| 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. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- 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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| 8. |
- Chen, Hongjian, et al.
(författare)
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Polymer microbubbles loaded with gold nanoparticles as hybrid contrast agent for computed tomography and ultrasound
- 2020
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Ingår i: Biomedical Research and Clinical Practice. - London, United Kingdom : Open Access Text Pvt, Ltd.. - 2397-9631. ; 5, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Microbubbles (MBs) with size below 10 μm are commonly used as an ultrasound contrast agent (UCA). The aim of the novel UCA developed in our lab is to support imaging modalities other than ultrasound to form hybrid contrast agents. The hybrid contrast agents through the synergistic effect can potentially improve the diagnostic outcome of the combined multimodal imaging technique. In this study, we modified the polyvinyl alcohol (PVA) MB fabrication protocol to encapsulate the gold nanoparticles into the shell and also in the core of the MBs. Furthermore, we evaluated the morphology, nonlinear ultrasound response, and X-ray property of dual modal contrast agents. The results revealed that the loading of the gold nanoparticles into the PVA MB core is a promising step towards the development of the dual modal contrast agent.
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| 9. |
- Chen, Hongjian, et al.
(författare)
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Sequence design for ultrasound imaging of polyvinyl alcohol microbubbles
- 2019
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Konferensbidrag (refereegranskat)abstract
- Nonlinear behavior of the ultrasound contrast agent (UCA) offers a unique feature to be distinguished from the surrounding tissue. In a recent years several methods were developed to enhance the nonlinear response of UCA. Crucial for efficient differentiation of the nonlinear response of UCA from the surrounding tissue is to design the contrast pulse sequence specific to the unique nonlinear properties that the particular UCA is offering.In the previous study, the nonlinear response from a novel polyvinyl alcohol (PVA) microbubbles (MB), in ultra-harmonic region was investigated over a pressure range from 50 kPa to 300 kPa. In this study, five contrast pulse sequences and reference B-mode sequence were designed to visualize PVA MB. The performance of those sequences were evaluated and compared.
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| 10. |
- Chen, Hongjian, et al.
(författare)
-
Sequence design for ultrasound imaging of polyvinyl alcohol microbubbles
- 2020
-
Konferensbidrag (refereegranskat)abstract
- In the previous study [1], a novel contrast pulse sequence, CPS4, was introduced. The CPS4 combined sub-harmonic, ultra-harmonic and pulse inverse imaging to provide an improved contrast-to-tissue ratio (CTR). The CPS4 emits two pairs of transmitting waves at frequencies of f0/2 and 2*f0 with inversed phase within each pair and filters the received echoes at the frequency of f0. However, the performance of CPS4 was not optimized. Simulation study [2] shows that there is a pressure threshold for the sub-harmonic response generation of the ultrasound contrast agent (UCA). The threshold is expected to reach its local minima with the transmitting frequency around the resonance frequency. By lowering the threshold, more MBs could be excited to response sub-harmonic signal which could improve the CTR of CPS4.The current study aims to investigate frequency-dependent performance of CPS4 with the polyvinyl alcohol microbubbles (PVA MBs). First a linear oscillator model adapted from Hoff and Church[3, 4] was built for single PVA MB. The attenuation and phase velocity of a PVA MB suspension were obtained to calibrate the linear oscillator. The model was used to estimate the resonance frequency of the MBs. The transmitting frequency of CPS4 for sub-harmonic was set at four frequency points around the local minima, i.e. resonance frequency. The performance of CPS4 at different frequencies were evaluated.
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| 11. |
- Faridi, M. A., et al.
(författare)
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Microbubble assisted cell sorting by acoustophoresis
- 2016
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Ingår i: 20th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2016. - : Chemical and Biological Microsystems Society. - 9780979806490 ; , s. 1677-1678
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Konferensbidrag (refereegranskat)abstract
- Polymer shelled gas microbubbles (MBs) are used to sort cells in a microfluidic chip under acoustic standing waves (SW). When particles are subjected to SW based on their acoustic contrast factor (ACF) they migrate to nodes (positive contrast factor particles; PACP) or antinodes (negative acoustic contrast particles; NACP)[1]. We have bounded functionalized MBs with cells such that, they can be selectively migrated to antinodes under SW and sorted from unbounded cell both in no flow and flow conditions. Here we demonstrate acoustic mediated microbubble tagged cell sorting with 75% efficiency.
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| 12. |
- Ghorbani, Morteza, et al.
(författare)
-
Acoustic Response of a Novel Class of Pickering Stabilized Perfluorodroplets
- 2019
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Konferensbidrag (refereegranskat)abstract
- IntroductionAcoustic Droplet Vaporization (ADV) is a phase change phenomenon in which the liquid state, in the form of droplets, is converted to gas as a result of bursts in the excited ultrasound field. Having a wide range of medical applications, ADV has drawn considerable attention in imaging [1], diagnosis and critical medical treatment [2]. Therefore, benefitting from its broad potentials, with the consideration of its capability in localized noninvasive energy exposure, it is possible to utilize its effect in different medical applications from targeted drug delivery [3] to embolotherapy [4].Apart from the droplet characterization and ADV effectiveness on the applied region, the physics of ADV and particularly the ultrasound analysis is an essential parameter in the initiation of the vaporization. This part, which is related to acoustic wave physics, implies that ADV is mostly dependent on ultrasound pressure, frequency and temperature. In this sense, Miles et al. [5] tried to find incident negative pressure - called as ADV threshold- which is necessary for the induction of nucleation. It was successfully shown that the negative pressure required for the nucleation prior to collapse can be determined via perturbation analysis of a compressible inviscid flow around a droplet for various frequencies and diameters. In addition, the fluid medium which constitutes the droplet emulsion and the surrounding fluid constructs a significant field within ADV. In this regard, there are many studies which illustrated that the diameter of the droplets subjected to the acoustic waves undergoes a significant expansion of 5 to 6 times of their regular sizes [6-8].In this study, a new type of pickering stabilized perfluorodroplets (PFC) was examined under the effect of the different acoustic parameters to evaluate its potential in the acoustic droplet vaporization process. To assess the pressure effects on the stabilized droplets, the acoustic power within the ultrasound tests was varied and the phase trasnition was characterized according to the experimental conditions. Opticell® was utilized as the transparent device to visualize the droplets, which were exposed to the acoustic waves with the aid of the microscope and multi-well microplate.MethodsMaterials and emulsion preparationPerfluoropentane (PFC5) was purchased from Apollo Scientific (City, U.K.). Bleached sulfite pulp (from Nordic Paper Seffle AB, Sweden) was used in the production of the cationic cellulose nanofibers (CNFs). The CNF suspension (1.32 wt%) were prepared as described previously [9]. The CNFs had a dimension of 3.9 ± 0.8 nm in width and a length in the micrometer range. The amount of cationic groups was 0.13 mmol per g fiber, obtained from conductometric titration [9]. A suspension of CNF (0.28 wt%) was prepared by diluting the stock CNF with MilliQ-water (pH of diluted CNF suspension was 9.5). The suspension was treated with ultra-sonication at amplitude of 90% for 180 s (Sonics, Vibracell W750). The suspension was brought to room temperature. An amount of 36 g of the 0.28 wt% CNF suspension was mixed with 1 g of PFC5. The mixture was sonicated for 60s at an amplitude of 80% (under ice-cooling) to obtain the CNF-stabilized PFC5 droplets.The protocol for the acoustic tests100 μL of CNF-stabilized PFC5 droplets were added to 1900 μL of deionized water in order to prepare the solution which were exposed to the ultrasound waves. The droplet sample, diluted 1:19 in distilled water was introduced to the Opticell® and the acoustic waves at a fixed frequency and different powers were applied to the trageted area inside the Opticell® which is located inside a water bath. The ultrasound triggered sample then was placed under a 20X magnification objective of upright transmitted light microscope (ECLIPSE Ci-S, Nikon, Tokyo, Japan). The acoustic tests were performed using high-power tone burst pulser-receiver (SNAP Mark IV, Ritec, Inc., Warwick, RI, USA) equipped with a transducer (V382-SU Olympus NDT, Waltham, MA ) operating at the frequency of 3.5 MHz. The emulsion of CNF-stabilized PFC5 droplets were exposed to the power range which has the acsending trend from -30 to 0 dB at the given frequency. To investigate the droplet size variations at each power between, the droplets were collected inside the Opticell® and the droplet diameter was measured with the aid of the ImageJ software (version 1.50b, National institutes of health, USA) to determine the concentration and size distribution. The Gaussian distribution is ploted with mean value and standad deviation recover from the experimental data. An in-house image edge detection MATLAB™ script (MathWorks Inc., Natick, MA) were applied to analyze the images obtained from the microscope and provides the size and volume distributions.ResultsThe size of PFP droplets is an important parameter to controll in the therapeutic applications. Here, a new type of Pickering stabilized perfluorodroplets were prepared where the PFP/water interface was stabilized with cellulose nanofibers (CNF) and the size of the droplets could easily be controlled by varying the amount of CNF added. The resulting droplets were investigated using a single crystal transducer. Apart from the medical applications, controlling the droplet size is important from droplet dynamics point of view, becausethe interfacial energy is crucial in the assumption of the critical nucleus radius. Therefore, it is possible to estimate the negative peak pressure required for the phase transition once the droplet is controlled and interfacial energy deposited inside and on the surface of the droplet are balanced.According to the results in Figure 1, there is an appreciable rise of the size of the droplets after ultrasound waves exposure, particularly at -8 dB power. The experiments were performed for 30 seconds at different powers ranging from -30 to 0 dB, while the frequency was kept constant at 3.5 MHz, burst width in cycles was selected as 12 and repetition rate was set to 100. Images included in Figure 1 demonstrate major transitions in the intervals at -16, -8 and 0 dB. As shown in this figure, the droplet size increased with the power rise and more bubbles with bigger sizes appears at higher powers. This outcome implies the significant role of the applied frequency and power on the phase shift and subsequent mechanisms as a result of the acoustic wave exposure on the new nontoxic and incompatible droplet type.Figure 2 shows the average number of droplets and volume distribution at the corresponding powers to the Figure 1. It is shown that while the average diameter of the droplets is around 3.5 µm, the generated bubbles, as a result of the ADV, reaches up to 15 µm at the highest possible power. For each set of experiment (corresponding to a given power) 32 images were taken, thus, to reduce the errors and obtain the standard deviation (approximately 0.8 for all the cases), the presented diagrams for the droplet distributions exhibits the mean value for all of the acquired images. Therefore, it is shown that the droplet emulsion exhibited in NO US in Figure 2, which shows the regular view and distribution range of the CNF-stabilized PFC5 droplets at the room temperature, experiences ADV process with the diameter rise of about 5 times at the highest power when the frequency is fixed at 3.5 MHz.ConclusionsThe results show that there is appreciable rise on the size of the droplets after ultrasound waves exposure at a fixed frequency. Acoustic droplet vaporization (ADV) was illustrated at different powers for CNF-stabilized PFC5 droplets as a new class of pickering stabilized perfluorodroplets with the increase in the size of the droplets and following phase trasition to bubbles. Diameter increase of 5 times were obtained after the ultrasound exposure indicating the efficiency of the suggested droplets for the ADV process and therapeutic applications. References[1] Arena CB, Novell A, Sheeran PS, Puett C, Moyer LC, Dayton PA, Dual-Frequency Acoustic Droplet Vaporization Detection for Medical Imaging 2015, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, 62: 9.[2] Kripfgans OD, Fowlkes JB, Miller DL, Eldevik OP, Carson PL, Acoustic droplet vaporization for therapeutic and diagnostic applications 2000, Ultrasound Med. Biol, 26:1177–1189.[3] Kang ST, Yeh CK, Intracellular Acoustic Droplet Vaporization in a Single Peritoneal Macrophage for Drug Delivery Applications 2011, Langmuir, 27:13183–13188.[4] Zhu M, Jiang L, Fabiilli ML, Zhang A, Fowlkes JB, Xu LX, Treatment of murine tumors using acoustic droplet vaporization-enhanced high intensity focused 2013, Ultrasound Phys. Med. Biol, 58:6179–6191.[5] Miles CJ, Doering CR, Kripfgans OD, Nucleation pressure threshold in acoustic droplet vaporization 2016, Journal of Applied Physics, 120:034903.[6] Sheeran PS, Wong VP, Luois S, McFarland RJ, Ross WD, Feingold S, Matsunaga TO, Dayton PA, Decafluorobutane as a phase-change contrast agent for low-energy extravascular ultrasonic imaging 2011, Ultrasound Med. Biol, 37:1518–1530.[7] Kripfgans OD, Fowlkes JB, Miller DL, Eldevik OP, Carson PL, Acoustic droplet vaporization for therapeutic and diagnostic applications 2000, Ultrasound Med. Biol, 26:1177–1189.[8] Kang S, Huang Y, Yeh C, Characterization of acoustic droplet vaporization for control of bubble generation under flow conditions 2014, Ultrasound Med. Biol, 40:551–561.[9] Svagan AJ, Benjamins JW, Al-Ansari Z, Shalom DB, Müllertz A, Wågberg L, Löbmann K, Solid cellulose nanofiber based foams–towards facile design of sustained drug delivery systems 2016, J. Control Release, 244:74–82 (Part A).
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| 13. |
- Ghorbani, Morteza, et al.
(författare)
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Facile Hydrodynamic Cavitation ON CHIP via Cellulose Nanofibers Stabilized Perfluorodroplets inside Layer-by-Layer Assembled SLIPS Surfaces
- 2019
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Ingår i: Chemical Engineering Journal. - : Elsevier. - 1385-8947 .- 1873-3212.
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Tidskriftsartikel (refereegranskat)abstract
- The tremendous potential of “hydrodynamic cavitation on microchips” has been highlighted during recent years in various applications. Cavitating flow patterns, substantially depending upon thermophysical and geometrical characteristics, promote diverse industrial and engineering applications, including food and biomedical treatment. Highly vaporous and fully developed patterns in microfluidic devices are of particular interest. In this study, the potential of a new approach, which includes cellulose nanofiber (CNF)- stabilized perfluorodroplets (PFC5s), was assessed inside microfluidic devices. The surfaces of these devices were modified by assembling various sizes of silica nanoparticles, which facilitated in the generation of cavitation bubbles. To examine the pressure effects on the stabilized droplets in the microfluidic devices, the upstream pressure was varied, and the cavitation phenomenon was characterized under different experimental conditions. The results illustrate generation of interesting, fully developed, cavitating flows at low pressures for the stabilized droplets, which has not been previously observed in the literature. Supercavitation flow pattern, filling the entire microchannel, were recorded at the upstream pressure of 1.7 MPa for the case of CNF-stabilized PFC5s, which hardly corresponds to cavitation inception for pure water in the same microfluidic device.
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| 14. |
- Ghorbani, Morteza, et al.
(författare)
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Intensifying cavitating flows in microfluidic devices with poly(vinyl alcohol) (PVA) microbubbles
- 2018
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Ingår i: Physics of fluids. - : American Institute of Physics (AIP). - 1070-6631 .- 1089-7666. ; 30:10
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Tidskriftsartikel (refereegranskat)abstract
- Cavitation and the energy associated with the collapse of resulting cavitation bubbles constitute an important research subject. The collapse of the hydrodynamic cavitation bubbles at the outlet of the flow elements leads to a high energy release and generates localized shock waves and a large temperature rise on exposed surfaces. The concept of “hydrodynamic cavitation on chip” is an emerging topic which emphasizes phase change phenomena in microscale and their utilizations in energy and biomedical applications. This study is aimed to investigate the potential of poly(vinyl alcohol) (PVA) Microbubbles (MBs) to generate cavitation bubbles and to evaluate their effects on flow regimes and energy dissipation. For this, three different microchannel configurations with different roughness elements were considered. The structural side wall and surface roughened channels were fabricated along with the smooth channel according to the techniques adopted from semiconductor based microfabrication. The upstream pressure varied from 1 to 7 MPa, and the flow patterns were recorded and analyzed using a high-speed camera. The pressure was locally measured at three locations along the microfluidic devices to determine the conditions for fully developed cavitating flows. The results were compared to the pure water case, and different trends for the cavitating flow pattern transitions were obtained for the water-PVA MB solution case. Accordingly, the twin cavity clouds extended to the end of the side wall roughened channel at a lower upstream pressure for the case of PVA MBs, while the smooth and surface roughened channels do not demonstrate this flow pattern. In addition, the cavitation number has the lowest values under the same working conditions for the case of PVA MBs. Moreover, the impact pressure generated by the bubble collapse inside the side wall roughened channel for the case of PVA MBs was notably higher than that for pure water.
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| 15. |
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| 16. |
- Ghorbani, Morteza, et al.
(författare)
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Unravelling the Acoustic and Thermal Responses of Perfluorocarbon Liquid Droplets Stabilized with Cellulose Nanofibers
- 2019
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Ingår i: Langmuir. - : American Chemical Society. - 0743-7463 .- 1520-5827. ; 35:40, s. 13090-13099
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Tidskriftsartikel (refereegranskat)abstract
- The attractive colloidal and physicochemical properties of cellulose nanofibers (CNFs) at interfaces have recently been exploited in the facile production of a number of environmentally benign materials, e.g. foams, emulsions, and capsules. Herein, these unique properties are exploited in a new type of CNF-stabilized perfluoropentane droplets produced via a straightforward and simple mixing protocol. Droplets with a comparatively narrow size distribution (ca. 1-5 μm in diameter) were fabricated, and their potential in the acoustic droplet vaporization process was evaluated. For this, the particle-stabilized droplets were assessed in three independent experimental examinations, namely temperature, acoustic, and ultrasonic standing wave tests. During the acoustic droplet vaporization (ADV) process, droplets were converted to gas-filled microbubbles, offering enhanced visualization by ultrasound. The acoustic pressure threshold of about 0.62 MPa was identified for the cellulose-stabilized droplets. A phase transition temperature of about 22 °C was observed, at which a significant fraction of larger droplets (above ca. 3 μm in diameter) were converted into bubbles, whereas a large part of the population of smaller droplets were stable up to higher temperatures (temperatures up to 45 °C tested). Moreover, under ultrasound standing wave conditions, droplets were relocated to antinodes demonstrating the behavior associated with the negative contrast particles. The combined results make the CNF-stabilized droplets interesting in cell-droplet interaction experiments and ultrasound imaging.
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| 17. |
- Grishenkov, Dmitry, 1983-, et al.
(författare)
-
Acoustic properties of polymer-shelled ultrasound contrast agents. Bulk volume vs. microcapillary
- 2009
-
Ingår i: 16th International Congress on Sound and Vibration 2009, ICSV 2009. - Krakow. - 9781615677368 ; , s. 2515-2522
-
Konferensbidrag (refereegranskat)abstract
- The focus of contrast-enhanced ultrasound research has developed beyond detecting the blood pool to new areas such as perfusion imaging, drug and gene therapy, and targeted imaging. Polymer-shelled microbubbles are proposed as a new generation of ultrasound contrast agents (UCAs) which fulfil the requirements of these applications. With a shelf-life of several months and possibility to conjugate pharmacological molecules to their surface, these UCAs will allow not only to enhance the contrast of ultrasound images, but also to function as carriers of drugs to be delivered locally. In this study, the results of an experimental investigation of three types of UCAs stabilized by thick poly vinyl alcohol (PVA) shell are presented. These UCAs are synthesized from a PVA aqueous solution under varied pH values and temperature. The UCAs differ from each other in their average diameter, shell thickness and polydispersity. Knowledge of the peak negative pressure at which the solid shell fractures is paramount for a proper use of UCAs. Therefore, the dependence of this quantity on temperature and number of cycles in the incident pulse is examined. Much of the blood volume resides in the microcirculation, with capillaries playing a particularly important role in patho-physiology and drug delivery. In this sense in vitro characterization of the UCAs oscillation was moved from bulk volume to the capillary scale, where tissue-bubble interaction takes place. The main conclusion to be drawn from these results is that the shell of the UCAs begin to fracture at values of mechanical index (MI) approved for clinical applications. The fatigue, i.e. the accumulation of damage within the shell of the UCAs, is found to play an important role in fracturing the shell. Finally adhesion of the UCAs to the elastic wall is studied and correlated with estimates of the shell’s visco-elastic constants. Open questions arising from this comparison are briefly discussed.
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| 18. |
- Grishenkov, Dmitry, 1983-, et al.
(författare)
-
Assessment of ultrasound-induced fracture of polymer-shelled ultrasound contrast agents using superharmonic technique
- 2012
-
Konferensbidrag (refereegranskat)abstract
- 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 wave. The novel approach based on detection of superharmonics (3f and 4f) is proposed for assessment of the fracture pressure threshold, Pthr. In vitro tests suggests that fatigue, i.e. accumulation of damage within the shell, is the major physical mechanism responsible for the fracturing process. It has been observed that there is a decrease of Pthr from 1.15±0.09 MPa to 0.9±0.05 MPa when the number of cycles in the pulse, N, increases from 6 to 12. It is worth noting that the reported pressure values are within clinically approved safety limits. The main conclusion to be drawn from our study is that superharmonic approach appears to be more sensitive in Pthr assessment than traditional second harmonic imaging. This claim is supported also by images acquired with a commercially available system, where contrast pulse sequencing technique, specific to third harmonic, is required for visualization of thick-shelled microbubbles.
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| 19. |
- Grishenkov, Dmitry, 1983-, et al.
(författare)
-
Characterization of Acoustic Properties of PVA-Shelled Ultrasound Contrast Agents
- 2010
-
Ingår i: Ultrasound Contrast Agents. - Italia : Springer-Verlag. - 9788847014930 ; , s. 99-108
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This work examines the acoustic behavior of ultrasound contrast agents made of poly (vinyl alcohol) (PVA) shelled microbubbles manufactured at three different pH and temperature conditions. Backscattering amplitude, attenuation coefficient and phase velocity of ultrasonic waves propagating through suspensions of PVA contrast agents were measured at temperature values ranging between 24 oC and 37 oC in a frequency range from 3 MHz to 13 MHz. A significant enhancement of the backscattering amplitude and displaying a weak dependence on temperature were observed. Attenuation and phase velocity, on the other hand, showed higher sensitivity to temperature variations. The dependence on system parameters such as the number of cycles, frequency, and exposure of the peak negative pressure, Pthr, at which ultrasound contrast agents fracture was also investigated. The effects of temperature, blood, and, wherever data are available, of the dimension of the microbubbles on Pthr are also considered. The large shell thickness notwithstanding, the results of this investigation show that at room temperature PVA contrast agents fracture at negative peak pressure values within the recommended safety limit. Furthermore, Pthr decreases with increasing temperature, radius of the microbubbles, and number of cycles of the incident wave. In conclusion, these results suggest that PVA-shelled microbubbles may offer a potentially viable system to be employed for both imaging and therapeutic purposes.
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| 20. |
- Grishenkov, Dmitry, 1983-, et al.
(författare)
-
Characterization of acoustic properties of PVA-shelled ultrasound contrast agents : linear properties (Part I)
- 2009
-
Ingår i: Ultrasound in Medicine and Biology. - : Elsevier BV. - 0301-5629 .- 1879-291X. ; 35:7, s. 1127-1138
-
Tidskriftsartikel (refereegranskat)abstract
- This work examines the linear acoustic behavior of ultrasound contrast agents made of three types of poly (vinyl alcohol) (PVA) shelled microbubbles manufactured at different pH and temperature conditions. Back-scattered power, attenuation coefficient and phase velocity of ultrasonic waves propagating through suspensions of PVA contrast agents were measured at temperature values ranging between 24 degrees C and 37 degrees C in a frequency range from 3 MHz to 13 MHz. Enhancement of the backscattered power higher than 20 dB and displaying a weak dependence on temperature was observed. Attenuation and phase velocity, on the other hand, showed higher sensitivity to temperature variations. A modified version of the Church model, which accounts for the dispersion of the dynamic modulus of the PVA shells, was developed to simultaneously fit the attenuation and phase velocity data at 24 degrees C. The frequency dependence of the storage modulus was found to be that of semiflexible polymeric networks. On the other hand, the frequency dependence of the dynamic loss modulus suggests that additional mechanisms, which may be related to the finite dimensions of the shell and/or to its inhomogeneity, may play a significant role in the dissipation of the acoustic energy. For the microbubbles of interest, this model predicts frequency dependent resonance frequency higher than 100 MHz.
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| 21. |
- Grishenkov, Dmitry, 1983-, et al.
(författare)
-
Characterization of acoustic properties of PVA-shelled ultrasound contrast agents : ultrasound-induced fracture (Part II)
- 2009
-
Ingår i: Ultrasound in Medicine and Biology. - : Elsevier BV. - 0301-5629 .- 1879-291X. ; 35:7, s. 1139-1147
-
Tidskriftsartikel (refereegranskat)abstract
- Knowledge of the magnitude of the peak negative pressure, P-thr, at which ultrasound contrast agents fracture is relevant for using these microbubbles both as devices for contrast enhancement purposes, as well as carriers of drugs to be delivered locally. In the second part of this communication, the acoustic properties of three types of microbubbles stabilized by poly (vinyl alcohol) (PVA) shells are further investigated. In particular, the dependence of P-thr on system parameters such as the number of cycles, frequency and exposure is examined. The effects of temperature, blood and, wherever data are available, of the dimension of the microbubbles on P-thr are also considered. The large shelf thickness notwithstanding, the results of this investigation show that at room temperature, PVA contrast agents fracture at negative peak pressure values within the recommended safety limit. Furthermore, P-thr decreases with increasing temperature, radius of the microbubbles and number of cycles of the incident wave. Fatigue seems to be a physical mechanism playing a dominant role in the fracture process. The effect of blood on P-thr varies according to condition under which the microbubbles have been synthesized, although stiffening of the shell is observed in most cases. In conclusion, these results suggest that PVA-shelled microbubbles may offer a potentially viable system to be employed for both imaging and therapeutic purposes.
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| 22. |
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| 23. |
- Grishenkov, Dmitry, 1983-, et al.
(författare)
-
In search of the optimal ultrasound heart perfusion imaging platform
- 2015
-
Ingår i: Journal of ultrasound in medicine. - : Wiley. - 0278-4297 .- 1550-9613. ; 34:9, s. 1599-1605
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveQuantification of the myocardial perfusion by contrast echocardiography (CEC) remains a challenge. Existing imaging phantoms used to evaluate the performance of ultrasound scanners do not comply with perfusion basics in the myocardium, where perfusion and motion are inherently coupled.MethodsTo contribute towards an improvement, we developed a CEC perfusion imaging platform based on isolated rat heart coupled to the ultrasound scanner. Perfusion was assessed using three different types of contrast agent: dextran-based Promiten®, phospholipid-shelled SonoVue®, and polymer-shelled MB-pH5-RT. The myocardial video-intensity was monitored over time from contrast administration to peak and two characteristic constants were calculated using exponential fit (A representing capillary volume and b representing inflow velocity).ResultsAcquired experimental evidence demonstrates that the application of all three types of contrast agent allow ultrasonic estimation of myocardial perfusion in the isolated rat heart. Video-intensity maps show that an increase in contrast concentration increases the late plateau values, A, mimicking increased capillary volume. Estimated values of the flow, proportional to Axb, increase when the pressure of the perfusate column increases from 80 to 110 cm of water. This finding is in agreement with the true values of the coronary flow increase measured by the flowmeter attached to the aortic cannula.ConclusionsThe described CEC perfusion imaging platform holds promise for standardized evaluation and optimization of ultrasound contrast perfusion imaging where real time inflow curves at low acoustic power semi-quantitatively reflect coronary flow.
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| 24. |
- Grishenkov, Dmitry, 1983-, et al.
(författare)
-
In vitro contrast-enhanced ultrasound measurements of capillary microcirculation : Comparison between polymer- and phospholipid-shelled microbubbles
- 2011
-
Ingår i: Ultrasonics. - : Elsevier BV. - 0041-624X .- 1874-9968. ; 51:1, s. 40-48
-
Tidskriftsartikel (refereegranskat)abstract
- The focus of contrast-enhanced ultrasound research has developed beyond visualizing the blood pool and its flow to new areas such as perfusion imaging, drug and gene therapy, and targeted imaging. In this work comparison between the application of polymer- and phospholipid-shelled ultrasound contrast agents (UCAs) for characterization of the capillary microcirculation is reported. All experiments are carried out using a microtube as a vessel phantom. The first set of experiments evaluates the optimal concentration level where backscattered signal from microbubbles depends on concentration linearly. For the polymer-shelled UCAs the optimal concentration level is reached at a value of about 2 x 10(4) MB/ml, whereas for the phospholipid-shelled UCAs the optimal level is found at about 1 x 10(5) MB/ml.Despite the fact that the polymer shell occupies 30% of the radius of microbubble, compared to 0.2% of the phospholipid-shelled bubble, approximately 5-fold lower concentration of the polymer UCA is needed for investigation compared to phospholipid-shelled analogues. In the second set of experiments, destruction/replenishment method with varied time intervals ranging from 2 ms to 3 s between destructive and monitoring pulses is employed. The dependence of the peak-to-peak amplitude of backscattered wave versus pulse interval is fitted with an exponential function of the time gamma = A( 1 - exp(-beta t)) where A represents capillary volume and the time constant beta represents velocity of the flow. Taking into account that backscattered signal is linearly proportional to the microbubble concentration, for both types of the UCAs it is observed that capillary volume is linearly proportional to the concentration of the microbubbles, but the estimation of the flow velocity is not affected by the change of the concentration. Using the single capillary model, for the phospholipid-shelled UCA a delay of about 0.2-0.3 s in evaluation of the perfusion characteristics is found while polymer-shelled UCA provide response immediately. The latter at the concentration lower than 3.6 x 10(5) MB/ml have no statistically significant delay (p < 0.01), do not cause any attenuation of the backscattered signal or saturation of the receiving part of the system. In conclusion, these results suggest that the novel polymer-shelled microbubbles have a potential to be used for perfusion evaluation.
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| 25. |
- Grishenkov, Dmitry, 1983-, et al.
(författare)
-
On comparison between polymer- and phospholipid-shelled microbubbles for contrast-enhanced ultrasound measurements of capillary microcirculation.
- 2011
-
Ingår i: Proceedings of the 34<sup>th</sup> Scandinavian Symposium on Physical Acoustics.
-
Konferensbidrag (refereegranskat)abstract
- The focus of contrast-enhanced ultrasound research has developed beyond visualizing the blood circulation to new areas such as perfusion and molecular imaging, drug and gene therapy. This work compares the application of polymer- and phospholipid-shelled ultrasound contrast agents (UCAs) employed for characterization of the capillary microcirculation. To quantify microcirculation destruction/replenishment technique with varied time intervals between destructive and monitoring pulses is used. The dependence of the peak-to-peak amplitude of backscattered wave versus pulse interval is fitted with an exponential function of the time y=A(1-exp(-βt)) , where A represents capillary volume and the time constant β represents velocity of the flow. Working under assumption that backscattered signal is linearly proportional to the microbubble concentration, for both types of the UCAs it is observed that capillary volume, A, is in linearly relationship with the concentration, and the flow velocity, β, remain unchanged. Using 500 µm diameter microtube as a vessel phantom a delay of about 0.25 s in evaluation of the perfusion characteristics is found for the phospholipid-shelled UCA, while polymer-shelled UCA provide response immediately. In conclusion, these results suggest that the novel polymer-shelled microbubbles have a potential to be used for perfusion evaluation.
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| 26. |
- Grishenkov, Dmitry, 1983-, et al.
(författare)
-
On the acoustic properties of polymer-shell ultrasonic contrast agents.
- 2008
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Polymer-shelled microbubbles have become the focus of intense research for their enhanced shelf life and demonstrated chemical versatility. These are properties highly sought after in the ultrasonic contrast agents (UCAs) of the next generation, which will be engineered not only to enhance the contrast of ultrasound-based images, but also to function as carriers of drugs to be delivered locally. Here, the results of an experimental investigation of three potentially new UCAs are presented. These microbubbles are stabilized by thick poly (vinyl alcohol) shells. These UCAs differ from each other in their dimensions and shell thickness (order of 0.5 microns). Fundamental to their use as drug carrier is the knowledge of the pressure threshold at which the shell of these UCAs fractures. Therefore, the dependence of this quantity on temperature, number of cycles of the incident pulse, nominal central frequency and pulse repetition frequency of the emitting transducer is examined. The effect of using blood instead of deionized water is also considered. The main conclusion to be drawn from these results is that their thick shell notwithstanding, these microbubbles begin to fracture at values of MI which can be acceptable in clinical applications. This claim is supported also by images acquired by means of commercially available imaging systems. Finally, these values of the pressure threshold are correlated with estimates of the shells’ visco-elastic constants obtained by fitting Church’s model to the frequency-dependent attenuation coefficient and phase velocity. Open questions arising from this comparison are briefly discussed.
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| 27. |
- Grishenkov, Dmitry, 1983-
(författare)
-
Polymer-shelled Ultrasound Contrast Agents : Characterization and Application
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ultrasound-based imaging technique is probably the most used approach for rapid investigationand monitoring of anatomical and physiological conditions of internal organs and tissues.Ultrasound-based techniques do not require the use of ionizing radiation making the tests anexceptionally safe and painless. Operating in the frequency range between 1 to 15 MHz, medicalultrasound provides reliable visual and quantitative information from both superficial structuressuch as muscles and tendons, and also deeper organs such as liver and kidney. From the technicalpoint of view medical ultrasound has a good spatial and temporal resolution. Ultrasound machineis mobile or even portable, which makes it truly bedside modality. And last but not the least,ultrasound investigations are cheaper in comparison to other real time imaging techniques. Ultrasound imaging techniques can be greatly improved by the use of contrast agents to enhancethe signal from the area of interest (e.g. cardiac or liver tissues) relative to the background.Typically ultrasound contrast agent (UCA) is a suspension of the microbubbles consisting of agas core encapsulated within the solid shell. Generally these devices are injected systemically andfunction to passively enhance the ultrasound echo. In recent years, the UCAs have evolved frombeing just a visualization tool to become a new multifunctional and complex device for drug orgene therapy and targeted imaging. The overall objective of the project is to test novel polymer shelled microbubbles (MBs) as apossible new generation of ultrasound contrast agents. During the first year of the project an innovative criterion based on cross-correlation analysis toassess the pressure threshold at which ultrasonic waves fracture the polymer shell of microbubblehas been developed. In addition, acoustic properties of these microbubbles which are relevant totheir use both as contrast agents and drug carriers for localized delivery have been preliminarytested. Furthermore, in order to reconstruct viscoelastic properties of the shell the originalChurch’s model (1995) has been implemented. In collaboration with Karolinska Institutet, imagesof the microbubbles have been acquired with conventional imaging system. These imagesdemonstrate the potential of the novel polymer-shelled microbubbles to be used as contractenhancing agents. The objective of the second year was to describe the acoustic and mechanical properties ofdifferent types of microbubbles synthesised under varied conditions. This task was divided in twointerrelated parts. In the first part acoustic characterization has been completed in low intensityregion with the study of backscattered power, attenuation and phase velocity. In order torecalculate mechanical properties of the shell existing theoretical model has been furtheriimodified to accommodate the frequency dependence of viscoelastic properties andsimultaneously fit the attenuation and phase velocity data. The results concerning acoustic andmechanical properties of the microbubbles have been sent as a feedback to the manufacture inorder to optimize fabrication protocol for effective image acquisition. In the second part acousticcharacterization has been performed in high intensity region under varied parameters ofexperimental set-up. The results that illustrate the dependence of the fracture pressure thresholdon the system parameters allows us to discuss the potential role of polymer-shelled UCAs as drugcarriers and formulate the protocol for save, localized, cavitation-mediated drug delivery. For the third year the major task was to move on from the bulk volume in vitro tests towards themicrocapillary study and even further to incorporate the microcapillary into the tissue mimickingultrasound phantom. The last study has the objective to take into account the wave propagationthrough tissue. And last but not the least, the application of the polymer-shelled microbubblesfor evaluation of perfusion characteristics, i.e. capillary volume and velocity of the flow, has beenperformed. Similar tests are carried out with commercially available phospholipid-shelled UCA.Using destruction/replenishment technique it is suggested that the novel polymer-shelledmicrobubbles have a potential for a more accurate perfusion evaluation compared to that ofcommercially available phospholipid-shelled UCA. In conclusion, proposed polymer-shelled gas-core microbubbles provide a viable system to beused among the next generation of ultrasound contrast agents, which facilitate not only imageenhancement relevant to diagnostics but also localized and specific drug delivery for non-invasivetherapy even in acute conditions.
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| 28. |
- Grishenkov, Dmitry, 1983-
(författare)
-
Three modality contrast imaging using multi-functionalized microballoons
- 2011
-
Konferensbidrag (refereegranskat)abstract
- In vivo multimodality imaging is a fast growing field in medical research and, although the achievements at clinical level of this diagnostic method are recent, it is already one of the most promising approaches in the diagnosis of diseases in many research addressed medical centres. At present in this area, the USA plays the protagonist role as a result of the amount of resources engaged in the arena in the last decade. Both government and private companies agree, when considering the potential of this approach, that it is one of the foremost medical advancements as it will lead to early diagnosis of diseases with high impact on the societies of western countries. Multimodality imaging is currently viewed as a simple and powerful integration of two or more imaging methods (e.g. PET-CT). 3MICRON is an ambitious project which gathers some of the most advanced European medical and technical institutions together to address the design of new strategies in diagnostics, and to push the potential of medical imaging beyond the state-of-the-art. The multimodality approaches are supported by a class of next-generation micro/nanodevices called microballoons. These subsystems are able to implement the function of an ultrasound contrast agent with other imaging methods (SPECT, MRI). In the future, they may act as a minimally invasive drug delivery method and hyperthermia device. In 3MICRON, this multi-functional device will be tested in vitro and in vivo in order to assess bioclearance and cytoxicity effects toward high impact diseases, e.g. cardiovascular and inflammation pathologies. Finally, selected types of microballoons will undergo pre-clinical screening for a consolidated assessment of the “bench-to-bed” pathway for these new microdevices.
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| 29. |
- Grishenkov, Dmitry, 1983-, et al.
(författare)
-
Ultrasound contrast agent loaded with nitric oxide as a theranostic microdevice : Theranostic contrast agent loaded with nitric oxide
- 2015
-
Ingår i: Drug Design, Development and Therapy. - 1177-8881. ; 9, s. 2409-2419
-
Tidskriftsartikel (refereegranskat)abstract
- The current study describes novel multifunctional polymer-shelled microbubbles (MBs) loaded with nitric oxide (NO) for integrated therapeutic and diagnostic applications, i.e. theranostics, of myocardial ischemia. We used gas filled MBs with an average diameter of 4 µm stabilized by a biocompatible shell of poly(vinyl)alcohol. In vitro acoustic tests showed a sufficient enhancement of the backscattered power (20 dB) acquired from the MBs suspension. The values of attenuation coefficient (0.8 dB/cm MHz) and phase velocities (1517 m/s) were comparable to those reported for the soft tissue. Moreover, polymer MBs demonstrate increased stability compared to clinically approved contrast agents with fracture threshold of about 900 kPa. In vitro chemiluminescence measurements demonstrated that dry powder of NO-loaded MBs releases its gas content in about 2 hours following an exponential decay profile with an exponential time constant equal 36 min. The application of high power ultrasound pulse (MI=1.2) on the MBs resuspended in saline decreases the exponential time constant from 55 to 4 min in air saturated solution and from 17 to 10 min in degased solution. Thus, ultrasound-triggered release of NO is achieved. Cytotoxicity tests indicate that phagocytosis of the MBs by macrophages starts within 6 to 8 hours. This is suitable time for initial diagnostics, treatment and monitoring of the therapeutic effect using single injection of the proposed multifunctional MBs.
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| 30. |
- Grishenkov, Dmitry, 1983-, et al.
(författare)
-
Ultrasound contrast agent loaded with nitric oxide as a theranostic microdevise for myocardial ischemia
- 2013
-
Ingår i: European Heart Journal Cardiovascular Imaging.
-
Konferensbidrag (refereegranskat)abstract
- Cardiovascular disease (CVD) accounts for 1/3 of total global deaths worldwide. The most widespread CVD is ischemic heart disease. It is the leading cause of death in both genders, equally diagnosed in developed and developing countries with mortality exponentially increasing with age. Efforts of healthcare system should be primary focused on prevention, timely detection, efficient differentiation and instant treatment of the disease.
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| 31. |
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| 32. |
- Kothapalli, Satya V.V.N. 1985-, et al.
(författare)
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Investigation of Polymer-Shelled Microbubble Motions in Acoustophoresis
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The objective of this paper is to explore the trajectory motion of microsize (typically smaller than a redblood cell) encapsulated polymer-shelled gas bubbles propelled by radiation force in an acousticstanding-wave field and to compare the corresponding movements of solid polymer microbeads. Theexperimental setup consists of a microfluidic chip coupled to a piezoelectric crystal (PZT) with aresonance frequency of about 2.8 MHz. The microfluidic channel consists of a rectangular chamberwith a width, w, corresponding to one wavelength of the ultrasound standing wave. It creates one fullwave ultrasound of a standing-wave pattern with two pressure nodes at4w and43w and threeantinodes at 0,2w , and w. The peak-to-peak amplitude of the electrical potential over the PZT wasvaried between 1 and 10 volts. From Gor’kov’s potential equation, the acoustic contrast factor, Φ, forthe polymer-shelled microbubbles was calculated to about -60.7. Experimental results demonstratethat the polymer-shelled microbubbles are translated and accumulated at the pressure antinode planes.This trajectory motion of polymer-shelled microbubbles toward the pressure antinode plane is similarto what has been described for other acoustic contrast particles with a negative Φ. First, primaryradiation forces dragged the polymer-shelled microbubbles into proximity with each other at thepressure antinode planes. Then, secondary radiation forces caused them to aggregate at different spotsalong the channel. The relocation time for polymer-shelled microbubbles was 40 times shorter thanthat for polymer microbeads, and in contrast to polymer microbeads, the polymer-shelledmicrobubbles were actuated even at driving voltages (proportional to radiation forces) as low as 1 volt.In short, the polymer-shelled microbubbles demonstrate the behavior attributed to the negativeacoustic contrast factor particles and thus can be trapped at the antinode plane and thereby seperatedfrom solid particles, such as cells. This phenomenon could be utilized in exploring future applications,such as bioassay, bioaffinity, and cell interaction studies in vitro in a well-controlled environment.
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| 33. |
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| 34. |
- Kothapalli, Veera Venkata Satya Naray, 1985-, et al.
(författare)
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Coded Excitation Technique in Detection of Polymeric-Shelled Ultrasound contrast Agents: in Vitro Study
- 2011
-
Ingår i: 8th International Conference on Nanosciences & Nanotechnologies (NN11) 12-15 July 2011, Thessaloniki, Greece..
-
Konferensbidrag (refereegranskat)abstract
- 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 high pressure (1 MPa) ultrasonic pulse. Nevertheless, diagnostic imaging typically utilizes the intermediate pressure level, where nonlinear oscillation of the microbubbles give rise to harmonic component in the received echo. It was observed that at pressure level of 400 kPa, Pulse Inversion (PI) technique fail to distinguish between the regions filled with polymer UCA and surrounding ultrasound phantom, mimicking liver tissue. In this paper, a coded excitation technique is proposed to characterize the non-linear properties of the polymer-shelled microbubbles in vitro at intermediate pressure. For a decade ago, coded excitation technique has been adopted into the ultrasound scanners in order to increase the signal-to-noise ratio (SNR) and penetration depth, while matching filters compensates the decrease in axial resolution. In the proposed method, a time domain signal is modulated by a several window functions (e.g. Blackman-Harries, Hanning, Hamming, and Kaiser-Bessel) with or without linear chirp pulses constructed for experiments in vitro. Our preliminary results suggest that coded excitation technique offers an increase of approximately 15dB in contrast-to-tissue ration (CTR) compared to the result achieved from a commercially available Pulse Inversion technique. In conclusion, proposed polymer-shelled microbubbles provide a viable system to be used among the next generation of UCAs, and in combination with improved signal handling is superior not only in image enhancement relevant to diagnostics but also in localized and specific drug delivery for non-invasive therapy.
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| 35. |
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| 36. |
- Kothapalli, Veera Venkata Satya Naray, 1985-, et al.
(författare)
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Optimization of driving pulse envelopes in detection of harmonic response from lipid-shelled ultrasound contrast agent
- 2012
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Ingår i: 19th International Congress on Sound and Vibration 2012, ICSV 2012. - 9781622764655 ; , s. 1882-1889
-
Konferensbidrag (refereegranskat)abstract
- The assessment of the harmonic response is commonly used in analysis of the signals from ultrasound contrast agents (UCAs). Theoretical and experimental studies report that acoustic behavior of UCAs strongly depends on insonation pressure. Other system parameters, such as the number of cycles, driving and repetition frequency and the pulse shape are equally important. The major focus of this work is to investigate the effect of the shape of driving pulse envelopes on detection of second- (2f), super- (3f, 4f, 5f), sub- (f/2), and ultra-harmonics (3f/2). In this paper, numerical simulations on thin-shelled lipidic UCA have been performed. The simulation results indicate that, high sidelobe suppression envelopes (e.g. 4-term Blackman-Harris), manage to detect second and third harmonic with harmonic-to-fundamental ratio (HFR) of 32 and 69 dB, respectively, at low acoustic pressure of 5 kPa. However, conventional low sidelobe suppression envelopes (e.g. rectangular, cos-tapered, Hanning, Gaussian) fail to identify the harmonic response. Yet the increase of the insonation pressure to 200 kPa leads to increase of the broadband noise. This negatively effects the frequency resolution when high suppression sidelobe envelopes are applied to the driving pulse. As a result, the application of conventional envelopes in harmonic response detection at intermediate acoustic pressure, is recommended. It is also worth mentioning, that at high isonation pressure of 0.9 MPa, cos-tapered envelope, having a side lobe fall-off equal to 18 dB/octave, is able to identify the sub- and ultra-harmonics. In conclusion our study demonstrates that the driving pulse envelope should be selected according to the incident pressure for the complete exploitation of the unique nonlinear signature from UCA. A compromise could be found with the application of adjustable Kaiser-Bessel envelope where by varying the β parameter from 0 to 10 one goes from low to high sidelobe suppression envelope.
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| 37. |
- Kothapalli, Veera Venkata Satya Naray, 1985-, et al.
(författare)
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Unique pumping-out fracturing mechanism of a polymer-shelled contrast agent : An acoustic characterization and optical visualization
- 2014
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Ingår i: IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control. - 0885-3010 .- 1525-8955. ; 62:3, s. 451-462
-
Tidskriftsartikel (refereegranskat)abstract
- This work describes the fracturing mechanism of air-filled microbubbles (MBs) encapsulated by a cross-linked poly(vinyl alcohol) (PVA) shell. The radial oscillation and fracturing events following the ultrasound exposure were visualized with an ultrahigh-speed camera, and backscattered timedomain signals were acquired with the acoustic setup specific for harmonic detection. No evidence of gas emerging from defects in the shell with the arrival of the first insonation burst was found. In optical recordings, more than one shell defect was noted, and the gas core was drained without any sign of air extrusion when several consecutive bursts of 1 MPa amplitude were applied. In acoustic tests, the backscattered peak-to-peak voltage gradually reached its maximum and exponentially decreased when the PVA-based MB suspension was exposed to approximately 20 consecutive bursts arriving at pulse repetition frequencies of 100 and 500 Hz. Taking into account that the PVA shell is porous and possibly contains large air pockets between the cross-linked PVA chains, the aforementioned acoustic behavior might be attributed to pumping gas from these pockets in combination with gas release from the core through shell defects. We refer to this fracturing mechanism as pumping-out behavior, and this behavior could have potential use for the local delivery of therapeutic gases, such as nitric oxide.
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| 38. |
- Loskutova, Ksenia, 1995-, et al.
(författare)
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A Study on the Acoustic Response of Pickering Perfluoropentane Droplets in Different Media
- 2021
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343.
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Tidskriftsartikel (refereegranskat)abstract
- Acoustic droplet vaporization (ADV) is the physical process of liquid-to-gas phase transition mediated by pressure variations in an ultrasound field. In this study, the acoustic response of novel particle-stabilized perfluoropentane droplets was studied in bulk and confined media. The oil/water interface was stabilized by cellulose nanofibers. First, their acoustic responses under idealized conditions were examined to assess their susceptibility to undergo ADV. Second, the droplets were studied in a more realistic setting and placed in a confined medium. Lastly, an imaging setup was developed and tested on the droplets. The acoustic response could be seen when the amplitude of the peak negative pressure (PNP) was above 200 kPa, suggesting that this is the vaporization pressure threshold for these droplets. Increasing the PNP resulted in a decrease in signal intensity over time, suggesting a more destructive behavior. The imaging setup was able to differentiate between the droplets and the surrounding tissue. Results obtained within this study suggest that these droplets have potential in terms of ultrasound-mediated diagnostics and therapy.
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| 39. |
- Loskutova, Ksenia, et al.
(författare)
-
Assessment of the Mechanical Propertiesof Cellulose Nanofiber-Stabilized Droplets Using Acoustophoresis
- 2021
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Konferensbidrag (refereegranskat)abstract
- In this work, the compressibility of Pickering-stabilized perfluoropentane droplets was determined by using acoustophoresis. Polyamide beads with known density, size and compressibility were used to calculate the pressure amplitude inside the microchannel. The results show that the compressibility of CNF-stabilized droplets is significantly higher than for water, but lower than for pure PFC5. This shows promising potential for these droplets to be used in ultrasound-mediated clinical applications. It has also been shown that acoustophoresis can successfully measure the compressibility of pressure-sensitive particles for small USW pressure amplitudes. As the droplets relocate to pressure anti-nodes just as gas-filled microbubbles, it would be possible to study cell-droplet and cell-gasbubble in the same setup.
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| 40. |
- Loskutova, Ksenia, et al.
(författare)
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Biocompatibility of Cellulose Nanofiber-Coated Perfluoropentane Droplets
- 2023
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Konferensbidrag (refereegranskat)abstract
- The cellulose nanofiber(CNF)-shelled perfluoropentane (PFP) droplets were the subject of the evaluation in this work. CNF-shelled PFP droplets Mechanical and acoustic properties were studied previously and reported elsewhere [1-4], however more insights into the biological effects of these droplets are needed to translate previous in vitro tests into in vivo applications as drug carriers in ultrasound-mediated drug delivery. The aim of this work is to investigate the effect of CNF-shelled PFP droplets on cell viability of 4T1 cells, a murine breast cancer cell line. Cells were exposed to different concentrations of droplets with or without the addition of paclitaxel, i.e. a hydrophobic cancer drug.[1]. Ghorbani M, Olofsson K, Benjamins J-W, Loskutova K, Paulraj T, Wiklund M, Grishenkov D, Svagan A J, Unravelling the Acoustic and Thermal Responses of Perfluorocarbon Liquid Droplets Stabilized with Cellulose Nanofibers, Langmuir 35(40): 13090-13099, 2019.[2]. Song X, Loskutova K, Chen H, Shen G, Grishenkov D, Deriving acoustic properties for perfluoropentane droplets with viscoelastic cellulose nanofiber shell via numerical simulations, The Journal of the Acoustical Society of America 150(3): 1750-1761, 2021.[3]. Loskutova K, Nimander D, Gouwy I, Chen H, Ghorbani M, Svagan A J, Grishenkov D, A Study on the Acoustic Response of Pickering Perfluoropentane Droplets in Different Media, ACS Omega 6(8): 5670-5678, 2019.[4]. Loskutova K, Olofsson K, Hammarström B, Wiklund M, Svagan A J, Grishenkov D, Measuring the Compressibility of Cellulose Nanofiber-Stabilized Microdroplets Using Acoustophoresis, Micromachines 12(12): 1465, 2021.
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| 41. |
- Loskutova, Ksenia, et al.
(författare)
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Cellulose Nanofiber-Coated Perfluoropentane Droplets: Fabrication and Biocompatibility Study
- 2023
-
Ingår i: International Journal of Nanomedicine. - 1176-9114 .- 1178-2013. ; 18, s. 1835-1847
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To study the effect of cellulose nanofiber (CNF)-shelled perfluoropentane (PFP) droplets on the cell viability of 4T1 breast cancer cells with or without the addition of non-encapsulated paclitaxel.Methods: The CNF-shelled PFP droplets were produced by mixing a CNF suspension and PFP using a homogenizer. The volume size distribution and concentration of CNF-shelled PFP droplets were estimated from images taken with an optical microscope and analyzed using Fiji software and an in-house Matlab script. The thermal stability was qualitatively assessed by comparing the size distribution and concentration of CNF-shelled PFP droplets at room temperature (~22°) and 37°C. The cell viability of 4T1 cells was measured using a 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Additionally, a hemolysis assay was performed to assess blood compatibility of CNF-shelled PFP droplets.Results: The droplet diameter and concentration of CNF-shelled PFP droplets decreased after 48 hours at both room temperature and 37°C. In addition, the decrease in concentration was more significant at 37°C, from 3.50 ± 0.64× 10^6 droplets/mL to 1.94 ± 0.10× 10^6 droplets/mL, than at room temperature, from 3.65 ± 0.29× 10^6 droplets/mL to 2.56 ± 0.22× 10^6 droplets/mL. The 4T1 cell viability decreased with increased exposure time and concentration of paclitaxel, but it was not affected by the presence of CNF-shelled PFP droplets. No hemolysis was observed at any concentration of CNF-shelled PFP droplets.Conclusion: CNF-shelled PFP droplets have the potential to be applied as drug carriers in ultrasound-mediated therapy.
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| 42. |
- Loskutova, Ksenia, et al.
(författare)
-
Measuring the Compressibility of Cellulose Nanofiber-Stabilized Microdroplets Using Acoustophoresis
- 2021
-
Ingår i: Micromachines. - : MDPI. - 2072-666X. ; 12:12, s. 1465-
-
Tidskriftsartikel (refereegranskat)abstract
- Droplets with a liquid perfluoropentane core and a cellulose nanofiber shell have the potential to be used as drug carriers in ultrasound-mediated drug delivery. However, it is necessary to understand their mechanical properties to develop ultrasound imaging sequences that enable in vivo imaging of the vaporization process to ensure optimized drug delivery. In this work, the compressibility of droplets stabilized with cellulose nanofibers was estimated using acoustophoresis at three different acoustic pressures. Polyamide particles of known size and material properties were used for calibration. The droplet compressibility was then used to estimate the cellulose nanofiber bulk modulus and compare it to experimentally determined values. The results showed that the acoustic contrast factor for these droplets was negative, as the droplets relocated to pressure antinodes during ultrasonic actuation. The droplet compressibility was 6.6-6.8 x10(-10) Pa-1, which is higher than for water (4.4x10(-10) Pa-1) but lower than for pure perfluoropentane (2.7x10(-9) Pa-1). The compressibility was constant across different droplet diameters, which was consistent with the idea that the shell thickness depends on the droplet size, rather than being constant.
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| 43. |
- Loskutova, Ksenia
(författare)
-
Perfluorocarbon microdroplets stabilized by cellulose nanofibers : Toward ultrasound-mediated diagnostics and therapy
- 2023
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ultrasound contrast agents consist of gas-filled micrometer-sized bubbles that are injectedinto the blood stream. Ultrasound contrast agents are an invaluable tool for ultrasound imaging of the cardiac muscle and highly vascularized structures such as kidneys and the liver. The ability of gas-filled microbubbles to enhance contrast in ultrasound imaging comes from their increased scattering ability due to significantly lower compressibility compared to surrounding soft tissues.The discovery of acoustic droplet vaporization, the phase-transition of liquid-filleddroplets into gas-filled microbubbles upon ultrasound exposure, has expanded the potential utility of ultrasound-mediated diagnostics and therapy to include applications such as gas embolization, histotripsy, and localized drug delivery. Multiple requirements are put onto both gas-filled microbubbles and phase-change contrast agents: they have to be non-toxic, acoustically active at clinically relevant pressure amplitudes, and their dynamic behavior has to be predictable to maximize the therapeutic or diagnostic effect while minimizing mechanical damage to surrounding healthy tissue. Novel designs of phase-change contrast agents that are able to undergo acoustic droplet vaporization could enable improved in vivo stability compared to conventional gas-filled ultrasound contrast agents.Pickering emulsions, with solid particles used as stabilizing agents instead of surfactants, have an increased stability compared to conventional emulsions. Cellulose-based Pickering emulsions in particular have previously been investigated for biomedical applications. Cellulose is a suitable material in biomedical applications as it originates from renewable sources, is biocompatible, and the surface can be easily modified. To the author’s current knowledge, cellulose-based Pickering emulsions have not previously been investigated for ultrasound-mediated applications. It is necessary to know the mechanical and acoustic properties of novel formulations and their impact on biological cells for their translation into in vivo research and future clinical use.In this thesis, the acoustic, mechanical, and biological properties of cellulose nanofiber(CNF)-shelled perfluoropentane (PFP) droplets, a type of Pickering emulsion, were investigated for ultrasound-mediated medical applications. Firstly, the current state-of-the-art and development of phase-change contrast agents, the mechanism behind acoustic droplet vaporization, and potential ultrasound-mediated medical applications were investigated. Secondly, a theoretical model that would describe and predict the acoustic response of CNF-shelled PFP droplets undergoing acoustic droplet vaporization was developed. Thirdly, the compressibility of CNF-shelled PFP droplets using an acoustophoretic setup was measured. Later, the effect of the geometry of the surrounding medium and acoustic parameters on the acoustic response of CNF-shelled PFP droplets was explored. Finally, the biocompatibility of CNF-shelled PFP droplets cells was investigated through a hemolysis assay and measurement of change in cell viability of breast cancer cells.The CNF shell has a significant impact on the predicted resonance behavior and compressibility of CNF-shelled PFP droplets, as it has significantly larger bulk and Young’s modulus than previously reported shell materials. The predicted linear resonance behavior was in the upper range of medical ultrasound (5-8 MHz), making harmonic imaging at optimal conditions difficult. However, it was demonstrated that CNF-shelled PFP droplets could be imaged using a nonlinear ultrasound imaging sequence at a frequency regularly used in clinics. Thus, CNF-shelled PFP droplets were able to undergo acoustic droplet vaporization at clinically relevant conditions. The peak negative pressure of the incident acoustic wave had a significant impact on the acoustic response of CNF-shelled PFP droplets, as higher acoustic pressure amplitudes resulted in a more disruptive behavior. Finally, CNF-shelled PFP droplets did not influence the cell viability of breast cancer cells. This was true regardless of whether or not a non-encapsulated cytotoxic drug with a known impact on cell viability was present. In summary, the results of this work showed that CNF-shelled PFP droplets are biocompatible and acoustically active at clinically relevant conditions, which shows that cellulose-based Pickering emulsions have potential in ultrasound-mediated diagnostics and therapy.
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| 44. |
- Loskutova, Ksenia, et al.
(författare)
-
Review on Acoustic Droplet Vaporization in Ultrasound Diagnostics and Therapeutics
- 2019
-
Ingår i: BioMed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141.
-
Forskningsöversikt (refereegranskat)abstract
- Acoustic droplet vaporization (ADV) is the physical process in which liquid undergoes phase transition to gas after exposure to a pressure amplitude above a certain threshold. In recent years, new techniques in ultrasound diagnostics and therapeutics have been developed which utilize microformulations with various physical and chemical properties. The purpose of this review is to give the reader a general idea on how ADV can be implemented for the existing biomedical applications of droplet vaporization. In this regard, the recent developments in ultrasound therapy which shed light on the ADV are considered. Modern designs of capsules and nanodroplets (NDs) are shown, and the material choices and their implications for function are discussed. The influence of the physical properties of the induced acoustic field, the surrounding medium, and thermophysical effects on the vaporization are presented. Lastly, current challenges and potential future applications towards the implementation of the therapeutic droplets are discussed.
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| 45. |
- Nordenfur, Tim, 1990-, et al.
(författare)
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Safety of arterial shear wave elastography-ex-vivo assessment of induced strain and strain rates
- 2022
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Ingår i: Biomedical Engineering & Physics Express. - : IOP Publishing. - 2057-1976. ; 8:5
-
Tidskriftsartikel (refereegranskat)abstract
- Shear wave elastography (SWE) is a promising technique for characterizing carotid plaques and assessing local arterial stiffness. The mechanical stress to which the tissue is subjected during SWE using acoustic radiation force (ARF), leading to strain at a certain strain rate, is still relatively unknown. Because SWEis increasingly used for arterial applications where the mechanical stress could potentially lead to significant consequences, it is important to understand the risks of SWE-induced strain and strain rate. The aim of this study was to investigate the safety of SWE in terms of induced arterial strain and strain rate ex-vivo and in a human carotid artery in-vivo. SWE was performed on six porcine aortae as a model of the human carotid artery using different combinations of ARF push parameters (push voltage: 60/90 V, aperture width: f/1.0/1.5, push length: 100/150/200 mu s) and distance to push position. The largest induced strain and strain rate were 1.46% and 54 s(-1) (90 V, f/ 1.0, 200 mu s), respectively. Moreover, the SWE-induced strains and strain rates increased with increasing push voltage, aperture, push length, and decreasing distance between the region of interest and the push. In the human carotid artery, the SWE-induced maximum strain was 0.06% and the maximum strain rate was 1.58 s(-1), compared with the maximum absolute strain and strain rate of 12.61% and 5.12 s(-1), respectively, induced by blood pressure variations in the cardiac cycle. Our results indicate that ex-vivo arterial SWE does not expose the artery to higher strain rate than normal blood pressure variations, and to strain one order of magnitude higher than normal blood pressure variations, at the push settings and distances from the region of interest used in this study.
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| 46. |
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| 47. |
- Pecorari, Claudio, et al.
(författare)
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Characterization of ultrasound-induced fracture of polymer-shelled ultrasonic contrast agents by correlation analysis
- 2007
-
Ingår i: Journal of the Acoustical Society of America. - : Acoustical Society of America (ASA). - 0001-4966 .- 1520-8524. ; 122:4, s. 2425-2430
-
Tidskriftsartikel (refereegranskat)abstract
- Beyond a characteristic value of the negative peak pressure, ultrasound fracture the shell of ultrasonic contrast agents (UCAs). Existing criteria for ascertaining this threshold value exploit the dependence of the amplitude of the UCA acoustic response on the incident pressure. However, under the common experimental conditions used in this work, these criteria appear to be unreliable when they are applied to UCAs that are stabilized by a thick polymeric shell. An alternative criterion for determining the onset of shell fracture is introduced here, which uses variations of the shape of the acoustic time-domain response of an UCA suspension. Experimental evidence is presented that links the changes of the cross-correlation coefficient between consecutive time-domain signals to the fracture of the shells, and consequent release of air microbubbles. In principle, this criterion may be used to characterize similar properties of other types of particles that cannot undergo inertial cavitation.
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| 48. |
- Poehlman, Melanie, et al.
(författare)
-
Magnetic microbubbles for multimodality imaging : the importance of the shell structure for low and high frequency mechanics
- 2013
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Konferensbidrag (refereegranskat)abstract
- There is a growing interest in magnetic microbubbles (MBs) for simultaneous enhanced ultrasound (US) and enhanced magnetic resonance imaging (MRI) to support well-established imaging procedures as well as new emerging diagnostic and therapeutic applications. However, the development of hybrid contrast agents is challenging, because their design needs to satisfy a variety of requirements such as a sufficient stability of the probe for the circulation within the cardiovascular system, the production of an adequate US echo signal and a reasonable reduced relaxation time of nearby located protons. The studied magnetic MBs consist of an air-filled core, which is encapsulated by a soft hydrogel-like shell composed of poly(vinyl alcohol) and superparamagnetic iron oxide nanoparticles (SPIONs)[1]. Two strategies were used to combine magnetic nanoparticles with the polymeric shell: SPIONs were either covalently attached to the shell surface via a post-chemical treatment or embedded physically inside the shell during the MBs’ synthesis. In particular, we were interested on the impact of the used SPIONs integration strategy on low and high frequency mechanics of the magnetic MBs. Therefore, we used a straightforward characterization of the MBs on the single particle level to correlate the synthesis with the MBs’ morphological properties and low frequency mechanics that were studied in quasi-static force measurements with atomic force microscopy. High frequency mechanics were investigated by exposure of an ensemble of MBs to an acoustic field. By further correlation of low and high frequency mechanics, we were able to bridge the gap between synthesis and the MBs macroscopic properties relevant for their application. The shown approach offers the possibility to sustainable design and optimize complex probes based on an improved understanding of structure/property relations.
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| 49. |
- Rokhsar Talabazar, Farzad, et al.
(författare)
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Design and fabrication of a vigorous "cavitation-on-a-chip" device with a multiple microchannel configuration
- 2021
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Ingår i: Microsystems & Nanoengineering. - : Springer Nature. - 2055-7434. ; 7:1
-
Tidskriftsartikel (refereegranskat)abstract
- Hydrodynamic cavitation is one of the major phase change phenomena and occurs with a sudden decrease in the local static pressure within a fluid. With the emergence of microelectromechanical systems (MEMS), high-speed microfluidic devices have attracted considerable attention and been implemented in many fields, including cavitation applications. In this study, a new generation of 'cavitation-on-a-chip' devices with eight parallel structured microchannels is proposed. This new device is designed with the motivation of decreasing the upstream pressure (input energy) required for facile hydrodynamic cavitation inception. Water and a poly(vinyl alcohol) (PVA) microbubble (MB) suspension are used as the working fluids. The results show that the cavitation inception upstream pressure can be reduced with the proposed device in comparison with previous studies with a single flow restrictive element. Furthermore, using PVA MBs further results in a reduction in the upstream pressure required for cavitation inception. In this new device, different cavitating flow patterns with various intensities can be observed at a constant cavitation number and fixed upstream pressure within the same device. Moreover, cavitating flows intensify faster in the proposed device for both water and the water-PVA MB suspension in comparison to previous studies. Due to these features, this next-generation 'cavitation-on-a-chip' device has a high potential for implementation in applications involving microfluidic/organ-on-a-chip devices, such as integrated drug release and tissue engineering.
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| 50. |
- Seyedmirzaei Sarraf, S., et al.
(författare)
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Fundamentals, biomedical applications and future potential of micro-scale cavitation-a review
- 2022
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Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 22:12, s. 2237-2258
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Tidskriftsartikel (refereegranskat)abstract
- Thanks to the developments in the area of microfluidics, the cavitation-on-a-chip concept enabled researchers to control and closely monitor the cavitation phenomenon in micro-scale. In contrast to conventional scale, where cavitation bubbles are hard to be steered and manipulated, lab-on-a-chip devices provide suitable platforms to conduct smart experiments and design reliable devices to carefully harness the collapse energy of cavitation bubbles in different bio-related and industrial applications. However, bubble behavior deviates to some extent when confined to micro-scale geometries in comparison to macro-scale. Therefore, fundamentals of micro-scale cavitation deserve in-depth investigations. In this review, first we discussed the physics and fundamentals of cavitation induced by tension-based as well as energy deposition-based methods within microfluidic devices and discussed the similarities and differences in micro and macro-scale cavitation. We then covered and discussed recent developments in bio-related applications of micro-scale cavitation chips. Lastly, current challenges and future research directions towards the implementation of micro-scale cavitation phenomenon to emerging applications are presented.
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