| 1. |
- Grishenkov, Dmitry, 1983-
(författare)
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Polymer-shelled Ultrasound Contrast Agents : Characterization and Application
- 2010
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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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| 2. |
- 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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| 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, 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- Chen, Hongjian, et al.
(författare)
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Sequence design for ultrasound imaging of polyvinyl alcohol microbubbles
- 2020
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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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| 8. |
- 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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| 9. |
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| 10. |
- 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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