Dynamics of acoustic droplet vaporization in gas embolotherapy.
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ABSTRACT:
SUBMITTER: Qamar A
PROVIDER: S-EPMC2862051 | biostudies-other | 2010 Apr
REPOSITORIES: biostudies-other
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Project description:Acoustically sensitive emulsion droplets composed of a liquid perfluorocarbon have the potential to be a highly efficient system for local drug delivery, embolotherapy, or for tumor imaging. The physical mechanisms underlying the acoustic activation of these phase-change emulsions into a bubbly dispersion, termed acoustic droplet vaporization, have not been well understood. The droplets have a very high activation threshold; its frequency dependence does not comply with homogeneous nucleation theory and localized nucleation spots have been observed. Here we show that acoustic droplet vaporization is initiated by a combination of two phenomena: highly nonlinear distortion of the acoustic wave before it hits the droplet and focusing of the distorted wave by the droplet itself. At high excitation pressures, nonlinear distortion causes significant superharmonics with wavelengths of the order of the droplet size. These superharmonics strongly contribute to the focusing effect; therefore, the proposed mechanism also explains the observed pressure thresholding effect. Our interpretation is validated with experimental data captured with an ultrahigh-speed camera on the positions of the nucleation spots, where we find excellent agreement with the theoretical prediction. Moreover, the presented mechanism explains the hitherto counterintuitive dependence of the nucleation threshold on the ultrasound frequency. The physical insight allows for the optimization of acoustic droplet vaporization for therapeutic applications, in particular with respect to the acoustic pressures required for activation, thereby minimizing the negative bioeffects associated with the use of high-intensity ultrasound.
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Project description:Acoustic droplet vaporization (ADV) is the selective vaporization of liquid microdroplets using ultrasound, resulting in gas bubbles. The ADV process has been proposed as a tool in biomedical applications such as gas embolotherapy, drug delivery, and phase-change contrast agents. Using a 7.5 MHz focused transducer, the initial gas nucleus formed in perfluorocarbon microdroplets was directly visualized using ultra-high speed imaging. The experimental results of initial nucleation site location were compared to a 2D axisymmetric linear acoustic model investigating the focal spot of the acoustic wave within the microdroplets. Results suggest a wavelength to droplet diameter dependence on nucleation site formation.
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Project description:One application of acoustic droplet vaporization (ADV), a method of converting biocompatible microdroplets into microbubbles, is to enhance locally high intensity focused ultrasound (HIFU) therapy. Two objectives are pursued here: (1) the controlled creation of a bubble trench prior to HIFU using ADV and (2) use of the trench for increasing ablation volumes, lowering acoustic powers, and decreasing therapy duration. Thermally responsive phantoms were made with perfluorocarbon emulsion. Compound lesions were formed in a laboratory setting and a clinical magnetic resonance imaging (MRI)-guided HIFU system. Linear and spiral patterned compound lesions were generated in trenches. A larger fraction of the HIFU beam is contained to increase the generation of heat. Using the laboratory system, a 90 mm linear length spiral trench was formed in 30 s with mechanical beam steering. Comparatively, the clinical HIFU system formed a 19.9 mm linear length spiral trench in approximately 1 s with electronic beam steering. Lesions were imaged optically and with MRI. A uniform thermal ablation volume of 3.25 mL was achieved in 55.4 s (4-times faster than standard clinical HIFU and 14-times larger volume versus sum of individual lesions). Single lesions showed a 400% volume increase.
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