Assessment of ultrasound-induced fracture of polymer-shelled ultrasound contrast agents using superharmonic technique

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

Assessment of ultrasound-induced fracture of polymer-shelled ultrasound contrast agents using superharmonic technique

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

Targeted Hydrodynamic Cavitating Flows via Ultrasound Waves via Pickering Stabilized Perfluorodroplets

QC 20200226</p

Review on Acoustic Droplet Vaporization in Ultrasound Diagnostics and Therapeutics

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.QC 20190716</p

Sequence design for ultrasound imaging of polyvinyl alcohol microbubbles

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.QC 20181120</p

Characterization of acoustic properties of PVA-shelled ultrasound contrast agents: ultrasound-induced fracture (Part II)

Knowledge of the magnitude of the peak negative pressure, Pthr, 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 Pthr 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 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. Fatigue seems to be a physical mechanism playing a dominant role in the fracture process. The effect of blood on Pthr 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