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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. 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

  3. Ultrasound despeckling for contrast enhancement.

    PubMed

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

    2010-07-01

    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

  4. Contrast-Enhanced Endoscopic Ultrasound

    PubMed Central

    Dietrich, Christoph F.; Sharma, M.; Hocke, M.

    2012-01-01

    The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) introduced guidelines on the use of contrast-enhanced ultrasound (CEUS) in 2004. This EFSUMB-document focused mainly on liver applications. However, new applications extending beyond the liver were developed thereafter. Increased interest in recent years in CEUS technique and in the application of CEUS in novel fields like endoscopic ultrasound (EUS) has revolutionized indications and applications. As a result, the EFSUMB initiated a new update of the guidelines in 2011 to include this additional knowledge. Some of the contrast-enhanced EUS (CE-EUS) indications are established, whereas others are preliminary; these latter indications are categorized as emergent CEUS applications since the available evidence is insufficient for general recommendation. This article focuses on the use of CE-EUS in various clinical settings. The reader will get an overview of current indications and possible applications of CE-EUS. This involves the introduction of different contrast studies including color Doppler techniques (known as contrast-enhanced high mechanical index endosonography or CEHMI-EUS) as well as more modern high-resolution contrast-enhanced techniques (known as contrast-enhanced low mechanical index endosonography or CELMI EUS). PMID:24949350

  5. 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. PMID:21222650

  6. 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

  7. Contrast enhanced ultrasound of breast cancer.

    PubMed

    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

  8. Contrast enhanced ultrasound of sentinel lymph nodes

    PubMed Central

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

    2013-01-01

    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. PMID:26675994

  9. 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

  10. Contrast-enhanced and targeted ultrasound.

    PubMed

    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

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

    PubMed Central

    2012-01-01

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

  12. Contrast-enhanced ultrasound: The evolving applications

    PubMed Central

    Xu, Hui-Xiong

    2009-01-01

    Contrast-enhanced ultrasound (CEUS) is a major breakthrough for ultrasound imaging in recent years. By using a microbubble contrast agent and contrast-specific imaging software, CEUS is able to depict the micro- and macro-circulation of the targeted organ, which in turn leads to improved performance in diagnosis. Due to the special dual blood supply system in the liver, CEUS is particularly suitable for liver imaging. It is evident that CEUS facilitates improvement for characterization of focal liver lesions (FLLs), detection of liver malignancy, guidance for interventional procedures, and evaluation of treatment response after local therapies. CEUS has been demonstrated to be equal to contrast-enhanced computed tomography or magnetic resonance imaging for the characterization of FLLs. In addition, the applicability of CEUS has expanded to non-liver structures such as gallbladder, bile duct, pancreas, kidney, spleen, breast, thyroid, and prostate. The usefulness of CEUS in these applications is confirmed by extensive literature production. Novel applications include detecting bleeding sites and hematomas in patients with abdominal trauma, guiding percutaneous injection therapy and therefore achieving the goal of using interventional ultrasonography in managing splenic trauma, assessing the activity of Crohn’s disease, and detecting suspected endoleaks after endovascular abdominal aneurysm repair. Contrast-enhanced intraoperative ultrasound (US) and intracavitary use of CEUS have been developed and clinically studied. The potential use of CEUS involves sentinel lymph node detection, drug or gene delivery, and molecular imaging. In conclusion, the advent of CEUS has greatly enhanced the usefulness of US and even changed the status of US in clinical practice. The application of CEUS in the clinic is continuously evolving and it is expected that its use will be expanded further in the future. PMID:21160717

  13. Contrast enhanced ultrasound of renal masses

    PubMed Central

    Ignee, Andre; Straub, Bernd; Schuessler, Gudrun; Dietrich, Christoph Frank

    2010-01-01

    Contrast enhanced ultrasound (CEUS) has gained clinical importance over the last years for the characterization of hepatic masses. Its role in extrahepatic indications has been investigated repeatedly but has been less comprehensively studied. Currently more than 50% of renal masses are incidentally diagnosed, mostly by B-mode ultrasound. The method of choice for characterization of renal lesions is contrast enhanced computed tomography (CECT). In the case of cystic lesions CECT refers to the Bosniak classification for cystic lesions to assess the risk of malignant behavior. The majority of masses are renal cell carcinoma, but the exact proportion is controversial. Disadvantages of CECT are a significant risk for patients with impaired renal function, allergic reactions and hyperthyroidism due to iodinated contrast agents. Several studies concerning CEUS for the characterization of both solid and cystic renal lesions have been published, but prospective multicenter studies are missing, the presented data being mainly descriptive. The aim of the this manuscript is to review the current literature for CEUS in renal masses, to summarize the available data and focus on possible concepts for studies in the future. PMID:21160736

  14. Photoacoustic cell for ultrasound contrast agent characterization.

    PubMed

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

    2010-10-01

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

  15. Photoacoustic cell for ultrasound contrast agent characterization

    NASA Astrophysics Data System (ADS)

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

    2010-10-01

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

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

    PubMed

    McAllister Byun, Tara; 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 neutralised. 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 neutralised 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 in this article. PMID:26325303

  17. 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

  18. Recent Experiences and Advances in Contrast-Enhanced Subharmonic Ultrasound

    PubMed Central

    Eisenbrey, John R.; Liu, Ji-Bin; Forsberg, Flemming

    2015-01-01

    Nonlinear contrast-enhanced ultrasound imaging schemes strive to suppress tissue signals in order to better visualize nonlinear signals from blood-pooling ultrasound contrast agents. Because tissue does not generate a subharmonic response (i.e., signal at half the transmit frequency), subharmonic imaging has been proposed as a method for isolating ultrasound microbubble signals while suppressing surrounding tissue signals. In this paper, we summarize recent advances in the use of subharmonic imaging in vivo. These advances include the implementation of subharmonic imaging on linear and curvilinear arrays, intravascular probes, and three-dimensional probes for breast, renal, liver, plaque, and tumor imaging. PMID:26090430

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. Feasibility of percutaneous contrast ultrasound-guided cholecystography in dogs.

    PubMed

    Ji, Seoyeoun; Jung, Sunyoung; Kim, Boeun; Jung, Joohyun; Yoon, Junghee; Choi, Mincheol

    2015-01-01

    Differentiating hepatocellular disease versus biliary obstruction can be challenging in dogs presented for icterus. The purpose of this prospective study was to determine the feasibility of percutaneous contrast ultrasound-guided cholecystography in dogs. Ten normal dogs weighing 7.6-13.0 kg (median 9.8 kg) were recruited. All dogs were considered normal based on complete blood count, serum chemistry profile, ultrasound examination, and percutaneous radiographic cholecystography. Percutaneous contrast ultrasound-guided cholecystography was performed using 0.5 ml of commercially available contrast agent and two conventional ultrasound machines for simultaneous scanning at two different locations. Two observers independently evaluated the time to initial detection of contrast in the proximal duodenum and duration of contrast enhancement via visual monitoring. Dynamic contrast enhancement was calculated using time-intensity curves. Mean (± SD) and median (range) of time to initial detection were 8.60 s (± 3.35) and 8.0 s (2.0-11.0), respectively, and mean and median duration were 50.45 s (± 23.24) and 53.0 s (20.0 - 70.0), respectively. Mean, median, and range of peak intensity were 114.1 mean pixel value (MPV) (SD ± 30.7), 109.2 MPV, and 79.7-166.7, respectively, and mean, median, and range of time to peak intensity were 26.1 s (SD ± 7.1 s), 24.0 s, and 19.0-41.0 s, respectively. Findings indicated that percutaneous contrast ultrasound-guided cholecystography is a feasible technique for detecting and quantifying patency of the bile duct in normal dogs. Future studies are needed to assess the diagnostic utility of this technique for dogs with biliary obstruction. PMID:25403172

  5. Tunable Diacetylene Polymerized Shell Microbubbles as Ultrasound Contrast Agents

    PubMed Central

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

    2012-01-01

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

  6. Filtering and detection of low contrast structures on ultrasound images

    NASA Astrophysics Data System (ADS)

    Vargas-Quintero, Lorena; Escalante-Ramírez, Boris; Arámbula, Fernando

    2012-06-01

    In this paper, we propose a detection method of low contrast structures in medical ultrasound images. Since noise speckle makes difficult the analysis of ultrasound images, two approaches based on the wavelet and Hermite-transforms for enhancement and noise reduction are compared. These techniques assume that speckle pattern is a random signal characterized by a Rayleigh distribution and affects the image as a multiplicative noise. For the wavelet-based approach, a Bayesian estimator at subband level for pixel classification is used. All the estimation parameters are calculated using an adjustment method derived from the first and second order statistical moments. The Hermite method computes a mask to find those pixels that are corrupted by speckle. In this work, we consider a statistical detection model that depends on the variable size and contrast of the image speckle. The algorithms have been evaluated using several real and synthetic ultrasound images. Combinations of the implemented methods can be helpful for automatic detection applications of tumors in mammographic ultrasound images. The employed filtering techniques are quantitatively and qualitatively compared with other previously published methods applied on ultrasound medical images.

  7. Using ultrasound to steer ultrasound contrast agents: Implications for targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Clark, Alicia; Aliseda, Alberto

    2013-11-01

    Ultrasound can be used to manipulate ultrasound contrast agents (UCAs), micron-sized bubbles used in ultrasound imaging to increase image contrast. The Bjerknes force, resulting from the lagged response of the microbubbles to the oscillatory ultrasound pressure field, can be utilized to steer the microbubbles to a targeted area in the vasculature, with the microbubbles serving as drug delivery vectors and injectors. The response of microbubbles to ultrasound in a sheared flow has shown a complex coupling of ultrasound-induced volume oscillations with hydrodynamic forces: Saffman lift and the Bjerknes force. In this work, the relative influence of these two forces acting in the across-streamlines direction is determined as a function of the Reynolds and Womersley and the excitation to bubble natural frequency ratio. We use in-vitro experiments to study the behavior of microbubbles in physiologically-realistic pulsatile flows. Quantitative information about microbubble trajectories in physiological conditions is necessary to develop models in order to control ultrasound steering of bubble-based drug delivery vectors in the human vasculature.

  8. Contrast-enhanced ultrasound in oncology

    PubMed Central

    Rasmussen, F.

    2011-01-01

    Abstract In patients with known malignant disease, 51% of liver lesions less than 1.5 cm turn out to be benign. Whether the probability of malignancy is high or low, further investigations are often necessary to definitely exclude malignancy. Contrast-enhanced ultrasonography has a prominent role in lesion characterization with a diagnostic accuracy comparable with computed tomography and magnetic resonance imaging. Anti-angiogenic treatment is common in most oncological institutions and the response evaluation is a new challenge with a research focus on the change in tumour vasculature and perfusion. In planning biopsies, CEUS can identify necrotic and viable areas of tumours and improve the diagnostic accuracy. PMID:22186152

  9. 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.

  10. 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.

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

    PubMed

    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. PMID:26459771

  12. 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.

  13. 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

    2014-01-01

    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 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

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

    PubMed

    Miele, Vittorio; 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. Superparamagnetic nanoparticle-inclusion microbubbles for ultrasound contrast agents

    NASA Astrophysics Data System (ADS)

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

    2008-11-01

    We have developed a new type of ultrasound (US) contrast agent, consisting of a gas core, a layer of superparamagnetic iron oxide Fe3O4 nanoparticles (SPIO) and an oil in water outermost layer. The newly developed US contrast agent microbubbles have a mean diameter of 760 nm with a polydisperity index (PI) of 0.699. Our in vitro and in vivo experiments have shown that they have the following advantages compared to gas-encapsulated microbbubbles without SPIO inclusion: (1) they provide better contrast for US images; (2) the SPIO-inclusion microbubbles generate a higher backscattering signal; the mean grey scale is 97.9, which is 38.6 higher than that of microbubbles without SPIO; and (3) since SPIO can also serve as a contrast agent of magnetic resonance images (MRI) in vitro, they can be potentially used as contrast agents for double-modality (MRI and US) clinical studies.

  17. Role of contrast enhanced ultrasound in hepatic imaging.

    PubMed

    Dhamija, Ekta; Paul, Shashi B

    2014-01-01

    Grey scale ultrasound (US) is the first line imaging modality used for the evaluation of liver by the radiologists and clinicians worldwide. It is a simple, inexpensive, safe and an easily available technique. US has the ability to delineate the hepatic parenchyma and differentiate the cystic from solid hepatic lesions. However, it has limited accuracy in the detection and characterization of focal liver lesions (FLL). CEUS is a major breakthrough in ultrasound imaging which evolved with the aim of overcoming these limitations of US. With the use of ultrasound contrast agents (UCAs), CEUS has the ability to detect the intranodular hemodynamics and thereby provide information of the enhancement pattern of the lesion resulting in reliable characterization of the FLL. This capability brings it at par with the cross sectional contrast enhanced imaging techniques of computed tomography and magnetic resonance imaging. UCAs are safe, non-nephrotoxic and thus can be used to evaluate patients with renal failure as well. The technique of CEUS is simple, requires few minutes to perform, portable, lacks ionising radiation and above all is a cost-effective modality. These advantages have made CEUS an established modality for hepatic imaging. Besides detection and characterization of FLL, it also plays a vital role in the management and repeated follow up of treated patients of FLL. Newer clinical applications of CEUS with promising results are also being unravelled . This review highlights the multifaceted role of CEUS in hepatic imaging and its upcoming clinical applications. PMID:26012317

  18. Contrast enhanced ultrasound in pediatric patients: a real challenge.

    PubMed

    Schreiber-Dietrich, D G; Cui, X W; Piscaglia, F; Gilja, O H; Dietrich, C F

    2014-10-01

    Ultrasound (US) imaging in the paediatric population has been a routine technique for decades, in part because of the advantages it offers over other imaging modalities. Off-label use (and its funding) is of the utmost importance in paediatrics because many drugs have not been evaluated in randomised trials in children. As a consequence such drugs are not specifically approved for use in children. This is also true for the contrast agents used in CEUS. The off-label use of CEUS in paediatric patients illustrates the need to deal with unresolved legal issues while at the same time balancing this with the need for high diagnostic performance in daily clinical routine. In addition to approved indications with a focus on the liver and Doppler enhancement, CEUS is safe and effective for the examination of many organs, as recently highlighted by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). This article provides a summary of the available literature describing the utility of CEUS in paediatric patients. Furthermore, we suggest the establishment of a registry to collect data on safety and applications of ultrasound contrast agents in children. A paediatric registry has recently been introduced by EFSUMB (www.efsumb.org). PMID:25313631

  19. 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.

  20. 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. PMID:25453958

  1. Second harmonic inversion for ultrasound contrast harmonic imaging

    NASA Astrophysics Data System (ADS)

    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

    2011-06-01

    Ultrasound contrast agents (UCAs) are small micro-bubbles that behave nonlinearly when exposed to an ultrasound wave. This nonlinear behavior can be observed through the generated higher harmonics in a back-scattered echo. In past years several techniques have been proposed to detect or image harmonics produced by UCAs. In these proposed works, the harmonics generated in the medium during the propagation of the ultrasound wave played an important role, since these harmonics compete with the harmonics generated by the micro-bubbles. We present a method for the reduction of the second harmonic generated during nonlinear-propagation-dubbed second harmonic inversion (SHI). A general expression for the suppression signals is also derived. The SHI technique uses two pulses, p' and p'', of the same frequency f0 and the same amplitude P0 to cancel out the second harmonic generated by nonlinearities of the medium. Simulations show that the second harmonic is reduced by 40 dB on a large axial range. Experimental SHI B-mode images, from a tissue-mimicking phantom and UCAs, show an improvement in the agent-to-tissue ratio (ATR) of 20 dB compared to standard second harmonic imaging and 13 dB of improvement in harmonic power Doppler.

  2. 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

  3. 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

  4. Adaptive windowing in contrast-enhanced intravascular ultrasound imaging.

    PubMed

    Lindsey, Brooks D; Martin, K Heath; Jiang, Xiaoning; Dayton, Paul A

    2016-08-01

    Intravascular ultrasound (IVUS) is one of the most commonly-used interventional imaging techniques and has seen recent innovations which attempt to characterize the risk posed by atherosclerotic plaques. One such development is the use of microbubble contrast agents to image vasa vasorum, fine vessels which supply oxygen and nutrients to the walls of coronary arteries and typically have diameters less than 200μm. The degree of vasa vasorum neovascularization within plaques is positively correlated with plaque vulnerability. Having recently presented a prototype dual-frequency transducer for contrast agent-specific intravascular imaging, here we describe signal processing approaches based on minimum variance (MV) beamforming and the phase coherence factor (PCF) for improving the spatial resolution and contrast-to-tissue ratio (CTR) in IVUS imaging. These approaches are examined through simulations, phantom studies, ex vivo studies in porcine arteries, and in vivo studies in chicken embryos. In phantom studies, PCF processing improved CTR by a mean of 4.2dB, while combined MV and PCF processing improved spatial resolution by 41.7%. Improvements of 2.2dB in CTR and 37.2% in resolution were observed in vivo. Applying these processing strategies can enhance image quality in conventional B-mode IVUS or in contrast-enhanced IVUS, where signal-to-noise ratio is relatively low and resolution is at a premium. PMID:27161022

  5. Ultrasound contrast agents and their use in monitoring therapy

    NASA Astrophysics Data System (ADS)

    Ferrara, Katherine; Dayton, Paul; Shortencarrier, Michaelann; Kruse, Dustin

    2003-10-01

    The shell of ultrasound contrast agents can be modified to include a molecular targeting ligand, and the properties of the agent with and without molecular targeting can be used to monitor changes produced by a therapy. We have investigated the use of ligands targeted to an integrin expressed in cancer, whose expression correlates with tumor grade. Acoustic studies illustrate a 3- to 20-fold increase in echo amplitude from integrin-expressing cells exposed to the targeted contrast agent, as compared to controls, and depending on cell type, stimulation, and targeting ligand. Changes in integrin expression with therapy may be important in future studies. We have also developed a system to quantify small changes in vascular parameters due to effects of new anti-angiogenic drugs using the intrinsic properties of contrast agents. Regions containing intravascular contrast agents are identified using a strategy that combines subharmonic and phase inversion imaging. As predicted by a Rayleigh-Plesset analysis, this strategy can successfully detect flow over a range of transmission frequencies from 4-6 MHz. We demonstrate that regions of viable tumor as small as 1 mm, as verified by histology, can be detected and show similar morphology to images acquired with computed tomography (CT).

  6. Intraoperative Contrast Enhanced Ultrasound Evaluates the Grade of Glioma

    PubMed Central

    Cheng, Ling-Gang; He, Wen; Zhang, Hong-Xia; Song, Qian; Ning, Bin; Li, Hui-Zhan; He, Yan; Lin, Song

    2016-01-01

    Objective. The aim of our study was to investigate the value of intraoperative contrast enhanced ultrasound (CEUS) for evaluating the grade of glioma and the correlation between microvessel density (MVD) and vascular endothelial growth factor (VEGF). Methods. We performed intraoperative conventional ultrasound (CUS) and CEUS on 88 patients with gliomas. All of the patients have undergone surgery and obtained the results of pathology. All patients have undergone intraoperative CUS and CEUS to compare the characteristics of different grade gliomas and the results of CUS and CEUS were compared with pathological results. Results. The time to start (TTS) and time to peak (TTP) of low grade glioma (LGG) were similar to those of edema and normal brain surrounding glioma. The enhanced extent of LGG was higher than that of the normal brain and edema. The TTS and TTP of high grade glioma were earlier than those of the edema and normal brain surrounding glioma. The enhancement of HGG was higher than that of LGG. The absolute peak intensity (API) was correlated with MVD and VEGF. Conclusion. Intraoperative CEUS could help in determining boundary of peritumoral brain edema of glioma. Intraoperative CEUS parameters in cerebral gliomas could indirectly reflect the information of MVD and VEGF. PMID:27069921

  7. 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

  8. Contrast imaging ultrasound detects abnormalities in the marmoset ovary.

    PubMed

    Hastings, J M; Morris, K D; Allan, D; Wilson, H; Millar, R P; Fraser, H M; Moran, C M

    2012-12-01

    The development of a functional vascular tree within the primate ovary is critical for reproductive health. To determine the efficacy of contrast agents to image the microvascular environment within the primate ovary, contrast ultrasonography was performed in six reproductive-aged female common marmosets (Callithrix jacchus) during the late luteal phase of the cycle, following injection of Sonovue™. Regions of interest (ROIs), representing the corpus luteum (CL) and noncorpus luteum ovarian tissue (NCLOT), were selected during gray-scale B-mode ultrasound imaging. The magnitude of backscatter intensity of CL and NCLOT ROIs were calculated in XnView, post hoc: subsequent gamma-variate modeling was implemented in Matlab to determine perfusion parameters. Histological analysis of these ovaries revealed a total of 11 CL, nine of which were identified during contrast ultrasonography. The median enhancement ratio was significantly increased in the CL (5.54AU; 95% CI -2.21-68.71) compared to the NCLOT (2.82AU; 95% CI 2.73-15.06; P < 0.05). There was no difference in time parameters between the CL and NCLOT. An additional avascular ROI was identified in the ovary of Animal 5, both histologically and by ultrasonography. This cystic ROI displayed a markedly lower enhancement ratio (0.79AU) and higher time parameters than mean CL and NCLOT, including time to peak and time to wash out. These data demonstrate, for the first time, the ability of commercially available contrast agents, to differentiate structures within the nonhuman primate ovary. Contrast-enhanced ultrasonography has a promising future in reproductive medicine. PMID:22890799

  9. Benign liver lesions: grey-scale and contrast-enhanced ultrasound appearances

    PubMed Central

    Obaro, A E

    2015-01-01

    Ultrasound is often the first point of detection of liver lesions, with up to 75% of liver lesions detected at ultrasound having benign histology. In 2012, NICE issued recommendations that ultrasound contrast be used for the evaluation of incidentally discovered liver lesions. This has been demonstrated to provide a rapid and cost-effective evaluation for incidental liver lesions, in many cases precluding the need for further CT or MRI scans. The aim of this review is to demonstrate the ultrasound features of benign liver lesions, and to demonstrate their further characterisation with contrast ultrasound.

  10. 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

  11. 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

  12. 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

  13. Indocyanine green-loaded photoacoustic nanodroplets: dual contrast nanoconstructs for enhanced photoacoustic and ultrasound imaging.

    PubMed

    Hannah, Alexander; Luke, Geoffrey; Wilson, Katheryne; Homan, Kimberly; Emelianov, Stanislav

    2014-01-28

    Recently, perfluorocarbon (PFC) nanodroplets were introduced as contrast agents for imaging and image-guided therapy. For example, in sonography, high-intensity ultrasound pulses were used to phase-transition liquid perfluorocarbon to produce gas microbubbles. More recently, perfluorocarbon nanodroplets with encapsulated gold nanorods were used as dual ultrasound/photoacoustic contrast agents. To expedite clinical translation, we synthesized and characterized ICG-loaded perfluorocarbon nanodroplets, i.e., constructs comprising biocompatible, nontoxic and biologically safe materials. We then demonstrated enhanced photoacoustic contrast through optically triggered phase transition of PFC nanodroplets and ultrasound contrast from the resulting PFC bubbles. We assessed the quality enhancement of photoacoustic and ultrasound images through analysis of contrast and contrast-to-noise ratio. We further investigated the changes in image contrast due to increased ambient temperature. Our studies suggest that ICG-loaded perfluorocarbon nanodroplets may become a valuable tool for various imaging modalities, and have promising therapeutic applications. PMID:24303934

  14. BROADBAND ATTENUATION MEASUREMENTS OF PHOSPHOLIPID-SHELLED ULTRASOUND CONTRAST AGENTS

    PubMed Central

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

    2014-01-01

    The aim of this study was to characterize the frequency-dependent acoustic attenuation of three phospholipid-shelled ultrasound contrast agents (UCAs): Definity, MicroMarker and echogenic liposomes. A broadband through-transmission technique allowed for measurement over 2 to 25 MHz with a single pair of transducers. Viscoelastic shell parameters of the UCAs were estimated using a linearized model developed by N. de Jong, L. Hoff, T. Skotland and N. Bom (Ultrasonics 1992; 30:95–103). The effect of diluent on the attenuation of these UCA suspensions was evaluated by performing attenuation measurements in 0.5% (w/v) bovine serum albumin and whole blood. Changes in attenuation and shell parameters of the UCAs were investigated at room temperature (25°C) and physiologic temperature (37°C). The attenuation of the UCAs diluted in 0.5% (w/v) bovine serum albumin was found to be identical to the attenuation of UCAs in whole blood. For each UCA, attenuation was higher at 37°C than at 25°C, underscoring the importance of conducting characterization studies at physiologic temperature. Echogenic liposomes exhibited a larger increase in attenuation at 37°C versus 25°C than either Definity or MicroMarker. PMID:24262056

  15. 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.

  16. Using light scattering to measure the response of individual ultrasound contrast microbubbles subjected to pulsed ultrasound in vitro.

    PubMed

    Guan, Jingfeng; Matula, Thomas J

    2004-11-01

    Light scattering was used to measure the radial pulsations of individual ultrasound contrast microbubbles subjected to pulsed ultrasound. Highly diluted Optison or Sonazoid microbubbles were injected into either a water bath or an aqueous solution containing small quantities of xanthan gum. Individual microbubbles were insonified by ultrasound pulses from either a commercial diagnostic ultrasound machine or a single element transducer. The instantaneous response curves of the microbubbles were measured. Linear and nonlinear microbubble oscillations were observed. Good agreement was obtained by fitting a bubble dynamics model to the data. The pulse-to-pulse evolution of individual microbubbles was investigated, the results of which suggest that the shell can be semipermeable, and possibly weaken with subsequent pulses. There is a high potential that light scattering can be used to optimize diagnostic ultrasound techniques, understand microbubble evolution, and obtain specific information about shell parameters. PMID:15603131

  17. 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.

  18. 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

  19. Conventional ultrasound and contrast-enhanced ultrasound in evaluating the severity of Crohn’s disease

    PubMed Central

    Liu, Chang; Xu, Xiao-Rong; Xu, Hui-Xiong; Liu, Zhan-Ju; Zhang, Yi-Feng; Sun, Li-Ping; Xu, Jun-Mei; Liu, Lin-Na; Guo, Le-Hang; Bo, Xiao-Wan

    2015-01-01

    Objective: To evaluate the value of conventional ultrasound and contrast-enhanced ultrasound (CEUS) in determining the severity of active Crohn’s disease. Methods: Thirty-seven patients who were considered to be in active period of Crohn’s disease were included. Conventional ultrasound was employed to measure the thicknesses of interior, exterior and the whole bowel walls. Qualitative and quantitative CEUS analysis of the interior, exterior and the whole intestinal walls were also performed. Correlations between these methods and the severity of Crohn’s disease were assessed. Results: Endoscopy grading system identified 19 patients with mild disease and 18 with severe disease. In discriminating severe Crohn’s disease from mild disease, the cut-off value for the thickness of the entire bowel wall was 6.8 mm by receiver operating characteristic (ROC) analysis, with area under ROC (AUROC) of 0.84, sensitivity of 94.4%, specificity of 68.4%, positive predictive value (PPV) of 61.1%, negative predictive value (NPV) of 69.2%, and Youden’s index of 0.628. The cut-off value for thickness of the interior intestinal wall was 4.8 mm (AUROC, 0.81; sensitivity, 88.9%; specificity, 63.2%; PPV, 85.7%; NPV, 69.6%; Youden’s index, 0.521). The sensitivity, specificity, PPV, NPV, accuracy, and Youden’s index of CEUS qualitative analysis were 100% (18/18), 57.9% (11/19), 64.3% (18/26), 100% (11/11), 78.4% (29/37), and 0.579, respectively. Quantitative comparison revealed that patients with mild disease and those with severe disease differed only in Imax of inner bowel wall enhancement (2746.9 ± 911 vs. 12814.5 ± 9802.4; P = 0.02) and Imax of entire wall enhancement (2106 ± 660 vs. 9864 ± 6994; P = 0.03). The cut-off value for the Imax of the entire bowel wall was 3067, with the AUROC of 0.96, sensitivity of 100%, specificity of 67.7%, PPV of 100%, NPV of 88.9%, and Youden’s index of 0.677; and the cut-off value for the Imax of the interior intestinal layer was 3356

  20. 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

  1. 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. PMID:26441654

  2. Contrast-Enhanced Ultrasound: Practical Review for the Assessment of Hepatic and Renal Lesions.

    PubMed

    Denham, Stephanie LeeAnn Wilson; Alexander, Lauren F; Robbin, Michelle L

    2016-06-01

    The use of microbubble contrast greatly enhances the ability of ultrasound to delineate structures and therefore aid in diagnosis. Ultrasound microbubble contrast agents are composed of low-solubility gas encapsulated in a biomaterial shell. These agents use the physics of ultrasound imaging to effectively identify and characterize focal hepatic and renal lesions. Not only can contrast agents be used to evaluate multiple phases of lesion contrast enhancement, but ultrasound also allows for real-time study of enhancement patterns. The short half-life and intravascular location of the microbubbles allows for multiple, sequential administrations of contrast to observe enhancement of lesions in different sites. Furthermore, the ability to perform imaging without ionizing radiation and the lack of nephrotoxicity make contrast-enhanced ultrasound an ideal evaluation method for patients who need serial surveillance or in whom imaging options are severely limited because of renal insufficiency. These techniques are widely used in many countries for diagnostic radiological purposes; however, the lack of both Food and Drug Administration approval and reimbursement for noncardiac hospital-based imaging has delayed widespread use in the United States. Despite these limitations, continued research and innovations in ultrasound contrast make it essential to have a working knowledge of the typical enhancement patterns of frequently seen hepatic and renal lesions as these techniques offer an alternative option for contrast imaging. PMID:27233070

  3. DNA-Coated Microbubbles with Biochemically-Tunable Ultrasound Contrast Activity

    PubMed Central

    Nakatsuka, Matthew A.; Hsu, Mark J.

    2013-01-01

    Changing the mechanical properties of the microbubble shell in response to a biochemical stimulus leads to vast changes in both ultrasound-induced bubble dynamics and contrast-enhanced ultrasound imaging. Here, DNA-coated microbubbles are shown to be a simple and highly versatile platform that can silence and re-activate contrast activity in response to the introduction and removal of biochemical stimuli. PMID:21956383

  4. 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.

  5. Highly Uniform Perfluoropropane-Loaded Cerasomal Microbubbles As a Novel Ultrasound Contrast Agent.

    PubMed

    Zhang, Chunyang; Wang, Zhu; Wang, Chunan; Li, Xiongjun; Liu, Jie; Xu, Ming; Xu, Shuyu; Xie, Xiaoyan; Jiang, Qing; Wang, Wei; Cao, Zhong

    2016-06-22

    Microbubbles are widely used as ultrasound contrast agents owing to their excellent echoing characteristics under ultrasound radiation. However, their short sonographic duration and wide size distribution still hinder their application. Herein, we present a hard-template approach to produce perfluoropropane-loaded cerasomal microbubbles (PLCMs) with uniform size and long sonographic duration. The preparation of PLCMs includes deposition of Si-lipids onto functionalized CaCO3 microspheres, removal of their CaCO3 cores and mild infusion of perfluoropropane. In vitro and in vivo experiments showed that PLCMs had excellent echoing characteristics under different ultrasound conditions. More importantly, PLCMs could be imaged for much longer than SonoVue (commercially used microbubbles) under the same ultrasound parameters and concentrations. Our results demonstrated that PLCMs have great potential for use as a novel contrast agent in ultrasound imaging. PMID:26114237

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

  7. 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.

  8. Efficacy of contrast enhanced grey scale ultrasound in characterisation of hepatic focal lesions: A pilot study

    PubMed Central

    Joshi, P.; George, R.A.; Tyagi, A.K.; Sinha, Anamika

    2014-01-01

    Background Contrast enhanced ultrasound (CEUS) has recently gained widespread acceptance as an adjunct to conventional grey scale ultrasound. The present pilot study was undertaken to evaluate the efficacy of this technique in characterisation of hepatic focal lesions. Methods Adult patients who had at least one focal liver lesion underwent ultrasound evaluation in regular and contrast mode before and after intravenous administration of sulphur hexafluoride. The diagnoses were confirmed by comparison with a reference standard (multidetector CT), response to treatment or pathological correlation. Results The rate of correct diagnosis for unenhanced ultrasound was 54%, CEUS was 72% and multidetector CT (MDCT) was 92%. A comparison of unenhanced ultrasound versus CEUS using the McNemar test yielded a p value of 0.0704 (>0.05). However, comparison of CEUS versus MDCT using the McNemar test yielded a p value of 0.0265 (<0.05). Additionally, comparison of unenhanced ultrasound versus MDCT using the McNemar test yielded a p value of <0.0001. Conclusion CEUS increases diagnostic efficacy over unenhanced ultrasound but does not have any significant advantages over MDCT. Currently it may be used as a problem solving tool in atypical haemangiomas, echogenic focal liver lesions, contrast sensitivity and to avoid multiple studies utilising ionising radiation. PMID:25378775

  9. Contrast-enhanced molecular ultrasound differentiates endoglin genotypes in mouse embryos.

    PubMed

    Denbeigh, J M; Nixon, B A; Lee, J J Y; Jerkic, M; Marsden, P A; Letarte, M; Puri, M C; Foster, F S

    2015-01-01

    Targeted ultrasound contrast imaging has the potential to become a reliable molecular imaging tool. A better understanding of the quantitative aspects of molecular ultrasound technology could facilitate the translation of this technique to the clinic for the purposes of assessing vascular pathology and detecting individual response to treatment. The objective of this study was to evaluate whether targeted ultrasound contrast-enhanced imaging can provide a quantitative measure of endogenous biomarkers. Endoglin, an endothelial biomarker involved in the processes of development, vascular homeostasis, and altered in diseases, including hereditary hemorrhagic telangiectasia type 1 and tumor angiogenesis, was the selected target. We used a parallel plate perfusion chamber in which endoglin-targeted (MBE), rat isotype IgG2 control and untargeted microbubbles were perfused across endoglin wild-type (Eng+/+), heterozygous (Eng+/-) and null (Eng-/-) embryonic mouse endothelial cells and their adhesion quantified. Microbubble binding was also assessed in late-gestation, isolated living transgenic Eng+/- and Eng+/+ embryos. Nonlinear contrast-specific ultrasound imaging performed at 21 MHz was used to collect contrast mean power ratios for all bubble types. Statistically significant differences in microbubble binding were found across genotypes for both in vitro (p<0.05) and embryonic studies (p<0.001); MBE binding was approximately twofold higher in Eng+/+ cells and embryos compared with their Eng+/- counterparts. These results suggest that molecular ultrasound is capable of reliably differentiating between molecular genotypes and relating receptor densities to quantifiable molecular ultrasound levels. PMID:25298070

  10. 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

  11. 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

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    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.

  13. 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. PMID:26323823

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

    NASA Astrophysics Data System (ADS)

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

    2012-11-01

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

  15. Diagnostic and therapeutic research on ultrasound microbubble/nanobubble contrast agents (Review).

    PubMed

    Ma, Jing; Xu, Chang Song; Gao, Feng; Chen, Ming; Li, Fan; Du, Lian Fang

    2015-09-01

    The contrast enhanced imaging function of ultrasound contrast agents (UCAs) has been extensively investigated using physical acoustic signatures. It has a number of novel applications, including tissue‑specific molecular imaging and multi‑modal imaging. In addition there are numerous other therapeutic applications of UCAs, for example as vehicles for drug or gene delivery. These uses are discussed, as well as the acoustically‑induced biological effects, including ultrasound targeted microbubble destruction (UTMD). This review also explores the considerations for the safe use of UCA from an acoustic standpoint. The scope of the application of UCA has markedly expanded in recent years, and it is a rapidly growing field of medical research. The current article reviews recent advances in the diagnostic and therapeutic applications of ultrasound microbubble/nanobubble contrast agents. PMID:26081968

  16. 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.

  17. 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

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

    PubMed

    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-iCEUS s t a r t ) and after (3D-iCEUS e n d ) tumor resection. Based on rigid registration techniques, a preselected vascular segment in cT1MR is searched in 3D-iCEUS s t a r t and 3D-iCEUS e n d data. The method was validated by using three similarity measures (Normalized Gradient Field, Normalized Mutual Information and Normalized Cross Correlation). Tests were performed on data obtained from ten patients overcoming a brain tumor operation and it succeeded in nine cases. Despite the small size of the vascular structures, the artifacts in the ultrasound images and the brain tissue deformations, blood vessels were successfully identified. PMID:27070610

  19. Effect of gas-containing microspheres and echo contrast agents on free radical formation by ultrasound.

    PubMed

    Kondo, T; Misík, V; Riesz, P

    1998-09-01

    Stabilized microbubbles (microspheres) are widely used to enhance the contrast of ultrasound imaging. Our data provide direct evidence that the contrast agents, Levovist, PVC-AN (polyvinylidene chloride-acrylonitryl copolymer), and Albunex (compared to 5% human albumin), at concentrations comparable to those used for ultrasound imaging, enhance H2O2 production (through the superoxide-dependent pathway) in air-saturated aqueous solutions exposed to 47 kHz ultrasound above the cavitation threshold. These agents also act as scavengers of .H atoms and .OH radicals, thus lowering H2O2 formation (by recombination of .OH radicals) in argon-saturated solutions. EPR spin trapping also reveals that secondary radicals derived from the contrast agents are produced by reactions with .H and .OH which are formed by pyrolysis of water inside cavitation bubbles. In addition, the contrast agents themselves undergo pyrolysis reactions in the cavitation bubbles as demonstrated by formation of methyl radicals. Possible deleterious consequences of the formation of sonochemical intermediates may have to be assessed, particularly since some of the echo contrast agents have been shown to lower the cavitation threshold of diagnostic ultrasound. Unlike the microspheres formed from organic molecules, inorganic microspheres, Eccospheres, because of their stability and inert nature with respect to participation in free radical processes, appear to be suitable tools for enhancing the yields of aqueous sonochemical reactions. PMID:9741598

  20. 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. PMID:25701526

  1. 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

  2. Feasibility and Usefulness of Intra-Cavitary Contrast-Enhanced Ultrasound in Percutaneous Nephrostomy.

    PubMed

    Cui, Xin-Wu; Ignee, Andre; Maros, Tiberius; Straub, Bernd; Wen, Jian-Guo; Dietrich, Christoph F

    2016-09-01

    The aim of this study was to evaluate the feasibility and utility of intra-cavitary contrast enhanced ultrasound (ICCEUS) in guiding percutaneous nephrostomy (PCN) and assessing complications. Forty-five ultrasound-guided PCNs were performed in 35 patients with hydronephrosis resulting from urinary tract obstruction. Ultrasound contrast agent (0.1 mL diluted in 20-30 mL saline) was injected through the puncture needle and the drainage tube to precisely locate the device and obstruction, with the fluoroscopy results considered the gold standard. ICCEUS was performed again the next day to assess complications. All 45 PCNs were successfully performed under the guidance of ultrasound. With ICCEUS, we could confirm the correct insertion of needle and catheter and locate the obstruction in all 35 patients, with fluoroscopic results as the gold standard. Catheter dislodgement was diagnosed by administration of ultrasound contrast agent in 5 patients. Hematoma (1 patient) and urine leakage (1 patient) were also observed. With the advantages of lack of exposure to radiation, performance in real time and bedside availability, ICCEUS has the potential to become a new modality to guide PCN and assess catheter-related complications. PMID:27262520

  3. Selective imaging of adherent targeted ultrasound contrast agents

    PubMed Central

    Zhao, S; Kruse, D E; Ferrara, K W; Dayton, P A

    2007-01-01

    The goal of ultrasonic molecular imaging is the detection of targeted contrast agents bound to receptors on endothelial cells. We propose imaging methods that can distinguish adherent microbubbles from tissue and from freely circulating microbubbles, each of which would otherwise obscure signal from molecularly targeted adherent agents. The methods are based on a harmonic signal model of the returned echoes over a train of pulses. The first method utilizes an ‘image–push–image’ pulse sequence where adhesion of contrast agents is rapidly promoted by acoustic radiation force and the presence of adherent agents is detected by the signal change due to targeted microbubble adhesion. The second method rejects tissue echoes using a spectral high-pass filter. Free agent signal is suppressed by a pulse-to-pulse low-pass filter in both methods. An overlay of the adherent and/or flowing contrast agents on B-mode images can be readily created for anatomical reference. Contrast-to-tissue ratios from adherent microbubbles exceeding 30 dB and 20 dB were achieved for the two methods proposed, respectively. The performance of these algorithms is compared, emphasizing the significance and potential applications in ultrasonic molecular imaging. PMID:17404455

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

    PubMed

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

    2015-04-01

    Zenker's diverticulum (ZD) may be misdiagnosed on conventional ultrasound as a thyroid nodule or other lesion. A barium esophagram is usually used to confirm the diagnosis; however, this procedure exposes the patient to radiation. The aim of this study was to evaluate the feasibility of using swallow contrast-enhanced ultrasound (swallow-CEUS) to diagnose ZD. Ten consecutive patients with ZD (7 men and 3 women, aged 67 ± 11 y) were included in the study. In 4 patients, ZD was incidentally found on head and neck ultrasound, and in 6 patients, ZD was suspected because of dysphagia. All lesions could be detected on conventional ultrasound before swallow-CEUS. Ten healthy volunteers (8 men and 2 women, aged 60 ± 12 y) were chosen as a control group. Written informed consent was obtained. With the patient in the sitting or upright position, conventional ultrasound was performed first to image the lesion, then the patient was asked to swallow ultrasound contrast agent (UCA) (2-4 drops of SonoVue diluted with about 200 mL of tap water). Transity of the contrast agent in the esophagus was imaged with CEUS. Retention of the UCA in the diverticulum was monitored for at least 3 min. All patients underwent a barium esophagram as the gold standard. Swallow-CEUS revealed that in all patients (100%), the UCA was transported from the pharynx to the esophagus while the patient swallowed. ZD appeared as a pouch-shaped structure at the posterior pharyngo-esophageal junction that retained UCA longer than 3 min. The barium esophagram confirmed the diagnosis of ZD in all patients. For the 10 volunteers, no abnormal structure (retaining UCA) was detected during or after swallowing of UCA. With the advantages of no radiation and bedside availability, swallow-CEUS may become a method of choice in confirmation of the diagnosis of ZD, especially when ZD is suspected on conventional ultrasound. PMID:25701519

  5. 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. PMID:25682465

  6. 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. PMID:25906100

  7. The Value of Contrast-Enhanced Ultrasound in the Diagnosis of Cesarean Scar Pregnancy

    PubMed Central

    Xiong, Xi; Yan, Ping; Gao, Chunyan; Sun, Qiulei; Xu, Fenglian

    2016-01-01

    Objective. To evaluate the value of contrast-enhanced ultrasound (CEUS) in the cesarean scar pregnancy (CSP). Methods. Clinical data from 92 patients with lower uterine segment pregnancy, who underwent conventional ultrasound and CEUS examination in the Department of Obstetrics and Gynecology, were collected by Xinqiao Hospital Third Military Medical University from March 2014 to March 2015. The parameters of ultrasound contrast time-intensity curve (TIC), including arrival time, time to peak, time from peak to one half, basic intensity, peak intensity, and wash-in slope, were analyzed. Results. Of the 92 cases of patients with pregnancy in the lower uterine segment, 52 cases were CSP, and 40 cases were intrauterine pregnancy. CEUS was significantly better than conventional ultrasound in terms of sensitivity, negative predictive value, Youden index, and diagnostic accuracy (P < 0.05). There was no significant difference in specificity and positive predictive value (P > 0.05). Conclusion. CEUS has a higher accuracy than conventional ultrasound in diagnosis of CSP. PMID:27340659

  8. Nanobubble Ultrasound Contrast Agents for Enhanced Delivery of Thermal Sensitizer to Tumors Undergoing Radiofrequency Ablation

    PubMed Central

    Perera, Reshani H.; Solorio, Luis; Wu, Hanping; Gangolli, Mihika; Silverman, Eric; Hernandez, Christopher; Peiris, Pubudu M.; Broome, Ann-Marie

    2013-01-01

    Purpose Pluronic has been shown to sensitize various tumor cell lines to chemotherapy and hyperthermia by altering the membrane fluidity, depleting ATP, and modulating the heat shock protein 70 expression. In our prior work, Pluronic was also used to formulate nanosized ultrasound contrast agents. In the current study we evaluate the use of these contrast agents as vehicles for image-guided delivery of Pluronic to improve outcomes of tumor radiofrequency (RF) ablation. Methods Lipid-shelled Pluronic nanobubbles were prepared and examined for size distribution, zeta potential, stability, biodistribution, accumulation of nanobubbles in the tumor, and treatment efficacy. LS174-T xenograft tumor-bearing mice were used to evaluate tumor growth suppression and measure treatment efficacy after RF ablation. Results The average diameter of Pluronic bubbles was 230 nm, and initial bubble echogenicity was 16 dB. In vitro, cells exposed to Pluronic nanobubbles exhibited low cytotoxicity in the absence of ultrasound, even if heat (43°C) was applied. When the cells were exposed to Pluronic nanobubbles, heat, and ultrasound; viability was significantly reduced. In vivo, tumors treated with ultrasound-modulated nanobubbles prior to RF ablation showed a significant reduction in growth compared to the RF alone (P<0.05). Conclusion Lipid and Pluronic-shelled, echogenic nanobubbles combined with ultrasound modulation can serve as an effective theranostic method for sensitization of tumors to RF ablation. PMID:23943542

  9. Effect of focused ultrasound applied with an ultrasound contrast agent on the tight junctional integrity of the brain microvascular endothelium

    PubMed Central

    Sheikov, Nickolai; McDannold, Nathan; Sharma, Shipra; Hynynen, Kullervo

    2008-01-01

    Previous studies have investigated a potential method for targeted drug delivery in the central nervous system that uses focused ultrasound bursts combined with an ultrasound contrast agent to temporarily disrupt the blood-brain barrier (BBB). The purpose of this work was to investigate the integrity of the tight junctions (TJs) in rat brain microvessels after this BBB disruption. 1.5-MHz ultrasound bursts in combination with a gas contrast agent (Optison) was applied at two locations in the brain in 25 rats to induce BBB disruption. Using immunoelectron microscopy, the distributions of the TJ-specific transmembrane proteins occludin, claudin-1, claudin-5, and of submembranous ZO-1 were examined at 1, 2, 4, 6 and 24 h after sonication. A quantitative evaluation of the protein expression was made by counting the number of immunosignals per micrometer in the junctional clefts. BBB disruption at the sonicated locations was confirmed by the leakage of intravenously administered horseradish peroxidase (HRP, m.w. 40,000 Da) and lanthanum chloride (La3+, m.w. ~ 139 Da). Leakage of these agents was observed at 1 and 2 h and in a few vessels at 4 h after ultrasound application. These changes were paralleled by the apparent disintegration of the TJ complexes, as evidenced by the redistribution and loss of the immunosignals for occludin, claudin-5 and ZO-1. Claudin-1 seemed less involved. At 6 and 24 h after sonication, no HRP or lanthanum leakage was observed, and the barrier function of the TJs, as indicated by the localization and density of immunosignals, appeared to be completely restored. This study provides the first direct evidence that ultrasound bursts combined with a gas contrast agent cause disassembling of the TJ molecular structure, leading to loss of the junctional barrier functions in brain microvessels. The BBB disruption appears to last up to 4 h after sonication and permits the paracellular passage of agents with molecular weights up to at least 40 k

  10. 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

  11. Clinical Value of Contrast-Enhanced Ultrasound in Diagnosis of Hyperechoic Liver Lesions

    PubMed Central

    Liu, Junjie; Wang, Dan; Li, Hongxue; Li, Hang; Zhou, Ting; Zhao, Shengfa; Ding, Zhanling

    2015-01-01

    Background The purpose of this study was to investigate the values of contrast-enhanced ultrasound (CEUS) in the diagnosis and differential diagnosis of hyperechoic liver lesions. Material/Methods The CEUS findings of 102 patients with hyperechoic liver lesions identified by 2-dimensional ultrasound in the Affiliated Tumor Hospital of Guangxi Medical University were reviewed and analyzed. Results A total of 135 lesions were analyzed, of which malignant lesions were found in 72 patients and benign lesions in 63, with a CEUS accuracy rate of 91.11%, which was significantly higher than that of conventional ultrasound (74.81%; P<0.05). Conclusions CEUS can improve the accuracy rate of ultrasonography in the diagnosis and differential diagnosis of hyperechoic liver lesions. PMID:26394170

  12. 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

  13. 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

  14. 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. PMID:26025507

  15. Dynamic Vascular Pattern (DVP), a quantification tool for contrast enhanced ultrasound.

    PubMed

    Cui, X W; Ignee, A; Jedrzejczyk, M; Dietrich, C F

    2013-05-01

    Contrast-enhanced ultrasound (CEUS) is widely applied in tumour diagnosis, especially for focal liver lesions (FLL), due to its high sensitivity and specificity. According to the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) CEUS guidelines (2012) and non-liver guidelines (2011), the majority of tumours, regardless of location, show specific CEUS enhancement patterns that can distinguish benign from malignant lesions. However, even experienced clinicians evaluating FLL may find occasional irregularities in these patterns, due to particular FLL pathologies, that make a definitive diagnosis difficult. Hence, there is a need to train physicians to utilize contrast enhancement kinetics to aid in the correct interpretation of data from CEUS examinations in patients with divergent liver tumour pathologies. Here we report on a CEUS quantitation software, SonoLiver®, to verify and improve diagnostic accuracy in the characterization of suspicious liver lesions through the analysis of dynamic vascular patterns (DVP). PMID:23681894

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

  17. Dynamic contrast-enhanced ultrasound of slaughterhouse porcine livers in machine perfusion.

    PubMed

    Izamis, Maria-Louisa; Efstathiades, Andreas; Keravnou, Christina; Leen, Edward L; Averkiou, Michalakis A

    2014-09-01

    The aim of this study was to enable investigations into novel imaging and surgical techniques by developing a readily accessible, versatile liver machine perfusion system. Slaughterhouse pig livers were used, and dynamic contrast-enhanced ultrasound was introduced to optimize the procurement process and provide real-time perfusion monitoring. The system comprised a single pump, oxygenator, bubble trap and two flowmeters for pressure-controlled perfusion of the vessels using an off-the-shelf perfusate at room temperature. Successful livers exhibited homogeneous perfusion in both the portal vein and hepatic artery with dynamic contrast-enhanced ultrasound, which correlated with stable oxygen uptake, bile production and hepatic resistance and normal histology at the end of 3 h of perfusion. Dynamic contrast-enhanced ultrasound revealed perfusion abnormalities invisible to the naked eye, thereby providing context to the otherwise systemic biochemical/hemodynamic measurements and focal biopsy findings. The model developed here is a simple, cost-effective approach for stable ex vivo whole-organ machine perfusion. PMID:25023101

  18. Stable Encapsulation of Air in Mesoporous Silica Nanoparticles: Fluorocarbon-Free Nanoscale Ultrasound Contrast Agents.

    PubMed

    Yildirim, Adem; Chattaraj, Rajarshi; Blum, Nicholas T; Goldscheitter, Galen M; Goodwin, Andrew P

    2016-06-01

    While gas-filled micrometer-sized ultrasound contrast agents vastly improve signal-to-noise ratios, microbubbles have short circulation lifetimes and poor extravasation from the blood. Previously reported fluorocarbon-based nanoscale contrast agents are more stable but their contrast is generally lower owing to their size and dispersity. The contrast agents reported here are composed of silica nanoparticles of ≈100 nm diameter that are filled with ≈3 nm columnar mesopores. Functionalization of the silica surface with octyl groups and resuspension with Pluronic F127 create particles with pores that remain filled with air but are stable in buffer and serum. Administration of high intensity focused ultrasound (HIFU) allows sensitive imaging of the silica nanoparticles down to 10(10) particles mL(-1) , with continuous imaging for at least 20 min. Control experiments with different silica particles supported the hypothesis that entrapped air could be pulled into bubble nuclei, which can then in turn act as acoustic scatterers. This process results in very little hemolysis in whole blood, indicating potential for nontoxic blood pool imaging. Finally, the particles are lyophilized and reconstituted or stored in PBS (phosphate-buffered saline, at least for four months) with no loss in contrast, indicating stability to storage and reformulation. PMID:26990167

  19. Quantitative evaluation of microvascular blood flow by contrast-enhanced ultrasound (CEUS).

    PubMed

    Greis, Christian

    2011-01-01

    Ultrasound contrast agents consist of tiny gas-filled microbubbles the size of red blood cells. Due to their size distribution, they are purely intravascular tracers which do not extravasate into the interstitial fluid, and thus they are perfect agents for imaging blood distribution and flow. Using ultrasound scanners with contrast-specific software, the specific microbubble-derived echo signals can be separated from tissue signals in realtime, allowing selective imaging of the contrast agent. The signal intensity obtained lies in a linear relationship to the amount of microbubbles in the target organ, which allows easy and reliable assessment of relative blood volume. Imaging of the contrast wash-in and wash-out after bolus injection, or more precisely using the flash-replenishment technique, allows assessment of regional blood flow velocity. Commercially available quantification software packages can calculate time-related intensity values from the contrast wash-in and wash-out phase for each image pixel from stored video clips. After fitting of a mathematical model curve according to the respective kinetic model (bolus or flash-replenishment kinetics), time/intensity curves (TIC) can be calculated from single pixels or user-defined regions of interest (ROI). Characteristic parameters of these TICs (e.g. peak intensity, area under the curve, wash-in rate, etc.) can be displayed as color-coded parametric maps on top of the anatomical image, to identify cold and hot spots with abnormal perfusion. PMID:22214685

  20. Liver metastases: Contrast-enhanced ultrasound compared with computed tomography and magnetic resonance.

    PubMed

    Cantisani, Vito; Grazhdani, Hektor; Fioravanti, Cristina; Rosignuolo, Maria; Calliada, Fabrizio; Messineo, Daniela; Bernieri, Maria Giulia; Redler, Adriano; Catalano, Carlo; D'Ambrosio, Ferdinando

    2014-08-01

    The development of ultrasound contrast agents with excellent tolerance and safety profiles has notably improved liver evaluation with ultrasound (US) for several applications, especially for the detection of metastases. In particular, contrast enhanced ultrasonography (CEUS) allows the display of the parenchymal microvasculature, enabling the study and visualization of the enhancement patterns of liver lesions in real time and in a continuous manner in all vascular phases, which is similar to contrast-enhanced computed tomography (CT) and contrast-enhanced magnetic resonance imaging. Clinical studies have reported that the use of a contrast agent enables the visualization of more metastases with significantly improved sensitivity and specificity compared to baseline-US. Furthermore, studies have shown that CEUS yields sensitivities comparable to CT. In this review, we describe the state of the art of CEUS for detecting colorectal liver metastases, the imaging features, the literature reports of metastases in CEUS as well as its technique, its clinical role and its potential applications. Additionally, the updated international consensus panel guidelines are reported in this review with the inherent limitations of this technique and best practice experiences. PMID:25110428

  1. [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. PMID:23108903

  2. 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.

  3. 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. PMID:26689151

  4. 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. PMID:19948357

  5. Mechanical stability of hollow spherical nano-aggregates as ultrasound contrast agent.

    PubMed

    Hadinoto, Kunn

    2009-06-01

    Gas-filled hollow nanoparticulate aggregates designed for use as an ultrasound contrast agent and as an ultrasound-mediated nanoparticulate drug delivery vehicle are manufactured by spray drying of nanoparticulate suspension at a fast convective drying rate. The gas outward diffusion from the hollow particles during insonication reduces the shell mechanical stability hence shortening the lifespan of the ultrasound contrast agent. The present work aims to develop a formulation method to produce micron-size hollow nanoparticulate aggregates with high shell mechanical stability by controlling the shell thickness-to-particle radius (S/R) ratio. The impacts of changing (1) the spray drying parameters, (2) nanoparticulate suspension concentration, and (3) surfactant inclusion (i.e. phospholipids) on the particle morphology and the S/R ratio are investigated. Biocompatible PMMA-MeOPEGMA nanoparticles of varying sizes (i.e. 50+/-20, 110+/-40, and 230+/-80 nm) are used as the model nanoparticles. The results indicate that the S/R ratio increases with decreasing particle size and the shell mechanical stability is linearly dependent on the S/R ratio. The effects of the spray drying parameters and nanoparticle concentration are found to be minimal in the absence of the phospholipids. The S/R ratio can be significantly increased by using larger size nanoparticles with the phospholipids inclusion. PMID:19446772

  6. 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

  7. The Degree of Contrast Washout on Contrast-Enhanced Ultrasound in Distinguishing Intrahepatic Cholangiocarcinoma from Hepatocellular Carcinoma.

    PubMed

    Han, Jing; Liu, Yubo; Han, Feng; Li, Qing; Yan, Cuiju; Zheng, Wei; Wang, Jianwei; Guo, Zhixing; Wang, Jun; Li, Anhua; Zhou, Jianhua

    2015-12-01

    We aim to assess the role and degree of contrast washout in the differential diagnosis of intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS). Fifty-six histopathology-confirmed ICC nodules and 184 HCC nodules were included in this study. The nodules' washout degree on CEUS at 1, 2 and 3 min was semi-quantitatively and qualitatively assessed using gray-scale video signal intensity. Semi-quantitative assessment showed that the washout degree of ICCs at 1, 2 and 3 min were significantly lower than those of HCCs (p < 0.001) and similar results were found in the same size range subgroups. There were no significant differences in the washout degree of ICCs between patients with chronic hepatitis and those without. The areas under receiver operating characteristic curves, using the nodules' washout degree at 1, 2 and 3 min to differentiate ICC from HCC, were 0.957, 0.979 and 0.982, respectively. The qualitative assessment showed the washout of ICCs was more rapid and obvious than that of HCCs. At 3 min, moderate and marked washout were observed in all ICCs, but in only 12.5% HCCs (p < 0.001). In conclusion, ICCs displayed much higher degree of contrast washout than HCCs on CEUS, which allowed for differentiation from HCCs. PMID:26386477

  8. 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.

  9. 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. PMID:27087694

  10. Calibration of an Ultrasound Tomography System for Medical Imaging with 2D Contrast-Source Inversion

    NASA Astrophysics Data System (ADS)

    Faucher, Gabriel Paul

    This dissertation describes two possible methods for the calibration of an ultrasound tomography system developed at University of Manitoba's Electromagnetic Imaging Laboratory for imaging with the contrast-source inversion algorithm. The calibration techniques are adapted from existing procedures employed for microwave tomography. A theoretical model of these calibration principles is developed in order to provide a rationale for the effectiveness of the proposed procedures. The applicability of such an imaging algorithm and calibration methods in the context of ultrasound are discussed. Also presented are 2D and 3D finite-difference time-domain update equations for the simulation of acoustic wave propagation in inhomogeneous media. Details regarding the application of an absorbing boundary-condition, point-source modelling and the treatment of penetrable objects are included in this document.

  11. In vivo pulsed magneto-motive ultrasound imaging using high-performance magnetoactive contrast nanoagents

    NASA Astrophysics Data System (ADS)

    Mehrmohammadi, Mohammad; Shin, Tae-Hyun; Qu, Min; Kruizinga, Pieter; Truby, Ryan L.; Lee, Jae-Hyun; Cheon, Jinwoo; Emelianov, Stanislav Y.

    2013-10-01

    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.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

  12. 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

  13. 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.

  14. 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

    2016-04-01

    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. PMID:27010717

  15. Enzyme-Degradable Hybrid Polymer/Silica Microbubbles as Ultrasound Contrast Agents.

    PubMed

    Tsao, Nadia H; Hall, Elizabeth A H

    2016-06-28

    The fabrication of an enzyme-degradable polymer/silica hybrid microbubble is reported that produces an ultrasound contrast image. The polymer, a triethoxysilane end-capped polycaprolactone (SiPCL), is used to incorporate enzyme-degradable components into a silica microbubble synthesis, and to impart increased elasticity for enhanced acoustic responsiveness. Formulations of 75, 85, and 95 wt % SiPCL in the polymer feed produced quite similar ratios of SiPCL and silica in the final bubble but different surface properties. The data suggest that different regions of the microbubbles were SiPCL-rich: the inner layer next to the polystyrene template core and the outer surface layer, thereby creating a sandwiched silica-rich layer of the bubble shell. Overall, the thickness of the microbubble shell was dependent on the starting TEOS concentration and the reaction time. Despite the layered structure, the microbubble could be efficiently degraded by lipase enzyme, but was stable without enzyme. The ultrasound contrast showed a general trend of increase in image intensity with SiPCL feed ratio, although the 95 wt % SiPCL bubbles did not produce a contrast image, probably due to bubble collapse. At higher normalized peak negative acoustic pressure (mechanical index, MI), a nonlinear frequency response also emerges, characterized by the third harmonic at around 3f0, and increases with MI. The threshold MI transition from linear to nonlinear response increased with decrease in SiPCL. PMID:27245495

  16. Consistency analysis of contrast-enhanced ultrasound and contrast-enhanced CT in diagnosis of small hepatocellular carcinoma

    PubMed Central

    Liu, Jun-Jie; Li, Hong-Xue; Chen, Zhao-Bei; Yang, Wei-Ping; Zhao, Sheng-Fa; Chen, Jie; Bai, Tao; Li, Hang; Li, Le-Qun

    2015-01-01

    To compare the consistency of contrast-enhanced ultrasound (CEUS) and contrast-enhance CT (CECT) in diagnosis of 1~2 cm and 2.1~3 cm small hepatocellular carcinoma (HCC) and evaluate the value of CEUS in diagnosis of HCC. Methods: A total of 74 patients (89 lesions) with small HCC and cirrhosis background were retrospectively analyzed. All of the eighty-nine lesions were confirmed by histopathological examination of surgical samples or needle biopsy. All the cases were divided into 1~2 cm group and 2.1~3 cm group. The CEUS and CECT enhanced pattern and diagnosis results of the two groups were compared and the consistency between the two imaging methods were statistically analyzed. Results: In the diagnosis of 1.0-2.0 cm HCC, CEUS and CECT had a moderate consistency in arterial phase, CEUS showed a tolerable consistency with CECT in portal venous and delayphase. The two imaging methods have a better consistency for the diagnosis in 2.1-3.0 cm HCC. Conclusion: CEUS can be used as a supplement to provide important diagnostic information in clinical practice when positive results or definite diagnoses cannot obtain. PMID:26885093

  17. 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

  18. 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

  19. 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. PMID:25195785

  20. 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).

  1. Ultrasound

    MedlinePlus Videos and Cool Tools

    Ultrasound is a useful procedure for monitoring the baby's development in the uterus. Ultrasound uses inaudible sound waves to ... no known risks for ultrasound at present, it is highly recommended that pregnant women consult their physician ...

  2. 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 ...

  3. Review of dynamic contrast-enhanced ultrasound guidance in ablation therapy for hepatocellular carcinoma

    PubMed Central

    Minami, Yasunori; Kudo, Masatoshi

    2011-01-01

    Local ablative techniques-percutaneous ethanol injection, microwave coagulation therapy and radiofrequency ablation (RFA)-have been developed to treat unresectable hepatocellular carcinoma (HCC). The success rate of percutaneous ablation therapy for HCC depends on correct targeting of the tumor via an imaging technique. However, probe insertion often is not completely accurate for small HCC nodules, which are poorly defined on conventional B-mode ultrasound (US) alone. Thus, multiple sessions of ablation therapy are frequently required in difficult cases. By means of two breakthroughs in US technology, harmonic imaging and the development of second-generation contrast agents, dynamic contrast-enhanced harmonic US imaging with an intravenous contrast agent can depict tumor vascularity sensitively and accurately, and is able to evaluate small hypervascular HCCs even when B-mode US cannot adequately characterize the tumors. Therefore, dynamic contrast-enhanced US can facilitate RFA electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of dynamic contrast-enhanced US guidance in ablation therapy for liver cancer is an efficient approach. Here, we present an overview of the current status of dynamic contrast-enhanced US-guided ablation therapy, and summarize the current indications and outcomes of reported clinical use in comparison with that of other modalities. PMID:22174544

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  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. Ultrasound phase contrast thermal imaging with reflex transmission imaging methods in tissue phantoms

    PubMed Central

    Farny, Caleb H.; Clement, Gregory T.

    2009-01-01

    Thermal imaging measurements using ultrasound phase contrast have been performed in tissue phantoms heated with a focused ultrasound source. Back projection and reflex transmission imaging principles were employed to detect sound speed-induced changes in the phase caused by an increase in the temperature. The temperature was determined from an empirical relationship for the temperature dependence on sound speed. The phase contrast was determined from changes in the sound field measured with a hydrophone scan conducted before and during applied heating. The lengthy scanning routine used to mimic a large two-dimensional array required a steady-state temperature distribution within the phantom. The temperature distribution in the phantom was validated with magnetic resonance (MR) thermal imaging measurements. The peak temperature was found to agree within 1°C with MR and good agreement was found between the temperature profiles. The spatial resolution was 0.3 × 0.3 × 0.3 mm, comparing favorably with the 0.625 × 0.625 × 1.5 mm MR spatial resolution. PMID:19683380

  13. Correlation of rupture dynamics to the nonlinear backscatter response from polymer-shelled ultrasound contrast agents.

    PubMed

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

    2015-03-01

    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 prerupture 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

  14. 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

  15. Validation of Dynamic Contrast-Enhanced Ultrasound in Predicting Outcomes of Antiangiogenic Therapy for Solid Tumors

    PubMed Central

    Lassau, Nathalie; Bonastre, Julia; Kind, Michèle; Vilgrain, Valérie; Lacroix, Joëlle; Cuinet, Marie; Taieb, Sophie; Aziza, Richard; Sarran, Antony; Labbe-Devilliers, Catherine; Gallix, Benoit; Lucidarme, Olivier; Ptak, Yvette; Rocher, Laurence; Caquot, Louis-Michel; Chagnon, Sophie; Marion, Denis; Luciani, Alain; Feutray, Sylvaine; Uzan-Augui, Joëlle; Coiffier, Benedicte; Benastou, Baya; Koscielny, Serge

    2014-01-01

    Objectives Dynamic contrast-enhanced ultrasound (DCE-US) has been used in single-center studies to evaluate tumor response to antiangiogenic treatments: the change of area under the perfusion curve (AUC), a criterion linked to blood volume, was consistently correlated with the Response Evaluation Criteria in Solid Tumors response. The main objective here was to do a multicentric validation of the use of DCE-US to evaluate tumor response in different solid tumor types treated by several antiangiogenic agents. A secondary objective was to evaluate the costs of the procedure. Materials and Methods This prospective study included patients from 2007 to 2010 in 19 centers (8 teaching hospitals and 11 comprehensive cancer centers). All patients treated with antiangiogenic therapy were eligible. Dynamic contrast-enhanced ultrasound examinations were performed at baseline as well as on days 7, 15, 30, and 60. For each examination, a perfusion curve was recorded during 3 minutes after injection of a contrast agent. Change from baseline at each time point was estimated for each of 7 fitted criteria. The main end point was freedom from progression (FFP). Criterion/time-point combinations with the strongest correlation with FFP were analyzed further to estimate an optimal cutoff point. Results A total of 1968 DCE-US examinations in 539 patients were analyzed. The median follow-up was 1.65 years. Variations from baseline were significant at day 30 for several criteria, with AUC having the most significant association with FFP (P = 0.00002). Patients with a greater than 40% decrease in AUC at day 30 had better FFP (P = 0.005) and overall survival (P = 0.05). The mean cost of each DCE-US was 180€, which corresponds to $250 using the current exchange rate. Conclusions Dynamic contrast-enhanced ultrasound is a new functional imaging technique that provides a validated criterion, namely, the change of AUC from baseline to day 30, which is predictive of tumor progression in a large

  16. 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

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

    PubMed Central

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

    2014-01-01

    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. PMID:25234874

  18. 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. PMID:21725127

  19. Use of Contrast-Enhanced Ultrasound in the Differential Diagnosis of Adrenal Tumors in Dogs.

    PubMed

    Bargellini, Paolo; Orlandi, Riccardo; Dentini, Alfredo; Paloni, Chiara; Rubini, Giuseppe; Fonti, Paolo; Diana, Alessia; Peterson, Mark E; Boiti, Cristiano

    2016-01-01

    We evaluated the diagnostic accuracy of the contrast-enhanced ultrasonography (CEUS), using a second-generation microbubble contrast agent, in differentiating the different types of adrenal mass lesions in 24 dogs. At B-mode ultrasound, 9 lesions involved the right adrenal gland, 14 the left, and 1 was bilateral. Each dog received a bolus of the contrast agent into the cephalic vein, immediately followed by a 5-mL saline flush. The first contrast enhancement of each adrenal lesion was evaluated qualitatively to assess the degree of enhancement and its distribution during the wash-in and wash-out phases, as well as the presence of non-vascularized areas and specific vascular patterns. Pathological diagnoses were determined in all dogs by histopathology or by cytology. Combining enhancement degree and vascularity resulted in the best predictive model, allowing CEUS to differentiate adrenocortical adenoma (n=10), adenocarcinoma (n=7), and pheochromocytoma (n=7) with an accuracy of 91.7% (P < 0.001). Combining enhancement degree and vascularity, CEUS can discriminate malignant versus benign adrenal lesions with a sensitivity of 100.0%, a specificity of 80.0%, and an accuracy of 91.7% (P < 0.001). In conclusion, results of this study confirm that CEUS is useful for differentiating between the different types of adrenal tumors in dogs. PMID:27008325

  20. 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. PMID:27403642

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

    PubMed

    Kim, Tae Kyoung; Jang, Hyun-Jung

    2014-04-01

    Contrast-enhanced ultrasound (CEUS) using microbubble contrast agents are useful for the diagnosis of the nodules in liver cirrhosis. CEUS can be used as a problem-solving method for indeterminate nodules on computed tomography (CT) or magnetic resonance imaging (MRI) or as an initial diagnostic test for small newly detected liver nodules. CEUS has unique advantages over CT and MRI including no renal excretion of contrast, real-time imaging capability, and purely intravascular contrast. Hepatocellular carcinoma (HCC) is characterized by arterial-phase hypervascularity and later washout (negative enhancement). Benign nodules such as regenerative nodules or dysplastic nodules are usually isoechoic or slightly hypoechoic in the arterial phase and isoechoic in the late phase. However, there are occasional HCC lesions with atypical enhancement including hypovascular HCC and hypervascular HCC without washout. Cholangiocarcinomas are infrequently detected during HCC surveillance and mostly show rim-like or diffuse hypervascularity followed by rapid washout. Hemangiomas are often found at HCC surveillance and are easily diagnosed by CEUS. CEUS can be effectively used in the diagnostic work-up of small nodules detected at HCC surveillance. CEUS is also useful to differentiate malignant and benign venous thrombosis and to guide and monitor the local ablation therapy for HCC. PMID:24707142

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

    PubMed Central

    Kim, Tae Kyoung; Jang, Hyun-Jung

    2014-01-01

    Contrast-enhanced ultrasound (CEUS) using microbubble contrast agents are useful for the diagnosis of the nodules in liver cirrhosis. CEUS can be used as a problem-solving method for indeterminate nodules on computed tomography (CT) or magnetic resonance imaging (MRI) or as an initial diagnostic test for small newly detected liver nodules. CEUS has unique advantages over CT and MRI including no renal excretion of contrast, real-time imaging capability, and purely intravascular contrast. Hepatocellular carcinoma (HCC) is characterized by arterial-phase hypervascularity and later washout (negative enhancement). Benign nodules such as regenerative nodules or dysplastic nodules are usually isoechoic or slightly hypoechoic in the arterial phase and isoechoic in the late phase. However, there are occasional HCC lesions with atypical enhancement including hypovascular HCC and hypervascular HCC without washout. Cholangiocarcinomas are infrequently detected during HCC surveillance and mostly show rim-like or diffuse hypervascularity followed by rapid washout. Hemangiomas are often found at HCC surveillance and are easily diagnosed by CEUS. CEUS can be effectively used in the diagnostic work-up of small nodules detected at HCC surveillance. CEUS is also useful to differentiate malignant and benign venous thrombosis and to guide and monitor the local ablation therapy for HCC. PMID:24707142

  3. 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.

  4. Utility of contrast-enhanced ultrasound with SonoVue in biopsy of small subpleural nodules

    PubMed Central

    Wang, Jinlin; Zhou, Dazhi; Xie, Xiaohong; Shen, Panxiao; Zeng, Yunxiang

    2015-01-01

    Objectives: This study aimed to evaluate the diagnostic accuracy and complication rates of contrast-enhanced ultrasound (CEUS)-guided biopsy of small subpleural nodules with SonoVue. Methods: CEUS-guided biopsies with SonoVue and conventional ultrasound were performed to determine nodule size, texture and biopsy route. After baseline ultrasonography, all patients received an intravenous injection of 4 mL of SonoVue, followed by 5 mL of saline flush. CEUS was obtained using a convex probe and contrast-specific imaging software. The lesion was observed using a contrast agent. Biopsies were performed during real-time visualisation of the target lesion. Results: A total of 51 patients (34 males and 17 females; average age, 54.8 ± 5.8 years) with subpleural nodules were enrolled. The median nodule size was 1.92 ± 0.75 cm (0.9-2.5 cm). Forty-eight of 51 procedures (94.1%) provided adequate material for histological analysis. Thirty patients (62.5%) were malignant and 18 patients (37.5%) were benign at the definitive diagnosis. The true positive and true negative result were 28 (58.3%) and 18 (37.5%), no false positive result was seen and two (4.2%) provided a false negative result. The sensitivity, specificity, positive and negative predictive values for the malignant diagnosis were 93.3, 100, 100 and 90%, respectively. The diagnostic accuracy was 95.8% (46/48), the standard error and the 95% CI were 2.8% and 86%-99%. An asymptomatic pneumothorax was present in one patient with no chest tube placement required. A small amount of hemoptysis was observed in another patient, which stopped spontaneously without treatment. Conclusions: CEUS-guided biopsy with SonoVue exhibits high diagnostic accuracy and low complication rates. It is especially advantageous for biopsies of small subpleural nodules. PMID:26629103

  5. Atherosclerotic carotid lumen segmentation in combined B-mode and contrast enhanced ultrasound images

    NASA Astrophysics Data System (ADS)

    Akkus, Zeynettin; Carvalho, Diego D. B.; Klein, Stefan; van den Oord, Stijn C. H.; Schinkel, Arend F. L.; de Jong, Nico; van der Steen, Antonius F. W.; Bosch, Johan G.

    2014-03-01

    Patients with carotid atherosclerotic plaques carry an increased risk of cardiovascular events such as stroke. Ultrasound has been employed as a standard for diagnosis of carotid atherosclerosis. To assess atherosclerosis, the intima contour of the carotid artery lumen should be accurately outlined. For this purpose, we use simultaneously acquired side-by-side longitudinal contrast enhanced ultrasound (CEUS) and B-mode ultrasound (BMUS) images and exploit the information in the two imaging modalities for accurate lumen segmentation. First, nonrigid motion compensation is performed on both BMUS and CEUS image sequences, followed by averaging over the 150 time frames to produce an image with improved signal-to-noise ratio (SNR). After that, we segment the lumen from these images using a novel method based on dynamic programming which uses the joint histogram of the CEUS and BMUS pair of images to distinguish between background, lumen, tissue and artifacts. Finally, the obtained lumen contour in the improved-SNR mean image is transformed back to each time frame of the original image sequence. Validation was done by comparing manual lumen segmentations of two independent observers with automated lumen segmentations in the improved-SNR images of 9 carotid arteries from 7 patients. The root mean square error between the two observers was 0.17+/-0.10mm and between automated and average of manual segmentation of two observers was 0.19+/-0.06mm. In conclusion, we present a robust and accurate carotid lumen segmentation method which overcomes the complexity of anatomical structures, noise in the lumen, artifacts and echolucent plaques by exploiting the information in this combined imaging modality.

  6. 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

  7. 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

  8. 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

  9. ACOUSTIC CHARACTERIZATION AND PHARAMACOKINETIC ANALYSES OF NEW NANOBUBBLE ULTRASOUND CONTRAST AGENTS

    PubMed Central

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

    2013-01-01

    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 rate 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 the

  10. 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

  11. Automated benign & malignant thyroid lesion characterization and classification in 3D contrast-enhanced ultrasound.

    PubMed

    Acharya, U Rajendra; S, Vinitha Sree; Molinari, Filippo; Garberoglio, Roberto; Witkowska, Agnieszka; Suri, Jasjit S

    2012-01-01

    In this work, we present a Computer Aided Diagnosis (CAD) based technique for automatic classification of benign and malignant thyroid lesions in 3D contrast-enhanced ultrasound images. The images were obtained from 20 patients. Fine needle aspiration biopsy and histology confirmed malignancy. Discrete Wavelet Transform (DWT) and texture based features were extracted from the thyroid images. The resulting feature vectors were used to train and test three different classifiers: K-Nearest Neighbor (K-NN), Probabilistic Neural Network (PNN), and Decision Tree (DeTr) using ten-fold cross validation technique. Our results show that combination of DWT and texture features in the K-NN classifier resulted in a classification accuracy of 98.9%, a sensitivity of 98%, and a specificity of 99.8%. Thus, the preliminary results of the proposed technique show that it could be adapted as an adjunct tool that can give valuable second opinions to the doctors regarding the nature of the thyroid nodule. The technique is cost-effective, non-invasive, fast, completely automated and gives more objective and reproducible results compared to manual analysis of the ultrasound images. We however intend to establish the clinical applicability of this technique by evaluating it with more data in the future. PMID:23365926

  12. History force effects on contrast agent microbubbles in an ultrasound field

    NASA Astrophysics Data System (ADS)

    Garbin, Valeria; Dollet, Benjamin; van Wijngaarden, Leen; de Jong, Nico; Lohse, Detlef; Versluis, Michel

    2008-11-01

    We study experimentally the radial and translational dynamics of an ultrasound contrast agent microbubble pair pulsating in an ultrasound field. The two bubbles attract each other through the so-called secondary Bjerknes force; quantifying these bubble-bubble interactions is therefore crucial for optimized medical imaging protocols. Using optical tweezers, we trap and control the distance between two microbubbles (BR-14, Bracco Research S.A., Geneva). We position the bubble pair away from the sample chamber wall, to prevent wall effects and quantify purely the acoustic bubble-bubble interaction and the dissipation due to viscosity in the fluid. The ultra-high speed Brandaris camera recorded the bubble dynamics at 15 million frames per second; from the optical measurements we track the instantaneous bubble radii and positions. We write a force balance for each bubble, assuming a no-slip boundary condition since the bubble interface is coated with a lipid monolayer to prevent dissolution. By comparison with the experimental results, we find that history effects are crucial to correctly account for the viscous forces.

  13. 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. PMID:22341597

  14. 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

  15. Hepatosplenic sarcoidosis: contrast-enhanced ultrasound findings and implications for clinical practice.

    PubMed

    Tana, Claudio; Dietrich, Christoph F; Schiavone, Cosima

    2014-01-01

    Sarcoidosis is a complex granulomatous disease that affects virtually every organ and tissue, with a prevalence that varies significantly among the sites involved. The role of conventional imaging, such as computed tomography and magnetic resonance imaging, in the assessment of hepatosplenic sarcoidosis is well established by revealing organ enlargement, multiple discrete nodules, and lymphadenopathy. In this review, we aim to describe contrast-enhanced ultrasound (CEUS) findings in liver and spleen involvement by sarcoidosis, reporting evidence from the literature and cases from our experience, after a brief update on safety profile, cost-effectiveness, and clinical indications of this novel technique. Furthermore, we highlight potential advantages of CEUS in assessing hepatosplenic sarcoidosis that may be useful in the clinical practice. PMID:25215299

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

    NASA Astrophysics Data System (ADS)

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

    1997-04-01

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

  17. 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

  18. Continuous Dynamic Registration of Microvascularization of Liver Tumors with Contrast-Enhanced Ultrasound

    PubMed Central

    Wiesinger, Isabel; Stroszczynski, Christian; Wiggermann, Philipp; Jung, Ernst-Michael

    2014-01-01

    Aim. To evaluate the diagnostic value of quantification of liver tumor microvascularization using contrast-enhanced ultrasound (CEUS) measured continuously from the arterial phase to the late phase (3 minutes). Material and Methods. We present a retrospective analysis of 20 patients with malignant (n = 13) or benign (n = 7) liver tumors. The tumors had histopathologically been proven or clearly identified using contrast-enhanced reference imaging with either 1.5 T MRI (liver specific contrast medium) or triphase CT and follow-up. CEUS was performed using a multifrequency transducer (1–5 MHz) and a bolus injection of 2.4 mL sulphur hexafluoride microbubbles. A retrospective perfusion analysis was performed to determine TTP (time-to-peak), RBV (regional blood volume), RBF (regional blood flow), and Peak. Results. Statistics revealed a significant difference (P < 0.05) between benign and malignant tumors in the RBV, RBF, and Peak but not in TTP (P = 0.07). Receiver operating curves (ROC) were generated for RBV, RBF, Peak, and TTP with estimated ROC areas of 0.97, 0.96, 0.98, and 0.76, respectively. Conclusion. RBV, RBF, and Peak continuously measured over a determined time period of 3 minutes could be of valuable support in differentiating malignant from benign liver tumors. PMID:24991432

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

    PubMed Central

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

    2010-01-01

    The extensive use of imaging techniques in differential diagnosis of abdominal conditions and screening of hepatocellular carcinoma in patients with chronic hepatic diseases, has led to an important increase in identification of focal liver lesions. The development of contrast-enhanced ultrasound (CEUS) opens a new window in the diagnosis and follow-up of these lesions. This technique offers obvious advantages over the computed tomography and magnetic resonance, without a decrease in its sensitivity and specificity. The new second generation contrast agents, due to their intravascular distribution, allow a continuous evaluation of the enhancement pattern, which is crucial in characterization of liver lesions. The dual blood supply in the liver shows three different phases, namely arterial, portal and late phases. The enhancement during portal and late phases can give important information about the lesion’s behavior. Each liver lesion has a different enhancement pattern that makes possible an accurate approach to their diagnosis. The role of emerging techniques as a contrast-enhanced three-dimensional US is also discussed. In this article, the advantages, indications and technique employed during CEUS and the different enhancement patterns of most benign and malignant focal liver lesions are discussed. PMID:21225000

  20. 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. PMID:26112374

  1. Immunological evaluation of the new stable ultrasound contrast agent LK565: a phase one clinical trial

    PubMed Central

    Funke, B; Maerz, HK; Okorokow, S; Polata, S; Lehmann, I; Sack, U; Wild, P; Geisler, T; Zotz, RJ

    2004-01-01

    Background Ultrasound contrast agents (UCAs) allow the enhancement of vascular definition, thereby providing more diagnostic information. LK565 is a new second-generation UCA based on synthetic polymers of aspartic acid which is eliminated from the blood stream via phagocytosis. LK565 forms very stable air-filled microspheres and is capable of repeated passage through the pulmonary capillary bed after peripheral intravenous injection. This characteristic allows examination of the cardiac function or extracardiac vessel abnormalities up to 15 minutes. Methods A phase one clinical study was conducted on 15 healthy volunteers to identify the development of an undesirable immune response. Phagocytosis capacity, TNF-α secretion, and MHC class II upregulation of monocytes was monitored, as well as microsphere specific antibody development (IgM, IgG). Furthermore, the kinetics of the activation surface markers CD69, CD25, CD71, and CD11b on leukocytes were analyzed. Results Due to LK565-metabolism the administration of the UCA led to saturation of phagocytes which was reversible after 24 hrs. Compared to positive controls neither significant TNF-α elevation, neither MHC class II and activation surface markers upregulation, nor specific antibody development was detectable. Conclusion The administration of LK565 provides a comfortable duration of signal enhancement, esp. in echocardiography, without causing a major activation cascade or triggering an adaptive immune response. To minimize the risk of undesirable adverse events such as anaphylactoid reactions, immunological studies should be included in clinical trials for new UCAs. The use of LK565 as another new ultrasound contrast agent should be encouraged as a safe means to provide additional diagnostic information. PMID:15357870

  2. A New Method for Discriminating between Bronchial and Pulmonary Arterial Phases using Contrast-Enhanced Ultrasound.

    PubMed

    Hong-Xia, Zhang; Wen, He; Ling-Gang, Cheng; Wen-Jia, Cai; Shuo, Li; Li-Juan, Du; Hai-Man, Song; Yang, Zhao

    2016-07-01

    This study aimed to explore the value of a real-time comparative observation method using contrast-enhanced ultrasound (CEUS) for discriminating between bronchial and pulmonary arterial phases in diagnosing lung diseases. Forty-nine patients with 50 pulmonary lesions (45 peripheral lesions and five central lesions with obstructive atelectasis, including 36 malignant tumors, five tuberculomas, four inflammatory pseudotumors and five pneumonia lesions) detected via computed tomography and visible on ultrasonography were enrolled in this study. The arterial phases were determined by comparing contrast agent arrival time (AT) in the peripheral lung lesion with that in adjacent lung tissue, referred to as a real-time comparative observation method. Detection rates of this observation method were 100% (50/50) for pulmonary arterial phase and 88% (44/50) for bronchial arterial phase. Using the instrument's built-in graphing and analysis software, a time-intensity curve was constructed based on a chosen region of interest within the lesion where enhancement was the most obvious. Commonly used perfusion indicators in CEUS, such as AT, time-to-peak and peak intensity, were obtained from the time-intensity curve. Percutaneous puncture biopsies were performed under ultrasound guidance, and specimens of all 50 lesions were examined pathologically. AT was significantly shorter in patients with pneumonia than in those with malignant tumors or chronic inflammation (p < 0.05), whereas no difference was seen between those with malignant tumors and those with chronic inflammation. No significant differences in time-to-peak or peak intensity were seen among those with various lung diseases (p > 0.05). This is the first description of a real-time comparative observation method using CEUS for determining the arterial phases in the lungs. This method is accurate, simple to perform and provides a direct display. It is expected to become a practical and feasible tool for diagnosing

  3. 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. PMID:26765518

  4. Contrast-Enhanced Ultrasound for the Characterization of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma

    PubMed Central

    Liu, Guang-Jian; Wang, Wei; Lu, Ming-De; Xie, Xiao-Yan; Xu, Hui-Xiong; Xu, Zuo-Feng; Chen, Li-Da; Wang, Zhu; Liang, Jin-Yu; Huang, Yang; Li, Wei; Liu, Jin-Ya

    2015-01-01

    Purpose and methods The ability of contrast-enhanced ultrasound (CEUS) to differentiate between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is still controversial. We reviewed the CEUS imaging of 819 patients (HCC=546, ICC=273) with an established pathological diagnosis. The enhancement patterns of lesions and the diagnostic performance of CEUS were analyzed. Results Arterial hyperenhancement followed by washout was observed in 92.3% (504/546) of the HCC lesions and 85.7% (234/273) of the ICC lesions on CEUS (p<0.05). Additionally, the ICCs presented contrast washout much earlier than the HCCs, with an average time of 27.5 seconds after injecting the contrast agent compared with 70.1 seconds for the HCCs (p<0.05). Peripheral rim-like enhancement was observed in 68.5% (187/273) of the ICCs, which was significantly more common than that in the HCCs (2.0%, 11/546) (p<0.05). When using arterial hyperenhancement with a washout phase later than 43 seconds after injecting the contrast agent and with no peripheral rim-like enhancement as the diagnostic criteria for HCC ≤5 cm in diameter, the area under the curve was 0.808, with 64.1% sensitivity, 97.4% specificity and 73.6% accuracy. Conclusions Although ICC may show the typical enhancement pattern of HCC on CEUS, peripheral rim-like enhancement and quick contrast washout show high efficiency in the differentiation of HCC from ICC. PMID:26779444

  5. Ultrasound

    MedlinePlus

    Ultrasound uses high-frequency sound waves to make images of organs and structures inside the body. ... An ultrasound machine makes images so that organs inside the body can be examined. The machine sends out high- ...

  6. The role of contrast-enhanced ultrasound imaging in the follow-up of patients post-endovascular aneurysm repair.

    PubMed

    Jawad, Nadia; Parker, Pamela; Lakshminarayan, Raghuram

    2016-02-01

    Endovascular aneurysm repair is a minimally invasive technique for the treatment of abdominal aortic aneurysms. Patients who undergo endovascular aneurysm repair are potentially at risk of developing problems related to the graft such as the development of endoleaks. Endoleaks can cause expansion of the aneurysmal sac, which can potentially lead to rupture. It is for this reason that lifelong surveillance of patients is required to assess the graft and the aneurysmal sac. This article discusses the role of contrast-enhanced ultrasound in the follow-up of patients post-endovascular aneurysm repair. Contrast-enhanced ultrasound is rapidly becoming a powerful, accurate and cost-effective tool to complement computed tomography in the follow-up of endovascular aneurysm repair patients. Real-time imaging of contrast filling into the arterial system means that contrast-enhanced ultrasound is an excellent problem-solving tool, particularly when assessing for the type and anatomy of endoleaks. In some instances, contrast-enhanced ultrasound can detect endoleaks when other modalities are equivocal. PMID:27433275

  7. Contrast-enhanced ultrasound for diagnosing, staging and assessment of operability of pancreatic cancer.

    PubMed

    Grossjohann, Hanne Sønder

    2012-12-01

    We have evaluated the usefulness of contrast-enhanced ultrasound (CEUS) for diagnosing, staging and assessment of operability of pancreatic head tumors. For some years CEUS has been used with great success for diagnosis of focal liver lesions but when we started our trial, it was still relatively untested in the pancreas. This PhD thesis is based on a methodological study, two clinical studies and an intra-/interobserver study. The methodological study consists of material collected from investigations made on 14 experimental pigs. First, we examined the pig pancreas with CEUS. Hereafter we repeated the CEUS examination after venous injection of the gastrointestinal hormones secretin and cholecystokinin. We investigated if the contrast-enhancement would intensify after hormone stimulation. The clinical studies consist of material collected from examinations of 49 patients referred to our hospital with the diagnosis, suspicion of pancreatic cancer. All patients had a conventional ultrasound examination and a CEUS examination. In addition, some of the patients also had a CEUS examination after stimulation with secretin and cholecystokinin. All patients had a 64-slice-CT examination and a biopsy was taken for histopathological verification. We studied whether CEUS was useful for assessment of tumor classification, tumor staging and tumor resectability. We also tested if hormone stimulation of the pancreas during CEUS could intensify contrast-enhancement of healthy pancreatic tissue and thus contribute to a better demarcation of a tumor. Finally, we tested the intra-/interobserver agreement of our visual interpretation of the contrast-enhanced ultrasound images and the concordance between the visual interpretation and histopathological test results. From the results of the methodological study it seemed possible to intensify contrast-enhancement using the gastrointestinal hormones by 3%. During the clinical studies it emerged that hormone stimulation did not improve

  8. 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.

  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. 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. PMID:19942499

  11. Common ultrasound and contrast-enhanced ultrasonography in the diagnosis of hepatic artery pseudoaneurysm after liver transplantation

    PubMed Central

    Ren, Xiuyun; Luo, Yukun; Gao, Nong; Niu, Hong; Tang, Jie

    2016-01-01

    The diagnostic value of common ultrasound and contrast-enhanced ultrasonography (CEUS) in hepatic artery pseudoaneurysm (HAP) after liver transplantation was investigated. From January 2005 to November 2015, information was collected on 2,085 cases of orthotopic liver transplantation. The cases included 1,617 men and 468 women. Common ultrasound and CEUS were used to monitor arterial blood flow following surgery, and the complications were assessed. Instruments used included Acuson Sequoia 512 and Mylab Twice, and the contrast agent was SonoVue. The standard of common ultrasound in the diagnosis of HAP was follicular structure, which had arterial blood flow signal present beside the hepatic artery. The diagnostic criteria of HAP using CEUS were abnormal and round contrast enhancement zone and perfusion of the contrast agent in the zone near the hepatic artery. The diagnostic standard of HAP was computed tomographic angiography (CTA) and emergency operation. Eight cases of HAP were diagnosed in 2,085 patients after liver transplantation (0.38%). Three cases of HAP were diagnosed successfully by common ultrasound while 5 cases were missed. Sensitivity, specificity and diagnostic accuracy for common ultrasound was 37.5, 100 and 99.76%, respectively. Six cases of HAP were diagnosed by CEUS and 2 cases were missed. Sensitivity, specificity and diagnostic accuracy for CEUS was 75, 100 and 99.9%, respectively. Collectively, CEUS is a convenient and effective diagnostic method for HAP following liver transplantation, the diagnostic sensitivity was obviously higher than that of the common ultrasound, and it was more convenient than CTA. Nevertheless, the diagnosis of pseudoaneurysm with deep location, and unsatisfactory grayscale images were easily missed. PMID:27446316

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

    PubMed Central

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

    2013-01-01

    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. PMID:26675552

  13. Is Contrast Enhanced Ultrasound (CEUS) ready for use in daily practice for evaluation of focal liver lesions?

    PubMed

    Sporea, Ioan; Şirli, Roxana

    2014-03-01

    Abdominal ultrasound is one of the most popular imaging methods due to its feasibility, low cost and accessibility. Contrast Enhanced Ultrasound (CEUS) with second generation contrast agents became in the last years a useful tool for the characterization of focal liver lesions (FLL) so that EFSUMB issued guidelines for its use in clinical practice. Several large studies proved that CEUS has similar performance to more expensive imaging methods such as contrast enhanced CT and contrast enhanced MRI for the characterization of FLL. Also, several studies proved that CEUS is cost-effective as a first-line imaging method. Considering all these data, we think that CEUS is ready to be used in daily practice for the evaluation of FLL. PMID:24567923

  14. 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

  15. Contrast-enhanced ultrasound in the biliary system: Potential uses and indications.

    PubMed

    Xu, Hui-Xiong

    2009-12-31

    Conventional ultrasound (US) is the first-line imaging investigation for biliary diseases. However, it is lack of the ability to depict the microcirculation of some lesions which may lead to failure in diagnosis for some biliary diseases. The use of contrast-enhanced US (CEUS) has reached the field of bile duct disease in recent years and promising results have been achieved. In this review, the methodology, image interpretation, enhancement pattern, clinical usefulness, and indications for CEUS in the biliary system are summarized. CEUS may be indicated in the biliary system under the following circumstances: (1) Where there is a need to make a characterization of intrahepatic cholangiocarcinoma (ICC); (2) For differentiation diagnosis between ICC and other tumors (i.e. hepatocellular carcinoma or liver metastasis) or infectious diseases; (3) For differentiation diagnosis between biliary cystadenoma and biliary cystadenocarcinoma; (4) To detect malignant change in Caroli's disease; (5) To depict the extent of Klatskin's tumor with greater clarity; (6) To make a distinction between gallbladder cholesterol polyp, adenoma and polypoid cancer; (7) To make a distinction between chronic cholecystitis with thickened wall and gallbladder cancer; (8) For differentiation diagnosis between motionless sludge and gallbladder cancer; (9) For differentiation diagnosis between common bile duct cancer and sludge or stone without acoustic shadowing; and (10) In patients who are suspected of having a drop of their percutaneous transhepatic cholangiodrainage tube, US contrast agent can be administered to through the tube detect the site of the tube. PMID:21160719

  16. 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.

  17. Management of hepatocellular carcinoma: The role of contrast-enhanced ultrasound

    PubMed Central

    Zheng, Shu-Guang; Xu, Hui-Xiong; Liu, Lin-Na

    2014-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common neoplasm and the third cause of cancer death worldwide. Contrast enhanced ultrasound (CEUS) has been applied for more than ten years and plays increasingly important roles in the management of HCC. On the basis of the Guideline and Good Clinical Practice Recommendations for CEUS in the liver-update 2012 and related literature about the management of HCC, we summarize the main roles and applications of CEUS in the management of HCC, including HCC surveillance, diagnosis, CEUS-guided treatment, treatment response evaluation and follow-up. The diagnostic algorithm for HCC is also suggested. Meanwhile, the comparisons between CEUS and contrast enhanced computed tomography/magnetic resonance imaging (CECT/CEMRI) in these areas are made. Although CEUS is subject to the same limitation as ordinary US and is inferior to CECT/CEMRI in some aspects, CEUS has proved to be of great value in the management of HCC with inherent advantages, such as sufficient high safety profile making it suitable for patients with renal failure or allergic to iodine, absence of radiation, easy reproducibility and high temporal resolution. The tremendous application of CEUS to the diagnosis and treatment of HCC provides more opportunities for patients with HCC diagnosed at different stages. PMID:24578787

  18. 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

  19. 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

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

    SciTech Connect

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

    2007-09-15

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

  1. Plasma sterilization of poly lactic acid ultrasound contrast agents: surface modification and implications for drug delivery.

    PubMed

    Eisenbrey, John R; Hsu, Jennifer; Wheatley, Margaret A

    2009-11-01

    Poly lactic acid (PLA) ultrasound contrast agents (CA) have been developed previously in our laboratory for ultrasound (US) imaging, as well as surface coated with doxorubicin to create a potential targeted platform of chemotherapeutic delivery using focused US. However, we have previously found it impossible to sterilize these agents while at the same time maintaining their acoustic properties, a task that would probably require fabrication within a clean facility. The purpose of this paper is to investigate the feasibility of using plasma to sterilize these CA while maintaining maximum echogenicity, a step that would greatly facilitate in vivo investigations. Effects of plasma exposure time (1, 3 and 6 min) and intensity (low-10 mA, 6.8 W; medium-15 mA, 10.5 W; and high-25 mA, 18 W) on the CAs' acoustic properties, surface morphology, zeta potential, capacity to carry chemotherapeutics and overall sterility are described. Both increases in plasma intensity and exposure time increased CA zeta potential and also significantly increased drug payload. High-intensity plasma exposure for 3 min was found to be an optimal sterilization protocol for maximal (100%) preservation of CA echogenicity. Plasma exposure resulted in sterile samples and maintained original CA enhancement of 20 dB and acoustic half-life over 75 min, while increasing CA zeta potential by 11 mV and doxorubicin loading efficiency by 10%. This study not only shows how a highly temperature- and pressure-sensitive agent can be sterilized using plasma, but also that surface modification can be used to increase surface binding of the drug. PMID:19766380

  2. 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. PMID:23927202

  3. Diagnostic value of contrast-enhanced ultrasound in solid thyroid nodules with and without enhancement.

    PubMed

    Wu, Qiong; Wang, Yan; Li, Yi; Hu, Bing; He, Zhi-Yan

    2016-08-01

    We aimed to investigate different enhancement patterns of solid thyroid nodules on contrast-enhanced ultrasound (CEUS) and then to evaluate the corresponding diagnostic performance in the differentiation of benign and malignant nodules with and without enhancement. 229 solid thyroid nodules in 196 patients who had undergone both conventional ultrasound and CEUS examinations were classified into enhancement and non-enhancement groups. Besides, different enhancement patterns in the enhancement group were characterised with five indicators including arrival time, mode of entrance, echo intensity, homogeneity, and washout time. Then aforementioned indicators were compared between benign and malignant nodules of different sizes (<10 mm and >10 mm), and diagnostic performance of significant enhancement indicators was calculated. As for the enhancement group, there were statistically significant differences of <10 mm subgroup among three CEUS indicators including arrival time, mode of entrance, and washout time between malignant and benign thyroid nodules (p < 0.05), while all CEUS indicators showed statistically significant differences in the total group and ≥10 mm subgroup (p < 0.05). All the five CEUS indicators displayed better diagnostic performance with specificity (92.86, 92.14, 95.71, 90.71, and 90.71 %, respectively) and diagnostic accuracy (80.79, 79.48, 74.67, 75.11, and 81.66 %, respectively), while the sensitivity and negative predictive value of non-enhancement were 95.51 and 95.83 %, respectively, with an accuracy of 77.29 %. CEUS is a very promising diagnostic technique that could improve the diagnostic accuracy of identifying benign thyroid lesions to spare a large number of patients an unnecessary invasive procedure. PMID:26732040

  4. Contrast Ultrasound Imaging Does Not Affect Heat Shock Protein 70 Expression in Cholesterol-Fed Rabbit Aorta

    PubMed Central

    Smith, Brendon W.; Simpson, Douglas G.; Miller, Rita J.; Erdman, John W.; O’Brien, William D.

    2015-01-01

    Objectives Diagnostic ultrasound imaging is enhanced by the use of circulating microbubble contrast agents (UCAs), but the interactions between ultrasound, UCAs, and vascular tissue are not fully understood. We hypothesized that ultrasound with a UCA would stress the vascular tissue and increase levels of heat shock protein 70 (Hsp70), a cellular stress protein. Methods Male New Zealand White rabbits (n = 32) were fed a standard chow diet (n = 4) or a 1% cholesterol, 10% fat, and 0.11% magnesium diet (n = 28). At 21 days, 24 rabbits on the cholesterol diet were either exposed to ultrasound (3.2-MHz f/3 transducer; 2.1 MPa; mechanical index, 1.17; 10 Hz pulse repetition frequency; 1.6 micro -seconds pulse duration; 2 minutes exposure duration at 4 sites along the aorta) with the UCA Definity (1× concentration, 1 mL/min; Lantheus Medical Imaging, North Billerica, MA) or sham exposed with a saline vehicle injection (n = 12 per group). Four rabbits on the cholesterol diet and 4 on the chow diet served as cage controls and were not exposed to ultrasound or restrained for blood sample collection. Animals were euthanized 24 hours after exposure, and aortas were quickly isolated and frozen in liquid nitrogen. Aorta lysates from the area of ultrasound exposure were analyzed for Hsp70 level by Western blot. Blood plasma was analyzed for cholesterol, Hsp70, and von Willebrand factor, a marker of endothelial function. Results Plasma total cholesterol levels increased to an average of 705 mg/dL. Ultrasound did not affect plasma von Willebrand factor, plasma Hsp70, or aorta Hsp70. Restraint increased Hsp70 (P < .001, analysis of variance). Conclusions Restraint, but not ultrasound with the UCA or cholesterol feeding, significantly increased Hsp70. PMID:26112623

  5. 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

  6. Contrast-enhanced ultrasound assessment of complex cystic lesions in renal transplant recipients with acquired cystic kidney disease: preliminary experience.

    PubMed

    Paudice, N; Zanazzi, M; Agostini, S; Bertelli, E; Caroti, L; Carta, P; Moscarelli, L; Tsalouchos, A; Salvadori, M; Bertoni, E

    2012-09-01

    We prospectively studied the potential value of contrast-enhanced ultrasound (CEUS) to characterize complex acquired cystic kidney disease (ACKD) or suspected solid renal masses, avoiding the risk of inducing acute kidney injury in 138 renal transplant recipients by contrast-enhanced computed tomography (CT). Forty-three cases (31%) had ACKD; 15 ACKD patients (35%) showed suspicious or nondiagnostic ultrasound. The latter subgroup underwent CEUS and, if the suspicion was confirmed, a contrast-enhanced CT. Thirty five lesions were identified in the 15 patients studied by CEUS. According to the Bosniak classification, 27 cysts were type I (BI), four type II (BII), two type III (BIII) with enhancement at the level of thickened septa; we also identified two solid enhancing lesions (BIV). We followed the BI and BII lesions with serial CEUS, while the remaining four cases underwent contrast-enhanced CT showing two solid lesions and two complex cysts with contrast enhancement in the septea. The four patients underwent surgical resection yielding three renal cell carcinomas one papillary carcinoma as the pathological findings. This preliminary study characterized solid nodules and BIII lesions for further evaluation by CT. CEUS seems to correctly characterize BI and BII cysts that are not clearly defined by standard ultrasound. PMID:22974874

  7. Preservation of imaging capability in sensitive ultrasound contrast agents after indirect plasma sterilization.

    PubMed

    Albala, Lorenzo; Ercan, Utku K; Joshi, Suresh G; Eisenbrey, John R; Teraphongphom, Nutte; Wheatley, Margaret A

    2015-10-15

    Many injectables are not amenable to standard sterilization methods, which destroy sensitive materials. This is particularly true for ultrasound contrast agents (UCA) consisting of gas bubbles stabilized by a surfactant or polymer shell. We investigated a new method to achieve safe and effective sterilization in production by introducing dielectric-barrier discharge non-thermal plasma. A dielectric-barrier discharge was generated to first produce plasma-treated phosphate-buffered saline (PTPBS), which was used as a sterilant solution for our UCA SE61, avoiding direct heat, pressure, chemicals, or radiation. Treated samples were tested for acoustic properties in vitro and in a flow phantom, and for sterility by standard methods. Three minutes plasma treatment of phosphate-buffered saline (PBS) proved effective. The samples showed significant inactivation of inoculated bacteria upon PTPBS treatment as compared to un-treated-PBS (p=0.0022). The treated and untreated samples showed no statistical significance (p>0.05) in acoustic response or bubble diameter (mean±SEM: 2.52±0.31 μm). Nile Red was used to model intercalation of drug in the hydrophobic shell, intercalated successfully into SE61, and was unaffected by plasma treatment. The PTPBS completely sterilized suspensions of UCA, and it did not compromise the acoustic properties of the agent or its ability to retain a hydrophobic compound. PMID:26241754

  8. Phospholipid decoration of microcapsules containing perfluorooctyl bromide used as ultrasound contrast agents.

    PubMed

    Díaz-López, Raquel; Tsapis, Nicolas; Libong, Danielle; Chaminade, Pierre; Connan, Carole; Chehimi, Mohamed M; Berti, Romain; Taulier, Nicolas; Urbach, Wladimir; Nicolas, Valérie; Fattal, Elias

    2009-03-01

    We present here an easy method to modify the surface chemistry of polymeric microcapsules of perfluorooctyl bromide used as ultrasound contrast agents (UCAs). Capsules were obtained by a solvent emulsification-evaporation process with phospholipids incorporated in the organic phase before emulsification. Several phospholipids were reviewed: fluorescent, pegylated and biotinylated phospholipids. The influence of phospholipid concentration on microcapsule size and morphology was evaluated. Only a fraction of the phospholipids is associated to microcapsules, the rest being dissolved with the surfactant in the aqueous phase. Microscopy shows that phospholipids are present within the shell and that the core/shell structure is preserved up to 0.5 mg fluorescent phospholipids, up to about 0.25 mg pegylated phospholipids or biotinylated phospholipids (for 100 mg of polymer, poly(lactide-co-glycolide) (PLGA)). HPLC allows quantifying phospholipids associated to capsules: they correspond to 10% of pegylated phospholipids introduced in the organic phase. The presence of pegylated lipids at the surface of capsules was confirmed by X-ray photon electron spectroscopy (XPS). The pegylation did not modify the echographic signal arising from capsules. Finally biotinylated microcapsules incubated with neutravidin tend to aggregate, which confirms the presence of biotin at the surface. These results are encouraging and future work will consist of nanocapsule surface modification for molecular imaging. PMID:19097640

  9. Diagnostic value of contrast-enhanced ultrasound in papillary thyroid microcarcinoma

    PubMed Central

    CHEN, HONG YAN; LIU, WEI YAN; ZHU, HUI; JIANG, DAO WEN; WANG, DONG HUA; CHEN, YONGQI; LI, WEIHUA; PAN, GAOFENG

    2016-01-01

    The aim of the present study was to explore the value and characteristics of contrast-enhanced ultrasound (CEUS) in the diagnosis of papillary thyroid microcarcinoma (PTMC). By analyzing CEUS information of 130 nodules obtained from 106 patients with PTMC, who had been diagnosed by surgery and pathological analysis, CEUS characteristics of PTMC nodules were concluded. Based on the results, the PTMC nodules were divided into three groups as follows: 32 nodules (24.62%) were found to be enhanced earlier than the surrounding normal thyroid tissue, 95 nodules (73.08%) were enhanced at the same time as the normal thyroid tissue and 3 nodules (2.30%) were enhanced later than the normal thyroid tissue. The results also demonstrated that the peak enhancement intensity of the 130 nodules was lower compared with the irregular intensity of the normal parenchyma in corresponding thyroids, and that PTMC enhancement washed out faster than in normal thyroid parenchyma. In conclusion, the PTMC characteristics that CEUS can detect may improve the diagnostic accuracy and provide valuable information for the treatment of the disease. PMID:27168773

  10. The Mechanical Effects of Ultrasound Contrast Agents on Micro-vessels

    NASA Astrophysics Data System (ADS)

    Hosseinkhah, N.; Hynynen, K.

    2011-09-01

    Ultrasound activated contrast agents inside microvessels induce mechanical effects on the vessel wall. It is important to use the bubbles safely and avoid rupturing the vessels. The objective of this work was to develop a three dimensional model of a bubble, blood and micro-vessels in order to investigate the mechanical effects (mainly the fluid shear stress and the circumferential stress) by a non-inertial microbubble on the vessel wall. A finite element method was used to solve for this model numerically. The blood vessel was simulated as having a viscoelastic, elastic or a rigid wall. Acoustic pressure and frequency were varied and the values for fluid shear stress and circumferential stress on the vessel wall were calculated. The circumferential stress could exceed the vascular strength in rigid microvessels if the applied acoustic pressure is above 260 kPa. Also the values for fluid shear stress are large enough to induce hemolysis or damage the cell membrane close to the oscillating bubble. Next, the streamlines and stagnation points are obtained for a rigid and a flexible vessel.

  11. 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).

  12. Use of Contrast-Enhanced Ultrasound in Carotid Atherosclerotic Disease: Limits and Perspectives

    PubMed Central

    Varetto, Gianfranco; Gibello, Lorenzo; Castagno, Claudio; Quaglino, Simone; Ripepi, Matteo; Benintende, Emilio; Gattuso, Andrea; Garneri, Paolo; Zan, Stefano; Capaldi, Giacomo; Bertoldo, Ugo; Rispoli, Pietro

    2015-01-01

    Contrast-enhanced ultrasound (CEUS) has recently become one of the most versatile and powerful diagnostic tools in vascular surgery. One of the most interesting fields of application of this technique is the study of the carotid atherosclerotic plaque vascularization and its correlation with neurological symptoms (transient ischemic attack, minor stroke, and major stroke) and with the characteristics of the “vulnerable plaque” (surface ulceration, hypoechoic plaques, intraplaque hemorrhage, thinner fibrous cap, and carotid plaque neovascularization at histopathological analysis of the sample after surgical removal). The purpose of this review is to collect all the original studies available in literature (24 studies with 1356 patients enrolled) and to discuss the state of the art, limits, and future perspectives of CEUS analysis. The results of this work confirm the reliability of this imaging study for the detection of plaques with high risk of embolization; however, a shared, user-friendly protocol of imaging analysis is not available yet. The definition of this operative protocol becomes mandatory in order to compare results from different centers and to validate a cerebrovascular risk stratification of the carotid atherosclerotic lesions evaluated with CEUS. PMID:26180793

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

    PubMed

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

    2016-10-01

    Contrast agents are currently being modified to combine diagnostic and therapeutic capabilities. For ultrasound (US) imaging with polymeric contrast agents, it is necessary to modify the shell to create "stealth" microbubbles but without these modifications sacrificing the agent's ability to interact with the focused US beam. We hypothesize that addition of the classic immune shielding molecule polyethylene glycol (PEG) to a polylactide (PLA) microbubble shell will affect the acoustic and physical properties of the resulting agents. In an effort to determine the best formulation to achieve a balance between stealth and acoustic activity, we compared two PEGylation techniques; addition of increasing amounts of PEG-PLA copolymer and employing incorporation of a PEG lipid (LipidPEG) into the shell. Loss of acoustic enhancement occurred in a dose-dependent manner for both types of PEGylated agents (loss of signal occurred at >5 wt% PEG-PLA and >1 wt% LipidPEG), while immune activation was also reduced in a dose-dependent manner for the PEG-PLA agents. This study shows that the balance between acoustic behavior and improved immune avoidance was scalable and successful to different degrees with both PEGylation methods, and was best achieved using for PEG-PLA at 5 wt% and for LipidPEG at 1 wt%. Studies are ongoing to evaluate the best method for the targeting and drug delivery capabilities of these agents for applications in cancer treatment. This study represents the basis for understanding the consequences of making modifications to the native polymeric shell. PMID:27388945

  14. Dynamic contrast-enhanced ultrasound for differential diagnosis of submandibular gland disease.

    PubMed

    Strieth, Sebastian; Siedek, Vanessa; Rytvina, Margarita; Gürkov, Robert; Berghaus, Alexander; Clevert, Dirk-André

    2014-01-01

    Intensity-time gradients (ITGs) of contrast-enhanced ultrasound (CEUS) can be used for non-invasive monitoring of gland-preserving treatment effects in sialolithiasis-related chronic sialadenitis as well as for imaging vascularization in tumors. The aim of this clinical trial was to evaluate feasibility to distinguish different entities of submandibular gland disease including inflammatory alterations of the submandibular gland as well as benign and malignant tumors. In this prospective clinical study, ITGs in 30 patients with sialolithiasis-related chronic sialadenitis or an unilateral submandibular mass and 18 disease-free submandibular gland controls were quantitatively analyzed by CEUS using the contrast agent SonoVue. In addition, clinical complaints according to visual analog scales (VAS) were documented. VAS data documented significantly less complaints only in benign tumors compared with the other pathologies of the submandibular gland. In parallel, CEUS-derived ITGs revealed significantly reduced ITGs only in benign tumors (n = 5) compared to the controls (n = 18). Despite of comparably reduced wash-in velocities in malignant lesions (n = 3) statistical significance was not reached. Chronic sialadenitis (n = 18) and its sclerosing variant (Küttner tumor, n = 4) revealed comparable ITGs as controls. Tumors of the submandibular gland present with reduced functional microcirculatory networks comparing with healthy gland controls and chronically inflamed submandibular glands. Thus, dynamic CEUS-derived ITGs in combination with conventional clinical measures--for example VAS--appear as a safe and promising strategy for non-invasive diagnostic workup of submandibular lesions and warrant further validation in a larger set of patients. PMID:23625388

  15. Comparison of Superb Micro-Vascular Ultrasound Imaging (SMI) and Contrast-Enhanced Ultrasound (CEUS) for Detection of Endoleaks After Endovascular Aneurysm Repair (EVAR)

    PubMed Central

    Gabriel, Marcin; Tomczak, Jolanta; Snoch-Ziółkiewicz, Magdalena; Dzieciuchowicz, Łukasz; Strauss, Ewa; Oszkinis, Grzegorz

    2016-01-01

    Patient: Male, 68 Final Diagnosis: Unusual clinical course Symptoms: None Medication: — Clinical Procedure: Angio CT Specialty: Surgery Objective: Challenging differential diagnosis Background: High-resolution contrast-enhanced ultrasound is one of methods used in the detection and characterization of endoleaks, which is a frequent complication after EVAR. A new technology provided by Toshiba’s AplioTM 500 ultrasound system, called Superb Micro-Vascular Imaging (SMI), is dedicated specifically to imaging very low flow states and appears to be a promising new method for detection of endoleaks. Case Report: After endovascular treatment, a 68-year-old patient who had stent-graft implantation underwent clinical examinations, including contrast-enhanced ultrasound (CEUS), superb micro-vascular imaging (SMI), and computed tomographic angiography (CTA), revealing additional information about abnormal blood flow localized in the periphery of the sack of the left common iliac artery aneurysm. By using CEUS and SMI, the endoleak was clearly visible. Conclusions: This case report illustrates the potential clinical value of this advanced Doppler technology (SMI) and how it could influence clinical management. PMID:26806053

  16. Specific contrast ultrasound using sterically stabilized microbubbles for early diagnosis of thromboembolic disease in a rabbit model

    PubMed Central

    Vlašín, Michal; Lukáč, Robert; Kauerová, Zuzana; Kohout, Pavel; Mašek, Josef; Bartheldyová, Eliška; Koudelka, Štěpán; Korvasová, Zina; Plocková, Jana; Hronová, Nikola; Turánek, Jaroslav

    2014-01-01

    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. PMID:24688175

  17. 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.

  18. 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. PMID:27512847

  19. Microflow imaging of contrast-enhanced ultrasound for evaluation of neovascularization in peripheral lung cancer

    PubMed Central

    Wang, Song; Yang, Wei; Fu, Jing-Jing; Sun, Yu; Zhang, Hui; Bai, Jing; Chen, Min-Hua; Yan, Kun

    2016-01-01

    Abstract 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. PMID:27512847

  20. Automatic motion estimation using flow parameters for dynamic contrast-enhanced ultrasound

    NASA Astrophysics Data System (ADS)

    Barrois, Guillaume; Coron, Alain; Lucidarme, Olivier; Bridal, S. Lori

    2015-03-01

    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.

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

    NASA Astrophysics Data System (ADS)

    Andersen, Klaus Scheldrup; Jensen, Jørgen Arendt

    2010-01-01

    Local blood pressure measurements provide important information on the state of health of organs in the body and can be used to diagnose diseases in the heart, lungs, and kidneys. This paper presents an experimental setup for investigating the ambient pressure sensitivity of a contrast agent using diagnostic ultrasound. The setup resembles a realistic clinical setup utilizing a single array transducer for transmit and receive. The ambient pressure sensitivity of SonoVue (Bracco, Milano, Italy) was measured twice using two different acoustic driving pressures, which were selected based on a preliminary experiment. To compensate for variations in bubble response and to make the estimates more robust, the relation between the energy of the subharmonic and the fundamental component was chosen as a measure over the subharmonic peak amplitude. The preliminary study revealed the growth stage of the subharmonic component to occur at acoustic driving pressures between 300 and 500 kPa. Based on this, the pressure sensitivity was investigated using a driving pressure of 485 and 500 kPa. At 485 kPa, a linear pressure sensitivity of 0.42 dB/kPa was found having a linear correlation coefficient of 0.94. The second measurement series at 485 kPa showed a sensitivity of 0.41 dB/kPa with a correlation coefficient of 0.89. Based on the measurements at 500 kPa, this acoustic driving pressure was concluded to be too high causing the bubbles to be destroyed. The pressure sensitivity for these two measurement series were 0.42 and 0.25 dB/kPa with linear correlation coefficients of 0.98 and 0.93, respectively.

  2. Ultrasound

    MedlinePlus

    ... please enable JavaScript. Ultrasound uses high-frequency sound waves to make images of organs and structures inside ... examined. The machine sends out high-frequency sound waves, which reflect off body structures. A computer receives ...

  3. Quantitative Assessment of Cancer Vascular Architecture by Skeletonization of High-resolution 3-D Contrast-enhanced Ultrasound Images

    PubMed Central

    Molinari, F.; Meiburger, K. M.; Giustetto, P.; Rizzitelli, S.; Boffa, C.; Castano, M.; Terreno, E.

    2014-01-01

    The accurate characterization and description of the vascular network of a cancer lesion is of paramount importance in clinical practice and cancer research in order to improve diagnostic accuracy or to assess the effectiveness of a treatment. The aim of this study was to show the effectiveness of liposomes as an ultrasound contrast agent to describe the 3-D vascular architecture of a tumor. Eight C57BL/6 mice grafted with syngeneic B16-F10 murine melanoma cells were injected with a bolus of 1,2-Distearoyl-sn-glycero-3-phosphocoline (DSPC)-based non-targeted liposomes and with a bolus of microbubbles. 3-D contrast-enhanced images of the tumor lesions were acquired in three conditions: pre-contrast, after the injection of microbubbles, and after the injection of liposomes. By using a previously developed reconstruction and characterization image processing technique, we obtained the 3-D representation of the vascular architecture in these three conditions. Six descriptive parameters of these networks were also computed: the number of vascular trees (NT), the vascular density (VD), the number of branches, the 2-D curvature measure, the number of vascular flexes of the vessels, and the 3-D curvature. Results showed that all the vascular descriptors obtained by liposome-based images were statistically equal to those obtained by using microbubbles, except the VD which was found to be lower for liposome images. All the six descriptors computed in pre-contrast conditions had values that were statistically lower than those computed in presence of contrast, both for liposomes and microbubbles. Liposomes have already been used in cancer therapy for the selective ultrasound-mediated delivery of drugs. This work demonstrated their effectiveness also as vascular diagnostic contrast agents, therefore proving that liposomes can be used as efficient “theranostic” (i.e. therapeutic + diagnostic) ultrasound probes. PMID:24206210

  4. Stability of echogenic liposomes as a blood pool ultrasound contrast agent in a physiologic flow phantom

    PubMed Central

    Radhakrishnan, Kirthi; Haworth, Kevin J.; Huang, Shao-Ling; Klegerman, Melvin E.; McPherson, David D.; Holland, Christy K.

    2016-01-01

    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 acoustic properties. Further in vivo

  5. Role of contrast-enhanced ultrasound in follow-up assessment after ablation for hepatocellular carcinoma

    PubMed Central

    Zheng, Shu-Guang; Xu, Hui-Xiong; Lu, Ming-De; Xie, Xiao-Yan; Xu, Zuo-Feng; Liu, Guang-Jian; Liu, Lin-Na

    2013-01-01

    AIM: To assess the usefulness of contrast-enhanced ultrasound (CEUS) during follow-up after percutaneous ablation therapy for hepatocellular carcinoma (HCC). METHODS: A total of 141 patients with HCCs who received percutaneous ablation therapy were assessed by paired follow-up CEUS and contrast-enhanced computed tomography (CECT). The follow-up scheme was designed prospectively and the intervals between CEUS and CECT examinations were less than 14 d. Both images of follow-up CEUS and CECT were reviewed by radiologists. The ablated lesions were evaluated and classified as local tumor progression (LTP) and LTP-free. LTP was defined as regrowth of tumor inside or adjacent to the successfully treated nodule. The detected new intrahepatic recurrences were also evaluated and defined as presence of intrahepatic new foci. On CEUS and CECT, LTP and new intrahepatic recurrence both were displayed as typical enhancement pattern of HCC (i.e., hyper-enhancing during the arterial phase and washout in the late phase). With CECT as the reference standard, the ability of CEUS in detecting LTP or new intrahepatic recurrence during follow-up was evaluated. RESULTS: During a follow-up period of 1-31 mo (median, 4 mo), 169 paired CEUS and CECT examinations were carried out for the 141 patients. For a total of 221 ablated lesions, 266 comparisons between CEUS and CECT findings were performed. Thirty-three LTPs were detected on CEUS whereas 40 LTPs were detected on CECT, there was significant difference (P < 0.001). In comparison with CECT, the numbers of false positive and false negative LTPs detected on CEUS were 6 and 13, respectively; the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy of CEUS in detecting LTPs were 67.5%, 97.4%, 81.8%, 94.4% and 92.3%, respectively. Meanwhile, 131 new intrahepatic recurrent foci were detected on CEUS whereas 183 were detected on CECT, there was also significant difference (P < 0.05). In

  6. 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

  7. 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

  8. 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

  9. When is contrast-enhanced sonography preferable over conventional ultrasound combined with Doppler imaging in renal transplantation?

    PubMed Central

    Zeisbrich, Markus; Kihm, Lars P.; Drüschler, Felix; Zeier, Martin; Schwenger, Vedat

    2015-01-01

    Conventional ultrasound in combination with colour Doppler imaging is still the standard diagnostic procedure for patients after renal transplantation. However, while conventional ultrasound in combination with Doppler imaging can diagnose renal artery stenosis and vein thrombosis, it is not possible to display subtle microvascular tissue perfusion, which is crucial for the evaluation of acute and chronic allograft dysfunctions. In contrast, real-time contrast-enhanced sonography (CES) uses gas-filled microbubbles not only to visualize but also to quantify renal blood flow and perfusion even in the small renal arterioles and capillaries. It is an easy to perform and non-invasive imaging technique that augments diagnostic capabilities in patients after renal transplantation. Specifically in the postoperative setting, CES has been shown to be superior to conventional ultrasound in combination with Doppler imaging in uncovering even subtle microvascular disturbances in the allograft perfusion. In addition, quantitative perfusion parameters derived from CES show predictive capability regarding long-term kidney function. PMID:26413289

  10. 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

  11. Effectiveness of contrast-enhanced harmonic endoscopic ultrasound for the evaluation of solid pancreatic masses

    PubMed Central

    Park, Jin-Seok; Kim, Hyung Kil; Bang, Byoung Wook; Kim, Sang Gu; Jeong, Seok; Lee, Don Haeng

    2014-01-01

    AIM: To evaluate the usefulness of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) in differentiating between pancreatic adenocarcinomas and other pancreatic disease. METHODS: This retrospective cohort study evaluated 90 patients who were seen between November 2010 and May 2013. All these patients had solid pancreatic masses that had a hypoechoic appearance on EUS. All patients underwent CH-EUS to evaluate this diagnostic method’s usefulness. The mass lesions observed on CH-EUS were classified into three categories based on their echo intensity: hypoenhanced, isoenhanced, and hyperenhanced lesions. We adjusted the sensitivity and the specificity of each category for detecting malignancies. We also estimated the accuracy of CH-EUS by comparing it to a pathological diagnosis. RESULTS: Of the 90 patients, 62 had a pancreatic adenocarcinoma. Fifty-seven out of 62 pancreatic adenocarcinomas showed a hypoenhanced pattern on CH-EUS. The sensitivity was 92%, the specificity 68% and the accuracy approximately 82%. The area under the curve of the receiver operating characteristic analysis for CH-EUS was 0.799. There is a significant association between the hypoenhanced pattern on CH-EUS and pancreatic duct adenocarcinoma (χ2 = 35.264, P < 0.001). In pathological examinations, the number of specimens for EUS-fine needle aspiration (EUS-FNA) was considered insufficient for diagnosis in three patients, and in two patients, the results were reported to be negative for malignancy. Pancreatic masses in all five patients revealed a hypoenhanced pattern with CH-EUS. Three patients were diagnosed with pancreatic adenocarcinoma based on the pathology results of a biopsy, and the remaining two patients were clinically diagnosed with malignancy. CONCLUSION: CH-EUS is useful for distinguishing between pancreatic adenocarcinoma and other pancreatic disease. When a pancreatic mass shows a hypoenhanced pattern on CH-EUS but involves either insufficient samples or negative

  12. 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

  13. Percutaneous Ultrasound-Guided Laser Ablation with Contrast-Enhanced Ultrasonography for Hyperfunctioning Parathyroid Adenoma: A Preliminary Case Series

    PubMed Central

    Jiang, Tianan; Chen, Fen; Zhou, Xiang; Hu, Ying; Zhao, Qiyu

    2015-01-01

    The study was to evaluate the safety and effectiveness of ultrasound-guided percutaneous laser ablation (pLA) as a nonsurgical treatment for primary parathyroid adenoma. Surgery was contraindicated in, or refused by, the included patients. No lesion enhancement on contrast-enhanced ultrasound immediately after pLA was considered “complete ablation.” Nodule size, serum calcium, and parathyroid hormone level were compared before and after pLA. Complete ablation was achieved in all 21 patients with 1 (n = 20) or 2 (n = 1) sessions. Nodule volume decreased from 0.93 ± 0.58 mL at baseline to 0.53 ± 0.38 and 0.48 ± 0.34 mL at 6 and 12 months after pLA (P < 0.05). At 1 day, 6 months, and 12 months after pLA, serum PTH decreased from 15.23 ± 3.00 pmol/L at baseline to 7.41 ± 2.79, 6.95 ± 1.78, and 6.90 ± 1.46 pmol/L, serum calcium decreased from 3.77 ± 0.77 mmol/L at baseline to 2.50 ± 0.72, 2.41 ± 0.37, and 2.28 ± 0.26 mmol/L, respectively (P < 0.05). At 12 months, treatment success (normalization of PTH and serum calcium) was achieved in 81%. No serious complications were observed. Ultrasound-guided pLA with contrast-enhanced ultrasound is a viable alternative to surgery for primary parathyroid adenoma. PMID:26788059

  14. Percutaneous Ultrasound-Guided Laser Ablation with Contrast-Enhanced Ultrasonography for Hyperfunctioning Parathyroid Adenoma: A Preliminary Case Series.

    PubMed

    Jiang, Tianan; Chen, Fen; Zhou, Xiang; Hu, Ying; Zhao, Qiyu

    2015-01-01

    The study was to evaluate the safety and effectiveness of ultrasound-guided percutaneous laser ablation (pLA) as a nonsurgical treatment for primary parathyroid adenoma. Surgery was contraindicated in, or refused by, the included patients. No lesion enhancement on contrast-enhanced ultrasound immediately after pLA was considered "complete ablation." Nodule size, serum calcium, and parathyroid hormone level were compared before and after pLA. Complete ablation was achieved in all 21 patients with 1 (n = 20) or 2 (n = 1) sessions. Nodule volume decreased from 0.93 ± 0.58 mL at baseline to 0.53 ± 0.38 and 0.48 ± 0.34 mL at 6 and 12 months after pLA (P < 0.05). At 1 day, 6 months, and 12 months after pLA, serum PTH decreased from 15.23 ± 3.00 pmol/L at baseline to 7.41 ± 2.79, 6.95 ± 1.78, and 6.90 ± 1.46 pmol/L, serum calcium decreased from 3.77 ± 0.77 mmol/L at baseline to 2.50 ± 0.72, 2.41 ± 0.37, and 2.28 ± 0.26 mmol/L, respectively (P < 0.05). At 12 months, treatment success (normalization of PTH and serum calcium) was achieved in 81%. No serious complications were observed. Ultrasound-guided pLA with contrast-enhanced ultrasound is a viable alternative to surgery for primary parathyroid adenoma. PMID:26788059

  15. Ultrasonograpy of VX-2 Liver Tumor in Rabbit Treated by High Intensity Focused Ultrasound Combined with Microbubble Contrast Agent

    NASA Astrophysics Data System (ADS)

    Xiaojuan, Ji; Jinqing, Li; Zhibiao, Wang; Jianzhong, Zou; Wenzhi, Chen; Jin, Bai

    2007-05-01

    Objective: To assess the value of sonographic appearance and to investigate the sonographic character of VX-2 liver tumor in rabbit treated by high intensity focused ultrasound (HIFU) combined with microbubble contrast agent. Methods: Forty-five rabbits bearing VX-2 tumors were randomly averagely assigned into three groups. In group A irradiation was sustained until the target region became hyperechoic. In group B therapy was stopped as soon as hyperecho occurred, and in group C irradiation time was prolonged to ensure the occurrence of coagulation necrosis. Results: Exposure duration for tumors treated purely with HIFU was the longest, whilst the use of microbubble contrast agent combined with HIFU shortened the exposure duration significantly. The gross examination and ultrasonogram coagulation necrosis area measurements correlated strongly (r=0.986,P<0.05) in the microbubble-enhanced HIFU group. Conclusion: It was feasible to enhance HIFU therapy with microbubble contrast agent. The characteristic change in the ultrasound images made it possible to assess the enhanced HIFU therapeutic efficacy in order to adjust the treatment program.

  16. Evaluation of Liver Ischemia-Reperfusion Injury in Rabbits Using a Nanoscale Ultrasound Contrast Agent Targeting ICAM-1

    PubMed Central

    Xie, Fang; Li, Zhi-Ping; Wang, Hong-Wei; Fei, Xiang; Jiao, Zi-Yu; Tang, Wen-Bo; Tang, Jie; Luo, Yu-Kun

    2016-01-01

    Objective To assess the feasibility of ultrasound molecular imaging in the early diagnosis of liver ischemia-reperfusion injury (IRI) using a nanoscale contrast agent targeting anti-intracellular adhesion molecule-1 (anti-ICAM-1). Methods The targeted nanobubbles containing anti-ICAM-1 antibody were prepared using the avidin-biotin binding method. Human hepatic sinusoidal endothelial cells (HHSECs) were cultured at the circumstances of hypoxia/reoxygenation (H/R) and low temperature. The rabbit liver IRI model (I/R group) was established using the Pringle’s maneuver. The time-intensity curve of the liver contrast ultrasonographic images was plotted and the peak intensity, time to peak, and time of duration were calculated. Results The size of the targeted nanobubbles were 148.15 ± 39.75 nm and the concentration was 3.6–7.4 × 109/ml, and bound well with the H/R HHSECs. Animal contrast enhanced ultrasound images showed that the peak intensity and time of duration of the targeted nanobubbles were significantly higher than that of common nanobubbles in the I/R group, and the peak intensity and time of duration of the targeted nanobubbles in the I/R group were also significantly higher than that in the SO group. Conclusion The targeted nanobubbles have small particle size, stable characteristic, and good targeting ability, which can assess hepatic ischemia-reperfusion injury specifically, noninvasively, and quantitatively at the molecular level. PMID:27120181

  17. Intense acoustic burst ultrasound modulated optical tomography for elasticity mapping of soft biological tissue mimicking phantom: a laser speckle contrast analysis study

    NASA Astrophysics Data System (ADS)

    Singh, M. Suheshkumar; Rajan, K.; Vasu, R. M.

    2014-03-01

    This report addresses the assessment of variation in elastic property of soft biological tissues non-invasively using laser speckle contrast measurement. The experimental as well as the numerical (Monte-Carlo simulation) studies are carried out. In this an intense acoustic burst of ultrasound (an acoustic pulse with high power within standard safety limits), instead of continuous wave, is employed to induce large modulation of the tissue materials in the ultrasound insonified region of interest (ROI) and it results to enhance the strength of the ultrasound modulated optical signal in ultrasound modulated optical tomography (UMOT) system. The intensity fluctuation of speckle patterns formed by interference of light scattered (while traversing through tissue medium) is characterized by the motion of scattering sites. The displacement of scattering particles is inversely related to the elastic property of the tissue. We study the feasibility of laser speckle contrast analysis (LSCA) technique to reconstruct a map of the elastic property of a soft tissue-mimicking phantom. We employ source synchronized parallel speckle detection scheme to (experimentally) measure the speckle contrast from the light traversing through ultrasound (US) insonified tissue-mimicking phantom. The measured relative image contrast (the ratio of the difference of the maximum and the minimum values to the maximum value) for intense acoustic burst is 86.44 % in comparison to 67.28 % for continuous wave excitation of ultrasound. We also present 1-D and 2-D image of speckle contrast which is the representative of elastic property distribution.

  18. Development and Optimization of a Doxorubicin Loaded Poly Lactic Acid Contrast Agent for Ultrasound Directed Drug Delivery

    PubMed Central

    Eisenbrey, J.R.; Burstein, O. Mualem; Kambhampati, R.; Forsberg, F.; Liu, J-B.; Wheatley, M.A.

    2010-01-01

    An echogenic, intravenous drug delivery platform is proposed in which an encapsulated chemotherapeutic can travel to a desired location and drug delivery can be triggered using external, focused ultrasound at the area of interest. Three methods of loading poly lactic acid (PLA) shelled ultrasound contrast agents (UCA) with doxorubicin are presented. Effects on encapsulation efficiency, in vitro enhancement, stability, particle size, morphology and release during UCA rupture are compared by loading method and drug concentration. An agent containing doxorubicin within the shell was selected as an ideal candidate for future hepatocellular carcinoma studies. The agent achieved a maximal drug load of 6.2 mg Dox/g PLA with an encapsulation efficiency of 20.5%, showed a smooth surface morphology and tight size distribution (poly dispersity index = 0.309) with a peak size of 1865 nm. Acoustically, the agent provided 19 dB of enhancement in vitro at a dosage of 10 µg/ml, with a half life of over 15 mins. In vivo, the agent provided ultrasound enhancement of 13.4 ± 1.6 dB within the ascending aorta of New Zealand rabbits at a dose of 0.15 ml/kg. While the drug-incorporated agent is thought to be well suited for future drug delivery experiments, this study has shown that agent properties can be tailored for specific applications based on choice of drug loading method. PMID:20060024

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

    PubMed Central

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

    2016-01-01

    This study is to prepare a hematoporphyrin monomethyl ether (HMME)-loaded poly(lactic-co-glycolic acid) (PLGA) microcapsules (HMME/PLGA), which could not only function as efficient contrast agent for ultrasound (US)/photoacoustic (PA) imaging, but also as a synergistic agent for high intensity focused ultrasound (HIFU) ablation. Sonosensitizer HMME nanoparticles were integrated into PLGA microcapsules with the double emulsion evaporation method. After characterization, the cell-killing and cell proliferation-inhibiting effects of HMME/PLGA microcapsules on ovarian cancer SKOV3 cells were assessed. The US/PA imaging-enhancing effects and synergistic effects on HIFU were evaluated both in vitro and in vivo. HMME/PLGA microcapsules were highly dispersed with well-defined spherical morphology (357 ± 0.72 nm in diameter, PDI = 0.932). Encapsulation efficiency and drug-loading efficiency were 58.33 ± 0.95% and 4.73 ± 0.15%, respectively. The HMME/PLGA microcapsules remarkably killed the SKOV3 cells and inhibited the cell proliferation, significantly enhanced the US/PA imaging results and greatly enhanced the HIFU ablation effects on ovarian cancer in nude mice by the HMME-mediated sono-dynamic chemistry therapy (SDT). HMME/PLGA microcapsules represent a potential multifunctional contrast agent for HIFU diagnosis and treatment, which might provide a novel strategy for the highly efficient imaging-guided non-invasive HIFU synergistic therapy for cancers by SDT in clinic. PMID:27535093

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

    PubMed

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

    2016-01-01

    This study is to prepare a hematoporphyrin monomethyl ether (HMME)-loaded poly(lactic-co-glycolic acid) (PLGA) microcapsules (HMME/PLGA), which could not only function as efficient contrast agent for ultrasound (US)/photoacoustic (PA) imaging, but also as a synergistic agent for high intensity focused ultrasound (HIFU) ablation. Sonosensitizer HMME nanoparticles were integrated into PLGA microcapsules with the double emulsion evaporation method. After characterization, the cell-killing and cell proliferation-inhibiting effects of HMME/PLGA microcapsules on ovarian cancer SKOV3 cells were assessed. The US/PA imaging-enhancing effects and synergistic effects on HIFU were evaluated both in vitro and in vivo. HMME/PLGA microcapsules were highly dispersed with well-defined spherical morphology (357 ± 0.72 nm in diameter, PDI = 0.932). Encapsulation efficiency and drug-loading efficiency were 58.33 ± 0.95% and 4.73 ± 0.15%, respectively. The HMME/PLGA microcapsules remarkably killed the SKOV3 cells and inhibited the cell proliferation, significantly enhanced the US/PA imaging results and greatly enhanced the HIFU ablation effects on ovarian cancer in nude mice by the HMME-mediated sono-dynamic chemistry therapy (SDT). HMME/PLGA microcapsules represent a potential multifunctional contrast agent for HIFU diagnosis and treatment, which might provide a novel strategy for the highly efficient imaging-guided non-invasive HIFU synergistic therapy for cancers by SDT in clinic. PMID:27535093

  1. Ultrasound (US) transducer of higher operating frequency detects photoacoustic (PA) signals due to the contrast in elastic property

    NASA Astrophysics Data System (ADS)

    Singh, Mayanglambam Suheshkumar; Jiang, Huabei

    2016-02-01

    We report our study that shows selection in operating frequency of US-transducer used for boundary detection of PA-signals, which result due to the contrast in elastic property distribution ( E ( r → ) ) in sample material other than that of optical absorption coefficient (μa). Studies were carried out, experimentally, in tissue-mimicking Agar phantoms employing acoustic resolution photoacoustic microscopy (AR-PAM) system as an imaging unit. In the experiments, various transducers having different operating frequencies, ranging from 1MHz to 50MHz, were employed for studying frequency response of the photoacoustic signals. The study shows that, for detecting photoacoustic signals due to the contrast in elastic property, ultrasound transducer with higher operating frequency (˜50MHz) is demanded.

  2. Skeletonization approach for characterization of benign vs. malignant single thyroid nodules using 3D contrast enhanced ultrasound

    NASA Astrophysics Data System (ADS)

    Molinari, Filippo; Mantovani, Alice; Deandrea, Maurilio; Limone, Paolo; Garberoglio, Roberto; Suri, Jasjit S.

    2011-03-01

    High-resolution ultrasonography (HRUS) has potentialities in differential diagnosis between malignant and benign thyroid lesions, but interpretative pitfalls remain and accuracy is still poor. We developed an image processing technique for characterizing the intra-nodular vascularization of thyroid lesions. Twenty nodules (ten malignant) were analyzed by 3-D contrast-enhanced ultrasound imaging. The 3-D volumes were preprocessed and skeletonized. Seven vascular parameters were computed on the skeletons: number of vascular trees (NT); vascular density (VD); number of branching nodes (or branching points) (NB); mean vessel radius (MR); 2-D (DM) and 3-D (SOAM) tortuosity; and inflection count metric (ICM). Results showed that the malignant nodules had higher values of NT (83.1 vs. 18.1), VD (00.4 vs. 0.01), NB (1453 vs. 552), DM (51 vs. 18), ICM (19.9 vs. 8.7), and SOAM (26 vs. 11). Quantification of nodular vascularization based on 3-D contrast-enhanced ultrasound and skeletonization could help differential diagnosis of thyroid lesions.

  3. Preoperative Gross Classification of Gastric Adenocarcinoma: Comparison of Double Contrast-Enhanced Ultrasound and Multi-Detector Row CT.

    PubMed

    Yan, Caoxin; Bao, Xiaofeng; Shentu, Weihui; Chen, Jian; Liu, Chunmei; Ye, Qin; Wang, Liuhong; Tan, Yangbin; Huang, Pintong

    2016-07-01

    The aim of this study was to compare the accuracy of multi-detector computed tomography (MDCT) with double contrast-enhanced ultrasound (DCEUS), in which intravenous microbubbles are used alongside oral contrast-enhanced ultrasound, in determining the gross classification of patients with gastric carcinoma (GC). Altogether, 239 patients with GC proved by histology after endoscopic biopsy were included in this study. DCEUS and MDCT were performed pre-operatively. The diagnostic accuracies of DCEUS and MDCT in determining the gross classification were calculated and compared. The overall accuracy of DCEUS in determining the gross appearance of GC was higher than that of MDCT (84.9% vs. 79.9%, p < 0.001). There was no significant difference in accuracy between DCEUS and MDCT for Borrmann I and IV classifications of advanced gastric cancer (χ(2), p = 0.323 for Borrmann type I, p = 0.141 for Borrmann type IV). The accuracy of DCEUS for early GC and Borrmann II and III classifications of GC was higher than that of MDCT (χ(2), p = 0.000 for all). DCEUS may be regarded as a valuable complementary tool to MDCT in determining the gross appearance of gastric adenocarcinoma pre-operatively. PMID:27072076

  4. Functional Flow Patterns and Static Blood Pooling in Tumors Revealed by Combined Contrast-Enhanced Ultrasound and Photoacoustic Imaging.

    PubMed

    Bar-Zion, Avinoam; Yin, Melissa; Adam, Dan; Foster, F Stuart

    2016-08-01

    Alterations in tumor perfusion and microenvironment have been shown to be associated with aggressive cancer phenotypes, raising the need for noninvasive methods of tracking these changes. Dynamic contrast-enhanced ultrasound (DCEUS) and photoacoustic (PA) imaging serve as promising candidates-one has the ability to measure tissue perfusion, whereas the other can be used to monitor tissue oxygenation and hemoglobin concentration. In this study, we investigated the relationship between the different functional parameters measured with DCEUS and PA imaging, using two morphologically different hind-limb tumor models and drug-induced alterations in an orthotopic breast tumor model. Imaging results showed some correlation between perfusion and oxygen saturation maps and the ability to sensitively monitor antivascular treatment. In addition, DCEUS measurements revealed different vascular densities in the core of specific tumors compared with their rims. Noncorrelated perfusion and hemoglobin concentration measurements facilitated discrimination between blood lakes and necrotic areas. Taken together, our results illustrate the utility of a combined contrast-enhanced ultrasound method with photoacoustic imaging to visualize blood flow patterns in tumors. Cancer Res; 76(15); 4320-31. ©2016 AACR. PMID:27325651

  5. Conditionally Increased Acoustic Pressures in Nonfetal Diagnostic Ultrasound Examinations Without Contrast Agents: A Preliminary Assessment

    PubMed Central

    Nightingale, Kathryn R.; Church, Charles C.; Harris, Gerald; Wear, Keith A.; Bailey, Michael R.; Carson, Paul L.; Jiang, Hui; Sandstrom, Kurt L.; Szabo, Thomas L.; Ziskin, Marvin C.

    2016-01-01

    The mechanical index (MI) has been used by the US Food and Drug Administration (FDA) since 1992 for regulatory decisions regarding the acoustic output of diagnostic ultrasound equipment. Its formula is based on predictions of acoustic cavitation under specific conditions. Since its implementation over 2 decades ago, new imaging modes have been developed that employ unique beam sequences exploiting higher-order acoustic phenomena, and, concurrently, studies of the bioeffects of ultrasound under a range of imaging scenarios have been conducted. In 2012, the American Institute of Ultrasound in Medicine Technical Standards Committee convened a working group of its Output Standards Subcommittee to examine and report on the potential risks and benefits of the use of conditionally increased acoustic pressures (CIP) under specific diagnostic imaging scenarios. The term “conditionally” is included to indicate that CIP would be considered on a per-patient basis for the duration required to obtain the necessary diagnostic information. This document is a result of that effort. In summary, a fundamental assumption in the MI calculation is the presence of a preexisting gas body. For tissues not known to contain preexisting gas bodies, based on theoretical predications and experimentally reported cavitation thresholds, we find this assumption to be invalid. We thus conclude that exceeding the recommended maximum MI level given in the FDA guidance could be warranted without concern for increased risk of cavitation in these tissues. However, there is limited literature assessing the potential clinical benefit of exceeding the MI guidelines in these tissues. The report proposes a 3-tiered approach for CIP that follows the model for employing elevated output in magnetic resonance imaging and concludes with summary recommendations to facilitate Institutional Review Board (IRB)-monitored clinical studies investigating CIP in specific tissues. PMID:26112617

  6. A novel dual-targeted ultrasound contrast agent provides improvement of gene delivery efficiency in vitro.

    PubMed

    Xu, Jinfeng; Zeng, Xinxin; Liu, Yingying; Luo, Hui; Wei, Zhanghong; Liu, Huiyu; Zhou, Yuli; Zheng, Hairong; Zhou, Jie; Tan, Guanghong; Yan, Fei

    2016-07-01

    Ultrasound-targeted microbubble destruction (UTMD) has become a novel gene/drug delivery method in cancer therapeutic application. However, the gene transfection efficiency mediated by UTMD is still unsatisfactory. Here, we introduced iRGD/CCR2 dual-targeted cationic microbubbles (MBiRGD/CCR2) which was modified with PEI-600 and coated with iRGD peptides and anti-CCR-2 antibodies. It showed that MBiRGD/CCR2 had a 25.83 ± 1.57 mV surface zeta potential and good stability. The experiments in vitro showed MBiRGD/CCR2 had higher binding efficiency with both bEnd.3 cells and MCF-7 cells than that of iRGD or CCR2 single-targeted cationic microbubbles (MBiRGD or MBCCR2) (P < 0.05 for both). Agarose gel electrophoresis assay showed that MBiRGD/CCR2 can effectively load pGPU6/GFP/Neo-shAKT2 plasmid DNA. Compared with the plain MBs (MBcontrol) or single-targeted cationic MBs including MBiRGD and MBCCR2 (P < 0.05 for all), the dual-targeted cationic MBiRGD/CCR2 groups had higher gene transfection efficiency under US exposure. It showed that the dual-targeted cationic MBiRGD/CCR2 has a potential value to be used as an ultrasound imaging probe for ultrasound image-guided tumor gene therapy. PMID:26733178

  7. Doppler photoacoustic and Doppler ultrasound in blood with optical contrast agent

    NASA Astrophysics Data System (ADS)

    Sheinfeld, Adi; Eyal, Avishay

    2013-03-01

    Photoacoustic Doppler flowmetry as well as Doppler ultrasound were performed in acoustic resolution regime on tubes filled with flowing blood with indocyanine green (ICG) at different concentrations. The photoacoustic excitation utilized a pair of directly-modulated fiber-coupled 830nm laser-diodes, modulated with either CW or tone-bursts for depthresolved measurements. The amplitude of the Doppler peak in photoacoustic Doppler measurements was found to be proportional to the ICG concentration. Photoacoustic Doppler was measured in ICG at human safe concentrations, but not in whole blood. Comparing the results between the two modalities implied that using a wavelength with higher optical absorption may improve the photoacoustic signal in blood.

  8. Role of contrast-enhanced ultrasound in evaluating the efficiency of ultrasound guided percutaneous microwave ablation in patients with renal cell carcinoma

    PubMed Central

    Li, Xin; Liang, Ping; Yu, Jie; Yu, Xiao-Ling; Liu, Fang-Yi; Cheng, Zhi-Gang; Han, Zhi-Yu

    2013-01-01

    Background The aim of the study was to evaluate the efficiency and feasibility of contrast-enhanced ultrasound (CEUS) with Sonovue in assessing of renal cell carcinomas (RCCs) following ultrasound (US)-guided percutaneous microwave ablation (MWA). Patinets and methods Seventy-nine patients (60 males and 19 females) with 83 lesions (mean size 3.2±1.6 cm) were treated by US-guided percutaneous MWA. The CEUS results of the third day after the ablation were compared with the synchronous contrast-enhanced computed tomography (CT)/magnetic resonance imaging (MRI) results and biopsy pathological results. The follow-up was performed by CEUS and CT/MRI after 1, 3, 6 months and every 6 months subsequently. The combination of clinical follow-up results and CT/MRI imaging findings was the reference standard of CEUS results for evaluating the therapeutic effect. The identification of residual or recurrence tumour was assessed by two blinded radiologists. Results On the third day after MWA, CEUS showed 68 of 83 lesions (68/83, 81.9%) successfully ablated and 15 of 83 (18.1%) with residual tumours. Among residual tumours, 13 (86.7%) were confirmed by contrast-enhanced CT/MRI findings and biopsy results. The sensitivity, specificity, accuracy, positive and negative predictive value of CEUS evaluating the short-term MWA effectiveness were 100%, 97.1%, 97.6%, 86.7% and 100%, respectively. During the six years follow-up (median 26 months), the CEUS showed recurrence in 7 patients, and six of them achieved consistent results on CEUS and CT/MRI imaging. The sensitivity, specificity, accuracy, positive and negative predictive value for CEUS evaluating long-term MWA effectiveness were 85.7%, 98.7%, 97.6%, 85.7% and 98.7%, respectively. Conclusions The post-procedural CEUS demonstrated as an effective and feasible method in evaluating a therapeutic effect of RCCs following MWA. PMID:24294186

  9. Ultrasound Molecular Imaging of the Breast Cancer Neovasculature using Engineered Fibronectin Scaffold Ligands: A Novel Class of Targeted Contrast Ultrasound Agent

    PubMed Central

    Abou-Elkacem, Lotfi; Wilson, Katheryne E.; Johnson, Sadie M.; Chowdhury, Sayan M.; Bachawal, Sunitha; Hackel, Benjamin J.; Tian, Lu; Willmann, Jürgen K.

    2016-01-01

    Molecularly-targeted microbubbles (MBs) are increasingly being recognized as promising contrast agents for oncological molecular imaging with ultrasound. With the detection and validation of new molecular imaging targets, novel binding ligands are needed that bind to molecular imaging targets with high affinity and specificity. In this study we assessed a novel class of potentially clinically translatable MBs using an engineered 10th type III domain of human-fibronectin (MB-FN3VEGFR2) scaffold-ligand to image VEGFR2 on the neovasculature of cancer. The in vitro binding of MB-FN3VEGFR2 to a soluble VEGFR2 was assessed by flow-cytometry (FACS) and binding to VEGFR2-expressing cells was assessed by flow-chamber cell attachment studies under flow shear stress conditions. In vivo binding of MB-FN3VEGFR2 was tested in a transgenic mouse model (FVB/N Tg(MMTV/PyMT634Mul) of breast cancer and control litter mates with normal mammary glands. In vitro FACS and flow-chamber cell attachment studies showed significantly (P<0.01) higher binding to VEGFR2 using MB-FN3VEGFR2 than control agents. In vivo ultrasound molecular imaging (USMI) studies using MB-FN3VEGFR2 demonstrated specific binding to VEGFR2 and was significantly higher (P<0.01) in breast cancer compared to normal breast tissue. Ex vivo immunofluorescence-analysis showed significantly (P<0.01) increased VEGFR2-expression in breast cancer compared to normal mammary tissue. Our results suggest that MBs coupled to FN3-scaffolds can be designed and used for USMI of breast cancer neoangiogenesis. Due to their small size, stability, solubility, the lack of glycosylation and disulfide bonds, FN3-scaffolds can be recombinantly produced with the advantage of generating small, high affinity ligands in a cost efficient way for USMI. PMID:27570547

  10. Ultrasound Molecular Imaging of the Breast Cancer Neovasculature using Engineered Fibronectin Scaffold Ligands: A Novel Class of Targeted Contrast Ultrasound Agent.

    PubMed

    Abou-Elkacem, Lotfi; Wilson, Katheryne E; Johnson, Sadie M; Chowdhury, Sayan M; Bachawal, Sunitha; Hackel, Benjamin J; Tian, Lu; Willmann, Jürgen K

    2016-01-01

    Molecularly-targeted microbubbles (MBs) are increasingly being recognized as promising contrast agents for oncological molecular imaging with ultrasound. With the detection and validation of new molecular imaging targets, novel binding ligands are needed that bind to molecular imaging targets with high affinity and specificity. In this study we assessed a novel class of potentially clinically translatable MBs using an engineered 10(th) type III domain of human-fibronectin (MB-FN3VEGFR2) scaffold-ligand to image VEGFR2 on the neovasculature of cancer. The in vitro binding of MB-FN3VEGFR2 to a soluble VEGFR2 was assessed by flow-cytometry (FACS) and binding to VEGFR2-expressing cells was assessed by flow-chamber cell attachment studies under flow shear stress conditions. In vivo binding of MB-FN3VEGFR2 was tested in a transgenic mouse model (FVB/N Tg(MMTV/PyMT634Mul) of breast cancer and control litter mates with normal mammary glands. In vitro FACS and flow-chamber cell attachment studies showed significantly (P<0.01) higher binding to VEGFR2 using MB-FN3VEGFR2 than control agents. In vivo ultrasound molecular imaging (USMI) studies using MB-FN3VEGFR2 demonstrated specific binding to VEGFR2 and was significantly higher (P<0.01) in breast cancer compared to normal breast tissue. Ex vivo immunofluorescence-analysis showed significantly (P<0.01) increased VEGFR2-expression in breast cancer compared to normal mammary tissue. Our results suggest that MBs coupled to FN3-scaffolds can be designed and used for USMI of breast cancer neoangiogenesis. Due to their small size, stability, solubility, the lack of glycosylation and disulfide bonds, FN3-scaffolds can be recombinantly produced with the advantage of generating small, high affinity ligands in a cost efficient way for USMI. PMID:27570547

  11. Usefulness of contrast-enhanced ultrasound for detection of carotid plaque ulceration in patients with symptomatic carotid atherosclerosis.

    PubMed

    ten Kate, Gerrit L; van Dijk, Anouk C; van den Oord, Stijn C H; Hussain, Burhan; Verhagen, Hence J M; Sijbrands, Eric J G; van der Steen, Antonius F W; van der Lugt, Aad; Schinkel, Arend F L

    2013-07-15

    Previous data have indicated that carotid plaque ulceration is a strong predictor of cerebrovascular events. Standard ultrasound and color Doppler ultrasound (CDUS) scans have poor diagnostic accuracy for the detection of carotid plaque ulceration. The aim of the present prospective study was to assess the value of contrast-enhanced ultrasound (CEUS) scans for the detection of carotid plaque ulceration. The Institutional Ethics Committee approved the study protocol, and all patients provided informed consent. The patients had symptomatic stenosis of the internal carotid artery and underwent carotid computed tomographic angiography as part of their clinical evaluation. All patients underwent a CDUS examination in conjunction with CEUS. Carotid plaque ulceration was defined as the presence of ≥1 disruptions in the plaque-lumen border ≥1 × 1 mm. Carotid computed tomographic angiography was used as reference technique. The study population consisted of 20 patients (mean age 64 ± 9 years, 80% men), and 39 carotid arteries were included in the present analysis. Computed tomographic angiography demonstrated that the plaque surface was smooth in 15 (38%), irregular in 7 (18%) and ulcerated in 17 (44%) carotid arteries. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CDUS for the detection of ulceration was 29%, 73%, 54%, 46%, and 57%, respectively. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of CEUS for the detection of ulceration was 88%, 59%, 72%, 63%, and 87%, respectively. CEUS had superior sensitivity and diagnostic accuracy for the assessment of carotid plaque ulceration compared with CDUS. CEUS improved the intrareader and inter-reader variability for the assessment of carotid plaque ulceration compared with CDUS. In conclusion, CEUS could be an additional method for the detection of carotid plaque ulceration. The role of CDUS for the assessment of

  12. Contrast-enhanced ultrasound findings of post-transplant lymphoproliferative disorder in a transplanted kidney: A case report and literature review

    PubMed Central

    Lampe, Alyssa; Duddalwar, Vinay A; Djaladat, Hooman; Aron, Manju; Gulati, Mittul

    2015-01-01

    Post-transplant lymphoproliferative disorder occurs in approximately one percent of kidney transplant recipients. We evaluated a seventy-seven year-old man with a solid mass in his transplant kidney. On contrast enhanced ultrasound, the mass enhanced but remained persistently hypovascular throughout exam. The enhancement pattern of the mass differed from that typical of clear cell renal cell carcinoma, the main differential diagnosis. Final pathology after partial nephrectomy confirmed post-transplant lymphoproliferative disorder. This is the first report of contrast enhanced ultrasound findings in a renal mass diagnosed as post-transplant lymphoproliferative disorder. Contrast enhanced ultrasound has a promising role in imaging of renal masses, particularly relevant in transplant patients due to the lack of nephrotoxicity. PMID:26629291

  13. Ultrasound Contrast Plane Wave Imaging Based on Bubble Wavelet Transform: In Vitro and In Vivo Validations.

    PubMed

    Wang, Diya; Zong, Yujin; Yang, Xuan; Hu, Hong; Wan, Jinjin; Zhang, Lei; Bouakaz, Ayache; Wan, Mingxi

    2016-07-01

    The aim of the study described here was to develop an ultrasound contrast plane wave imaging (PWI) method based on pulse-inversion bubble wavelet transform imaging (PIWI) to improve the contrast-to-tissue ratio of contrast images. A pair of inverted "bubble wavelets" with plane waves was constructed according to the modified Herring equation. The original echoes were replaced by the maximum wavelet correlation coefficients obtained from bubble wavelet correlation analysis. The echoes were then summed to distinguish microbubbles from tissues. In in vivo experiments on rabbit kidney, PIWI improved the contrast-to-tissue ratio of contrast images up to 4.5 ± 1.5 dB, compared with that obtained in B-mode (p < 0.05), through use of a pair of inverted plane waves. The disruption rate and infusion time of microbubbles in PIWI-based PWI were then quantified using two perfusion parameters, area under the curve and half transmit time estimated from time-intensity curves, respectively. After time-intensity curves were denoised by detrended fluctuation analysis, the average area under the curve and half transit time of PIWI-based PWI were 55.94% (p < 0.05) and 20.51% (p < 0.05) higher than those of conventional focused imaging, respectively. Because of its high contrast-to-tissue ratio and low disruption of microbubbles, PIWI-based PWI has a long infusion time and is therefore beneficial for transient monitoring and perfusion assessment of microbubbles circulating in vessels. PMID:27067280

  14. Intravascular ultrasound-guided central vein angioplasty and stenting without the use of radiographic contrast agents.

    PubMed

    Matthews, Ray; Thomas, Joseph

    2008-05-01

    Patients with contraindications to iodinated radiographic contrast agents present a significant challenge during endovascular intervention. A 46-year-old man with end-stage renal disease and a normally functioning left upper extremity arteriovenous fistula presented with severe left arm edema. The patient's history included repeated severe anaphylactoid reactions with severe respiratory distress upon exposure to iodinated contrast. In an attempt to avoid the use of iodinated contrast, angioplasty and stent placement of a severe central venous stenosis were performed using only fluoroscopy and intravascular sonography. In patients unable to receive iodinated contrast secondary to anaphylactoid reactions, intravascular sonography can be used to guide angioplasty and stenting of central venous stenosis. PMID:18286503

  15. Numerical modeling of the 3D dynamics of ultrasound contrast agent microbubbles using the boundary integral method

    NASA Astrophysics Data System (ADS)

    Wang, Qianxi; Manmi, Kawa; Calvisi, Michael L.

    2015-02-01

    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. While various models have been developed to describe the spherical oscillations of contrast agents, the treatment of nonspherical behavior has received less attention. However, the nonspherical dynamics of contrast agents are thought to play an important role in therapeutic applications, for example, enhancing the uptake of therapeutic agents across cell membranes and tissue interfaces, and causing tissue ablation. In this paper, a model for nonspherical contrast agent dynamics based on the boundary integral method is described. The effects of the encapsulating shell are approximated by adapting Hoff's model for thin-shell, spherical contrast agents. A high-quality mesh of the bubble surface is maintained by implementing a hybrid approach of the Lagrangian method and elastic mesh technique. The numerical model agrees well with a modified Rayleigh-Plesset equation for encapsulated spherical bubbles. Numerical analyses of the dynamics of UCAs in an infinite liquid and near a rigid wall are performed in parameter regimes of clinical relevance. The oscillation amplitude and period decrease significantly due to the coating. A bubble jet forms when the amplitude of ultrasound is sufficiently large, as occurs for bubbles without a coating; however, the threshold amplitude required to incite jetting increases due to the coating. When a UCA is near a rigid boundary subject to acoustic forcing, the jet is directed towards the wall if the acoustic wave propagates perpendicular to the boundary. When the acoustic wave propagates parallel to the rigid boundary, the jet direction has components both along the wave direction and towards the boundary that depend mainly on the dimensionless standoff distance of the bubble from the boundary. In all cases, the jet

  16. Contrast-enhanced ultrasound for imaging blunt abdominal trauma - indications, description of the technique and imaging review.

    PubMed

    Cokkinos, D; Antypa, E; Stefanidis, K; Tserotas, P; Kostaras, V; Parlamenti, A; Tavernaraki, K; Piperopoulos, P N

    2012-02-01

    Patients with blunt abdominal trauma are initially imaged with ultrasound (US) for the evaluation of free abdominal fluid. However, lacerations of solid organs can be overlooked. Although computed tomography (CT) is the gold standard technique for abdominal trauma imaging, overutilization, ionizing radiation, need to transport the patient and potential artifacts are well known disadvantages. Contrast-enhanced US (CEUS) can be used as an imaging tool between the two methods. It can easily and reliably reveal solid abdominal organ injuries in patients with low-energy localized trauma and decrease the number of CT scans performed. It can be rapidly performed at the patient's bedside with no need for transportation. There are only very few contraindications and anaphylactoid reactions are extremely rare. Altogether, CEUS has proved to be very helpful for the initial imaging of traumatic lesions of the liver, kidney and spleen, as well as for patient follow-up. PMID:22274907

  17. Correction of Non-Linear Propagation Artifact in Contrast-Enhanced Ultrasound Imaging of Carotid Arteries: Methods and in Vitro Evaluation.

    PubMed

    Yildiz, Yesna O; Eckersley, Robert J; Senior, Roxy; Lim, Adrian K P; Cosgrove, David; Tang, Meng-Xing

    2015-07-01

    Non-linear propagation of ultrasound creates artifacts in contrast-enhanced ultrasound images that significantly affect both qualitative and quantitative assessments of tissue perfusion. This article describes the development and evaluation of a new algorithm to correct for this artifact. The correction is a post-processing method that estimates and removes non-linear artifact in the contrast-specific image using the simultaneously acquired B-mode image data. The method is evaluated on carotid artery flow phantoms with large and small vessels containing microbubbles of various concentrations at different acoustic pressures. The algorithm significantly reduces non-linear artifacts while maintaining the contrast signal from bubbles to increase the contrast-to-tissue ratio by up to 11 dB. Contrast signal from a small vessel 600 μm in diameter buried in tissue artifacts before correction was recovered after the correction. PMID:25935597

  18. A comparative study of contrast enhanced ultrasound and contrast enhanced magnetic resonance imaging for the detection and characterization of hepatic hemangiomas.

    PubMed

    Fang, Liang; Zhu, Zheng; Huang, Beijian; Ding, Hong; Mao, Feng; Li, Chaolun; Zeng, Mengsu; Zhou, Jianjun; Wang, Ling; Wang, Wenping; Chen, Yue

    2015-04-01

    This study aims to compare contrast enhanced ultrasound (CEUS) and contrast enhanced magnetic resonance imaging (CEMRI) for the detection and characterization of hepatic hemangiomas. Included in this retrospective study were 83 histopathologically confirmed lesions of hemangioma in 66 hospitalized patients who underwent both CEUS and CEMRI and received surgery. The enhancement patterns on CEUS and CEMRI in each lesion were compared and analyzed. In addition, data obtained by the two modalities were then compared with the pathological findings to determine their value in differential diagnosis of hepatic hemangiomas. CEUS diagnosed 78 lesions of hemangioma against 80 by CEMRI. There were no statistical significant differences in the diagnostic value between CEUS and CEMRI in terms of sensitivity (88.0% vs. 92.8%), specificity (99.0% vs. 99.4%), accuracy (97.3% vs. 98.4%), positive predictive value (93.6% vs. 96.3%), and negative predictive value (98.0% vs. 98.8%) (p > 0.05, all). In the arterial phase, the main enhancement pattern on both CEUS and CEMRI was peripheral nodular enhancement (73 vs. 76), but lesions with diffuse enhancement on CEUS outnumbered those on CEMRI (3 vs. 1) and lesions with circular enhancement on CEMRI outnumbered those on CEUS (3 vs. 2). In the portal venous phase and delayed phase, the main enhancement pattern was hyperechoic change on CEUS and hyperintense on CEMRI (66 vs. 65), some lesions presented isoechoic change (12 vs. 15). These results suggested CEUS, an equivalent to CEMRI, may have an added diagnostic value in hemangiomas. PMID:25971695

  19. Versatile utilization of real-time intraoperative contrast-enhanced ultrasound in cranial neurosurgery: technical note and retrospective case series.

    PubMed

    Lekht, Ilya; Brauner, Noah; Bakhsheshian, Joshua; Chang, Ki-Eun; Gulati, Mittul; Shiroishi, Mark S; Grant, Edward G; Christian, Eisha; Zada, Gabriel

    2016-03-01

    OBJECTIVE Intraoperative contrast-enhanced ultrasound (iCEUS) offers dynamic imaging and provides functional data in real time. However, no standardized protocols or validated quantitative data exist to guide its routine use in neurosurgery. The authors aimed to provide further clinical data on the versatile application of iCEUS through a technical note and illustrative case series. METHODS Five patients undergoing craniotomies for suspected tumors were included. iCEUS was performed using a contrast agent composed of lipid shell microspheres enclosing perflutren (octafluoropropane) gas. Perfusion data were acquired through a time-intensity curve analysis protocol obtained using iCEUS prior to biopsy and/or resection of all lesions. RESULTS Three primary tumors (gemistocytic astrocytoma, glioblastoma multiforme, and meningioma), 1 metastatic lesion (melanoma), and 1 tumefactive demyelinating lesion (multiple sclerosis) were assessed using real-time iCEUS. No intraoperative complications occurred following multiple administrations of contrast agent in all cases. In all neoplastic cases, iCEUS replicated enhancement patterns observed on preoperative Gd-enhanced MRI, facilitated safe tumor debulking by differentiating neoplastic tissue from normal brain parenchyma, and helped identify arterial feeders and draining veins in and around the surgical cavity. Intraoperative CEUS was also useful in guiding a successful intraoperative needle biopsy of a cerebellar tumefactive demyelinating lesion obtained during real-time perfusion analysis. CONCLUSIONS Intraoperative CEUS has potential for safe, real-time, dynamic contrast-based imaging for routine use in neurooncological surgery and image-guided biopsy. Intraoperative CEUS eliminates the effect of anatomical distortions associated with standard neuronavigation and provides quantitative perfusion data in real time, which may hold major implications for intraoperative diagnosis, tissue differentiation, and quantification of

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

    NASA Astrophysics Data System (ADS)

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

    2010-04-01

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

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

    PubMed

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

    2010-04-01

    Novel biocompatible nanobubbles were fabricated by ultrasonication of a mixture of Span 60 and polyoxyethylene 40 stearate (PEG40S) followed by differential centrifugation to isolate the relevant subpopulation from the parent suspensions. Particle sizing analysis and optical microscopy inspection indicated that the freshly generated micro/nanobubble suspension was polydisperse and the size distribution was bimodal with large amounts of nanobubbles. To develop a nano-sized contrast agent that is small enough to leak through tumor pores, a fractionation to extract smaller bubbles by variation in the time of centrifugation at 20g (relative centrifuge field, RCF) was suggested. The results showed that the population of nanobubbles with a precisely controlled mean diameter could be sorted from the initial polydisperse suspensions to meet the specified requirements. The isolated bubbles were stable over two weeks under the protection of perfluoropropane gas. The acoustic behavior of the nano-sized contrast agent was evaluated using power Doppler imaging in a normal rabbit model. An excellent power Doppler enhancement was found in vivo renal imaging after intravenous injection of the obtained nanobubbles. Given the broad spectrum of potential clinical applications, the nano-sized contrast agent may provide a versatile adjunct for ultrasonic imaging enhancement and/or treatment of tumors. PMID:20220227

  2. An In Vitro Study of the Correlation Between Bubble Distribution, Acoustic Emission, and Cell Damage by Contrast Ultrasound

    PubMed Central

    Fowlkes, J. Brian; Miller, Douglas L.

    2009-01-01

    The objective of this study was to investigate the influences of total exposure duration and pulse-to-pulse bubble distribution on contrast-mediated cell damage. Murine macrophage cells were grown as monolayers on thin polyester sheets. Contrast agent microbubbles were attached to these cells by incubation. Focused ultrasound exposures (Pr = 2 MPa) were implemented at a frequency of 2.25 MHz with 46 cycle pulses and pulse repetition frequencies (PRF) of 1 kHz, 500 Hz, 100 Hz, and 10 Hz in a degassed water bath at 10 or 100 pulses. A 1 MHz receive transducer measured the scattered signal. The frequency spectrum was normalized to a control spectrum from linear scatterers. Photomicrographs were captured before, during, and after exposure at a frame rate of 2000 fps and a pixel resolution of 960 × 720. Results clearly show that cell death is increased, up to 60%, by increasing total exposure duration from 0 ms to 100 ms. There was an increasing difference in cell damage between a 10-pulse exposure and a 100-pulse exposure with increasing PRF. The greatest change in damage occurred at 1000 Hz PRF with a 53% increase between 10-pulse and 100-pulse exposures. For each pulse from 0 to 10, an overlay of the 2 μm bubble count with corresponding emission shows consistent behavior in its pulse-to-pulse changes, indicating a correlation between acoustic emission, bubble distribution, and cell damage. PMID:19411217

  3. Contrast Enhanced Abdominal Ultrasound in the Assessment of Ileal Inflammation in Crohn’s Disease: A Comparison with MR Enterography

    PubMed Central

    Horjus Talabur Horje, C. S.; Roovers, L.; Groenen, M. J. M.; Wahab, P. J.

    2015-01-01

    Background and Aims To prospectively examine the feasibility and accuracy of Contrast Enhanced Ultrasound (CEUS) in the assessment of Crohn’s disease (CD) activity in the terminal ileum in comparison to Magnetic Resonance Enterography (MRE), using endoscopy as a reference standard. Methods 105 consecutive patients with alleged clinically active CD were assessed by MRE and CEUS. CEUS of the terminal ileum was performed using an intravenous microbubble contrast enhancer. Accuracy values of CEUS and MRE for the presence of active terminal ileitis were evaluated using the Receiver Operating Characteristic method, using endoscopic findings as a reference standard. Sensitivity and specificity values of MRE and CEUS were compared by the McNemar test. Results CEUS was feasible in 98% of patients, MRE in all. Optimal diagnostic accuracy in CEUS was obtained at a peak intensity value of 10%, showing 100% sensitivity, 92% specificity and an accuracy of 99% in demonstrating ileal mucosal inflammation. For MRE, overall sensitivity, specificity and accuracy were, 87%, 100%, and 88%, respectively. CEUS and MRE were highly correlated in assessing length and wall thickness of the terminal ileum. CEUS identified 11 of 16 MRE-detected strictures, but no fistulae. Conclusion The accuracy of CEUS is comparable to that of MRE in the assessment of active, uncomplicated terminal ileal CD and therefore a valuable bedside alternative to MRE in the follow-up of these patients. PMID:26322970

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

    PubMed Central

    2015-01-01

    Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are both regarded as primary liver cancers, having different biological behaviors and prognoses. Correct differentiation between them is essential for surgical planning and prognosis assessment. In 2005, the American Association for the Study of Liver Diseases (AASLD) recommended that noninvasive diagnosis of HCC is achievable by a single dynamic technique (including contrast-enhanced ultrasound (CEUS)) showing intense arterial uptake followed by washout of contrast in the venous-delayed phases. However, CEUS has been dropped from the diagnostic techniques in the latest AASLD guideline according to the opinion of some authors from Europe that CEUS may offer false positive HCC diagnosis in patients with ICC. Since the update of AASLD guideline has been released, increased attention has been paid to this interesting topic. Remarkable controversy over this issue is present and this removal was not well received in Europe and Asia. This commentary summarized the opinions for the role of CUES in differentiation between HCC and ICC in recent years. It is concluded that prospective studies with strict design and large case series are mandatory to solve the controversies and stratification of ICC in terms of tumor size and liver background is also essential. PMID:26090401

  5. Contrast enhanced ultrasound with quantitative perfusion analysis for objective characterization of pancreatic ductal adenocarcinoma: A feasibility study.

    PubMed

    D'Onofrio, Mirko; Canestrini, Stefano; Crosara, Stefano; De Robertis, Riccardo; Pozzi Mucelli, Roberto

    2014-03-28

    The aim of this study was to determine whether contrast enhanced ultrasound (CEUS) quantitative perfusion analysis allows an objective characterization of ductal adenocarcinoma (ADK) of the pancreas. Patients with pancreatic ADK underwent CEUS. All examinations were performed on an Acuson S2000 system (Siemens, Erlangen, Germany) after the iv administration of 2.4 mL contrast agent (SonoVue(®), Bracco, Milan, Italy). All lesions were pathologically proved. An operator manually drew different regions of interest within the tumor and the adjacent parenchyma to allow the quantitative perfusion analysis. The mean values of peak of enhancement, time to peak and ascending curve were calculated and compared using the Student's t test. The quantitative perfusion analysis was possible in all lesions. The mean values of the peak of enhancement, time to peak and ascending curve were 17.19%, 7.97 s and 159.52% s within the tumor and 33.57%, 8.89 s and 355.29% s within the adjacent parenchyma. The peak of enhancement and the ascending curve values were significantly different within the tumor and the adjacent parenchyma. Thus, CEUS allows the quantitative perfusion analysis of pancreatic ductal adenocarcinoma. PMID:24765238

  6. Contrast enhanced ultrasound with quantitative perfusion analysis for objective characterization of pancreatic ductal adenocarcinoma: A feasibility study

    PubMed Central

    D’Onofrio, Mirko; Canestrini, Stefano; Crosara, Stefano; Robertis, Riccardo De; Mucelli, Roberto Pozzi

    2014-01-01

    The aim of this study was to determine whether contrast enhanced ultrasound (CEUS) quantitative perfusion analysis allows an objective characterization of ductal adenocarcinoma (ADK) of the pancreas. Patients with pancreatic ADK underwent CEUS. All examinations were performed on an Acuson S2000 system (Siemens, Erlangen, Germany) after the iv administration of 2.4 mL contrast agent (SonoVue®, Bracco, Milan, Italy). All lesions were pathologically proved. An operator manually drew different regions of interest within the tumor and the adjacent parenchyma to allow the quantitative perfusion analysis. The mean values of peak of enhancement, time to peak and ascending curve were calculated and compared using the Student’s t test. The quantitative perfusion analysis was possible in all lesions. The mean values of the peak of enhancement, time to peak and ascending curve were 17.19%, 7.97 s and 159.52% s within the tumor and 33.57%, 8.89 s and 355.29% s within the adjacent parenchyma. The peak of enhancement and the ascending curve values were significantly different within the tumor and the adjacent parenchyma. Thus, CEUS allows the quantitative perfusion analysis of pancreatic ductal adenocarcinoma. PMID:24765238

  7. [Color-coded duplex sonography and ultrasound contrast medium in the study of peripheral arteries--initial clinical experiences].

    PubMed

    Fobbe, F; Ohnesorge, I; Reichel, M; Dollinger, P; Schürmann, R; Wolf, K J

    1992-08-01

    Ultrasound contrast agents (US-CA) amplify reflected sound waves. Most substances used as contrast agents are destroyed when passing the lungs. SH U 508 is a new US-CA that can pass the lungs without impairment after peripheral intravenous application. In a clinical trial of this US-CA, we investigated its effect on the visualization of blood movement in peripheral arteries by color-coded Duplex sonography (CCDS). The leg arteries of 20 patients with severe chronic arterial occlusion were examined by CCDS (QAD I and Platinum) after i.v. application of the US-CA. After passage of the pulmonary capillaries, the US-CA amplified blood flow signals in the arterial system in a dose-dependent manner with both systems used. Undesired side-effects were not observed. The amplification produced by appropriate concentrations of the US-CA markedly improved the visualization of blood movement. Further studies are required to determine the optimal dosage and application technique as well as the indication for using this US-CA. PMID:1411473

  8. Reliability of contrast-enhanced ultrasound for the assessment of muscle perfusion in health and peripheral arterial disease.

    PubMed

    Thomas, Kate N; Cotter, James D; Lucas, Samuel J E; Hill, Brigid G; van Rij, André M

    2015-01-01

    We investigated the reliability of contrast-enhanced ultrasound (CEUS) in assessing calf muscle microvascular perfusion in health and disease. Response to a post-occlusive reactive hyperaemia test was repeated on two occasions >48 h apart in healthy young (28 ± 7 y) and elderly controls (70 ± 5 y), and in peripheral arterial disease patients (PAD, 69 ± 7 y; n = 10, 9 and 8 respectively). Overall, within-individual reliability was poor (coefficient of variation [CV] range: 15-87%); the most reliable parameter was time to peak (TTP, 15-48% CV). Nevertheless, TTP was twice as long in elderly controls and PAD compared to young (19.3 ± 10.4 and 22.0 ± 8.6 vs. 8.9 ± 6.2 s respectively; p < 0.01), and area under the curve for contrast intensity post-occlusion (a reflection of blood volume) was ∼50% lower in elderly controls (p < 0.01 versus PAD and young). Thus, CEUS assessment of muscle perfusion during reactive hyperaemia demonstrated poor reliability, yet still distinguished differences between PAD patients, elderly and young controls. PMID:25308937

  9. Interaction of an ultrasound-activated contrast microbubble with a wall at arbitrary separation distances.

    PubMed

    Doinikov, Alexander A; Bouakaz, Ayache

    2015-10-21

    Both in vitro and in vivo, contrast agent microbubbles move near bounding surfaces, such as the wall of an experimental container or the wall of a blood vessel. This problem inspires interest in theoretical models that predict the effect of a wall on the dynamics of a contrast microbubble. There are models for a bubble at a large distance from a wall and for a bubble adherent to a wall. The aim of the present study is to develop a generalized model that describes the dynamics of a contrast microbubble at arbitrary distances from a wall and thereby make it possible to simulate the acoustic response of the bubble starting from large separation distances up to contact between the bubble and the wall. The wall is assumed to be a plane. Therefore, the developed model applies for in vitro investigations of contrast agents in experimental containers. It can also be used as a first approximation to the case of a contrast microbubble within a large blood vessel. The derivation of the model is based on the multipole expansion of the bubble velocity potential, the image source method, and the Lagrangian formalism. The model consists of two coupled equations, one of which describes the bubble radial oscillation and the second describes the translation of the bubble center. Numerical simulations are performed to determine how the acoustic response of a contrast microbubble depends on the separation distance near walls of different types: rigid, plastic, arterial, etc. The dynamics of the bubble encapsulation is described by the Marmottant shell model. The properties of the plastic wall correspond to OptiCell chambers commonly used in experiments. The results of the simulations show that the bubble resonance frequency near a wall depends on both the separation distance and the wall material properties. In particular, the rigid wall makes the resonance frequency decrease with decreasing separation distance, whereas in the vicinity of the OptiCell wall and the arterial wall, the

  10. Interaction of an ultrasound-activated contrast microbubble with a wall at arbitrary separation distances

    NASA Astrophysics Data System (ADS)

    Doinikov, Alexander A.; Bouakaz, Ayache

    2015-10-01

    Both in vitro and in vivo, contrast agent microbubbles move near bounding surfaces, such as the wall of an experimental container or the wall of a blood vessel. This problem inspires interest in theoretical models that predict the effect of a wall on the dynamics of a contrast microbubble. There are models for a bubble at a large distance from a wall and for a bubble adherent to a wall. The aim of the present study is to develop a generalized model that describes the dynamics of a contrast microbubble at arbitrary distances from a wall and thereby make it possible to simulate the acoustic response of the bubble starting from large separation distances up to contact between the bubble and the wall. The wall is assumed to be a plane. Therefore, the developed model applies for in vitro investigations of contrast agents in experimental containers. It can also be used as a first approximation to the case of a contrast microbubble within a large blood vessel. The derivation of the model is based on the multipole expansion of the bubble velocity potential, the image source method, and the Lagrangian formalism. The model consists of two coupled equations, one of which describes the bubble radial oscillation and the second describes the translation of the bubble center. Numerical simulations are performed to determine how the acoustic response of a contrast microbubble depends on the separation distance near walls of different types: rigid, plastic, arterial, etc. The dynamics of the bubble encapsulation is described by the Marmottant shell model. The properties of the plastic wall correspond to OptiCell chambers commonly used in experiments. The results of the simulations show that the bubble resonance frequency near a wall depends on both the separation distance and the wall material properties. In particular, the rigid wall makes the resonance frequency decrease with decreasing separation distance, whereas in the vicinity of the OptiCell wall and the arterial wall, the