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An Investigation of Material and Acoustic Properties of Ultrasound Contrast Agents for Non-Invasive Pressure Measurement /

Record Type:	Electronic resources : Monograph/item
Title/Author:	An Investigation of Material and Acoustic Properties of Ultrasound Contrast Agents for Non-Invasive Pressure Measurement // Roozbeh Hassanzadeh Azami.
Author:	Hassanzadeh Azami, Roozbeh,
Description:	1 electronic resource (128 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
Contained By:	Dissertations Abstracts International85-12B.
Subject:	Mechanical engineering. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31302265
ISBN:	9798382800462

An Investigation of Material and Acoustic Properties of Ultrasound Contrast Agents for Non-Invasive Pressure Measurement /
Hassanzadeh Azami, Roozbeh,

An Investigation of Material and Acoustic Properties of Ultrasound Contrast Agents for Non-Invasive Pressure Measurement /Roozbeh Hassanzadeh Azami. - 1 electronic resource (128 pages)

Source: Dissertations Abstracts International, Volume: 85-12, Section: B.

The use of ultrasound imaging technology as a non-invasive diagnostic method has spread widely due to its safety, affordability, and convenience. To improve the image quality for applications such as vasculature structure assessment and cardiography where there is poor contrast between blood containing vessels and tissues, contrast enhanced ultrasound utilizing novel signal processing techniques and contrast agents was introduced. Ultrasound contrast agents are micron size gas bubbles (hereafter bubbles or microbubbles) capable of producing acoustic signals in response to ultrasound waves which differentiates them from the surrounding tissue and enhances the image contrast. Optimization of the microbubbles design and production to exhibit desired acoustic response for specific applications is the subject of extensive research efforts. In this thesis we characterize the material and acoustic properties of different types of microbubbles and provide implications for novel applications of ultrasound imaging. In Chapter 2, we investigated the effects of shell chemical composition on the microbubble's characteristics. We used acoustic attenuation measurement experiments along with bubble dynamic physical models to investigate the effect of varying lipid and polyethylene glycol (PEG) molar ratios on material properties, stability, and resonance frequency of bubbles. The PEG chain configuration was shown to influence the materials property. At high PEG ratios, chains form a brush configuration while otherwise will conform a mushroom-like shape. In the brush regime, the shell elasticity and resonance frequency were significantly lower than mushroom regime, however, inside each configuration regimes no significant difference was detected among bubbles with different shell compositions. The stability of bubbles inside air saturated water were measured over 60 minutes and bubbles with higher PEG ratios (10% and 20%) were most stable ones and maintained 60% of their initial total attenuation. Optical microscopy size measurement revealed addition of PEG improved production yield, however, it did not affect the mean size. In conclusion, 10% PEG and 90% DPPC lipid shell formulation has shown the best overall stability and production yield.In Chapter 3, we studied the effect of ambient pressure variation on the acoustic response of the 10% PEG lipid microbubbles. The motivation behind this project was a novel method for non-invasive blood pressure measurement called Subharmonic Aided Pressure Estimation (SHAPE). This method utilizes the strong correlation between the subharmonic signal from contrast agents and ambient pressure to determine the pressure inside critical organs. Subharmonic generation is a threshold phenomenon and requires acoustic excitation amplitudes higher than a certain value. We determined the correlation between ambient pressure and subharmonic amplitude using a wide range of acoustic parameters before and after the subharmonic threshold. The result of this section presents two key observations: first, at acoustic parameters beyond the subharmonic threshold, increasing ambient pressure results in a linear decrease of subharmonic amplitude. Second, before the threshold, increasing overpressure will trigger subharmonic generation and enhance it. The finding of this study addressed the contradictory observations in literature.With the SHAPE method gaining progress in clinical trials, it is important to characterize the commercially available contrast agents for use in SHAPE for new applications. In Chapter 4, we investigated the ambient pressure sensitivity of the acoustic response of SonoVue microbubbles, commercial contrast agent approved by United States Food and Drug Administration. We identified different subharmonic generation and ambient pressure sensitivity trends and categorized the underlying conditions. We found that SonoVue generated significant subharmonic response at far below the excitation threshold expected for a lipid microbubble (called Type I subharmonic). This subharmonic response disappears after a few cycles of pressurization resulting in the SHAPE correlation switching from negative to positive. The sensitivity of subharmonic generated beyond the regular lipid bubble subharmonic threshold (called Type II subharmonic) is, however, a consistent linear decrease with overpressure during all pressurizing cycles. We hypothesize that high diffusivity of sulfur hexafluoride leads to bubbles shrinkage and buckling, which is associated with subharmonic production, and multiple pressurization cycles and bubble transition between elastic and buckled stages leads to SonoVue unique behavior. To test this hypothesis, SonoVue microbubbles with a modified gas core were studied in the next chapter.In Chapter 5, to further probe the role of the gas core in the existence and transient behavior of Type I subharmonic in original SonoVue, we exchanged its sulfur hexafluoride core with more commercially used perfluorobutane gas, which has a lower diffusivity. The modified SonoVue did not generate subharmonic at low acoustic pressures and no transient behavior dependent on time or pressurizing cycles was observed. In addition, optical size measurement revealed no differences between the mean size of the original and modified SonoVue which is one of the determining factors in subharmonic generation. The results of this last chapter hint at the significant role of the gas core in bubble dynamics and acoustic behavior and supports the hypothesis laid out in the previous chapter.The research findings presented in this dissertation provides further insights into the microbubble's acoustics for biomedical applications. In particular, the characteristics of ambient pressure sensitivity of subharmonic response presented in this research can be utilized to optimize current SHAPE methods and guide the development of appropriate protocols as new applications emerge.

English

ISBN: 9798382800462Subjects--Topical Terms:

649730
Mechanical engineering.
Subjects--Index Terms:

Ultrasound imaging

An Investigation of Material and Acoustic Properties of Ultrasound Contrast Agents for Non-Invasive Pressure Measurement /
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520 $a The use of ultrasound imaging technology as a non-invasive diagnostic method has spread widely due to its safety, affordability, and convenience. To improve the image quality for applications such as vasculature structure assessment and cardiography where there is poor contrast between blood containing vessels and tissues, contrast enhanced ultrasound utilizing novel signal processing techniques and contrast agents was introduced. Ultrasound contrast agents are micron size gas bubbles (hereafter bubbles or microbubbles) capable of producing acoustic signals in response to ultrasound waves which differentiates them from the surrounding tissue and enhances the image contrast. Optimization of the microbubbles design and production to exhibit desired acoustic response for specific applications is the subject of extensive research efforts. In this thesis we characterize the material and acoustic properties of different types of microbubbles and provide implications for novel applications of ultrasound imaging. In Chapter 2, we investigated the effects of shell chemical composition on the microbubble's characteristics. We used acoustic attenuation measurement experiments along with bubble dynamic physical models to investigate the effect of varying lipid and polyethylene glycol (PEG) molar ratios on material properties, stability, and resonance frequency of bubbles. The PEG chain configuration was shown to influence the materials property. At high PEG ratios, chains form a brush configuration while otherwise will conform a mushroom-like shape. In the brush regime, the shell elasticity and resonance frequency were significantly lower than mushroom regime, however, inside each configuration regimes no significant difference was detected among bubbles with different shell compositions. The stability of bubbles inside air saturated water were measured over 60 minutes and bubbles with higher PEG ratios (10% and 20%) were most stable ones and maintained 60% of their initial total attenuation. Optical microscopy size measurement revealed addition of PEG improved production yield, however, it did not affect the mean size. In conclusion, 10% PEG and 90% DPPC lipid shell formulation has shown the best overall stability and production yield.In Chapter 3, we studied the effect of ambient pressure variation on the acoustic response of the 10% PEG lipid microbubbles. The motivation behind this project was a novel method for non-invasive blood pressure measurement called Subharmonic Aided Pressure Estimation (SHAPE). This method utilizes the strong correlation between the subharmonic signal from contrast agents and ambient pressure to determine the pressure inside critical organs. Subharmonic generation is a threshold phenomenon and requires acoustic excitation amplitudes higher than a certain value. We determined the correlation between ambient pressure and subharmonic amplitude using a wide range of acoustic parameters before and after the subharmonic threshold. The result of this section presents two key observations: first, at acoustic parameters beyond the subharmonic threshold, increasing ambient pressure results in a linear decrease of subharmonic amplitude. Second, before the threshold, increasing overpressure will trigger subharmonic generation and enhance it. The finding of this study addressed the contradictory observations in literature.With the SHAPE method gaining progress in clinical trials, it is important to characterize the commercially available contrast agents for use in SHAPE for new applications. In Chapter 4, we investigated the ambient pressure sensitivity of the acoustic response of SonoVue microbubbles, commercial contrast agent approved by United States Food and Drug Administration. We identified different subharmonic generation and ambient pressure sensitivity trends and categorized the underlying conditions. We found that SonoVue generated significant subharmonic response at far below the excitation threshold expected for a lipid microbubble (called Type I subharmonic). This subharmonic response disappears after a few cycles of pressurization resulting in the SHAPE correlation switching from negative to positive. The sensitivity of subharmonic generated beyond the regular lipid bubble subharmonic threshold (called Type II subharmonic) is, however, a consistent linear decrease with overpressure during all pressurizing cycles. We hypothesize that high diffusivity of sulfur hexafluoride leads to bubbles shrinkage and buckling, which is associated with subharmonic production, and multiple pressurization cycles and bubble transition between elastic and buckled stages leads to SonoVue unique behavior. To test this hypothesis, SonoVue microbubbles with a modified gas core were studied in the next chapter.In Chapter 5, to further probe the role of the gas core in the existence and transient behavior of Type I subharmonic in original SonoVue, we exchanged its sulfur hexafluoride core with more commercially used perfluorobutane gas, which has a lower diffusivity. The modified SonoVue did not generate subharmonic at low acoustic pressures and no transient behavior dependent on time or pressurizing cycles was observed. In addition, optical size measurement revealed no differences between the mean size of the original and modified SonoVue which is one of the determining factors in subharmonic generation. The results of this last chapter hint at the significant role of the gas core in bubble dynamics and acoustic behavior and supports the hypothesis laid out in the previous chapter.The research findings presented in this dissertation provides further insights into the microbubble's acoustics for biomedical applications. In particular, the characteristics of ambient pressure sensitivity of subharmonic response presented in this research can be utilized to optimize current SHAPE methods and guide the development of appropriate protocols as new applications emerge.
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