| 1. |
- Abbasiasl, Taher, et al.
(författare)
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Effect of intensified cavitation using poly (vinyl alcohol) microbubbles on spray atomization characteristics in microscale
- 2020
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Ingår i: AIP Advances. - : American Institute of Physics (AIP). - 2158-3226. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- In this study, cavitating flows inside a transparent cylindrical nozzle with an inner diameter of 0.9 mm were visualized, and the effect of cavitation on atomization characteristics of emerging sprays was investigated. Different patterns of cavitating flows inside the nozzle were visualized using a high-speed camera. In-house codes were developed to process the captured images to study the droplet size distribution and droplet velocity in different flow regimes. The results show that cavitating flows at the microscale have significant effects on atomization characteristics of the spray. Two working fluids, namely, water and poly(vinyl alcohol) microbubble (PVA MB) suspension, were employed. Accordingly, the injection pressures were detected as 690 kPa, 1035 kPa, and 1725 kPa for cavitation inception, supercavitation, and hydraulic flip flow regimes in the case of water, respectively. The corresponding pressures for the aforementioned patterns for PVA MB suspension were 590 kPa, 760 kPa, and 1070 kPa, respectively. At the microscale, as a result of a higher volume fraction of cavitation bubbles inside the nozzle, there is no large difference between the cavitation numbers corresponding to cavitating and hydraulic flip flows. Although the percentage of droplets with diameters smaller than 200 μm was roughly the same for both cases of water and PVA MB suspension, the Sauter mean diameter was considerably lower in the case of PVA MBs. Moreover, higher droplet velocities were achieved in the case of PVA MBs at lower injection pressures.
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| 2. |
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| 3. |
- Brismar, Torkel B., et al.
(författare)
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Magnetite Nanoparticles Can Be Coupled to Microbubbles to Support Multimodal Imaging
- 2012
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 13:5, s. 1390-1399
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Tidskriftsartikel (refereegranskat)abstract
- Microbubbles (MBs) are commonly used as injectable ultrasound contrast agent (UCA) in modern ultrasonography. Polymer-shelled UCAs present additional potentialities with respect to marketed lipid-shelled UCAs. They are more robust; that is, they have longer shelf and circulation life, and surface modifications are quite easily accomplished to obtain enhanced targeting and local drug delivery. The next generation of UCAs will be required to support not only ultrasound-based imaging methods but also other complementary diagnostic approaches such as magnetic resonance imaging or computer tomography. This work addresses the features of MBs that could function as contrast agents for both ultrasound and magnetic resonance imaging. The results indicate that the introduction of iron oxide nanoparticles (SPIONs) in the poly(vinyl alcohol) shell or on the external surface of the MBs does not greatly decrease the echogenicity of the host MBs compared with the unmodified one. The presence of SPIONs provides enough magnetic susceptibility to the MBs to accomplish good detectability both in vitro and in vivo. The distribution of SPIONs on the shell and their aggregation state seem to be key factors for the optimization of the transverse relaxation rate.
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| 4. |
- Capece, Sabrina, et al.
(författare)
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A general strategy for obtaining biodegradable polymer shelled microbubbles as theranostic devices
- 2013
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Ingår i: Chemical Communications. - 1359-7345 .- 1364-548X. ; 49:51, s. 5763-5765
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Tidskriftsartikel (refereegranskat)abstract
- Fabrication of multifunctional ultrasound contrast agents (UCAs) has been recently addressed by several research groups. A versatile strategy for the synthesis of UCA precursors in the form of biodegradable vesicles with a biocompatible crosslinked polymer shell is described. Upon ultrasound irradiation, acoustic droplet vaporization transforms such particles into microbubbles behaving as UCAs. This proof of concept entails the features of a potential theranostic microdevice.
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| 5. |
- Capese, Sabrina, et al.
(författare)
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A general strategy for the obtainment of biodegradable polymer shelled microbubbles as theranostic device
- 2013
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Konferensbidrag (refereegranskat)abstract
- IntroductionFabrication of multifunctional ultrasound contrast agents (UCAs) has been addressed by many research groups.1,2 Recently a poly(vinyl alcohol) shelled microbubble 3 has shown a remarkable chemical and physical stability and versatility for the surface functionalization, leading to a platform for multimodality imaging (ultrasounds, magnetic resonance, single photon emission computer tomography) and targeting inflammation and tumours4. In this contribution we present a new strategy for the synthesis of UCAs precursors in the form of vesicles with a biodegradable crosslinked polymer shell.MethodsDeposition of methacryloyl-derivative of hydrophilic and biodegradable polymers as dextran (DexMA50) or hyaluronic acid (HAMA30) on a lipid vesicle with a liquid perfluoropentane core, 5,6 followed by a photopolymerization of the methacrylate moiety allows the obtainment of polymer shelled vesicles.ResultsLipid shelled vesicles with a perfluorocarbon (PFC) core (Figure 1a) undergo an acoustic droplet vaporization (ADV),7 upon ultrasounds (US) irradiation, transforming such particles into ultrasound effective microbubbles (Fig 1b). The process is reversible as the US are switched off (Fig 1c). In the “microbubble” state, i.e. during US irradiation, the system is echogenic at low mechanical index, allowing their use as UCAs. In this contribution we show that additional functions can be implemented into the microbubbles. For example, we demonstrated the possibility to obtain shells with a thermoreversible behaviour.ConclusionsThis new class of polymer shelled vesicles/microbubbles entails features desired in a potential theranostic microdevice.
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| 6. |
- Chen, Hongjian, et al.
(författare)
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A mathematical model of polyvinyl alcohol microbubbles
- 2020
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Konferensbidrag (refereegranskat)abstract
- Microbubbles (MBs) as ultrasound contrast agents (UCAs) are increasingly accepted in the medical diagnostics. Their unique acoustic features enable the efficient detection of the MBs at a very low volume fraction. An improved understanding of the MBs dynamics could accelerate the development of UCA detection, i.e., enhanced ultrasound imaging techniques. Thereby, considerable efforts were dedicated to establishing models to interpret the dynamics of the microbubbles.The joint endeavors of Rayleigh[1], Plesset[2], and other researchers led to the Rayleigh-Plesset equation, which describes the dynamics of the free MBs. The free MBs as a UCA has limited value because of their short lifespan in the human body. Additional coatings around the gas core with various materials were employed to extend the lifespan of the MBs. As a result, the models of the MBs evolved to explain the effects of the encapsulation. At the same time, many simplified assumptions were made. However, the diversity and the complexity of the MBs shell make some simplified assumptions invalided.For instance, the polyvinyl alcohol (PVA) shell of the PVA MBs is heterogeneous and exhibit frequency-dependent mechanical properties, which were often neglected in previous studies.
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| 7. |
- Chen, Hongjian
(författare)
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Exploring Polymer-Shelled Microbubbles: Detection Modeling and Application
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ultrasound imaging (US) is widely used in clinical practice. Given the low cost and easy access to the ultrasound machine, US has a great potential to improve the health care condition for the majority of the population in the world. The US could be significantly improved by injecting ultrasound contrast agents to opacify the bloodstream. The polymer-shelled microbubbles (MB) are promising candidates for the next generation ultrasound contrast agent. In the current doctoral work, one of the polymer-shelled MBs, the polyvinyl alcohol (PVA) MB was investigated.In Study I and Study II, I developed a novel contrast pulse sequence, CPS4, to efficiently detect the PVA MBs. The CPS4 is a combination of the sub-harmonic (SH), ultra-harmonic, and pulse inversion techniques. The comparison of the performance of each individual technique and CPS4 was carried out in a tissue-mimicking phantom. The CPS4 demonstrated the highest contrast-to-tissue ratio among all four imaging techniques. However, the SH response of the CPS4 was not fully excited. The high SH pressure threshold, above which the SH response is generated, was suspected to be the reason for the weak SH signal. Therefore, I wanted to optimize the performance of the CPS4 for the PVA MBs detection by boosting the SH signal. The optimization strategy was to lower the frequency-dependent SH threshold by setting the SH excitation frequency, which is the frequency of the ultrasound wave that excites the SH response, at the damped resonance frequency of the PVA MBs. To estimate the damped resonance frequency, a mathematical model based on the Church’s model with frequency-dependent material properties was proposed. The mechanical parameters of the new model were estimated by fitting the measured attenuation coefficient of the PVA MBs suspension with the simulated one. The calibrated model was employed to predict the damped resonance frequency of the PVA MBs, i.e., the optimized SH excitation frequency for the CPS4. The performance of the CPS4 was evaluated in-vitro, driving the system at four SH excitation frequencies in the proximity of the damped resonance frequency of the PVA MBs suspension. The best performance was observed at the SH excitation frequency of 11.25 MHz, which is in line with the simulated damped resonance frequency of 10.85 MHz. The in vitro experiment also revealed that the small particles constituting the artificial blood solution might interact with the PVA MBs and decreased the response echoes in a nonlinear and frequency-dependent fashion. Thus, more efforts are needed to move our model-guided optimization methods for the CPS4 towards clinical application.In Study III, I modified the PVA MBs to support the dual-modal imaging of CT and US. The main idea of the modification is to incorporate the gold nanoparticles with the PVA MBs. The success of the modification is dependent on the amount of the gold nanoparticles carried by the modified PVA MBs. Two routes were proposed to fabricate candidates that support dual-modal imaging. In the first route, the gold nanoparticles were added during the fabrication of PVA MBs. Thus, the gold nanoparticles were embedded in the PVA shell during its formation (candidate named AuNP-S-MB). In the second route, the gold nanoparticles were loaded into the core of the PVA MBs, substituting air by increasing the permeability (candidate named AuNP-Capsule). The CT revealed an insignificant amount of gold nanoparticles was embedded in the shell of AuNP-S-MB, while detectable gold nanoparticles were loaded into AuNP-Capsule. Moreover, the CT-number of the surrounding liquid of AuNP-Capsule is low, i.e., the gold nanoparticles were locked in the AuNP-Capsule, making the second route a promising step towards the further development of the dual-modal contrast agent for CT and US.In Study IV, I studied the effect of PVA MBs on the cavitation flows in microscale. The cavitation in clinical practices generates great pressure, which might be harmful and damage cells or beneficial and facilitate the treatment. A better understanding of cavitation generation mechanisms could avoid harmful cavitation, increase the safety of the clinical protocol, and increase the therapeutic cavitation, empower the treatments. Therefore, the effect of PVA MBs on cavitation is of great interest. More specifically, the effect of PVA MBs on the hydrodynamic cavitation was studied. Three microfluidic devices with different wall roughness and structure were fabricated. Two working fluids, PVA MBs suspension and water, were driven with controlled pressure through different microfluidic devices. The high-speed visualization revealed that the PVA MBs trigger the inception of hydrodynamic cavitation at a lower upstream pressure and enhance the cavitation flow in all three microfluidic devices. Furthermore, it takes a longer time for the cavitation bubbles to disappear in the PVA MB suspension.To conclude the doctoral work, I developed a novel detection sequence, CPS4, optimized it for PVA MBs with a model-guided method, modified the PVA MB to extend its application, and studied the effect of PVA MB on hydrodynamic cavitation. The work promotes the PVA MBs for pre-clinical study, as well as provides an insight into the studies of other clinically approved ultrasound contrast agents. The methodology developed and presented within the thesis can be transferred to other clinically approved ultrasound contrast agents. For instance, the CPS4 and model-guided optimization method could be employed to improve CPS4 to other ultrasound contrast agents.
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| 8. |
- Chen, Hongjian, et al.
(författare)
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Model-guided customization of a contrast pulse sequence for polyvinyl alcohol microbubbles
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Simulations of microbubbles (MBs) suggest that the excitation threshold for sub-harmonic generation is frequency-dependent. The minimum threshold, dependent on models and assumptions, might appear near the resonance frequency. Given that, in the current study, attempts were made to optimize a novel contrast pulse sequence, CPS4, for the in-house ultrasound contrast agent, polyvinyl alcohol microbubbles (PVA MBs) by setting the transmitting frequency near their resonance frequency to boost the sub-harmonic response. An improved model for PVA MBs was proposed to predict the resonance frequency. An in-vitro experiment was performed to evaluate the performance of CPS4 at different transmitting frequencies. The experiment results suggest the optimal performance of CPS4 with PVA MBs aqueous suspension appeared at the transmitting frequency of 11.25 MHz, which agrees with the values of the damped resonance frequency determined from simulation. The influence of the liquid environment on the performance of the CPS4 was also studied. The replacement of water with artificial blood degrades the contrast-to tissue ratio of CPS4 and shifts the optimal performance to the higher transmitting frequency.
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| 9. |
- Chen, Hongjian, et al.
(författare)
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On the Development of a Novel Contrast Pulse Sequence for Polymer-Shelled Microbubbles
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Ingår i: IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control. - 0885-3010 .- 1525-8955.
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Tidskriftsartikel (refereegranskat)abstract
- Contrast agents are routinely used in ultrasound examinations. Nonlinear ultrasound imaging techniques have been developed over decades to enhance the contrast between the tissue and the blood pool after the injection of ultrasound contrast agents. In this study, we introduce a new contrast pulse sequence, CPS4. The CPS4 combines pulse inversion, sub-harmonic, and ultra-harmonic techniques to remove propagation distortion while capturing the unique sub-harmonic, and ultra-harmonic responses from ultrasound contrast agents. The novel CPS4 and conventional pulse inversion, sub-harmonic, and ultra-harmonic techniques were used to detect the presence of a research-grade, thick shell, polymer microbubble in a tissue-mimicking flow phantom. The contrast-to-tissue ratio (CTR) obtained from the applications of all techniques were compared. The results show that the highest CTR of approximately 16 dB was obtained using CPS4, which was superior to the individual reference techniques: pulse inversion, sub-harmonic, and ultra-harmonic techniques, at all scenarios considered in this study.
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| 10. |
- Chen, Hongjian, et al.
(författare)
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On the Development of a Novel Contrast Pulse Sequence for Polymer-Shelled Microbubbles
- 2021
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Ingår i: IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control. - : Institute of Electrical and Electronics Engineers (IEEE). - 0885-3010 .- 1525-8955. ; 68:5, s. 1569-1579
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Tidskriftsartikel (refereegranskat)abstract
- Contrast agents are routinely used in ultrasound examinations. Nonlinear ultrasound imaging techniques have been developed over decades to enhance the contrast between the tissue and the blood pool after the injection of ultrasound contrast agents (UCAs). In this study, we introduce a new contrast pulse sequence, CPS4. The CPS4 combines pulse inversion (PI), subharmonic (SH), and ultraharmonic (UH) techniques to remove propagation distortion while capturing the unique SH and UH responses from UCAs. The novel CPS4 and conventional PI, SH, and UH techniques were used to detect the presence of a research-grade, thick-shell, polymer microbubble in a tissue-mimicking flow phantom. The contrast-to-tissue ratios (CTRs) obtained from the applications of all techniques were compared. The results show that the highest CTR of approximately 16 dB was obtained using CPS4, which was superior to the individual reference techniques: PI, SH, and UH techniques, in all scenarios considered in this study.
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