High-frequency dynamics of ultrasound contrast agents

Sun, Yang; Kruse, Dustin E.; Dayton, Paul A.; Ferrara, Katherine W.

doi:10.1109/tuffc.2005.1561667

Cited by 51 publications

(14 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At 0.30 MPa, nonlinear oscillations may induce the fourth and fifth harmonics, and bubble expansions may lead to BBB opening. In simulations, the resonance frequency of a 1–2 μ m diameter microbubble was about 4–8 MHz (Sassaroli and Hynynen 2005, Sun et al 2005), which included the fourth and fifth harmonics of 1.5 MHz. As a result, the fourth and fifth harmonics detected by the broadband hydrophone might serve as a reliable indicator of BBB opening.…”

Section: Discussionmentioning

confidence: 99%

In vivotranscranial cavitation threshold detection during ultrasound-induced blood–brain barrier opening in mice

Tung¹,

Vlachos²,

Choi³

et al. 2010

Phys. Med. Biol.

223

161

View full text Add to dashboard Cite

The in vivo cavitation response associated with blood–brain barrier (BBB) opening as induced by transcranial focused ultrasound (FUS) in conjunction with microbubbles was studied in order to better identify the underlying mechanism in its noninvasive application. A cylindrically focused hydrophone, confocal with the FUS transducer, was used as a passive cavitation detector (PCD) to identify the threshold of inertial cavitation (IC) in the presence of Definity® microbubbles (mean diameter range: 1.1–3.3 μm, Lantheus Medical Imaging, MA, USA). A vessel phantom was first used to determine the reliability of the PCD prior to in vivo use. A cerebral blood vessel was simulated by generating a cylindrical channel of 610 μm in diameter inside a polyacrylamide gel and by saturating its volume with microbubbles. The microbubbles were sonicated through an excised mouse skull. Second, the same PCD setup was employed for in vivo noninvasive (i.e. transdermal and transcranial) cavitation detection during BBB opening. After the intravenous administration of Definity® microbubbles, pulsed FUS was applied (frequency: 1.525 or 1.5 MHz, peak-rarefactional pressure: 0.15–0.60 MPa, duty cycle: 20%, PRF: 10 Hz, duration: 1 min with a 30 s interval) to the right hippocampus of twenty-six (n = 26) mice in vivo through intact scalp and skull. T1 and T2-weighted MR images were used to verify the BBB opening. A spectrogram was generated at each pressure in order to detect the IC onset and duration. The threshold of BBB opening was found to be at a 0.30 MPa peak-rarefactional pressure in vivo. Both the phantom and in vivo studies indicated that the IC pressure threshold had a peak-rarefactional amplitude of 0.45 MPa. This indicated that BBB opening may not require IC at or near the threshold. Histological analysis showed that BBB opening could be induced without any cellular damage at 0.30 and 0.45 MPa. In conclusion, the cavitation response could be detected without craniotomy in mice and IC may not be required for BBB opening at relatively low pressures.

show abstract

Section: Discussionmentioning

confidence: 99%

In vivotranscranial cavitation threshold detection during ultrasound-induced blood–brain barrier opening in mice

Tung¹,

Vlachos²,

Choi³

et al. 2010

Phys. Med. Biol.

223

161

View full text Add to dashboard Cite

show abstract

“…[40][41][42][43] In this field, as bubbles are good scatterers of sound, they can be employed to enhance signals. Since the volume oscillations of a bubble are generally nonlinear ͓see Fig.…”

Section: Discussionmentioning

confidence: 99%

The stability of a bubble in a weakly viscous liquid subject to an acoustic traveling wave

Shaw¹

2009

Physics of Fluids

View full text Add to dashboard Cite

The volume oscillations, translation, and axisymmetric deformation of a bubble in an acoustic traveling wave are considered. Assuming the bubble translation and deformation is small, but placing no restriction on the volume oscillations, a combination of the Rayleigh dissipation function and perturbation analysis is employed to account for the effects of viscosity in the absence of vorticity to third order in the small interaction terms. Contributions from the acoustic field are also determined to this order, while the free oscillation terms are drawn from a previously derived model correct to the same order of analysis. To permit the study of large amplitude acoustic forcing, appropriate compressibility terms are phenomenologically added to the volume pulsation equation. Stability maps of driving pressure versus driving frequency and driving pressure versus the equilibrium bubble radius are presented. A predominant number of results are for micron-sized bubbles driven in the ultrasonic regime, but the behavior of larger bubbles driven at frequencies in the kilohertz range is also considered. In all cases, bubbles driven above the natural frequency of their respective volume oscillations are markedly more stable with regard to the acoustic driving amplitude, consistent with previous observations. Below these respective natural frequency values, the stability/instability fronts display a much more complex structure. Accounting for shape mode viscous damping causes a general increase in bubble stability, together with a reduction in the stability/instability front complexity. In the case of micron-sized bubbles this stabilization is markedly more significant for bubbles driven above the natural frequency of the respective volume mode oscillations; for larger bubbles driven in the kilohertz range, the influence of shape mode damping is less significant.

show abstract

“…The stability tests of submicron bubbles were listed in File S1 (Figure S1–S2). The resonance frequency of submicron bubbles were estimated at 10 MHz based on a standard procedure that literature has proposed (see Method S1, Table S1 and Figure S3–S4 in File S1) [24].…”

Section: Methodsmentioning

confidence: 99%

Submicron-Bubble-Enhanced Focused Ultrasound for Blood–Brain Barrier Disruption and Improved CNS Drug Delivery

et al. 2014

View full text Add to dashboard Cite

The use of focused ultrasound (FUS) with microbubbles has been proven to induce transient blood–brain barrier opening (BBB-opening). However, FUS-induced inertial cavitation of microbubbles can also result in erythrocyte extravasations. Here we investigated whether induction of submicron bubbles to oscillate at their resonant frequency would reduce inertial cavitation during BBB-opening and thereby eliminate erythrocyte extravasations in a rat brain model. FUS was delivered with acoustic pressures of 0.1–4.5 MPa using either in-house manufactured submicron bubbles or standard SonoVue microbubbles. Wideband and subharmonic emissions from bubbles were used to quantify inertial and stable cavitation, respectively. Erythrocyte extravasations were evaluated by in vivo post-treatment magnetic resonance susceptibility-weighted imaging, and finally by histological confirmation. We found that excitation of submicron bubbles with resonant frequency-matched FUS (10 MHz) can greatly limit inertial cavitation while enhancing stable cavitation. The BBB-opening was mainly caused by stable cavitation, whereas the erythrocyte extravasation was closely correlated with inertial cavitation. Our technique allows extensive reduction of inertial cavitation to induce safe BBB-opening. Furthermore, the safety issue of BBB-opening was not compromised by prolonging FUS exposure time, and the local drug concentrations in the brain tissues were significantly improved to 60 times (BCNU; 18.6 µg versus 0.3 µg) by using chemotherapeutic agent-loaded submicron bubbles with FUS. This study provides important information towards the goal of successfully translating FUS brain drug delivery into clinical use.

show abstract

High-frequency dynamics of ultrasound contrast agents

Cited by 51 publications

References 39 publications

In vivotranscranial cavitation threshold detection during ultrasound-induced blood–brain barrier opening in mice

In vivotranscranial cavitation threshold detection during ultrasound-induced blood–brain barrier opening in mice

The stability of a bubble in a weakly viscous liquid subject to an acoustic traveling wave

Submicron-Bubble-Enhanced Focused Ultrasound for Blood–Brain Barrier Disruption and Improved CNS Drug Delivery

Contact Info

Product

Resources

About