of GCH in rats by 1.6 MHz intermittent diagnostic ultrasound with contrast agent (similar to Definity). GCH was measured as a percentage of glomeruli with hemorrhage found in histological sections for groups of rats scanned at different peak rarefactional pressure amplitudes. Results There was a significant difference between the magnitude of the GCH between the two anesthetics at 2.3 MPa with 45.6 % GCH for ketamine only, increasing to 63.2 % GCH for ketamine plus xylazine anesthesia (P<0.001). However, the thresholds for the two anesthesia methods were virtually identical at 1.0 MPa, based on linear regression of the exposure response data. Conclusions Therefore, thresholds for CEDUS induced injury of the microvasculature appears to be minimally affected by anesthesia methods. PMID:26764276

  1. Quantitative contrast-enhanced ultrasound measurement of cerebrospinal fluid flow for the diagnosis of ventricular shunt malfunction

    PubMed Central

    Hartman, Robin; Aglyamov, Salavat; Fox, Douglas J.; Emelianov, Stanislav

    2015-01-01

    Object Cerebral shunt malfunction is common but often difficult to effectively diagnose. Current methods are invasive, involve ionizing radiation, and can be costly. This work investigated the feasibility of quantitatively measuring cerebrospinal fluid flow in a shunt catheter using contrast-enhanced ultrasound. Methods A syringe pump was used to push a solution of gas-filled microbubbles at specific flow rates through a shunt catheter while a high-frequency ultrasound imaging system was used to collect ultrasound images for off-line processing. Displacement maps and velocity profiles were generated using a speckle tracking method based on a cross-correlation algorithm. An additional correction factor, to account for a predictable underestimation and to adjust the measured flow rates, was calculated based on the geometry of the ultrasound imaging plane and assuming a simple model of laminar flow. Results The developed method was able to differentiate between physiologically relevant flow rates from 0.0 to 0.09 ml/min with reasonable certainty. The quantitative measurement of flow rates through the catheter using this method was determined to be in good agreement with the expected flow rate. Conclusions This study demonstrated that contrast-enhanced ultrasound has the potential to be used as a minimally invasive and cost-effective alternative method for outpatient shunt malfunction diagnosis. PMID:26090831

  2. Pulmonary blood volume measured by contrast enhanced ultrasound: a comparison with transpulmonary thermodilution.

    PubMed

    Herold, I H F; Soliman Hamad, M A; van Assen, H C; Bouwman, R A; Korsten, H H M; Mischi, M

    2015-07-01

    Blood volume quantification is essential for haemodynamic evaluation guiding fluid management in anaesthesia and intensive care practice. Ultrasound contrast agent (UCA)-dilution measured by contrast enhanced ultrasound (CEUS) can provide the UCA mean transit time (MTT) between the right and left heart, enabling the assessment of the intrathoracic blood volume (ITBV(UCA)). The purpose of the present study was to investigate the agreement between UCA-dilution using CEUS and transpulmonary thermodilution (TPTD) in vitro and in vivo. In an in vitro setup, with variable flows and volumes, we injected a double indicator, ice-cold saline with SonoVue(®), and performed volume measurements using transesophageal echo and thermodilution by PiCCO(®). In a pilot study, we assigned 17 patients undergoing elective cardiac surgery for pulmonary blood volume (PBV) measurement using TPTD by PiCCO(®) and ITBV by UCA-dilution. Correlation coefficients and Bland-Altman analysis were performed for all volume measurements. In vitro, 73 experimental MTT's were obtained using PiCCO(®) and UCA-dilution. The volumes by PiCCO(®) and UCA-dilution correlated with true volumes; r(s)=0.96 (95% CI, 0.93-0.97; P<0.0001) and r(s)=0.97 (95% CI, 0.95-0.98; P<0.0001), respectively. The bias of PBV by PiCCO(®) and ITBV(UCA) were -380 ml and -42 ml, respectively. In 16 patients, 86 measurements were performed. The correlation between PBV by PiCCO(®) and ITBV(UCA) was r(s)=0.69 (95% CI 0.55-0.79; P<0.0001). Bland-Altman analysis revealed a bias of -323 ml. ITBV assessment with CEUS seems a promising technique for blood volume measurement, which is minimally-invasive and bedside applicable. ISRCTN90330260. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Contrast ultrasound in hepatocellular carcinoma at a tertiary liver center: First Indian experience

    PubMed Central

    Laroia, Shalini Thapar; Bawa, Simranjeet Singh; Jain, Deepak; Mukund, Amar; Sarin, Shiv

    2013-01-01

    AIM: To assess the role of contrast enhanced ultrasonography in evaluation of hepatocellular carcinoma (HCC) at the first Indian tertiary liver center. METHODS: Retrospective analysis of contrast enhanced ultrasound (CEUS) examinations over 24 mo for diagnosis, surveillance, characterization and follow up of 50 patients in the context of HCC was performed. The source and indication of referrals, change in referral rate, accuracy and usefulness of CEUS in a tertiary liver center equipped with a 64 slice dual energy computer tomography (CT) and 3 tesla magnetic resonance imaging (MRI) were studied. Sonovue (BR1, Bracco, Italy, a second generation contrast agent) was used for contrast US studies. Contrast enhanced CT/MRI or both were performed in all patients. The findings were taken as a baseline reference and correlation was done with respect to contrast US. Contrast enhanced MRI was performed using hepatocyte specific gadobenate dimeglumine (Gd-BOPTA). Iomeron (400 mg; w/v) was used for dynamic CT examinations. RESULTS: About 20 (40%) of the examinations were referred from clinicians for characterization of a mass from previous imaging. About 15 (30%) were performed for surveillance in chronic liver disease; 5 (10%) examinations were performed for monitoring lesions after radiofrequency ablation (RFA); 3 (6%) were post trans-arterial chemo-embolization (TACE) assessments and 3 (6%) were patients with h/o iodinated contrast allergy. About 2 (4%) were performed on hemodynamically unstable patients in the intensive care with raised alpha fetoprotein and 2 (4%) patients were claustrophobic. The number of patients referred from clinicians steadily increased from 12 in the first 12 mo of the study to 38 in the last 12 mo. CEUS was able to diagnose 88% of positive cases of HCC as per reference standards. In the surveillance group, specificity was 53.3% vs 100% by CT/MRI. Post RFA and TACE specificity of lesion characterization by CEUS was 100% in single/large mass

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

    PubMed

    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

  5. Research on respiratory motion correction method based on liver contrast-enhanced ultrasound images of single mode

    NASA Astrophysics Data System (ADS)

    Zhang, Ji; Li, Tao; Zheng, Shiqiang; Li, Yiyong

    2015-03-01

    To reduce the effects of respiratory motion in the quantitative analysis based on liver contrast-enhanced ultrasound (CEUS) image sequencesof single mode. The image gating method and the iterative registration method using model image were adopted to register liver contrast-enhanced ultrasound image sequences of single mode. The feasibility of the proposed respiratory motion correction method was explored preliminarily using 10 hepatocellular carcinomas CEUS cases. The positions of the lesions in the time series of 2D ultrasound images after correction were visually evaluated. Before and after correction, the quality of the weighted sum of transit time (WSTT) parametric images were also compared, in terms of the accuracy and spatial resolution. For the corrected and uncorrected sequences, their mean deviation values (mDVs) of time-intensity curve (TIC) fitting derived from CEUS sequences were measured. After the correction, the positions of the lesions in the time series of 2D ultrasound images were almost invariant. In contrast, the lesions in the uncorrected images all shifted noticeably. The quality of the WSTT parametric maps derived from liver CEUS image sequences were improved more greatly. Moreover, the mDVs of TIC fitting derived from CEUS sequences after the correction decreased by an average of 48.48+/-42.15. The proposed correction method could improve the accuracy of quantitative analysis based on liver CEUS image sequences of single mode, which would help in enhancing the differential diagnosis efficiency of liver tumors.

  6. Contrast-enhanced ultrasound findings in a case of primary chest chondrosarcoma mimicking a porta hepatis mass.

    PubMed

    Liu, Jin-Ya; Zhou, Lu-Yao; Liang, Jin-Yu; Lu, Ming-De; Wang, Wei

    2015-04-01

    We report a case of a 32-year-old woman who presented with upper abdominal pain. The physical examination revealed a palpable hard mass with a well-demarcated lower margin. Laboratory tests indicated hepatitis B viral infection. Computed tomography scan with intravenous contrast depicted a huge well-demarcated heterogeneous mass at the porta hepatis with irregular peripheral rim enhancement. Contrast-enhanced ultrasound showed peripheral irregular hyper-enhancement in the artery phase and hypo-enhancement in the portal and late phases. The postoperative histopathologic examination confirmed the diagnosis of low-grade chondrosarcoma. This is the first report of contrast-enhanced ultrasound findings of chondrosarcoma. There is some differential diagnosis to be discussed.

  7. 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.

    PubMed

    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 < 0.001) in enhancement between 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.

  8. Effect of Anesthesia Carrier Gas on In-Vivo Circulation Times of Ultrasound Microbubble Contrast Agents in Rats

    PubMed Central

    Mullin, Lee; Gessner, Ryan; Kwan, James; Kaya, Mehmet; Borden, Mark A.; Dayton, Paul A.

    2012-01-01

    Purpose Microbubble contrast agents are currently implemented in a variety of both clinical and preclinical ultrasound imaging studies. The therapeutic and diagnostic capabilities of these contrast agents are limited by their short in-vivo lifetimes, and research to lengthen their circulation times is ongoing. In this manuscript, observations are presented from a controlled experiment performed to evaluate differences in circulation times for lipid shelled perfluorocarbon-filled contrast agents circulating within rodents as a function of inhaled anesthesia carrier gas. Methods The effects of two common anesthesia carrier gas selections - pure oxygen and medical air – were observed within five rats. Contrast agent persistence within the kidney was measured and compared for oxygen and air anesthesia carrier gas for six bolus contrast injections in each animal. Simulations were performed to examine microbubble behavior with changes in external environment gases. Results A statistically significant extension of contrast circulation time was observed for animals breathing medical air compared to breathing pure oxygen. Simulations support experimental observations and indicate that enhanced contrast persistence may be explained by reduced ventilation/perfusion mismatch and classical diffusion, in which nitrogen plays a key role by contributing to the volume and diluting other gas species in the microbubble gas core. Conclusion: Using medical air in place of oxygen as the carrier gas for isoflurane anesthesia can increase the circulation lifetime of ultrasound microbubble contrast agents. PMID:21246710

  9. Acute mortality in critically ill patients undergoing echocardiography with or without an ultrasound contrast agent.

    PubMed

    Main, Michael L; Hibberd, Mark G; Ryan, Amy; Lowe, Timothy J; Miller, Paula; Bhat, Gajanan

    2014-01-01

    The objective of this observational study was to compare 48-h all-cause mortality (as well as hospital stay mortality) among critically ill patients who underwent echocardiography either with or without an ultrasound contrast agent (UCA). The safety of perflutren-based UCAs has been questioned by the U.S. Food and Drug Administration (particularly when administered to critically ill patients) following rare reports of deaths or life-threatening adverse reactions that occurred in close temporal relationship to UCA administration. This was a retrospective observational outcome study conducted in critically ill patients to compare all-cause 48-h and hospital stay mortality subsequent to echocardiography procedures performed either with or without a UCA. The study utilized discharge data from a database maintained by Premier, Inc. (Charlotte, North Carolina). Premier's database is the largest U.S. hospital-based, service-level comparative database for quality and outcomes research, and provides detailed resource utilization data along with patients' primary and secondary diagnoses and procedure billing codes. A propensity score-matching algorithm between UCA-enhanced echocardiography patients and non-contrast-enhanced echocardiography patients was utilized to reduce the potential for imbalance in covariates of selected patients in the comparison of mortality between groups. Patients undergoing echocardiography with a UCA had lower mortality at 48 h compared with patients undergoing non-contrast-enhanced echocardiography (1.70% vs. 2.50%), with an odds ratio = 0.66 (95% confidence interval [CI]: 0.54 to 0.80). Patients undergoing echocardiography with a UCA had lower hospital stay mortality compared with patients undergoing noncontrast echocardiography (14.85% vs. 15.66%), with an odds ratio = 0.89 (95% CI: 0.84 to 0.96). In critically ill, propensity-matched hospitalized patients undergoing echocardiography, use of a UCA is associated with a 28% lower mortality at

  10. "Compression-only" behavior: a second-order nonlinear response of ultrasound contrast agent microbubbles.

    PubMed

    Sijl, Jeroen; Overvelde, Marlies; Dollet, Benjamin; Garbin, Valeria; de Jong, Nico; Lohse, Detlef; Versluis, Michel

    2011-04-01

    Oscillating phospholipid-coated ultrasound contrast agent microbubbles display a so-called "compression-only" behavior, where it is observed that the bubbles compress efficiently while their expansion is suppressed. Here, a theoretical understanding of the source of this nonlinear behavior is provided through a weakly nonlinear analysis of the shell buckling model proposed by Marmottant et al. [J. Acoust. Soc. Am. 118, 3499-3505 (2005)]. It is shown that the radial dynamics of the bubble can be considered as a superposition of a linear response at the fundamental driving frequency and a second-order nonlinear low-frequency response that describes the negative offset of the mean bubble radius. The analytical solution deduced from the weakly nonlinear analysis shows that the compression-only behavior results from a rapid change of the shell elasticity with bubble radius. In addition, the radial dynamics of single phospholipid-coated microbubbles was recorded as a function of both the amplitude and the frequency of the driving pressure pulse. The comparison between the experimental data and the theory shows that the magnitude of compression-only behavior is mainly determined by the initial phospholipids concentration on the bubble surface, which slightly varies from bubble to bubble.

  11. Marriage Strategy of Structure and Composition Designs for Intensifying Ultrasound & MR & CT Trimodal Contrast Imaging.

    PubMed

    Zhang, Kun; Chen, Hangrong; Li, Pei; Bo, Xiaowan; Li, Xiaolong; Zeng, Zeng; Xu, Huixiong

    2015-08-26

    Despite great efforts having been devoted to the design of multimodal imaging probe, almost all design principles of nanotheranostic agents subordinate to simple assemblies of building blocks, resulting in complex preparation process and discounted ability, that is, 1 + 1 < 2. In this report, a novel design strategy, marriage of structure design and composition design that can maximize imaging ability of each building block, ultimately achieving 1 + 1 ≥ 2, has been established. Moreover, a high-efficient ultrasound (US) & MR & CT trimodal contrast agent acts as model to instantiate this design strategy, wherein nanoparticles-induced nonlinear scattering and rattle-type structure-induced double scattering enhancing US imaging, and uniform distribution of Mn(2+) paramagentic centers and "core-satellite" structure of Au atoms favoring enhanced MR imaging and CT imaging, respectively have been validated, achieving optimization of structure design. Importantly, the selected components, silica, Au and MnO are endowed with excellent biocompatibility, displaying the marriage strategy of composition design with aforementioned structure optimization. In in vivo evaluations, such a biocompatible trimodal probe is demonstrated of excellent performance in intensifying CT, MR and US imaging in vivo, especially after positively charged modification by PEI promoting more probes retained in tumor. More importantly, as a universal design strategy, the involved principles in constructing such a US&MR&CT trimodal imaging probe promise great potentials in guiding designs of other materials-based multimodal imaging probe.

  12. New quantification methods for carotid intra-plaque neovascularization using contrast-enhanced ultrasound.

    PubMed

    Akkus, Zeynettin; Hoogi, Assaf; Renaud, Guillaume; van den Oord, Stijn C H; Ten Kate, Gerrit L; Schinkel, Arend F L; Adam, Dan; de Jong, Nico; van der Steen, Antonius F W; Bosch, Johan G

    2014-01-01

    As carotid intra-plaque neovascularization (IPN) is linked to progressive atherosclerotic disease and plaque vulnerability, its accurate quantification might allow early detection of plaque vulnerability. We therefore developed several new quantitative methods for analyzing IPN perfusion and structure. From our analyses, we derived six quantitative parameters-IPN surface area (IPNSA), IPN surface ratio (IPNSR), plaque mean intensity, plaque-to-lumen enhancement ratio, mean plaque contrast percentage and number of micro-vessels (MVN)-and compared these with visual grading of IPN by two independent physicians. A total of 45 carotid arteries with symptomatic stenosis in 23 patients were analyzed. IPNSA (correlation r = 0.719), IPNSR (r = 0.538) and MVN (r = 0.484) were found to be significantly correlated with visual scoring (p < 0.01). IPNSA was the best match to visual scoring. These results indicate that IPNSA, IPNSR and MVN may have the potential to replace qualitative visual scoring and to measure the degree of carotid IPN. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  13. Preservation of imaging capability in sensitive ultrasound contrast agents after indirect plasma sterilization.

    PubMed

    Albala, Lorenzo; Ercan, Utku K; Joshi, Suresh G; Eisenbrey, John R; Teraphongphom, Nutte; Wheatley, Margaret A

    2015-10-15

    Many injectables are not amenable to standard sterilization methods, which destroy sensitive materials. This is particularly true for ultrasound contrast agents (UCA) consisting of gas bubbles stabilized by a surfactant or polymer shell. We investigated a new method to achieve safe and effective sterilization in production by introducing dielectric-barrier discharge non-thermal plasma. A dielectric-barrier discharge was generated to first produce plasma-treated phosphate-buffered saline (PTPBS), which was used as a sterilant solution for our UCA SE61, avoiding direct heat, pressure, chemicals, or radiation. Treated samples were tested for acoustic properties in vitro and in a flow phantom, and for sterility by standard methods. Three minutes plasma treatment of phosphate-buffered saline (PBS) proved effective. The samples showed significant inactivation of inoculated bacteria upon PTPBS treatment as compared to un-treated-PBS (p=0.0022). The treated and untreated samples showed no statistical significance (p>0.05) in acoustic response or bubble diameter (mean±SEM: 2.52±0.31 μm). Nile Red was used to model intercalation of drug in the hydrophobic shell, intercalated successfully into SE61, and was unaffected by plasma treatment. The PTPBS completely sterilized suspensions of UCA, and it did not compromise the acoustic properties of the agent or its ability to retain a hydrophobic compound. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Use of intravital microscopy to study the microvascular behavior of microbubble-based ultrasound contrast agents.

    PubMed

    Schneider, Michel; Broillet, Anne; Tardy, Isabelle; Pochon, Sibylle; Bussat, Philippe; Bettinger, Thierry; Helbert, Alexandre; Costa, Maria; Tranquart, François

    2012-04-01

    The study describes the use of intravital microscopy (IVM) to assess the behavior of ultrasound contrast agents (UCAs), including targeted UCAs, in the microcirculation of rodents. IVM was performed on various exteriorized organs: hamster cheek pouch, rat mesentery, liver, spinotrapezius muscle, and mouse cremaster muscle. A dorsal skin-fold chamber with MatBIII tumor cells was also implanted in rats. Nontargeted UCAs (SonoVue(®) and BR14) and targeted UCAs (BR55 and P-selectin targeted microbubbles) were tested. IVM was used to measure microbubble size, determine their persistence, and observe their behavior in the blood circulation. Intravenous and intra-arterial injections of high doses of UCAs did not modify the local microvascular hemodynamics. No microbubble coalescence and no increased size were observed. Adhesion of some microbubbles to leukocytes was observed in various microcirculation models. Microbubbles are captured by Kupffer cells in the liver. Targeted microbubbles were shown to adhere specifically to endothelial receptors without compromising local blood flow. These results support the safety of both targeted and nontargeted UCAs as no microvascular flow alteration or plugging of microvessels were observed. They confirm that binding observed with targeted microbubbles are due to the binding of these microbubbles to specific endothelial receptors. © 2012 John Wiley & Sons Ltd.

  15. Role of contrast-enhanced harmonic endoscopic ultrasound in submucosal tumors

    PubMed Central

    Alvarez-Sanchez, Maria Victoria; Gincul, Rodica; Lefort, Christine; Napoleon, Bertrand

    2016-01-01

    With the widespread use of endoscopy, gastrointestinal submucosal lesions are now more commonly discovered. Although endoscopic ultrasound (EUS) is superior to all other imaging techniques for the diagnosis of submucosal tumors (SMTs), it is still suboptimal for differentiating hypoechoic lesions arising from the fourth sonographic gastrointestinal wall layer, which encompass tumors with very different prognosis. EUS tissue acquisition has provided with the unique opportunity to obtain histological confirmation, but it is not accurate enough to evaluate the malignant potential of gastrointestinal stromal tumors (GISTs). In the last years, contrast-enhanced harmonic EUS (CH-EUS) emerged as a powerful imaging modality to assess the microperfusion patterns of pancreatic tumors. Based on the distinct microvascularity of malignant SMTs, it was hypothesized that CH-EUS might also assist in the differential diagnosis of SMTs. Preliminary experience in this field is now available and suggests CH-EUS as a performant modality to distinguish between benign SMTs and GISTs and to evaluate the malignant potential of GISTs. High expectations are also relied on CH-EUS for the monitoring of antiangiogenic treatments of GISTs and the evaluation of gastrointestinal neuroendocrine tumors (NETs). PMID:28000626

  16. Role of contrast-enhanced harmonic endoscopic ultrasound in submucosal tumors.

    PubMed

    Alvarez-Sanchez, Maria Victoria; Gincul, Rodica; Lefort, Christine; Napoleon, Bertrand

    2016-01-01

    With the widespread use of endoscopy, gastrointestinal submucosal lesions are now more commonly discovered. Although endoscopic ultrasound (EUS) is superior to all other imaging techniques for the diagnosis of submucosal tumors (SMTs), it is still suboptimal for differentiating hypoechoic lesions arising from the fourth sonographic gastrointestinal wall layer, which encompass tumors with very different prognosis. EUS tissue acquisition has provided with the unique opportunity to obtain histological confirmation, but it is not accurate enough to evaluate the malignant potential of gastrointestinal stromal tumors (GISTs). In the last years, contrast-enhanced harmonic EUS (CH-EUS) emerged as a powerful imaging modality to assess the microperfusion patterns of pancreatic tumors. Based on the distinct microvascularity of malignant SMTs, it was hypothesized that CH-EUS might also assist in the differential diagnosis of SMTs. Preliminary experience in this field is now available and suggests CH-EUS as a performant modality to distinguish between benign SMTs and GISTs and to evaluate the malignant potential of GISTs. High expectations are also relied on CH-EUS for the monitoring of antiangiogenic treatments of GISTs and the evaluation of gastrointestinal neuroendocrine tumors (NETs).

  17. Simulation of noninvasive blood pressure estimation using ultrasound contrast agent microbubbles.

    PubMed

    Li, Fei; Wang, Ling; Fan, Yubo; Li, Deyu

    2012-04-01

    The microbubble ultrasound contrast agent (UCA) has been widely recognized as a potential noninvasive tool for blood pressure measurement. However, UCA indices such as the shift in the resonance frequency and echo amplitude have problems of low resolution, nonlinear relationship with blood pressure, etc. In this paper, a novel UCA index, the shift in the subharmonic optimal driving frequency (SSODF) of microbubbles, is proposed. The effectiveness of the index for estimating blood pressure was evaluated by performing a microbubble acoustic response simulation. The behavior of commercial UCA microbubbles was investigated as a function of the driving acoustic pressure (in kilopascals) and ambient overpressure (in millimeters of mercury). Simulation results showed that for a 1.6-μm-diameter microbubble, SSODF increased linearly with the overpressure in a range of 0 to 200 mmHg and was maximum (2.07 MHz) at 380 kPa. Changes of the overpressure as small as 5 mmHg can be detected using SSODF. For a population of microbubbles with a Gaussian size distribution (mean diameter: 1.6 μm, standard deviation: 0.2 μm), SSODF was 1.7 MHz at 280 kPa. With further experimental validation, the proposed method may be developed as a novel noninvasive technique for accurate blood pressure measurement.

  18. Estimating concentration of ultrasound contrast agents with backscatter coefficients: Experimental and theoretical aspects

    PubMed Central

    Leithem, Scott M.; Lavarello, Roberto J.; O’Brien, William D.; Oelze, Michael L.

    2012-01-01

    Ultrasound contrast agents (UCAs) have been explored as a means to enhance therapeutic techniques. Because the effectiveness of these techniques relies on the UCA concentration at a target site, it would be beneficial to estimate UCA concentration noninvasively. In this study, a noninvasive method for estimating UCA concentration was developed in vitro. Backscatter coefficients (BSCs) estimated from measurements of Definity® UCAs were fitted to a theoretical scattering model in the 15–25 MHz range using a Levenberg-Marquardt regression technique. The model was defined by the UCA size distribution and concentration, and therefore concentration estimates were extracted directly from the fit. Calculation of the BSC was accomplished using planar reference measurements from the back wall of a Plexiglas® chamber and an average of 500 snapshots of ultrasonic backscatter from UCAs flowing through the chamber. In order to verify the ultrasonically derived UCA concentration estimates, a sample of the UCAs was extracted from the flow path and the concentration was estimated with a hemacytometer. UCA concentrations of 1, 2, and 5 times the dose recommended by the manufacturer were used in experiments. All BSC-based estimates were within one standard deviation of hemacytometer based estimates for peak rarefactional pressures of 100–400 kPa. PMID:22423724

  19. Impact of parametric imaging on contrast-enhanced ultrasound of breast cancer.

    PubMed

    Noro, Aya; Nakamura, Takashi; Hirai, Toshiko; Haga, Masayo; Kobayashi, Toyoki; Hayashi, Akinobu; Kozuka, Yuji; Nakai, Tokiko; Ogura, Toru; Ogawa, Tomoko

    2016-04-01

    To prospectively evaluate the usefulness of contrast-enhanced ultrasound (CEUS) using parametric imaging for breast cancer in a multicenter study. A total of 65 patients with breast cancer were included in this study. CEUS was performed, and still images on peak time (S), accumulated images (A) and parametric images (P) were generated from the raw data. Four blind reviewers ranked the best visible images as first place, and determined second and third place consecutively. We compared the average ranking of each image. The maximal diameter of the tumor determined on ultrasonography and MRI was compared with the corresponding pathological maximal diameter for 48 of the 65 patients. The correlation between the diameter determined by two experts and two beginners was analyzed. The average rank of visibility was as follows: P, 1.44; A, 2.04; and S, 2.52. The correlation between each image and the pathology was as follows: P, r = 0.664; A, r = 0.630; S, r = 0.717; and MRI, r = 0.936. There were no significant differences among the correlation between the experts and beginners in each image. The use of parametric imaging improves the visibility of CEUS. The maximal diameter of the tumor determined on CEUS correlates substantially with the pathology.

  20. Surfactant-stabilized contrast agent on the nanoscale for diagnostic ultrasound imaging.

    PubMed

    Wheatley, Margaret A; Forsberg, Flemming; Dube, Neal; Patel, Mihir; Oeffinger, Brian E

    2006-01-01

    Ultrasound contrast agents (CA) are generally micron-sized stabilized gas bubbles, injected IV. However, to penetrate beyond the vasculature and accumulate in targets such as tumors, CA must be an order of magnitude smaller. We describe a method of achieving nanometer-sized, surfactant-stabilized CA by differential centrifugation. High g force was shown to destroy bubble integrity. Optimal conditions (300 rpm for 3 min) produced an agent with a mean diameter of 450 nm, which gave 25.5 dB enhancement in vitro at a dose of 10 microL/mL, with a 13 min half-life. In vivo, the CA produced excellent power Doppler and grey-scale pulse inversion harmonic images at low acoustic power when administered. In vivo dose-response curves obtained in three rabbits showed enhancement between 20 and 25 dB for dosages above 0.025 mL/kg. These results encourage further investigation of the possible diagnostic and therapeutic benefits of using nanoparticles as CA, including passive targeting and accumulation in tumors.

  1. Erythrocytes and microbubble contrast agents, improve the therapeutic efficiency of high intensity focused ultrasound

    NASA Astrophysics Data System (ADS)

    Takegami, Kenji; Kaneko, Yukio; Watanabe, Toshiaki; Maruyama, Toshiyuki; Matsumoto, Yoichiro; Nagawa, Hirokazu

    2005-03-01

    Erythrocytes, an well as Levovist microbubble contrast agent, enhance the heating effect of high intensity focused ultrasound (HIFU) and increase the coagulation volume produced by HIFU irradiation. In vitro experiments used human plasma with various concentrations of human erythrocytes in combination with or without Levovist. In vivo experiments used eight Japan white rabbits with three levels of anaemia. Using a 2.17 MHz transducer, HIFU was applied for 60 seconds, and the temperature rise and the volume of coagulation necrosis was evaluated. There was a significant correlation between the HIFU-induced temperature rise and hematocrit, with a correlation coefficient of 0.998 (p=0.0001). Although the temperature rise was smaller at low hematocrit, it was significantly increased by adding Levovist to the suspension (p<0.01). The mean volume of coagulation necrosis was significantly higher in the rabbits with higher hematocrit (p<0.01), and that in the moderate anaemia group was significantly increased by using Levovist (p<0.01).

  2. Diagnostic accuracy of contrast-enhanced ultrasound for characterization of kidney lesions in patients with and without chronic kidney disease.

    PubMed

    Chang, Emily Hueywen; Chong, Wui Kheong; Kasoji, Sandeep Kumar; Fielding, Julia Rose; Altun, Ersan; Mullin, Lee B; Kim, Jung In; Fine, Jason Peter; Dayton, Paul Alexander; Rathmell, Wendy Kimryn

    2017-08-09

    Patients with chronic kidney disease are at increased risk of cystic kidney disease that requires imaging monitoring in many cases. However, these same patients often have contraindications to contrast-enhanced computed tomography and magnetic resonance imaging. This study evaluates the accuracy of contrast-enhanced ultrasound (CEUS), which is safe for patients with chronic kidney disease, for the characterization of kidney lesions in patients with and without chronic kidney disease. We performed CEUS on 44 patients, both with and without chronic kidney disease, with indeterminate or suspicious kidney lesions (both cystic and solid). Two masked radiologists categorized lesions using CEUS images according to contrast-enhanced ultrasound adapted criteria. CEUS designation was compared to histology or follow-up imaging in cases without available tissue in all patients and the subset with chronic kidney disease to determine sensitivity, specificity and overall accuracy. Across all patients, CEUS had a sensitivity of 96% (95% CI: 84%, 99%) and specificity of 50% (95% CI: 32%, 68%) for detecting malignancy. Among patients with chronic kidney disease, CEUS sensitivity was 90% (95% CI: 56%, 98%), and specificity was 55% (95% CI: 36%, 73%). CEUS has high sensitivity for identifying malignancy of kidney lesions. However, because specificity is low, modifications to the classification scheme for contrast-enhanced ultrasound could be considered as a way to improve contrast-enhanced ultrasound specificity and thus overall performance. Due to its sensitivity, among patients with chronic kidney disease or other contrast contraindications, CEUS has potential as an imaging test to rule out malignancy. This trial was registered in clinicaltrials.gov, NCT01751529 .

  3. In Vivo Noninvasive Characterization of Brown Adipose Tissue Blood Flow by Contrast Ultrasound in Mice

    PubMed Central

    Baron, David M.; Clerte, Maeva; Brouckaert, Peter; Raher, Michael J.; Flynn, Aidan W.; Zhang, Haihua; Carter, Edward A.; Picard, Michael H.; Bloch, Kenneth D.; Buys, Emmanuel S.; Scherrer-Crosbie, Marielle

    2012-01-01

    Background Interventions to increase brown adipose tissue (BAT) volume and activation are being extensively investigated as therapies to decrease the body weight in obese subjects. Noninvasive methods to monitor these therapies in animal models and humans are rare. We investigated whether contrast ultrasound (CU) performed in mice could detect BAT and measure its activation by monitoring BAT blood flow. After validation, CU was used to study the role of uncoupling protein 1 (UCP1) and nitric oxide synthases in the acute regulation of BAT blood flow. Methods and Results Blood flow of interscapular BAT was assessed in mice (n=64) with CU by measuring the signal intensity of continuously infused contrast microbubbles. Blood flow of BAT estimated by CU was 0.5±0.1 (mean±SEM) dB/s at baseline and increased 15-fold during BAT stimulation by norepinephrine (NE, 1 μg·kg−1·min−1). Assessment of BAT blood flow using CU was correlated to that performed with fluorescent microspheres (R2=0.86, p<0.001). To evaluate whether intact BAT activation is required to increase BAT blood flow, CU was performed in UCP1-deficient (UCP1−/−) mice with impaired BAT activation. Norepinephrine infusion induced a smaller increase in BAT blood flow in UCP1−/− mice than in wild-type mice. Finally, we investigated whether NOS played a role in acute NE-induced changes of BAT blood flow. Genetic and pharmacologic inhibition of NOS3 attenuated the NE-induced increase in BAT blood flow. Conclusions These results indicate that CU can detect BAT in mice, and estimate BAT blood flow in mice with functional differences in BAT. PMID:22776888

  4. Evaluation of Perfusion Quantification Methods with Ultrasound Contrast Agents in a Machine-Perfused Pig Liver.

    PubMed

    Averkiou, M; Keravnou, C P; Izamis, M L; Leen, E

    2016-05-03

    Purpose: To evaluate dynamic contrast-enhanced ultrasound (DCEUS) as a tool for measuring blood flow in the macro- and microcirculation of an ex-vivo machine-perfused pig liver and to confirm the ability of DCEUS to accurately detect induced flow rate changes so that it could then be used clinically for monitoring flow changes in liver tumors. Materials and Methods: Bolus injections of contrast agents in the hepatic artery (HA) and portal vein (PV) were administered to 3 machine-perfused pig livers. Flow changes were induced by the pump of the machine perfusion system. The induced flow rates were of clinical relevance (150 - 400 ml/min for HA and 400 - 1400 ml/min for PV). Quantification parameters from time-intensity curves [rise time (RT), mean transit time (MTT), area under the curve (AUC) and peak intensity (PI)] were extracted in order to evaluate whether the induced flow changes were reflected in these parameters. Results: A linear relationship between the image intensity and the microbubble concentration was confirmed first, while time parameters (RT and MMT) were found to be independent of concentration. The induced flow changes which propagated from the larger vessels to the parenchyma were reflected in the quantification parameters. Specifically, RT, MTT and AUC correlated with flow rate changes. Conclusion Machine-perfused pig liver is an excellent test bed for DCEUS quantification approaches for the study of the hepatic vascular networks. DCEUS quantification parameters (RT, MTT, and AUC) can measure relative flow changes of about 20 % and above in the liver vasculature. DCEUS quantification is a promising tool for real-time monitoring of the vascular network of tumors. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Color duplex ultrasound and contrast-enhanced ultrasound in comparison to MS-CT in the detection of endoleak following endovascular aneurysm repair.

    PubMed

    Clevert, D-A; Minaifar, N; Weckbach, S; Kopp, R; Meimarakis, G; Clevert, D-A; Reiser, M

    2008-01-01

    The purpose of this study was to compare Color Duplex Ultrasound (CDU), Contrast-Enhanced Ultrasound (CEUS) and Multislice Computed Tomography (MS-CT) angiography in the routine follow up of patients following Endovascular Repair (EVAR) of Abdominal Aortic Aneurysm (AAA).43 consecutive patients with AAA underwent endovascular aneurysm repair and were imaged with CDU, CEUS and MS-CT angiography at regular intervals after the procedure. Each imaging modality was evaluated for the detection of endoleaks. The presence of endoleaks was analyzed and the conspicuity of findings was assessed.CTA was used as gold standard in determining the presence of endoleaks. CDU was true positive for endoleaks in 5/43 patients (11.6%) and false positive for endoleaks in 2/43 patients (4.6%). The sensitivity of CDU was therefore 33.3% and its specificity 92.8%; the positive and negative predictive values were 0.71 and 0.72, respectively. CEUS was true positive for the detection of endoleaks in 15/43 patients (34.9%) and false positive in 2/43 patients (4.6%). The sensitivity of CEUS was therefore 100% and its specificity 93%; the positive and negative predictive values were 0.88 and 1. In the follow up the two false positive endoleaks in CEUS were confirmed as true positive endoleaks by CEUS and MS-CT. In our small patient group, contrast-enhanced ultrasound seemed to be more accurately in demonstrating endoleaks after EVAR than MS-CT angiography and may be considered as a primary surveillance modality whereas duplex ultrasound scanning alone is not as sensitive as CEUS and MS-CT angiography in detection of endoleaks. Especially in patients with contraindications for CT contrast agents (e.g. due to renal failure or severe allergy) CEUS provides a good alternative to MS-CT.

  6. Hollow silica and silica-boron nano/microparticles for contrast-enhanced ultrasound to detect small tumors

    PubMed Central

    Liberman, Alexander; Martinez, H. Paul; Ta, Casey N.; Barback, Christopher V.; Mattrey, Robert F.; Kono, Yuko; Blair, Sarah L.; Trogler, William C.; Kummel, Andrew C.; Wu, Zhe

    2013-01-01

    Diagnosing tumors at an early stage when they are easily curable and may not require systemic chemotherapy remains a challenge to clinicians. In order to improve early cancer detection, gas filled hollow boron-doped silica particles have been developed, which can be used for ultrasound-guided breast conservation therapy. The particles are synthesized using a polystyrene template and subsequently calcinated to create hollow, rigid nanoporous microspheres. The microshells are filled with perfluoropentane vapor. Studies were performed in phantoms to optimize particle concentration, injection dose, and the ultrasound settings such as pulse frequency and mechanical index. In vitro studies have shown that these particles can be continuously imaged by US up to 48 min and their signal lifetime persisted for 5 days. These particles could potentially be given by intravenous injection and, in conjunction with contrast-enhanced ultrasound, be utilized as a screening tool to detect smaller breast cancers before they are detectible by traditional mammography. PMID:22498299

  7. Processing of subharmonic signals from ultrasound contrast agents to determine ambient pressures.

    PubMed

    Dave, Jaydev K; Halldorsdottir, Valgerdur G; Eisenbrey, John R; Forsberg, Flemming

    2012-04-01

    Subharmonic-aided pressure estimation (SHAPE) is a technique that utilizes the subharmonic emissions, occurring at half the insonation frequency, from ultrasound contrast agents to estimate ambient pressures. The purpose of this work was to compare the performance of different processing techniques for the raw radiofrequency (rf) data acquired for SHAPE. A closed loop flow system was implemented circulating reconstituted Sonazoid (GE Healthcare, Oslo, Norway; 0.2 ml for 750 ml diluent) and the beam-formed unprocessed rf data were obtained from a 4 mm diameter lumen of a Doppler flow phantom (ATS Laboratories, Inc., Bridgeport, CT) using a SonixRP scanner (Ultrasonix, Richmond, BC, Canada). The transmit frequency and incident acoustic pressures were set to 2.5 MHz and 0.22 MPa, respectively, in order to elicit Sonazoid subharmonic emissions that are ambient-pressure sensitive. The time-varying ambient pressures within the flow phantom were recorded by a Millar pressure catheter. Four techniques for extracting the subharmonic amplitude from the rf data were tested along with two noise filtering techniques to process this data. Five filter orders were tested for the noise removing filters. The performance was evaluated based on the least root-mean-square errors reported after linear least-square regression analyses of the subharmonic data and the pressure catheter data and compared using a repeated ANOVA. When the subharmonic amplitudes were extracted as the mean value within a 0.2 MHz bandwidth about 1.25 MHz and when the resulting temporally-varying subharmonic signal was median filtered with an order of 500, the filtered subharmonic signal significantly predicted the ambient pressures (r2 = 0.90; p < 0.001) with the least error. The resulting root mean square and mean absolute errors were 8.16 +/- 0.26 mmHg and 6.70 +/- 0.17 mmHg, respectively. Thus, median processing the subharmonic data extracted as the mean value within a 0.2 MHz bandwidth about the theoretical

  8. Ultrasound triggered cell death in vitro with doxorubicin loaded poly lactic-acid contrast agents.

    PubMed

    Eisenbrey, J R; Huang, P; Hsu, J; Wheatley, M A

    2009-12-01

    Traditional chemotherapy generally results in systemic toxicity, which also limits drug levels at the area of need. Two ultrasound contrast agents (UCA), with diameters between 1-2 microm in diameter and shell thicknesses of 100-200 nm, composed of poly lactic-acid (PLA), one loaded by surface adsorption and the other loaded by drug incorporation in the shell, were compared in vitro for potential use in cancer therapy. These poly lactic-acid (PLA) UCA platforms contain a gas core that in an ultrasound (US) field can cause the UCA to oscillate or rupture. Following a systemic injection of drug loaded UCA with external application of US focused at the area of interest, this platform could potentially increase drug toxicity at the area of need, while protecting healthy tissue through microencapsulation of the drug. In vitro toxicity in MDA-MB-231 breast cancer cells of the surface-adsorbed and shell-incorporated doxorubicin (Dox) loaded UCA were examined at 5 MHz insonation using a pulse repetition frequency of 100 Hz at varying pressure amplitudes. Both platforms resulted in equivalent cell death compared to free Dox and US when insonated at peak positive pressure amplitudes of 1.26 MPa and above. While no significant changes in cell death were seen for surface adsorbed Dox-UCA with or without insonation, cell death using the platform with Dox incorporated within the shell increased from 16.12% to 25.78% (p=0.0272), approaching double the potency of the platform when insonated at peak positive pressure amplitudes of 1.26 MPa and above. This mechanism is believed to be the result of UCA rupture at higher insonation pressure amplitudes, resulting in more exposed drug and shell surface area as well as increased cellular uptake of Dox containing polymer shell fragments. This study has shown that a polymer UCA with drug housed within the shell may be used for US-triggered cell death. US activation can be used to make a carrier significantly more potent once in the area of

  9. Specific contrast ultrasound using sterically stabilized microbubbles for early diagnosis of thromboembolic disease in a rabbit model.

    PubMed

    Vlašín, Michal; Lukáč, Robert; Kauerová, Zuzana; Kohout, Pavel; Mašek, Josef; Bartheldyová, Eliška; Koudelka, Štěpán; Korvasová, Zina; Plocková, Jana; Hronová, Nikola; Turánek, Jaroslav

    2014-04-01

    Specific contrast ultrasound is widely applied in diagnostic procedures on humans but remains underused in veterinary medicine. The objective of this study was to evaluate the use of microbubble-based contrast for rapid ultrasonographic diagnosis of thrombosis in small animals, using male New Zealand white rabbits (average weight about 3.5 kg) as a model. It was hypothesized that the use of microbubble-based contrast agents will result in a faster and more precise diagnosis in our model of thrombosis. A pro-coagulant environment had been previously established by combining endothelial denudation and external vessel wall damage. Visualization of thrombi was achieved by application of contrast microbubbles [sterically stabilized, phospholipid-based microbubbles filled with sulfur hexafluoride (SF₆) gas] and ultrasonography. As a result, rapid and clear diagnosis of thrombi in aorta abdominalis was achieved within 10 to 30 s (mean: 17.3 s) by applying microbubbles as an ultrasound contrast medium. In the control group, diagnosis was not possible or took 90 to 180 s. Therefore, sterically stabilized microbubbles were found to be a suitable contrast agent for the rapid diagnosis of thrombi in an experimental model in rabbits. This contrast agent could be of practical importance in small animal practice for rapid diagnosis of thrombosis.

  10. Fibrinolytic effects of transparietal ultrasound associated with intravenous infusion of an ultrasound contrast agent: study of a rat model of acute cerebral stroke.

    PubMed

    Moumouh, Ahmed; Barentin, Laurent; Tranquart, François; Serrierre, Sophie; Bonnaud, Isabelle; Tasu, Jean Pierre

    2010-01-01

    The aim of this study was to evaluate the thrombolytic effect of focused transparietal ultrasound in combination with a specific contrast agent (microbubbles) in acute cerebral ischemia. Acute cerebral ischemia was induced in 10 rats by intra-arterial clots injection. Five rats (group 1) were treated with a combination of transparietal ultrasound (probe 2 MHz, acoustic power 500 mW/cm(2)) and intravenous injection of 0.6 mL of the ultrasound contrast agent (UCA) sulfur hexafluoride. Five rats (group 2) were treated by fibrinolytic intravenous infusion (recombinant tissue plasminogen activator). Cerebral cellular energy production was determined by measuring the cellular phosphorylation using phosphorus magnetic spectroscopy before and during ischemia induction and after treatment. Measures were performed on a dedicated 2.35T magnet. The ratio phosphocreatine (P(Cr)) on inorganic phosphate (P(i)), P(Cr)/P(i), estimation of the oxidative phosphorylation metabolism and the intracellular pH (pHi) were measured in the two groups. Compared with the ischemia induction period, both treatments were associated with an increase of P(Cr)/P(i) and pHi values, respectively, +80% and +100% in group 1 (p=0.07) and +100% and +80% in group 2 (p=0.04). There was no significant difference between the two groups for the response treatment. To conclude, treatment with intravenous fibrinolytic infusion and treatment with focused ultrasound in combination with UCA seems to be equally effective in treating acute cerebral ischemia in rats. (E-mail: j.p.tasu@chu-poitiers.fr).

  11. Intraductally applied contrast-enhanced ultrasound (IA-CEUS) for improved visualization of obstructive diseases of the salivary glands, primary results.

    PubMed

    Zengel, P; Siedek, V; Berghaus, A; Clevert, D A

    2010-01-01

    Obstructive diseases of the salivary glands are often based on Sialolithiasis; however, conventional radiological imaging or ultrasound does not provide a diagnosis in 5-10% of all cases. It was the aim of our study to examine the effectiveness and viability of an intraductal applied contrast-enhanced ultrasound (IA-CEUS) to improve the visualization of obstructive diseases of the salivary glands in comparison to conventional ultrasound and clinical symptoms. The study included fifteen patients with swelling of indeterminate cause and/or pain of one or more salivary glands. A high-end ultrasound machine (Siemens, ACUSON, S 2000, Germany) with a multi-frequency linear 9 MHz transducer was used to carry out contrast-enhanced ultrasound with SonoVue. All patients were examined using all diagnostic ultrasound tools of the study. The results show that the procedure is easy and convenient to perform, as well as efficient, but more significantly, that the intraductal contrast agent improved the diagnostic assessment capabilities of ultrasound for patients with obstructive salivary gland diseases, thereby helping to identify the best treatment. In comparison to conventional ultrasound, the use of an intraductal applied contract-enhanced ultrasound not only improved the visualization of the glandular duct system as a whole, but was less time-consuming as well as more reproducible. Thus, IA-CEUS with an intraductal applied contrast agent (IA-CEUS) is a promising tool that provides additional helpful information and an improvement for cases involving patients with unclear symptoms.

  12. Portal vein thrombosis with contrast-enhanced ultrasound in a patient with hepatocellular carcinoma: a case study.

    PubMed

    Salman, Saba

    2012-05-01

    Portal vein thrombosis (PVT) is the presence of thrombus in the portal vein that causes partial or complete occlusion. It is prevalent in hepatocellular carcinoma (HCC), where it can be either bland or malignant depending on the presence of invasion. Recent studies have identified contrast-enhanced ultrasound (CEUS) as the most reliable method of imaging to make this distinction. The arterial neovascularisation that is evident in a neoplastic thrombus can be visualised on CEUS with enhancement and pulsation, witnessed in real-time. This case study describes the use of contrast-enhanced ultrasound used as a non-invasive method to define the bland and malignant components of portal vein thrombosis in a 76-year-old male with hepatocellular carcinoma and cirrhosis.

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

    PubMed

    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.

  14. Improving the quantification of contrast enhanced ultrasound using a Bayesian approach

    NASA Astrophysics Data System (ADS)

    Rizzo, Gaia; Tonietto, Matteo; Castellaro, Marco; Raffeiner, Bernd; Coran, Alessandro; Fiocco, Ugo; Stramare, Roberto; Grisan, Enrico

    2017-03-01

    Contrast Enhanced Ultrasound (CEUS) is a sensitive imaging technique to assess tissue vascularity, that can be useful in the quantification of different perfusion patterns. This can be particularly important in the early detection and staging of arthritis. In a recent study we have shown that a Gamma-variate can accurately quantify synovial perfusion and it is flexible enough to describe many heterogeneous patterns. Moreover, we have shown that through a pixel-by-pixel analysis the quantitative information gathered characterizes more effectively the perfusion. However, the SNR ratio of the data and the nonlinearity of the model makes the parameter estimation difficult. Using classical non-linear-leastsquares (NLLS) approach the number of unreliable estimates (those with an asymptotic coefficient of variation greater than a user-defined threshold) is significant, thus affecting the overall description of the perfusion kinetics and of its heterogeneity. In this work we propose to solve the parameter estimation at the pixel level within a Bayesian framework using Variational Bayes (VB), and an automatic and data-driven prior initialization. When evaluating the pixels for which both VB and NLLS provided reliable estimates, we demonstrated that the parameter values provided by the two methods are well correlated (Pearson's correlation between 0.85 and 0.99). Moreover, the mean number of unreliable pixels drastically reduces from 54% (NLLS) to 26% (VB), without increasing the computational time (0.05 s/pixel for NLLS and 0.07 s/pixel for VB). When considering the efficiency of the algorithms as computational time per reliable estimate, VB outperforms NLLS (0.11 versus 0.25 seconds per reliable estimate respectively).

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

    PubMed

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

    2012-04-01

    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. 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. 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<0.05). Malignant lesions more often showed heterogeneous and centripetal enhancement, whereas benign lesions mainly showed homogeneous and centrifugal enhancement. The detectable rate of peripheral radial or penetrating vessels was significantly higher in malignant lesions than in benign ones (p<0.001). For quantitative analysis, malignant lesions showed significantly higher (p=0.031) and faster enhancement (p=0.025) than benign ones, and its time to peak was significantly shorter (p=0.002). The areas under the ROC curve for qualitative, quantitative and combined analysis were 0.910 (A(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). 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. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. High-contrast and low-computational complexity medical ultrasound imaging using beamspace capon method.

    PubMed

    Okumura, Shigeaki; Taki, Hirofumi; Sato, Toru

    2015-01-01

    Several adaptive beamforming techniques have been proposed to improve the quality of medical ultrasound images. The beamspace (BS) Capon method is one common method used to depict high-resolution images with low computational complexity. However, the complexity is not low enough for real-time imaging in clinical situations because the conventional BS Capon method employs a time-delay process and a transition process from elementspace signal processing to BS signal processing at all points of interest. Thus, we propose a technique that replaces the time-delay process using a steering vector. In addition, the Capon method employs a spatial averaging (SA) technique to stabilize the estimation in intensity. However, when the averaging size is not adequate, the estimated intensity might be smaller than that given by the delay-and-sum (DAS) method. Because most medical diagnoses are presented based on the estimation of intensity acquired by the DAS beamformer, accurate estimation of intensity is also required. Therefore, we propose a compensation technique that uses both small and large sizes for SA. In an experiment, the -6 dB beam width, sidelobe level, and estimation error in the intensity of the proposed method were 0.17 mm, -27 dB, and 0.92 dB, respectively, where those of the conventional BS Capon method were 0.29 mm, -22 dB, and 8.1 dB. The complexity of the proposed method is one-fourteenth that of the conventional method. Compared with conventional methods, the proposed method succeeded in depicting a higher-contrast image with accurate intensity estimation and lower computational complexity.

  17. Microflow imaging of contrast-enhanced ultrasound for evaluation of neovascularization in peripheral lung cancer.

    PubMed

    Wang, Song; Yang, Wei; Fu, Jing-Jing; Sun, Yu; Zhang, Hui; Bai, Jing; Chen, Min-Hua; Yan, Kun

    2016-08-01

    The aim of this study was to investigate the role of microflow imaging (MFI) of contrast-enhanced ultrasound (CEUS) for evaluating microvascular architecture of different types of peripheral lung cancer (PLC) and to explore the correlated pathological basis.Ninety-five patients with PLC were enrolled in this study. Two radiologists independently evaluated the microvascular architecture of PLC with MFI. The interobserver agreement was measured with Kappa test. The diagnosis value of MFI was calculated. With pathological analysis, the correlation between MFI and microvascular density (MVD)/microvascular diameter (MD) was evaluated.Of the 95 PLCs, MFI were mainly classified "dead wood" (27.4%, 25.3%), "vascular" (47.4%, 49.5%), and "cotton" (20.0%, 20.0%) patterns by the 2 readers. Kappa test showed a good agreement between the 2 readers (Kappa = 0.758). The "dead wood" can be regarded as a specific diagnostic factor for squamous carcinoma; the sensitivity, specificity, and accuracy was 62.9%, 93.3%, and 82.1%, respectively. The "vascular" and "cotton" patterns correlated well with adenocarcinoma and SCLC (small cell lung cancer); diagnostic sensitivity, specificity, and accuracy were 86.7%, 65.7%, and 78.9%, respectively. MVD of "dead wood" was lower than "vascular" and "cotton," while MD was bigger than the other 2 patterns (P < 0.05). There was a good correlation between MFI and histopathological types of PLC as well as between MFI and MVD/MD (P < 0.05).MFI has the advantage to display the microvascular architecture of PLCs and might become a promising diagnostic method of histopathological types of PLC. MFI features also correlated well with its pathological basis, including MVD and MD.

  18. Contrast-harmonic endoscopic ultrasound for the diagnosis of pancreatic adenocarcinoma: a prospective multicenter trial.

    PubMed

    Gincul, Rodica; Palazzo, Maxime; Pujol, Bertrand; Tubach, Florence; Palazzo, Laurent; Lefort, Christine; Fumex, Fabien; Lombard, Alexandra; Ribeiro, Daniel; Fabre, Monique; Hervieu, Valerie; Labadie, Michel; Ponchon, Thierry; Napoléon, Bertrand

    2014-05-01

    Histology is the gold standard for the diagnosis of pancreatic adenocarcinoma. However, the negative predictive value of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for the diagnosis remains low. The aims of this prospective multicenter study were: (1) to compare the performance of contrast-harmonic EUS (CH-EUS) with that of EUS-FNA for the diagnosis of pancreatic adenocarcinoma; (2) to assess the intra- and interobserver concordances of CH-EUS. A total of 100 consecutive patients with a solid pancreatic mass of unknown origin were prospectively included at three centers (July 2009 - April 2010). All patients were examined by CH-EUS followed by EUS-FNA. Absence of vascular enhancement at CH-EUS was regarded as a sign for pancreatic adenocarcinoma. The final diagnosis (gold standard) was based on pathological examination (EUS-FNA, surgery) or 12-month follow-up.  The final diagnoses were: 69 adenocarcinoma, 10 neuroendocrine tumors, 13 chronic pancreatitis, and 8 other lesions. In diagnosing adenocarcinoma, CH-EUS and EUS-FNA had respective accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 95 %, 96 %, 94 %, 97 %, and 91 %, and of 95 %, 93 %, 100 %, 100 %, and 86 % without significant difference. Five false-negative cases with EUS-FNA were correctly classified by CH-EUS. Interobserver agreement (seven endosonographers) was good (kappa 0.66). Intraobserver agreement was good to excellent (kappa 0.76 for junior, 0.90 for senior). The performance of CH-EUS for the diagnosis of pancreatic adenocarcinoma was excellent. The good intra- and interobserver concordances suggest an excellent reproducibility. CH-EUS could help to guide the choice between surgery and follow-up when EUS-FNA is inconclusive. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Automatic motion estimation using flow parameters for dynamic contrast-enhanced ultrasound.

    PubMed

    Barrois, Guillaume; Coron, Alain; Lucidarme, Olivier; Bridal, S Lori

    2015-03-21

    Dynamic contrast-enhanced ultrasound (DCE-US) sequences are subject to motion which can disturb functional flow quantification. This can make estimated parameters more variable or unreliable. Methods that compensate for motion are therefore desirable. The most commonly used motion correction techniques in DCE-US register the images in the sequence with respect to a user-selected reference image. However, this image may not include all features that are representative of the whole sequence. Moreover, image-based registration neglects pertinent, functional-flow information contained in the DCE-US sequence. An operator-free method is proposed that combines the motion estimation and flow-parameter quantification (M/Q method) in a single mathematical framework. This method is based on a realistic multiplicative model of the DCE-US noise. By computing likelihood in this model, motion and flow parameters are both estimated iteratively. First, the maximization is accomplished by estimating functional and motion parameters. Then, a final registration based on a non-parametric temporal smoothing of the sequence is performed. This method is compared to a conventional (mutual information) registration method where all the images of the sequence are registered with respect to a reference image chosen by an expert. The two methods are evaluated on simulated sequences and DCE-US sequences acquired in patients (N = 15). The M/Q method demonstrates significantly (p < 0.05) lower Dice coefficients and Hausdorff distance than the conventional method on the simulated data sets. On the in vivo sequences analysed, the M/Q methods outperformed the conventional method in terms of mean Dice and Hausdorff distance on 80% of the sequences, and in terms of standard deviation of Dice and Hausdorff distance on 87% of the sequences.

  20. Quantification of tumor perfusion using dynamic contrast-enhanced ultrasound: impact of mathematical modeling

    NASA Astrophysics Data System (ADS)

    Doury, Maxime; Dizeux, Alexandre; de Cesare, Alain; Lucidarme, Olivier; Pellot-Barakat, Claire; Bridal, S. Lori; Frouin, Frédérique

    2017-02-01

    Dynamic contrast-enhanced ultrasound has been proposed to monitor tumor therapy, as a complement to volume measurements. To assess the variability of perfusion parameters in ideal conditions, four consecutive test-retest studies were acquired in a mouse tumor model, using controlled injections. The impact of mathematical modeling on parameter variability was then investigated. Coefficients of variation (CV) of tissue blood volume (BV) and tissue blood flow (BF) based-parameters were estimated inside 32 sub-regions of the tumors, comparing the log-normal (LN) model with a one-compartment model fed by an arterial input function (AIF) and improved by the introduction of a time delay parameter. Relative perfusion parameters were also estimated by normalization of the LN parameters and normalization of the one-compartment parameters estimated with the AIF, using a reference tissue (RT) region. A direct estimation (rRTd) of relative parameters, based on the one-compartment model without using the AIF, was also obtained by using the kinetics inside the RT region. Results of test-retest studies show that absolute regional parameters have high CV, whatever the approach, with median values of about 30% for BV, and 40% for BF. The positive impact of normalization was established, showing a coherent estimation of relative parameters, with reduced CV (about 20% for BV and 30% for BF using the rRTd approach). These values were significantly lower (p  <  0.05) than the CV of absolute parameters. The rRTd approach provided the smallest CV and should be preferred for estimating relative perfusion parameters.

  1. Using a Commercial Ultrasound Contrast Agent for Viral-Mediated Gene Transfer In Vitro and In Vivo

    NASA Astrophysics Data System (ADS)

    Howard, Candace M.; Forsberg, Flemming; Liu, Ji-Bin; Merton, Daniel A.; Minimo, Corrado; Claudio, Pier P.

    2007-05-01

    This study evaluated the feasibility of site-specific gene delivery mediated by diagnostic ultrasound using genes encapsulated in commercially available ultrasound contrast agents in vitro and in vivo. Five different commercially available contrast agents were tested in vitro for their ability to enclose an adenoviral vector carrying GFP. Prostate cancer cells (DU 145) or non small cell lung cancer cells (H23) were plated in 80 culture wells and insonified at 207 or 535 kPa peak negative pressure for 1 min after administration of 0.1 ml of bubbles reconstituted with the viral vector. Experiments were repeated with the delivery vehicle incubated with complement to inactivate unenclosed Adeno-GFP and with controls. After 24 hours transduction efficiency was demonstrated by fluorescent microscopy. In vivo 15 nude mice with 21 melanoma tumors (DB-1) implanted received 0.1 ml injections of contrast. Mice were split into 3 control and 4 active groups and ultrasound was performed for 4 min at 4 MHz using an Aplio scanner (Toshiba America Medical Systems, Tustin, CA). Tumors, heart, lungs and liver were harvested 48 hours later. Specimens underwent regular and fluorescent microscopy and were stained using an antibody against GFP. In vitro all contrast agents produced more fluorescence at 207 kPa than at 535 kPa. However, only Imagent (IMCOR Pharmaceuticals, San Diego, CA) was able to induce marked gene transduction with the inactivating agent. In vivo systemic delivery of Adeno-GFP carrying microbubbles following pre-treatment with the inactivating agent resulted in specific transduction of the tumor cells only with no uptake in heart, lungs or liver (unlike the controls). In conclusion, specific viral gene transduction has been obtained in vitro and in vivo through the use of ultrasound and Imagent microbubbles as delivery vehicles.

  2. Off-Label Use of Ultrasound Contrast Agents for Intravenous Applications in Children: Analysis of the Existing Literature.

    PubMed

    Rosado, Elsa; Riccabona, Michael

    2016-03-01

    The purpose of this study was to collect and analyze the published data related to intravenous (IV) use of ultrasound (US) contrast agents in children. We searched the literature to collect all of the published studies reporting the IV administration of a second-generation US contrast agent in children. We analyzed 9 case series and 5 case reports, as well as 5 individual cases, of pediatric contrast-enhanced US use reported in a study group that also included adults. We found that 502 children underwent contrast-enhanced US examinations (mean age, 9.7 years; range, 1 day-18 years). Most patients (89%) were injected with the sulfur hexafluoride contrast agent SonoVue (Bracco SpA, Milan, Italy). The mean dose used was 1.5 mL (range, 0.1-9.6 mL). Only 10 patients (2%) had adverse reactions related to the contrast agent administration: 1 life-threatening anaphylactic shock and 9 mild transitory adverse effects. We additionally found 38 papers in which the study groups included at least 1 child; thus, we obtained a total of 540 reported cases of off-label use of IV US contrast agents in children. The most frequent target organ was the liver, and most indications were related to space-occupying lesion characterization and abdominal evaluations after blunt trauma. Some studies also evaluated the diagnostic performance of contrast-enhanced US in different clinical scenarios and found very good accuracy. Concordance between contrast-enhanced US imaging and the respective reference-standard imaging methods ranged between 83% and 100% in different studies. Our results support the idea that the IV use of US contrast agents in children is safe, feasible, diagnostically robust, and effective. © 2016 by the American Institute of Ultrasound in Medicine.

  3. Pulmonary transit time measurement by contrast-enhanced ultrasound in left ventricular dyssynchrony

    PubMed Central

    Saporito, Salvatore; Mischi, Massimo; van Assen, Hans C; Bouwman, R Arthur; de Lepper, Anouk G W; van den Bosch, Harrie C M; Korsten, Hendrikus H M; Houthuizen, Patrick

    2016-01-01

    Background Pulmonary transit time (PTT) is an indirect measure of preload and left ventricular function, which can be estimated using the indicator dilution theory by contrast-enhanced ultrasound (CEUS). In this study, we first assessed the accuracy of PTT-CEUS by comparing it with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Secondly, we tested the hypothesis that PTT-CEUS correlates with the severity of heart failure, assessed by MRI and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Methods and results Twenty patients referred to our hospital for cardiac resynchronization therapy (CRT) were enrolled. DCE-MRI, CEUS, and NT-proBNP measurements were performed within an hour. Mean transit time (MTT) was obtained by estimating the time evolution of indicator concentration within regions of interest drawn in the right and left ventricles in video loops of DCE-MRI and CEUS. PTT was estimated as the difference of the left and right ventricular MTT. Normalized PTT (nPTT) was obtained by multiplication of PTT with the heart rate. Mean PTT-CEUS was 10.5±2.4s and PTT-DCE-MRI was 10.4±2.0s (P=0.88). The correlations of PTT and nPTT by CEUS and DCE-MRI were strong; r=0.75 (P=0.0001) and r=0.76 (P=0.0001), respectively. Bland–Altman analysis revealed a bias of 0.1s for PTT. nPTT-CEUS correlated moderately with left ventricle volumes. The correlations for PTT-CEUS and nPTT-CEUS were moderate to strong with NT-proBNP; r=0.54 (P=0.022) and r=0.68 (P=0.002), respectively. Conclusions (n)PTT-CEUS showed strong agreement with that by DCE-MRI. Given the good correlation with NT-proBNP level, (n)PTT-CEUS may provide a novel, clinically feasible measure to quantify the severity of heart failure. Clinical Trial Registry: NCT01735838 PMID:27249553

  4. Impact of contrast-enhanced ultrasound in patients with renal function impairment

    PubMed Central

    Girometti, Rossano; Stocca, Tiziano; Serena, Elena; Granata, Antonio; Bertolotto, Michele

    2017-01-01

    AIM To investigate the role of contrast enhanced ultrasound (CEUS) in evaluating patients with renal function impairment (RFI) showing: (1) acute renal failure (ARF) of suspicious vascular origin; or (2) suspicious renal lesions. METHODS We retrospectively evaluated patients addressed to CEUS over an eight years period to rule-out vascular causes of ARF (first group of 50 subjects) or assess previously found suspicious renal lesions (second group of 41 subjects with acute or chronic RFI). After preliminary grey-scale and color Doppler investigation, each kidney was investigated individually with CEUS, using 1.2-2.4 mL of a sulfur hexafluoride-filled microbubble contrast agent. Image analysis was performed in consensus by two readers who reviewed digital clips of CEUS. We calculated the detection rate of vascular abnormalities in the first group and performed descriptive statistics of imaging findings for the second group. RESULTS In the first group, CEUS detected renal infarction or cortical ischemia in 18/50 patients (36%; 95%CI: 23.3-50.9) and 1/50 patients (2%; 95%CI: 0.1-12), respectively. The detection rate of infarction was significantly higher (P = 0.0002; McNemar test) compared to color Doppler ultrasonography (10%). No vascular causes of ARF were identified in the remaining 31/50 patients (62%). In the second group, CEUS detected 41 lesions on 39 patients, allowing differentiation between solid lesions (21/41; 51.2%) vs complex cysts (20/41; 48.8%), and properly addressing 15/39 patients to intervention when feasible based on clinical conditions (surgery and cryoablation in 13 and 2 cases, respectively). Cysts were categorized Bosniak II, IIF, III and IV in 8, 5, 4 and 3 cases, respectively. In the remaining two patients, CEUS found 1 pseudolesion and 1 subcapsular hematoma. CONCLUSION CEUS showed high detection rate of renal perfusion abnormalities in patients with ARF, influencing the management of patients with acute or chronic RFI and renal masses

  5. Stability of echogenic liposomes as a blood pool ultrasound contrast agent in a physiologic flow phantom.

    PubMed

    Radhakrishnan, Kirthi; Haworth, Kevin J; Huang, Shao-Ling; Klegerman, Melvin E; McPherson, David D; Holland, Christy K

    2012-11-01

    Echogenic liposomes (ELIP) are multifunctional ultrasound contrast agents (UCAs) with a lipid shell encapsulating both air and an aqueous core. ELIP are being developed for molecular imaging and image-guided therapeutic delivery. Stability of the echogenicity of ELIP in physiologic conditions is crucial to their successful translation to clinical use. In this study, we determined the effects of the surrounding media's dissolved air concentration, temperature transition and hydrodynamic pressure on the echogenicity of a chemically modified formulation of ELIP to promote stability and echogenicity. ELIP samples were diluted in porcine plasma or whole blood and pumped through a pulsatile flow system with adjustable hydrodynamic pressures and temperature. B-mode images were acquired using a clinical diagnostic scanner every 5 s for a total duration of 75 s. Echogenicity in porcine plasma was assessed as a function of total dissolved gas saturation. ELIP were added to plasma at room temperature (22 °C) or body temperature (37 °C) and pumped through a system maintained at 22 °C or 37 °C to study the effect of temperature transitions on ELIP echogenicity. Echogenicity at normotensive (120/80 mmHg) and hypertensive pressures (145/90 mmHg) was measured. ELIP were echogenic in plasma and whole blood at body temperature under normotensive to hypertensive pressures. Warming of samples from room temperature to body temperature did not alter echogenicity. However, in plasma cooled rapidly from body temperature to room temperature or in degassed plasma, ELIP lost echogenicity within 20 s at 120/80 mmHg. The stability of echogenicity of a modified ELIP formulation was determined in vitro at body temperature, physiologic gas concentration and throughout the physiologic pressure range. However, proper care should be taken to ensure that ELIP are not cooled rapidly from body temperature to room temperature as they will lose their echogenic properties. Further in

  6. Contrast-Enhanced Ultrasound in the Diagnosis of Gallbladder Diseases: A Multi-Center Experience

    PubMed Central

    Liu, Lin-Na; Xu, Hui-Xiong; Lu, Ming-De; Xie, Xiao-Yan; Wang, Wen-Ping; Hu, Bing; Yan, Kun; Ding, Hong; Tang, Shao-Shan; Qian, Lin-Xue; Luo, Bao-Ming; Wen, Yan-Ling

    2012-01-01

    Objective To assess the usefulness of contrast–enhanced ultrasound (CEUS) in differentiating malignant from benign gallbladder (GB) diseases. Methods This study had institutional review board approval. 192 patients with GB diseases from 9 university hospitals were studied. After intravenous bonus injection of a phospholipid-stabilized shell microbubble contrast agent, lesions were scanned with low acoustic power CEUS. A multiple logistic regression analysis was performed to identify diagnostic clues from 17 independent variables that enabled differentiation between malignant and benign GB diseases. Receiver operating characteristic (ROC) curve analysis was performed. Results Among the 17 independent variables, multiple logistic regression analysis showed that the following 4 independent variables were associated with the benign nature of the GB diseases, including the patient age, intralesional blood vessel depicted on CEUS, contrast washout time, and wall intactness depicted on CEUS (all P<0.05). ROC analysis showed that the patient age, intralesional vessels on CEUS, and the intactness of the GB wall depicted on CEUS yielded an area under the ROC curve (Az) greater than 0.8 in each and Az for the combination of the 4 significant independent variables was 0.915 [95% confidence interval (CI): 0.857–0.974]. The corresponding Az, sensitivity, and specificity for the age were 0.805 (95% CI: 0.746–0.863), 92.2%%, and 59.6%; for the intralesional vessels on CEUS were 0.813 (95% CI: 0.751–0.875), 59.8%, and 98.0%; and for the GB wall intactness were 0.857 (95% CI: 0.786–0.928), 78.4%, and 92.9%. The cut-off values for benign GB diseases were patient age <53.5 yrs, dotted intralesional vessels on CEUS and intact GB wall on CEUS. Conclusion CEUS is valuable in differentiating malignant from benign GB diseases. Branched or linear intralesional vessels and destruction of GB wall on CEUS are the CEUS features highly suggestive of GB malignancy and the patient age

  7. Impact of Filling Gas on Subharmonic Emissions of Phospholipid Ultrasound Contrast Agents.

    PubMed

    Kanbar, Emma; Fouan, Damien; Sennoga, Charles A; Doinikov, Alexander A; Bouakaz, Ayache

    2017-02-14

    Subharmonic signals backscattered from gas-filled lipid-shelled microbubbles have generated significant research interest because they can improve the detection and sensitivity of contrast-enhanced ultrasound imaging. However, the emission of subharmonic signals is strongly characterized by a temporal dependence, the origins of which have not been sufficiently elucidated. The features that influence subharmonic emissions need to be identified not only to better develop next-generation microbubble contrast agents, but also to develop more efficient subharmonic imaging (SHI) modes and therapeutic strategies. We examined the effect of microbubble filling gas on subharmonic emissions. Phospholipid shelled-microbubbles with different gaseous compositions such as sulfur hexafluoride (SF6), octafluoropropane (C3F8) or decafluorobutane (C4F10), nitrogen (N2)/C4F10 or air were insonated using a driving frequency of 10 MHz and peak negative pressure of 450 kPa, and their acoustic responses were tracked by monitoring both second harmonic and subharmonic emissions. Microbubbles were first acoustically characterized with their original gas and then re-characterized after substitution of the original gas with air, SF6 or C4F10. A measureable change in intensity of the subharmonic emissions with a 20- to 40-min delayed onset and increasing subharmonic emissions of the order 12-18 dB was recorded for microbubbles filled with C4F10. Substitution of C4F10 with air eliminated the earlier observed delay in subharmonic emissions. Significantly, substitution of SF6 for C4F10 successfully triggered a delay in the subharmonic emissions of the resultant agents, whereas substitution of C4F10 for SF6 eliminated the earlier observed suppression of subharmonic emissions, clearly suggesting that the type of filling gas contained in the microbubble agent influences subharmonic emissions in a time-dependent manner. Because our agents were dispersed in air-stabilized phosphate-buffered saline

  8. Quantitative measurement of high intensity focused ultrasound pressure field by optical phase contrast method applying non-continuous phase unwrapping algorithm

    NASA Astrophysics Data System (ADS)

    Syahid, Mohd; Oyama, Seiji; Yasuda, Jun; Yoshizawa, Shin; Umemura, Shin-ichiro

    2015-07-01

    A fast and accurate ultrasound pressure field measurement is necessary for the progress of ultrasound application in medicine. In general, a hydrophone is used to measure the ultrasound field, which takes a long measurement time and might disturb the ultrasound field. Hence, we proposed a new method categorized in an optical method called Phase Contrast method to overcome the drawback in the hydrophone method. The proposed method makes use of the spatial DC spectrum formed in the focal plane to measure the modulated optical phase induced by ultrasound propagation in water. In this study, we take into account the decreased intensity of the DC spectrum at high ultrasound intensity to increase the measurement accuracy of the modulated optical phase. Then, we apply a non-continuous phase unwrapping algorithm to unwrap the modulated optical phase at high ultrasound intensity. From, the unwrapped result, we evaluate the quantitativeness of the proposed method.

  9. Targeted contrast-enhanced ultrasound imaging of angiogenesis in an orthotopic mouse tumor model of renal carcinoma.

    PubMed

    Wei, Shuping; Fu, Ninghua; Sun, Yu; Yang, Zhijian; Lei, Li; Huang, Pengfei; Yang, Bin

    2014-06-01

    Previous studies have reported that microbubbles bearing targeting ligands to molecular markers of angiogenesis can be successfully detected by ultrasound imaging in various animal models of solid cancer. In the present study, we sought to investigate the activity of microbubbles targeted to vascular endothelial growth factor receptor 2 (VEGFR2) in an orthotopic model of renal cell carcinoma (RCC). Microbubbles conjugated to an anti-VEGFR2 antibody (MBV) were compared with microbubbles conjugated to an isotype control antibody (MBC) or naked microbubbles (MBN). An orthotopic mouse model of human RCC was established by surgically implanting an established tumor within the renal capsule in mice. Tumor growth and blood flow were verified by B-mode and color Doppler ultrasound imaging. VEGFR2 expression within the tumor and renal parenchyma was detected by immunohistochemistry. The duration of contrast enhancement of MBV was much longer than those of MBN and MBC when assessed over 10 min. The baseline-subtracted contrast intensity within the tumor was higher for MBV than for MBC and MBN (p < 0.01). Additionally, the contrast intensity for MBV was significantly higher in the tumor region than in normal parenchyma (p < 0.01). Microbubbles targeting VEGFR2 exhibit suitable properties for imaging angiogenesis in orthotopic models of renal cell carcinoma, with potential applications in life science research and clinical medicine. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  10. Noninvasive detection of vertebral artery stenosis: a comparison of contrast-enhanced MR angiography, CT angiography, and ultrasound.

    PubMed

    Khan, Sofia; Rich, Philip; Clifton, Andrew; Markus, Hugh S

    2009-11-01

    Vertebral stenosis is associated with a high risk of recurrent stroke, but noninvasive imaging techniques to identify it have lacked sensitivity. Contrast-enhanced MR angiography and CT angiography have been recently developed and appear to have better sensitivity. However, no prospective studies have compared both of these techniques with ultrasound against the gold standard of intra-arterial angiography in the same group of patients. Forty-six patients were prospectively recruited in whom intra-arterial angiography was being performed. Contrast-enhanced MR angiography, CT angiography, and duplex ultrasound were also performed. Angiographic images were analyzed blinded to patient identity by 2 experienced neuroradiologists. Contrast-enhanced MR angiography had the highest sensitivity and specificity (Radiologist 1, 0.83 and 0.91, respectively; Radiologist 2, 0.89 and 0.87) for detecting >or=50% stenosis. CT angiography had good sensitivity (Radiologist 1, 0.68; Radiologist 2, 0.58) and excellent specificity (Radiologist 1, 0.92; Radiologist 2, 0.93), whereas duplex had low sensitivity (0.44) but excellent specificity (0.95). For vertebral origin stenosis >or=50%, sensitivities were similar for contrast-enhanced MR angiography (Radiologist 1, 0.91; Radiologist 2, 0.82) but relatively higher for CT angiography (Radiologist 1, 0.82; Radiologist 2, 0.82) and duplex (0.67). Contrast-enhanced MR angiography is the most sensitive noninvasive technique to detect vertebral artery stenosis and also has high specificity. CT angiography has good sensitivity and high specificity. In contrast, ultrasound has low sensitivity and will miss many vertebral stenoses.

  11. Contrast-Enhanced Ultrasound Differentiation Between Low and High-Grade Bladder Urothelial Carcinoma and Correlation With Tumor Microvessel Density.

    PubMed

    Guo, Suping; Xu, Pan; Zhou, Aiyun; Wang, Gongxian; Chen, Weimin; Mei, Jinhong; Xiao, Fan; Liu, Juan; Zhang, Cheng

    2017-05-27

    Time-intensity curves (TICs) of contrast-enhanced ultrasound (CEUS) were analyzed retrospectively to differentiate between low-grade and high-grade bladder urothelial carcinoma, and to investigate correlation with tumor microvessel density (MVD). The data of 105 patients with pathologically confirmed bladder urothelial carcinoma (55 low-grade and 50 high-grade) were reviewed. Lesions were examined before surgery using conventional ultrasound and CEUS with TIC analysis. The TIC parameters time from peak to one-half the signal intensity (TPH) and the corresponding descending slope (DS) of the low-grade and high-grade groups were compared, and receiver operating characteristic curves constructed. The MVDs of the resectioned tissue specimens were quantified via immunohistochemistry for CD34. Based on conventional ultrasound, the low-grade and high-grade groups were similar in tumor shape, number, topography, internal echo, height, width, and vascularity. The TPH of the high-grade group was significantly longer than that of the low-grade group, and the DS was lower. The cutoff points of TPH and DS for differentiating low-grade and high-grade bladder urothelial carcinoma were 48.06 seconds and 0.15 dB/seconds, respectively (area under the receiver operating characteristic curve = 0.79 for both). The mean MVDs per high-power field of the low-grade and high-grade groups were 41.39 16.65 and 51.03 20.16, respectively (P = .009). The TPH correlated linearly with MVD (P < .01), as did the DS (P < .01). Contrast-enhanced ultrasound can be used to differentiate low from high-grade bladder urothelial carcinoma. The TIC parameters of CEUS reflect the MVD of bladder urothelial tumors and may be helpful for evaluating tumor angiogenesis, with implications for clinical diagnosis, treatment, and prognosis. © 2017 by the American Institute of Ultrasound in Medicine.

  12. Clinical value of dynamic 3-dimensional contrast-enhanced ultrasound imaging for the assessment of hepatocellular carcinoma ablation.

    PubMed

    Wang, Yandong; Jing, Xiang; Ding, Jianmin

    2016-01-01

    The aim of the study was to investigate the performance of dynamic 3-dimensional contrast-enhanced ultrasound (3D-CEUS) on assessment of efficacy of local ablation therapy of hepatocellular carcinoma (HCC) with contrast-enhanced computed tomography (CT) as reference standard. Eighty-nine HCC lesions from 75 patients undergoing ultrasound-guided percutaneous thermal ablation or chemical ablation were studied by both dynamic 3D-CEUS and contrast-enhanced CT 1month after ablation. Imaging results from two imaging modalities were evaluated independently by experienced readers to determine whether the treated lesions were ablated incompletely (residual unablated tumor) or completely. Sensitivity, specificity, positive and negative predictive values, and accuracy to identify incomplete ablation were calculated for dynamic 3D-CEUS imaging with contrast-enhanced CT as reference standard. Contrast-enhanced CT reported that 80.9% (72/89) of all the treated lesions were completely ablated and 19.1% (17/89) were incompletely ablated. The dynamic 3D-CEUS identified 82.0% (73/89) and 18.0% (16/89) of lesions as completely and incompletely ablated, respectively. With contrast-enhanced CT as the reference standard, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of dynamic 3D-CEUS for identifying residual unablated tumor were 88.2% (15/17), 98.6% (71/72), 93.8% (15/16), 97.3% (71/73), and 96.6% (86/89), respectively. The Kappa value for identifying residual unablated tumor between contrast-enhanced CT and dynamic 3D-CEUS was 0.89. Dynamic 3D-CEUS is highly consistent with contrast-enhanced CT in assessment of efficacy of HCC ablation and has potential to serve as an alternative to contrast-enhanced CT in the follow-up assessment after HCC ablation. Published by Elsevier Inc.

  13. Contrast-enhanced ultrasound with SonoVue in the evaluation of postoperative complications in pediatric liver transplant recipients

    PubMed Central

    Bonini, G.; Pezzotta, G.; Morzenti, C.; Agazzi, R.; Nani, R.

    2007-01-01

    Purpose To evaluate the utility of contrast-enhanced sonography in the study of pediatric liver transplant recipients and its potential impact in reducing the need for invasive diagnostic procedures. Materials and methods From October 2002 to December 2003 we performed routine color Doppler ultrasound and contrast-enhanced ultrasound studies on 30 pediatric patients who had undergone liver transplantation. Findings indicative of complications were confirmed with invasive studies (angiography, computed tomography, and PTC). Results Contrast-enhanced sonography correctly identified four of the five cases of hepatic artery thrombosis and all those involving the portal (n = 6) and hepatic vein (n = 3) thrombosis. It failed to identify one case of hepatic artery thrombosis characterized by collateral circulation arising from the phrenic artery and the single case of hepatic artery stenosis. The latter was more evident on color Doppler, which revealed a typical tardus parvus waveform. The use of contrast offered no significant advantages in the study of biliary complications although it did provide better visualization of bile leaks. Conclusions Contrast-enhanced sonography improves diagnostic confidence and reduces the need for more invasive imaging studies in the postoperative follow-up of pediatric liver transplant recipients. PMID:23396596

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

    PubMed Central

    Ma, Shuhua; Wu, Xiaomin; Tian, Shuangming; Zhao, Yongfeng

    2016-01-01

    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 (P < 0.05); at the final evaluation, the volume decreased from 6.16 ± 5.21 mL to 0.05 ± 0.01 mL. Thyroid functions did not show significant differences at one month after ablation compared with that before (P > 0.05). 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. PMID:27999819

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

    PubMed

    Ma, Shuhua; Zhou, Ping; Wu, Xiaomin; Tian, Shuangming; Zhao, Yongfeng

    2016-01-01

    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 (P < 0.05); at the final evaluation, the volume decreased from 6.16 ± 5.21 mL to 0.05 ± 0.01 mL. Thyroid functions did not show significant differences at one month after ablation compared with that before (P > 0.05). 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.

  16. Ultrasound-Triggered Phase Transition Sensitive Magnetic Fluorescent Nanodroplets as a Multimodal Imaging Contrast Agent in Rat and Mouse Model

    PubMed Central

    Chen, Yunchao; Luo, Binhua; Liu, Xuhan; Liu, Wei; Xu, Haibo; Yang, Xiangliang

    2013-01-01

    Ultrasound-triggered phase transition sensitive nanodroplets with multimodal imaging functionality were prepared via premix Shirasu porous glass (SPG) membrane emulsification method. The nanodroplets with fluorescence dye DiR and SPIO nanoparticles (DiR-SPIO-NDs) had a polymer shell and a liquid perfluoropentane (PFP) core. The as-formed DiR-SPIO-NDs have a uniform size of 385±5.0 nm with PDI of 0.169±0.011. The TEM and microscopy imaging showed that the DiR-SPIO-NDs existed as core-shell spheres, and DiR and SPIO nanoparticles dispersed in the shell or core. The MTT and hemolysis studies demonstrated that the nanodroplets were biocompatible and safe. Moreover, the proposed nanodroplets exhibited significant ultrasound-triggered phase transition property under clinical diagnostic ultrasound irradiation due to the vaporization of PFP inside. Meanwhile, the high stability and R2 relaxivity of the DiR-SPIO-NDs suggested its applicability in MRI. The in vivo T2-weighted images of MRI and fluorescence images both showed that the image contrast in liver and spleen of rats and mice model were enhanced after the intravenous injection of DiR-SPIO-NDs. Furthermore, the ultrasound imaging (US) in mice tumor as well as MRI and fluorescence imaging in liver of rats and mice showed that the DiR-SPIO-NDs had long-lasting contrast ability in vivo. These in vitro and in vivo findings suggested that DiR-SPIO-NDs could potentially be a great MRI/US/fluorescence multimodal imaging contrast agent in the diagnosis of liver tissue diseases. PMID:24391983

  17. Ultrasound-triggered phase transition sensitive magnetic fluorescent nanodroplets as a multimodal imaging contrast agent in rat and mouse model.

    PubMed

    Cheng, Xin; Li, Huan; Chen, Yunchao; Luo, Binhua; Liu, Xuhan; Liu, Wei; Xu, Haibo; Yang, Xiangliang

    2013-01-01

    Ultrasound-triggered phase transition sensitive nanodroplets with multimodal imaging functionality were prepared via premix Shirasu porous glass (SPG) membrane emulsification method. The nanodroplets with fluorescence dye DiR and SPIO nanoparticles (DiR-SPIO-NDs) had a polymer shell and a liquid perfluoropentane (PFP) core. The as-formed DiR-SPIO-NDs have a uniform size of 385 ± 5.0 nm with PDI of 0.169 ± 0.011. The TEM and microscopy imaging showed that the DiR-SPIO-NDs existed as core-shell spheres, and DiR and SPIO nanoparticles dispersed in the shell or core. The MTT and hemolysis studies demonstrated that the nanodroplets were biocompatible and safe. Moreover, the proposed nanodroplets exhibited significant ultrasound-triggered phase transition property under clinical diagnostic ultrasound irradiation due to the vaporization of PFP inside. Meanwhile, the high stability and R2 relaxivity of the DiR-SPIO-NDs suggested its applicability in MRI. The in vivo T2-weighted images of MRI and fluorescence images both showed that the image contrast in liver and spleen of rats and mice model were enhanced after the intravenous injection of DiR-SPIO-NDs. Furthermore, the ultrasound imaging (US) in mice tumor as well as MRI and fluorescence imaging in liver of rats and mice showed that the DiR-SPIO-NDs had long-lasting contrast ability in vivo. These in vitro and in vivo findings suggested that DiR-SPIO-NDs could potentially be a great MRI/US/fluorescence multimodal imaging contrast agent in the diagnosis of liver tissue diseases.

  18. 33 CFR 165.110 - Safety and Security Zone; Liquefied Natural Gas Carrier Transits and Anchorage Operations, Boston...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...; Liquefied Natural Gas Carrier Transits and Anchorage Operations, Boston, Massachusetts. 165.110 Section 165... Limited Access Areas First Coast Guard District § 165.110 Safety and Security Zone; Liquefied Natural Gas... ahead and one mile astern, and 500 yards on each side of any liquefied natural gas carrier (LNGC) vessel...

  19. 33 CFR 165.110 - Safety and Security Zone; Liquefied Natural Gas Carrier Transits and Anchorage Operations, Boston...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...; Liquefied Natural Gas Carrier Transits and Anchorage Operations, Boston, Massachusetts. 165.110 Section 165... Limited Access Areas First Coast Guard District § 165.110 Safety and Security Zone; Liquefied Natural Gas... ahead and one mile astern, and 500 yards on each side of any liquefied natural gas carrier (LNGC) vessel...

  20. 33 CFR 165.110 - Safety and Security Zone; Liquefied Natural Gas Carrier Transits and Anchorage Operations, Boston...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...; Liquefied Natural Gas Carrier Transits and Anchorage Operations, Boston, Massachusetts. 165.110 Section 165... Limited Access Areas First Coast Guard District § 165.110 Safety and Security Zone; Liquefied Natural Gas... ahead and one mile astern, and 500 yards on each side of any liquefied natural gas carrier (LNGC) vessel...

  1. 33 CFR 165.110 - Safety and Security Zone; Liquefied Natural Gas Carrier Transits and Anchorage Operations, Boston...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...; Liquefied Natural Gas Carrier Transits and Anchorage Operations, Boston, Massachusetts. 165.110 Section 165... Limited Access Areas First Coast Guard District § 165.110 Safety and Security Zone; Liquefied Natural Gas... ahead and one mile astern, and 500 yards on each side of any liquefied natural gas carrier (LNGC) vessel...

  2. 33 CFR 165.110 - Safety and Security Zone; Liquefied Natural Gas Carrier Transits and Anchorage Operations, Boston...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...; Liquefied Natural Gas Carrier Transits and Anchorage Operations, Boston, Massachusetts. 165.110 Section 165... Limited Access Areas First Coast Guard District § 165.110 Safety and Security Zone; Liquefied Natural Gas... ahead and one mile astern, and 500 yards on each side of any liquefied natural gas carrier (LNGC) vessel...

  3. Microbubbles as drug-delivery vectors: steering ultrasound contrast agents in arterial flow using the Bjerknes force

    NASA Astrophysics Data System (ADS)

    Aliseda, Alberto; Clark, Alicia

    2012-11-01

    Micron-sized coated microbubbles, commonly referred to as ultrasound contrast agents (UCAs), have been identified as potential targeted drug delivery vectors with applications in cancer chemotherapy and thrombolysis. The Bjerknes force, produced by the fluctuating pressure field created by the ultrasound waves acting on the oscillating bubble with a phase lag induced by the liquid's inertia and viscosity, can be used to direct the microbubbles to specific targeted areas in the circulatory system. While this phenomenon is well understood in a quiescent fluid, we need a better understanding of the dynamics of microbubbles in the complex pulsatile flow found in the human circulatory system. The non-linear interactions of ultrasound volume oscillations and flow-induced stresses are explored via high speed imaging of UCAs under in vitro flow that reproduces conditions in large arteries (relatively high Reynolds and Womersley numbers). This improved understanding will be used to manipulate and steer UCAs with ultrasound, in conjunction with hydrodynamic forces. NSF CAREER, NSF Graduate Research Fellowship.

  4. Quantitative analysis of vascular heterogeneity in breast lesions using contrast-enhanced 3-D harmonic and subharmonic ultrasound imaging.

    PubMed

    Sridharan, Anush; Eisenbrey, John R; Machado, Priscilla; Ojeda-Fournier, Haydee; Wilkes, Annina; Sevrukov, Alexander; Mattrey, Robert F; Wallace, Kirk; Chalek, Carl L; Thomenius, Kai E; Forsberg, Flemming

    2015-03-01

    Ability to visualize breast lesion vascularity and quantify the vascular heterogeneity using contrast-enhanced 3-D harmonic (HI) and subharmonic (SHI) ultrasound imaging was investigated in a clinical population. Patients (n = 134) identified with breast lesions on mammography were scanned using power Doppler imaging, contrast-enhanced 3-D HI, and 3-D SHI on a modified Logiq 9 scanner (GE Healthcare). A region of interest corresponding to ultrasound contrast agent flow was identified in 4D View (GE Medical Systems) and mapped to raw slice data to generate a map of time-intensity curves for the lesion volume. Time points corresponding to baseline, peak intensity, and washout of ultrasound contrast agent were identified and used to generate and compare vascular heterogeneity plots for malignant and benign lesions. Vascularity was observed with power Doppler imaging in 84 lesions (63 benign and 21 malignant). The 3-D HI showed flow in 8 lesions (5 benign and 3 malignant), whereas 3-D SHI visualized flow in 68 lesions (49 benign and 19 malignant). Analysis of vascular heterogeneity in the 3-D SHI volumes found benign lesions having a significant difference in vascularity between central and peripheral sections (1.71 ± 0.96 vs. 1.13 ± 0.79 dB, p < 0.001, respectively), whereas malignant lesions showed no difference (1.66 ± 1.39 vs. 1.24 ± 1.14 dB, p = 0.24), indicative of more vascular coverage. These preliminary results suggest quantitative evaluation of vascular heterogeneity in breast lesions using contrast-enhanced 3-D SHI is feasible and able to detect variations in vascularity between central and peripheral sections for benign and malignant lesions.

  5. Quantitative Analysis of Vascular Heterogeneity in Breast Lesions Using Contrast-Enhanced 3-D Harmonic and Subharmonic Ultrasound Imaging

    PubMed Central

    Sridharan, Anush; Eisenbrey, John R.; Machado, Priscilla; Ojeda-Fournier, Haydee; Wilkes, Annina; Sevrukov, Alexander; Mattrey, Robert F.; Wallace, Kirk; Chalek, Carl L.; Thomenius, Kai E.; Forsberg, Flemming

    2015-01-01

    Ability to visualize breast lesion vascularity and quantify the vascular heterogeneity using contrast-enhanced 3-D harmonic (HI) and subharmonic (SHI) ultrasound imaging was investigated in a clinical population. Patients (n = 134) identified with breast lesions on mammography were scanned using power Doppler imaging, contrast-enhanced 3-D HI, and 3-D SHI on a modified Logiq 9 scanner (GE Healthcare). A region of interest corresponding to ultrasound contrast agent flow was identified in 4D View (GE Medical Systems) and mapped to raw slice data to generate a map of time-intensity curves for the lesion volume. Time points corresponding to baseline, peak intensity, and washout of ultrasound contrast agent were identified and used to generate and compare vascular heterogeneity plots for malignant and benign lesions. Vascularity was observed with power Doppler imaging in 84 lesions (63 benign and 21 malignant). The 3-D HI showed flow in 8 lesions (5 benign and 3 malignant), whereas 3-D SHI visualized flow in 68 lesions (49 benign and 19 malignant). Analysis of vascular heterogeneity in the 3-D SHI volumes found benign lesions having a significant difference in vascularity between central and peripheral sections (1.71 ± 0.96 vs. 1.13 ± 0.79 dB, p < 0.001, respectively), whereas malignant lesions showed no difference (1.66 ± 1.39 vs. 1.24 ± 1.14 dB, p = 0.24), indicative of more vascular coverage. These preliminary results suggest quantitative evaluation of vascular heterogeneity in breast lesions using contrast-enhanced 3-D SHI is feasible and able to detect variations in vascularity between central and peripheral sections for benign and malignant lesions. PMID:25935933

  6. Ultrasound

    MedlinePlus Videos and Cool Tools

    ... 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 uterus. The sound waves bounce off solid structures in the body ...

  7. Ultrasound

    MedlinePlus

    ... called multiples) To screen for birth defects, like spina bifida or heart defects . Screening means seeing if your ... example, if the ultrasound shows your baby has spina bifida, she may be treated in the womb before ...

  8. Ultrasound

    MedlinePlus

    ... a pregnant woman and assess her fetus Diagnose gallbladder disease Evaluate flow in blood vessels Guide a ... For some ultrasound exams, such as of the gallbladder, your doctor may ask that you not eat ...

  9. Contrast enhancement and elastography in endoscopic ultrasound: an update of clinical applications in pancreatic diseases.

    PubMed

    Serrani, Marta; Lisotti, Andrea; Caletti, Giancarlo; Fusaroli, Pietro

    2016-08-01

    It is well established that endoscopic ultrasound (EUS) is fundamental in the characterization of many diseases concerning different organs, i.e. pancreaticobiliary diseases, gastrointestinal pathologic conditions, and lymph nodes of unknown origin. It is also well known that many factors can hamper the accuracy of EUS, i.e. biliary stents, chronic pancreatitis, poor operator's expertise. These factors can also lead to suboptimal accuracy when cytological confirmation through EUS-fine needle aspiration (EUS-FNA) is indicated. In recent years, new technological tools have rapidly increased their clinical impact improving the diagnostic power of EUS and EUS-FNA. Among these new tools, the most investigated and useful ones are represented by contrast harmonic-EUS (CH-EUS) and EUS-elastography (EUS-E). The purpose of this paper is to provide, through a review of the literature, an update of the applications of CH-EUS and EUS-E in the routine clinical practice in pancreatic diseases. We discussed the first reports and applications of these techniques in our previous review published in Minerva Medica. The applications of CH-EUS and EUS-E to the study of pancreatic diseases appear feasible and safe. The use of both techniques is very simple and does not require any relevant additional workload for the endoscopic personnel. CH-EUS is now considered an important and accurate tool in the diagnosis of solid pancreatic masses and in the differential diagnosis of pancreatic cystic lesions. CH-EUS targeted FNA is an active field of research. However the available studies show that CH-EUS increases FNA accuracy by a little extent, without statistical significance; moreover, CH-EUS FNA showed a trend toward being more efficient vs. simple EUS FNA (less needle passes and more abundance in cytological material) but this trend did not reach statistical significance. On the other hand, the clinical impact of EUS-E in terms of differential diagnosis of pancreatic masses is still under

  10. Investigation of the acute plantar fasciitis with contrast-enhanced ultrasound and shear wave elastography - first results.

    PubMed

    Putz, Franz Josef; Hautmann, Matthias G; Banas, Miriam; Jung, Ernst Michael

    2017-09-04

    The plantar fasciitis is a common disease with a high prevalence in public and a frequent cause of heel pain. In our pilot study, we wanted to characterise the feasibility of shear-wave elastography and contrast-enhanced ultrasound (CEUS) in the assessment of the plantar fasciitis. 23 cases of painful heels were examined by B-Mode ultrasound, Power Doppler (PD), shear wave elastography and contrast-enhanced ultrasound before anti-inflammatory radiation. Time-intensity-curves were analysed by the integrated software. The results for area-under-the-curve (AUC), peak, time-to-peak (TTP) and mean-transit-time (MTT) were compared between the plantar fascia and the surrounding tissue. All cases showed thickening of the plantar fascia, in most cases with interstitial oedema (87.0%). Shear wave elastography showed inhomogeneous stiffness of the plantar fascia. 83.3% of cases showed a visible hyperperfusion in CEUS at the proximal plantar fascia in comparison to the surrounding tissue. This hyperperfusion could also be found in 75.0% of cases with no signs of vascularisation in PD. AUC (p = 0.0005) and peak (p = 0.037) were significantely higher in the plantar fascia than in the surrounding tissue. CEUS and shear wave elastography are new diagnostic tools in the assessment of plantar fasciitis and can provide quantitative parameters for monitoring therapy.

  11. Assessment of murine colorectal cancer by micro-ultrasound using three dimensional reconstruction and non-linear contrast imaging

    PubMed Central

    Freeling, Jessica L; Rezvani, Khosrow

    2016-01-01

    The relatively low success rates of current colorectal cancer (CRC) therapies have led investigators to search for more specific treatments. Vertebrate models of colorectal cancer are essential tools for the verification of new therapeutic avenues such as gene therapy. The evaluation of colorectal cancer in mouse models has been limited due to the lack of an accurate quantitative and longitudinal noninvasive method. This work introduces a method of three-dimensional micro-ultrasound reconstruction and microbubble administration for the comprehensive and longitudinal evaluation of CRC progression. This approach enabled quantification of both tumor volume and relative vascularity using a well-established inducible murine model of colon carcinogenesis. This inducible model recapitulated the adenocarcinoma sequence that occurs in human CRC allowing systematic in situ evaluation of the ultrasound technique. The administration of intravenous microbubbles facilitated enhancement of colon vascular contrast and quantification of relative vascularity of the mid and distal colon of the mouse in three dimensions. In addition, two-dimensional imaging in the sagittal orientation of the colon using Non-Linear Contrast Mode enabled calculation of relative blood volume and perfusion as the microbubbles entered the colon microvasculature. Quantitative results provided by the outlined protocol represent a noninvasive tool that can more accurately define CRC development and progression. This ultrasound technique will allow the practical and economical longitudinal study of murine CRC in both basic and preclinical studies. PMID:28053998

  12. High Resolution Ultrasound Superharmonic Perfusion Imaging: In Vivo Feasibility and Quantification of Dynamic Contrast-Enhanced Acoustic Angiography.

    PubMed

    Lindsey, Brooks D; Shelton, Sarah E; Martin, K Heath; Ozgun, Kathryn A; Rojas, Juan D; Foster, F Stuart; Dayton, Paul A

    2017-04-01

    Mapping blood perfusion quantitatively allows localization of abnormal physiology and can improve understanding of disease progression. Dynamic contrast-enhanced ultrasound is a low-cost, real-time technique for imaging perfusion dynamics with microbubble contrast agents. Previously, we have demonstrated another contrast agent-specific ultrasound imaging technique, acoustic angiography, which forms static anatomical images of the superharmonic signal produced by microbubbles. In this work, we seek to determine whether acoustic angiography can be utilized for high resolution perfusion imaging in vivo by examining the effect of acquisition rate on superharmonic imaging at low flow rates and demonstrating the feasibility of dynamic contrast-enhanced superharmonic perfusion imaging for the first time. Results in the chorioallantoic membrane model indicate that frame rate and frame averaging do not affect the measured diameter of individual vessels observed, but that frame rate does influence the detection of vessels near and below the resolution limit. The highest number of resolvable vessels was observed at an intermediate frame rate of 3 Hz using a mechanically-steered prototype transducer. We also demonstrate the feasibility of quantitatively mapping perfusion rate in 2D in a mouse model with spatial resolution of ~100 μm. This type of imaging could provide non-invasive, high resolution quantification of microvascular function at penetration depths of several centimeters.

  13. Neural progenitor cells labeling with microbubble contrast agent for ultrasound imaging in vivo

    PubMed Central

    Cui, Wenjin; Tavri, Sidhartha; Benchimol, Michael J.; Itani, Malak; Olson, Emilia S.; Zhang, Hong; Decyk, Marika; Ramirez, Rosemarie G.; Barback, Christopher V.; Kono, Yuko; Mattrey, Robert F.

    2013-01-01

    Tracking neuroprogenitor cells (NPCs) that are used to target tumors, infarction or inflammation, is paramount for cell-based therapy. We employed ultrasound imaging that can detect a single microbubble because it can distinguish its unique signal from those of surrounding tissues. NPCs efficiently internalized positively charged microbubbles allowing a clinical ultrasound system to detect a single cell at 7 MHz. When injected intravenously, labeled NPCs traversed the lungs to be imaged in the left ventricle and the liver where they accumulated. Internalized microbubbles were not only less sensitive to destruction by ultrasound, but remained visible in vivo for days as compared to minutes when given free. The extended longevity provides ample time to allow cells to reach their intended target. We were also able to transfect NPCs in vitro when microbubbles were preloaded with GFP plasmid only when cells were insonated. Transfection efficiency and cell viability were both greater than 90%. PMID:23578557

  14. Intraductally applied contrast-enhanced ultrasound (IA-CEUS) for evaluating obstructive disease and secretory dysfunction of the salivary glands.

    PubMed

    Zengel, Pamela; Berghaus, A; Weiler, C; Reiser, M; Clevert, D A

    2011-06-01

    Obstructive diseases of the salivary glands are a common problem, usually based on sialolithiasis, duct stenosis, foreign bodies or other more rare causes. Secretory dysfunction, often associated with Sjögren syndrome or post radiation treatment, is also a frequent problem. Several diagnostic tools exist to classify the disease; however conventional radiological imaging or ultrasound does not provide a diagnosis in 5-10% of all cases. Intraductally applied contrast-enhanced ultrasound (IA-CEUS) improves the visualization of obstructive diseases of the salivary glands. IA-CEUS is a promising tool for assessing the ductal system and to diagnose and characterize abnormalities. This study describes the assessment of IA-CEUS in diagnosing different obstructive and chronic inflammatory conditions of the salivary glands.

  15. Development of a theoretical model describing sonoporation activity of cells exposed to ultrasound in the presence of contrast agents

    PubMed Central

    Forbes, Monica M.; O’Brien, William D.

    2012-01-01

    Sonoporation uses ultrasound, with the aid of ultrasound contrast agents (UCAs), to enhance cell permeabilization, thereby allowing delivery of therapeutic compounds noninvasively into specific target cells. The objective of this study was to determine if a computational model describing shear stress on a cell membrane due to microstreaming would successfully reflect sonoporation activity with respect to the peak rarefactional pressure. The theoretical models were compared to the sonoporation results from Chinese hamster ovary cells using Definity® at 0.9, 3.15, and 5.6 MHz and were found to accurately describe the maximum sonoporation activity, the pressure where a decrease in sonoporation activity occurs, and relative differences between maximum activity and the activity after that decrease. Therefore, the model supports the experimental findings that shear stress on cell membranes secondary to oscillating UCAs results in sonoporation. PMID:22501051

  16. Effect of molecular weight, crystallinity, and hydrophobicity on the acoustic activation of polymer-shelled ultrasound contrast agen