Stability analysis of ultrasound thick-shell contrast agents.
Ontology highlight
ABSTRACT:
SUBMITTER: Lu X
PROVIDER: S-EPMC3272711 | biostudies-other | 2012 Jan
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Monodisperse gas microbubbles, encapsulated with a shell of photopolymerizable diacetylene lipids and phospholipids, were produced by microfluidic flow focusing, for use as ultrasound contrast agents. The stability of the polymerized shell microbubbles against both aggregation and gas dissolution under physiological conditions was studied. Polyethylene glycol (PEG) 5000, which was attached to the diacetylene lipids, was predicted by molecular theory to provide more steric hindrance against aggregation than PEG 2000, and this was confirmed experimentally. The polymerized shell microbubbles were found to have higher shell-resistance than nonpolymerizable shell microbubbles and commercially available microbubbles (Vevo MicroMarker). The acoustic stability under 7.5 MHz ultrasound insonation was significantly greater than that for the two comparison microbubbles. The acoustic stability was tunable by varying the amount of diacetylene lipid. Thus, our polymerized shell microbubbles are a promising platform for ultrasound contrast agents.
| S-EPMC3302155 | biostudies-literature
Project description:Ultrasound contrast agents (UCAs) are designed to be used below 10 MHz, but interest is growing in studying the response of agents to high-frequency ultrasound. In this study, the subharmonic response of polymer-shelled UCAs with a mean diameter of 1.1 mum excited with 40-MHz tone-bursts of 1-20 cycles was analyzed. UCAs were diluted in water and streamed through a flow phantom that permitted single-bubble backscatter events to be acquired at peak-negative pressures from 0.75 to 5.0 MPa. At each exposure condition, 1000 single-bubble-backscatter events were digitized. Subharmonic content at 20 MHz was screened using a conventional and a singular-value-decomposition (SVD) method. The conventional method evaluated each event spectrum individually while the SVD method treated the 1000-event data set at one time. A subharmonic score (SHS) indicative of how much subharmonic content a 1000-event data set contained was computed for both methods. Empirical-simulation results indicated that SHSs obtained from the two methods were linearly related. Also, experimental data with both methods indicated that subharmonic likelihood increased with pulse duration and peaked near 2 MPa. The SVD method also yielded quantitative information about subharmonic events not available with the conventional method.
| S-EPMC2719484 | biostudies-other
Project description:SignificanceAn effective contrast agent for concurrent multimodal photoacoustic (PA) and ultrasound (US) imaging must have both high optical absorption and high echogenicity. Integrating a highly absorbing dye into the lipid shell of gas core nanobubbles (NBs) adds PA contrast to existing US contrast agents but may impact agent ultrasonic response.AimWe report on the development and ultrasonic characterization of lipid-shell stabilized C3F8 NBs with integrated Sudan Black (SB) B dye in the shell as dual-modal PA-US contrast agents.ApproachPerfluoropropane NBs stabilized with a lipid shell including increasing concentrations of SB B dye were formulated by amalgamation (SBNBs). Physical properties of SBNBs were characterized using resonant mass measurement, transmission electron microscopy and pendant drop tensiometry. Concentrated bubble solutions were imaged for 8 min to assess signal decay. Diluted bubble solutions were stimulated by a focused transducer to determine the response of individual NBs to long cycle (30 cycle) US. For assessment of simultaneous multimodal contrast, bulk populations of SBNBs were imaged using a PA and US imaging platform.ResultsWe produced high agent yield (∼1011) with a mean diameter of ∼200 to 300 nm depending on SB loading. A 40% decrease in bubble yield was measured for solutions with 0.3 and 0.4 mg / ml SB. The addition of SB to the shell did not substantially affect NB size despite an increase in surface tension by up to 8 mN / m. The bubble decay rate increased after prolonged exposure (8 min) by dyed bubbles in comparison to their undyed counterparts (2.5-fold). SB in bubble shells increased gas exchange across the shell for long cycle US. PA imaging of these agents showed an increase in power (up to 10 dB) with increasing dye.ConclusionsWe added PA contrast function to NBs. The addition of SB increased gas exchange across the NB shell. This has important implications in their use as multimodal agents.
| S-EPMC8781525 | biostudies-literature
Project description:The main constituent of an ultrasound contrast agent (UCA) is gas-filled microbubbles. An average UCA contains billions per ml. These microbubbles are excellent ultrasound scatterers due to their high compressibility. In an ultrasound field they act as resonant systems, resulting in harmonic energy in the backscattered ultrasound signal, such as energy at the subharmonic, ultraharmonic and higher harmonic frequencies. This harmonic energy is exploited for contrast enhanced imaging to discriminate the contrast agent from surrounding tissue. The amount of harmonic energy that the contrast agent bubbles generate depends on the bubble characteristics in combination with the ultrasound field applied. This paper summarizes different strategies to characterize the UCAs. These strategies can be divided into acoustic and optical methods, which focus on the linear or nonlinear responses of the contrast agent bubbles. In addition, the characteristics of individual bubbles can be determined or the bubbles can be examined when they are part of a population. Recently, especially optical methods have proven their value to study individual bubbles. This paper concludes by showing some examples of optically observed typical behavior of contrast bubbles in ultrasound fields.
| S-EPMC2727586 | biostudies-other
Project description:Liquid perfluorocarbon-based nanodroplets are stable enough to be used in extravascular imaging, but provide limited contrast enhancement due to their small size, incompressible core, and small acoustic impedance mismatch with biological fluids. Here we show a novel approach to overcoming this limitation by using a heating-cooling cycle, which we will refer to as thermal modulation (TM), to induce echogenicity of otherwise stable but poorly echogenic nanodroplets without triggering a transient phase shift. We apply thermal modulation to high-boiling point tetradecafluorohexane (TDFH) nanodroplets stabilized with a bovine serum albumin (BSA) shell. BSA-TDFH nanodroplets with an average diameter under 300 nanometers showed an 11.9 ± 5.4 mean fold increase in echogenicity on the B-mode and a 13.9 ± 6.9 increase on the nonlinear contrast (NLC) mode after thermal modulation. Once activated, the particles maintained their enhanced echogenicity (p < 0.001) for at least 13 h while retaining their nanoscale size. Our data indicate that thermally modulated nanodroplets can potentially serve as theranostic agents or sensors for various applications of contrast-enhanced ultrasound.
| S-EPMC8469504 | biostudies-literature
Project description:Our group recently presented a simple strategy using the non-ionic surfactant, Pluronic, as a size control excipient to produce nanobubbles in the 100-nm range, which exhibited stability and echogenicity on par with clinically available microbubbles. The objective of the present study was to evaluate biodistribution and extravasation of the Pluronic-stabilized lipid nanobubbles compared with microbubbles in 2 experimental tumor models in mice. Standard lipid-stabilized perfluoropropane bubbles (Pluronic L10) and lipid-stabilized perfluoropropane nanobubbles were intravenously injected into mice bearing either an orthotopic mouse breast cancer (BC4 T1) or subcutaneous mouse ovarian cancer (OVCAR-3) through the tail vein to perform perfusion dynamic studies. No significant differences between the nanobubble and microbubble groups were observed in the peak enhancement of the 3 tested regions (tumor, liver and kidney). However, the decay rates of nanobubble in the tumor and kidney of BC4 T1-bearing mice, as well as in mice with OVRCAR-3 tumors were significantly slower than those of the microbubble. To quantify extravasation, fluorescently labeled bubbles were intravenously injected into mice bearing the same tumors. Histologic analysis showed that nanobubbles were retained in tumor tissue to a greater extent compared with microbubbles in both tumor models at the 3-h time point. Our results demonstrate unique nanobubble behavior compared with microbubbles and support augmented application of these agents in ultrasound molecular imaging and drug delivery beyond the tumor vasculature.
| S-EPMC6689247 | biostudies-literature
Project description:A versatile platform for the development of new ultrasound contrast agents is demonstrated through a one-pot synthesis and fluorination of submicron polydopamine (PDA-F) nanoparticles. The fluorophilicity of these particles allows loading with perfluoropentane (PFP) droplets that display strong and persistent ultrasound contrast in aqueous suspension and ex vivo tissue samples. Contrast under continuous imaging by color Doppler persists for 1 h in 135 nm PDA-F samples, even at maximum clinical imaging power (MI = 1.9). Additionally, use of a Cadence Contrast Pulse Sequence (CPS) results in a non-linear response suitable for imaging at 0.5 mg mL-1. Despite the PFP volatility and the lack of a hollow core, PDA-F particles display minimal signal loss after storage for over a week. The ability to tune size, metal-chelation, and add covalently-bound organic functionality offers myriad possibilities for extending this work to multimodal imaging, targeted delivery, and therapeutic functionality.
| S-EPMC6319376 | biostudies-literature
Project description: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.
| S-EPMC4965150 | biostudies-literature
Project description:Ultrasonography is a fundamental diagnostic imaging tool in everyday clinical practice. Here, we are unique in describing the use of functionalized multiwalled carbon nanotubes (MWCNTs) as hyperechogenic material, suggesting their potential application as ultrasound contrast agents. Initially, we carried out a thorough investigation to assess the echogenic property of the nanotubes in vitro. We demonstrated their long-lasting ultrasound contrast properties. We also showed that ultrasound signal of functionalized MWCNTs is higher than graphene oxide, pristine MWCNTs, and functionalized single-walled CNTs. Qualitatively, the ultrasound signal of CNTs was equal to that of sulfur hexafluoride (SonoVue), a commercially available contrast agent. Then, we found that MWCNTs were highly echogenic in liver and heart through ex vivo experiments using pig as an animal model. In contrast to the majority of ultrasound contrast agents, we observed in a phantom bladder that the tubes can be visualized within a wide variety of frequencies (i.e., 5.5-10 MHz) and 12.5 MHz using tissue harmonic imaging modality. Finally, we demonstrated in vivo in the pig bladder that MWCNTs can be observed at low frequencies, which are appropriate for abdominal organs. Importantly, we did not report any toxicity of CNTs after 7 d from the injection by animal autopsy, organ histology and immunostaining, blood count, and chemical profile. Our results reveal the enormous potential of CNTs as ultrasound contrast agents, giving support for their future applications as theranostic nanoparticles, combining diagnostic and therapeutic modalities.
| S-EPMC3478634 | biostudies-literature
Project description:For contrast ultrasound imaging, the most efficient contrast agents comprise highly compressible gas-filled microbubbles. These micrometer-sized particles are typically filled with low-solubility perfluorocarbon gases, and coated with a thin shell, often a lipid monolayer. These particles circulate in the bloodstream for several minutes; they demonstrate good safety and are already in widespread clinical use as blood pool agents with very low dosage necessary (sub-mg per injection). As ultrasound is an ubiquitous medical imaging modality, with tens of millions of exams conducted annually, its use for molecular/targeted imaging of biomarkers of disease may enable wider implementation of personalised medicine applications, precision medicine, non-invasive quantification of biomarkers, targeted guidance of biopsy and therapy in real time. To achieve this capability, microbubbles are decorated with targeting ligands, possessing specific affinity towards vascular biomarkers of disease, such as tumour neovasculature or areas of inflammation, ischaemia-reperfusion injury or ischaemic memory. Once bound to the target, microbubbles can be selectively visualised to delineate disease location by ultrasound imaging. This review discusses the general design trends and approaches for such molecular ultrasound imaging agents, which are currently at the advanced stages of development, and are evolving towards widespread clinical trials.
| S-EPMC6319889 | biostudies-literature