The study was designed to investigate whether ultrasound-mediated microbubble destruction can enhance the transplantation of bone marrow mesenchymal stem cells (BMSCs) fo..
Tachibana and Tachibana (4) first described the impact of a nonimaging low-frequency ultrasound transducer and microbubbles on the effectiveness of fibrinolytic agents. These investigators observed, in an in vitro model, that the combination of urokinase, low-frequency ultrasound, and microbubbles resulted in an increased rate of fibrinolysis when compared with urokinase plus ultrasound or urokinase alone. In vitro studies have also indicated that cavitation plays an important role in ultrasound-induced thrombolysis (3). These cavitation thresholds have been shown to be lowered in the presence of microbubbles. Our study documents the importance of cavitation for producing thrombolysis with ultrasound in vivo, in that only when we applied the cavitation-producing high-MI impulses did we achieve a high degree of success in recanalizing the acutely thrombosed grafts.. Ultrasound, used alone or in combination with microbubbles, has potentiated the clinical effect of fibrinolytic agents in the ...
Microbubbles are microspheres containing a shell-encapsulated gas, which are used as intravascular ultrasound contrast agents in diagnostic echocardiography (1). Although microbubbles may vary in their shell composition, all expand and contract (vibrate) when exposed to specific frequencies of ultrasound at appropriate acoustic pressures (2). Increasingly, bioeffects caused by ultrasound-induced microbubble vibration in vivo have been harnessed for therapeutic gain. Ultrasound-induced microbubble vibrations enhance gene delivery and thrombolysis ("sonothrombolysis"), and transiently open the normally impervious blood-brain barrier in pre-clinical models (3-5). In the realm of gene delivery, ultrasound-targeted microbubble vibrations that culminate in microbubble destruction hold the promise of a noninvasive, nonimmunogenic, nonviral means of delivering genes to a target via simple intravenous injection. This approach offers an ideal "theranostic tool," using navigation of the ultrasound beam to ...
Previous animal studies have proven the feasibility of enhancing collateral function by delivery of angiogenic factors to the myocardium [1, 2, 22-24]. Intramyocardial gene transfer allows nonviral vector delivery directly to the target area. Plasmid delivery methods are relatively safer, but their transfection efficiencies are low even after direct injection. Recently, researchers have begun to use microbubble contrast agents as a diagnostic imaging tool and as a gene carrier [11-14]. Some studies have shown that ultrasound, used either alone or in combination with microbubbles, can delivery of genes to specific tissues, including the myocardium and increase gene expression [25-28].. Systemic administration of HGF by ultrasound-targeted microbubble destruction for therapeutic angiogenesis has been demonstrated to be effective [3-6]. More, US/MB has been used to enhance the delivery of HGF into the skeletal muscle by direct intramuscular injection of a naked plasmid into the rat hind limbs [27]. ...
TY - JOUR. T1 - Smaller intravenous perfluorocarbon-containing microbubbles produce greater myocardial contrast with intermittent harmonic imaging and better delineation of risk area during acute myocardial ischemia. AU - Porter, Thomas Richard. AU - Li, Shouping. AU - Kilzer, Karen. PY - 1997/1/1. Y1 - 1997/1/1. N2 - The purpose of this article was to determine whether applying negative or positive pressure to perfluorocarbon-containing microbubbles before intravenous injection would improve the myocardial contrast when using newer imaging techniques such as harmonic and intermittent imaging. Perfluorocarbon-containing microbubbles were exposed to sustained negative or positive pressure before intravenous injection in 10 dogs. Microbubble size distribution and concentration were measured after each exposure. Peak myocardial video-intensity with intermittent harmonic imaging with each sample was compared. Microbubbles exposed to -200 mm Hg pressure before intravenous injection produced both the ...
A 61-year-old man presented with unstable angina (Braunwald class 2B). Coronary angiography revealed a mild lesion on the very proximal segment of the left anterior descending coronary artery (LAD) and a significant stenosis (80%) in the mid-segment. Intracoronary ultrasound was used to further evaluate proximal coronary artery stenosis. It was found to be a soft plaque without significant luminal stenosis but without clear definition of the luminal-intimal boundary.. Intravenous injection of gas-filled microbubble ultrasound contrast agents have been used for endocardial border detection, especially when they are sonicated by acoustic power and produce harmonics. We performed continuous intracoronary ultrasound recordings (EndoSonics; 20 MHz) in the proximal left anterior descending coronary artery before (Figure 1, A), during (Figure 1, B) and after injection (Figure 1, C) of 4 mL of SonoVue (ultrasound contrast agent with lyophilized capsule filled with sulfurhexafluoride). Simultaneously ...
BACKGROUND: Ultrasound/microbubble-mediated gene delivery has the potential to be targeted to tissue deep in the body by directing the ultrasound beam following vector administration. Application of this technology would be minimally invasive and benefit from the widespread clinical experience of using ultrasound and microbubble contrast agents. In this study we evaluate the targeting ability and spatial distribution of gene delivery using focused ultrasound. METHODS: Using a custom-built exposure tank, Chinese hamster ovary cells in the presence of SonoVue microbubbles and plasmid encoding beta-galactosidase were exposed to ultrasound in the focal plane of a 1 MHz transducer. Gene delivery and cell viability were subsequently assessed. Characterisation of the acoustic field and high-resolution spatial analysis of transfection were used to examine the relationship between gene delivery efficiency and acoustic pressure. RESULTS: In contrast to that seen in the homogeneous field close to the ...
The localization of microbubbles to a treatment site has been shown to be essential to their effectiveness in therapeutic applications such as targeted drug delivery and gene therapy. A variety of different strategies for achieving localization has been investigated, including biochemical targeting, acoustic radiation force, and the incorporation of superparamagnetic nanoparticles into microbubbles to enable their manipulation using an externally applied magnetic field. The third of these strategies has the advantage of concentrating microbubbles in a target region without exposing them to ultrasound, and can be used in conjunction with biochemical targeting to achieve greater specificity. Magnetic microbubbles have been shown to be effective for therapeutic delivery in vitro and in vivo. Whether this technique can be successfully applied in humans however remains an open question. The aim of this study was to determine the range of flow conditions under which targeting could be achieved. In vitro
Induced air flotation (IAF) was developed using a rotating-flow microbubble generator for water treatment. This newly-developed generator can produce fine microbubbles with diameters on the order of micrometers, whereas it has to use a large quantity of water as propulsion, especially when surfactant-free water is used. That is to say, if the microbubble generator is utilized in flotation, the recycle ratio in IAF will be very high. To overcome this problem, we applied a centrifugal pump and altered the air-induced way of the generator. Microbubble size, microbubble concentration and particle removal efficiency of the improved microbubble generating method were compared with those of traditional ones.,BR,The best performance occurred in the improved method where gas and water were simultaneously induced and mixed by the pump, and dispersed through the rotating-flow microbubble generator. Microbubble size was decreased, while microbubble concentration was increased by the improved method. ...
TY - JOUR. T1 - Therapeutic arteriogenesis by ultrasound-mediated VEGF165 plasmid gene delivery to chronically ischemic skeletal muscle. AU - Leong-Poi, Howard. AU - Kuliszewski, Michael A.. AU - Lekas, Michael. AU - Sibbald, Matthew. AU - Teichert-Kuliszewska, Krystyna. AU - Klibanov, Alexander L.. AU - Stewart, Duncan J.. AU - Lindner, Jonathan. PY - 2007/8. Y1 - 2007/8. N2 - Current methods of gene delivery for therapeutic angiogenesis are invasive, requiring either intraarterial or intramuscular administration. A noninvasive method of gene delivery has been developed using ultrasound-mediated destruction of intravenously administered DNA-bearing carrier microbubbles during their microcirculatory transit. Here we show that chronic ischemia could be markedly improved by ultrasound-mediated destruction of microbubbles bearing vascular endothelial growth factor-165 (VEGF165) plasmid DNA. Using a model of severe chronic hindlimb ischemia in rats, we demonstrated that ultrasound mediated ...
This paper reported the development of a multifunctional contrast agent for near infrared (NIR) fluorescent/ultrasonic bimodal imaging and gene delivery. CuInS2-ZnS alloyed quantum dots (ZCIS QDs) were coated with polyethyleneimine (PEI) to complex plasmid DNA (pDNA), followed by adsorption onto the surface of microbubbles (MBs) generated from the surfactant mixture of Span 60 and Tween 80. It was found that the obtained composite agent of [email protected]@PEI/pDNA had excellent capability to enhance both ultrasound and fluorescence imaging. In addition, an in vitro cell experiment showed that pDNA could be released from [email protected]@PEI/pDNA and internalized by target HeLa cells to realize a relatively high transfection efficiency by ultrasound-targeted microbubble destruction. Furthermore, the cytotoxicity, immune toxicity and histological evaluation showed that [email protected]@PEI/pDNA had a good biocompatibility for medical application. Therefore, such a multifunction agent could operate as a promising platform ...
PubMedID: 27502060 | Noninvasive Contrast-Enhanced Ultrasound Molecular Imaging Detects Myocardial Inflammatory Response in Autoimmune Myocarditis. | Circulation. Cardiovascular imaging | 8/1/2016
Hypoxia-inducible factor 1α (HIF-1α) plays a critical protective role in ischemic heart disease. Under normoxic conditions, HIF-1α was degraded by oxygen-dependent prolyl hydroxylase-2 (PHD2). Gene therapy has become a promising strategy to inhibit the degradation of HIF-1α and to improve cardiac function after ischemic injury. However, conventional gene delivery systems are difficult to achieve a targeted and localized gene delivery into the ischemic myocardia. Here, we report the localized myocardial delivery of shRNA against PHD2 through ultrasound-targeted microbubble destruction (UTMD) for protection the heart from acute myocardial infarction ...
Microbubbles are broadly used as ultrasound contrast agents. In this paper we use a low-cost flow focusing microchannel fabrication method for preparing microbubble contrast agents by using some surface active agents and a viscosity enhancing material to obtain appropriate microbubbles with desired lifetime and stability for any in vitro infusion for velocity measurement. All the five parameters that govern the bubble size extract and some efforts are done to achieve the smallest bubbles by adding suitable surfactant concentrations. By using these microbubbles for the echo-particle image velocimetry method, we experimentally determine the velocity field of steady state and pulsatile pipe flows.. ...
A method and assembly are provided which use cavitation induced by an ultrasound beam for creating a controlled surgical lesion in a selected treatment volume of a patient, such as an internal body cavity or organ. First, a plurality of microbubbles are provided in the treatment volume. Preferably, the threshold for cavitation of microbubbles in the treatment volume is lowered compared with the threshold for cavitation in surrounding tissues. The expected location of the surgical lesion within the treatment volume may be previewed, and then the microbubbles in the treatment volume are cavitated with the ultrasound beam to create the controlled surgical lesion. In addition, substances can be associated with the microbubbles such that cavitation of the microbubbles delivers the substances to the treatment volume. Preferably, the creation of the surgical lesion at the expected lesion location is then verified. Using the method and assembly of the present invention, the cavitation threshold within the
Engineering brown fat into skeletal muscle using ultrasound-targeted microbubble destruction gene delivery in obese Zucker rats: Proof of concept design IUBMB Life 2017 [BMP7 ...
Engineering brown fat into skeletal muscle using ultrasound-targeted microbubble destruction gene delivery in obese Zucker rats: Proof of concept design IUBMB Life 2017 [BMP7 ...
Leong-Poi and colleagues used monoclonal antibodies against murine αv or echistatin, a viper venom disintegrin containing the well known RGD (arginine-glycine-aspartic acid) sequence [8]. Antibody-bearing and echistatin-conjugated microbubbles exhibited high potential to image activated endothelium in subcutaneously implanted Matrigel plugs enriched with fibroblast growth factor-2 (FGF-2). Microbubble retention inside the microvasculature was much higher as compared to non-targeted microbubbles, however, no significant differences in the retention of both types of targeted microbubbles were observed. Thus, monoclonal antibodies against murine αv and echistatin can be used for targeted imaging approaches.. In another study, Leong-Poi and colleagues applied echistatin-conjugated microbubbles to assess endogeneous and therapeutic arteriogenesis in a hindlimb ischemia model in rats [9]. They observed an increase in retention of integrin-binding microbubbles prior to a measurable increase in blood ...
There are salient features common to most of the commercially produced ultrasound contrast agents. The microbubbles in these agents do not aggregate, are biologically inert and safe,18,19 remain entirely within the vascular space,20,21 have an intravascular rheology that is very similar to that of erythrocytes,20-22 respond nonlinearly to ultrasound,23-25 and are eliminated from the body via the reticuloendothelial system with their gas escaping from the lungs.. A key technical advance in MCE was online signal processing of ultrasound backscatter from insonified microbubbles.26 Before that, it was not possible to separate bubble signals from myocardial backscatter without offline image processing.27 Unlike tissue, microbubbles are compressible and oscillate in an ultrasound field. At even a low mechanical index, these oscillations become nonlinear, that is, during each oscillation the microbubbles expand more than they contract. The term nonlinear in this context means that the output of a ...
Ultrasound contrast agents (UCAs) have been in the echocardiographic "toolbox" for many years. Two such agents (Definity [Lantheus Medical Imaging, North Billerica, Massachusetts] and Optison [GE Healthcare, Princeton, New Jersey]) are approved by the U.S. Food and Drug Administration (FDA) and are commercially available for left ventricular cavity opacification in patients with technically difficult echocardiograms. The greater, still unrealized value of these unique erythrocyte tracers, however, resides in their ability to depict the spatial distribution of myocardial perfusion and to quantify intramyocardial blood volume, properties that render UCAs ideal for the detection and localization of coronary artery disease (CAD).. UCAs have had a checkered history, particularly with respect to myocardial perfusion imaging. The literature is replete with studies showing the promise of myocardial contrast echocardiography (MCE) for CAD detection (1,2). Studies in dogs dating back to the early 1980s ...
Microbubbles are truly tiny, tiny bubbles, pinhead-size and smaller -- microscopic. Many types of aquarium equipment can generate microbubbles but, paradoxically, they can interfere with many other ...
This study has been performed to examine which cells are responsible for the hepatic clearance of the new ultrasound contrast agent Sonazoid and to study whether uptake of these gas microbubbles disturbs the function of the cells involved. Sonazoid w
The third speaker (P. Nihoyannopoulos from London - UK) nicely reported to the audience the extreme flexibility of Echocardiography and the added values of ultrasound contrast agent (microbubbles) which can be used either to further increase the quality of images with the aim of a better definition of endocardial borders or to evaluate myocardial perfusion. The latter takes advantage of the high spatial and temporal resolution of Echocardiography. Over the years, both the equipment (second harmonic, pulsed power etc.) and the contrast agents (stability, dimension of microbubbles, etc) have been progressively improved in such a way that nowadays, it is realistic to envisage the use of contrast echocardiography to assess myocardial perfusion either in baseline condition (myocardial infarction, etc) or during stress. In the latter case, the use of contrast agent can improve both the evaluation of functional reserve and the presence of underperfused area and in such a way further improve the already ...
Microbubble contrast agents were originally developed to enhance echogenicity in diagnostic sonography. However, their somewhat unique acoustic response and facility to transduct energy into spatially focussed regimes, together with the clinical demand for non-invasive adjuncts and options to conventional therapy, have seen interest in exploring the therapeutic potential of microbubbbles grow steadily within this past decade. For the purposes of the present study, we examined the ultrasonically stimulated response of many such microbubbles by controlling their spatial placement with bespoke optical traps. The objective was to improve our understanding of their statistical behaviour and to feed this information into realistic computational models so that processes might be more easily optimised. Hence, individual microbubbles of commercial [low-index] ultrasound contrast agent were isolated from a parent population by selection using a Laguerre-Gaussian optical trap, and subsequently manipulated ...
Under certain acoustic conditions, these microbubbles can also be made to induce bioeffects, including the local and reversible opening cell membranes to allow entry of therapeutics - sonoporation. Either through co-injection of a therapeutic or through attaching the payload to the bubble itself, microbubbles are emerging as a targeted drug/gene delivery vehicle - for example in cancer and cardiovascular disease applications - whereby drug deposition is limited to the precise location where the microbubbles intersect with the focused ultrasound beam.. We are an interdisciplinary research group at the interface of physics and biology. Our research projects focus on both the acoustics and biophysics of biomedical ultrasound therapeutics.. Our first research interest is in studying the basic physics of ultrasound-stimulated microbubble vibrations, and other acoustically sensitive agents. A more complete understanding of the dynamic response of bubbles will aid in contrast image quality and ...
DESCRIPTION (provided by applicant): Novel strategies for promoting angiogenesis are being developed to treat patients with chronic coronary artery disease or peripheral vascular disease who are not amenable to revascularization. The overall purpose of this proposal is to apply novel contrast-enhanced ultrasound techniques to non-invasively assess molecular and cellular processes that are thought to contribute to angiogenesis. Contrast-enhanced ultrasound has been used to non-invasively assess microvascular perfusion in ischemic heart and limb disease, and can provide information on blood flow and blood volume in the different vascular compartments. Novel microbubble contrast agents targeted to either alpha-v integrins or to activate leukocytes have been developed to non-invasively image integrin expression and inflammation. The first aim will be to apply these techniques to spatially and temporally characterize the relation between alpha-v integrin expression, the cellular inflammatory ...
Ultrasound imaging techniques can be greatly improved by the use of ultrasound contrast agents. Knowledge of the peak negative pressure at which contrast agents fracture is paramount for the imaging application as well as for local drug delivery. Gasholdning microbubbles encapsulated into biocompatible poly vinyl alcohol shells are of particular interest for their enhanced shelf life and demonstratedchemical versatility. A gas core allows microbubbles to efficiently scatter ultrasound waves. In vitro ultrasound tests showed a sufficient enhancement of the backscattered power (25±1 dB), comparable to the soft tissue attenuation coefficients (0.8±0.04 dB/cm MHz) and phase velocities (1519±2 m/s). At temperature values between 24 and 37 °C the monotonic increase of the attenuation and phase velocity with frequency indicates that thick-shelled microbubbles do not resonate in a typical medical ultrasound frequency range of 1-15 MHz. In fact, they work as an amplifier of the incident acoustic ...
Stabilized microbubbles with a size between 1-5 µm are used as ultrasound contrast agents in the clinical routine. They have shown convincing results for the vascular characterization of tissues as well as in echocardiography. Due to their size, mic
C. F. Caskey, Stieger-Vanegas, S. M., Qin, S., Dayton, P. A., and Ferrara, K. W., "Direct observations of ultrasound microbubble contrast agent interaction with the microvessel wall.", The Journal of the Acoustical Society of America, vol. 122, no. 2, pp. 1191-200, 2007. ...
Molecularly-targeted microbubbles (MBs) are increasingly being recognized as promising contrast agents for oncological molecular imaging with ultrasound. With the detection and validation of new molecular imaging targets, novel binding ligands are needed that bind to molecular imaging targets with high affinity and specificity. In this study we assessed a novel class of potentially clinically translatable MBs using an engineered 10th type III domain of human-fibronectin (MB-FN3VEGFR2) scaffold-ligand to image VEGFR2 on the neovasculature of cancer. The in vitro binding of MB-FN3VEGFR2 to a soluble VEGFR2 was assessed by flow-cytometry (FACS) and binding to VEGFR2-expressing cells was assessed by flow-chamber cell attachment studies under flow shear stress conditions. In vivo binding of MB-FN3VEGFR2 was tested in a transgenic mouse model (FVB/N Tg(MMTV/PyMT634Mul) of breast cancer and control litter mates with normal mammary glands. In vitro FACS and flow-chamber cell attachment studies showed ...
We may soon be able to assess cancer prognosis on patients using a technique like this. The more angiogenesis, the more aggressive a tumor is likely to be," Lindner said. "This microbubble technique may be able to tell people and their physicians exactly whats likely to happen with a tumor in the future. If we know it has a certain amount of angiogenesis, then we know a tumor might be susceptible to treatment with new anti-tumor or anti-neoplastic agents developed to shrink tumors ...
The recent FDA mandated "black box" warning reported a total of 11 deaths related to contrast administration: 10 following Definity and 1 following Optison (8). Although 4 occurred during or within 30 min of Definity use, mitigating factors could have explained the deaths.. Before the black box warning, there were multiple studies that demonstrated the safety of these contrast agents (16,17). Recently presented data suggested that contrast use in echocardiography is safe, and the FDA modified the professional labeling for Optison and Definity contrast agents originally announced in November 2007. The warning currently states that it is contraindicated to administer contrast to patients with R→L, bidirectional, or transient R→L cardiac shunts and to patients with hypersensitivity to perflutren. This study was designed to evaluate the safety profile and incremental benefit of UCA use during stress echocardiography in a multicenter setting. As has been the case, serious adverse events (death or ...
Tip Headlines: Ultrasound-targeted microbubble may help deliver novel drug to the heart. Cardiovascular health linked to cellular aging. Patients own connective tissues may serve as future dialysis access tubes. microRNA 128 may restore hearts self-healing ability.
The present invention relates to polymer-based gas-containing contrast agents in which microbubbles of gas are encapsulated by non-polymerizable wall-forming block or graft copolymer surfactants. The polymer surfactants are preferably biodegradable and include block and graft copolymers containing linkages of formula (I): --(O)m --CO--O--C(R1 R2)--O--CO--(O)n --(I) where R1 and R2 each represent a hydrogen atom or a carbon-attached monovalent organic group, or R1 and R2 together form a carbon-attached divalent organic group and m and n are each zero or 1.
A method of excavating tissue in the body, including bringing a catheter (60) to a location, injecting microbubbles (84) at the location and causing cavitation of tissue (76) at the location using ultrasound. Preferably, the microbubbles (84) are injected directly into the tissue, such as by using a hollow needle (62). Alternatively, microbubbles (84) are injected into the vascular bed of the tissue at the location, so that the capillaries (86) are infused with microbubbles (84).
Results-The recanalization rates of platelet- and erythrocyte-rich microthrombi in mesenteric microvessels were higher (P,0.05), and the cerebral infarct volumes and neurological scores of rats with either microthrombi were lower in the US+MB group than in the CON group (P,0.01). The infarct volumes and neurological scores were greater in the r-tPA group than in the US+MB and US+MB+r-tPA groups after treatment of rats with platelet-rich microthrombi (P,0.05). In contrast, after treatment of rats with erythrocyte-rich microthrombi, the infarct volumes and neurological scores were similar in the r-tPA and US+MB groups, but smaller in the US+MB+r-tPA group (P,0.05). ...
A novel ultrasound contrast agent (UCA) based on air-filled polymer-shelled microbubbles, is prepared within 3MiCRON project for multimodality approach covering ultrasound, MRI and SPECT investigation. These bubbles have thick, about 30% of the radius, shell providing greater stability and longer half life in a pulmonary circulation compare to commercially available phospholipid UCAs. In addition, extensive storage capacity and possibility to incorporate drugs or pharmacological relevant materials are inherited to these bubbles. Understanding the behavior of the UCA under ultrasound exposure is paramount to the proper and total exploitation of all unique features that these gas-filled microdevice offers. Even though, thickness of the polymeric shell is considerably higher than of commercial UCAs, the enhancement of backscattered power of about 25 dB produced from suspension insonified at low pressure (100 kPa) was observed. It should be noted that thick polymer shell could still be disrupted by ...
Novel membrane-forming amphiphilic lipopeptides comprising one or more peptide moieties containing 2-50 aminoacyl residues and one or more hydrocarbon chains containing 5-50 carbon atoms. Such lipopeptides may be used in the formation of stabilized gas microbubble dispersions suitable for use as diagnostic and/or therapeutic agents, for example as ultrasound contrast agents.
Random, unbiased fragmentation of DNA is necessary for next-generation sequencing (NGS) and chromatin immunoprecipitation (ChIP). Since DNA fragmentation can be a very problematic step for both NGS and ChIP, any technology that increased the efficiency and consistency of this step will be highly desirable for both research laboratories and in clinical diagnostics. Also, a technology that could make this step easier with no new equipment and very little cost to the laboratory would be ideal. We propose to apply the use of lipid encapsulated microbubbles to the fragmentation of DNA from both purified genomic and formaldehyde crosslinked samples. We have recently explored the feasibility of this technology, and our results were impressive. Preliminary data indicate that microbubbles can greatly improve the consistency of acoustic DNA fragmentation. Additionally, these bubbles are added in microliter volumes to the DNA or cell suspension at a cost ranging from one to ten cents per well, and can be ...
Ultrasound-mediated delivery of a novel nanoparticle-microbubble platform. A major obstacle in delivery of nanoparticles (NPs) to tumor cells is the low uptake and heterogeneous distribution of the NPs in tumor tissue. Ultrasound (US) may improve the delivery of encapsulated drug in various ways depending on the frequency and intensity applied, by inducing heating, radiation force or cavitation. We have developed a novel multimodal, multifunctional drug delivery system consisting of microbubbles stabilized by polymeric NPs to be used in US-mediated delivery of NPs. Miniemulsion polymerization was used to prepare NPs of the biocompatible and biodegradable polymer poly(butyl-2-cyanoacrylate) (PBCA). The NPs were coated with PEG to improve the circulation time and biodistribution. Microbubbles stabilized by these NPs were prepared by mixing the NP dispersion with proteins and air using an ultra-turrax. The aim of the present work was to study the cellular uptake of the NP in vitro and the ...
Efficiency of drug delivery enhanced by acoustic pressure during blood–brain barrier disruption induced by focused ultrasound Feng-Yi Yang, Pei-Yi LeeDepartment of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, TaiwanPurpose: We evaluated the delivery efficiency of intravenously injected large molecular agents, before and after disruption of the blood–brain barrier (BBB-D), induced by focused ultrasound (FUS) using various acoustic parameters.Materials and methods: Male Sprague-Dawley rats were injected intravenously with Evans blue (EB) before or after BBB-D induction by pulsed FUS. We used a 1.0 MHz pulsed FUS with four acoustic power settings and an ultrasound contrast agent (UCA) at four different doses to induce BBB-D resulting from cavitation. The permeability of the BBB was assessed quantitatively based on the extravasation of EB. Contrast enhanced magnetic resonance imaging (MRI) was used to monitor the gadolinium deposition associated with FUS.
Results Compared with control groups (Sham and shSchamble rats), there was significant decreased in EF in the study (shPHD2) at seven days, which recovered at 14 and 28 days after LAD ligation; but there was a much more pronounced decreased in EF for the shSchamble rats at 7, 14, and 28 days, which did not recover after 28 days (Figure1). Compared with shScramble control group, CVF was decrease at seven days (4.81%±0.8 vs 3.9%±0.68), 14 days (6.5%±0.78 vs 4.2%±0.69) and 28 days (8.2%±0.7 vs 4.25%±0.58) in shPHD2 group; PCVA was also decrease at seven days (0.45%±0.14 vs 0.52%±0.13), 14 days (0.79%±0.24 vs 0.69%±0.21) and 28 days (0.94%±0.25 vs 0.69%±0.23) in shPHD2 group. A significant reduction in capillary density within the infarcted area was noted in shPHD2 group when compared with the control shSchamble group (643.6±170.5/mm2 vs 1908.7±353.4/mm2). Immunohistochemistry explanted hearts also confirmed that the group had significantly higher levels of HIF1a expressions. In order ...
Abstract: Slowly varying, conservative, one degree of freedom Hamiltonian systems are analyzed in the case of a saddle-center bifurcation. At the bifurcation, a homoclinic orbit connects to a nonhyperbolic saddle point. Using averaging for strongly nonlinear oscillations, action is an adiabatic invariant before and after the slow passage of the homoclinic orbit. The homoclinic orbit is assumed to be crossed near to its creation in the saddle-center bifurcation, a dynamic unfolding. A large sequence of nearly homoclinic orbits with autonomous saddle approaches is matched to the strongly nonlinear oscillations valid before and after. Connection formulas are computed, determining the change in the action due to the slow passage through the unfolding of the saddle-center bifurcation. If the energy in one specific saddle region is particularly small, as occurs near the boundaries of the basin of attraction, then the solution in only that saddle region satisfies the nonautonomous Painlevi I ...
Lantheus Medical Imaging, formerly Bristol-Myers Squibb MedicalImaging, has initiated a multicenter Phase IV observational study toevaluate the safety profile of Definity Vial for injectable suspensionin patients with suboptimal echocardiograms and provide safetyinformation on the use of ultrasound contrast agents in routineclinical practice.
In atherosclerosis, local generation of reactive oxygen species amplifies the inflammatory response and contributes to plaque vulnerability. We used molecular imaging to test whether inhibition of NADPH oxidase with apocynin would reduce endothelial inflammatory activation and endothelial-platelet interactions, thereby interrupting progression to high-risk plaque phenotype. METHODS AND RESULTS: Mice deficient for both the low-density lipoprotein receptor and Apobec-1 were studied at 30 weeks of age and again after 10 weeks with or without apocynin treatment (10 or 50 mg/kg per day orally). In vivo molecular imaging of vascular cell adhesion molecule-1 (VCAM 1) P-selectin, and platelet glycoprotein-1balpha (GPIbalpha) in the thoracic aorta was performed with targeted contrast-enhanced ultrasound molecular imaging. Arterial elastic modulus and pulse wave transit time were assessed using ultrahigh frequency ultrasound and invasive hemodynamic measurements. Plaque size and composition were assessed ...
inproceedings{BUT100643, author="Vladimír {Slávik} and Radim {Kolář} and Vratislav {Harabiš} and Radovan {Jiřík}", title="Rician inverse Gaussian model of scattering in ultrasound contrast media", annote="A statistical analysis of 1st and 2nd harmonic echoes backscattered from contrast media using Rician inverse Gaussian (RiIG) envelope model is described. Knowledge of statistics of the scattered signal may contribute to perfusion analysis. A range of ultrasound contrast agent (UCA) concentrations is examined. The RiIG distribution was fitted to image histograms, using Matlab Global optimization toolbox. Influence of simulated attenuation was also tested. Analysis of resulting RiIG distribution parameters shows that while its parameters alpha and beta do not follow any properties of the changing concentration, parameter delta shows logarithmic dependence on concentration in range of 3.125 - 50 mg/l. Taking into account simulated attenuation, we observed that the range and shape of the ...
Nico de Jong, graduated from Delft University of Technology, The Netherlands, in 1978. He got his M.Sc. in physics specialised in the field of pattern recognition. Since 1980, he is staff member of the thoraxcenter of the Erasmus Medical Center, Rotterdam. In 1993 he received his Ph.D. for Acoustic properties of ultrasound contrast agents. In 2003 he became part-time professor at the University of Twente in the group Physics of Fluids headed by Detlef Lohse (Spinoza-winner 2005). He is organizer of the annual European Symposium on Ultrasound Contrast Imaging, held in Rotterdam and attended by approximately 175 scientists from universities and industries all over the world. He is on the safety committee of WFUMB (World Federation of Ultrasound in Medicine and Biology), assiociate editor of UMB and has been guest editor for special issues of different journals. Over the last 5 years he has given more than 30 invited lectures and has given numerous scientific presentations for international ...
Gas or air filled microbubble suspensions in aqueous phases usable as imaging contrast agents in ultrasonic echography. They contain laminarized surfactants and, optionally, hydrophilic stabilizers. The laminarized surfactants can be in the form of liposomes. The suspensions are obtained by exposing the laminarized surfactants to air or a gas before or after admixing with an aqueous phase.
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Lipid nanocarriers are considered as suitable carriers to formulate lipophilic drugs, transport them and also deliver more specifically at appropriate biological sites.