Ultrafast Microscopy Imaging of Acoustic Cluster Therapy Bubbles: Activation and Oscillation

Wamel, Annemieke van; Mühlenpfordt, Melina; Hansen, Rune; Healey, Andrew; Villanueva, Flordeliza S.; Kotopoulis, Spiros; Davies, Catharina de Lange; Chen, Xucai

doi:10.1016/j.ultrasmedbio.2022.05.009

Cited by 9 publications

(6 citation statements)

References 53 publications

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“…A possible explanation for the shear stress dependence on frequency is that the shear stress is proportional to the quantity, f 3/2 e [where e ¼ (R max À R 0 )/R 0 is the relative radial expansion and R 0 and R max are initial and maximum bubble radii, respectively], and this also determines the velocity gradient. 28,46 As the frequency increases, the magnitude of the bubble oscillation increases, reaching a maximum at 3.25 MHz, the resonant frequency, resulting in the increase of shear stress. When the frequency is further increased, the bubble oscillation rapidly decreases, thus the quantity f 3/2 e falls, resulting in the reduction of shear stress.…”

Section: Peak Values Of Stressmentioning

confidence: 99%

“…Whereas the studies mentioned above deal with the behavior of single bubbles, others are concerned with the practical application of multiple bubbles in the clinical domain. Several experimental 27,28 and theoretical studies [29][30][31][32][33] have investigated the stress induced by trains or clouds of multiple bubbles. (See Appendix Table III for a summary of their results.)…”

Section: Introductionmentioning

confidence: 99%

“…(See Appendix Table III for a summary of their results.) Considering a cloud of bubbles near a solid wall, van Wamel et al 28 observed that the shear stress at the wall increases with the acoustic pressure, while a simulation by Matsumoto and Yoshizawa 29 suggested that the internal pressure in the center bubble in a MB cluster reaches a maximum at an insonation frequency of 110 kHz. Maeda and Colonius 32 simulated the dynamics of cloud cavitation in an ultrasonic field and reported that the acoustic pressure due to the cloud when not interacting with the vessel wall increased according to a bubble interaction parameter determined by the bubble radius and void fraction (taken to mean, the volume fraction of bubbles divided by the total volume).…”

Section: Introductionmentioning

confidence: 99%

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Three-dimensional numerical analysis of wall stress induced by asymmetric oscillation of microbubble trains inside micro-vessels

Pang

Bai

et al. 2023

Physics of Fluids

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Understanding the stress patterns produced by microbubbles (MB) in blood vessels is important in enhancing the efficacy and safety of ultrasound-assisted therapy, diagnosis and drug delivery. In this study, the wall stress produced by a non-spherical oscillation of MBs within the lumen of micro-vessels was numerically analyzed using a three-dimensional finite element method. We systematically simulated configurations containing an odd number of bubbles from three to nine, equally spaced along the long axis of the vessel, insonated at an acoustic pressure of 200 kPa. We observed that 3 MBs were sufficient to simulate the stress state of an infinite number of bubbles. As the bubble spacing increased the interaction between them weakened to the point that they could be considered to act independently. In the relationship between stress and acoustic frequency there were differences between the single and 3 MB cases. The stress induced by 3MBs was greater than the single bubble case. When the bubbles were near the wall, the shear stress peak was largely independent of vessel radius, but the circumferential stress peak increased with the radius. This study offers further insight into our understanding of, the magnitude and distribution of stresses produced by multiple ultrasonically excited MBs inside capillaries.

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Section: Peak Values Of Stressmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Three-dimensional numerical analysis of wall stress induced by asymmetric oscillation of microbubble trains inside micro-vessels

Pang

Bai

et al. 2023

Physics of Fluids

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“…ACT ® is based on microclusters of microbubbles (negatively charged) and microdroplets (positively charged) forming large microbubbles under ultrasound exposure. A high-frequency ultrasound exposure initiates the activation step, causing oscillating microbubbles to transfer energy to the microdroplets, leading to an instant vaporisation of the microdroplets, forming larger ACT ® bubbles with a diameter of 20-22 µm [28,30]. Subsequently, a low-frequency ultrasound exposure induces the oscillations of the large microbubbles, the enhancement step, subjecting the surrounding tissue to biomechanical effects.…”

Section: Introductionmentioning

confidence: 99%

Real-Time Multiphoton Intravital Microscopy of Drug Extravasation in Tumours during Acoustic Cluster Therapy

Fernandez,

Snipstad,

Bjørkøy

et al. 2024

Cells

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Optimising drug delivery to tumours remains an obstacle to effective cancer treatment. A prerequisite for successful chemotherapy is that the drugs reach all tumour cells. The vascular network of tumours, extravasation across the capillary wall and penetration throughout the extracellular matrix limit the delivery of drugs. Ultrasound combined with microbubbles has been shown to improve the therapeutic response in preclinical and clinical studies. Most studies apply microbubbles designed as ultrasound contrast agents. Acoustic Cluster Therapy (ACT®) is a novel approach based on ultrasound-activated microbubbles, which have a diameter 5–10 times larger than regular contrast agent microbubbles. An advantage of using such large microbubbles is that they are in contact with a larger part of the capillary wall, and the oscillating microbubbles exert more effective biomechanical effects on the vessel wall. In accordance with this, ACT® has shown promising therapeutic results in combination with various drugs and drug-loaded nanoparticles. Knowledge of the mechanism and behaviour of drugs and microbubbles is needed to optimise ACT®. Real-time intravital microscopy (IVM) is a useful tool for such studies. This paper presents the experimental setup design for visualising ACT® microbubbles within the vasculature of tumours implanted in dorsal window (DW) chambers. It presents ultrasound setups, the integration and alignment of the ultrasound field with the optical system in live animal experiments, and the methodologies for visualisation and analysing the recordings. Dextran was used as a fluorescent marker to visualise the blood vessels and to trace drug extravasation and penetration into the extracellular matrix. The results reveal that the experimental setup successfully recorded the kinetics of extravasation and penetration distances into the extracellular matrix, offering a deeper understanding of ACT’s mechanisms and potential in localised drug delivery.

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“…As the time-averaged steady flow velocity is typically 3 orders of magnitude lower than the instantaneous oscillatory velocity of the bubble wall Ṙ, we deem shear stress due steady microstreaming negligible as compared to non-steady shear stress. To estimate non-steady shear stress, the acoustic boundary layer thickness δ = 2µ(ρω) −1 is often used as the relevant length scale over which the bubble wall velocity Ṙ decays (i.e., ∂v/∂z ≈ Ṙ/δ) [9,40,188]. However, this is only the case for a bubble in the unbounded liquid oscillating at small amplitudes of oscillation (⟨R ϵ ⟩ ≪ R 0 ).…”

Section: Discussion On Potential Mechanism(s) Of Sonoporationmentioning

confidence: 99%

Control of monodisperse microbubble properties for high-precision medical applications

van Elburg

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Ultrafast Microscopy Imaging of Acoustic Cluster Therapy Bubbles: Activation and Oscillation

Cited by 9 publications

References 53 publications

Three-dimensional numerical analysis of wall stress induced by asymmetric oscillation of microbubble trains inside micro-vessels

Three-dimensional numerical analysis of wall stress induced by asymmetric oscillation of microbubble trains inside micro-vessels

Real-Time Multiphoton Intravital Microscopy of Drug Extravasation in Tumours during Acoustic Cluster Therapy

Control of monodisperse microbubble properties for high-precision medical applications

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