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

PubMed

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

2016-01-01

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. 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. 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). RGD-MBs enable noninvasive in vivo visualization of changes in tumor angiogenesis during tumor growth in subcutaneous cancer xenografts.

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

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

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

PubMed

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

2011-06-01

We evaluated the ability of the phosphodiesterase-5 inhibitor vardenafil to increase prostate microcirculation during power Doppler ultrasound. We also evaluated the results of contrast and vardenafil enhanced targeted biopsies compared to those of standard 12-core random biopsies to detect cancer. Between May 2008 and January 2010, 150 consecutive patients with prostate specific antigen more than 4 ng/ml at first diagnosis with negative digital rectal examination and transrectal ultrasound, and no clinical history of prostatitis underwent contrast enhanced power Doppler ultrasound (bolus injection of 2.4 ml SonoVue® contrast agent), followed by vardenafil enhanced power Doppler ultrasound (1 hour after oral administration of vardenafil 20 mg). All patients underwent standard 12-core transrectal ultrasound guided random prostate biopsy plus 1 further sampling from each suspected hypervascular lesion detected by contrast and vardenafil enhanced power Doppler ultrasound. Prostate cancer was detected in 44 patients (29.3%). Contrast and vardenafil enhanced power Doppler ultrasound detected suspicious, contrast enhanced and vardenafil enhanced areas in 112 (74.6%) and 110 patients (73.3%), and was diagnostic for cancer in 32 (28.5%) and 42 (38%), respectively. Analysis of standard technique, and contrast and vardenafil enhanced power Doppler ultrasound findings by biopsy core showed significantly higher detection using vardenafil vs contrast enhanced power Doppler ultrasound and standard technique (41.2% vs 22.7% and 8.1%, p <0.005 and <0.001, respectively). The detection rate of standard plus contrast or vardenafil enhanced power Doppler ultrasound was 10% and 11.7% (p not significant). Vardenafil enhanced power Doppler ultrasound enables excellent visualization of the microvasculature associated with cancer and can improve the detection rate compared to contrast enhanced power Doppler ultrasound and the random technique. Copyright © 2011 American Urological

Towards Dynamic Contrast Specific Ultrasound Tomography

NASA Astrophysics Data System (ADS)

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

2016-10-01

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

Towards Dynamic Contrast Specific Ultrasound Tomography.

PubMed

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

2016-10-05

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

Towards Dynamic Contrast Specific Ultrasound Tomography

PubMed Central

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

2016-01-01

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

Ultrasound imaging beyond the vasculature with new generation contrast agents.

PubMed

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

2015-01-01

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

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

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.

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

PubMed

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

2017-10-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

Vascular applications of contrast-enhanced ultrasound imaging.

PubMed

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

2017-07-01

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

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

PubMed

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

2015-12-01

An accurate method for detecting contrast agents using diagnostic ultrasound imaging systems is proposed. Contrast agents, such as microbubbles, passing through a blood vessel during ultrasound imaging are detected as blinking signals in the temporal axis, because their intensity value is constantly in motion. Ultrasound contrast agents are detected by evaluating the intensity variation of a pixel in the temporal axis. Conventional methods are based on simple subtraction of ultrasound images to detect ultrasound contrast agents. Even if the subject moves only slightly, a conventional detection method will introduce significant error. In contrast, the proposed technique employs spatiotemporal analysis of the pixel intensity variation over several frames. Experiments visualizing blood vessels in the mouse tail illustrated that the proposed method performs efficiently compared with conventional approaches. We also report that the new technique is useful for observing temporal changes in microvessel density in subiliac lymph nodes containing tumors. The results are compared with those of contrast-enhanced computed tomography. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Aptamer-conjugated nanobubbles for targeted ultrasound molecular imaging.

PubMed

Wang, Chung-Hsin; Huang, Yu-Fen; Yeh, Chih-Kuang

2011-06-07

Targeted ultrasound contrast agents can be prepared by some specific bioconjugation techniques. The biotin-avidin complex is an extremely useful noncovalent binding system, but the system might induce immunogenic side effects in human bodies. Previous proposed covalently conjugated systems suffered from low conjugation efficiency and complex procedures. In this study, we propose a covalently conjugated nanobubble coupling with nucleic acid ligands, aptamers, for providing a higher specific affinity for ultrasound targeting studies. The sgc8c aptamer was linked with nanobubbles through thiol-maleimide coupling chemistry for specific targeting to CCRF-CEM cells. Further improvements to reduce the required time and avoid the degradation of nanobubbles during conjugation procedures were also made. Several investigations were used to discuss the performance and consistency of the prepared nanobubbles, such as size distribution, conjugation efficiency analysis, and flow cytometry assay. Further, we applied our conjugated nanobubbles to ex vivo ultrasound targeted imaging and compared the resulting images with optical images. The results indicated the availability of aptamer-conjugated nanobubbles in targeted ultrasound imaging and the practicability of using a highly sensitive ultrasound system in noninvasive biological research.

A Targeting Microbubble for Ultrasound Molecular Imaging

PubMed Central

Yeh, James Shue-Min; Sennoga, Charles A.; McConnell, Ellen; Eckersley, Robert; Tang, Meng-Xing; Nourshargh, Sussan; Seddon, John M.; Haskard, Dorian O.; Nihoyannopoulos, Petros

2015-01-01

Rationale Microbubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (strept)avidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(strept)avidin conjugation chemistry have been explored, only a few reached the stage of ultrasound imaging in vivo, none were reported/evaluated to show all three of the following properties desired for clinical applications: (i) low degree of non-specific bubble retention in more than one non-reticuloendothelial tissue; (ii) effective for real-time imaging; and (iii) effective for acoustic quantification of molecular targets to a high degree of quantification. Furthermore, disclosures of the compositions and methodologies enabling reproduction of the bubbles are often withheld. Objective To develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging. Methods and Results Microbubbles with a previously unreported generic (non-targeting components) composition were grafted with anti-E-selectin F(ab’)2 using maleimide-thiol conjugation, to produce E-selectin targeting microbubbles. The resulting targeting bubbles showed high specificity to E-selectin in vitro and in vivo. Non-specific bubble retention was minimal in at least three non-reticuloendothelial tissues with inflammation (mouse heart, kidneys, cremaster). The bubbles were effective for real-time ultrasound imaging of E-selectin expression in the inflamed mouse heart and kidneys, using a clinical ultrasound scanner. The acoustic signal intensity of the targeted bubbles retained in the heart correlated strongly with the level of E-selectin expression (|r|≥0.8), demonstrating a high degree of non-invasive molecular quantification. Conclusions Targeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described

[Contrast-enhanced ultrasound (CEUS) and image fusion for procedures of liver interventions].

PubMed

Jung, E M; Clevert, D A

2018-06-01

Contrast-enhanced ultrasound (CEUS) is becoming increasingly important for the detection and characterization of malignant liver lesions and allows percutaneous treatment when surgery is not possible. Contrast-enhanced ultrasound image fusion with computed tomography (CT) and magnetic resonance imaging (MRI) opens up further options for the targeted investigation of a modified tumor treatment. Ultrasound image fusion offers the potential for real-time imaging and can be combined with other cross-sectional imaging techniques as well as CEUS. With the implementation of ultrasound contrast agents and image fusion, ultrasound has been improved in the detection and characterization of liver lesions in comparison to other cross-sectional imaging techniques. In addition, this method can also be used for intervention procedures. The success rate of fusion-guided biopsies or CEUS-guided tumor ablation lies between 80 and 100% in the literature. Ultrasound-guided image fusion using CT or MRI data, in combination with CEUS, can facilitate diagnosis and therapy follow-up after liver interventions. In addition to the primary applications of image fusion in the diagnosis and treatment of liver lesions, further useful indications can be integrated into daily work. These include, for example, intraoperative and vascular applications as well applications in other organ systems.

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

PubMed

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

2016-12-07

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

Ultrasound-Mediated Vascular Gene Transfection by Cavitation of Endothelial-Targeted Cationic Microbubbles

PubMed Central

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

2013-01-01

OBJECTIVES Ultrasound-mediated gene delivery can be amplified by acoustic disruption of microbubble carriers that undergo cavitation. We hypothesized that endothelial targeting of microbubbles bearing cDNA is feasible and, through optimizing proximity to the vessel wall, increases the efficacy of gene transfection. BACKGROUND Contrast ultrasound-mediated gene delivery is a promising approach for site-specific gene therapy, although there are concerns with the reproducibility of this technique and the safety when using high-power ultrasound. METHODS Cationic lipid-shelled decafluorobutane microbubbles bearing a targeting moiety were prepared and compared with nontargeted microbubbles. Microbubble targeting efficiency to endothelial adhesion molecules (P-selectin or intercellular adhesion molecule [ICAM]-1) was tested using in vitro flow chamber studies, intravital microscopy of tumor necrosis factor-alpha (TNF-α)–stimulated murine cremaster muscle, and targeted contrast ultrasound imaging of P-selectin in a model of murine limb ischemia. Ultrasound-mediated transfection of luciferase reporter plasmid charge coupled to microbubbles in the post-ischemic hindlimb muscle was assessed by in vivo optical imaging. RESULTS Charge coupling of cDNA to the microbubble surface was not influenced by the presence of targeting ligand, and did not alter the cavitation properties of cationic microbubbles. In flow chamber studies, surface conjugation of cDNA did not affect attachment of targeted microbubbles at microvascular shear stresses (0.6 and 1.5 dyne/cm2). Attachment in vivo was also not affected by cDNA according to intravital microscopy observations of venular adhesion of ICAM-1–targeted microbubbles and by ultrasound molecular imaging of P-selectin–targeted microbubbles in the post-ischemic hindlimb in mice. Transfection at the site of high acoustic pressures (1.0 and 1.8 MPa) was similar for control and P-selectin–targeted microbubbles but was associated with

Targeted ultrasound contrast imaging of matrix metalloproteinase-2 in ischemia-reperfusion rat model: ex vivo and in vivo studies.

PubMed

Su, Haili; Du, Yongfeng; Qian, Yunqiu; Zong, Yujin; Li, Jun; Zhuang, Ran; He, Jianguo; Wei, Zhangrui; Zhang, Jun; Zhou, Xiaodong

2011-04-01

We hypothesized that post-myocardial ischemia-reperfusion (I/R) remodeling associated matrix metalloproteinase-2 (MMP(2)) activation could be detected by using novel MMP(2) targeted ultrasound imaging. We study the combination of MMP(2)-targeted microbubbles (TMB(2)) and control microbubbles with myocardium in 1 week post-I/R rats. In in vitro studies, TMB(2) significantly bound within the risk area (RA) of 1-week post-I/R myocardial sections while rare binding was observed in the control area (CA). In in vivo studies, increased focal retention of TMB(2) was observed within the RA, with the higher myocardial video intensity (RA 42.85 ± 20.12 dB versus CA 25.85 ± 13.40 dB, p < 0.01). However, there was no difference of control microbubble retention in both CA and RA. A targeted ultrasound contrast imaging approach that employs novel TMB(2) has the potential to provide a less-invasive, higher-resolution technique for in vivo localization of MMP(2) activation and tracking of MMP-mediated post-I/R remodeling.

Acoustic cavitation of individual ultrasound contrast agent microbubbles confined in capillaries

NASA Astrophysics Data System (ADS)

Almaqwashi, Ali; McIntyre, David; Ammi, Azzdine

2011-10-01

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

Nanobubbles as ultrasound contrast agent for facilitating small cell lung cancer imaging

PubMed Central

Wang, Jin-Ping; Zhou, Xiao-Lin; Yan, Ji-Ping; Zheng, Rong-Qin; Wang, Wei

2017-01-01

Background This study is to investigate whether liposome-loaded nanobubbles (NBs) have the potentials to carry anti-pro-gastrin releasing peptide (proGRP) antibody and enhance ultrasound imaging of small cell lung cancer (SCLC). Methods NBs were loaded with an antibody against SCLC (H446 cell line). A nude mouse model of SCLC tumor was established by a subcutaneous injection of tumor cell suspension in the dorsal skin. Images for contrast-enhanced ultrasound (CEUS) of xenograft tumors in the model were obtained through an intravenous injection of blank and targeting NBs. Results The targeted NBs showed a high binding affinity (90.2 ± 3.24%) of the H446 cells in vitro as compared to the blank NBs that have no affinity of the cells. In process of tumor imaging, no mice died of the NB application. CEUS imaging of the targeted NBs manifested significant increases in half-peak time, area under the curve and peak intensity as compared to the blank NBs. In the model of SCLC, treatment with targeting NBs resulted in a large amount of fluorescent dye accumulated in the tumor tissue but not the liver tissue. Conclusion Our results indicate that NBs can carry antibody traveling to the SCLC cells, whereas application of NBs is safe and reliable in serving as ultrasound contrast agents for improving SCLC imaging. PMID:29100457

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

PubMed

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

2014-05-28

The Enhanced Permeability and Retention (EPR) effect is extensively used in drug delivery research. Taking into account that EPR is a highly variable phenomenon, we have here set out to evaluate if contrast-enhanced functional ultrasound (ceUS) imaging can be employed to characterize EPR-mediated passive drug targeting to tumors. Using standard fluorescence molecular tomography (FMT) and two different protocols for hybrid computed tomography-fluorescence molecular tomography (CT-FMT), the tumor accumulation of a ~10 nm-sized near-infrared-fluorophore-labeled polymeric drug carrier (pHPMA-Dy750) was evaluated in CT26 tumor-bearing mice. In the same set of animals, two different ceUS techniques (2D MIOT and 3D B-mode imaging) were employed to assess tumor vascularization. Subsequently, the degree of tumor vascularization was correlated with the degree of EPR-mediated drug targeting. Depending on the optical imaging protocol used, the tumor accumulation of the polymeric drug carrier ranged from 5 to 12% of the injected dose. The degree of tumor vascularization, determined using ceUS, varied from 4 to 11%. For both hybrid CT-FMT protocols, a good correlation between the degree of tumor vascularization and the degree of tumor accumulation was observed, within the case of reconstructed CT-FMT, correlation coefficients of ~0.8 and p-values of <0.02. These findings indicate that ceUS can be used to characterize and predict EPR, and potentially also to pre-select patients likely to respond to passively tumor-targeted nanomedicine treatments. Copyright © 2014 Elsevier B.V. All rights reserved.

Novel dual-mode nanobubbles as potential targeted contrast agents for female tumors exploration.

PubMed

Yang, Hengli; Zhou, Tian; Cai, Wenbin; Yi, Xiaomin; Liu, Xi; Wang, Yixiao; Zhang, Li; Duan, Yunyou

2016-10-01

The purpose of this study was to prepare tumor-specific dual-mode nanobubbles as both ultrasound contrast agents (UCAs) and near-infrared fluorescence (NIRF) imaging agents for female tumors. Recent studies have demonstrated the conjugation of anti-tumor ligands on the surface of nanobubbles for use as molecule-targeting ultrasound contrast agents for tumor visualization. However, this complicated procedure has also posed a challenge to nanobubble stability. Thus, in the present study, we combined the fluorescent dye, NIRF IR-780 iodide, which has lipid solubility and tumor-targeting characteristics, with the phospholipid film of nanobubbles that we constructed. We then characterized the physical features of the IR-780-nanobubbles, observed their tumor-targeting capacity in multiple female tumor cell types in vitro, and verified their capability for use in tumor-specific ultrasound contrast imaging and NIRF imaging in vivo. The results showed that the new IR-780-nanobubbles had a uniform nano-size (442.5 ± 48.6 nm) and stability and that they were safe and effective at NIRF imaging and ultrasound imaging in vitro. The IR-780-nanobubbles were found to automatically accumulate on different female tumor cells in vitro with a considerable targeting rate (close to 40 %) but did not accumulate on cardiac muscle cells used as a negative control. Importantly, the IR-780-nanobubbles can detect female tumors precisely via dual-mode imaging in vivo. In conclusion, the new dual-mode IR-780-nanobubbles are stable and have potential advantages in non-invasive tumor-specific detection for female tumors via contrast-enhanced ultrasound and NIRF imaging.

Ultrasound Activated Contrast Imaging for Prostate Cancer Detection

DTIC Science & Technology

2007-03-01

SUBTITLE 5a. CONTRACT NUMBER Ultrasound Activated Contrast Imaging for Prostate Cancer Detection 5b. GRANT NUMBER DAMD17-03-1-0119 5c. PROGRAM...ABSTRACT: The current project proposes todevelop a novel ultrasound contrast imaging technique (called EEI) for better visualization of the

Molecular Imaging of Vasa Vasorum Neovascularization via DEspR-targeted Contrast-enhanced Ultrasound Micro-imaging in Transgenic Atherosclerosis Rat Model

PubMed Central

Decano, Julius L.; Moran, Anne Marie; Ruiz-Opazo, Nelson; Herrera, Victoria L. M.

2011-01-01

Purpose Given that carotid vasa vasorum neovascularization is associated with increased risk for stroke and cardiac events, the present in vivo study was designed to investigate molecular imaging of carotid artery vasa vasorum neovascularization via target-specific contrast-enhanced ultrasound (CEU) micro-imaging. Procedures Molecular imaging was performed in male transgenic rats with carotid artery disease and non-transgenic controls using dual endothelin1/VEGFsp receptor (DEspR)-targeted microbubbles (MBD) and the Vevo770 micro-imaging system and CEU imaging software. Results DEspR-targeted CEU-positive imaging exhibited significantly higher contrast intensity signal (CIS)-levels and pre-/post-destruction CIS-differences in seven of 13 transgenic rats, in contrast to significantly lower CIS-levels and differences in control isotype-targeted microbubble (MBC)-CEU imaging (n =8) and in MBD CEU-imaging of five non-transgenic control rats (P<0.0001). Ex vivo immunofluorescence analysis demonstrated binding of MBD to DEspR-positive endothelial cells; and association of DEspR-targeted increased contrast intensity signals with DEspR expression in vasa vasorum neovessel and intimal lesions. In vitro analysis demonstrated dose-dependent binding of MBD to DEspR-positive human endothelial cells with increasing %cells bound and number of MBD per cell, in contrast to MBC or non-labeled microbubbles (P<0.0001). Conclusion In vivo DEspR-targeted molecular imaging detected increased DEspR-expression in carotid artery lesions and in expanded vasa vasorum neovessels in transgenic rats with carotid artery disease. Future studies are needed to determine predictive value for stroke or heart disease in this transgenic atherosclerosis rat model and translational applications. PMID:20972637

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

PubMed

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

2012-12-01

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

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

PubMed

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

2012-04-01

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

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-D Quantitative Dynamic Contrast Ultrasound for Prostate Cancer Localization.

PubMed

Schalk, Stefan G; Huang, Jing; Li, Jia; Demi, Libertario; Wijkstra, Hessel; Huang, Pintong; Mischi, Massimo

2018-04-01

To investigate quantitative 3-D dynamic contrast-enhanced ultrasound (DCE-US) and, in particular 3-D contrast-ultrasound dispersion imaging (CUDI), for prostate cancer detection and localization, 43 patients referred for 10-12-core systematic biopsy underwent 3-D DCE-US. For each 3-D DCE-US recording, parametric maps of CUDI-based and perfusion-based parameters were computed. The parametric maps were divided in regions, each corresponding to a biopsy core. The obtained parameters were validated per biopsy location and after combining two or more adjacent regions. For CUDI by correlation (r) and for the wash-in time (WIT), a significant difference in parameter values between benign and malignant biopsy cores was found (p < 0.001). In a per-prostate analysis, sensitivity and specificity were 94% and 50% for r, and 53% and 81% for WIT. Based on these results, it can be concluded that quantitative 3-D DCE-US could aid in localizing prostate cancer. Therefore, we recommend follow-up studies to investigate its value for targeting biopsies. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

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

Ultrasound-Targeted Microbubble Destruction to Deliver siRNA Cancer Therapy

PubMed Central

Carson, Andrew R; McTiernan, Charles F; Lavery, Linda; Grata, Michelle; Leng, Xiaoping; Wang, Jianjun; Chen, Xucai; Villanueva, Flordeliza S

2012-01-01

Microbubble contrast agents can specifically deliver nucleic acids to target tissues when exposed to ultrasound treatment parameters that mediate microbubble destruction. In this study, we evaluated whether microbubbles and ultrasound targeted microbubble destruction (UTMD) could be used to enhance delivery of EGFR-directed small inhibitory RNA (siRNA) to murine squamous cell carcinomas. Custom designed microbubbles efficiently bound siRNA and mediated RNAse protection. UTMD-mediated delivery of microbubbles loaded with EGFR-directed siRNA to murine squamous carcinoma cells in vitro reduced EGFR expression and EGF-dependent growth, relative to delivery of control siRNA. Similarly, serial UTMD-mediated delivery of EGFR siRNA to squamous cell carcinoma in vivo decreased EGFR expression and increased tumor doubling times, relative to controls receiving EGFR siRNA loaded microbubbles but not ultrasound or control siRNA loaded microbubbles and UTMD. Taken together, our results offer a preclinical proof of concept for customized microbubbles and UTMD to deliver gene-targeted siRNA for cancer therapy. PMID:23010078

Preparation and Imaging Investigation of Dual-targeted C3F8-filled PLGA Nanobubbles as a Novel Ultrasound Contrast Agent for Breast Cancer.

PubMed

Du, Jing; Li, Xiao-Yu; Hu, He; Xu, Li; Yang, Shi-Ping; Li, Feng-Hua

2018-03-01

Molecularly-targeted contrast enhanced ultrasound (US) imaging is a promising imaging strategy with large potential for improving diagnostic accuracy of conventional US imaging in breast cancer detection. Therefore, we constructed a novel dual-targeted nanosized US contrast agent (UCA) directed at both vascular endothelial growth factor receptor 2 (VEGFR2) and human epidermal growth factor receptor 2 (HER2) based on perfluoropropane (C 3 F 8 )-filled poly(lactic-co-glycolic acid) (PLGA) (NBs) for breast cancer detection. In vitro, single- or dual-targeted PLGA NBs showed high target specificities and better effects of target enhancement in VEGFR2 or HER2-positive cells. In vivo, US imaging signal in the murine breast cancer model was significantly higher (P < 0.01) for dual-targeted NBs than single-targeted and non-targeted NBs. Small animal fluorescence imaging further confirmed the special affinity of the dual-targeted nanosized contrast agent to both VEGFR2 and HER2. Immunofluorescence and immunohistochemistry staining confirmed the expressions of VEGFR2 and HER2 on tumor neovasculature and tumor cells of breast cancer. In conclusions, the feasibility of using dual-targeted PLGA NBs to enhance ultrasonic images is demonstrated in vitro and in vivo. This may be a promising approach to target biomarkers of breast cancer for two site-specific US molecular imaging.

VEGFR2-Targeted Ultrasound Imaging Agent Enhances the Detection of Ovarian Tumors at Early Stage in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

PubMed

Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Machado, Sergio A; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

2015-07-01

Tumor-associated neoangiogenesis (TAN) is an early event in ovarian cancer (OVCA) development. Increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) by TAN vessels presents a potential target for early detection by ultrasound imaging. The goal of this study was to examine the suitability of VEGFR2-targeted ultrasound contrast agents in detecting spontaneous OVCA in laying hens. Effects of VEGFR2-targeted contrast agents in enhancing the intensity of ultrasound imaging from spontaneous ovarian tumors in hens were examined in a cross-sectional study. Enhancement in the intensity of ultrasound imaging was determined before and after injection of VEGFR2-targeted contrast agents. All ultrasound images were digitally stored and analyzed off-line. Following scanning, ovarian tissues were collected and processed for histology and detection of VEGFR2-expressing microvessels. Enhancement in visualization of ovarian morphology was detected by gray-scale imaging following injection of VEGFR2-targeted contrast agents. Compared with pre-contrast, contrast imaging enhanced the intensities of ultrasound imaging significantly (p < 0.0001) irrespective of the pathological status of ovaries. In contrast to normal hens, the intensity of ultrasound imaging was significantly (p < 0.0001) higher in hens with early stage OVCA and increased further in hens with late stage OVCA. Higher intensities of ultrasound imaging in hens with OVCA were positively correlated with increased (p < 0.0001) frequencies of VEGFR2-expressing microvessels. The results of this study suggest that VEGFR2-targeted contrast agents enhance the visualization of spontaneous ovarian tumors in hens at early and late stages of OVCA. The laying hen may be a suitable model to test new imaging agents and develop targeted therapeutics. © The Author(s) 2014.

Acoustic bubble sorting for ultrasound contrast agent enrichment.

PubMed

Segers, Tim; Versluis, Michel

2014-05-21

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

A Computational Observer For Performing Contrast-Detail Analysis Of Ultrasound Images

NASA Astrophysics Data System (ADS)

Lopez, H.; Loew, M. H.

1988-06-01

Contrast-Detail (C/D) analysis allows the quantitative determination of an imaging system's ability to display a range of varying-size targets as a function of contrast. Using this technique, a contrast-detail plot is obtained which can, in theory, be used to compare image quality from one imaging system to another. The C/D plot, however, is usually obtained by using data from human observer readings. We have shown earlier(7) that the performance of human observers in the task of threshold detection of simulated lesions embedded in random ultrasound noise is highly inaccurate and non-reproducible for untrained observers. We present an objective, computational method for the determination of the C/D curve for ultrasound images. This method utilizes digital images of the C/D phantom developed at CDRH, and lesion-detection algorithms that simulate the Bayesian approach using the likelihood function for an ideal observer. We present the results of this method, and discuss the relationship to the human observer and to the comparability of image quality between systems.

Dynamic Contrast-Enhanced Ultrasound Identifies Microcirculatory Alterations in Sepsis-Induced Acute Kidney Injury.

PubMed

Lima, Alexandre; van Rooij, Tom; Ergin, Bulent; Sorelli, Michele; Ince, Yasin; Specht, Patricia A C; Mik, Egbert G; Bocchi, Leonardo; Kooiman, Klazina; de Jong, Nico; Ince, Can

2018-05-15

We developed quantitative methods to analyze microbubble kinetics based on renal contrast-enhanced ultrasound imaging combined with measurements of sublingual microcirculation on a fixed area to quantify early microvascular alterations in sepsis-induced acute kidney injury. Prospective controlled animal experiment study. Hospital-affiliated animal research institution. Fifteen female pigs. The animals were instrumented with a renal artery flow probe after surgically exposing the kidney. Nine animals were given IV infusion of lipopolysaccharide to induce septic shock, and six were used as controls. Contrast-enhanced ultrasound imaging was performed on the kidney before, during, and after having induced shock. Sublingual microcirculation was measured continuously using the Cytocam on the same spot. Contrast-enhanced ultrasound effectively allowed us to develop new analytical methods to measure dynamic variations in renal microvascular perfusion during shock and resuscitation. Renal microvascular hypoperfusion was quantified by decreased peak enhancement and an increased ratio of the final plateau intensity to peak enhancement. Reduced intrarenal blood flow could be estimated by measuring the microbubble transit times between the interlobar arteries and capillary vessels in the renal cortex. Sublingual microcirculation measured using the Cytocam in a fixed area showed decreased functional capillary density associated with plugged sublingual capillary vessels that persisted during and after fluid resuscitation. In our lipopolysaccharide model, with resuscitation targeted at blood pressure, the contrast-enhanced ultrasound imaging can identify renal microvascular alterations by showing prolonged contrast enhancement in microcirculation during shock, worsened by resuscitation with fluids. Concomitant analysis of sublingual microcirculation mirrored those observed in the renal microcirculation.

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

PubMed

Stride, E P; Coussios, C C

2010-01-01

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

Technical aspects of contrast-enhanced ultrasound (CEUS) examinations: tips and tricks.

PubMed

Greis, C

2014-01-01

Ultrasound contrast agents have substantially extended the clinical value of ultrasound, allowing the assessment of blood flow and distribution in real-time down to microcapillary level. Selective imaging of contrast agent signals requires a contrast-specific imaging mode on the ultrasound scanner, allowing real-time separation of tissue and contrast agent signals. The creation of a contrast image requires a specific interaction between the insonated ultrasound wave and the contrast agent microbubbles, leading to persistent oscillation of the bubbles. Several technical and procedural parameters have a significant influence on the quality of CEUS images and should be controlled carefully to obtain good image quality and a reliable diagnosis. Achieving the proper balance between the respective parameters is a matter of technical knowledge and experience. Appropriate training and education should be mandatory for every investigator performing CEUS examinations.

Superhydrophobic silica nanoparticles as ultrasound contrast agents.

PubMed

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

2017-05-01

Microbubbles have been widely studied as ultrasound contrast agents for diagnosis and as drug/gene carriers for therapy. However, their size and stability (lifetime of 5-12min) limited their applications. The development of stable nanoscale ultrasound contrast agents would therefore benefit both. Generating bubbles persistently in situ would be one of the promising solutions to the problem of short lifetime. We hypothesized that bubbles could be generated in situ by providing stable air nuclei since it has been found that the interfacial nanobubbles on a hydrophobic surface have a much longer lifetime (orders of days). Mesoporous silica nanoparticles (MSNs) with large surface areas and different levels of hydrophobicity were prepared to test our hypothesis. It is clear that the superhydrophobic and porous nanoparticles exhibited a significant and strong contrast intensity compared with other nanoparticles. The bubbles generated from superhydrophobic nanoparticles sustained for at least 30min at a MI of 1.0, while lipid microbubble lasted for about 5min at the same settings. In summary MSNs have been transformed into reliable bubble precursors by making simple superhydrophobic modification, and made into a promising contrast agent with the potentials to serve as theranostic agents that are sensitive to ultrasound stimulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Ultrasound contrast agents: an overview.

PubMed

Cosgrove, David

2006-12-01

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

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.

High-frequency ultrasound-guided disruption of glycoprotein VI-targeted microbubbles targets atheroprogressison in mice.

PubMed

Metzger, Katja; Vogel, Sebastian; Chatterjee, Madhumita; Borst, Oliver; Seizer, Peter; Schönberger, Tanja; Geisler, Tobias; Lang, Florian; Langer, Harald; Rheinlaender, Johannes; Schäffer, Tilman E; Gawaz, Meinrad

2015-01-01

Targeted contrast-enhanced ultrasound (CEU) using microbubble agents is a promising non-invasive imaging technique to evaluate atherosclerotic lesions. In this study, we decipher the diagnostic and therapeutic potential of targeted-CEU with soluble glycoprotein (GP)-VI in vivo. Microbubbles were conjugated with the recombinant fusion protein GPVI-Fc (MBGPVI) that binds with high affinity to atherosclerotic lesions. MBGPVI or control microbubbles (MBC) were intravenously administered into ApoE(-/-) or wild type mice and binding of the microbubbles to the vessel wall was visualized by high-resolution CEU. CEU molecular imaging signals of MBGPVI were substantially enhanced in the aortic arch and in the truncus brachiocephalicus in ApoE(-/-) as compared to wild type mice. High-frequency ultrasound (HFU)-guided disruption of MBGPVI enhanced accumulation of GPVI in the atherosclerotic lesions, which may interfere with atheroprogression. Thus, we establish targeted-CEU with soluble GPVI as a novel non-invasive molecular imaging method for atherosclerosis. Further, HFU-guided disruption of GPVI-targeted microbubbles is an innovate therapeutic approach that potentially prevents progression of atherosclerotic disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed

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

2018-04-09

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

Interleukin 16- (IL-16-) Targeted Ultrasound Imaging Agent Improves Detection of Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

PubMed

Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Adur, Malavika K; Utterback, Chet W; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

2015-01-01

Limited resolution of transvaginal ultrasound (TVUS) scanning is a significant barrier to early detection of ovarian cancer (OVCA). Contrast agents have been suggested to improve the resolution of TVUS scanning. Emerging evidence suggests that expression of interleukin 16 (IL-16) by the tumor epithelium and microvessels increases in association with OVCA development and offers a potential target for early OVCA detection. The goal of this study was to examine the feasibility of IL-16-targeted contrast agents in enhancing the intensity of ultrasound imaging from ovarian tumors in hens, a model of spontaneous OVCA. Contrast agents were developed by conjugating biotinylated anti-IL-16 antibodies with streptavidin coated microbubbles. Enhancement of ultrasound signal intensity was determined before and after injection of contrast agents. Following scanning, ovarian tissues were processed for the detection of IL-16 expressing cells and microvessels. Compared with precontrast, contrast imaging enhanced ultrasound signal intensity significantly in OVCA hens at early (P < 0.05) and late stages (P < 0.001). Higher intensities of ultrasound signals in OVCA hens were associated with increased frequencies of IL-16 expressing cells and microvessels. These results suggest that IL-16-targeted contrast agents improve the visualization of ovarian tumors. The laying hen may be a suitable model to test new imaging agents and develop targeted anti-OVCA therapeutics.

Contrast-enhanced ultrasound (CEUS) in blunt abdominal trauma

PubMed Central

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

2016-01-01

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

Contrast-enhanced intravascular ultrasound pulse sequences for bandwidth-limited transducers.

PubMed

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

2013-04-01

We demonstrate two methods for vasa vasorum imaging using contrast-enhanced intravascular ultrasound, which can be performed using commercial catheters. Plaque neovascularization was recognized as an independent marker of coronary artery plaque vulnerability. IVUS-based methods to image the microvessels available to date require high bandwidth (-6 dB relative frequency bandwidth >70%), which are not routinely available commercially. We explored the potential of ultraharmonic imaging and chirp reversal imaging for vasa vasorum imaging. In vitro recordings were performed on a tissue-mimicking phantom using a commercial ultrasound contrast agent and a transducer with a center frequency of 34 MHz and a -6 dB relative bandwidth of 56%. Acoustic peak pressures <500 kPa were used. A tissue-mimicking phantom with channels down to 200 μm in diameter was successfully imaged by the two contrast detection sequences while the smallest channel stayed invisible in conventional intravascular ultrasound images. Ultraharmonic imaging provided the best contrast agent detection. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. All rights reserved.

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

PubMed

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

2016-04-01

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

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

NASA Astrophysics Data System (ADS)

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

2006-05-01

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

Acoustic microstreaming due to an ultrasound contrast microbubble near a wall

NASA Astrophysics Data System (ADS)

Mobadersany, Nima; Sarkar, Kausik

2017-11-01

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

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

Dual-frequency piezoelectric transducers for contrast enhanced ultrasound imaging.

PubMed

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

2014-11-04

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

The Subharmonic Behavior and Thresholds of High Frequency Ultrasound Contrast Agents

NASA Astrophysics Data System (ADS)

Allen, John

2016-11-01

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

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.

Breast Cancer Detection by B7-H3-Targeted Ultrasound Molecular Imaging.

PubMed

Bachawal, Sunitha V; Jensen, Kristin C; Wilson, Katheryne E; Tian, Lu; Lutz, Amelie M; Willmann, Jürgen K

2015-06-15

Ultrasound complements mammography as an imaging modality for breast cancer detection, especially in patients with dense breast tissue, but its utility is limited by low diagnostic accuracy. One emerging molecular tool to address this limitation involves contrast-enhanced ultrasound using microbubbles targeted to molecular signatures on tumor neovasculature. In this study, we illustrate how tumor vascular expression of B7-H3 (CD276), a member of the B7 family of ligands for T-cell coregulatory receptors, can be incorporated into an ultrasound method that can distinguish normal, benign, precursor, and malignant breast pathologies for diagnostic purposes. Through an IHC analysis of 248 human breast specimens, we found that vascular expression of B7-H3 was selectively and significantly higher in breast cancer tissues. B7-H3 immunostaining on blood vessels distinguished benign/precursors from malignant lesions with high diagnostic accuracy in human specimens. In a transgenic mouse model of cancer, the B7-H3-targeted ultrasound imaging signal was increased significantly in breast cancer tissues and highly correlated with ex vivo expression levels of B7-H3 on quantitative immunofluorescence. Our findings offer a preclinical proof of concept for the use of B7-H3-targeted ultrasound molecular imaging as a tool to improve the diagnostic accuracy of breast cancer detection in patients. ©2015 American Association for Cancer Research.

Improving Sensitivity in Ultrasound Molecular Imaging by Tailoring Contrast Agent Size Distribution: In Vivo Studies

PubMed Central

Streeter, Jason E.; Gessner, Ryan; Miles, Iman; Dayton, Paul A.

2010-01-01

Molecular imaging with ultrasound relies on microbubble contrast agents (MCAs) selectively adhering to a ligand-specific target. Prior studies have shown that only small quantities of microbubbles are retained at their target sites, therefore, enhancing contrast sensitivity to low concentrations of microbubbles is essential to improve molecular imaging techniques. In order to assess the effect of MCA diameter on imaging sensitivity, perfusion and molecular imaging studies were performed with microbubbles of varying size distributions. To assess signal improvement and MCA circulation time as a function of size and concentration, blood perfusion was imaged in rat kidneys using nontargeted size-sorted MCAs with a Siemens Sequoia ultrasound system (Siemans, Mountain View, CA) in cadence pulse sequencing (CPS) mode. Molecular imaging sensitivity improvements were studied with size-sorted αvβ3-targeted bubbles in both fibrosarcoma and R3230 rat tumor models. In perfusion imaging studies, video intensity and contrast persistence was ≈8 times and ≈3 times greater respectively, for “sorted 3-micron” MCAs (diameter, 3.3 ± 1.95 μm) when compared to “unsorted” MCAs (diameter, 0.9 ± 0.45 μm) at low concentrations. In targeted experiments, application of sorted 3-micron MCAs resulted in a ≈20 times video intensity increase over unsorted populations. Tailoring size-distributions results in substantial imaging sensitivity improvement over unsorted populations, which is essential in maximizing sensitivity to small numbers of MCAs for molecular imaging. PMID:20236606

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.

Evaluation of targeting errors in ultrasound-assisted radiotherapy

PubMed Central

Wang, Michael; Rohling, Robert; Duzenli, Cheryl; Clark, Brenda; Archip, Neculai

2014-01-01

A method for validating the start-to-end accuracy of a 3D ultrasound-based patient positioning system for radiotherapy is described. A radiosensitive polymer gel is used to record the actual dose delivered to a rigid phantom after being positioned using 3D ultrasound guidance. Comparison of the delivered dose with the treatment plan allows accuracy of the entire radiotherapy treatment process, from simulation to 3D ultrasound guidance, and finally delivery of radiation, to be evaluated. The 3D ultrasound patient positioning system has a number of features for achieving high accuracy and reducing operator dependence. These include using tracked 3D ultrasound scans of the target anatomy acquired using a dedicated 3D ultrasound probe during both the simulation and treatment sessions, automatic 3D ultrasound-to-ultrasound registration, and use of infra-red LED (IRED) markers of the optical position sensing system for registering simulation CT to ultrasound data. The mean target localization accuracy of this system was 2.5mm for four target locations inside the phantom, compared to 1.6mm obtained using the conventional patient positioning method of laser alignment. Since the phantom is rigid, this represents the best possible set-up accuracy of the system. Thus, these results suggest that 3D ultrasound-based target localization is practically feasible and potentially capable of increasing the accuracy of patient positioning for radiotherapy in sites where day-to-day organ shifts are greater than 1mm in magnitude. PMID:18723271

Development of Targeted Nanobubbles for Ultrasound Imaging and Ablation of Metastatic Prostate Cancer Lesions

DTIC Science & Technology

2013-08-01

AD_________________ Award Number: W81XWH-12-1-0284 TITLE: Development of Targeted Nanobubbles for...REPORT TYPE Annual 3. DATES COVERED 15 July 2012 - 14 July 2013 4. TITLE AND SUBTITLE Development of Targeted Nanobubbles for Ultrasound...be able to formulate nanodroplets contrast agents with tunable size, PFP content, and shell flexibility to obtain stable and echogenic nanobubbles

[Contrast-enhanced ultrasound in animal models].

PubMed

Paprottka, P M; Zengel, P; Ingrisch, M; Cyran, C C; Eichhorn, M; Reiser, M F; Nikolaou, K; Clevert, D-A

2011-06-01

In the past the detection of tumor perfusion was achieved solely via invasive procedures, such as intravital microscopy or with the help of costly modalities, such as multidetector computed tomography (MDCT), magnetic resonance tomography (MRT) or the combined use of positron emission tomography and computed tomography (PET/CT). Ultrasound offers the non-invasive display of organs without usage of ionizing radiation and it is widely available. However, colour-coded ultrasound and power Doppler do not allow the detection of tumor microcirculation. The introduction of contrast-enhanced ultrasound (CEUS) as well as new high-frequency ultrasound probes made it possible to detect and quantify tumor microcirculation with high resolution. CEUS has been used clinically on human beings for more than 10 years. During the last years different tumor models in experimental animals were used for the establishment of this new technique, e.g. in rats, hamsters and mice. CEUS allows the detection of functional parameters, such as the angiogenetic metabolic status of tissue pretreatment and posttreatment. Further research is required to solve the problems of absolute quantification of these perfusion parameters to allow the comparison of CEUS with other modalities (e.g. MRT and CT).

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

PubMed

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

2013-10-01

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

Nonthermal ablation in the rat brain using focused ultrasound and an ultrasound contrast agent: long-term effects

PubMed Central

McDannold, Nathan; Zhang, Yongzhi; Vykhodtseva, Natalia

2016-01-01

OBJECTIVE Thermal ablation with transcranial MRI-guided focused ultrasound (FUS) is currently under investigation as a less invasive alternative to radiosurgery and resection. A major limitation of the method is that its use is currently restricted to centrally located brain targets. The combination of FUS and a microbubble-based ultrasound contrast agent greatly reduces the ultrasound exposure level needed to ablate brain tissue and could be an effective means to increase the “treatment envelope” for FUS in the brain. This method, however, ablates tissue through a different mechanism: destruction of the microvasculature. It is not known whether nonthermal FUS ablation in substantial volumes of tissue can safely be performed without unexpected effects. The authors investigated this question by ablating volumes in the brains of normal rats. METHODS Overlapping sonications were performed in rats (n = 15) to ablate a volume in 1 hemisphere per animal. The sonications (10-msec bursts at 1 Hz for 60 seconds; peak negative pressure 0.8 MPa) were combined with the ultrasound contrast agent Optison (100 μl/kg). The rats were followed with MRI for 4–9 weeks after FUS, and the brains were examined with histological methods. RESULTS Two weeks after sonication and later, the lesions appeared as cyst-like areas in T2-weighted MR images that were stable over time. Histological examination demonstrated well-defined lesions consisting of a cyst-like cavity that remained lined by astrocytic tissue. Some white matter structures within the sonicated area were partially intact. CONCLUSIONS The results of this study indicate that nonthermal FUS ablation can be used to safely ablate tissue volumes in the brain without unexpected delayed effects. The findings are encouraging for the use of this ablation method in the brain. PMID:26848919

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

PubMed

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

2016-11-01

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

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

PubMed Central

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

2016-01-01

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

Real-time 3-D contrast-enhanced transcranial ultrasound and aberration correction.

PubMed

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

2008-09-01

Contrast-enhanced (CE) transcranial ultrasound (US) and reconstructed 3-D 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 3-D contrast-enhanced transcranial ultrasound. Using real-time 3-D (RT3D) ultrasound and microbubble contrast agent, we scanned 17 healthy volunteers via a single temporal window and nine via the suboccipital 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 suboccipital 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.

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

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.

Ultrasound Molecular Imaging: Moving Towards Clinical Translation

PubMed Central

Abou-Elkacem, Lotfi; Bachawal, Sunitha V.; Willmann, Jürgen K.

2015-01-01

Ultrasound is a widely available, cost-effective, real-time, non-invasive and safe imaging modality widely used in the clinic for anatomical and functional imaging. With the introduction of novel molecularly-targeted ultrasound contrast agents, another dimension of ultrasound has become a reality: diagnosing and monitoring pathological processes at the molecular level. Most commonly used ultrasound molecular imaging contrast agents are micron sized, gas-containing microbubbles functionalized to recognize and attach to molecules expressed on inflamed or angiogenic vascular endothelial cells. There are several potential clinical applications currently being explored including earlier detection, molecular profiling, and monitoring of cancer, as well as visualization of ischemic memory in transient myocardial ischemia, monitoring of disease activity in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a first clinical grade ultrasound contrast agent (BR55), targeted at a molecule expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2; VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted ultrasound imaging is being explored in first inhuman clinical trials in various cancer types. This review describes the design of ultrasound molecular imaging contrast agents, imaging techniques, and potential future clinical applications of ultrasound molecular imaging. PMID:25851932

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.

Cumulative phase delay imaging for contrast-enhanced ultrasound tomography.

PubMed

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

2015-11-07

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.

Multispectral photoacoustic decomposition with localized regularization for detecting targeted contrast agent

NASA Astrophysics Data System (ADS)

Tavakoli, Behnoosh; Chen, Ying; Guo, Xiaoyu; Kang, Hyun Jae; Pomper, Martin; Boctor, Emad M.

2015-03-01

Targeted contrast agents can improve the sensitivity of imaging systems for cancer detection and monitoring the treatment. In order to accurately detect contrast agent concentration from photoacoustic images, we developed a decomposition algorithm to separate photoacoustic absorption spectrum into components from individual absorbers. In this study, we evaluated novel prostate-specific membrane antigen (PSMA) targeted agents for imaging prostate cancer. Three agents were synthesized through conjugating PSMA-targeting urea with optical dyes ICG, IRDye800CW and ATTO740 respectively. In our preliminary PA study, dyes were injected in a thin wall plastic tube embedded in water tank. The tube was illuminated with pulsed laser light using a tunable Q-switch ND-YAG laser. PA signal along with the B-mode ultrasound images were detected with a diagnostic ultrasound probe in orthogonal mode. PA spectrums of each dye at 0.5 to 20 μM concentrations were estimated using the maximum PA signal extracted from images which are obtained at illumination wavelengths of 700nm-850nm. Subsequently, we developed nonnegative linear least square optimization method along with localized regularization to solve the spectral unmixing. The algorithm was tested by imaging mixture of those dyes. The concentration of each dye was estimated with about 20% error on average from almost all mixtures albeit the small separation between dyes spectrums.

MRI-guided targeted blood-brain barrier disruption with focused ultrasound: histological findings in rabbits.

PubMed

McDannold, Nathan; Vykhodtseva, Natalia; Raymond, Scott; Jolesz, Ferenc A; Hynynen, Kullervo

2005-11-01

Focused ultrasound offers a method to disrupt the blood-brain barrier (BBB) noninvasively and reversibly at targeted locations. The purpose of this study was to test the safety of this method by searching for ischemia and apoptosis in areas with BBB disruption induced by pulsed ultrasound in the presence of preformed gas bubbles and by looking for delayed effects up to one month after sonication. Pulsed ultrasound exposures (sonications) were performed in the brains of 24 rabbits under monitoring by magnetic resonance imaging (MRI) (ultrasound: frequency = 1.63 MHz, burst length = 100 ms, PRF = 1 Hz, duration = 20 s, pressure amplitude 0.7 to 1.0 MPa). Before sonication, an ultrasound contrast agent (Optison, GE Healthcare, Milwaukee, WI, USA) was injected IV. BBB disruption was confirmed with contrast-enhanced MR images. Whole brain histologic examination was performed using haematoxylin and eosin staining for general histology, vanadium acid fuchsin-toluidine blue staining for ischemic neurons and TUNEL staining for apoptosis. The main effects observed were tiny regions of extravasated red blood cells scattered around the sonicated locations, indicating affected capillaries. Despite these vasculature effects, only a few cells in some of the sonicated areas showed evidence for apoptosis or ischemia. No ischemic or apoptotic regions were detected that would indicate a compromised blood supply was induced by the sonications. No delayed effects were observed either by MRI or histology up to 4 wk after sonication. Ultrasound-induced BBB disruption is possible without inducing substantial vascular damage that would result in ischemic or apoptotic death to neurons. These findings indicate that this method is safe for targeted drug delivery, at least when compared with the currently available invasive methods.

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

PubMed Central

Dayton, Paul A.; Pearson, David; Clark, Jarrod; Simon, Scott; Schumann, Patricia A.; Zutshi, Reena; Matsunaga, Terry O.; Ferrara, Katherine W.

2008-01-01

The goal of targeted ultrasound contrast agents is to significantly and selectively enhance the detection of a targeted vascular site. In this manuscript, three distinct contrast agents targeted to the αvβ3 integrin are examined. The αvβ3 integrin has been shown to be highly expressed on metastatic tumors and endothelial cells during neovascularization, and its expression has been shown to correlate with tumor grade. Specific adhesion of these contrast agents to αvβ3-expressing cell monolayers is demonstrated in vitro, and compared with that of nontargeted agents. Acoustic studies illustrate a backscatter amplitude increase from monolayers exposed to the targeted contrast agents of up to 13-fold (22 dB) relative to enhancement due to control bubbles. A linear dependence between the echo amplitude and bubble concentration was observed for bound agents. The decorrelation of the echo from adherent targeted agents is observed over successive pulses as a function of acoustic pressure and bubble density. Frequency–domain analysis demonstrates that adherent targeted bubbles exhibit high-amplitude narrowband echo components, in contrast to the primarily wideband response from free microbubbles. Results suggest that adherent targeted contrast agents are differentiable from free-floating microbubbles, that targeted contrast agents provide higher sensitivity in the detection of angiogenesis, and that conventional ultrasound imaging techniques such as signal subtraction or decorrelation detection can be used to detect integrin-expressing vasculature with sufficient signal-to-noise. PMID:15296677

Cumulative phase delay imaging - A new contrast enhanced ultrasound modality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demi, Libertario, E-mail: l.demi@tue.nl; Sloun, Ruud J. G. van; Mischi, Massimo

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 platemore » (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.« less

Pinched flow fractionation of microbubbles for ultrasound contrast agent enrichment

NASA Astrophysics Data System (ADS)

Versluis, Michel; Kok, Maarten; Segers, Tim

2014-11-01

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

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

PubMed

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

2013-12-01

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

Ultrasound molecular imaging: Moving toward clinical translation.

PubMed

Abou-Elkacem, Lotfi; Bachawal, Sunitha V; Willmann, Jürgen K

2015-09-01

Ultrasound is a widely available, cost-effective, real-time, non-invasive and safe imaging modality widely used in the clinic for anatomical and functional imaging. With the introduction of novel molecularly-targeted ultrasound contrast agents, another dimension of ultrasound has become a reality: diagnosing and monitoring pathological processes at the molecular level. Most commonly used ultrasound molecular imaging contrast agents are micron sized, gas-containing microbubbles functionalized to recognize and attach to molecules expressed on inflamed or angiogenic vascular endothelial cells. There are several potential clinical applications currently being explored including earlier detection, molecular profiling, and monitoring of cancer, as well as visualization of ischemic memory in transient myocardial ischemia, monitoring of disease activity in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a first clinical grade ultrasound contrast agent (BR55), targeted at a molecule expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2; VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted ultrasound imaging is being explored in first inhuman clinical trials in various cancer types. This review describes the design of ultrasound molecular imaging contrast agents, imaging techniques, and potential future clinical applications of ultrasound molecular imaging. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Hadamard-Encoded Multipulses for Contrast-Enhanced Ultrasound Imaging.

PubMed

Gong, Ping; Song, Pengfei; Chen, Shigao

2017-11-01

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

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

PubMed

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

1998-12-01

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

Contrast-enhanced ultrasound evaluation of pancreatic cancer xenografts in nude mice after irradiation with sub-threshold focused ultrasound for tumor ablation

PubMed Central

Wang, Rui; Guo, Qian; Chen, Yi Ni; Hu, Bing; Jiang, Li Xin

2017-01-01

We evaluated the efficacy of contrast-enhanced ultrasound for assessing tumors after irradiation with sub-threshold focused ultrasound (FUS) ablation in pancreatic cancer xenografts in nude mice. Thirty tumor-bearing nude mice were divided into three groups: Group A received sham irradiation, Group B received a moderate-acoustic energy dose (sub-threshold), and Group C received a high-acoustic energy dose. In Group B, B-mode ultrasound (US), color Doppler US, and dynamic contrast-enhanced ultrasound (DCE-US) studies were conducted before and after irradiation. After irradiation, tumor growth was inhibited in Group B, and the tumors shrank in Group C. In Group A, the tumor sizes were unchanged. In Group B, contrast-enhanced ultrasound (CEUS) images showed a rapid rush of contrast agent into and out of tumors before irradiation. After irradiation, CEUS revealed contrast agent perfusion only at the tumor periphery and irregular, un-perfused volumes of contrast agent within the tumors. DCE-US perfusion parameters, including peak intensity (PI) and area under the curve (AUC), had decreased 24 hours after irradiation. PI and AUC were increased 48 hours and 2weeks after irradiation. Time to peak (TP) and sharpness were increased 24 hours after irradiation. TP decreased at 48 hours and 2 weeks after irradiation. CEUS is thus an effective method for early evaluation after irradiation with sub-threshold FUS. PMID:28402267

Ultrasound contrast agents for bleeding detection and acoustic hemostasis

NASA Astrophysics Data System (ADS)

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

2005-04-01

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

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2012-09-01

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

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

PubMed

Minami, Yasunori; Kudo, Masatoshi

2009-12-31

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

A cMUT probe for ultrasound-guided focused ultrasound targeted therapy.

PubMed

Gross, Dominique; Coutier, Caroline; Legros, Mathieu; Bouakaz, Ayache; Certon, Dominique

2015-06-01

Ultrasound-mediated targeted therapy represents a promising strategy in the arsenal of modern therapy. Capacitive micromachined ultrasonic transducer (cMUT) technology could overcome some difficulties encountered by traditional piezoelectric transducers. In this study, we report on the design, fabrication, and characterization of an ultrasound-guided focused ultrasound (USgFUS) cMUT probe dedicated to preclinical evaluation of targeted therapy (hyperthermia, thermosensitive liposomes activation, and sonoporation) at low frequency (1 MHz) with simultaneous ultrasonic imaging and guidance (15 to 20 MHz). The probe embeds two types of cMUT arrays to perform the modalities of targeted therapy and imaging respectively. The wafer-bonding process flow employed for the manufacturing of the cMUTs is reported. One of its main features is the possibility of implementing two different gap heights on the same wafer. All the design and characterization steps of the devices are described and discussed, starting from the array design up to the first in vitro measurements: optical (microscopy) and electrical (impedance) measurements, arrays' electroacoustic responses, focused pressure field mapping (maximum peak-to-peak pressure = 2.5 MPa), and the first B-scan image of a wire-target phantom.

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

PubMed

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

2010-01-01

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

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

PubMed

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

2015-03-01

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

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

Recent advances in ultrasound-triggered therapy.

PubMed

Yang, Chaopin; Li, Yue; Du, Meng; Chen, Zhiyi

2018-04-27

As a non-invasive and real-time diagnostic technique, ultrasound has provided a novel strategy for targeted treatment. With the rapid development of ultrasonic technique and ultrasound contrast agents (UCAs), spatiotemporally controllable application of ultrasound with or without UCAs makes it possible for site-specific delivery of therapeutic agents and targeted modulation with minimal side effects, which indicated a promising therapy in clinical use. This review will describe the main mechanism of targeted therapy induced by ultrasound briefly, then focus on the current application of ultrasound mediated targeted therapy in various fields including tumour, cardiovascular disease, central nervous system, skeletal muscle system diseases and stem cells therapy. In addition, ongoing challenges of ultrasound-mediated targeted therapy for further research and its clinical use are reviewed.

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

PubMed

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

2013-06-01

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

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

PubMed Central

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

2016-01-01

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

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

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. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2012-11-01

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

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

PubMed Central

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

2016-01-01

Background The utero-placental vascular supply is a critical determinant of placental function and fetal growth. Current methods for the in vivo assessment of placental blood flow are limited. Objective Here we demonstrate the feasibility of utilizing contrast-enhanced ultrasound to visualize and quantify perfusion kinetics in the intervillous space of the primate placenta. Study design Pregnant Japanese macaques were studied at mid second trimester and in the early third trimester. Markers of injury were assessed in placenta samples from animals with or without contrast-enhanced ultrasound exposure (n=6/group). Human subjects were recruited immediately prior to scheduled first trimester pregnancy termination. All studies were performed with maternal intravenous infusion of lipid-shelled octofluoropropane microbubbles with image acquisition using a multipulse contrast-specific algorithm with destruction-replenishment analysis of signal intensity for assessment of perfusion. Results In macaques, rate of perfusion in the intervillous space was increased with advancing gestation. No evidence of microvascular hemorrhage or acute inflammation was found in placental villous tissue and expression levels of caspase-3, nitrotyrosine and HSP70 as markers of apoptosis, nitrative and oxidative stress respectively were unchanged by contrast-enhanced ultrasound exposure. In humans, placental perfusion was visualized at 11wks gestation and preliminary data reveal regional differences in intervillous space perfusion within an individual placenta. By electron microscopy, we demonstrate no evidence of ultrastructure damage to the microvilli on the syncytiotrophoblast following first trimester ultrasound studies. Conclusions Use of contrast-enhanced ultrasound did not result in placental structural damage, and was able to identify intervillous space perfusion rate differences within a placenta. Contrast-enhanced ultrasound may offer a safe clinical tool for the identification of

Transabdominal contrast-enhanced ultrasound imaging of the prostate.

PubMed

Mischi, Massimo; Demi, Libertario; Smeenge, Martijn; Kuenen, Maarten P J; Postema, Arnoud W; de la Rosette, Jean J M C H; Wijkstra, Hessel

2015-04-01

Numerous age-related pathologies affect the prostate gland, the most menacing of which is prostate cancer (PCa). The diagnostic tools for prostate investigation are invasive, requiring biopsies when PCa is suspected. Novel dynamic contrast-enhanced ultrasound (DCE-US) imaging approaches have been proposed recently and appear promising for minimally invasive localization of PCa. Ultrasound imaging of the prostate is traditionally performed with a transrectal probe because the location of the prostate allows for high-resolution images using high-frequency transducers. However, DCE-US imaging requires lower frequencies to induce bubble resonance and, thus, improve contrast-to-tissue ratio. For this reason, in this study we investigate the feasibility of quantitative DCE-US imaging of the prostate via the abdomen. The study included 10 patients (age = 60.7 ± 5.7 y) referred for a needle biopsy study. After having given informed consent, patients underwent DCE-US with both transabdominal and transrectal probes. Time-intensity contrast curves were derived using both approaches and their model-fit quality was compared. Although further improvements are expected by optimization of the transabdominal settings, the results of transabdominal and transrectal DCE-US are closely comparable, confirming the feasibility of transabdominal DCE-US; transabdominal curve fitting revealed an average determination coefficient r(2) = 0.91 (r(2) > 0.75 for 78.6% of all prostate pixels) compared with r(2) = 0.91 (r(2) > 0.75 for 81.6% of all prostate pixels) by the transrectal approach. Replacing the transrectal approach with more acceptable transabdominal scanning for prostate investigation is feasible. This approach would improve patient comfort and represent a useful option for PCa localization and monitoring. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Improved Contrast-Enhanced Ultrasound Imaging With Multiplane-Wave Imaging.

PubMed

Gong, Ping; Song, Pengfei; Chen, Shigao

2018-02-01

Contrast-enhanced ultrasound (CEUS) imaging has great potential for use in new ultrasound clinical applications such as myocardial perfusion imaging and abdominal lesion characterization. In CEUS imaging, contrast agents (i.e., microbubbles) are used to improve contrast between blood and tissue because of their high nonlinearity under low ultrasound pressure. However, the quality of CEUS imaging sometimes suffers from a low signal-to-noise ratio (SNR) in deeper imaging regions when a low mechanical index (MI) is used to avoid microbubble disruption, especially for imaging at off-resonance transmit frequencies. In this paper, we propose a new strategy of combining CEUS sequences with the recently proposed multiplane-wave (MW) compounding method to improve the SNR of CEUS in deeper imaging regions without increasing MI or sacrificing frame rate. The MW-CEUS method emits multiple Hadamard-coded CEUS pulses in each transmission event (i.e., pulse-echo event). The received echo signals first undergo fundamental bandpass filtering (i.e., the filter is centered on the transmit frequency) to eliminate the microbubble's second-harmonic signals because they cannot be encoded by pulse inversion. The filtered signals are then Hadamard decoded and realigned in fast time to recover the signals as they would have been obtained using classic CEUS pulses, followed by designed recombination to cancel the linear tissue responses. The MW-CEUS method significantly improved contrast-to-tissue ratio and SNR of CEUS imaging by transmitting longer coded pulses. The image resolution was also preserved. The microbubble disruption ratio and motion artifacts in MW-CEUS were similar to those of classic CEUS imaging. In addition, the MW-CEUS sequence can be adapted to other transmission coding formats. These properties of MW-CEUS can potentially facilitate CEUS imaging for many clinical applications, especially assessing deep abdominal organs or the heart.

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

NASA Astrophysics Data System (ADS)

McDannold, N.; Vykhodtseva, N.; Hynynen, K.

2006-02-01

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

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

PubMed

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

2015-07-01

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

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

PubMed

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

2014-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2014-01-01

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

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

PubMed

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

2005-10-01

To detect specific cardiomyocyte injury induced by myocardial contrast material-enhanced echocardiography (ie, myocardial contrast echocardiography) in rats and to ascertain the influences of contrast material dose and ultrasound exposure on this injury. All animal procedures were approved by the university committee for the use and care of animals. Myocardial contrast echocardiography with 1:4 electrocardiographic (ECG) triggering was performed at 1.5 MHz in 61 anesthetized rats. Evans blue (EB) dye was injected as the vital stain for cardiomyocyte injury. At the start of myocardial contrast echocardiography, which lasted 10 minutes, perflutren lipid microsphere-based contrast material was infused through the tail vein for 5 minutes. Premature heartbeats were counted from the ECG record. The numbers of EB-stained cells counted on sections of heart specimens obtained 24 hours after myocardial contrast echocardiography and then either fresh frozen or embedded in paraffin were determined by using fluorescence microscopy. Results were compared statistically by using t tests and Mann-Whitney rank sum tests. EB-stained cells were concentrated in the anterior region of the myocardium. In the paraffin-embedded specimens, EB-stained cells were often accompanied by but largely separate from areas of inflammatory cell infiltration. At end-systolic triggering with a 50 microL/kg dose of microsphere contrast material, the EB-stained cell count increased with increasing peak rarefactional pressure amplitude, with significantly increased cell counts at 1.6 MPa (P < .02) and 2.0 MPa (P < .005) relative to the cell counts at sham myocardial contrast echocardiography. Premature heartbeats had a similar exposure-response relationship; however, number of premature heartbeats and EB-stained cell count did not appear to be directly related (coefficient of determination r2 = 0.03). The EB-stained cell counts at end-diastolic triggering were not significantly different from those at end

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

PubMed Central

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

2013-01-01

The cavitation response of circulating microbubbles to targeted ultrasound can be used for noninvasive, site-specific delivery of shell-loaded materials. One challenge for microbubble-mediated delivery of lipophilic compounds is the limitation of drug loading into the microbubble shell, which is commonly a single phospholipid monolayer. In this study, we investigated the use of natural lung surfactant extract (Survanta®, Abbott Nutrition) as a microbubble shell material in order to improve drug payload and delivery. Pulmonary surfactant extracts such as Survanta contain hydrophobic surfactant proteins (SP-B and SP-C) that facilitate lipid folding and retention on lipid monolayers. Here, we show that Survanta-based microbubbles exhibit wrinkles in bright-field microscopy and increased lipid retention on the microbubble surface in the form of surface-associated aggregates observed with fluorescence microscopy. The payload of a model lipophilic drug (DiO), measured by flow cytometry, increased by over 2-fold compared to lipid-coated microbubbles lacking SP-B and SP-C. Lung surfactant microbubbles were highly echogenic to contrast enhanced ultrasound imaging at low acoustic intensities. At higher ultrasound intensity, excess lipid was observed to be acoustically cleaved for localized release. To demonstrate targeting, a biotinylated lipopolymer was incorporated into the shell, and the microbubbles were subjected to a sequence of radiation force and fragmentation pulses as they passed through an avidinated hollow fiber. Lung surfactant microbubbles showed a 3-fold increase in targeted deposition of the model fluorescent drug compared to lipid-only microbubbles. Our results demonstrate that lung surfactant microbubbles maintain the acoustic responsiveness of lipid-coated microbubbles with the added benefit of increased lipophilic drug payload. PMID:23781287

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

PubMed

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

2013-01-01

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

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

PubMed

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

2016-09-20

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

A modified commercial ultrasound scanner used for in vivo photoacoustic imaging of nude mice injected with non-targeted contrast agents

NASA Astrophysics Data System (ADS)

Jankovic, Ladislav; Shahzad, Khalid; Wang, Yao; Burcher, Michael; Scholle, Frank-Detlef; Hauff, Peter; Mofina, Sabine; Skobe, Mihaela

2008-02-01

Photoacoustic (PA) experiments were performed using a modified commercial ultrasound scanner equipped with an array transducer and a Nd:YAG pumped OPO laser. The contrast agent SIDAG (Bayer Schering Pharma AG, Germany), used to enhance the optical absorption, demonstrated an expected pharmacokinetic behavior of the dye in the tumor and in the bladder of the nude mice. A typical behavior in the tumor consisted of an initial linear increase in PA signal followed by an exponential decay. PA signal approached the pre-injection level after about one hour following the dye injection, which was consistent with the behavior for such contrast agents when used in other imaging modalities, such as fluorescence imaging. The in-vivo spectral PA data from the mouse bladder, conducted 1.5 hours after the dye injection, clearly demonstrated presence of the dye. The multi-spectral PA data was obtained at 760nm, 784nm and 850nm laser excitations. The PA intensities obtained at these three wavelengths accurately matched the dye absorption spectrum. In addition, in the kidney, a clearance organ for this contrast agent, both in-vivo and ex-vivo results demonstrated a significant increase (~ 40%) in the ratio of PA signal at 760nm (the peak of the dye absorption) relative to the signal at 850nm (<1% absorption), indicating significant amounts of the dye in this organ. Our initial results confirm the desired photoacoustic properties of the contrast agent, indicating its great potential to be used for imaging with a commercial array-based ultrasound scanner.

A theoretical investigation of chirp insonification of ultrasound contrast agents.

PubMed

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

2011-08-01

A theoretical investigation of second harmonic imaging of an Ultrasound Contrast Agent (UCA) under chirp insonification is considered. By solving the UCA's dynamical equation analytically, the effect that the chirp signal parameters and the UCA shell parameters have on the amplitude of the second harmonic frequency are examined. This allows optimal parameter values to be identified which maximise the UCA's second harmonic response. A relationship is found for the chirp parameters which ensures that a signal can be designed to resonate a UCA for a given set of shell parameters. It is also shown that the shell thickness, shell viscosity and shell elasticity parameter should be as small as realistically possible in order to maximise the second harmonic amplitude. Keller-Herring, Second Harmonic, Chirp, Ultrasound Contrast Agent. Copyright © 2011 Elsevier B.V. All rights reserved.

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

PubMed

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

2016-03-01

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

Accuracy of contrast-enhanced ultrasound in the detection of bladder cancer

PubMed Central

Nicolau, C; Bunesch, L; Peri, L; Salvador, R; Corral, J M; Mallofre, C; Sebastia, C

2011-01-01

Objective To assess the accuracy contrast-enhanced ultrasound (CEUS) in bladder cancer detection using transurethral biopsy in conventional cystoscopy as the reference standard and to determine whether CEUS improves the bladder cancer detection rate of baseline ultrasound. Methods 43 patients with suspected bladder cancer underwent conventional cystoscopy with transurethral biopsy of the suspicious lesions. 64 bladder cancers were confirmed in 33 out of 43 patients. Baseline ultrasound and CEUS were performed the day before surgery and the accuracy of both techniques for bladder cancer detection and number of detected tumours were analysed and compared with the final diagnosis. Results CEUS was significantly more accurate than ultrasound in determining presence or absence of bladder cancer: 88.37% vs 72.09%. Seven of eight uncertain baseline ultrasound results were correctly diagnosed using CEUS. CEUS sensitivity was also better than that of baseline ultrasound per number of tumours: 65.62% vs 60.93%. CEUS sensitivity for bladder cancer detection was very high for tumours larger than 5 mm (94.7%) but very low for tumours <5 mm (20%) and also had a very low negative predictive value (28.57%) in tumours <5 mm. Conclusion CEUS provided higher accuracy than baseline ultrasound for bladder cancer detection, being especially useful in non-conclusive baseline ultrasound studies. PMID:21123306

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

NASA Astrophysics Data System (ADS)

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

2013-07-01

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

Contrast-enhanced ultrasound in diagnosis of gallbladder adenoma.

PubMed

Yuan, Hai-Xia; Cao, Jia-Ying; Kong, Wen-Tao; Xia, Han-Sheng; Wang, Xi; Wang, Wen-Ping

2015-04-01

Gallbladder adenoma is a pre-cancerous neoplasm and needs surgical resection. It is difficult to differentiate adenoma from other gallbladder polyps using imaging examinations. The study aimed to illustrate characteristics of contrast-enhanced ultrasound (CEUS) and its diagnostic value in gallbladder adenoma. Thirty-seven patients with 39 gallbladder adenomatoid lesions (maximal diameter ≥10 mm and without metastasis) were enrolled in this study. Lesion appearances in conventional ultrasound and CEUS were documented. The imaging features were compared individually among gallbladder cholesterol polyp, gallbladder adenoma and malignant lesion. Adenoma lesions showed iso-echogenicity in ultrasound, and an eccentric enhancement pattern, "fast-in and synchronous-out" contrast enhancement pattern and homogeneous at peak-time enhancement in CEUS. The homogenicity at peak-time enhancement showed the highest diagnostic ability in differentiating gallbladder adenoma from cholesterol polyps. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Youden index were 100%, 90.9%, 92.9%, 100%, 95.8% and 0.91, respectively. The characteristic of continuous gallbladder wall shown by CEUS had the highest diagnostic ability in differentiating adenoma from malignant lesion (100%, 86.7%, 86.7%, 100%, 92.9% and 0.87, respectively). The characteristic of the eccentric enhancement pattern had the highest diagnostic ability in differentiating adenoma from cholesterol polyp and malignant lesion, with corresponding indices of 69.2%, 88.5%, 75.0%, 85.2%, 82.1% and 0.58, respectively. CEUS is valuable in differentiating gallbladder adenoma from other gallbladder polyps (≥10 mm in diameter). Homogeneous echogenicity on peak-time enhancement, a continuous gallbladder wall, and the eccentric enhancement pattern are important indicators of gallbladder adenoma on CEUS.

Integration of Real-Time Intraoperative Contrast-Enhanced Ultrasound and Color Doppler Ultrasound in the Surgical Treatment of Spinal Cord Dural Arteriovenous Fistulas.

PubMed

Della Pepa, Giuseppe Maria; Sabatino, Giovanni; Sturiale, Carmelo Lucio; Marchese, Enrico; Puca, Alfredo; Olivi, Alessandro; Albanese, Alessio

2018-04-01

In the surgical treatment of spinal dural arteriovenous fistulas (DAVFs), intraoperative definition of anatomic characteristics of the DAVF and identification of the fistulous point is mandatory to effectively exclude the DAVF. Intraoperative ultrasound and contrast-enhanced ultrasound integrated with color Doppler ultrasound was applied in the surgical setting for a cervical DAVF to identify the fistulous point and evaluate correct occlusion of the fistula. Integration of intraoperative ultrasound and contrast-enhanced ultrasound is a simple, cost-effective technique that provides an opportunity for real-time dynamic visualization of DAVF vascular patterns, identification of the fistulous point, and assessment of correct exclusion. Compared with other intraoperative tools, such as indocyanine green videoangiography, it allows the surgeon to visualize hidden anatomic and vascular structures, minimizing surgical manipulation and guiding the surgeon during resection. Copyright © 2018 Elsevier Inc. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

Comparative Effectiveness of Targeted Prostate Biopsy Using Magnetic Resonance Imaging Ultrasound Fusion Software and Visual Targeting: a Prospective Study.

PubMed

Lee, Daniel J; Recabal, Pedro; Sjoberg, Daniel D; Thong, Alan; Lee, Justin K; Eastham, James A; Scardino, Peter T; Vargas, Hebert Alberto; Coleman, Jonathan; Ehdaie, Behfar

2016-09-01

We compared the diagnostic outcomes of magnetic resonance-ultrasound fusion and visually targeted biopsy for targeting regions of interest on prostate multiparametric magnetic resonance imaging. Patients presenting for prostate biopsy with regions of interest on multiparametric magnetic resonance imaging underwent magnetic resonance imaging targeted biopsy. For each region of interest 2 visually targeted cores were obtained, followed by 2 cores using a magnetic resonance-ultrasound fusion device. Our primary end point was the difference in the detection of high grade (Gleason 7 or greater) and any grade cancer between visually targeted and magnetic resonance-ultrasound fusion, investigated using McNemar's method. Secondary end points were the difference in detection rate by biopsy location using a logistic regression model and the difference in median cancer length using the Wilcoxon signed rank test. We identified 396 regions of interest in 286 men. The difference in the detection of high grade cancer between magnetic resonance-ultrasound fusion biopsy and visually targeted biopsy was -1.4% (95% CI -6.4 to 3.6, p=0.6) and for any grade cancer the difference was 3.5% (95% CI -1.9 to 8.9, p=0.2). Median cancer length detected by magnetic resonance-ultrasound fusion and visually targeted biopsy was 5.5 vs 5.8 mm, respectively (p=0.8). Magnetic resonance-ultrasound fusion biopsy detected 15% more cancers in the transition zone (p=0.046) and visually targeted biopsy detected 11% more high grade cancer at the prostate base (p=0.005). Only 52% of all high grade cancers were detected by both techniques. We found no evidence of a significant difference in the detection of high grade or any grade cancer between visually targeted and magnetic resonance-ultrasound fusion biopsy. However, the performance of each technique varied in specific biopsy locations and the outcomes of both techniques were complementary. Combining visually targeted biopsy and magnetic resonance-ultrasound

[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. © Georg Thieme Verlag KG Stuttgart · New York.

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

PubMed

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

2010-01-01

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

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

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

Cardiac Arrhythmia and Injury Induced in Rats by Burst and Pulsed Mode Ultrasound with Gas Body Contrast Agent

PubMed Central

Miller, Douglas L.; Dou, Chunyan; Lucchesi, Benedict R.

2009-01-01

Objective Premature complexes (PCs) in the electrocardiogram (ECG) signal have been reported for myocardial contrast echocardiography and also for burst mode (physical therapy) ultrasound with gas body contrast agent at lower peak rarefactional pressure amplitudes (PRPAs). For contrast echocardiography, irreversibly injured cardiomyocytes have been associated with the arrhythmia. The objective was to determine if cardiomyocyte injury is associated with the PCs induced by the burst mode at lower PRPAs. Methods Anesthetized rats were exposed to focused 1.5 MHz ultrasound in a water bath. Evans blue dye was injected IP to stain injured cardiomyocytes and Definity ultrasound contrast agent was infused IV. Continuous burst mode simulated physical therapy ultrasound. Intermittent 2 ms bursts, or envelopes of pulses simulating diagnostic ultrasound, were triggered 1:4 at end systole. PCs were observed on ECG recordings and stained cardiomyocytes were counted in frozen sections. Results The continuous burst mode produced variable PCs and stained cells above 0.3 MPa PRPA. The triggered bursts above 0.3 MPa and pulse envelopes above 1.2 MPa produced statistically significant (P<0.01) PCs and stained cardiomyocytes. Conclusion Irreversible cardiomyocyte injury was associated with the development of PCs for burst mode and occurred at substantially lower PRPAs than for pulsed ultrasound. PMID:19854967

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

PubMed

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

2014-02-01

Ultrasound contrast agents (UCAs) can be employed to nucleate cavitation to achieve desired bioeffects, such as thrombolysis, in therapeutic ultrasound applications. Effective methods of enhancing thrombolysis with ultrasound have been examined at low frequencies (<1 MHz) and low amplitudes (<0.5 MPa). The objective of this study was to determine cavitation thresholds for two UCAs exposed to 120-kHz ultrasound. A commercial ultrasound contrast agent (Definity(®)) and echogenic liposomes were investigated to determine the acoustic pressure threshold for ultraharmonic (UH) and broadband (BB) generation using an in vitro flow model perfused with human plasma. Cavitation emissions were detected using two passive receivers over a narrow frequency bandwidth (540-900 kHz) and a broad frequency bandwidth (0.54-1.74 MHz). UH and BB cavitation thresholds occurred at the same acoustic pressure (0.3 ± 0.1 MPa, peak to peak) and were found to depend on the sensitivity of the cavitation detector but not on the nucleating contrast agent or ultrasound duty cycle.

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

NASA Astrophysics Data System (ADS)

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

2017-09-01

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

Limitations of contrast enhancement for infrared target identification

NASA Astrophysics Data System (ADS)

Du Bosq, Todd W.; Fanning, Jonathan D.

2009-05-01

Contrast enhancement and dynamic range compression are currently being used to improve the performance of infrared imagers by increasing the contrast between the target and the scene content. Automatic contrast enhancement techniques do not always achieve this improvement. In some cases, the contrast can increase to a level of target saturation. This paper assesses the range-performance effects of contrast enhancement for target identification as a function of image saturation. Human perception experiments were performed to determine field performance using contrast enhancement on the U.S. Army RDECOM CERDEC NVESD standard military eight target set using an un-cooled LWIR camera. The experiments compare the identification performance of observers viewing contrast enhancement processed images at various levels of saturation. Contrast enhancement is modeled in the U.S. Army thermal target acquisition model (NVThermIP) by changing the scene contrast temperature. The model predicts improved performance based on any improved target contrast, regardless of specific feature saturation or enhancement. The measured results follow the predicted performance based on the target task difficulty metric used in NVThermIP for the non-saturated cases. The saturated images reduce the information contained in the target and performance suffers. The model treats the contrast of the target as uniform over spatial frequency. As the contrast is enhanced, the model assumes that the contrast is enhanced uniformly over the spatial frequencies. After saturation, the spatial cues that differentiate one tank from another are located in a limited band of spatial frequencies. A frequency dependent treatment of target contrast is needed to predict performance of over-processed images.

Can the Contrast-Enhanced Ultrasound Washout Rate Be Used to Predict Microvascular Invasion in Hepatocellular Carcinoma?

PubMed

Zhu, Wei; Qing, Xiachuan; Yan, Feng; Luo, Yan; Li, Yongzhong; Zhou, Xiang

2017-08-01

The objective of this study was to investigate use of the washout rate of hepatocellular carcinoma on contrast-enhanced ultrasound (CEUS) for pre-operative determination of the presence of microvascular invasion. The study included 271 patients who underwent liver resection for hepatocellular carcinoma between April 2008 and December 2012, and were examined with contrast-enhanced ultrasound before surgery. Patients were followed up at 3-mo intervals for 3 y. Four washout patterns were classified according to the start time of washout: rapid, portal, delayed and slow. Rapid washout, presence of two or more tumors and tumor size ≥5 cm were identified as independent pre-operative predictors of microvascular invasion on multivariate analysis. Recurrence rates for patients with none, one, two or three predictors were 22.6%, 34.7%, 57.6% and 75.0%, respectively. In combination with tumor number and tumor size, contrast-enhanced ultrasound washout rate may have a role in identifying hepatocellular carcinoma patients with microvascular invasion. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

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

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

PubMed

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

2015-03-01

The aim of this study was to investigate the diagnostic values of conventional ultrasound and contrast-enhanced ultrasound (CEUS) in benign and malignant thyroid nodules with calcification. Conventional ultrasound and CEUS were performed in 122 patients with thyroid nodules with calcification. The thyroid nodules were characterized as benign or malignant by pathological diagnosis. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accordance rate of the two imaging methods were determined. The area under the receiver operating characteristics curve (AUC) was used to assess the diagnostic values of the two imaging methods. In 122 cases of thyroid nodules with calcification, 73 benign nodules and 49 malignant nodules were verified by pathological diagnosis. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accordance rate of conventional ultrasound were 50%, 77%, 59%, 69%, and 66%, respectively, and those of CEUS were 90%, 92%, 88%, 93%, and 91%, respectively. There were significant differences between the two imaging methods. AUCs of conventional ultrasound and CEUS were 0.628 ± 0.052 and 0.908 ± 0.031, suggesting low and high diagnostic values, respectively. CEUS has high diagnostic values, being significantly greater than those of conventional ultrasound, in differential diagnosis of benign and malignant thyroid nodules with calcification. Copyright © 2014. Published by Elsevier Taiwan.

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

PubMed

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

2016-01-01

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

Targeted delivery of cancer-specific multimodal contrast agents for intraoperative detection of tumor boundaries and therapeutic margins

NASA Astrophysics Data System (ADS)

Xu, Ronald X.; Xu, Jeff S.; Huang, Jiwei; Tweedle, Michael F.; Schmidt, Carl; Povoski, Stephen P.; Martin, Edward W.

2010-02-01

Background: Accurate assessment of tumor boundaries and intraoperative detection of therapeutic margins are important oncologic principles for minimal recurrence rates and improved long-term outcomes. However, many existing cancer imaging tools are based on preoperative image acquisition and do not provide real-time intraoperative information that supports critical decision-making in the operating room. Method: Poly lactic-co-glycolic acid (PLGA) microbubbles (MBs) and nanobubbles (NBs) were synthesized by a modified double emulsion method. The MB and NB surfaces were conjugated with CC49 antibody to target TAG-72 antigen, a human glycoprotein complex expressed in many epithelial-derived cancers. Multiple imaging agents were encapsulated in MBs and NBs for multimodal imaging. Both one-step and multi-step cancer targeting strategies were explored. Active MBs/NBs were also fabricated for therapeutic margin assessment in cancer ablation therapies. Results: The multimodal contrast agents and the cancer-targeting strategies were tested on tissue simulating phantoms, LS174 colon cancer cell cultures, and cancer xenograft nude mice. Concurrent multimodal imaging was demonstrated using fluorescence and ultrasound imaging modalities. Technical feasibility of using active MBs and portable imaging tools such as ultrasound for intraoperative therapeutic margin assessment was demonstrated in a biological tissue model. Conclusion: The cancer-specific multimodal contrast agents described in this paper have the potential for intraoperative detection of tumor boundaries and therapeutic margins.

Methotrexate-loaded PLGA nanobubbles for ultrasound imaging and Synergistic Targeted therapy of residual tumor during HIFU ablation.

PubMed

Zhang, Xuemei; Zheng, Yuanyi; Wang, Zhigang; Huang, Shuai; Chen, Yu; Jiang, Wei; Zhang, Hua; Ding, Mingxia; Li, Qingshu; Xiao, Xiaoqiu; Luo, Xin; Wang, Zhibiao; Qi, Hongbo

2014-06-01

High intensity focused ultrasound (HIFU) has attracted the great attention in tumor ablation due to its non-invasive, efficient and economic features. However, HIFU ablation has its intrinsic limitations for removing the residual tumor cells, thus the tumor recurrence and metastasis cannot be avoided in this case. Herein, we developed a multifunctional targeted poly(lactic-co-glycolic acid) (PLGA) nanobubbles (NBs), which not only function as an efficient ultrasound contrast agent for tumor imaging, but also a targeted anticancer drug carrier and excellent synergistic agent for enhancing the therapeutic efficiency of HIFU ablation. Methotrexate (MTX)-loaded NBs were synthesized and filled with perfluorocarbon gas subsequently using a facile but general double emulsion evaporation method. The active tumor-targeting monoclonal anti-HLA-G antibodies (mAbHLA-G) were further conjugated onto the surface of nanobubbles. The mAbHLA-G/MTX/PLGA NBs could enhance the ultrasound imaging both in vitro and in vivo, and the targeting efficiency to HLA-G overexpressing JEG-3 cells has been demonstrated. The elaborately designed mAbHLA-G/MTX/PLGA NBs can specifically target to the tumor cells both in vitro and in vivo, and their blood circulation time in vivo was much longer than non-targeted MTX/PLGA NBs. Further therapeutic evaluations showed that the targeted NBs as a synergistic agent can significantly improve the efficiency of HIFU ablation by changing the acoustic environment, and the focused ultrasound can promote the on-demand MTX release both in vitro and in vivo. The in vivo histopathology test and immunohistochemical analysis showed that the mAbHLA-G/MTX/PLGA NBs plus HIFU group presented most serious coagulative necrosis, the lowest proliferation index and the highest apoptotic index. Therefore, the successful introduction of targeted mAbHLA-G/MTX/PLGA NBs provides an excellent platform for the highly efficient, imaging-guided and non-invasive HIFU synergistic therapy

Molecular Ultrasound Imaging for the Detection of Neural Inflammation

NASA Astrophysics Data System (ADS)

Volz, Kevin R.

Molecular imaging is a form of nanotechnology that enables the noninvasive examination of biological processes in vivo. Radiopharmaceutical agents are used to selectively target biochemical markers, which permits their detection and evaluation. Early visualization of molecular variations indicative of pathophysiological processes can aid in patient diagnoses and management decisions. Molecular imaging is performed by introducing molecular probes into the body. Molecular probes are often contrast agents that have been nanoengineered to selectively target and tether to molecules, enabling their radiologic identification. Ultrasound contrast agents have been demonstrated as an effective method of detecting perfusion at the tissue level. Through a nanoengineering process, ultrasound contrast agents can be targeted to specific molecules, thereby extending ultrasound's capabilities from the tissue to molecular level. Molecular ultrasound, or targeted contrast enhanced ultrasound (TCEUS), has recently emerged as a popular molecular imaging technique due to its ability to provide real-time anatomical and functional information in the absence of ionizing radiation. However, molecular ultrasound represents a novel form of molecular imaging, and consequently remains largely preclinical. A review of the TCEUS literature revealed multiple preclinical studies demonstrating its success in detecting inflammation in a variety of tissues. Although, a gap was identified in the existing evidence, as TCEUS effectiveness for detection of neural inflammation in the spinal cord was unable to be uncovered. This gap in knowledge, coupled with the profound impacts that this TCEUS application could have clinically, provided rationale for its exploration, and use as contributory evidence for the molecular ultrasound body of literature. An animal model that underwent a contusive spinal cord injury was used to establish preclinical evidence of TCEUS to detect neural inflammation. Imaging was

Delivery of Hydrogen Sulfide by Ultrasound Targeted Microbubble Destruction Attenuates Myocardial Ischemia-reperfusion Injury

PubMed Central

Chen, Gangbin; Yang, Li; Zhong, Lintao; Kutty, Shelby; Wang, Yuegang; Cui, Kai; Xiu, Jiancheng; Cao, Shiping; Huang, Qiaobing; Liao, Wangjun; Liao, Yulin; Wu, Juefei; Zhang, Wenzhu; Bin, Jianping

2016-01-01

Hydrogen sulfide (H2S) is an attractive agent for myocardial ischemia-reperfusion injury, however, systemic delivery of H2S may cause unwanted side effects. Ultrasound targeted microbubble destruction has become a promising tool for organ specific delivery of bioactive substance. We hypothesized that delivery of H2S by ultrasound targeted microbubble destruction attenuates myocardial ischemia-reperfusion injury and could avoid unwanted side effects. We prepared microbubbles carrying hydrogen sulfide (hs-MB) with different H2S/C3F8 ratios (4/0, 3/1, 2/2, 1/3, 0/4) and determined the optimal ratio. Release of H2S triggered by ultrasound was investigated. The cardioprotective effect of ultrasound targeted hs-MB destruction was investigated in a rodent model of myocardial ischemia-reperfusion injury. The H2S/C3F8 ratio of 2/2 was found to be an optimal ratio to prepare stable hs-MB with higher H2S loading capability. Ultrasound targeted hs-MB destruction triggered H2S release and increased the concentration of H2S in the myocardium and lung. Ultrasound targeted hs-MB destruction limited myocardial infarct size, preserved left ventricular function and had no influence on haemodynamics and respiratory. This cardioprotective effect was associated with alleviation of apoptosis and oxidative stress. Delivery of H2S to the myocardium by ultrasound targeted hs-MB destruction attenuates myocardial ischemia-reperfusion injury and may avoid unwanted side effects. PMID:27469291

Novel 3-D laparoscopic magnetic ultrasound image guidance for lesion targeting

PubMed Central

Sindram, David; McKillop, Iain H; Martinie, John B; Iannitti, David A

2010-01-01

Objectives: Accurate laparoscopic liver lesion targeting for biopsy or ablation depends on the ability to merge laparoscopic and ultrasound images with proprioceptive instrument positioning, a skill that can be acquired only through extensive experience. The aim of this study was to determine whether using magnetic positional tracking to provide three-dimensional, real-time guidance improves accuracy during laparoscopic needle placement. Methods: Magnetic sensors were embedded into a needle and laparoscopic ultrasound transducer. These sensors interrupted the magnetic fields produced by an electromagnetic field generator, allowing for real-time, 3-D guidance on a stereoscopic monitor. Targets measuring 5 mm were embedded 3–5 cm deep in agar and placed inside a laparoscopic trainer box. Two novices (a college student and an intern) and two experts (hepatopancreatobiliary surgeons) targeted the lesions out of the ultrasound plane using either traditional or 3-D guidance. Results: Each subject targeted 22 lesions, 11 with traditional and 11 with the novel guidance (n = 88). Hit rates of 32% (14/44) and 100% (44/44) were observed with the traditional approach and the 3-D magnetic guidance approach, respectively. The novices were essentially unable to hit the targets using the traditional approach, but did not miss using the novel system. The hit rate of experts improved from 59% (13/22) to 100% (22/22) (P < 0.0001). Conclusions: The novel magnetic 3-D laparoscopic ultrasound guidance results in perfect targeting of 5-mm lesions, even by surgical novices. PMID:21083797

Value of contrast-enhanced ultrasound in the differential diagnosis of gallbladder lesion

PubMed Central

Zhang, Hui-Ping; Bai, Min; Gu, Ji-Ying; He, Ying-Qian; Qiao, Xiao-Hui; Du, Lian-Fang

2018-01-01

AIM To describe contrast-enhanced ultrasound (CEUS) features and evaluate differential diagnosis value of CEUS and conventional ultrasound for patients with benign and malignant gallbladder lesions. METHODS This study included 105 gallbladder lesions. Before surgical resection and pathological examination, conventional ultrasound and CEUS were performed to examine for lesions. Then, all the lesions were diagnosed as (1) benign, (2) probably benign, (3) probably malignant or (4) malignant using both conventional ultrasound and CEUS. The CEUS features of these gallbladder lesions were analyzed and diagnostic efficiency between conventional ultrasound and CEUS was compared. RESULTS There were total 17 cases of gallbladder cancer and 88 cases of benign lesion. Some gallbladder lesions had typical characteristics on CEUS (e.g., gallbladder adenomyomatosis had typical characteristics of small nonenhanced areas on CEUS). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CEUS were 94.1%, 95.5%, 80.0%, 98.8% and 95.2%, respectively. These were significantly higher than conventional ultrasound (82.4%, 89.8%, 60.9%, 96.3% and 88.6%, respectively). CEUS had an accuracy of 100% for gallbladder sludge and CEUS helped in differential diagnosis among gallbladder polyps, gallbladder adenoma and gallbladder cancer. CONCLUSION CEUS may provide more useful information and improve the diagnosis efficiency for the diagnosis of gallbladder lesions than conventional ultrasound. PMID:29456413

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

PubMed

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

2011-01-01

To compare morphological, power Doppler, and contrast-enhanced ultrasound (CEUS) features of the Achilles tendon between asymptomatic athletes and athletes who had undergone surgical repair of a previous rupture. Twenty-four athletes were divided in two groups (A and B). Group A included 14 patients with a median age of 32 years (range 27 to 47 years) who had undergone surgical repair for unilateral Achilles tendon rupture. Group B (control group) included 10 subjects with a median age of 34 years (range 27 to 40 years) with no previous or present history of tendinopathy. All patients were evaluated with ultrasound, power Doppler, and CEUS with second-generation contrast agent. We studied the uninjured Achilles tendon in athletes of group A and either the left or the right Achilles tendon of the athletes in group B. CEUS showed a significantly greater ability to detect a greater number of vascular spots within the uninjured tendon of group A compared to group B (<0.05). In athletes who had suffered a tear of an Achilles tendon, CEUS detected small vessels that were not identified by power Doppler ultrasound in the uninjured contralateral Achilles tendon. CEUS is useful to evaluate vascularity not detected by other imaging techniques. Vascularity in the uninjured tendon seems to be increased in patients who had a previous rupture. Copyright © 2011 Wiley Periodicals, Inc.

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

PubMed

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

2018-07-01

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

Usefulness of automatic measurement of contrast flow intensity: an innovative tool in contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization. A pilot study.

PubMed

Lisowska, A; Knapp, M; Tycinska, A; Sawicki, R; Kralisz, P; Lisowski, P; Sobkowicz, B; Musial, W I

2014-02-01

Contrast-enhanced ultrasound imaging of the carotid arteries (CECU) permits direct, real-time visualization of neovascularization in atherosclerotic plaques and is a confirmed predictor of unstable atheromatous lesions. The aim of the study was the assessment of a new, automatically measured index of intensity in quantitative estimation of the contrast flow through the carotid plaque (till now assessed only visually). Forty-four patients (mean age 70.4±11.4) with ultrasound diagnosed significant stenosis of internal carotid artery (ICA), after cerebrovascular or cardiovascular events, qualified for carotid artery stenting (CAS) were examined. The carotid ultrasound examinations with contrast agent Sonovue were performed. Visually in 22 patients (50%) contrast flow through the atherosclerotic plaques was found. In 17 patients (38.6%) massive, calcified atherosclerotic plaques were present. Patients with preserved contrast flow through the plaque more frequently had a history of cerebral stroke (P=0.04). Massive calcifications of atherosclerotic plaques correlated with a previous MI (P=0.03) and the degree of advancement of coronary artery disease (P=0.04), but not with a previous cerebral stroke. Contrast flow through the atherosclerotic plaque positively correlated with values of the index of intensity (r=0.69, P<0.00001). In patients with preserved contrast flow the mean value of the index of intensity was 22.24±3.55 dB as compared with 12.37±7.67 dB - a value present in patients without preserved contrast flow. No significant relation for the degree of calcifications and the value of the index of intensity was found. The assessment of the index of intensity is a novel, simple and automatic method to estimate the degree of contrast flow through the carotid plaque. The values of the index of intensity correlate with the contrast flow through the atherosclerotic plaque, but not with its calcification.

Long residence time of ultrasound microbubbles targeted to integrin in murine tumor model.

PubMed

Jun, Hong Young; Park, Seong Hoon; Kim, Hun Soo; Yoon, Kwon-Ha

2010-01-01

The aim of this study was to evaluate the intratumoral residence time of microbubbles (MBs) targeted to alpha(v)beta(3) integrin expressed in the endothelial cells of mice during the process of tumor angiogenesis. For the preparation of MBs, decafluorobutane gas was sonically dispersed in phosphate buffer saline containing L-A-phosphatidylcholine-distearoyl, polyethylene glycol 40 stearate, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[biotinyl(polyethylene glycol)2000] in a 77:15:8 molar ratio. Avidin-fluorescein isothiocyanate and biotin-cyclic arginine-glycine-aspartate-D-tyrosine-lysine (cRGD) or biotin-alanine-glycine-aspartate (AGD) conjugates were added to the reaction mixture. Adhesion testing of the targeting MBs was performed for the MS-1 cell line expressing alpha(v)beta(3) integrin in vitro. The in vivo acoustic properties of the MBs were assessed by clinical ultrasound on the HT1080 fibrosarcoma model (n = 8) for 1 hour. Cryosections were stained with hematoxylin and eosin and by immunohistochemical staining to identify expression of alpha(v)beta(3) integrin in the HT1080 tumor. The adherence of the MBs conjugated to cRGD was significantly greater than the adherence of the MBs conjugated to biotin-AGD (P < .01) for the MS-1 endothelial cell line. The acoustic enhancement on ultrasound was observed as a stable imaging window until 1 hour after injection of the MB conjugates in the mice. The MBs targeted via cRGD preferentially adhered to the vascular endothelium of the HT-1080 tumors. The findings of ultrasound imaging were correlated with immunohistochemical findings for the expression of alpha(v)beta(3) integrin on the vascular endothelium of the tumors. The prepared MBs conjugated with cRGD demonstrated a sufficient residence time to attach to the target integrin of tumor tissues. This finding suggests that the MBs are a potential molecular contrast agent that enables characterization of tumor angiogenesis and the monitoring of antitumor and

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

PubMed

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

2016-08-01

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

Extravasation Risk Using Ultrasound Guided Peripheral Intravenous Catheters for Computed Tomography Contrast Administration

PubMed Central

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

2016-01-01

Objective Ultrasound guided intravenous catheter (USGIV) insertion is increasingly being used for administration of intravenous contrast for computed tomography (CT) scans. The goal of this investigation was to evaluate the risk of contrast extravasation among patients receiving contrast through USGIV catheters. Methods A retrospective observational study of adult patients who underwent a contrast-enhanced CT scan at a tertiary-care emergency department during a recent 64-month period was conducted. The unadjusted prevalence of contrast extravasation was compared between patients with an USGIV and those with a standard peripheral IV inserted without ultrasound. Then, a two-stage sampling design was used to select a subset of the population for a multivariable logistic regression model evaluating USGIVs as a risk factor for extravasation while adjusting for potential confounders. Results In total, 40,143 patients underwent a contrasted CT scan, including 364 (0.9%) who had contrast administered through an USGIV. Unadjusted prevalence of extravasation was 3.6% for contrast administration through USGIVs and 0.3% for standard IVs (relative risk: 13.9, 95% CI: 7.7 to 24.6). After adjustment for potential confounders, CT contrast administered through USGIVs was associated with extravasation (adjusted odds ratio: 8.6; 95% CI: 4.6, 16.2). No patients required surgical management for contrast extravasation; one patient in the standard IV group was admitted for observation due to extravasation. Conclusions Patients who received contrast for a CT scan through an USGIV had a higher risk of extravasation than those who received contrast through a standard peripheral IV. Clinicians should consider this extravasation risk when weighing the risks and benefits of a contrast-enhanced CT scan in a patient with USGIV vascular access. PMID:27151898

Influence of ultrasound induced cavitation on magnetic resonance imaging contrast in the rat liver in the presence of macromolecular contrast agent.

PubMed

Frulio, Nora; Trillaud, Hervé; Deckers, Roel; Lepreux, Sébastien; Moonen, Chrit; Quesson, Bruno

2010-05-01

Local drug delivery by ultrasound (US)-induced cavitation is a promising strategy for increasing the drug concentration at the target location and for decreasing the systemic toxicity effects. The presence of microbubbles during sonication at the targeted location improves the likelihood for cavitation that can be exploited to increase the capillary permeability. The objective of this work was to evaluate the magnetic resonance imaging (MRI) contrast changes in hepatic tissue in vivo, induced by US-triggered cavitation and destruction of microbubbles (Sonovue), in the presence of a coinjected blood pool MRI contrast agent (Vistarem) used as a reporter macromolecule. The potential tissue damage induced by microbubbles destruction was also evaluated by histology. The change in the hepatic distribution of the macromolecular MRI contrast agent associated with cavitation was monitored at 1.5 T with a look-locker fast inversion recovery sequence to map the longitudinal relaxation rates, before and during 1 hour after intravenous administration of Vistarem and Sonovue. In 1 group of rats (n = 5), these microbubbles were immediately destroyed with a clinical echograph, using a high mechanical index (MI = 1.5) at low frequency (2 MHz). The control group (n = 7) received identical injections without application of US. The parametric relaxation rate images were computed, and the changes in time were analyzed to account for the potential effect of microbubble destruction by US on the permeability of the hepatic vessels. The animals were killed 1 day after the experiment for routine histology of the liver. For both groups of animals, after an initial increase, a transient decay of the longitudinal relaxation rate was observed, followed by a constant plateau after 20 minutes. The analysis of the mean relaxation rates in the liver showed significant (P < 0.01) higher values for the group with destruction of microbubbles as compared with the control group. The US

Characterization of Contrast Agent Microbubbles for Ultrasound Imaging and Therapy Research.

PubMed

Mulvana, Helen; Browning, Richard J; Luan, Ying; de Jong, Nico; Tang, Meng-Xing; Eckersley, Robert J; Stride, Eleanor

2017-01-01

The high efficiency with which gas microbubbles can scatter ultrasound compared with the surrounding blood pool or tissues has led to their widespread employment as contrast agents in ultrasound imaging. In recent years, their applications have been extended to include super-resolution imaging and the stimulation of localized bio-effects for therapy. The growing exploitation of contrast agents in ultrasound and in particular these recent developments have amplified the need to characterize and fully understand microbubble behavior. The aim in doing so is to more fully exploit their utility for both diagnostic imaging and potential future therapeutic applications. This paper presents the key characteristics of microbubbles that determine their efficacy in diagnostic and therapeutic applications and the corresponding techniques for their measurement. In each case, we have presented information regarding the methods available and their respective strengths and limitations, with the aim of presenting information relevant to the selection of appropriate characterization methods. First, we examine methods for determining the physical properties of microbubble suspensions and then techniques for acoustic characterization of both suspensions and single microbubbles. The next section covers characterization of microbubbles as therapeutic agents, including as drug carriers for which detailed understanding of their surface characteristics and drug loading capacity is required. Finally, we discuss the attempts that have been made to allow comparison across the methods employed by various groups to characterize and describe their microbubble suspensions and promote wider discussion and comparison of microbubble behavior.

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

PubMed

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

2017-12-01

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

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

PubMed

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

2018-06-01

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

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. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Relapses in three patients with Takayasu arteritis under tocilizumab treatment detected by contrast enhanced ultrasound.

PubMed

Czihal, Michael; Lottspeich, Christian; Schröttle, Angelika; Treitl, Karla Maria; Treitl, Marcus; Leipe, Jan; Schulze-Koops, Hendrik; Hoffmann, Ulrich; Dechant, Claudia

2018-02-01

Takayasu arteritis (TA) is a rare large vessel vasculitis, affecting the aorta and its major branches, typically in young women. In this case report, we present three cases of young women of Caucasian descent who experienced relapses while under treatment with the monoclonal humanized antibody to the interleukin 6 receptor, tocilizumab. Active vasculitic lesions of the supraaortic (common carotid and axillary) arteries were detected and characterized via high resolution contrast enhanced ultrasound. Based on these cases, we discuss the potential role of contrast enhanced ultrasound in the diagnosis and follow-up of TA as well as the current data on the efficacy of tocilizumab in the treatment of TA.

An experimental model to investigate the targeting accuracy of MR-guided focused ultrasound ablation in liver.

PubMed

Petrusca, Lorena; Viallon, Magalie; Breguet, Romain; Terraz, Sylvain; Manasseh, Gibran; Auboiroux, Vincent; Goget, Thomas; Baboi, Loredana; Gross, Patrick; Sekins, K Michael; Becker, Christoph D; Salomir, Rares

2014-01-16

Magnetic Resonance-guided High Intensity Focused Ultrasound (MRgHIFU) is a hybrid technology that aims to offer non-invasive thermal ablation of targeted tumors or other pathological tissues. Acoustic aberrations and non-linear wave propagating effects may shift the focal point significantly away from the prescribed (or, theoretical) position. It is therefore mandatory to evaluate the spatial accuracy of ablation for a given HIFU protocol and/or device. We describe here a method for producing a user-defined ballistic target as an absolute reference marker for MRgHIFU ablations. The investigated method is based on trapping a mixture of MR contrast agent and histology stain using radiofrequency (RF) ablation causing cell death and coagulation. A dedicated RF-electrode was used for the marker fixation as follows: a RF coagulation (4 W, 15 seconds) and injection of the mixture followed by a second RF coagulation. As a result, the contrast agent/stain is encapsulated in the intercellular space. Ultrasonography imaging was performed during the procedure, while high resolution T1w 3D VIBE MR acquisition was used right after to identify the position of the ballistic marker and hence the target tissue. For some cases, after the marker fixation procedure, HIFU volumetric ablations were produced by a phased-array HIFU platform. First ex vivo experiments were followed by in vivo investigation on four rabbits in thigh muscle and six pigs in liver, with follow-up at Day 7. At the end of the procedure, no ultrasound indication of the marker's presence could be observed, while it was clearly visible under MR and could be conveniently used to prescribe the HIFU ablation, centered on the so-created target. The marker was identified at Day 7 after treatment, immediately after animal sacrifice, after 3 weeks of post-mortem formalin fixation and during histology analysis. Its size ranged between 2.5 and 4 mm. Experimental validation of this new ballistic marker method was performed for

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

Nanobubble ultrasound contrast agents for enhanced delivery of thermal sensitizer to tumors undergoing radiofrequency ablation.

PubMed

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

2014-06-01

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. 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. 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 ºC) 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). Lipid and Pluronic-shelled, echogenic nanobubbles combined with ultrasound modulation can serve as an effective theranostic method for sensitization of tumors to RF ablation.

In Vivo Targeted, Responsive, and Synergistic Cancer Nanotheranostics by Magnetic Resonance Imaging-Guided Synergistic High-Intensity Focused Ultrasound Ablation and Chemotherapy.

PubMed

Tang, Hailin; Guo, Yuan; Peng, Li; Fang, Hui; Wang, Zhigang; Zheng, Yuanyi; Ran, Haitao; Chen, Yu

2018-05-09

As one of the most representative noninvasive therapeutic modalities, high-intensity focused ultrasound (HIFU) has shown great promise for cancer therapy, but its low therapeutic efficacy and biosafety significantly hinder further extensive clinical translation and application. In this work, we report on the construction of a multifunctional theranostic nanoplatform to synergistically enhance the HIFU-therapeutic efficacy based on nanomedicine. A targeted and temperature-responsive theranostic nanoplatform (PFH/DOX@PLGA/Fe 3 O 4 -FA) has been designed and fabricated for efficient ultrasound/magnetic resonance dual-modality imaging-guided HIFU/chemo synergistic therapy. Especially, the folate was conjugated onto the surface of the nanoplatform for achieving active targeting to hepatoma cells by receptor-ligand interaction, which facilitates accumulation of the nanoplatforms into the tumor site. The integrated superparamagnetic iron oxide nanoparticles could generate the contrast enhancement in T 2 -weighted magnetic resonance imaging. By virtue of the thermal effect as generated by HIFU, liquid-gas phase transition of perfluorohexane (PFH) in nanocomposites was induced to generate PFH microbubbles, which achieved the contrast-enhanced ultrasound imaging and significantly improved the HIFU ablation efficacy. The loaded anticancer drugs could be released from the nanocomposites in a controllable manner (both pH and HIFU responsiveness). These multifunctional nanocomposites have been demonstrated to efficiently suppress the tumor growth based on the enhanced and synergistic chemotherapy and HIFU ablation, providing an efficient theranostic nanoplatform for cancer treatment.

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

NASA Astrophysics Data System (ADS)

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

2006-08-01

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

Adaptive windowing in contrast-enhanced intravascular ultrasound imaging

PubMed Central

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

2016-01-01

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 200 µm. 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 4.2 dB, while combined MV and PCF processing improved spatial resolution by 41.7%. Improvements of 2.2 dB 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

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. Copyright © 2016 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2011-04-01

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

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

PubMed

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

2013-01-01

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

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

PubMed

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

2016-09-01

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

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

PubMed

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

2011-01-01

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

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

PubMed Central

Zhou, Jian-hua; Shan, Hong-bo; Ou, Wei; Mo, Yun-xian; Xiang, Jin; Wang, Yu; Wang, Si-yu

2018-01-01

Based on the option that ultrasound-guided core needle biopsy (US-CNB) of the enhanced portion of anterior mediastinal masses (AMMs) identified by contrast-enhanced ultrasound (CEUS) would harvest viable tissue and benefit the histological diagnoses, a retrospective study was performed to elucidate the correlation between the prebiopsy CEUS and diagnostic yield of AMMs and found that CEUS potentially improved the diagnostic yield of AMMs compared with conventional US with a significant increase in the cellularity of samples. Furthermore, the marginal blood flow signals and absence of necrosis can predict the diagnostic yield of AMM. It was concluded that US-CNB of the viable part of AMMs, as verified by CEUS, was able to harvest sufficient tissue with more cellularity that could be used for ancillary studies and improve the diagnostic yield. And CEUS was recommended to those patients with AMMs undergoing repeated US-CNB, with the absence of marginal blood signals or presence of necrosis. PMID:29581992

Contrast-enhanced ultrasound in portal venous system aneurysms: a multi-center study.

PubMed

Tana, Claudio; Dietrich, Christoph F; Badea, Radu; Chiorean, Liliana; Carrieri, Vincenzo; Schiavone, Cosima

2014-12-28

To investigate contrast-enhanced ultrasound (CEUS) findings in portal venous system aneurysms (PVSAs). In this multi-center, retrospective, case series study, we evaluated CEUS features of seven cases of PVSAs that were found incidentally on conventional ultrasound in the period 2007-2013. Three Ultrasound Centers were involved (Chieti, Italy, Bad Mergentheim, Germany, and Cluj-Napoca, Romania). All patients underwent CEUS with Sonovue(®) (Bracco, Milan, Italy) at a standard dose of 2.4 mL, followed by 10 mL of 0.9% saline solution. The examinations were performed using multifrequency transducers and low mechanical index. We considered aneurysmal a focal dilatation of the portal venous system with a size that was significantly greater than the remaining segments of the same vein, and that was equal or larger than 21 mm for the extrahepatic segments of portal venous system, main portal vein and bifurcation, and 9 mm for the intrahepatic branches. After contrast agent injection, all PVSAs were not enhanced in the arterial phase (starting 8-22 s). All PVSAs were then rapidly enhanced in the early portal venous phase (starting three to five seconds after the arterial phase, 11-30 s), with persistence and slow washout of the contrast agent in the late phase (starting 120 s). In all patients, CEUS confirmed the presence of a "to-and-fro" flow by showing a swirling pattern within the dilatation in the early portal venous phase. CEUS also improved the delineation of the lumen, and was reliable in showing its patency degree and integrity of walls. In one patient, CEUS showed a partial enhancement of the lumen with a uniformly nonenhancing area in the portal venous and late phases, suggesting thrombosis. In our case series, we found that CEUS could be useful in the assessment and follow-up of a PVSA. Further studies are needed to validate its diagnostic accuracy.

Contrast enhanced ultrasound of renal masses. A reappraisal of EFSUMB recommendations and possible emerging applications.

PubMed

Sparchez, Zeno; Radu, Pompilia; Sparchez, Mihaela; Crisan, Nicolae; Kacso, Gabriel; Petrut, Bogdan

2015-06-01

The main imagistic method for characterization of renal lesions is contrast enhanced computed tomography (CECT). Disadvantages of CECT are a contrast-induced nephropathy in patients with renal impairment, allergic reactions and high costs. Contrast-enhanced ultrasound (CEUS) evaluation of hepatic and non-hepatic lesions is a relatively new, but increasingly utilised, diagnostic method. In 2011 the European Federation of Societies of Ultrasound in Medicine and Biology (EFSUMB) updated the Guidelines and Recommendations on the Clinical Practice of CEUS and included in the recommendation the renal pathology. However, there are several possible new indications that have not been discussed (pyelocaliceal masses and renal vein thrombosis) and several issues that remain controversial such as the differentiation of benign and malignant tumours or the differentiation of lymphoma and metastasis. This study aims to review literature data, as well as reveal the latest findings in the field of renal CEUS.

HIFU Hemostasis of Liver Injuries Enhanced by Ultrasound Contrast Agents

NASA Astrophysics Data System (ADS)

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

2005-03-01

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

Cyanine 5.5 Conjugated Nanobubbles as a Tumor Selective Contrast Agent for Dual Ultrasound-Fluorescence Imaging in a Mouse Model

PubMed Central

Li, Jing; Wei, Qiong; Yuchi, Ming; He, Xiaoling; Ding, Mingyue; Zhou, Qibing

2013-01-01

Nanobubbles and microbubbles are non-invasive ultrasound imaging contrast agents that may potentially enhance diagnosis of tumors. However, to date, both nanobubbles and microbubbles display poor in vivo tumor-selectivity over non-targeted organs such as liver. We report here cyanine 5.5 conjugated nanobubbles (cy5.5-nanobubbles) of a biocompatible chitosan–vitamin C lipid system as a dual ultrasound-fluorescence contrast agent that achieved tumor-selective imaging in a mouse tumor model. Cy5.5-nanobubble suspension contained single bubble spheres and clusters of bubble spheres with the size ranging between 400–800 nm. In the in vivo mouse study, enhancement of ultrasound signals at tumor site was found to persist over 2 h while tumor-selective fluorescence emission was persistently observed over 24 h with intravenous injection of cy5.5-nanobubbles. In vitro cell study indicated that cy5.5-flurescence dye was able to accumulate in cancer cells due to the unique conjugated nanobubble structure. Further in vivo fluorescence study suggested that cy5.5-nanobubbles were mainly located at tumor site and in the bladder of mice. Subsequent analysis confirmed that accumulation of high fluorescence was present at the intact subcutaneous tumor site and in isolated tumor tissue but not in liver tissue post intravenous injection of cy5.5-nanobubbles. All these results led to the conclusion that cy5.5-nanobubbles with unique crosslinked chitosan–vitamin C lipid system have achieved tumor-selective imaging in vivo. PMID:23637799

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

PubMed

Mai, Liyi; Yao, Anna; Li, Jing; Wei, Qiong; Yuchi, Ming; He, Xiaoling; Ding, Mingyue; Zhou, Qibing

2013-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2018-03-01

Phase-change ultrasound contrast agent (PCCA), or nanodroplet, shows promise as an alternative to the conventional microbubble agent over a wide range of diagnostic applications. Meanwhile, high-frame-rate (HFR) ultrasound imaging with microbubbles enables unprecedented temporal resolution compared to traditional contrast-enhanced ultrasound imaging. The combination of HFR ultrasound imaging and PCCAs can offer the opportunity to observe and better understand PCCA behaviour after vaporisation captures the fast phenomenon at a high temporal resolution. In this study, we utilised HFR ultrasound at frame rates in the kilohertz range (5-20 kHz) to image native and size-selected PCCA populations immediately after vaporisation in vitro within clinical acoustic parameters. The size-selected PCCAs through filtration are shown to preserve a sub-micron-sized (mean diameter  <  200 nm) population without micron-sized outliers (>1 µm) that originate from native PCCA emulsion. The results demonstrate imaging signals with different amplitudes and temporal features compared to that of microbubbles. Compared with the microbubbles, both the B-mode and pulse-inversion (PI) signals from the vaporised PCCA populations were reduced significantly in the first tens of milliseconds, while only the B-mode signals from the PCCAs were recovered during the next 400 ms, suggesting significant changes to the size distribution of the PCCAs after vaporisation. It is also shown that such recovery in signal over time is not evident when using size-selective PCCAs. Furthermore, it was found that signals from the vaporised PCCA populations are affected by the amplitude and frame rate of the HFR ultrasound imaging. Using high-speed optical camera observation (30 kHz), we observed a change in particle size in the vaporised PCCA populations exposed to the HFR ultrasound imaging pulses. These findings can further the understanding of PCCA behaviour under HFR ultrasound imaging.

Research on respiratory motion correction method based on liver contrast-enhanced ultrasound images of single mode

NASA Astrophysics Data System (ADS)

Zhang, Ji; Li, Tao; Zheng, Shiqiang; Li, Yiyong

2015-03-01

To reduce the effects of respiratory motion in the quantitative analysis based on liver contrast-enhanced ultrasound (CEUS) image sequencesof single mode. The image gating method and the iterative registration method using model image were adopted to register liver contrast-enhanced ultrasound image sequences of single mode. The feasibility of the proposed respiratory motion correction method was explored preliminarily using 10 hepatocellular carcinomas CEUS cases. The positions of the lesions in the time series of 2D ultrasound images after correction were visually evaluated. Before and after correction, the quality of the weighted sum of transit time (WSTT) parametric images were also compared, in terms of the accuracy and spatial resolution. For the corrected and uncorrected sequences, their mean deviation values (mDVs) of time-intensity curve (TIC) fitting derived from CEUS sequences were measured. After the correction, the positions of the lesions in the time series of 2D ultrasound images were almost invariant. In contrast, the lesions in the uncorrected images all shifted noticeably. The quality of the WSTT parametric maps derived from liver CEUS image sequences were improved more greatly. Moreover, the mDVs of TIC fitting derived from CEUS sequences after the correction decreased by an average of 48.48+/-42.15. The proposed correction method could improve the accuracy of quantitative analysis based on liver CEUS image sequences of single mode, which would help in enhancing the differential diagnosis efficiency of liver tumors.

The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Short Version).

PubMed

Sidhu, Paul S; Cantisani, Vito; Dietrich, Christoph F; Gilja, Odd Helge; Saftoiu, Adrian; Bartels, Eva; Bertolotto, Michele; Calliada, Fabrizio; Clevert, Dirk-André; Cosgrove, David; Deganello, Annamaria; D'Onofrio, Mirko; Drudi, Francesco Maria; Freeman, Simon; Harvey, Christopher; Jenssen, Christian; Jung, Ernst-Michael; Klauser, Andrea Sabine; Lassau, Nathalie; Meloni, Maria Franca; Leen, Edward; Nicolau, Carlos; Nolsoe, Christian; Piscaglia, Fabio; Prada, Francesco; Prosch, Helmut; Radzina, Maija; Savelli, Luca; Weskott, Hans-Peter; Wijkstra, Hessel

2018-04-01

The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many established and emerging applications. © Georg Thieme Verlag KG Stuttgart · New York.

Contrast-Enhanced Ultrasound Angiogenesis Imaging by Mutual Information Analysis for Prostate Cancer Localization.

PubMed

Schalk, Stefan G; Demi, Libertario; Bouhouch, Nabil; Kuenen, Maarten P J; Postema, Arnoud W; de la Rosette, Jean J M C H; Wijkstra, Hessel; Tjalkens, Tjalling J; Mischi, Massimo

2017-03-01

The role of angiogenesis in cancer growth has stimulated research aimed at noninvasive cancer detection by blood perfusion imaging. Recently, contrast ultrasound dispersion imaging was proposed as an alternative method for angiogenesis imaging. After the intravenous injection of an ultrasound-contrast-agent bolus, dispersion can be indirectly estimated from the local similarity between neighboring time-intensity curves (TICs) measured by ultrasound imaging. Up until now, only linear similarity measures have been investigated. Motivated by the promising results of this approach in prostate cancer (PCa), we developed a novel dispersion estimation method based on mutual information, thus including nonlinear similarity, to further improve its ability to localize PCa. First, a simulation study was performed to establish the theoretical link between dispersion and mutual information. Next, the method's ability to localize PCa was validated in vivo in 23 patients (58 datasets) referred for radical prostatectomy by comparison with histology. A monotonic relationship between dispersion and mutual information was demonstrated. The in vivo study resulted in a receiver operating characteristic (ROC) curve area equal to 0.77, which was superior (p = 0.21-0.24) to that obtained by linear similarity measures (0.74-0.75) and (p <; 0.05) to that by conventional perfusion parameters (≤0.70). Mutual information between neighboring time-intensity curves can be used to indirectly estimate contrast dispersion and can lead to more accurate PCa localization. An improved PCa localization method can possibly lead to better grading and staging of tumors, and support focal-treatment guidance. Moreover, future employment of the method in other types of angiogenic cancer can be considered.

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

PubMed

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

2017-05-01

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

An experimental model to investigate the targeting accuracy of MR-guided focused ultrasound ablation in liver

PubMed Central

2014-01-01

Background Magnetic Resonance-guided High Intensity Focused Ultrasound (MRgHIFU) is a hybrid technology that aims to offer non-invasive thermal ablation of targeted tumors or other pathological tissues. Acoustic aberrations and non-linear wave propagating effects may shift the focal point significantly away from the prescribed (or, theoretical) position. It is therefore mandatory to evaluate the spatial accuracy of ablation for a given HIFU protocol and/or device. We describe here a method for producing a user-defined ballistic target as an absolute reference marker for MRgHIFU ablations. Methods The investigated method is based on trapping a mixture of MR contrast agent and histology stain using radiofrequency (RF) ablation causing cell death and coagulation. A dedicated RF-electrode was used for the marker fixation as follows: a RF coagulation (4 W, 15 seconds) and injection of the mixture followed by a second RF coagulation. As a result, the contrast agent/stain is encapsulated in the intercellular space. Ultrasonography imaging was performed during the procedure, while high resolution T1w 3D VIBE MR acquisition was used right after to identify the position of the ballistic marker and hence the target tissue. For some cases, after the marker fixation procedure, HIFU volumetric ablations were produced by a phased-array HIFU platform. First ex vivo experiments were followed by in vivo investigation on four rabbits in thigh muscle and six pigs in liver, with follow-up at Day 7. Results At the end of the procedure, no ultrasound indication of the marker’s presence could be observed, while it was clearly visible under MR and could be conveniently used to prescribe the HIFU ablation, centered on the so-created target. The marker was identified at Day 7 after treatment, immediately after animal sacrifice, after 3 weeks of post-mortem formalin fixation and during histology analysis. Its size ranged between 2.5 and 4 mm. Conclusions Experimental validation of this

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

PubMed

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

2012-06-01

To investigate the diagnostic accuracy, through quantitative analysis, of contrast-enhanced ultrasound (CEUS), using a microbubble contrast agent, in the differentiation of thyroid nodules. This prospective study enrolled 46 patients with solitary, scintigraphically non-functional thyroid nodules. These patients were scheduled for surgery and underwent preoperative CEUS with pulse-inversion harmonic imaging after intravenous microbubble contrast medium administration. Using histology as a standard of reference, time-intensity curves of benign and malignant nodules were compared by means of peak enhancement and wash-out enhancement relative to the baseline intensity using a mixed model ANOVA. ROC analysis was performed to assess the diagnostic accuracy in the differentiation of benign and malignant nodules on CEUS. The complete CEUS data of 42 patients (31/42 [73.8%] benign and 11/42 [26.2%] malignant nodules) revealed a significant difference (P < 0.001) in enhancement between benign and malignant nodules. Furthermore, based on ROC analysis, CEUS demonstrated sensitivity of 76.9%, specificity of 84.8% and accuracy of 82.6%. Quantitative analysis of CEUS using a microbubble contrast agent allows the differentiation of benign and malignant thyroid nodules and may potentially serve, in addition to grey-scale and Doppler ultrasound, as an adjunctive tool in the assessment of patients with thyroid nodules. • Contrast-enhanced ultrasound (CEUS) helps differentiate between benign and malignant thyroid nodules. • Quantitative CEUS analysis yields sensitivity of 76.9% and specificity of 84.8%. • CEUS may be a potentially useful adjunct in assessing thyroid nodules.

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

PubMed

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

2012-11-27

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

A Tissue-Mimicking Ultrasound Test Object Using Droplet Vaporization to Create Point Targets

PubMed Central

Carneal, Catherine M.; Kripfgans, Oliver D.; Krücker, Jochen; Carson, Paul L.; Fowlkes, J. Brian

2012-01-01

Ultrasound test objects containing reference point targets could be useful for evaluating ultrasound systems and phase aberration correction methods. Polyacrylamide gels containing albumin-stabilized droplets (3.6 µm mean diameter) of dodecafluoropentane (DDFP) are being developed for this purpose. Perturbation by ultrasound causes spontaneous vaporization of the superheated droplets to form gas bubbles, a process termed acoustic droplet vaporization (ADV). The resulting bubbles (20 to 160 µm diameter) are small compared with acoustic wavelengths in diagnostic ultrasound and are theoretically suitable for use as point targets (phase errors <20° for typical f-numbers). Bubbles distributed throughout the material are convenient for determining the point spread function in an imaging plane or volume. Cooling the gel causes condensation of the DDFP droplets, which may be useful for storage. Studying ADV in such viscoelastic media could provide insight into potential bioeffects from rapid bubble formation. PMID:21937339

Improving performance of nanoscale ultrasound contrast agents using N,N-diethylacrylamide stabilization.

PubMed

Perera, Reshani H; Wu, Hanping; Peiris, Pubudu; Hernandez, Christopher; Burke, Alan; Zhang, Helen; Exner, Agata A

2017-01-01

The design of nanoscale yet highly echogenic agents for imaging outside of the vasculature and for ultrasound-mediated drug delivery remains a formidable challenge. We have previously reported on formulation of echogenic perfluoropropane gas nanobubbles stabilized by a lipid-pluronic surfactant shell. In the current work we describe the development of a new generation of these nanoparticles which consist of perfluoropropane gas stabilized by a surfactant and lipid membrane and a crosslinked network of N,N-diethylacrylamide. The resulting crosslinked nanobubbles (CL-PEG-NB) were 95.2±25.2nm in diameter and showed significant improvement in stability and retention of echogenic signal over 24h. In vivo analysis via ultrasound and fluorescence mediated tomography showed greater tumor extravasation and accumulation with CL-PEG-NB compared to microbubbles. Together these results demonstrate the capabilities and advantages of a new, more stable, nanometer-scale ultrasound contrast agent that can be utilized in future work for diagnostic scans and molecular imaging. Copyright © 2016 Elsevier Inc. All rights reserved.

Nonspherical dynamics and shape mode stability of ultrasound contrast agent microbubbles

NASA Astrophysics Data System (ADS)

Calvisi, Michael

2016-11-01

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

Modeling the effects of contrast enhancement on target acquisition performance

NASA Astrophysics Data System (ADS)

Du Bosq, Todd W.; Fanning, Jonathan D.

2008-04-01

Contrast enhancement and dynamic range compression are currently being used to improve the performance of infrared imagers by increasing the contrast between the target and the scene content, by better utilizing the available gray levels either globally or locally. This paper assesses the range-performance effects of various contrast enhancement algorithms for target identification with well contrasted vehicles. Human perception experiments were performed to determine field performance using contrast enhancement on the U.S. Army RDECOM CERDEC NVESD standard military eight target set using an un-cooled LWIR camera. The experiments compare the identification performance of observers viewing linearly scaled images and various contrast enhancement processed images. Contrast enhancement is modeled in the US Army thermal target acquisition model (NVThermIP) by changing the scene contrast temperature. The model predicts improved performance based on any improved target contrast, regardless of feature saturation or enhancement. To account for the equivalent blur associated with each contrast enhancement algorithm, an additional effective MTF was calculated and added to the model. The measured results are compared with the predicted performance based on the target task difficulty metric used in NVThermIP.

Feasibility of Retrograde Ureteral Contrast Injection to Guide Ultrasonographic Percutaneous Renal Access in the Nondilated Collecting System.

PubMed

Usawachintachit, Manint; Tzou, David T; Mongan, John; Taguchi, Kazumi; Weinstein, Stefanie; Chi, Thomas

2017-02-01

Ultrasound-guided percutaneous nephrolithotomy (PCNL) has become increasingly utilized. Patients with nondilated collecting systems represent a challenge: the target calix is often difficult to visualize. Here we report pilot study results for retrograde ultrasound contrast injection to aid in percutaneous renal access during ultrasound-guided PCNL. From April to July 2016, consecutive patients over the age of 18 years with nondilated collecting systems on preoperative imaging who presented for PCNL were enrolled. B-mode ultrasound imaging was compared with contrast-enhanced mode with simultaneous retrograde injection of Optison™ via an ipsilateral ureteral catheter. Five patients (four males and one female) with renal stones underwent PCNL with retrograde ultrasound contrast injection during the study period. Mean body mass index was 28.3 ± 5.6 kg/m 2 and mean stone size was 24.5 ± 12.0 mm. Under B-mode ultrasound, all patients demonstrated nondilated renal collecting systems that appeared as hyperechoic areas, where it was difficult to identify a target calix for puncture. Retrograde contrast injection facilitated delineation of all renal calices initially difficult to visualize under B-mode ultrasound. Renal puncture was then performed effectively in all cases with a mean puncture time of 55.4 ± 44.8 seconds. All PCNL procedures were completed without intraoperative complications and no adverse events related to ultrasound contrast injection occurred. Retrograde ultrasound contrast injection as an aide for renal puncture during PCNL is a feasible technique. By improving visualization of the collecting system, it facilitates needle placement in challenging patients without hydronephrosis. Future larger scale studies comparing its use to standard ultrasound-guided technique will be required to validate this concept.

High-contrast fast Fourier transform acousto-optical tomography of phantom tissues with a frequency-chirp modulation of the ultrasound.

PubMed

Forget, Benoît-Claude; Ramaz, François; Atlan, Michaël; Selb, Juliette; Boccara, Albert-Claude

2003-03-01

We report new results on acousto-optical tomography in phantom tissues using a frequency chirp modulation and a CCD camera. This technique allows quick recording of three-dimensional images of the optical contrast with a two-dimensional scan of the ultrasound source in a plane perpendicular to the ultrasonic path. The entire optical contrast along the ultrasonic path is concurrently obtained from the capture of a film sequence at a rate of 200 Hz. This technique reduces the acquisition time, and it enhances the axial resolution and thus the contrast, which are usually poor owing to the large volume of interaction of the ultrasound perturbation.

CT and Ultrasound Guided Stereotactic High Intensity Focused Ultrasound (HIFU)

NASA Astrophysics Data System (ADS)

Wood, Bradford J.; Yanof, J.; Frenkel, V.; Viswanathan, A.; Dromi, S.; Oh, K.; Kruecker, J.; Bauer, C.; Seip, R.; Kam, A.; Li, K. C. P.

2006-05-01

To demonstrate the feasibility of CT and B-mode Ultrasound (US) targeted HIFU, a prototype coaxial focused ultrasound transducer was registered and integrated to a CT scanner. CT and diagnostic ultrasound were used for HIFU targeting and monitoring, with the goals of both thermal ablation and non-thermal enhanced drug delivery. A 1 megahertz coaxial ultrasound transducer was custom fabricated and attached to a passive position-sensing arm and an active six degree-of-freedom robotic arm via a CT stereotactic frame. The outer therapeutic transducer with a 10 cm fixed focal zone was coaxially mounted to an inner diagnostic US transducer (2-4 megahertz, Philips Medical Systems). This coaxial US transducer was connected to a modified commercial focused ultrasound generator (Focus Surgery, Indianapolis, IN) with a maximum total acoustic power of 100 watts. This pre-clinical paradigm was tested for ability to heat tissue in phantoms with monitoring and navigation from CT and live US. The feasibility of navigation via image fusion of CT with other modalities such as PET and MRI was demonstrated. Heated water phantoms were tested for correlation between CT numbers and temperature (for ablation monitoring). The prototype transducer and integrated CT/US imaging system enabled simultaneous multimodality imaging and therapy. Pre-clinical phantom models validated the treatment paradigm and demonstrated integrated multimodality guidance and treatment monitoring. Temperature changes during phantom cooling corresponded to CT number changes. Contrast enhanced or non-enhanced CT numbers may potentially be used to monitor thermal ablation with HIFU. Integrated CT, diagnostic US, and therapeutic focused ultrasound bridges a gap between diagnosis and therapy. Preliminary results show that the multimodality system may represent a relatively inexpensive, accessible, and simple method of both targeting and monitoring HIFU effects. Small animal pre-clinical models may be translated to large

Nonlinear ultrasound imaging of nanoscale acoustic biomolecules

NASA Astrophysics Data System (ADS)

Maresca, David; Lakshmanan, Anupama; Lee-Gosselin, Audrey; Melis, Johan M.; Ni, Yu-Li; Bourdeau, Raymond W.; Kochmann, Dennis M.; Shapiro, Mikhail G.

2017-02-01

Ultrasound imaging is widely used to probe the mechanical structure of tissues and visualize blood flow. However, the ability of ultrasound to observe specific molecular and cellular signals is limited. Recently, a unique class of gas-filled protein nanostructures called gas vesicles (GVs) was introduced as nanoscale (˜250 nm) contrast agents for ultrasound, accompanied by the possibilities of genetic engineering, imaging of targets outside the vasculature and monitoring of cellular signals such as gene expression. These possibilities would be aided by methods to discriminate GV-generated ultrasound signals from anatomical background. Here, we show that the nonlinear response of engineered GVs to acoustic pressure enables selective imaging of these nanostructures using a tailored amplitude modulation strategy. Finite element modeling predicted a strongly nonlinear mechanical deformation and acoustic response to ultrasound in engineered GVs. This response was confirmed with ultrasound measurements in the range of 10 to 25 MHz. An amplitude modulation pulse sequence based on this nonlinear response allows engineered GVs to be distinguished from linear scatterers and other GV types with a contrast ratio greater than 11.5 dB. We demonstrate the effectiveness of this nonlinear imaging strategy in vitro, in cellulo, and in vivo.

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

Discrimination between neoplastic and non-neoplastic lesions in cirrhotic liver using contrast-enhanced ultrasound

PubMed Central

Xu, H-X; Lu, M-D; Liu, L-N; Zhang, Y-F; Guo, L-H; Xu, J-M; Liu, C

2012-01-01

Objectives To assess the value of contrast-enhanced ultrasound (CEUS) in differentiating hepatocellular carcinoma (HCC) from non-neoplastic lesion in cirrhotic liver in comparison with baseline ultrasound. Methods A total of 147 nodules (diameter ≤5.0 cm) in 133 cirrhotic patients (mean age±standard deviation: 52±13 years, range 20–82 years; gender: 111 males and 22 females) were examined with CEUS. There were 116 HCCs, 26 macroregenerative nodules and 5 high-grade dysplastic nodules. CEUS was performed with a real-time contrast-specific mode and a sulphur hexafluoride-filled microbubble contrast agent. Results Hypervascularity was observed in 94.8% (110/116) HCCs, 3.8% (1/26) macroregenerative nodules and 60.0% (3/5) high-grade dysplastic nodules during arterial phase on CEUS. Detection rates of typical vascular pattern (i.e. hypervascularity during arterial phase and subsequent washout) in HCCs with a diameter of ≤2.0 cm, 2.1–3.0 cm and 3.1–5.0 cm were 69.2% (27/39), 97.1% (33/34) and 100.0% (43/43), respectively. CEUS significantly improved the sensitivity [88.8% (103/116) vs 37.1% (43/116), p<0.001], negative predictive value [70.5% (31/44) vs 31.5% (29/92), p<0.001], and accuracy [91.2% (134/147) vs 49.0% (72/147), p<0.001] in differentiating HCCs from non-neoplastic lesions when compared with baseline ultrasound. However, the sensitivity and accuracy of CEUS for HCCs ≤2.0 cm in diameter were significantly lower than those for HCCs of 2.1–3.0 cm and 3.1–5.0 cm in diameter. Conclusions CEUS improves diagnostic performance in differentiating HCCs from non-neoplastic nodules in cirrhotic patients compared with baseline ultrasound. Diagnosis of HCCs ≤2.0 cm diameter by CEUS is still a clinical concern, and thus needs further investigation. PMID:22553290

In Vivo Demonstration of Cancer Molecular Imaging with Ultrasound Radiation Force and Buried-Ligand Microbubbles

PubMed Central

Borden, Mark A.; Streeter, Jason E.; Sirsi, Shashank R.; Dayton, Paul A.

2015-01-01

In designing targeted contrast agent materials for imaging, the need to present a targeting ligand for recognition and binding by the target is counterbalanced by the need to minimize interactions with plasma components and to avoid recognition by the immune system. We have previously reported on a microbubble imaging probe for ultrasound molecular imaging that uses a buried-ligand surface architecture to minimize unwanted interactions and immunogenicity. Here we examine for the first time the utility of this approach for in vivo molecular imaging. In accordance with previous results, we showed a threefold increase in circulation persistence through the tumor of a fibrosarcoma model in comparison with controls. The buried-ligand microbubbles were then activated for targeted adhesion through the application of noninvasive ultrasound radiation forces applied specifically to the tumor region. Using a clinical ultrasound scanner, microbubbles were activated, imaged, and silenced. The results showed visually conspicuous images of tumor neovasculature and a twofold increase in ultrasound radiation force enhancement of acoustic contrast intensity for buried-ligand microbubbles, whereas no such increase was found for exposed-ligand microbubbles. We therefore conclude that the use of acoustically active buried-ligand microbubbles for ultrasound molecular imaging bridges the demand for low immunogenicity with the necessity of maintaining targeting efficacy and imaging conspicuity in vivo. PMID:23981781

Non-Invasive Targeted Peripheral Nerve Ablation Using 3D MR Neurography and MRI-Guided High-Intensity Focused Ultrasound (MR-HIFU): Pilot Study in a Swine Model.

PubMed

Huisman, Merel; Staruch, Robert M; Ladouceur-Wodzak, Michelle; van den Bosch, Maurice A; Burns, Dennis K; Chhabra, Avneesh; Chopra, Rajiv

2015-01-01

Ultrasound (US)-guided high intensity focused ultrasound (HIFU) has been proposed for noninvasive treatment of neuropathic pain and has been investigated in in-vivo studies. However, ultrasound has important limitations regarding treatment guidance and temperature monitoring. Magnetic resonance (MR)-imaging guidance may overcome these limitations and MR-guided HIFU (MR-HIFU) has been used successfully for other clinical indications. The primary purpose of this study was to evaluate the feasibility of utilizing 3D MR neurography to identify and guide ablation of peripheral nerves using a clinical MR-HIFU system. Volumetric MR-HIFU was used to induce lesions in the peripheral nerves of the lower limbs in three pigs. Diffusion-prep MR neurography and T1-weighted images were utilized to identify the target, plan treatment and immediate post-treatment evaluation. For each treatment, one 8 or 12 mm diameter treatment cell was used (sonication duration 20 s and 36 s, power 160-300 W). Peripheral nerves were extracted < 3 hours after treatment. Ablation dimensions were calculated from thermal maps, post-contrast MRI and macroscopy. Histological analysis included standard H&E staining, Masson's trichrome and toluidine blue staining. All targeted peripheral nerves were identifiable on MR neurography and T1-weighted images and could be accurately ablated with a single exposure of focused ultrasound, with peak temperatures of 60.3 to 85.7°C. The lesion dimensions as measured on MR neurography were similar to the lesion dimensions as measured on CE-T1, thermal dose maps, and macroscopy. Histology indicated major hyperacute peripheral nerve damage, mostly confined to the location targeted for ablation. Our preliminary results indicate that targeted peripheral nerve ablation is feasible with MR-HIFU. Diffusion-prep 3D MR neurography has potential for guiding therapy procedures where either nerve targeting or avoidance is desired, and may also have potential for post

Non-Invasive Targeted Peripheral Nerve Ablation Using 3D MR Neurography and MRI-Guided High-Intensity Focused Ultrasound (MR-HIFU): Pilot Study in a Swine Model

PubMed Central

Huisman, Merel; Staruch, Robert M.; Ladouceur-Wodzak, Michelle; van den Bosch, Maurice A.; Burns, Dennis K.; Chhabra, Avneesh; Chopra, Rajiv

2015-01-01

Purpose Ultrasound (US)-guided high intensity focused ultrasound (HIFU) has been proposed for noninvasive treatment of neuropathic pain and has been investigated in in-vivo studies. However, ultrasound has important limitations regarding treatment guidance and temperature monitoring. Magnetic resonance (MR)-imaging guidance may overcome these limitations and MR-guided HIFU (MR-HIFU) has been used successfully for other clinical indications. The primary purpose of this study was to evaluate the feasibility of utilizing 3D MR neurography to identify and guide ablation of peripheral nerves using a clinical MR-HIFU system. Methods Volumetric MR-HIFU was used to induce lesions in the peripheral nerves of the lower limbs in three pigs. Diffusion-prep MR neurography and T1-weighted images were utilized to identify the target, plan treatment and immediate post-treatment evaluation. For each treatment, one 8 or 12 mm diameter treatment cell was used (sonication duration 20 s and 36 s, power 160–300 W). Peripheral nerves were extracted < 3 hours after treatment. Ablation dimensions were calculated from thermal maps, post-contrast MRI and macroscopy. Histological analysis included standard H&E staining, Masson’s trichrome and toluidine blue staining. Results All targeted peripheral nerves were identifiable on MR neurography and T1-weighted images and could be accurately ablated with a single exposure of focused ultrasound, with peak temperatures of 60.3 to 85.7°C. The lesion dimensions as measured on MR neurography were similar to the lesion dimensions as measured on CE-T1, thermal dose maps, and macroscopy. Histology indicated major hyperacute peripheral nerve damage, mostly confined to the location targeted for ablation. Conclusion Our preliminary results indicate that targeted peripheral nerve ablation is feasible with MR-HIFU. Diffusion-prep 3D MR neurography has potential for guiding therapy procedures where either nerve targeting or avoidance is desired, and may

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).

Construction of ultrasonic nanobubbles carrying CAIX polypeptides to target carcinoma cells derived from various organs.

PubMed

Zhu, Lianhua; Guo, Yanli; Wang, Luofu; Fan, Xiaozhou; Xiong, Xingyu; Fang, Kejing; Xu, Dan

2017-09-29

Ultrasound molecular imaging is a novel diagnostic approach for tumors, whose key link is the construction of targeted ultrasound contrast agents. However, available targeted ultrasound contrast agents for molecular imaging of tumors are only achieving imaging in blood pool or one type tumor. No targeted ultrasound contrast agents have realized targeted ultrasound molecular imaging of tumor parenchymal cells in a variety of solid tumors so far. Carbonic anhydrase IX (CAIX) is highly expressed on cell membranes of various malignant solid tumors, so it's a good target for ultrasound molecular imaging. Here, targeted nanobubbles carrying CAIX polypeptides for targeted binding to a variety of malignant tumors were constructed, and targeted binding ability and ultrasound imaging effect in different types of tumors were evaluated. The mean diameter of lipid targeted nanobubbles was (503.7 ± 78.47) nm, and the polypeptides evenly distributed on the surfaces of targeted nanobubbles, which possessed the advantages of homogenous particle size, high stability, and good safety. Targeted nanobubbles could gather around CAIX-positive cells (786-O and Hela cells), while they cannot gather around CAIX-negative cells (BxPC-3 cells) in vitro, and the affinity of targeted nanobubbles to CAIX-positive cells were significantly higher than that to CAIX-negative cells (P < 0.05). Peak intensity and duration time of targeted nanobubbles and blank nanobubbles were different in CAIX-positive transplanted tumor tissues in vivo (P < 0.05). Moreover, targeted nanobubbles in CAIX-positive transplanted tumor tissues produced higher peak intensity and longer duration time than those in CAIX-negative transplanted tumor tissues (P < 0.05). Finally, immunofluorescence not only confirmed targeted nanobubbles could pass through blood vessels to enter in tumor tissue spaces, but also clarified imaging differences of targeted nanobubbles in different types of transplanted tumor tissues

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

NASA Astrophysics Data System (ADS)

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

2016-12-01

Modelling and biomedical applications of ultrasound contrast agent (UCA) microbubbles have attracted a great deal of attention. In this review, we summarize a series of researches done in our group, including (i) the development of an all-in-one solution of characterizing coated bubble parameters based on the light scattering technique and flow cytometry; (ii) a novel bubble dynamic model that takes into consideration both nonlinear shell elasticity and viscosity to eliminate the dependences of bubble shell parameters on bubble size; (iii) the evaluation of UCA inertial cavitation threshold and its relationship with shell parameters; and (iv) the investigations of transfection efficiency and the reduction of cytotoxicity in gene delivery facilitated by UCAs excited by ultrasound exposures. Projects supported by the National Natural Science Foundation of China (Grant Nos. 81127901, 81227004, 11374155, 11274170, 11274176, 11474001, 11474161, 11474166, and 11674173), the National High-Technology Research and Development Program, China (Grant No. 2012AA022702), and Qing Lan Project of Jiangsu Province, China.

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

PubMed

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

2017-08-01

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

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

PubMed

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

2016-02-10

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

Contrast enhanced ultrasound (CEUS) with MRI image fusion for monitoring focal therapy of prostate cancer with high intensity focused ultrasound (HIFU)1.

PubMed

Apfelbeck, M; Clevert, D-A; Ricke, J; Stief, C; Schlenker, B

2018-01-01

Reduced acceptance of radical prostatectomy in patients with low risk or intermediate risk prostate cancer has significantly changed treatment strategies in prostate cancer (PCa) during the last years. Focal therapy of the prostate with high intensity focused ultrasound (HIFU) is an organ-preserving treatment for prostate cancer with less impairment of health-related quality of life. Follow-up after HIFU therapy by imaging modalities remains a major problem as eg. MRI performs poorly. Contrast enhanced ultrasound (CEUS) allows to monitor the vascular architecture of organs non-invasively. However, only limited data are available using CEUS to define successful and complete HIFU treatment of the prostate. In this study, we aimed to evaluate short-term image findings using CEUS and image fusion before and after HIFU treatment. Prospective single arm study in patients with uni- or bilateral, low or intermediate risk prostate cancer or recurrent cancer after radiotherapy treated with HIFU at our institution between October 2016 and November 2017. HIFU hemiablation or whole gland treatment was performed using the Focal One® device. PCa was diagnosed either by multiparametric magnetic resonance imaging (mpMRI) followed by MRI fusion based targeted biopsy combined with 12 core transrectal ultrasound (TRUS) guided biopsy or 12 core random biopsy only. Monitoring of the target region before, immediately and 24 hours after the ablation was done by CEUS in combination with image fusion using an axial T2-weighted MRI sequence. 6 consecutive patients with Gleason score (GS) 6, 5 patients with GS 7a prostate cancer and one patient with biochemical recurrence after radiotherapy were included in the study. Three patients underwent whole gland treatment due to histological proven bilateral PCa or recurrent PCa after radiotherapy. Hemiablation was performed in 9 patients with unilateral tumor and no PIRADS 4 or 5 lesion in the contralateral lobe. Median patient age was 69.8 years

Gd(III)-DOTA-modified sonosensitive liposomes for ultrasound-triggered release and MR imaging

NASA Astrophysics Data System (ADS)

Jung, Suk Hyun; Na, Kyunga; Lee, Seul A.; Cho, Sun Hang; Seong, Hasoo; Shin, Byung Cheol

2012-08-01

Ultrasound-sensitive (sonosensitive) liposomes for tumor targeting have been studied in order to increase the antitumor efficacy of drugs and decrease the associated severe side effects. Liposomal contrast agents having Gd(III) are known as a nano-contrast agent system for the efficient and selective delivery of contrast agents into pathological sites. The objective of this study was to prepare Gd(III)-DOTA-modified sonosensitive liposomes (GdSL), which could deliver a model drug, doxorubicin (DOX), to a specific site and, at the same time, be capable of magnetic resonance (MR) imaging. The GdSL was prepared using synthesized Gd(III)-DOTA-1,2-distearoyl- sn-glycero-3-phosphoethanolamine lipid. Sonosensitivity of GdSL to 20-kHz ultrasound induced 33% to 40% of DOX release. The relaxivities ( r 1) of GdSL were 6.6 to 7.8 mM-1 s-1, which were higher than that of MR-bester®. Intracellular uptake properties of GdSL were evaluated according to the intensity of ultrasound. Intracellular uptake of DOX for ultrasound-triggered GdSL was higher than that for non-ultrasound-triggered GdSL. The results of our study suggest that the paramagnetic and sonosensitive liposomes, GdSL, may provide a versatile platform for molecular imaging and targeted drug delivery.

Partial segmental thrombosis of the corpus cavernosum (PSTCC) diagnosed by contrast-enhanced ultrasound: a case report.

PubMed

Sauer, Stephanie; Goltz, Jan P; Gassenmaier, Tobias; Kunz, Andreas S; Bley, Thorsten A; Klein, Detlef; Petritsch, Bernhard

2014-12-17

Partial segmental thrombosis of the corpus cavernosum (PSTCC) is a rare disease predominantly occurring in young men. Cardinal symptoms are pain and perineal swelling. Although several risk factors are described in the literature, the exact etiology of penile thrombosis remains unclear in most cases. MRI or ultrasound (US) is usually used for diagnosing this condition. We report a case of penile thrombosis after left-sided varicocele ligature in a young patient. The diagnosis was established using contrast-enhanced ultrasound (CEUS) and was confirmed by contrast-enhanced magnetic resonance imaging (ceMRI). Successful conservative treatment consisted of systemic anticoagulation using low molecular weight heparin and acetylsalicylic acid. PSTCC is a rare condition in young men and appears with massive pain and perineal swelling. In case of suspected PSTCC utilization of CEUS may be of diagnostic benefit.

Effect of Anesthesia Carrier Gas on In-Vivo Circulation Times of Ultrasound Microbubble Contrast Agents in Rats

PubMed Central

Mullin, Lee; Gessner, Ryan; Kwan, James; Kaya, Mehmet; Borden, Mark A.; Dayton, Paul A.

2012-01-01

Purpose Microbubble contrast agents are currently implemented in a variety of both clinical and preclinical ultrasound imaging studies. The therapeutic and diagnostic capabilities of these contrast agents are limited by their short in-vivo lifetimes, and research to lengthen their circulation times is ongoing. In this manuscript, observations are presented from a controlled experiment performed to evaluate differences in circulation times for lipid shelled perfluorocarbon-filled contrast agents circulating within rodents as a function of inhaled anesthesia carrier gas. Methods The effects of two common anesthesia carrier gas selections - pure oxygen and medical air – were observed within five rats. Contrast agent persistence within the kidney was measured and compared for oxygen and air anesthesia carrier gas for six bolus contrast injections in each animal. Simulations were performed to examine microbubble behavior with changes in external environment gases. Results A statistically significant extension of contrast circulation time was observed for animals breathing medical air compared to breathing pure oxygen. Simulations support experimental observations and indicate that enhanced contrast persistence may be explained by reduced ventilation/perfusion mismatch and classical diffusion, in which nitrogen plays a key role by contributing to the volume and diluting other gas species in the microbubble gas core. Conclusion: Using medical air in place of oxygen as the carrier gas for isoflurane anesthesia can increase the circulation lifetime of ultrasound microbubble contrast agents. PMID:21246710

Annexin V conjugated nanobubbles: A novel ultrasound contrast agent for in vivo assessment of the apoptotic response in cancer therapy.

PubMed

Zhou, Tian; Cai, Wenbin; Yang, Hengli; Zhang, Huizhong; Hao, Minghua; Yuan, Lijun; Liu, Jie; Zhang, Li; Yang, Yilin; Liu, Xi; Deng, Jianling; Zhao, Ping; Yang, Guodong; Duan, Yunyou

2018-04-28

In vivo assessment of apoptotic response to cancer therapy is believed to be very important for optimizing management of treatment. However, few noninvasive strategies are currently available to monitor the therapeutic response in vivo. Ultrasonography has been used to detect apoptotic cell death in vivo, but a high-frequency transducer is needed. Fortunately, the capability of ultrasound contrast agents (UCAs) to exit the leaky vasculature of tumors enables ultrasound-targeted imaging of molecular events in response to cancer therapy. In this study, we prepared a novel nano-sized UCA, namely, Annexin V-conjugated nanobubbles (AV-NBs, 635.5 ± 25.4 nm). In vitro studies revealed that AV-NBs were relatively stable and highly echogenic. Moreover, these AV-NBs could easily extravasate into the tumor vasculature and recognize the apoptotic cells with high specificity and affinity in tumors sensitive to chemotherapy. Ultrasound imaging results demonstrated that AV-NBs had higher echogenicity and significantly greater enhancement compared with the untargeted control NBs (P < 0.01) inside the tumors after chemotherapy. Taken together, this study provides a promising method to accurately evaluate therapeutic effects at the molecular level to support cancer management. Copyright © 2018 Elsevier B.V. All rights reserved.

[Contrast-enhanced ultrasound for the characterization of incidental liver lesions - an economical evaluation in comparison with multi-phase computed tomography].

PubMed

Giesel, F L; Delorme, S; Sibbel, R; Kauczor, H-U; Krix, M

2009-06-01

The aim of the study was to conduct a cost-minimization analysis of contrast-enhanced ultrasound (CEUS) compared to multi-phase computed tomography (M-CT) as the diagnostic standard for diagnosing incidental liver lesions. Different scenarios of a cost-covering realization of CEUS in the ambulant sector in the general health insurance system of Germany were compared to the current cost situation. The absolute savings potential was estimated using different approaches for the calculation of the incidence of liver lesions which require further characterization. CEUS was the more cost-effective method in all scenarios in which CEUS examinations where performed at specialized centers (122.18-186.53 euro) compared to M-CT (223.19 euro). With about 40 000 relevant liver lesions per year, systematic implementation of CEUS would result in a cost savings of 4 m euro per year. However, the scenario of a cost-covering CEUS examination for all physicians who perform liver ultrasound would be the most cost-intensive approach (e. g., 407.87 euro at an average utilization of the ultrasound machine of 25 %, and a CEUS ratio of 5 %). A cost-covering realization of the CEUS method can result in cost savings in the German healthcare system. A centralized approach as proposed by the DEGUM should be targeted.

Feasibility of Using Volumetric Contrast-Enhanced Ultrasound with a 3-D Transducer to Evaluate Therapeutic Response after Targeted Therapy in Rabbit Hepatic VX2 Carcinoma.

PubMed

Kim, Jeehyun; Kim, Jung Hoon; Yoon, Soon Ho; Choi, Won Seok; Kim, Young Jae; Han, Joon Koo; Choi, Byung-Ihn

2015-12-01

The aim of this study was to assess the feasibility of using dynamic contrast-enhanced ultrasound (DCE-US) with a 3-D transducer to evaluate therapeutic responses to targeted therapy. Rabbits with hepatic VX2 carcinomas, divided into a treatment group (n = 22, 30 mg/kg/d sorafenib) and a control group (n = 13), were evaluated with DCE-US using 2-D and 3-D transducers and computed tomography (CT) perfusion imaging at baseline and 1 d after the first treatment. Perfusion parameters were collected, and correlations between parameters were analyzed. In the treatment group, both volumetric and 2-D DCE-US perfusion parameters, including peak intensity (33.2 ± 19.9 vs. 16.6 ± 10.7, 63.7 ± 20.0 vs. 30.1 ± 19.8), slope (15.3 ± 12.4 vs. 5.7 ± 4.5, 37.3 ± 20.4 vs. 15.7 ± 13.0) and area under the curve (AUC; 1004.1 ± 560.3 vs. 611.4 ± 421.1, 1332.2 ± 708.3 vs. 670.4 ± 388.3), had significantly decreased 1 d after the first treatment (p = 0.00). In the control group, 2-D DCE-US revealed that peak intensity, time to peak and slope had significantly changed (p < 0.05); however, volumetric DCE-US revealed that peak intensity, time-intensity AUC, AUC during wash-in and AUC during wash-out had significantly changed (p = 0.00). CT perfusion imaging parameters, including blood flow, blood volume and permeability of the capillary vessel surface, had significantly decreased in the treatment group (p = 0.00); however, in the control group, peak intensity and blood volume had significantly increased (p = 0.00). It is feasible to use DCE-US with a 3-D transducer to predict early therapeutic response after targeted therapy because perfusion parameters, including peak intensity, slope and AUC, significantly decreased, which is similar to the trend observed for 2-D DCE-US and CT perfusion imaging parameters. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Cumulative phase delay between second harmonic and fundamental components--a marker for ultrasound contrast agents.

PubMed

Demi, Libertario; Wijkstra, Hessel; Mischi, Massimo

2014-12-01

Several imaging techniques aimed at detecting ultrasound contrast agents (UCAs) echo signals, while suppressing signals coming from the surrounding tissue, have been developed. These techniques are especially relevant for blood flow, perfusion, or contrast dispersion quantification. However, despite several approaches being presented, improving the understanding of the ultrasound/UCAs interaction may support further development of imaging techniques. In this paper, the physical phenomena behind the formation of harmonic components in tissue and UCAs, respectively, are addressed as a possible way to recognize the origin of the echo signals. Simulations based on a modified Rayleigh, Plesset, Noltingk, Neppiras, and Poritsky equation and transmission and backscattering measurements of ultrasound propagating through UCAs performed with a single element transducer and a submergible hydrophone, are presented. Both numerical and in vitro results show the occurrence of a cumulative time delay between the second harmonic and fundamental component which increases with UCA concentration and propagation path length through UCAs, and that was clearly observable at frequencies ( f0 = 2.5 MHz) and pressure regimes (mechanical index = 0.1) of interest for imaging. Most importantly, this delay is not observed in the absence of UCAs. In conclusion, the reported phenomenon represents a marker for UCAs with potential application for imaging.

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

PubMed

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

2012-07-01

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

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

DTIC Science & Technology

2009-03-01

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

Role of Contrast-enhanced Ultrasound in the Evaluation of Inflammatory Arthritis

PubMed Central

Zhao, Chen-Yang; Jiang, Yu-Xin; Li, Jian-Chu; Xu, Zhong-Hui; Zhang, Qing; Su, Na; Yang, Meng

2017-01-01

Objective: Contrast-enhanced ultrasound (CEUS) is a well-established imaging modality which has been put into clinical use in recent years with the development of second-generation contrast agent and imaging devices, and its applications in the assessment of inflammatory arthritis, such as rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, have provoked abundant discussion and researches among radiologists and rheumatologists. To summarize the achievements of clinical studies on CEUS in the application of arthritis, and to keep up with the latest progresses of the imaging technique, we reviewed the literature in recent years, hoping to establish the role of CEUS in joint diseases. Data Sources: PubMed and EMBASE. Study Selection: We searched the database with the conditions “contrast-enhanced ultrasound AND arthritis” with the time limitation of recent 10 years. Clinical studies applying CEUS in inflammatory arthritis and review articles about development of CEUS in joint diseases in English were selected. Results: As it is proved by most studies in recent years, by delineating microvasculature within the inflamed joints, CEUS can indicate early arthritis with high sensitivity and specificity. Moreover, the imaging of CEUS has been proved to be consistent with histopathological changes of inflammatory arthritis. Quantitative analysis of CEUS permits further evaluation of disease activity. CEUS also plays a significant role in the therapeutic monitoring of the disease, which has been backed up by a number of studies. Conclusions: CEUS may be a new choice for the rheumatologists to evaluate inflammatory arthritis, because of its low price, ability to provide dynamic pictures, and high sensitivity to angiogenesis. It can also be applied in disease classification and therapeutic monitoring. More studies about CEUS need to be done to set up the diagnostic standards. PMID:28685724

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

PubMed

Huang, Cuiyuan; Zhang, Hong; Bai, Ruidan

2017-07-01

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

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

PubMed

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

2013-08-01

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

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

PubMed Central

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

2011-01-01

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

Multiparametric dynamic contrast-enhanced ultrasound imaging of prostate cancer.

PubMed

Wildeboer, Rogier R; Postema, Arnoud W; Demi, Libertario; Kuenen, Maarten P J; Wijkstra, Hessel; Mischi, Massimo

2017-08-01

The aim of this study is to improve the accuracy of dynamic contrast-enhanced ultrasound (DCE-US) for prostate cancer (PCa) localization by means of a multiparametric approach. Thirteen different parameters related to either perfusion or dispersion were extracted pixel-by-pixel from 45 DCE-US recordings in 19 patients referred for radical prostatectomy. Multiparametric maps were retrospectively produced using a Gaussian mixture model algorithm. These were subsequently evaluated on their pixel-wise performance in classifying 43 benign and 42 malignant histopathologically confirmed regions of interest, using a prostate-based leave-one-out procedure. The combination of the spatiotemporal correlation (r), mean transit time (μ), curve skewness (κ), and peak time (PT) yielded an accuracy of 81% ± 11%, which was higher than the best performing single parameters: r (73%), μ (72%), and wash-in time (72%). The negative predictive value increased to 83% ± 16% from 70%, 69% and 67%, respectively. Pixel inclusion based on the confidence level boosted these measures to 90% with half of the pixels excluded, but without disregarding any prostate or region. Our results suggest multiparametric DCE-US analysis might be a useful diagnostic tool for PCa, possibly supporting future targeting of biopsies or therapy. Application in other types of cancer can also be foreseen. • DCE-US can be used to extract both perfusion and dispersion-related parameters. • Multiparametric DCE-US performs better in detecting PCa than single-parametric DCE-US. • Multiparametric DCE-US might become a useful tool for PCa localization.

Ultrasound Biomicroscopy in Small Animal Research: Applications in Molecular and Preclinical Imaging

PubMed Central

Greco, A.; Mancini, M.; Gargiulo, S.; Gramanzini, M.; Claudio, P. P.; Brunetti, A.; Salvatore, M.

2012-01-01

Ultrasound biomicroscopy (UBM) is a noninvasive multimodality technique that allows high-resolution imaging in mice. It is affordable, widely available, and portable. When it is coupled to Doppler ultrasound with color and power Doppler, it can be used to quantify blood flow and to image microcirculation as well as the response of tumor blood supply to cancer therapy. Target contrast ultrasound combines ultrasound with novel molecular targeted contrast agent to assess biological processes at molecular level. UBM is useful to investigate the growth and differentiation of tumors as well as to detect early molecular expression of cancer-related biomarkers in vivo and to monitor the effects of cancer therapies. It can be also used to visualize the embryological development of mice in uterus or to examine their cardiovascular development. The availability of real-time imaging of mice anatomy allows performing aspiration procedures under ultrasound guidance as well as the microinjection of cells, viruses, or other agents into precise locations. This paper will describe some basic principles of high-resolution imaging equipment, and the most important applications in molecular and preclinical imaging in small animal research. PMID:22163379

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

PubMed

Zidan, Ahmed S; Aldawsari, Hibah

2015-01-01

Delivering drugs to intracerebral regions can be accomplished by improving the capacity of transport through blood-brain barrier. Using sertraline as model drug for brain targeting, the current study aimed at modifying its liposomal vesicles with mannopyranoside. Box-Behnken design was employed to statistically optimize the ultrasound parameters, namely ultrasound amplitude, time, and temperature, for maximum mannosylation capacity, sertraline entrapment, and surface charge while minimizing vesicular size. Moreover, in vitro blood-brain barrier transport model was established to assess the transendothelial capacity of the optimized mannosylated vesicles. Results showed a dependence of vesicular size, mannosylation capacity, and sertraline entrapment on cavitation and bubble implosion events that were related to ultrasound power amplitude, temperature. However, short ultrasound duration was required to achieve >90% mannosylation with nanosized vesicles (<200 nm) of narrow size distribution. Optimized ultrasound parameters of 65°C, 27%, and 59 seconds for ultrasound temperature, amplitude, and time were elucidated to produce 81.1%, 46.6 nm, and 77.6% sertraline entrapment, vesicular size, and mannosylation capacity, respectively. Moreover, the transendothelial ability was significantly increased by 2.5-fold by mannosylation through binding with glucose transporters. Hence, mannosylated liposomes processed by ultrasound could be a promising approach for manufacturing and scale-up of brain-targeting liposomes.

Ultrasound-responsive nanobubbles contained with peptide-camptothecin conjugates for targeted drug delivery.

PubMed

Xie, Xiangyang; Lin, Wen; Liu, Hui; Deng, Jianping; Chen, Ying; Liu, Hong; Fu, Xudong; Yang, Yang

2016-10-01

To improve the targeting delivery efficiency of anticancer drug to tumor sites, a new strategy combining cell-permeable peptide (CPP) and ultrasound was reported in this article. In this study, we devised and tested a strategy for functional payload delivery to cells by loading CPP-camptothecin conjugate (CPP-CPT) into nanobubble (CPP-CPT NB). Here, CPP existing in the conjugation form of CPP and CPT was hidden in nanobubble to cloak the penetration activity of CPP. Meanwhile, local tumor ultrasound was utilized to achieve specific targeting of CPP-CPT to the tumor cells. The mean particle size of the prepared CPP-CPT NB was ∼200 nm, and the drug entrapment efficiency was >80%. Stimulated by ultrasound, over 90% of the entrapped CPP-CPTs would release from the nanobubbles. Subsequent research demonstrated that the CPP-CPT NB showed effective cellular uptake and significant cytotoxic activity in HeLa cells in vitro. Additionally, after systemic administration in mice, CPP-CPT NB with ultrasound showed a higher tumor inhibition effect in nude mice xenografted HeLa cells tumors and excellent body safety when compared with normal CPT injection group. In conclusion, the carrier constructed in this study would be a safe and efficiently drug delivery system for specific cancer treatment.

[Ultrasonography of the prostate gland : From B‑image through multiparametric ultrasound to targeted biopsy].

PubMed

Steinkohl, F; Luger, A; Bektic, J; Aigner, F

2017-08-01

Prostate cancer is the most frequent cancer in men. The diagnosis is normally achieved by a systematic prostate biopsy; however, this is a randomized approach by which a substantial number of significant carcinomas go undetected. For this reason, in recent years imaging techniques have been continuously developed, which enable visualization and therefore targeted biopsies. The use of systematic biopsies is a standard procedure for the detection of prostate cancer. The quality of biopsies can be increased if the prostate is examined for the presence of suspected cancerous alterations during the biopsy. This can be carried out using multiparametric transrectral ultrasound. Multiparametric ultrasound within the framework of a targeted biopsy increases the detection rate of significant prostate carcinomas with a simultaneous decrease in detection of insignificant carcinomas; however, the diagnostic reliability and the evidence level of multiparametric transrectal ultrasound are not yet sufficiently high to be able to replace a systematic biopsy. In the hands of a well-trained examiner multiparametric transrectal ultrasound represents a good method for detection of prostate carcinomas. With the progression in technical developments of ultrasound technology, the detection rate will presumably be further increased.

Microbubbles in Ultrasound-Triggered Drug and Gene Delivery

PubMed Central

Hernot, Sophie; Klibanov, Alexander L.

2008-01-01

Ultrasound contrast agents, in the form of gas-filled microbubbles, are becoming popular in perfusion monitoring; they are employed as molecular imaging agents. Microbubbles are manufactured from biocompatible materials, they can be injected intravenously, and some are approved for clinical use. Microbubbles can be destroyed by ultrasound irradiation. This destruction phenomenon can be applied to targeted drug delivery and enhancement of drug action. The ultrasonic field can be focused at the target tissues and organs; thus, selectivity of the treatment can be improved, reducing undesirable side effects. Microbubbles enhance ultrasound energy deposition in the tissues and serve as cavitation nuclei, increasing intracellular drug delivery. DNA delivery and successful tissue transfection is observed in the areas of the body where ultrasound is applied after intravascular administration of microbubbles and plasmid DNA. Accelerated blood clot dissolution in the areas of insonation by cooperative action of thrombolytic agents and microbubbles is demonstrated in several clinical trials. PMID:18486268

Broadband attenuation measurements of phospholipid-shelled ultrasound contrast agents.

PubMed

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

2014-02-01

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. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Phospholipid Capped Mesoporous Nanoparticles for Targeted High Intensity Focused Ultrasound Ablation.

PubMed

Yildirim, Adem; Chattaraj, Rajarshi; Blum, Nicholas T; Shi, Dennis; Kumar, Kaushlendra; Goodwin, Andrew P

2017-09-01

The mechanical effects of cavitation can be effective for therapy but difficult to control, thus potentially leading to off-target side effects in patients. While administration of ultrasound active agents such as fluorocarbon microbubbles and nanodroplets can locally enhance the effects of high intensity focused ultrasound (HIFU), it has been challenging to prepare ultrasound active agents that are small and stable enough to accumulate in tumors and internalize into cancer cells. Here, this paper reports the synthesis of 100 nm nanoparticle ultrasound agents based on phospholipid-coated, mesoporous, hydrophobically functionalized silica nanoparticles that can internalize into cancer cells and remain acoustically active. The ultrasound agents produce bubbles when subjected to short HIFU pulses (≈6 µs) with peak negative pressure as low as ≈7 MPa and at particle concentrations down to 12.5 µg mL -1 (7 × 10 9 particles mL -1 ). Importantly, ultrasound agents are effectively uptaken by cancer cells without cytotoxic effects, but HIFU insonation causes destruction of the cells by the acoustically generated bubbles, as demonstrated by (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and lactate dehydrogenase assays and flow cytometry. Finally, it is showed that the HIFU dose required to effectively eliminate cancer cells in the presence of ultrasound agents causes only a small temperature increase of ≈3.5 °C. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed

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

2018-05-01

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

Nonlinear acoustics in biomedical ultrasound

NASA Astrophysics Data System (ADS)

Cleveland, Robin O.

2015-10-01

Ultrasound is widely used to image inside the body; it is also used therapeutically to treat certain medical conditions. In both imaging and therapy applications the amplitudes employed in biomedical ultrasound are often high enough that nonlinear acoustic effects are present in the propagation: the effects have the potential to be advantageous in some scenarios but a hindrance in others. In the case of ultrasound imaging the nonlinearity produces higher harmonics that result in images of greater quality. However, nonlinear effects interfere with the imaging of ultrasound contrast agents (typically micron sized bubbles with a strong nonlinear response of their own) and nonlinear effects also result in complications when derating of pressure measurements in water to in situ values in tissue. High intensity focused ultrasound (HIFU) is emerging as a non-invasive therapeutic modality which can result in thermal ablation of tissue. For thermal ablation, the extra effective attenuation resulting from nonlinear effects can result in enhanced heating of tissue if shock formation occurs in the target region for ablation - a highly desirable effect. However, if nonlinearity is too strong it can also result in undesired near-field heating and reduced ablation in the target region. The disruption of tissue (histotripsy) and fragmentation of kidney stones (lithotripsy) exploits shock waves to produce mechanically based effects, with minimal heating present. In these scenarios it is necessary for the waves to be of sufficient amplitude that a shock exists when the waveform reaches the target region. This talk will discuss how underlying nonlinear phenomenon act in all the diagnostic and therapeutic applications described above.

Enhanced OH radical generation by dual-frequency ultrasound with TiO2 nanoparticles: its application to targeted sonodynamic therapy.

PubMed

Ninomiya, Kazuaki; Noda, Kyohei; Ogino, Chiaki; Kuroda, Shun-ichi; Shimizu, Nobuaki

2014-01-01

The present study demonstrated the enhanced hydroxyl (OH) radical generation by combined use of dual-frequency (0.5 MHz and 1 MHz) ultrasound (US) and titanium dioxide (TiO2) nanoparticles (NPs) as sonocatalyst. The OH radical generation became the maximum, when 0.5 MHz US was irradiated at an intensity of 0.8 W/cm(2) and 1 MHz US was irradiated at intensities at 0.4 W/cm(2) in the presence of TiO2 NPs under the examined conditions. After incorporation of TiO2 NPs modified with targeting protein pre-S1/S2, HepG2 cancer cells were subjected to the dual-frequency US at optimum irradiation intensities ("targeted-TiO2/dual-US treatment"). Growth of the HepG2 cells was reduced by 46% compared with the control condition after irradiation of dual-frequency US for 60s with TiO2 NPs incorporation. In contrast, HepG2 cell growth was almost the same as that in the control condition when cells were irradiated with either 0.5 MHz or 1 MHz ultrasound alone without TiO2 NP incorporation. Copyright © 2013 Elsevier B.V. All rights reserved.

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. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Stereotactic ultrasound for target volume definition in a patient with prostate cancer and bilateral total hip replacement.

PubMed

Boda-Heggemann, Judit; Haneder, Stefan; Ehmann, Michael; Sihono, Dwi Seno Kuncoro; Wertz, Hansjörg; Mai, Sabine; Kegel, Stefan; Heitmann, Sigrun; von Swietochowski, Sandra; Lohr, Frank; Wenz, Frederik

2015-01-01

Target-volume definition for prostate cancer in patients with bilateral metal total hip replacements (THRs) is a challenge because of metal artifacts in the planning computed tomography (CT) scans. Magnetic resonance imaging (MRI) can be used for matching and prostate delineation; however, at a spatial and temporal distance from the planning CT, identical rectal and vesical filling is difficult to achieve. In addition, MRI may also be impaired by metal artifacts, even resulting in spatial image distortion. Here, we present a method to define prostate target volumes based on ultrasound images acquired during CT simulation and online-matched to the CT data set directly at the planning CT. A 78-year-old patient with cT2cNxM0 prostate cancer with bilateral metal THRs was referred to external beam radiation therapy. T2-weighted MRI was performed on the day of the planning CT with preparation according to a protocol for reproducible bladder and rectal filling. The planning CT was obtained with the immediate acquisition of a 3-dimensional ultrasound data set with a dedicated stereotactic ultrasound system for online intermodality image matching referenced to the isocenter by ceiling-mounted infrared cameras. MRI (offline) and ultrasound images (online) were thus both matched to the CT images for planning. Daily image guided radiation therapy (IGRT) was performed with transabdominal ultrasound and compared with cone beam CT. Because of variations in bladder and rectal filling and metal-induced image distortion in MRI, soft-tissue-based matching of the MRI to CT was not sufficient for unequivocal prostate target definition. Ultrasound-based images could be matched, and prostate, seminal vesicles, and target volumes were reliably defined. Daily IGRT could be successfully completed with transabdominal ultrasound with good accordance between cone beam CT and ultrasound. For prostate cancer patients with bilateral THRs causing artifacts in planning CTs, ultrasound referenced to

Aptamer-conjugated and drug-loaded acoustic droplets for ultrasound theranosis.

PubMed

Wang, Chung-Hsin; Kang, Shih-Tsung; Lee, Ya-Hsuan; Luo, Yun-Ling; Huang, Yu-Fen; Yeh, Chih-Kuang

2012-02-01

Tumor therapy requires multi-functional treatment strategies with specific targeting of therapeutics to reduce general toxicity and increase efficacy. In this study we fabricated and functionally tested aptamer-conjugated and doxorubicin (DOX)-loaded acoustic droplets comprising cores of liquid perfluoropentane compound and lipid-based shell materials. Conjugation of sgc8c aptamers provided the ability to specifically target CCRF-CEM cells for both imaging and therapy. High-intensity focused ultrasound (HIFU) was introduced to trigger targeted acoustic droplet vaporization (ADV) which resulted in both mechanical cancer cell destruction by inertial cavitation and chemical treatment through localized drug release. HIFU insonation showed a 56.8% decrease in cell viability with aptamer-conjugated droplets, representing a 4.5-fold increase in comparison to non-conjugated droplets. In addition, the fully-vaporized droplets resulted in the highest DOX uptake by cancer cells, compared to non-vaporized or partially vaporized droplets. Optical studies clearly illustrated the transient changes that occurred upon ADV of droplet-targeted CEM cells, and B-mode ultrasound imaging revealed contrast enhancement by ADV in ultrasound images. In conclusion, our fabricated droplets functioned as a hybrid chemical and mechanical strategy for the specific destruction of cancer cells upon ultrasound-mediated ADV, while simultaneously providing ultrasound imaging capability. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

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

PubMed

Kim, Tae Kyoung; Jang, Hyun-Jung

2014-04-07

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

The utility of ultrasound in patients with melanoma.

PubMed

Uren, Roger F; Sanki, Amira; Thompson, John F

2007-11-01

The highest quality gray-scale ultrasound images are obtained with high-frequency transducers; however, such high frequencies do not penetrate more than a few centimeters into body tissue. Fortunately, in patients with melanoma, the structures of interest are close to the skin surface, making them ideal targets for examination with high-resolution ultrasound. These include primary cutaneous melanomas, uveal melanomas and the regional lymph nodes draining the skin that lie in the axilla, groin, neck and other locations. Although ultrasound study of primary melanomas arising in the skin and eye has provided some insights, a major role for ultrasound has evolved recently, to provide early detection of metastatic melanoma in regional lymph nodes. Ultrasound is clearly superior to clinical palpation of the nodes during follow-up and, when combined with guided fine-needle biopsy, allows the earliest possible surgical intervention for regional nodal metastases. In the future the use of ultrasound contrast agents may improve the sensitivity of ultrasound in the detection of very small metastatic deposits.

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

PubMed

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

2016-01-01

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

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

PubMed

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

2017-07-06

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

Optimization of contrast-to-tissue ratio by adaptation of transmitted ternary signal in ultrasound pulse inversion imaging.

PubMed

Ménigot, Sébastien; Girault, Jean-Marc

2013-01-01

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

Applicator for in-vitro ultrasound-activated targeted drug delivery

NASA Astrophysics Data System (ADS)

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

2012-10-01

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

Dynamics of Ultrasound Contrast Agents and Nonlinear Acoustic Waves: Experiments, Modeling, and Theories

NASA Astrophysics Data System (ADS)

Xia, Lang

Bubbles occur in many natural and biological flows as well as in numerous industrial phenomena, such as pumps, propellers, turbines, and chemical processing plants. They have been widely studied in the past leading to a large body of literature. However, bubbles appearing in different situations differ significantly in their physical characteristics and behaviors. Recently, bubbles of diameter less than 10 micrometers have found applications in diagnostic ultrasound imaging. These microbubble-based ultrasound contrast agents (UCA) are intravenously administered in patients before ultrasound imaging. Due to the compressive gas core, they generate substantial ultrasound echoes leading to significant enhancement of image quality and contrast. Free bubbles of a micrometer diameter experience a large surface tension induced Laplace pressure leading to their quick dissolution in milliseconds. UCAs are stabilized by coating them with a shell of lipids, polymers, proteins, and other surface-active materials and changing the gas content from air to a high molecular weight low solubility gas such as perfluorocarbon. The past literature of bubble dynamics are mostly restricted to free bubbles. The stabilizing shell of UCAs, however, critically affects their dynamics. In this thesis, we performed acoustic characterization of several UCAs coated with polymer and lipids. We experimentally measured their acoustic attenuation and scattering, of which the data were used in mathematical models to determine shell properties and nonlinear dynamics. Several different interfacial rheological models were employed. Experimental acoustic characterization was also extended to a novel type of nanoparticle suspension--polymersomes, vesicles encapsulated by amphiphilic polymers. The later part of the thesis is devoted to modeling the effects of the presence of coated microbubbles to the overall effective bulk properties of bubbly liquids. Introduction of microbubbles in the liquids does not

Renal Perfusion in Scleroderma Patients Assessed by Microbubble-Based Contrast-Enhanced Ultrasound

PubMed Central

Kleinert, Stefan; Roll, Petra; Baumgaertner, Christian; Himsel, Andrea; Mueller, Adelheid; Fleck, Martin; Feuchtenberger, Martin; Jenett, Manfred; Tony, Hans-Peter

2012-01-01

Objectives: Renal damage is common in scleroderma. It can occur acutely or chronically. Renal reserve might already be impaired before it can be detected by laboratory findings. Microbubble-based contrast-enhanced ultrasound has been demonstrated to improve blood perfusion imaging in organs. Therefore, we conducted a study to assess renal perfusion in scleroderma patients utilizing this novel technique. Materials and Methodology: Microbubble-based contrast agent was infused and destroyed by using high mechanical index by Siemens Sequoia (curved array, 4.5 MHz). Replenishment was recorded for 8 seconds. Regions of interests (ROI) were analyzed in renal parenchyma, interlobular artery and renal pyramid with quantitative contrast software (CUSQ 1.4, Siemens Acuson, Mountain View, California). Time to maximal Enhancement (TmE), maximal enhancement (mE) and maximal enhancement relative to maximal enhancement of the interlobular artery (mE%A) were calculated for different ROIs. Results: There was a linear correlation between the time to maximal enhancement in the parenchyma and the glomerular filtration rate. However, the other parameters did not reveal significant differences between scleroderma patients and healthy controls. Conclusion: Renal perfusion of scleroderma patients including the glomerular filtration rate can be assessed using microbubble-based contrast media. PMID:22670165

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

PubMed

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

2010-12-28

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

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

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

PubMed

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

2016-10-01

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

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

PubMed

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

2017-12-01

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

Investigation of the acute plantar fasciitis with contrast-enhanced ultrasound and shear wave elastography - first results.

PubMed

Putz, Franz Josef; Hautmann, Matthias G; Banas, Miriam C; Jung, Ernst Michael

2017-01-01

The plantar fasciitis is a common disease with a high prevalence in public and a frequent cause of heel pain. In our pilot study, we wanted to characterise the feasibility of shear-wave elastography and contrast-enhanced ultrasound (CEUS) in the assessment of the plantar fasciitis. 23 cases of painful heels were examined by B-Mode ultrasound, Power Doppler (PD), shear wave elastography and contrast-enhanced ultrasound before anti-inflammatory radiation. Time-intensity-curves were analysed by the integrated software. The results for area-under-the-curve (AUC), peak, time-to-peak (TTP) and mean-transit-time (MTT) were compared between the plantar fascia and the surrounding tissue. All cases showed thickening of the plantar fascia, in most cases with interstitial oedema (87.0%). Shear wave elastography showed inhomogeneous stiffness of the plantar fascia. 83.3% of cases showed a visible hyperperfusion in CEUS at the proximal plantar fascia in comparison to the surrounding tissue. This hyperperfusion could also be found in 75.0% of cases with no signs of vascularisation in PD. AUC (p = 0.0005) and peak (p = 0.037) were significantely higher in the plantar fascia than in the surrounding tissue. CEUS and shear wave elastography are new diagnostic tools in the assessment of plantar fasciitis and can provide quantitative parameters for monitoring therapy.

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

DTIC Science & Technology

2017-08-01

biodistribution studies with FMT, ultrasound imaging and ex vivo tissue analysis (months 10-14) 2d. Measure bubble dynamic parameters (months 10-14) 1...doctoral training studying post -transcriptional gene regulation National Institutes of Health-NICHD, Bethesda, MD Postdoctoral Fellow 02/1996 IRTA...and manage these studies . My research career has been hybrid consisting of experience in the biotech industry in addition to my academic position

Performance Evaluation of Adaptive Imaging Based on Multiphase Apodization with Cross-correlation: A Pilot Study in Abdominal Ultrasound.

PubMed

Shin, Junseob; Chen, Yu; Malhi, Harshawn; Chen, Frank; Yen, Jesse

2018-05-01

Degradation of image contrast caused by phase aberration, off-axis clutter, and reverberation clutter remains one of the most important problems in abdominal ultrasound imaging. Multiphase apodization with cross-correlation (MPAX) is a novel beamforming technique that enhances ultrasound image contrast by adaptively suppressing unwanted acoustic clutter. MPAX employs multiple pairs of complementary sinusoidal phase apodizations to intentionally introduce grating lobes that can be used to derive a weighting matrix, which mostly preserves the on-axis signals from tissue but reduces acoustic clutter contributions when multiplied with the beamformed radio-frequency (RF) signals. In this paper, in vivo performance of the MPAX technique was evaluated in abdominal ultrasound using data sets obtained from 10 human subjects referred for abdominal ultrasound at the USC Keck School of Medicine. Improvement in image contrast was quantified, first, by the contrast-to-noise ratio (CNR) and, second, by the rating of two experienced radiologists. The MPAX technique was evaluated for longitudinal and transverse views of the abdominal aorta, the inferior vena cava, the gallbladder, and the portal vein. Our in vivo results and analyses demonstrate the feasibility of the MPAX technique in enhancing image contrast in abdominal ultrasound and show potential for creating high contrast ultrasound images with improved target detectability and diagnostic confidence.

Entropy of Ultrasound-Contrast-Agent Velocity Fields for Angiogenesis Imaging in Prostate Cancer.

PubMed

van Sloun, Ruud J G; Demi, Libertario; Postema, Arnoud W; Jmch De La Rosette, Jean; Wijkstra, Hessel; Mischi, Massimo

2017-03-01

Prostate cancer care can benefit from accurate and cost-efficient imaging modalities that are able to reveal prognostic indicators for cancer. Angiogenesis is known to play a central role in the growth of tumors towards a metastatic or a lethal phenotype. With the aim of localizing angiogenic activity in a non-invasive manner, Dynamic Contrast Enhanced Ultrasound (DCE-US) has been widely used. Usually, the passage of ultrasound contrast agents thought the organ of interest is analyzed for the assessment of tissue perfusion. However, the heterogeneous nature of blood flow in angiogenic vasculature hampers the diagnostic effectiveness of perfusion parameters. In this regard, quantification of the heterogeneity of flow may provide a relevant additional feature for localizing angiogenesis. Statistics based on flow magnitude as well as its orientation can be exploited for this purpose. In this paper, we estimate the microbubble velocity fields from a standard bolus injection and provide a first statistical characterization by performing a spatial entropy analysis. By testing the method on 24 patients with biopsy-proven prostate cancer, we show that the proposed method can be applied effectively to clinically acquired DCE-US data. The method permits estimation of the in-plane flow vector fields and their local intricacy, and yields promising results (receiver-operating-characteristic curve area of 0.85) for the detection of prostate cancer.

Real-time measurement of renal blood flow in healthy subjects using contrast-enhanced ultrasound.

PubMed

Kalantarinia, Kambiz; Belcik, J Todd; Patrie, James T; Wei, Kevin

2009-10-01

Current methods for measuring renal blood flow (RBF) are time consuming and not widely available. Contrast-enhanced ultrasound (CEU) is a safe and noninvasive imaging technique suitable for assessment of tissue blood flow, which has been used clinically to assess myocardial blood flow. We tested the utility of CEU in monitoring changes in RBF in healthy volunteers. We utilized CEU to monitor the expected increase in RBF following a high protein meal in healthy adults. Renal cortical perfusion was assessed by CEU using low mechanical index (MI) power modulation Angio during continuous infusions of Definity. Following destruction of tissue microbubbles using ultrasound at a MI of 1.0, the rate of tissue replenishment with microbubbles and the plateau acoustic intensity (AI) were used to estimate the RBF velocity and cortical blood volume, respectively. Healthy adults (n = 19, mean age 26.6 yr) were enrolled. The A.beta parameter of CEU, representing mean RBF increased by 42.8%from a baseline of 17.05 +/- 6.23 to 23.60 +/- 6.76 dB/s 2 h after the ingestion of the high-protein meal (P = 0.002). Similarly, there was a 37.3%increase in the beta parameter, representing the geometric mean of blood velocity after the high protein meal (P < 0.001). The change in cortical blood volume was not significant (P = 0.89). Infusion time of Definity was 6.3 +/- 2.0 min. The ultrasound contrast agent was tolerated well with no serious adverse events. CEU is a fast, noninvasive, and practical imaging technique that may be useful for monitoring renal blood velocity, volume, and flow.

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

NASA Astrophysics Data System (ADS)

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

2007-05-01

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

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

PubMed

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

2007-12-01

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

Influence of nesting shell size on brightness longevity and resistance to ultrasound-induced dissolution during enhanced B-mode contrast imaging.

PubMed

Wallace, N; Dicker, S; Lewin, P; Wrenn, S P

2014-12-01

This study aims to bridge the gap between transport mechanisms of an improved ultrasound contrast agent (UCA) and its resulting behavior in a clinical imaging study. Phospholipid-shelled microbubbles nested within the aqueous core of a polymer microcapsule are examined for their use and feasibility as an improved UCA. The nested formulation provides contrast comparable to traditional formulations, specifically an SF6 microbubble coated by a DSPC PEG-3000 monolayer, with the advantage that contrast persists at least nine times longer in a mock clinical, in vitro setting. The effectiveness of the sample was measured using a contrast ratio in units of decibels (dB) which compares the brightness of the nested microbubbles to a reference value of a phantom tissue mimic. During a 40min imaging study, six nesting formulations with average outer capsule diameters of 1.95, 2.53, 5.55, 9.95, 14.95, and 20.51μm reached final contrast ratio values of 0.25, 2.35, 3.68, 4.51, 5.93, and 8.00dB, respectively. The starting contrast ratio in each case was approximately 8dB and accounts for the brightness attributed to the nesting shell. As compared with empty microcapsules (no microbubbles nested within), enhancement of the initial contrast ratio increased systematically with decreasing microcapsule size. The time required to reach a steady state in the temporal contrast ratio profile also varied with microcapsule diameter and was found to be 420s for each of the four smallest shell diameters and 210s and 150s, respectively, for the largest two shell diameters. All nested formulations were longer-lived and gave higher final contrast ratios than a control sample comprising un-nested, but otherwise equivalent, microbubbles. Specifically, the contrast ratio of the un-nested microbubbles decreased to a negative value after 4min of continuous ultrasound exposure with complete disappearance of the microbubbles after 15min whereas all nested formulations maintained positive contrast ratio

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.

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

PubMed

Ménigot, Sébastien; Girault, Jean-Marc

2016-09-01

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

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

PubMed

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

2006-10-01

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

Ultrasound internal tattooing.

PubMed

Couture, Olivier; Faivre, Magalie; Pannacci, Nicolas; Babataheri, Avin; Servois, Vincent; Tabeling, Patrick; Tanter, Mickael

2011-02-01

The ability of remotely tagging tissues in a controlled and three-dimensional manner during preoperative imaging could greatly help surgeons to identify targets for resection. The authors' objective is to selectively and noninvasively deposit markers under image guidance for such internal tattooing. This study describes the production of new ultrasound-inducible droplets carrying large payloads of fluorescent markers and the in vivo proof of concept of their remote and controlled deposition via focused ultrasound. The droplets are monodispersed multiple emulsions produced in a microfluidic system, consisting of aqueous fluorescein in perfluorocarbon in water. Their conversion (either by vaporization or cavitation) is performed remotely using a clinical ultrasonic imaging probe. When submitted to 5 MHz imaging pulses, the droplets vaporize in vitro at 1.4 MPa peak-negative pressure and eject their content. After several seconds, a brightly fluorescent spot (0.5 mm diameter) is observed at the focus of the transducer. Experiments in the chorioallantoique membrane of chicken eggs and chicken embryo demonstrate that the spot is stable and is easily seen by naked eye. These ultrasound-inducible multiple emulsions could be used to deliver large amounts of contrast agents, chemotherapy, and genetic materials in vivo using a conventional ultrasound scanner.

High Resolution Ultrasound Superharmonic Perfusion Imaging: In Vivo Feasibility and Quantification of Dynamic Contrast-Enhanced Acoustic Angiography.

PubMed

Lindsey, Brooks D; Shelton, Sarah E; Martin, K Heath; Ozgun, Kathryn A; Rojas, Juan D; Foster, F Stuart; Dayton, Paul A

2017-04-01

Mapping blood perfusion quantitatively allows localization of abnormal physiology and can improve understanding of disease progression. Dynamic contrast-enhanced ultrasound is a low-cost, real-time technique for imaging perfusion dynamics with microbubble contrast agents. Previously, we have demonstrated another contrast agent-specific ultrasound imaging technique, acoustic angiography, which forms static anatomical images of the superharmonic signal produced by microbubbles. In this work, we seek to determine whether acoustic angiography can be utilized for high resolution perfusion imaging in vivo by examining the effect of acquisition rate on superharmonic imaging at low flow rates and demonstrating the feasibility of dynamic contrast-enhanced superharmonic perfusion imaging for the first time. Results in the chorioallantoic membrane model indicate that frame rate and frame averaging do not affect the measured diameter of individual vessels observed, but that frame rate does influence the detection of vessels near and below the resolution limit. The highest number of resolvable vessels was observed at an intermediate frame rate of 3 Hz using a mechanically-steered prototype transducer. We also demonstrate the feasibility of quantitatively mapping perfusion rate in 2D in a mouse model with spatial resolution of ~100 μm. This type of imaging could provide non-invasive, high resolution quantification of microvascular function at penetration depths of several centimeters.

Modes of targets in water excited and identified using radiation pressure of modulated focused ultrasound

NASA Astrophysics Data System (ADS)

Daniel, Timothy; Fortuner, Auberry; Abawi, Ahmad; Kirsteins, Ivars; Marston, Philip

2016-11-01

The modulated radiation pressure (MRP) of ultrasound has been widely used to selectively excite low frequency modes of fluid objects. We previously used MRP to excite less compliant metallic object in water including the low frequency modes of a circular metal plate in water. A larger focused ultrasonic transducer allows us to drive modes of larger more-realistic targets. In our experiments solid targets are suspended by strings or supported on sand and the modulated ultrasound is focused on the target's surface. Target sound emissions were recorded and a laser vibrometer was used to measure the surface velocity of the target to give the magnitude of the target response. The source transducer was driven with a doublesideband suppressed carrier voltage as in. By varying the modulation frequency and monitoring target response, resonant frequencies can be measured and compared to finite element models. We also demonstrate the radiation torque of a focused first-order acoustic vortex beam associated with power absorption in the Stokes layer adjacent to a sphere. Funded by ONR.

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

PubMed

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

2013-12-28

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

Contrast-enhanced transrectal ultrasound (CE-TRUS) with cadence-contrast pulse sequence (CPS) technology for the identification of prostate cancer.

PubMed

Seitz, Michael; Gratzke, Christian; Schlenker, Boris; Buchner, Alexander; Karl, Alexander; Roosen, Alexander; Singer, Bernhard B; Bastian, Patrick J; Ergün, Süleyman; Stief, Christian G; Reich, Oliver; Tilki, Derya

2011-01-01

Various imaging modalities, such as magnetic resonance imaging (MRI), have been assessed with regard to their value in the detection of prostate cancer (CaP). However, there is a need for less time-consuming and more cost effective procedures in urology. In order to determine the ability of contrast-enhanced transrectal ultrasound (CE-TRUS) to identify CaP, we investigated patients scheduled for radical prostatectomy for CaP and radical cystoprostatectomy for bladder cancer. Between May and August 2008, 35 consecutive patients with CaP and muscle-invasive bladder carcinoma were prospectively enrolled in this single center study. All patients underwent B-mode TRUS and CE-TRUS (Sequoia 512 unit with an endocavity probe EV8C4, 8 MHz; Siemens, Erlangen, Germany) by one investigator blinded to any clinical data before radical surgery. Contrast-enhanced images were obtained after intravenous infusion of a bolus (2.4 ml) of the contrast agent SonoVue (Bracco, Milan, Italy). Ultrasound findings (CE-TRUS and B-mode TRUS) were correlated with step-section histology. On a per-patient basis, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for detecting CaP with CE-TRUS were 71.0%, 50.0%, 91.7%, and 18.2%, respectively. In comparison with B-mode TRUS (sensitivity 45.2%, specificity 75.0%, PPV 93.3%, and NPV 18.0%), CE-TRUS performed significantly better (P=0.004, McNemar test). On a per-prostate-lobe basis sensitivity, specificity, PPV, and NPV were 69.0%, 33.3%, 83.3%, and 18.2%. CE-TRUS detected prostate cancer with a modest sensitivity and a high PPV in a selected patient cohort. Future randomized-controlled multicenter studies are needed to further validate the value of CE-TRUS in the detection of CaP. Based on our results, CE-TRUS may not be recommended as a routine procedure in the diagnosis of CaP at present. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

High Resolution X-Ray Phase Contrast Imaging with Acoustic Tissue-Selective Contrast Enhancement

DTIC Science & Technology

2005-06-01

Ultrasonics Symp 1319 (1999). 17. Sarvazyan, A. P. Shear Wave Elasticity Imaging: A New Ultrasonic Technology of Medical Diagnostics. Ultrasound in...samples using acoustically modulated X-ray phase contrast imaging. 15. SUBJECT TERMS x-ray, ultrasound, phase contrast, imaging, elastography 16...x-rays, phase contrast imaging is based on phase changes as x-rays traverse a body resulting in wave interference that result in intensity changes in

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

NASA Astrophysics Data System (ADS)

Chen, Wen-Shiang

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

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

PubMed

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

2017-07-01

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

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Application of imaging fusion combining contrast-enhanced ultrasound and magnetic resonance imaging in detection of hepatic cellular carcinomas undetectable by conventional ultrasound.

PubMed

Dong, Yi; Wang, Wen-Ping; Mao, Feng; Ji, Zheng-Biao; Huang, Bei-Jian

2016-04-01

The aim of this study is to explore the value of volume navigation image fusion-assisted contrast-enhanced ultrasound (CEUS) in detection for radiofrequency ablation guidance of hepatocellular carcinomas (HCCs), which were undetectable on conventional ultrasound. From May 2012 to May 2014, 41 patients with 49 HCCs were included in this study. All lesions were detected by dynamic magnetic resonance imaging (MRI) and planned for radiofrequency ablation but were undetectable on conventional ultrasound. After a bolus injection of 2.4 ml SonoVue® (Bracco, Italy), LOGIQ E9 ultrasound system with volume navigation system (version R1.0.5, GE Healthcare, Milwaukee, WI, USA) was used to fuse CEUS and MRI images. The fusion time, fusion success rate, lesion enhancement pattern, and detection rate were analyzed. Image fusions were conducted successfully in 49 HCCs, the technical success rate was 100%. The average fusion time was (9.2 ± 2.1) min (6-12 min). The mean diameter of HCCs was 25.2 ± 5.3 mm (mean ± SD), and mean depth was 41.8 ± 17.2 mm. The detection rate of HCCs using CEUS/MRI imaging fusion (95.9%, 47/49) was significantly higher than CEUS (42.9%, 21/49) (P < 0.05). For small HCCs (diameter, 1-2 cm), the detection rate using imaging fusion (96.9%, 32/33) was also significantly higher than CEUS (18.2%, 6/33) (P < 0.01). All HCCs displayed a rapid wash-in pattern in the arterial phase of CEUS. Imaging fusion combining CEUS and MRI is a promising technique to improve the detection, precise localization, and accurate diagnosis of undetectable HCCs on conventional ultrasound, especially small and atypical HCCs. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

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

NASA Astrophysics Data System (ADS)

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

2017-10-01

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

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

PubMed

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

2017-10-04

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

Endoscopic ultrasound for the characterization and staging of rectal cancer. Current state of the method. Technological advances and perspectives.

PubMed

Gersak, Mariana M; Badea, Radu; Graur, Florin; Hajja, Nadim Al; Furcea, Luminita; Dudea, Sorin M

2015-06-01

Endoscopic ultrasound is the most accurate type of examination for the assessment of rectal tumors. Over the years, the method has advanced from gray-scale examination to intravenous contrast media administration and to different types of elastography. The multimodal approach of tumors (transrectal, transvaginal) is adapted to each case. 3D ultrasound is useful for spatial representation and precise measurement of tumor formations, using CT/MR image reconstruction; color elastography is useful for tumor characterization and staging; endoscopic ultrasound using intravenous contrast agents can help study the amount of contrast agent targeted at the level of the tumor formations and contrast wash-in/wash-out time, based on the curves displayed on the device. The transvaginal approach often allows better visualization of the tumor than the transrectal approach. Performing the procedure with the rectal ampulla distended with contrast agent may be seen as an optimization of the examination methodology. All these aspects are additional methods for gray-scale endoscopic ultrasound, capable of increasing diagnostic accuracy. This paper aims at reviewing the progress of transrectal and transvaginal ultrasound, generically called endoscopic ultrasound, for rectal tumor diagnosis and staging, with emphasis on the current state of the method and its development trends.

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

PubMed

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

2011-10-01

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

Early detection of ovarian cancer by serum marker and targeted ultrasound imaging | Division of Cancer Prevention

Cancer.gov

We propose to test the validity and specificity of our targeted ultrasound imaging probes in detecting early stage ovarian cancer (OVCA) by transvaginal ultrasound imaging (TVUS). We then test the predictive validity of these probes in a longitudinal study using the laying hen – the only widely available animal model of spontaneous OVCA. OVCA is a fatal gynecological

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

NASA Astrophysics Data System (ADS)

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

2016-08-01

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.

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

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

2016-08-18

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

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.

Contrast-enhanced imaging of SPIO-labeled platelets using magnetomotive ultrasound.

PubMed

Pope, Ava G; Wu, Gongting; McWhorter, Frances Y; Merricks, Elizabeth P; Nichols, Timothy C; Czernuszewicz, Tomasz J; Gallippi, Caterina M; Oldenburg, Amy L

2013-10-21

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.

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

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

PubMed

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

2015-01-01

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

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.

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

PubMed

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

2013-11-01

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

Use of Ultrasound Pulses Combined with Definity for Targeted Blood-Brain Barrier Disruption

NASA Astrophysics Data System (ADS)

McDannold, Nathan; Vykhodtseva, Natalia; Hynynen, Kullervo

2007-05-01

We have developed a method to combine an ultrasound contrast agent (USCA) with low-intensity focused ultrasound pulses combined to produce temporary blood-brain barrier disruption (BBBD), a potential non-invasive means for targeted drug delivery in the brain. All of our previous work used the USCA Optison. The purpose of this work was to test the feasibility of using the USCA Definity for BBBD. Thirty-six non-overlapping locations were sonicated through a craniotomy in experiments in the brains of nine rabbits (4 locations per rabbit; US frequency: 0.69MHz, burst: 10ms, PRF: 1Hz, duration: 20s; pressure amplitude: 0.2-1.5 MPa). Eleven locations were sonicated using Optison at 0.5 MPa. For both agents, the probability for BBBD was estimated to be 50% at 0.4 MPa using probit regression. In histology, small isolated areas of extravasated erythrocytes were observed in some locations. At 0.8 MPa and above, this extravasation was sometimes accompanied by tiny (dimensions of 100 μm or less) regions of damaged brain parenchyma. The magnitude of the BBBD was larger with Optison than with Definity at 0.5 MPa (P=0.04), and more areas with extravasated erythrocytes were observed (P=0.03). We conclude that BBBD is possible using Definity for the dosage of USCA and the acoustic parameters tested in this study. While the probability for BBBD as a function of pressure amplitude and the type of acute tissue effects was similar to findings with Optison, under these experimental conditions, Optison produced a larger effect.

Comparison of transducers with different frequencies in breast contrast-enhanced ultrasound (CEUS) using SonoVue as contrast agent.

PubMed

Wang, Yong-Mei; Fan, Wei; Zhang, Kai; Zhang, Li; Tan, Zhen; Ma, Rong

2016-07-01

To explore the effectiveness of different transducers in breast contrast-enhanced ultrasound (CEUS) using SonoVue(®) (Bracco, Plan-Les-Ouates, Switzerland) as the contrast agent. Breast CEUS was performed in 51 patients with 51 breast lesions using a low-frequency transducer (probe C5-1) and a high-frequency transducer (probe L12-5) separately. All image processes were reviewed for the presence of local blood perfusion defects and surrounding vessels. McNemar's test was conducted to compare the detection effectiveness between these two transducers. Pathological results revealed 38 malignant and 13 benign lesions. The two transducers showed no difference in detecting benign lesions. Among malignant lesions, CEUS conducted by probe C5-1 (frequency range from 1 to 5 MHz) presented 23 (60.5%) lesions with local blood perfusion defects and 26 (68.4%) lesions with surrounding vessels. Meanwhile, probe L12-5 (frequency range from 5 to 12 MHz) showed only 12 (31.6%) lesions with local blood perfusion defects and 12 (31.6%) lesions with surrounding vessel. Probe C5-1 was more sensitive than probe L12-5 in detecting malignant CEUS characteristics (p-value < 0.05). The low-frequency transducer was more sensitive than the high-frequency transducer in breast CEUS using SonoVue as the contrast agent. A new contrast agent with a higher resonance frequency, specially designed for high-frequency transducers, may be helpful in improving the clinical value of breast CEUS. The first study comparing different frequency transducers in breast CEUS of the same patient lesions. We brought out the requirement for CEUS contrast agents which are more suitable for high-frequency examinations.

Contrast-enhanced ultrasound measurement of pancreatic blood flow dynamics predicts type 1 diabetes progression in preclinical models.

PubMed

St Clair, Joshua R; Ramirez, David; Passman, Samantha; Benninger, Richard K P

2018-05-01

In type 1 diabetes (T1D), immune-cell infiltration into the islets of Langerhans (insulitis) and β-cell decline occurs many years before diabetes clinically presents. Non-invasively detecting insulitis and β-cell decline would allow the diagnosis of eventual diabetes, and provide a means to monitor therapeutic intervention. However, there is a lack of validated clinical approaches for specifically and non-invasively imaging disease progression leading to T1D. Islets have a denser microvasculature that reorganizes during diabetes. Here we apply contrast-enhanced ultrasound measurements of pancreatic blood-flow dynamics to non-invasively and predictively assess disease progression in T1D pre-clinical models. STZ-treated mice, NOD mice, and adoptive-transfer mice demonstrate altered islet blood-flow dynamics prior to diabetes onset, consistent with islet microvasculature reorganization. These assessments predict both time to diabetes onset and future responders to antiCD4-mediated disease prevention. Thus contrast-enhanced ultrasound measurements of pancreas blood-flow dynamics may provide a clinically deployable predictive marker for disease progression in pre-symptomatic T1D and therapeutic reversal.

Comparative analysis of renal flow using contrast power Doppler and gray-scale ultrasound

NASA Astrophysics Data System (ADS)

Sehgal, Chandra M.; Arger, Peter H.; Bovee, Kenneth C.; Pugh, Charles; Kirchhofer, Justin I.

1997-05-01

Our previous studies have shown that renal perfusion can be visualized by imaging the transit of a contrast agent through the parenchyma of the organ using gray scale (GS) and power Doppler (PD) ultrasound.However, the relative merits and the sensitivities of the two imaging methods are not known. This study compares the effectiveness of the two modes in visualizing kidney perfusion at the clinical dose of contrast agents. GS and PD images of the dog kidneys were recorded using a clinical ultrasound scanner at 4-7 MHz. A fixed longitudinal plane of the kidney was imaged by mounting the transducer on the animal with a specially designed holder. A dose of 0.1 m1/kg of Echogen was injected intravenously and GS and PD images were recorded simultaneously on two separate time-encoded video tapes during the passage of the contrast agent through the kidneys. The enhancement of GS and PD images was assessed qualitatively by three radiologists. The quantitative assessment was made by measuring the regional and global enhancements of digitized B-scan and PS images. Regional measurements were made by comparing brightness of the post contrast images with that of a pre-contrast reference image pixel by pixel. Student t-test was used to determine the statistical significance of the change. The regions representing statistically significant differences were encoded on the image in color with brightness proportional to the magnitude of change. The regions with no significant change were represented in GS. This generated a series of new images, referred to as StatMap, with color representing regions of perfusion. Changes in power Doppler images were visually detectable with high confidence in all five dogs by al three radiologists. There was no perceptible changes in B-scans. Computer analysis of PD images yielded characteristic indicator dilution curves in all five dogs with an initial rise time of 2-5 sec and a peak at 7-20 sec. The enhancement in PD lasted for 97-400 seconds. The

Intravenous and Intracavitary Use of Contrast-Enhanced Ultrasound in the Evaluation and Management of Complicated Pediatric Pneumonia.

PubMed

Deganello, Annamaria; Rafailidis, Vasileios; Sellars, Maria E; Ntoulia, Aikaterini; Kalogerakou, Kleanthi; Ruiz, Gary; Cosgrove, David O; Sidhu, Paul S

2017-09-01

Pediatric pneumonia can be complicated by necrotizing pneumonia or a parapneumonic effusion either in the form of an empyema or a clear effusion. Ultrasonography (US) and computed tomography represent well-established modalities for evaluation of complicated pediatric pneumonia. Contrast-enhanced ultrasound (CEUS) was recently introduced and is gaining increasing acceptance in pediatric imaging. In this case series, we present our initial experience with both intravenous and intracavitary use of CEUS in children with complicated pneumonia. Intravenous CEUS accurately and confidently showed necrotizing pneumonia and delineated pleural effusions, whereas intracavitary CEUS accurately identified the chest catheter location and patency and showed the presence of loculations, suggesting the use of fibrinolytics. © 2017 by the American Institute of Ultrasound in Medicine.

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

PubMed

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

2013-05-01

To investigate the value of contrast enhanced ultrasound (CEUS) imaging in the differential diagnosis between benign and malignant renal neoplasms. Two hundred and forty-five cases of renal space-occupying lesions confirmed by biopsy or surgical pathology were included in this study. The CEUS features of the renal space-occupying lesions, i.e., the enhancement degree, homogeneity of enhancement, washing-in and washing-out time and enhancement pattern, were retrospectively analyzed. There were 210 cases of malignant renal tumors and 35 cases of benign lesions. The CEUS modes of the malignant renal tumors included "quick in and quick out" 82 cases, "quick in and slow out" 64 cases, "slow in and quick out" 18 cases and "slow in and slow out" 46 cases; good enhancement 150 cases (71.4%) and inhomogeneous enhancement 180 cases (85.7%).Both the contrast agent filling defect area and solid component enhancement of solid-cystic tumors were important features of malignant renal tumors. In the 35 cases of benign lesions,the CEUS modes included "quick in and quick out" 4 cases, "quick in and slow out" 8 cases, "slow in and quick out" 10 cases and "slow in and slow out" 13 cases. Most of the benign tumors showed low enhancement 51.4% (18/35) and inhomogeneous enhancement 54.3% (19/35). There were significant differences between the malignant and benign renal neoplasms in CEUS mode, degree of enhancement and homogeneity of enhancement (P < 0.05), and in time of increasing, peak time, peak intensity and peak intensity ratio (P < 0.05). The accuracy rates of contrast-enhanced ultrasound for diagnosis of benign and malignant tumors were 77.1% and 83.8%, respectively, while the two-dimensional ultrasound diagnosis of benign and malignant tumors were 68.6% and 76.7%, respectively, with a significant difference (P < 0.05). CEUS may provide more information to improve the diagnostic accuracy for renal neoplasms, and may play important role in differential diagnosis between benign and

Volume quantification by contrast-enhanced ultrasound: an in-vitro comparison with true volumes and thermodilution.

PubMed

Herold, Ingeborg H F; Russo, Gianna; Mischi, Massimo; Houthuizen, Patrick; Saidov, Tamerlan; van het Veer, Marcel; van Assen, Hans C; Korsten, Hendrikus H M

2013-10-17

Contrast-enhanced ultrasound (CEUS) has recently been proposed as a minimally- invasive, alternative method for blood volume measurement. This study aims at comparing the accuracy of CEUS and the classical thermodilution techniques for volume assessment in an in-vitro set-up. The in-vitro set-up consisted of a variable network between an inflow and outflow tube and a roller pump. The inflow and outflow tubes were insonified with an ultrasound array transducer and a thermistor was placed in each tube. Indicator dilution curves were made by injecting indicator which consisted of an ultrasound-contrast-agent diluted in ice-cold saline. Both acoustic intensity- and thermo-dilution curves were used to calculate the indicator mean transit time between the inflow and outflow tube. The volumes were derived by multiplying the estimated mean transit time by the flow rate. We compared the volumes measured by CEUS with the true volumes of the variable network and those measured by thermodilution by Bland-Altman and intraclass-correlation analysis. The measurements by CEUS and thermodilution showed a very strong correlation (rs = 0.94) with a modest volume underestimation by CEUS of -40 ± 28 mL and an overestimation of 84 ± 62 mL by thermodilution compared with the true volumes. Both CEUS and thermodilution showed a high statistically significant correlation with the true volume (rs = 0.97 (95% CI, 0.95 - 0.98; P<0.0001) and rs = 0.96 (95% CI, 0.94 - 0.98; P<0.0001, respectively). CEUS volume estimation provides a strong correlation with both the true volumes in-vitro and volume estimation by thermodilution. It may therefore represent an interesting alternative to the standard, invasive thermodilution technique.

Ultrasound-based quantification of vitreous floaters correlates with contrast sensitivity and quality of life.

PubMed

Mamou, Jonathan; Wa, Christianne A; Yee, Kenneth M P; Silverman, Ronald H; Ketterling, Jeffrey A; Sadun, Alfredo A; Sebag, J

2015-01-22

Clinical evaluation of floaters lacks quantitative assessment of vitreous structure. This study used quantitative ultrasound (QUS) to measure vitreous opacities. Since floaters reduce contrast sensitivity (CS) and quality of life (Visual Function Questionnaire [VFQ]), it is hypothesized that QUS will correlate with CS and VFQ in patients with floaters. Twenty-two eyes (22 subjects; age = 57 ± 19 years) with floaters were evaluated with Freiburg acuity contrast testing (FrACT; %Weber) and VFQ. Ultrasonography used a customized probe (15-MHz center frequency, 20-mm focal length, 7-mm aperture) with longitudinal and transverse scans taken in primary gaze and a horizontal longitudinal scan through premacular vitreous in temporal gaze. Each scan set had 100 frames of log-compressed envelope data. Within each frame, two regions of interest (ROIs) were analyzed (whole-central and posterior vitreous) to yield three parameters (energy, E; mean amplitude, M; and percentage of vitreous filled by echodensities, P50) averaged over the entire 100-frame dataset. Statistical analyses evaluated E, M, and P50 correlations with CS and VFQ. Contrast sensitivity ranged from 1.19%W (normal) to 5.59%W. All QUS parameters in two scan positions within the whole-central ROI correlated with CS (R > 0.67, P < 0.001). P50 in the nasal longitudinal position had R = 0.867 (P < 0.001). Correlations with VFQ ranged from R = 0.52 (P < 0.013) to R = 0.65 (P < 0.001). Quantitative ultrasound provides quantitative measures of vitreous echodensity that correlate with CS and VFQ, providing objective assessment of vitreous structure underlying the functional disturbances induced by floaters, useful to quantify vitreous disease severity and the response to therapy. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

Ultrasound-Based Quantification of Vitreous Floaters Correlates with Contrast Sensitivity and Quality of Life

PubMed Central

Mamou, Jonathan; Wa, Christianne A.; Yee, Kenneth M. P.; Silverman, Ronald H.; Ketterling, Jeffrey A.; Sadun, Alfredo A.; Sebag, J.

2015-01-01

Purpose. Clinical evaluation of floaters lacks quantitative assessment of vitreous structure. This study used quantitative ultrasound (QUS) to measure vitreous opacities. Since floaters reduce contrast sensitivity (CS) and quality of life (Visual Function Questionnaire [VFQ]), it is hypothesized that QUS will correlate with CS and VFQ in patients with floaters. Methods. Twenty-two eyes (22 subjects; age = 57 ± 19 years) with floaters were evaluated with Freiburg acuity contrast testing (FrACT; %Weber) and VFQ. Ultrasonography used a customized probe (15-MHz center frequency, 20-mm focal length, 7-mm aperture) with longitudinal and transverse scans taken in primary gaze and a horizontal longitudinal scan through premacular vitreous in temporal gaze. Each scan set had 100 frames of log-compressed envelope data. Within each frame, two regions of interest (ROIs) were analyzed (whole-central and posterior vitreous) to yield three parameters (energy, E; mean amplitude, M; and percentage of vitreous filled by echodensities, P50) averaged over the entire 100-frame dataset. Statistical analyses evaluated E, M, and P50 correlations with CS and VFQ. Results. Contrast sensitivity ranged from 1.19%W (normal) to 5.59%W. All QUS parameters in two scan positions within the whole-central ROI correlated with CS (R > 0.67, P < 0.001). P50 in the nasal longitudinal position had R = 0.867 (P < 0.001). Correlations with VFQ ranged from R = 0.52 (P < 0.013) to R = 0.65 (P < 0.001). Conclusions. Quantitative ultrasound provides quantitative measures of vitreous echodensity that correlate with CS and VFQ, providing objective assessment of vitreous structure underlying the functional disturbances induced by floaters, useful to quantify vitreous disease severity and the response to therapy. PMID:25613948

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

PubMed

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

2010-06-15

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

Pediatric Sarcomas Are Targetable by MR-Guided High Intensity Focused Ultrasound (MR-HIFU): Anatomical Distribution and Radiological Characteristics.

PubMed

Shim, Jenny; Staruch, Robert M; Koral, Korgun; Xie, Xian-Jin; Chopra, Rajiv; Laetsch, Theodore W

2016-10-01

Despite intensive therapy, children with metastatic and recurrent sarcoma or neuroblastoma have a poor prognosis. Magnetic resonance guided high intensity focused ultrasound (MR-HIFU) is a noninvasive technique allowing the delivery of targeted ultrasound energy under MR imaging guidance. MR-HIFU may be used to ablate tumors without ionizing radiation or target chemotherapy using hyperthermia. Here, we evaluated the anatomic locations of tumors to assess the technical feasibility of MR-HIFU therapy for children with solid tumors. Patients with sarcoma or neuroblastoma with available cross-sectional imaging were studied. Tumors were classified based on the location and surrounding structures within the ultrasound beam path as (i) not targetable, (ii) completely or partially targetable with the currently available MR-HIFU system, and (iii) potentially targetable if a respiratory motion compensation technique was used. Of the 121 patients with sarcoma and 61 patients with neuroblastoma, 64% and 25% of primary tumors were targetable at diagnosis, respectively. Less than 20% of metastases at diagnosis or relapse were targetable for both sarcoma and neuroblastoma. Most targetable lesions were located in extremities or in the pelvis. Respiratory motion compensation may increase the percentage of targetable tumors by 4% for sarcomas and 10% for neuroblastoma. Many pediatric sarcomas are localized at diagnosis and are targetable by current MR-HIFU technology. Some children with neuroblastoma have bony tumors targetable by MR-HIFU at relapse, but few newly diagnosed children with neuroblastoma have tumors amenable to MR-HIFU therapy. Clinical trials of MR-HIFU should focus on patients with anatomically targetable tumors. © 2016 Wiley Periodicals, Inc.

Enhanced cytotoxic effect of cisplatin using diagnostic ultrasound and microbubbles in vitro

NASA Astrophysics Data System (ADS)

Sasaki, Noboru; Nakamura, Kensuke; Murakami, Masahiro; Lim, Sue Yee; Ohta, Hiroshi; Yamasaki, Masahiro; Takiguchi, Mitsuyoshi

2012-10-01

Diagnostic ultrasound has accomplished drug and gene delivery by ultrasound targeted microbubble destruction (UTMD). However, the efficacy of delivery is still relatively low. Therefore, we optimized conditions of UTMD using diagnostic ultrasound and ultrasound contrast agent microbubbles. Canine thyroid adenocarcinoma cells were cultured in a 96-well plate. After addition of cisplatin and Sonazoid®, the plate was inverted to raise microbubbles near cells and incubated. Cells were exposed to diagnostic ultrasound using a linear probe operated in the contrast harmonic imaging mode. The center frequency was 2.5 MHz with a mechanical index of 1.33 and a frame rate of 48 frames/sec. Cytotoxic effect of cisplatin was evaluated 24h after exposure using trypan blue dye exclusion test. We optimized incubation duration, cisplatin concentration, and the relationship between microbubble concentration and exposure duration. The optimum enhancement was observed at incubation duration of 5min, cisplatin concentration of 1 μg/ml, and microbubble concentration of 2.4 × 105 microbubbles/ml. Exposure duration did not influence the enhancement at the microbubble concentration of 2.4 × 105 microbubbles/ml. Our results suggest that relative low concentrations of drug and microbubbles with short exposure duration might be sufficient for drug delivery by UTMD using diagnostic ultrasound.

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

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

PubMed

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

2016-01-01

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

Preparation and in vitro evaluation of poly(D,L-lactide-co-glycolide) air-filled nanocapsules as a contrast agent for ultrasound imaging.

PubMed

Néstor, Mendoza-Muñoz; Kei, Noriega-Peláez Eddy; Guadalupe, Nava-Arzaluz María; Elisa, Mendoza-Elvira Susana; Adriana, Ganem-Quintanar; David, Quintanar-Guerrero

2011-10-01

The aim of this study was to prepare air-filled nanocapsules intended ultrasound contrast agents (UCAs) with a biodegradable polymeric shell composed of poly(d,l-lactide-co-glycolide) (PLGA). Because of their size, current commercial UCAs are not capable of penetrating the irregular vasculature that feeds growing tumors. The new generation of UCAs should be designed on the nanoscale to enhance tumor detection, in addition, the polymeric shell in contrast with monomolecular stabilized UCAs improves the mechanical properties against ultrasound pressure and lack of stability. The preparation method of air-filled nanocapsules was based on a modification of the double-emulsion solvent evaporation technique. Air-filled nanocapsules with a mean diameter of 370±96nm were obtained. Electronic microscopies revealed spherical-shaped particles with smooth surfaces and a capsular morphology, with a shell thickness of ∼50nm. Air-filled nanocapsules showed echogenic power in vitro, providing an enhancement of up to 15dB at a concentration of 0.045mg/mL at a frequency of 10MHz. Loss of signal for air-filled nanocapsules was 2dB after 30min, suggesting high stability. The prepared contrast agent in this work has the potential to be used in ultrasound imaging. Copyright © 2011 Elsevier B.V. All rights reserved.

[Contrast enhanced power Doppler and color Doppler ultrasound in breast masses: Efficiency in diagnosis and contributions to differential diagnosis].

PubMed

Algül, Ali; Balci, Pinar; Seçil, Mustafa; Canda, Tülay

2003-06-01

To compare ability of detection of vascular structures by utilizing ultrasonographic contrast agent (Levovist) prior to and following power Doppler ultrasound (PDUS) and colour Doppler ultrasound (CDUS) and to determine useful parameters in the differentiation of malignant and benign breast masses by means of verified data. Vascularisation characteristics of 38 breast masses (22 malignant, 16 benign) which were confirmed by mammography and B-mode sonography were evaluated by both CDUS and PDUS following and prior to intravenous contrast application. In addition, Vmax and RI values of vascular structures were calculated by Doppler spectral evaluation. Malignant lesions showed more vascularity than benign lesions both with and without contrast enhancement. With both methods, by utilizing contrast agent, central, penetrating and tortuous vascular structures became more significant in malignant lesions when compared with benign lesions. PDUS was able to detect vascular structures better than CDUS; however, the difference was not statistically significant. Presence of peripheral vascularity was not useful in differentiating malignant from benign lesions. Vmax and RI values were higher in malignant lesions and the difference was statistically significant. In both methods, Vmax > 15 cm/sec and RI > 0.80 (CDUS), and RI > 0.70 (PDUS) were accepted as malignancy parameters. Vascular patterns of breast masses as determined with PDUS and CDUS with contrast enhancement and Doppler spectral examinations enabled differentiation of malignant and benign breast lesions. Thus, it is possible to decrease the number of unnecessary surgical interventions.

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

PubMed

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

2015-09-01

Pediatric contrast-enhanced ultrasound (CEUS) is primarily performed outside the United States where a track record for safety in intravenous and intravesical applications has been established. Contrast-enhanced voiding urosonography (ceVUS) has also been shown to have a much higher rate of vesicoureteral reflux detection compared to voiding cystourethrography. US contrast agents available in the United States differ from those abroad. Optison® (GE Healthcare, Princeton, NJ) is such an US contrast agent. While Optison® has similar characteristics to other second-generation agents, it has never been used for ceVUS. In vitro optimization of dose and imaging parameters as well as assessment of contrast visualization when delivered in conditions similar to ceVUS are necessary starting points prior to in vivo applications. To optimize the intravesical use of Optison® in vitro for ceVUS before its use in pediatric studies. The experimental design simulated intravesical use. Using 9- and 12-MHz linear transducers, we scanned 20-mL syringes varying mechanical index, US contrast agent concentration (0.25%, 0.5%, 1.0%), solvent (saline, urine, radiographic contrast agent) and time out of refrigeration. We evaluated mechanical index settings and contrast duration, optimized the contrast dose, measured the effect of urine and radiographic contrast agent, and the impact of length of time of contrast outside of the refrigerator on US contrast appearance. We scanned 50-ml saline bags to assess the appearance and duration of US contrast with different delivery systems (injection vs. infusion). Consistent contrast visualization was achieved at a mechanical index of 0.06-0.17 and 0.11-0.48 for the L9 and L12 MHz transducers (P < 0.01), respectively. Thus, it was necessary to increase the mechanical index for better contrast visualization of the microbubbles with a higher transducer frequency. The lowest mechanical index for earliest visible microbubble destruction was 0

Minimally invasive ultrasound thermal therapy with MR thermal monitoring and guidance

NASA Astrophysics Data System (ADS)

Diederich, Chris J.; Stafford, R. Jason; Price, Roger E.; Nau, William H.; Tyreus, Per Daniel; Rivera, Belinda; Schomer, Donald; Olsson, Lars; Hazle, John D.

2001-06-01

In this study both transurethral and interstitial ultrasound thermal therapy were applied to thermally coagulate targeted portions of the canine prostate or brain and implanted TVT tumors while using MRI-based thermal mapping techniques to monitor the therapy. MRI was also used for target definition, positioning of the applicator, and evaluation of target viability post-therapy. The complex phase-difference mapping technique using an iGE-EPI sequence with lipid suppression was used for determining temperature elevations within the in vivo prostate or brain and surrounding structures. Calculated temperature distributions, thermal dose exposures, T2-wieghted & T1-contrast enhanced images, gross inspection, and histology of sectioned prostates and brains were in good agreement with each other in defining destroyed tissue zones. Interstitial and transurethral ultrasound applicators produce directed zones of thermal coagulation within targeted tissue and implanted tumor, which can be accurately monitored and evaluated by MRI.

Microbubble Enzyme-Linked Immunosorbent Assay for the Detection of Targeted Microbubbles in in Vitro Static Binding Assays.

PubMed

Wischhusen, Jennifer; Padilla, Frederic

2017-07-01

Targeted microbubbles (MBs) are ultrasound contrast agents that are functionalized with a ligand for ultrasound molecular imaging of endothelial markers. Novel targeted MBs are characterized in vitro by incubation in protein-coated wells, followed by binding quantification by microscopy or ultrasound imaging. Both methods provide operator-dependent results: Between 3 and 20 fields of view from a heterogeneous sample are typically selected for analysis by microscopy, and in ultrasound imaging, different acoustic settings affect signal intensities. This study proposes a new method to reproducibly quantify MB binding based on enzyme-linked immunosorbent assay (ELISA), in which bound MBs are revealed with an enzyme-linked antibody. MB-ELISA was adapted to in vitro static binding assays, incubating the MBs in inverted position or by agitation, and compared with microscopy. The specificity and sensitivity of MB-ELISA enable the reliable quantification of MB binding in a rapid, high-throughput and whole-well analysis, facilitating the characterization of new targeted contrast agents. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2016-02-01

Glomerular capillary hemorrhage can be induced by ultrasonic cavitation during contrast-enhanced diagnostic ultrasound (US) exposure, an important nonthermal US bioeffect. Recent studies of pulmonary US exposure have shown that thresholds for another nonthermal bioeffect of US, pulmonary capillary hemorrhage, is strongly influenced by whether xylazine is included in the specific anesthetic technique. The objective of this study was to determine the influence of xylazine on contrast-enhanced diagnostic US-induced glomerular capillary hemorrhage. In this study, anesthesia with ketamine only was compared to ketamine plus xylazine for induction of glomerular capillary hemorrhage in rats by 1.6-MHz intermittent diagnostic US with a microsphere contrast agent (similar to Definity; Lantheus Medical Imaging, Inc, North Billerica, MA). Glomerular capillary hemorrhage was measured as a percentage of glomeruli with hemorrhage found in histologic sections for groups of rats scanned at different peak rarefactional pressure amplitudes. There was a significant difference between the magnitude of the glomerular capillary hemorrhage between the anesthetics at 2.3 MPa, with 45.6% hemorrhage for ketamine only, increasing to 63.2% hemorrhage for ketamine plus xylazine (P < .001). However, the thresholds for the two anesthetic methods were virtually identical at 1.0 MPa, based on linear regression of the exposure response data. Thresholds for contrast-enhanced diagnostic US-induced injury of the microvasculature appear to be minimally affected by anesthetic methods. © 2016 by the American Institute of Ultrasound in Medicine.

Nanomaterials incorporated ultrasound contrast agents for cancer theranostics

PubMed Central

Fu, Lei; Ke, Heng-Te

2016-01-01

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

Jetting of a ultrasound contrast microbubble near a rigid wall

NASA Astrophysics Data System (ADS)

Sarkar, Kausik; Mobadersany, Nima

2017-11-01

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

Quantitative contrast-enhanced ultrasound for monitoring vedolizumab therapy in inflammatory bowel disease patients: a pilot study.

PubMed

Goertz, Ruediger S; Klett, Daniel; Wildner, Dane; Atreya, Raja; Neurath, Markus F; Strobel, Deike

2018-01-01

Background Microvascularization of the bowel wall can be visualized and quantified non-invasively by software-assisted analysis of derived time-intensity curves. Purpose To perform software-based quantification of bowel wall perfusion using quantitative contrast-enhanced ultrasound (CEUS) according to clinical response in patients with inflammatory bowel disease treated with vedolizumab. Material and Methods In a prospective study, in 18 out of 34 patients, high-frequency ultrasound of bowel wall thickness using color Doppler flow combined with CEUS was performed at baseline and after 14 weeks of treatment with vedolizumab. Clinical activity scores at week 14 were used to differentiate between responders and non-responders. CEUS parameters were calculated by software analysis of the video loops. Results Nine of 18 patients (11 with Crohn's disease and seven with ulcerative colitis) showed response to treatment with vedolizumab. Overall, the responder group showed a significant decrease in the semi-quantitative color Doppler vascularization score. Amplitude-derived CEUS parameters of mural microvascularization such as peak enhancement or wash-in rate decreased in responders, in contrast with non-responders. Time-derived parameters remained stable or increased during treatment in all patients. Conclusion Analysis of bowel microvascularization by CEUS shows statistically significant changes in the wash-in-rate related to response of vedolizumab therapy.

Localized Harmonic Motion Imaging for Focused Ultrasound Surgery Targeting

PubMed Central

Curiel, Laura; Hynynen, Kullervo

2011-01-01

Recently, an in vivo real-time ultrasound-based monitoring technique that uses localized harmonic motion (LHM) to detect changes in tissues during focused ultrasound surgery (FUS) has been proposed to control the exposure. This technique can potentially be used as well for targeting imaging. In the present study we evaluated the potential of using LHM to detect changes in stiffness and the feasibility of using it for imaging purposes in phantoms and in vivo tumor detection. A single-element FUS transducer (80 mm focal length, 100 mm diameter, 1.485 MHz) was used for inducing a localized harmonic motion and a separate ultrasound diagnostic transducer excited by a pulser/receiver (5 kHz PRF, 5 MHz) was used to track motion. The motion was estimated using cross-correlation techniques on the acquired RF signal. Silicon phantom studies were performed in order to determine the size of inclusion that was possible to detect using this technique. Inclusions were discerned from the surroundings as a reduction on LHM amplitude and it was possible to depict inclusions as small as 4 mm. The amplitude of the induced LHM was always lower at the inclusions as compared with the one obtained at the surroundings. Ten New Zealand rabbits had VX2 tumors implanted on their thighs and LHM was induced and measured at the tumor region. Tumors (as small as 10 mm in length and 4 mm in width) were discerned from the surroundings as a reduction on LHM amplitude. PMID:21683514

Trans-cranial opening of the blood-brain barrier in targeted regions using a stereotaxic brain atlas and focused ultrasound energy.

PubMed

Bing, Chenchen; Ladouceur-Wodzak, Michelle; Wanner, Clinton R; Shelton, John M; Richardson, James A; Chopra, Rajiv

2014-01-01

The blood-brain barrier (BBB) protects the brain by preventing the entry of large molecules; this poses a major obstacle for the delivery of drugs to the brain. A novel technique using focused ultrasound (FUS) energy combined with microbubble contrast agents has been widely used for non-invasive trans-cranial BBB opening. Traditionally, FUS research is conducted with magnetic resonance imaging (MRI) guidance, which is expensive and poses physical limitations due to the magnetic field. A system that could allow researchers to test brain therapies without MR intervention could facilitate and accelerate translational research. In this study, we present a novel FUS system that uses a custom-built FUS generator mounted on a motorized stereotaxic apparatus with embedded brain atlas to locally open the BBB in rodents. The system was initially characterized using a tissue-mimicking phantom. Rodent studies were also performed to evaluate whether non-invasive, localized BBB opening could be achieved using brain atlas-based targeting. Brains were exposed to pulsed focused ultrasound energy at 1.06 MHz in rats and 3.23 MHz in mice, with the focal pressure estimated to be 0.5-0.6 MPa through the skull. BBB opening was confirmed in gross tissue sections by the presence of Evans blue leakage in the exposed region of the brain and by histological assessment. The targeting accuracy of the stereotaxic system was better than 0.5 mm in the tissue-mimicking phantom. Reproducible localized BBB opening was verified with Evans blue dye leakage in 32/33 rats and had a targeting accuracy of ±0.3 mm. The use of higher frequency exposures in mice enabled a similar precision of localized BBB opening as was observed with the low frequency in the rat model. With this dedicated small-animal motorized stereotaxic-FUS system, we achieved accurate targeting of focused ultrasound exposures in the brain for non-invasive opening of the BBB. This system can be used as an alternative to MR

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.

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peruzzini, D.; Viti, J.; Erasmus MC, ’s-Gravendijkwal 230, Faculty Building, Ee 2302, 3015 CE Rotterdam

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 performedmore » 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.« less

Externally Delivered Focused Ultrasound for Renal Denervation.

PubMed

Neuzil, Petr; Ormiston, John; Brinton, Todd J; Starek, Zdenek; Esler, Murray; Dawood, Omar; Anderson, Thomas L; Gertner, Michael; Whitbourne, Rob; Schmieder, Roland E

2016-06-27

The aim of this study was to assess clinical safety and efficacy outcomes of renal denervation executed by an externally delivered, completely noninvasive focused therapeutic ultrasound device. Renal denervation has emerged as a potential treatment approach for resistant hypertension. Sixty-nine subjects received renal denervation with externally delivered focused ultrasound via the Kona Medical Surround Sound System. This approach was investigated across 3 consecutive studies to optimize targeting, tracking, and dosing. In the third study, treatments were performed in a completely noninvasive way using duplex ultrasound image guidance to target the therapy. Short- and long-term safety and efficacy were evaluated through use of clinical assessments, magnetic resonance imaging scans prior to and 3 and 24 weeks after renal denervation, and, in cases in which a targeting catheter was used to facilitate targeting, fluoroscopic angiography with contrast. All patients tolerated renal denervation using externally delivered focused ultrasound. Office blood pressure (BP) decreased by 24.6 ± 27.6/9.0 ± 15.0 mm Hg (from baseline BP of 180.0 ± 18.5/97.7 ± 13.7 mm Hg) in 69 patients after 6 months and 23.8 ± 24.1/10.3 ± 13.1 mm Hg in 64 patients with complete 1-year follow-up. The response rate (BP decrease >10 mm Hg) was 75% after 6 months and 77% after 1 year. The most common adverse event was post-treatment back pain, which was reported in 32 of 69 patients and resolved within 72 h in most cases. No intervention-related adverse events involving motor or sensory deficits were reported. Renal function was not altered, and vascular safety was established by magnetic resonance imaging (all patients), fluoroscopic angiography (n = 48), and optical coherence tomography (n = 5). Using externally delivered focused ultrasound and noninvasive duplex ultrasound, image-guided targeting was associated with substantial BP reduction without any major safety signals. Further

A Sensitive TLRH Targeted Imaging Technique for Ultrasonic Molecular Imaging

PubMed Central

Hu, Xiaowen; Zheng, Hairong; Kruse, Dustin E.; Sutcliffe, Patrick; Stephens, Douglas N.; Ferrara, Katherine W.

2010-01-01

The primary goals of ultrasound molecular imaging are the detection and imaging of ultrasound contrast agents (microbubbles), which are bound to specific vascular surface receptors. Imaging methods that can sensitively and selectively detect and distinguish bound microbubbles from freely circulating microbubbles (free microbubbles) and surrounding tissue are critically important for the practical application of ultrasound contrast molecular imaging. Microbubbles excited by low frequency acoustic pulses emit wide-band echoes with a bandwidth extending beyond 20 MHz; we refer to this technique as TLRH (transmission at a low frequency and reception at a high frequency). Using this wideband, transient echo, we have developed and implemented a targeted imaging technique incorporating a multi-frequency co-linear array and the Siemens Antares® imaging system. The multi-frequency co-linear array integrates a center 5.4 MHz array, used to receive echoes and produce radiation force, and two outer 1.5 MHz arrays used to transmit low frequency incident pulses. The targeted imaging technique makes use of an acoustic radiation force sub-sequence to enhance accumulation and a TLRH imaging sub-sequence to detect bound microbubbles. The radiofrequency (RF) data obtained from the TLRH imaging sub-sequence are processsed to separate echo signatures between tissue, free microbubbles, and bound microbubbles. By imaging biotin-coated microbubbles targeted to avidin-coated cellulose tubes, we demonstrate that the proposed method has a high contrast-to-tissue ratio (up to 34 dB) and a high sensitivity to bound microbubbles (with the ratio of echoes from bound microbubbles versus free microbubbles extending up to 23 dB). The effects of the imaging pulse acoustic pressure, the radiation force sub-sequence and the use of various slow-time filters on the targeted imaging quality are studied. The TLRH targeted imaging method is demonstrated in this study to provide sensitive and selective

Acute mortality in hospitalized patients undergoing echocardiography with and without an ultrasound contrast agent: results in 18,671 consecutive studies.

PubMed

Kusnetzky, Lisa L; Khalid, Adnan; Khumri, Taiyeb M; Moe, Tabitha G; Jones, Philip G; Main, Michael L

2008-04-29

We sought to define acute mortality in hospitalized patients undergoing clinically indicated echocardiography with and without use of an ultrasound contrast agent. The U.S. Food and Drug Administration recently issued a boxed warning and new contraindications for the perflutren-containing ultrasound contrast agents following post-marketing reports of 4 patient deaths that were temporally related to Definity (Bristol-Myers Squibb Medical Imaging, Billerica, Massachusetts) administration. To appreciate the incremental risk of any medical procedure, the ambient risk of untoward outcome in the population in question must first be defined. There are no published data on short-term major adverse cardiac events in hospitalized patients undergoing echocardiography, either with or without administration of an ultrasound contrast agent. A retrospective analysis of hospitalized patients undergoing clinically indicated echocardiography between January 2005 and October 2007, within Saint Luke's Health System, Kansas City, Missouri, was performed. Studies were separated into 2 groups, those performed without contrast enhancement (n = 12,475) and those performed with Definity (n = 6,196). Vital status within 24 h of the echocardiographic study was available for all patients using a combination of the Social Security Death Master File and Saint Luke's Health System medical records. Incidence of death within 24 h was compared by chi-square test between Definity and unenhanced procedures. Of the 18,671 patient events, 72 patients died within 24 h. Of those that underwent unenhanced echocardiography, 46 died within 24 h (0.37%). Of patients receiving Definity during the echocardiogram, 26 died within 24 h (0.42%). There was no statistical difference between these 2 groups (p = 0.60). No patient died within 1 h of the echocardiographic study. In a random sampling from the unenhanced (n = 201) and Definity groups (n = 202), patients who underwent Definity-enhanced echocardiography

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

PubMed Central

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

2017-01-01

We aimed to evaluate the diagnostic values of conventional ultrasound (US), ultrasound contrast (UC) and ultrasound elastography (UE) in distinguishing the benign and malignant thyroid nodules. A total of 100 patients with thyroid nodules receiving operative treatment were selected; they underwent the conventional US, UE and UC examinations before operation, respectively. The nodules received pathological examination after operation to distinguish benign from malignant lesions. The sensitivity, specificity and diagnostic accordance rate of each diagnostic method was evaluated by receiver operating characteristic (ROC) curve, and the area under the curve (AUC) of ROC was calculated. The manifestations of malignant thyroid nodules in conventional US examination were mostly the hypoecho, heterogeneous echo, irregular shape, unclear boundary, aspect ratio <1, microcalcification and irregular peripheral echo halo, and there were statistically significant differences compared with the benign nodules (P<0.05). UE showed that the differences between benign and malignant nodules in 2, 3 and 4 points were statistically significant (P<0.05). The manifestations of malignant nodules in UC were mostly the irregular shape, obscure boundary, no obvious enhancement, heterogeneous enhancement and visible perfusion defects, and there were statistically significant differences compared with the benign nodules (P<0.05). ROC curve showed that both sensitivity and specificity of UE and UC were superior to those of conventional US. AUC was the largest (AUC = 0.908) and the diagnostic value was the highest in the conventional US combined with UE and UC. Conventional US combined with elastography and UC can significantly improve the sensitivity, specificity and accuracy of diagnosis of benign and malignant thyroid nodules. PMID:28693244

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

PubMed

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

2017-07-01

We aimed to evaluate the diagnostic values of conventional ultrasound (US), ultrasound contrast (UC) and ultrasound elastography (UE) in distinguishing the benign and malignant thyroid nodules. A total of 100 patients with thyroid nodules receiving operative treatment were selected; they underwent the conventional US, UE and UC examinations before operation, respectively. The nodules received pathological examination after operation to distinguish benign from malignant lesions. The sensitivity, specificity and diagnostic accordance rate of each diagnostic method was evaluated by receiver operating characteristic (ROC) curve, and the area under the curve (AUC) of ROC was calculated. The manifestations of malignant thyroid nodules in conventional US examination were mostly the hypoecho, heterogeneous echo, irregular shape, unclear boundary, aspect ratio <1, microcalcification and irregular peripheral echo halo, and there were statistically significant differences compared with the benign nodules (P<0.05). UE showed that the differences between benign and malignant nodules in 2, 3 and 4 points were statistically significant (P<0.05). The manifestations of malignant nodules in UC were mostly the irregular shape, obscure boundary, no obvious enhancement, heterogeneous enhancement and visible perfusion defects, and there were statistically significant differences compared with the benign nodules (P<0.05). ROC curve showed that both sensitivity and specificity of UE and UC were superior to those of conventional US. AUC was the largest (AUC = 0.908) and the diagnostic value was the highest in the conventional US combined with UE and UC. Conventional US combined with elastography and UC can significantly improve the sensitivity, specificity and accuracy of diagnosis of benign and malignant thyroid nodules.

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

PubMed

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

2016-05-01

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

Constrained Adaptive Beamforming for Improved Contrast in Breast Ultrasound

DTIC Science & Technology

2007-06-01

Contr., vol. 54, no. 5, pp. 1045-1054, May 2007. Ranganathan , K. and W.F. Walker, “Cystic Resolution: A Performance Metric for Ultrasound Imaging...Ultrasonics Symposium. D.A. Guenther, Ranganathan , K. and W.F. Walker, “Design of Apodization Profiles Using a Cystic Resolution Metric for Ultrasound...diagnosis. 22 References: [1] V. Jackson, " Management of solid breast nodules: what is the role of sonography?," Radiology, vol. 196, pp. 14-15, 1995

Frequency sensitive mechanism in low-intensity ultrasound enhanced bioeffects

PubMed Central

Chama, Abdoulkadri; Subramanian, Anuradha; Viljoen, Hendrik J.

2017-01-01

This study presents two novel theoretical models to elucidate frequency sensitive nuclear mechanisms in low-intensity ultrasound enhanced bioeffects. In contrast to the typical 1.5 MHz pulsed ultrasound regime, our group previously experimentally confirmed that ultrasound stimulation of anchored chondrocytes at resonant frequency maximized gene expression of load inducible genes which are regulatory markers for cellular response to external stimuli. However, ERK phosphorylation displayed no frequency dependency, suggesting that the biochemical mechanisms involved in enhanced gene expression is downstream of ERK phosphorylation. To elucidate such underlying mechanisms, this study presents a theoretical model of an anchored cell, representing an in vitro chondrocyte, in an ultrasound field. The model results showed that the mechanical energy storage is maximized at the chondrocyte’s resonant frequency and the energy density in the nucleus is almost twice as high as in the cytoplasm. Next, a mechanochemical model was developed to link the mechanical stimulation of ultrasound and the increased mechanical energy density in the nucleus to the downstream targets of the ERK pathway. This study showed for the first time that ultrasound stimulation induces frequency dependent gene expression as a result of altered rates of transcription factors binding to chromatin. PMID:28763448

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

PubMed

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

2017-09-07

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

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

PubMed Central

Clevert, Dirk-Andre; Hirner-Eppeneder, Heidrun; Ingrisch, Michael; Moser, Matthias; Schuster, Jessica; Tadros, Dina; Schneider, Moritz; Kazmierczak, Philipp Maximilian; Reiser, Maximilian; Cyran, Clemens C.

2017-01-01

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

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

PubMed Central

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

2016-01-01

For many years, investigators have sought after high-resolution fluorescence imaging in centimeter-deep tissue because many interesting in vivo phenomena—such as the presence of immune system cells, tumor angiogenesis, and metastasis—may be located deep in tissue. Previously, we developed a new imaging technique to achieve high spatial resolution in sub-centimeter deep tissue phantoms named continuous-wave ultrasound-switchable fluorescence (CW-USF). The principle is to use a focused ultrasound wave to externally and locally switch on and off the fluorophore emission from a small volume (close to ultrasound focal volume). By making improvements in three aspects of this technique: excellent near-infrared USF contrast agents, a sensitive frequency-domain USF imaging system, and an effective signal processing algorithm, for the first time this study has achieved high spatial resolution (~ 900 μm) in 3-centimeter-deep tissue phantoms with high signal-to-noise ratio (SNR) and high sensitivity (3.4 picomoles of fluorophore in a volume of 68 nanoliters can be detected). We have achieved these results in both tissue-mimic phantoms and porcine muscle tissues. We have also demonstrated multi-color USF to image and distinguish two fluorophores with different wavelengths, which might be very useful for simultaneously imaging of multiple targets and observing their interactions in the future. This work has opened the door for future studies of high-resolution centimeter-deep tissue fluorescence imaging. PMID:27829050

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

NASA Astrophysics Data System (ADS)

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

2008-05-01

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

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

NASA Astrophysics Data System (ADS)

Han, Minah; Choi, Shinkook; Baek, Jongduk

2014-03-01

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

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

PubMed

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

2016-02-01

The purpose of this study was to optimize an ultrasound-targeted microbubble destruction (UTMD) technique to improve the in vivo transfection efficiency of the gene encoding enhanced green fluorescent protein (EGFP) in the synovial pannus in an antigen-induced arthritis rabbit model. A mixture of microbubbles and plasmids was locally injected into the knee joints of an antigen-induced arthritis (AIA) rabbits. The plasmid concentrations and ultrasound conditions were varied in the experiments. We also tested local articular and intravenous injections. The rabbits were divided into five groups: (1) ultrasound+microbubbles+plasmid; (2) ultrasound+plasmid; (3) microbubble+plasmid; (4) plasmid only; (5) untreated controls. EGFP expression was observed by fluorescent microscope and immunohistochemical staining in the synovial pannus of each group. The optimal plasmid dosage and ultrasound parameter were determined based on the results of EGFP expression and the present and absent of tissue damage under light microscopy. The irradiation procedure was performed to observe the duration of the EGFP expression in the synovial pannus and other tissues and organs, as well as the damage to the normal cells. The optimal condition was determined to be a 1-MHz ultrasound pulse applied for 5 min with a power output of 2 W/cm(2) and a 20% duty cycle along with 300 μg of plasmid. Under these conditions, the synovial pannus showed significant EGFP expression without significant damage to the surrounding normal tissue. The EGFP expression induced by the local intra-articular injection was significantly more increased than that induced by the intravenous injection. The EGFP expression in the synovial pannus of the ultrasound+microbubbles+plasmid group was significantly higher than that of the other four groups (P<0.05). The expression peaked on day 5, remained detectable on day 40 and disappeared on day 60. No EGFP expression was detected in the other tissues and organs. The UTMD

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

PubMed

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

2017-02-01

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

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

PubMed

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

2012-12-01

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

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

PubMed

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

2016-01-01

We performed a prospective study to evaluate the value of contrast-enhanced ultrasound (CEUS) in quantitative evaluation of renal cortex perfusion in patients suspected of early diabetic nephropathies (DN), with the estimated GFR (MDRD equation) as the gold standard. The study protocol was approved by the hospital review board; each patient gave written informed consent. Our study included 46 cases (21 males and 25 females, mean age 55.6 ± 4.14 years) of clinical confirmed early DN patients. After intravenous bolus injection of 1 ml sulfur hexafluoride microbubbles of ultrasound contrast agent, real time CEUS of renal cortex was performed successively using a 2-5 MHz convex probe. Time-intensity curves (TICs) and quantitative indexes were created with Qlab software. Receiver operating characteristic (ROC) curves were used to predict the diagnostic criteria of CEUS quantitative indexes, and their diagnostic efficiencies were compared with resistance index (RI) and peak systolic velocity (PSV) of renal segmental arteries by chi square test. Our control group included forty-five healthy volunteers. Difference was considered statistically significant with P <  0.05. Changes of area under curve (AUC), derived peak intensity (DPI) were statistically significant (P <  0.05). DPI less than 12 and AUC greater than 1400 had high utility in DN, with 71.7% and 67.3% sensitivity, 77.8% and 80.0% specificity. These results were significantly better than those obtained with RI and PSV which had no significant difference in early stage of DN (P > 0.05). CEUS might be helpful to improve early diagnosis of DN by quantitative analyses. AUC and DPI might be valuable quantitative indexes.

Contrast-enhanced magneto-photo-acoustic imaging in vivo using dual-contrast nanoparticles.

PubMed

Qu, Min; Mehrmohammadi, Mohammad; Truby, Ryan; Graf, Iulia; Homan, Kimberly; Emelianov, Stanislav

2014-06-01

By mapping the distribution of targeted plasmonic nanoparticles (NPs), photoacoustic (PA) imaging offers the potential to detect the pathologies in the early stages. However, optical absorption of the endogenous chromophores in the background tissue significantly reduces the contrast resolution of photoacoustic imaging. Previously, we introduced MPA imaging - a synergistic combination of magneto-motive ultrasound (MMUS) and PA imaging, and demonstrated MPA contrast enhancement using cell culture studies. In the current study, contrast enhancement was investigated in vivo using the magneto-photo-acoustic (MPA) imaging augmented with dual-contrast nanoparticles. Liposomal nanoparticles (LNPs) possessing both optical absorption and magnetic properties were injected into a murine tumor model. First, photoacoustic signals were generated from both the endogenous absorbers in the tissue and the liposomal nanoparticles in the tumor. Then, given significant differences in magnetic properties of tissue and LNPs, the magnetic response of LNPs (i.e. MMUS signal) was utilized to suppress the unwanted PA signals from the background tissue and thus improves the PA imaging contrast. In this study, we demonstrated the 3D MPA image of LNP-labeled xenografted tumor in a live animal. Compared to conventional PA imaging, the MPA images show significantly enhanced contrast between the nanoparticle-labeled tumor and the background tissue. Our results suggest the feasibility of MPA for high contrast in vivo mapping of dual-contrast nanoparticles.

Contrast-enhanced magneto-photo-acoustic imaging in vivo using dual-contrast nanoparticles☆

PubMed Central

Qu, Min; Mehrmohammadi, Mohammad; Truby, Ryan; Graf, Iulia; Homan, Kimberly; Emelianov, Stanislav

2014-01-01

By mapping the distribution of targeted plasmonic nanoparticles (NPs), photoacoustic (PA) imaging offers the potential to detect the pathologies in the early stages. However, optical absorption of the endogenous chromophores in the background tissue significantly reduces the contrast resolution of photoacoustic imaging. Previously, we introduced MPA imaging – a synergistic combination of magneto-motive ultrasound (MMUS) and PA imaging, and demonstrated MPA contrast enhancement using cell culture studies. In the current study, contrast enhancement was investigated in vivo using the magneto-photo-acoustic (MPA) imaging augmented with dual-contrast nanoparticles. Liposomal nanoparticles (LNPs) possessing both optical absorption and magnetic properties were injected into a murine tumor model. First, photoacoustic signals were generated from both the endogenous absorbers in the tissue and the liposomal nanoparticles in the tumor. Then, given significant differences in magnetic properties of tissue and LNPs, the magnetic response of LNPs (i.e. MMUS signal) was utilized to suppress the unwanted PA signals from the background tissue thus improving the PA imaging contrast. In this study, we demonstrated the 3D MPA imaging of LNP-labeled xenografted tumor in a live animal. Compared to conventional PA imaging, the MPA imaging show significantly enhanced contrast between the nanoparticle-labeled tumor and the background tissue. Our results suggest the feasibility of MPA imaging for high contrast in vivo mapping of dual-contrast nanoparticles. PMID:24653976

Piezoelectric Composite Micromachined Multifrequency Transducers for High-Resolution, High-Contrast Ultrasound Imaging for Improved Prostate Cancer Assessment

DTIC Science & Technology

2015-08-01

prostate cancer. In the preliminary in-vitro study , imaging resolution, contrast to tissue ratio, and lesion detectability will be assessed relative to...a Siemens EV- 8C4 transrectal ultrasound probe. In the in-vivo study , molecular imaging and microvascular mapping will both be performed to assess...single element tests, years 2 and 3 have included progress towards the design of the final a dual frequency linear array. These studies included the

pH/Ultrasound Dual-Responsive Gas Generator for Ultrasound Imaging-Guided Therapeutic Inertial Cavitation and Sonodynamic Therapy.

PubMed

Feng, Qianhua; Zhang, Wanxia; Yang, Xuemei; Li, Yuzhen; Hao, Yongwei; Zhang, Hongling; Hou, Lin; Zhang, Zhenzhong

2018-03-01

Herein, a pH/ultrasound dual-responsive gas generator is reported, which is based on mesoporous calcium carbonate (MCC) nanoparticles by loading sonosensitizer (hematoporphyrin monomethyl ether (HMME)) and modifying surface hyaluronic acid (HA). After pinpointing tumor regions with prominent targeting efficiency, HMME/MCC-HA decomposes instantaneously under the cotriggering of tumoral inherent acidic condition and ultrasound (US) irradiation, concurrently accompanying with CO 2 generation and HMME release with spatial/temporal resolution. Afterward, the CO 2 bubbling and bursting effect under US stimulus results in cavitation-mediated irreversible cell necrosis, as well as the blood vessel destruction to further occlude the blood supply, providing a "bystander effect." Meanwhile, reactive oxygen species generated from HMME can target the apoptotic pathways for effective sonodynamic therapy. Thus, the combination of apoptosis/necrosis with multimechanisms consequently results in a remarkable antitumor therapeutic efficacy, simultaneously minimizing the side effects on major organs. Moreover, the echogenic property of CO 2 make the nanoplatform as a powerful ultrasound contrast agent to identify cancerous lesions. Based on the above findings, such all-in-one drug delivery platform of HMME/MCC-HA is utilized to provide the US imaging guidance for therapeutic inertial cavitation and sonodynamic therapy simultaneously, which highlights possibilities of advancing cancer theranostics in biomedical fields. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dual-mode ultrasound arrays for image-guided targeting of atheromatous plaques

NASA Astrophysics Data System (ADS)

Ballard, John R.; Casper, Andrew J.; Liu, Dalong; Haritonova, Alyona; Shehata, Islam A.; Troutman, Mitchell; Ebbini, Emad S.

2012-11-01

A feasibility study was undertaken in order to investigate alternative noninvasive treatment options for atherosclerosis. In particular, the aim of this study was to investigate the potential use of Dual-Mode Ultrasound Arrays (DMUAs) for image guided treatment of atheromatous plaques. DMUAs offer a unique treatment paradigm for image-guided surgery allowing for robust image-based identification of tissue targets for localized application of HIFU. In this study we present imaging and therapeutic results form a 3.5 MHz, 64-element fenestrated prototype DMUA for targeting lesions in the femoral artery of familial hypercholesterolemic (FH) swine. Before treatment, diagnostic ultrasound was used to verify the presence of plaque in the femoral artery of the swine. Images obtained with the DMUA and a diagnostic (HST 15-8) transducer housed in the fenestration were analyzed and used for guidance in targeting of the plaque. Discrete therapeutic shots with an estimated focal intensity of 4000-5600 W/cm2 and 500-2000 msec duration were performed at several planes in the plaque. During therapy, pulsed HIFU was interleaved with single transmit focus imaging from the DMUA and M2D imaging from the diagnostic transducer for further analysis of lesion formation. After therapy, the swine's were recovered and later sacrificed after 4 and 7 days for histological analysis of lesion formation. At sacrifice, the lower half of the swine was perfused and the femoral artery with adjoining muscle was fixed and stained with H&E to characterize HIFU-induced lesions. Histology has confirmed that localized thermal lesion formation within the plaque was achieved according to the planned lesion maps. Furthermore, the damage was confined to the plaque tissue without damage to the intima. These results offer the promise of a new treatment potentially suited for vulnerable plaques. The results also provide the first real-time demonstration of DMUA technology in targeting fine tissue structures for

Target-specific contrast agents for magnetic resonance microscopy

PubMed Central

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

2009-01-01

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

Next generation ultrasound platforms for theranostics.

PubMed

Oddo, Letizia; Cerroni, Barbara; Domenici, Fabio; Bedini, Angelico; Bordi, Federico; Chiessi, Ester; Gerbes, Stefan; Paradossi, Gaio

2017-04-01

Microbubbles are a well-established contrast agent which improves diagnostic ultrasound imaging. During the last decade research has focused on expanding their use to include molecular imaging, targeted therapy and imaging modalities other than ultrasound. However, bioadhesion of targeted microbubbles under physiological flow conditions is still difficult to achieve, the main challenge being connected to the poor stability of lipid microbubbles in the body's circulation system. In this article, we investigate the use of polymeric microbubbles based on a poly (vinyl alcohol) shell as an alternative to lipid microbubbles. In particular, we report on the development of microbubble shell modification, using mild reaction conditions, with the aim of designing a multifunctional platform to enable diagnosis and therapy. Superparamagnetic iron oxide nanoparticles and a near infrared fluorescent probe, indocyanine green, are coupled to the bubbles surface in order to support magnetic resonance and fluorescence imaging. Furthermore, anchoring cyclic arginyl-glycyl-aspartic acid (RGD) peptide, and cyclodextrin molecules, allows targeting and drug loading, respectively. Last but not least, shell topography is provided by atomic force microscopy. These applications and features, together with the high echogenicity of poly (vinyl alcohol) microbubbles, may offer a more stable alternative to lipid microbubbles for the development of a multimodal theranostic platform. Copyright © 2016 Elsevier Inc. All rights reserved.

Interobserver Agreement for Contrast-Enhanced Ultrasound (CEUS)-Based Standardized Algorithms for the Diagnosis of Hepatocellular Carcinoma in High-Risk Patients.

PubMed

Schellhaas, Barbara; Pfeifer, Lukas; Kielisch, Christian; Goertz, Ruediger Stephan; Neurath, Markus F; Strobel, Deike

2018-06-07

 This pilot study aimed at assessing interobserver agreement with two contrast-enhanced ultrasound (CEUS) algorithms for the diagnosis of hepatocellular carcinoma (HCC) in high-risk patients.  Focal liver lesions in 55 high-risk patients were assessed independently by three blinded observers with two standardized CEUS algorithms: ESCULAP (Erlanger Synopsis of Contrast-Enhanced Ultrasound for Liver Lesion Assessment in Patients at risk) and ACR-CEUS-LI-RADSv.2016 (American College of Radiology CEUS-Liver Imaging Reporting and Data System). Lesions were categorized according to size and ultrasound contrast enhancement in the arterial, portal-venous and late phase. Interobserver agreement for assessment of enhancement pattern and categorization was compared between both CEUS algorithms. Additionally, diagnostic accuracy for the definitive diagnosis of HCC was compared. Histology and/or CE-MRI and follow-up served as reference standards.  55 patients were included in the study (male/female, 44/ 11; mean age: 65.9 years). 90.9 % had cirrhosis. Histological findings were available in 39/55 lesions (70.9 %). Reference standard of the 55 lesions revealed 48 HCCs, 2 intrahepatic cholangiocellular carcinomas (ICCs), and 5 non-HCC-non-ICC lesions. Interobserver agreement was moderate to substantial for arterial phase hyperenhancement (ĸ = 0.53 - 0.67), and fair to moderate for contrast washout in the portal-venous or late phase (ĸ = 0.33 - 0.53). Concerning the CEUS-based algorithms, the interreader agreement was substantial for the ESCULAP category (ĸ = 0.64 - 0.68) and fair for the CEUS-LI-RADS ® category (ĸ = 0.3 - 0.39). Disagreement between observers was mostly due to different perception of washout.  Interobserver agreement is better for ESCULAP than for CEUS-LI-RADS ® . This is mostly due to the fact that perception of contrast washout varies between different observers. However, interobserver agreement is good for

Biocompatible Nanocomplexes for Molecular Targeted MRI Contrast Agent

NASA Astrophysics Data System (ADS)

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

2009-07-01

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

Imaging features of hepatic angiomyolipomas on real-time contrast-enhanced ultrasound

PubMed Central

Wang, Z; Xu, H-X; Xie, X-Y; Xie, X-H; Kuang, M; Xu, Z-F; Liu, G-J; Chen, L-D; Lin, M-X; Lu, M-D

2010-01-01

The aim of this study was to evaluate the imaging features of hepatic angiomyolipoma (AML) on contrast-enhanced ultrasound (CEUS). The imaging features of 12 pathologically proven hepatic AML lesions in 10 patients who had undergone baseline ultrasound (BUS) and CEUS examinations were evaluated retrospectively. The enhancement extent, pattern and dynamic change, along with the enhancement process, on CEUS were analysed. The diagnostic results of BUS and CEUS before pathological examination were also recorded. The results showed that 75% (9/12) of the AML lesions exhibited mixed echogenicity on BUS and most showed remarkable hyperechogenicity in combination with a hypoechoic or anechoic portion. Arterial flow signals were detected in 75% (9/12) of the lesions on colour Doppler imaging. On CEUS, 66.7% (n = 8) of the 12 lesions exhibited hyperenhancement in the arterial phase, slight hyperenhancement (n = 2) or isoenhancement (n = 6) in the portal phase, and slight hyperenhancement (n = 1) or isoenhancement (n = 7) in the late phase. Three (25%) lesions exhibited hyperenhancement in the arterial phase and hypoenhancement in both portal and late phases. One (8.3%) lesion exhibited hypoenhancement throughout the CEUS process. Before pathological examination with BUS, only 3 (25%) lesions were correctly diagnosed as hepatic AML. Conversely, on CEUS, correct diagnoses were made for 66.8% (8/12) of hepatic AMLs. Therefore, arterial hyperenhancement and subsequent sustained enhancement on CEUS were found in the majority of hepatic AMLs. The combination of BUS and CEUS leads to the correct diagnosis in the majority of hepatic AMLs, and is higher than the success rate achieved by BUS alone. PMID:19723766

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

PubMed Central

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

2014-01-01

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

Piezoelectric Composite Micromachined Multifrequency Transducers for High-Resolution, High-Contrast Ultrasound Imaging for Improved Prostate Cancer Assessment

DTIC Science & Technology

2014-08-01

and in (b) a standard animal model of prostate cancer. In the preliminary in-vitro study , imaging resolution, contrast to tissue ratio, and lesion...detectability will be assessed relative to a Siemens EV- 8C4 transrectal ultrasound probe. In the in-vivo study , molecular imaging and microvascular...lesions will be imaged at several axial depths using our prototype array and the Siemens EV-8C4 clinical TRUS probe. A blinded reader study will be

Application of automatic threshold in dynamic target recognition with low contrast

NASA Astrophysics Data System (ADS)

Miao, Hua; Guo, Xiaoming; Chen, Yu

2014-11-01

Hybrid photoelectric joint transform correlator can realize automatic real-time recognition with high precision through the combination of optical devices and electronic devices. When recognizing targets with low contrast using photoelectric joint transform correlator, because of the difference of attitude, brightness and grayscale between target and template, only four to five frames of dynamic targets can be recognized without any processing. CCD camera is used to capture the dynamic target images and the capturing speed of CCD is 25 frames per second. Automatic threshold has many advantages like fast processing speed, effectively shielding noise interference, enhancing diffraction energy of useful information and better reserving outline of target and template, so this method plays a very important role in target recognition with optical correlation method. However, the automatic obtained threshold by program can not achieve the best recognition results for dynamic targets. The reason is that outline information is broken to some extent. Optimal threshold is obtained by manual intervention in most cases. Aiming at the characteristics of dynamic targets, the processing program of improved automatic threshold is finished by multiplying OTSU threshold of target and template by scale coefficient of the processed image, and combining with mathematical morphology. The optimal threshold can be achieved automatically by improved automatic threshold processing for dynamic low contrast target images. The recognition rate of dynamic targets is improved through decreased background noise effect and increased correlation information. A series of dynamic tank images with the speed about 70 km/h are adapted as target images. The 1st frame of this series of tanks can correlate only with the 3rd frame without any processing. Through OTSU threshold, the 80th frame can be recognized. By automatic threshold processing of the joint images, this number can be increased to 89 frames

4-D spatiotemporal analysis of ultrasound contrast agent dispersion for prostate cancer localization: a feasibility study.

PubMed

Schalk, Stefan G; Demi, Libertario; Smeenge, Martijn; Mills, David M; Wallace, Kirk D; de la Rosette, Jean J M C H; Wijkstra, Hessel; Mischi, Massimo

2015-05-01

Currently, nonradical treatment for prostate cancer is hampered by the lack of reliable diagnostics. Contrastultrasound dispersion imaging (CUDI) has recently shown great potential as a prostate cancer imaging technique. CUDI estimates the local dispersion of intravenously injected contrast agents, imaged by transrectal dynamic contrast-enhanced ultrasound (DCE-US), to detect angiogenic processes related to tumor growth. The best CUDI results have so far been obtained by similarity analysis of the contrast kinetics in neighboring pixels. To date, CUDI has been investigated in 2-D only. In this paper, an implementation of 3-D CUDI based on spatiotemporal similarity analysis of 4-D DCE-US is described. Different from 2-D methods, 3-D CUDI permits analysis of the entire prostate using a single injection of contrast agent. To perform 3-D CUDI, a new strategy was designed to estimate the similarity in the contrast kinetics at each voxel, and data processing steps were adjusted to the characteristics of 4-D DCE-US images. The technical feasibility of 4-D DCE-US in 3-D CUDI was assessed and confirmed. Additionally, in a preliminary validation in two patients, dispersion maps by 3-D CUDI were quantitatively compared with those by 2-D CUDI and with 12-core systematic biopsies with promising results.

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

PubMed

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

2016-05-01

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

Infrared small target detection based on multiscale center-surround contrast measure

NASA Astrophysics Data System (ADS)

Fu, Hao; Long, Yunli; Zhu, Ran; An, Wei

2018-04-01

Infrared(IR) small target detection plays a critical role in the Infrared Search And Track (IRST) system. Although it has been studied for years, there are some difficulties remained to the clutter environment. According to the principle of human discrimination of small targets from a natural scene that there is a signature of discontinuity between the object and its neighboring regions, we develop an efficient method for infrared small target detection called multiscale centersurround contrast measure (MCSCM). First, to determine the maximum neighboring window size, an entropy-based window selection technique is used. Then, we construct a novel multiscale center-surround contrast measure to calculate the saliency map. Compared with the original image, the MCSCM map has less background clutters and noise residual. Subsequently, a simple threshold is used to segment the target. Experimental results show our method achieves better performance.

Anthropomorphic cardiac ultrasound phantom.

PubMed

Smith, S W; Rinaldi, J E

1989-10-01

A new phantom is described which simulates the human cardiac anatomy for applications in ultrasound imaging, ultrasound Doppler, and color-flow Doppler imaging. The phantom consists of a polymer left ventricle which includes a prosthetic mitral and aortic valve and is connected to a mock circulatory loop. Aerated tap water serves as a blood simulating fluid and ultrasound contrast medium within the circulatory loop. The left ventricle is housed in a Lexan ultrasound visualization chamber which includes ultrasound viewing ports and acoustic absorbers. A piston pump connected to the visualization chamber by a single port pumps degassed water within the chamber which in turn pumps the left ventricle. Real-time ultrasound images and Doppler studies measure flow patterns through the valves and within the left ventricle.

Contrast-enhanced ultrasonography vs B-mode ultrasound for visualization of intima-media thickness and detection of plaques in human carotid arteries.

PubMed

Shah, Benoy N; Chahal, Navtej S; Kooner, Jaspal S; Senior, Roxy

2017-05-01

Carotid intima-media thickness (IMT) and plaque are recognized markers of increased risk for cerebrovascular events. Accurate visualization of the IMT and plaques is dependent upon image quality. Ultrasound contrast agents improve image quality during echocardiography-this study assessed whether contrast-enhanced ultrasound (CEUS) improves carotid IMT visualization and plaque detection in an asymptomatic population. Individuals free from known cardiovascular disease, enrolled in a community study, underwent B-mode and CEUS carotid imaging. Each carotid artery was divided into 10 segments (far and near walls of the proximal, mid and distal segments of the common carotid artery, the carotid bulb, and internal carotid artery). Visualization of the IMT complex and plaque assessments was made during both B-mode and CEUS imaging for all enrolled subjects, a total of 175 individuals (mean age 65±9 years). Visualization of the IMT was significantly improved during CEUS compared with B-mode imaging, in both near and far walls of the carotid arteries (% IMT visualization during B-mode vs CEUS imaging: 61% vs 94% and 66% vs 95% for right and left carotid arteries, respectively, P<.001 for both). Additionally, a greater number of plaques were detected during CEUS imaging compared with B-mode imaging (367 plaques vs 350 plaques, P=.02). Contrast-enhanced ultrasound improves visualization of the intima-media complex, in both near and far walls, of the common and internal carotid arteries and permits greater detection of carotid plaques. Further studies are required to determine whether there is incremental clinical and prognostic benefit related to superior plaque detection by CEUS. © 2017, Wiley Periodicals, Inc.

Ultrasound physics and instrumentation for pathologists.

PubMed

Lieu, David

2010-10-01

Interest in pathologist-performed ultrasound-guided fine-needle aspiration is increasing. Educational courses discuss clinical ultrasound and biopsy techniques but not ultrasound physics and instrumentation. To review modern ultrasound physics and instrumentation to help pathologists understand the basis of modern ultrasound. A review of recent literature and textbooks was performed. Ultrasound physics and instrumentation are the foundations of clinical ultrasound. The key physical principle is the piezoelectric effect. When stimulated by an electric current, certain crystals vibrate and produce ultrasound. A hand-held transducer converts electricity into ultrasound, transmits it into tissue, and listens for reflected ultrasound to return. The returning echoes are converted into electrical signals and used to create a 2-dimensional gray-scale image. Scanning at a high frequency improves axial resolution but has low tissue penetration. Electronic focusing moves the long-axis focus to depth of the object of interest and improves lateral resolution. The short-axis focus in 1-dimensional transducers is fixed, which results in poor elevational resolution away from the focal zone. Using multiple foci improves lateral resolution but degrades temporal resolution. The sonographer can adjust the dynamic range to change contrast and bring out subtle masses. Contrast resolution is limited by processing speed, monitor resolution, and gray-scale perception of the human eye. Ultrasound is an evolving field. New technologies include miniaturization, spatial compound imaging, tissue harmonics, and multidimensional transducers. Clinical cytopathologists who understand ultrasound physics, instrumentation, and clinical ultrasound are ready for the challenges of cytopathologist-performed ultrasound-guided fine-needle aspiration and core-needle biopsy in the 21st century.

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

PubMed

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

2017-09-01

A comparison is made of two contrast-enhanced ultrasound (CEUS) algorithms for the diagnosis of hepatocellular carcinoma (HCC) in high-risk patients: Erlanger Synopsis of Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at Risk (ESCULAP) and American College of Radiology Contrast-Enhanced Ultrasound-Liver Imaging Reporting and Data System (ACR-CEUS-LI-RADSv.2016). Focal liver lesions in 100 high-risk patients were assessed using both CEUS algorithms (ESCULAP and CEUS-LI-RADSv.2016) for a direct comparison. Lesions were categorized according to size and contrast enhancement in the arterial, portal venous and late phases.For the definite diagnosis of HCC, categories ESCULAP-4, ESCULAP-Tr and ESCULAP-V and CEUS-LI-RADS-LR-5, LR-Tr and LR-5-V were compared. In addition, CEUS-LI-RADS-category LR-M (definitely/probably malignant, but not specific for HCC) and ESCULAP-category C [intrahepatic cholangiocellular carcinoma (ICC)] were compared.Histology, CE-computed tomography and CE-MRI served as reference standards. The reference standard among 100 lesions included 87 HCCs, six ICCs and seven non-HCC-non-ICC-lesions. For the diagnosis of HCC, the diagnostic accuracy of CEUS was significantly higher with ESCULAP versus CEUS-LI-RADS (94.3%/72.4%; p<0.01). Sensitivity, specificity and positive predictive value (PPV) and negative predictive value for ESCULAP/CEUS-LI-RADS were 94.3%/72.4%; 61.5%/69.2%; 94.3%/94%; and 61.5%/27.3%, respectively.The diagnostic accuracy for ICC (LR-M/ESCULAP-C) was identical with both algorithms (50%), with higher PPV for ESCULAP-C versus LR-M (75 vs. 50%). CEUS-based algorithms contribute toward standardized assessment and reporting of HCC-suspect lesions in high-risk patients. ESCULAP shows significantly higher diagnostic accuracy, sensitivity and negative predictive value with no loss of specificity compared with CEUS-LI-RADS. Both algorithms have an excellent PPV. Arterial hyperenhancement is the key feature for the

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

PubMed

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

2017-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

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

PubMed

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

2018-05-01

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

Two- and three-dimensional ultrasound imaging to facilitate detection and targeting of taut bands in myofascial pain syndrome.

PubMed

Shankar, Hariharan; Reddy, Sapna

2012-07-01

Ultrasound imaging has gained acceptance in pain management interventions. Features of myofascial pain syndrome have been explored using ultrasound imaging and elastography. There is a paucity of reports showing the benefit clinically. This report provides three-dimensional features of taut bands and highlights the advantages of using two-dimensional ultrasound imaging to improve targeting of taut bands in deeper locations. Fifty-eight-year-old man with pain and decreased range of motion of the right shoulder was referred for further management of pain above the scapula after having failed conservative management for myofascial pain syndrome. Three-dimensional ultrasound images provided evidence of aberrancy in the architecture of the muscle fascicles around the taut bands compared to the adjacent normal muscle tissue during serial sectioning of the accrued image. On two-dimensional ultrasound imaging over the palpated taut band, areas of hyperechogenicity were visualized in the trapezius and supraspinatus muscles. Subsequently, the patient received ultrasound-guided real-time lidocaine injections to the trigger points with successful resolution of symptoms. This is a successful demonstration of utility of ultrasound imaging of taut bands in the management of myofascial pain syndrome. Utility of this imaging modality in myofascial pain syndrome requires further clinical validation. Wiley Periodicals, Inc.

Medical Imaging with Ultrasound: Some Basic Physics.

ERIC Educational Resources Information Center

Gosling, R.

1989-01-01

Discussed are medical applications of ultrasound. The physics of the wave nature of ultrasound including its propagation and production, return by the body, spatial and contrast resolution, attenuation, image formation using pulsed echo ultrasound techniques, measurement of velocity and duplex scanning are described. (YP)

Fabrication of Indocyanine Green and 2H, 3H-perfluoropentane loaded microbubbles for fluorescence and ultrasound imaging

NASA Astrophysics Data System (ADS)

He, Yutong; Wu, Qiang; Ma, Rong; Chang, Shufang; Shao, Pengfei; Xu, Ronald

2016-03-01

As a near-infrared (NIR) fluorescence dye, Indocyanine Green (ICG) has not gained broader clinical applications, owing to its multiple limitations such as concentration-dependent aggregation, low fluorescence quantum yield, poor physicochemical stability and rapid elimination from the body. In the meanwhile, 2H,3H-perfluoropentane (H-PFP) has been widely studied in ultrasound imaging as a vehicle for targeted delivery of contrast agents and drugs. We synthesized a novel dual-modal fluorescence and ultrasound contrast agent by encapsulating ICG and H-PFP in lipid microbubbles using a liquid-driven coaxial flow focusing (LDCFF) process. Uniform microbubbles with the sizes ranging from 1-10um and great ICG loading efficiency was achieved by this method. Our benchtop experiments showed that ICG/H-PFP microbubbles exhibited less aggregation, increased fluorescence intensity and more stable photostability compared to free ICG aqueous solution. Our phantom experiments demonstrated that ICG/H-PFP microbubbles enhanced the imaging contrasts in fluorescence imaging and ultrasonography. Our animal experiments indicated that ICG/H-PFP microbubbles extended the ICG life time and facilitated dual mode fluorescence and ultrasound imaging in vivo.

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

Contrast-enhanced ultrasound mapping of sentinel lymph nodes in oral tongue cancer-a pilot study.

PubMed

Gvetadze, Shalva R; Xiong, Ping; Lv, Mingming; Li, Jun; Hu, Jingzhou; Ilkaev, Konstantin D; Yang, Xin; Sun, Jian

2017-03-01

To assess the usefulness of contrast-enhanced ultrasound (CEUS) with peritumoral injection of microbubble contrast agent for detecting the sentinel lymph nodes for oral tongue carcinoma. The study was carried out on 12 patients with T1-2cN0 oral tongue cancer. A radical resection of the primary disease was planned; a modified radical supraomohyoid neck dissection was reserved for patients with larger lesions (T2, n = 8). The treatment plan and execution were not influenced by sentinel node mapping outcome. The Sonovue ™ contrast agent (Bracco Imaging, Milan, Italy) was utilized. After detection, the position and radiologic features of the sentinel nodes were recorded. The identification rate of the sentinel nodes was 91.7%; one patient failed to demonstrate any enhanced areas. A total of 15 sentinel nodes were found in the rest of the 11 cases, with a mean of 1.4 nodes for each patient. The sentinel nodes were localized in: Level IA-1 (6.7%) node; Level IB-11 (73.3%) nodes; Level IIA-3 (20.0%) nodes. No contrast-related adverse effects were observed. For oral tongue tumours, CEUS is a feasible and potentially widely available approach of sentinel node mapping. Further clinical research is required to establish the position of CEUS detection of the sentinel nodes in oral cavity cancers.

A targeted nanoglobular contrast agent from host-guest self-assembly for MR cancer molecular imaging

PubMed Central

Zhou, Zhuxian; Han, Zhen; Lu, Zheng-Rong

2016-01-01

The clinical application of nanoparticular Gd(III) based contrast agents for tumor molecular MRI has been hindered by safety concerns associated with prolonged tissue retention, although they can produce strong tumor enhancement. In this study, a targeted well-defined cyclodextrin-based nanoglobular contrast agent was developed through self-assembly driven by host-guest interactions for safe and effective cancer molecular MRI. Multiple β-cyclodextrins attached POSS (polyhedral oligomeric silsesquioxane) nanoglobule was used as host molecule. Adamantane–modified macrocyclic Gd(III) contrast agent, cRGD (cyclic RGDfK peptide) targeting ligand and fluorescent probe was used as guest molecules. The targeted host-guest nanoglobular contrast agent cRGD-POSS-βCD-(DOTA-Gd) specifically bond to αvβ3 integrin in malignant 4T1 breast tumor and provided greater contrast enhancement than the corresponding non-targeted agent. The agent also provided significant fluorescence signal in tumor tissue. The histological analysis of the tumor tissue confirmed its specific and effective targeting to αvβ3 integrin. The targeted imaging agent has a potential for specific cancer molecular MR and fluorescent imaging. PMID:26874280

A targeted nanoglobular contrast agent from host-guest self-assembly for MR cancer molecular imaging.

PubMed

Zhou, Zhuxian; Han, Zhen; Lu, Zheng-Rong

2016-04-01

The clinical application of nanoparticular Gd(III) based contrast agents for tumor molecular MRI has been hindered by safety concerns associated with prolonged tissue retention, although they can produce strong tumor enhancement. In this study, a targeted well-defined cyclodextrin-based nanoglobular contrast agent was developed through self-assembly driven by host-guest interactions for safe and effective cancer molecular MRI. Multiple β-cyclodextrins attached POSS (polyhedral oligomeric silsesquioxane) nanoglobule was used as host molecule. Adamantane-modified macrocyclic Gd(III) contrast agent, cRGD (cyclic RGDfK peptide) targeting ligand and fluorescent probe was used as guest molecules. The targeted host-guest nanoglobular contrast agent cRGD-POSS-βCD-(DOTA-Gd) specifically bond to αvβ3 integrin in malignant 4T1 breast tumor and provided greater contrast enhancement than the corresponding non-targeted agent. The agent also provided significant fluorescence signal in tumor tissue. The histological analysis of the tumor tissue confirmed its specific and effective targeting to αvβ3 integrin. The targeted imaging agent has a potential for specific cancer molecular MR and fluorescent imaging. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intraprocedure contrast enhanced ultrasound: the value in assessing the effect of ultrasound-guided high intensity focused ultrasound ablation for uterine fibroids.

PubMed

Peng, Song; Hu, Liang; Chen, Wenzhi; Chen, Jinyun; Yang, Caiyong; Wang, Xi; Zhang, Rong; Wang, Zhibiao; Zhang, Lian

2015-04-01

To investigate the value of microbubble contrast-enhanced ultrasound (CEUS) in evaluating the treatment response of uterine fibroids to HIFU ablation. Sixty-eight patients with a solitary uterine fibroid from the First Affiliated Hospital of Chongqing Medical University were included and analyzed. All patients underwent pre- and post-treatment magnetic resonance imaging (MRI) with a standardized protocol, as well as pre-evaluation, intraprocedure, and immediate post-treatment CEUS. CEUS and MRI were compared by different radiologists. In comparison with MRI, CEUS showed that the size of fibroids, volume of fibroids, size of non-perfused regions, non-perfused volume (NPV) or fractional ablation (NPV ratio) was similar to that of MRI. In terms of CEUS examination results, the median volume of fibroids was 75.2 (interquartile range, 34.2-127.3) cm(3), the median non-perfused volume was 54.9 (interquartile range, 28.0-98.1) cm(3), the mean fractional ablation was 83.7±13.6 (range, 30.0-100.0)%. In terms of MRI examination results, the median volume of fibroids was 74.1 (interquartile range, 33.4-116.2) cm(3). On the basis of contrast-enhanced T1-weighted images immediately after HIFU treatment, the median non-perfused volume was 58.5 (interquartile range, 27.7-100.0) cm(3), the average fractional ablation was 84.2±14.2 (range, 40.0-100.0)%. CEUS clearly showed the size of fibroids and the non-perfused areas of the fibroid. Results from CEUS correlated well with results obtained from MRI. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

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

Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood-brain barrier opening.

PubMed

Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel; Konofagou, Elisa E

2017-04-01

Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood-brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood-brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo.

Microcapsules: Reverse Sonoporation and Long-lasting, Safe Contrast

NASA Astrophysics Data System (ADS)

Wrenn, Steven; Dicker, Stephen; Small, Eleanor; Maghnouj, Abdelouahid; Hahn, Stephan A.; Mleczko, Michał; Hensel, Karin; Schmitz, Georg

We present a novel vehicle designed to serve the dual roles of enhanced ultrasound contrast and ultrasound-triggered drug delivery. The vehicle is comprised of a microcapsule that is filled with water in whose aqueous core a population of freely floating, phospholipid-coated microbubbles is suspended. At ultrasound intensities below the inertial cavitation threshold of the microbubbles, the microbubbles provide enhanced ultrasound contrast. The measured contrast is comparable in strength with SonoVue®. Encapsulation of microbubbles within microcapsules putatively eliminates - or at least significantly slows - dissolution of gas in the bulk aqueous medium, thereby avoiding disappearance of microbubbles that would otherwise occur due to pressure-induced gas diffusion across the surfactant monolayer coating the microbubble-water interface. Results suggest that our vehicle might provide longer lasting contrast in a clinical setting. We demonstrate that encapsulation of the microbubbles within microcapsules causes at least a doubling of the ultrasound intensity necessary to induce inertial cavitation. Moreover, no cell death was observed when cells were insonified in the presence of microbubble-containing microcapsules, whereas appreciable cell death occurs with unencapsulated microbubbles. These results point toward a potential safety benefit during ultrasound contrast imaging by using encapsulated microbubbles. Studies are underway to investigate the feasibility of ultrasound-triggered release of drug from the microcapsules, owing to inertial- or stable-cavitation, or both. Whereas leakage from polymeric microcapsule shells, such as poly(lactic acid), seemingly requires shell rupture and is exceedingly difficult to achieve, leakage across a lipid bilayer microcapsule shells appears feasible. Leakage across a bilayer shell has the additional benefit that the leakage mechanism can be tuned via phase behavior (liquid-ordered versus liquid-disordered) and cavitation

Focused Ultrasound-Induced Blood-Brain Barrier Opening: Association with Mechanical Index and Cavitation Index Analyzed by Dynamic Contrast-Enhanced Magnetic-Resonance Imaging

NASA Astrophysics Data System (ADS)

Chu, Po-Chun; Chai, Wen-Yen; Tsai, Chih-Hung; Kang, Shih-Tsung; Yeh, Chih-Kuang; Liu, Hao-Li

2016-09-01

Focused ultrasound (FUS) with microbubbles can temporally open the blood-brain barrier (BBB), and the cavitation activities of microbubbles play a key role in the BBB-opening process. Previous attempts used contrast-enhanced magnetic resonance imaging (CE-MRI) to correlate the mechanical index (MI) with the scale of BBB-opening, but MI only partially gauged acoustic activities, and CE-MRI did not fully explore correlations of pharmacodynamic/pharmacokinetic behaviors. Recently, the cavitation index (CI) has been derived to serve as an indicator of microbubble-ultrasound stable cavitation, and may also serve as a valid indicator to gauge the level of FUS-induced BBB opening. This study investigates the feasibility of gauging FUS-induced BBB opened level via the two indexes, MI and CI, through dynamic contrast-enhanced (DCE)-MRI analysis as well as passive cavitation detection (PCD) analysis. Pharmacodynamic/pharmacokinetic parameters derived from DCE-MRI were characterized to identify the scale of FUS-induced BBB opening. Our results demonstrated that DCE-MRI can successfully access pharmacodynamic/pharmacokinetic BBB-opened behavior, and was highly correlated both with MI and CI, implying the feasibility in using these two indices to gauge the scale of FUS-induced BBB opening. The proposed finding may facilitate the design toward using focused ultrasound as a safe and reliable noninvasive CNS drug delivery.

Focused Ultrasound-Induced Blood-Brain Barrier Opening: Association with Mechanical Index and Cavitation Index Analyzed by Dynamic Contrast-Enhanced Magnetic-Resonance Imaging.

PubMed

Chu, Po-Chun; Chai, Wen-Yen; Tsai, Chih-Hung; Kang, Shih-Tsung; Yeh, Chih-Kuang; Liu, Hao-Li

2016-09-15

Focused ultrasound (FUS) with microbubbles can temporally open the blood-brain barrier (BBB), and the cavitation activities of microbubbles play a key role in the BBB-opening process. Previous attempts used contrast-enhanced magnetic resonance imaging (CE-MRI) to correlate the mechanical index (MI) with the scale of BBB-opening, but MI only partially gauged acoustic activities, and CE-MRI did not fully explore correlations of pharmacodynamic/pharmacokinetic behaviors. Recently, the cavitation index (CI) has been derived to serve as an indicator of microbubble-ultrasound stable cavitation, and may also serve as a valid indicator to gauge the level of FUS-induced BBB opening. This study investigates the feasibility of gauging FUS-induced BBB opened level via the two indexes, MI and CI, through dynamic contrast-enhanced (DCE)-MRI analysis as well as passive cavitation detection (PCD) analysis. Pharmacodynamic/pharmacokinetic parameters derived from DCE-MRI were characterized to identify the scale of FUS-induced BBB opening. Our results demonstrated that DCE-MRI can successfully access pharmacodynamic/pharmacokinetic BBB-opened behavior, and was highly correlated both with MI and CI, implying the feasibility in using these two indices to gauge the scale of FUS-induced BBB opening. The proposed finding may facilitate the design toward using focused ultrasound as a safe and reliable noninvasive CNS drug delivery.

Aptamer-Targeted Gold Nanoparticles As Molecular-Specific Contrast Agents for Reflectance Imaging

PubMed Central

2008-01-01

Targeted metallic nanoparticles have shown potential as a platform for development of molecular-specific contrast agents. Aptamers have recently been demonstrated as ideal candidates for molecular targeting applications. In this study, we investigated the development of aptamer-based gold nanoparticles as contrast agents, using aptamers as targeting agents and gold nanoparticles as imaging agents. We devised a novel conjugation approach using an extended aptamer design where the extension is complementary to an oligonucleotide sequence attached to the surface of the gold nanoparticles. The chemical and optical properties of the aptamer−gold conjugates were characterized using size measurements and oligonucleotide quantitation assays. We demonstrate this conjugation approach to create a contrast agent designed for detection of prostate-specific membrane antigen (PSMA), obtaining reflectance images of PSMA(+) and PSMA(−) cell lines treated with the anti-PSMA aptamer−gold conjugates. This design strategy can easily be modified to incorporate multifunctional agents as part of a multimodal platform for reflectance imaging applications. PMID:18512972

Acoustic response of compliable microvessels containing ultrasound contrast agents

NASA Astrophysics Data System (ADS)

Qin, Shengping; Ferrara, Katherine W.

2006-10-01

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

MO-AB-210-00: Diagnostic Ultrasound Imaging Quality Control and High Intensity Focused Ultrasound Therapy Hands-On Workshop

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The goal of this ultrasound hands-on workshop is to demonstrate advancements in high intensity focused ultrasound (HIFU) and to demonstrate quality control (QC) testing in diagnostic ultrasound. HIFU is a therapeutic modality that uses ultrasound waves as carriers of energy. HIFU is used to focus a beam of ultrasound energy into a small volume at specific target locations within the body. The focused beam causes localized high temperatures and produces a well-defined regions of necrosis. This completely non-invasive technology has great potential for tumor ablation and targeted drug delivery. At the workshop, attendees will see configurations, applications, and hands-on demonstrationsmore » with on-site instructors at separate stations. The involvement of medical physicists in diagnostic ultrasound imaging service is increasing due to QC and accreditation requirements. At the workshop, an array of ultrasound testing phantoms and ultrasound scanners will be provided for attendees to learn diagnostic ultrasound QC in a hands-on environment with live demonstrations of the techniques. Target audience: Medical physicists and other medical professionals in diagnostic imaging and radiation oncology with interest in high-intensity focused ultrasound and in diagnostic ultrasound QC. Learning Objectives: Learn ultrasound physics and safety for HIFU applications through live demonstrations Get an overview of the state-of-the art in HIFU technologies and equipment Gain familiarity with common elements of a quality control program for diagnostic ultrasound imaging Identify QC tools available for testing diagnostic ultrasound systems and learn how to use these tools List of supporting vendors for HIFU and diagnostic ultrasound QC hands-on workshop: Philips Healthcare Alpinion Medical Systems Verasonics, Inc Zonare Medical Systems, Inc Computerized Imaging Reference Systems (CIRS), Inc. GAMMEX, Inc., Cablon Medical BV Steffen Sammet: NIH/NCI grant 5R25CA132822, NIH/NINDS grant

High-intensity interstitial ultrasound for thermal ablation of focal cancer targets in prostate

NASA Astrophysics Data System (ADS)

Salgaonkar, Vasant A.; Scott, Serena; Kurhanewicz, John; Diederich, Chris J.

2017-03-01

Recent advances in image based techniques such as multi-parametric MRI (MP-MRI) can provide precise targeting of focal disease in the prostate. Thermal ablation of such cancer targets while avoiding rectum, urethra, neurovascular bundles (NVB) and sphincter is clinically challenging. The approach described here employs multi-element ultrasound linear arrays designed for transperineal placement within prostate. They consist of independently powered sectored tubular transducers (6.5 - 8.0 MHz) that provide spatial control of energy deposition in angle and length. Volumetric ablation strategies were investigated through patient-specific biothermal models based on Pennes bioheat transfer equation. The acoustic and heat transfer models used here have been validated in several previous simulation and experimental studies. Focal disease sites in prostate were identified through multi-parametric MR images of representative patient cases (n=3). Focal cancer lesions and critical anatomy (prostate, urethra, rectum, bladder, seminal vesicles) were manually segmented (Mimics, Materialise) and converted to 3D finite element meshes (3-Matic, Materialise). The chosen test cases consisted of patients with medium and large sized glands and models of bulk tissue ablation covered volumes in a single quadrant in posterior prostate, hemi-gland targets and "hockey-stick" targets (lesions in three quadrants). Ultrasound applicator placement was determined such that devices were positioned along the prostate periphery while avoiding surrounding anatomy. Transducer sector angles were chosen based on applicator location within limits of fabrication practicability. Thermal models were numerically solved using finite element methods (FEM) in COMSOL Multiphysics. Temperature and thermal dose distributions were calculated to determine treated volumes (> 240 CEM43C, >52 °C) and safety profiles (<10 CEM43C, <45 °C) for nerve, rectal and urethral sparing. Modeling studies indicated that focal

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

NASA Astrophysics Data System (ADS)

Zhou, Yi-Tong; Crawshaw, Richard D.

1991-08-01

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

Gauging the likelihood of stable cavitation from ultrasound contrast agents

NASA Astrophysics Data System (ADS)

Bader, Kenneth B.; Holland, Christy K.

2013-01-01

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

Gauging the likelihood of stable cavitation from ultrasound contrast agents.

PubMed

Bader, Kenneth B; Holland, Christy K

2013-01-07

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

Gauging the likelihood of stable cavitation from ultrasound contrast agents

PubMed Central

Bader, Kenneth B; Holland, Christy K

2015-01-01

The mechanical index (MI) was formulated to gauge the likelihood of adverse bioeffects from inertial cavitation. However, the MI formulation did not consider bubble activity from stable cavitation. This type of bubble activity can be readily nucleated from ultrasound contrast agents (UCAs) and has the potential to promote beneficial bioeffects. Here, the presence of stable cavitation is determined numerically by tracking the onset of subharmonic oscillations within a population of bubbles for frequencies up to 7 MHz and peak rarefactional pressures up to 3 MPa. In addition, the acoustic pressure rupture threshold of an UCA population was determined using the Marmottant model. The threshold for subharmonic emissions of optimally sized bubbles was found to be lower than the inertial cavitation threshold for all frequencies studied. The rupture thresholds of optimally sized UCAs were found to be lower than the threshold for subharmonic emissions for either single cycle or steady state acoustic excitations. Because the thresholds of both subharmonic emissions and UCA rupture are linearly dependent on frequency, an index of the form ICAV = Pr/f (where Pr is the peak rarefactional pressure in MPa and f is the frequency in MHz) was derived to gauge the likelihood of subharmonic emissions due to stable cavitation activity nucleated from UCAs. PMID:23221109

Targeted Prostate Thermal Therapy with Catheter-Based Ultrasound Devices and MR Thermal Monitoring

NASA Astrophysics Data System (ADS)

Diederich, Chris; Ross, Anthony; Kinsey, Adam; Nau, Will H.; Rieke, Viola; Butts Pauly, Kim; Sommer, Graham

2006-05-01

Catheter-based ultrasound devices have significant advantages for thermal therapy procedures, including potential for precise spatial and dynamic control of heating patterns to conform to targeted volumes. Interstitial and transurethral ultrasound applicators, with associated treatment strategies, were developed for thermal ablation of prostate combined with MR thermal monitoring. Four types of multielement transurethral applicators were devised, each with different levels of selectivity and intended therapeutic goals: sectored tubular transducer devices with fixed directional heating patterns; planar and lightly focused curvilinear devices with narrow heating patterns; and multi-sectored tubular devices capable of dynamic angular control without applicator movement. These devices are integrated with a 4 mm delivery catheter, incorporate an inflatable cooling balloon (10 mm OD) for positioning within the prostate and capable of rotation via an MR-compatible motor. Similarly, interstitial devices (2.4 mm OD) have been developed for percutaneous implantation with fixed directional heating patterns (e.g., 180 deg.). In vivo experiments in canine prostate (n=15) under MR temperature imaging were used to evaluate the heating technology and develop treatment strategies. MR thermal imaging in a 0.5 T interventional MRI was used to monitor temperature contours and thermal dose in multiple slices through the target volume. Sectored transurethral devices produce directional coagulation zones, extending 15-20 mm radial distance to the outer prostate capsule. The curvilinear applicator produces distinct 2-3 mm wide lesions, and with sequential rotation and modulated dwell time can precisely conform thermal ablation to selected areas or the entire prostate gland. Multi-sectored transurethral applicators can dynamically control the angular heating profile and target large regions of the gland in short treatment times without applicator manipulation. Interstitial implants with

Anti-angiogenic therapy with contrast-enhanced ultrasound in colorectal cancer patients with liver metastasis.

PubMed

Wu, Zhiyong; Yang, Xiaowei; Chen, Li; Wang, Zhikuan; Shi, Yan; Mao, Hui; Dai, Guanghai; Yu, Xiaoling

2017-05-01

The aim of the study was to evaluate the efficacy of anti-angiogenic therapy with dynamic contrast-enhanced ultrasound (DCE-US) in colorectal cancer (CRC) patients with liver metastasis.A total of 50 CRC patients with liver metastasis who received bevacizumab (BEV)-based chemotherapy (BEV + FOLFOX6 protocol) were recruited into the present study. Before the study (d0), and 3, 7, 14, and 42 days (d3, d7, d14, and d42) after chemotherapy, DCE-US was performed, and tumor perfusion was evaluated quantitatively by retention time (RT), peak enhancement (PE), and wash-in area under the curve (WiAUC) on the basis of a contrast-uptake curve determined with original linear data.Routine ultrasonography was used to evaluate metastatic foci in the liver at baseline. A metastatic focus was selected for dynamic monitoring with ultrasound. The metastatic foci were 1.5 to 8 cm (median: 2.5 cm). The results of hemodynamics monitored at different time points, including RT, PE, and WiAUC, showed that RT at baseline was significantly different between groups (P < .001; Responder group: 10.54 seconds; nonresponder group: 15.33 seconds). The2 groups had opposite changes in RT (continuous increase in the responder group and transient reduction in the nonresponder). The RT of metastatic foci was normalized to that of adjacent normal liver as standard RT-quotient, a similar trend was observed, and no marked difference was noted in the standard RT-quotient between the 2 groups. The median progression-free survival was significantly higher in the increased-RT group (10.8 months) than the decreased-RT group (2.5 months) (P = .002). There were no significant differences in peak intensity and WiAUC between the 2 groups.DCE-US can be used to quantitatively evaluate the hemodynamics of liver metastasis in CRC patients who received bevacizumab-based chemotherapy.

Potential of Contrast-Enhanced Ultrasound as a Bedside Monitoring Technique in Cerebral Perfusion: a Systematic Review.

PubMed

Vinke, Elisabeth J; Kortenbout, Anna J; Eyding, Jens; Slump, Cornelis H; van der Hoeven, Johannes G; de Korte, Chris L; Hoedemaekers, Cornelia W E

2017-12-01

Contrast-enhanced ultrasound (CEUS) has been suggested as a new method to measure cerebral perfusion in patients with acute brain injury. In this systematic review, the tolerability, repeatability, reproducibility and accuracy of different CEUS techniques for the quantification of cerebral perfusion were assessed. We selected studies published between January 1994 and March 2017 using CEUS to measure cerebral perfusion. We included 43 studies (bolus kinetics n = 31, refill kinetics n = 6, depletion kinetics n = 6) with a total of 861 patients. Tolerability was reported in 28 studies describing 12 patients with mild and transient side effects. Repeatability was assessed in 3 studies, reproducibility in 2 studies and accuracy in 19 studies. Repeatability was high for experienced sonographers and significantly lower for less experienced sonographers. Reproducibility of CEUS was not clear. The sensitivity and specificity of CEUS for the detection of cerebral ischemia ranged from 75% to 96% and from 60% to 100%. Limited data on repeatability, reproducibility and accuracy may suggest that this technique could be feasible for use in acute brain injury patients. Copyright © 2017 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Doxorubicin Delivery into Tumor Cells by Stable Cavitation without Contrast Agents.

PubMed

Chettab, Kamel; Mestas, Jean-Louis; Lafond, Maxime; Saadna, Djamel Eddine; Lafon, Cyril; Dumontet, Charles

2017-02-06

Doxorubicin, alone or in combination with other anticancer agents, is one of the most widely used chemotherapeutic agents and is administered in a wide range of cancers. However, the use of doxorubicin is limited due to its potential serious adverse reactions. Previous studies have established the ability of high intensity focused ultrasound (HIFU) in combination with various contrast agents to increase intracellular doxorubicin delivery in a targeted and noninvasive manner. In this study, we developed a new sonoporation device generating and monitoring acoustic cavitation bubbles without any addition of contrast agents. The device was used to potentiate the delivery of active doxorubicin into both adherent and suspended cell lines. Combining doxorubicin with ultrasound resulted in a significant enhancement of doxorubicin intracellular delivery and a decrease in cell viability at 48 and 72 h, in comparison to doxorubicin alone. More importantly and unlike previous investigations, our procedure does not require the addition of contrast agents to generate acoustic cavitation and to achieve high levels of doxorubicin delivery. The successful translation of this approach for an in vivo application may allow a significant reduction in the dosage and the adverse effects of doxorubicin therapy in patients.

Development of contrast agents targeted to macrophage scavenger receptors for MRI of vascular inflammation

PubMed Central

Gustafsson, Björn; Youens, Susan; Louie, Angelique Y.

2008-01-01

Atherosclerosis is a leading cause of death in the U.S. Because there is a potential to prevent coronary and arterial diseases through early diagnosis, there is a need for methods to image arteries in the sub-clinical stage as well as clinical stage using various non-invasive techniques, including Magnetic Resonance Imaging (MRI). We describe a development of a novel MRI contrast agent targeted to plaques that will allow imaging of lesion formation. The contrast agent is directed to macrophages, one of the earliest components of developing plaques. Macrophages are labeled through the macrophage scavenger receptor A, a macrophage specific cell surface protein, using an MRI contrast agent derived from scavenger receptor ligands. We have synthesized and characterized these contrast agents with a range of relaxivities. In vitro studies show that the targeted contrast agent accumulates in macrophages and solution studies indicate that micromolar concentrations are sufficient to produce contrast in an MR image. Cell toxicity and initial biodistribution studies indicate low toxicity, no detectable retention in normal blood vessels, and rapid clearance from blood. The promising performance of this contrast agent targeted towards vascular inflammation opens doors to tracking of other inflammatory diseases such as tumor immunotherapy and transplant acceptance using MRI. PMID:16536488

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

PubMed

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

2010-07-01

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

Low-intensity focused ultrasound (LIFU)-induced acoustic droplet vaporization in phase-transition perfluoropentane nanodroplets modified by folate for ultrasound molecular imaging.

PubMed

Liu, Jianxin; Shang, Tingting; Wang, Fengjuan; Cao, Yang; Hao, Lan; Ren, JianLi; Ran, Haitao; Wang, Zhigang; Li, Pan; Du, Zhiyu

2017-01-01

The commonly used ultrasound (US) molecular probes, such as targeted microbubbles and perfluorocarbon emulsions, present a number of inherent problems including the conflict between US visualization and particle penetration. This study describes the successful fabrication of phase changeable folate-targeted perfluoropentane nanodroplets (termed FA-NDs), a novel US molecular probe for tumor molecular imaging with US. Notably, these FA-NDs can be triggered by low-intensity focused US (LIFU) sonication, providing excellent US enhancement in B-mode and contrast-enhanced US mode in vitro. After intravenous administration into nude mice bearing SKOV3 ovarian carcinomas, 1,1'-dioctadecyl-3,3,3',3' -tetramethylindotricarbocya-nine iodide-labeled FA-NDs were found to accumulate in the tumor region. FA-NDs injection followed by LIFU sonication exhibited remarkable US contrast enhancement in the tumor region. In conclusion, combining our elaborately developed FA-NDs with LIFU sonication provides a potential protocol for US molecular imaging in folate receptor-overexpressing tumors.

Low-intensity focused ultrasound (LIFU)-induced acoustic droplet vaporization in phase-transition perfluoropentane nanodroplets modified by folate for ultrasound molecular imaging

PubMed Central

Liu, Jianxin; Shang, Tingting; Wang, Fengjuan; Cao, Yang; Hao, Lan; Ren, JianLi; Ran, Haitao; Wang, Zhigang; Li, Pan; Du, Zhiyu

2017-01-01

The commonly used ultrasound (US) molecular probes, such as targeted microbubbles and perfluorocarbon emulsions, present a number of inherent problems including the conflict between US visualization and particle penetration. This study describes the successful fabrication of phase changeable folate-targeted perfluoropentane nanodroplets (termed FA-NDs), a novel US molecular probe for tumor molecular imaging with US. Notably, these FA-NDs can be triggered by low-intensity focused US (LIFU) sonication, providing excellent US enhancement in B-mode and contrast-enhanced US mode in vitro. After intravenous administration into nude mice bearing SKOV3 ovarian carcinomas, 1,1′-dioctadecyl-3,3,3′,3′ -tetramethylindotricarbocya-nine iodide-labeled FA-NDs were found to accumulate in the tumor region. FA-NDs injection followed by LIFU sonication exhibited remarkable US contrast enhancement in the tumor region. In conclusion, combining our elaborately developed FA-NDs with LIFU sonication provides a potential protocol for US molecular imaging in folate receptor-overexpressing tumors. PMID:28184161

Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood–brain barrier opening

PubMed Central

Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel

2016-01-01

Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood–brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood–brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo. PMID:27278929

Imaging Ultrasound Guidance and on-line Estimation of Thermal Behavior in HIFU Exposed Targets

NASA Astrophysics Data System (ADS)

Chauhan, Sunita; Haryanto, Amir

2006-05-01

Elevated temperatures have been used for many years to combat several diseases including treatment of certain types of cancers/tumors. High Intensity Focused Ultrasound (HIFU) has emerged as a potential non-invasive modality for trackless targeting of deep-seated cancers of human body. For the procedures which require thermal elevation such as hyperthermia and tissue ablation, temperature becomes a parameter of vital importance in order to monitor the treatment on-line. Also, embedding invasive temperature probes for this purpose beats the supremacy of the non-invasive ablating modality. In this paper, we describe the use of a non-invasive and inexpensive conventional imaging ultrasound modality for lesion positioning and estimation of thermal behavior of the tissue on exposure to HIFU. Representative results of our online lesion tracking algorithm for discerning lesioning behavior using image capture, processing and phase-shift measurements are presented.

Ultrasound guidance to perform intra-articular injection of gadolinium-based contrast material for magnetic resonance arthrography as an alternative to fluoroscopy: the time is now.