The researchers from the three universities solved a long standing
mystery of how superheated nanodroplets vaporise when hit by a pulse of
ultrasound. The findings were published last month in Proceedings of the National Academy of Sciences ("Acoustic droplet vaporization is initiated by superharmonic focusing").
The imaging method the team has been working on revolves around nanodroplets of a special liquid called perfluorocarbon that can be injected in a human body. These droplets can move out of the vascular system and enter the space in between the tumour cells. The idea is to activate these droplets with an intense pulse of ultrasound. This sound causes the droplets to vaporise, forming tiny bubbles of gas which can be viewed using ultrasound imaging equipment. | |||
The same method can also be used to administer toxic medicines carried into the tumour by the droplets. This should have no damaging side effects on healthy tissue in the rest of the body, making it a localised and controlled form of chemotherapy. | |||
The technique is still in its infancy. An important problem being the fact that the amplitude of the sound needs to be very high as to vaporise the droplets, while it may not be that high that damage may occur to healthy tissue. |
This work explains the long-standing puzzle of the physical mechanisms underlying acoustic droplet vaporization (ADV). ADV makes use of low-boiling-point perfluorocarbon droplets that become metastable once injected into the body, where they can be activated by high-intensity ultrasound. How ultrasound can physically trigger the vaporization remained elusive, also given the large mismatch between the ultrasound wavelength and the droplet size. Here we show that vaporization is preceded by nonlinear propagation of the ultrasound wave generating superharmonics. These high-frequency waves focus efficiently within the droplet, triggering vaporization. ADV shows great potential for advanced medical diagnosis and therapy. Our new understanding allows for further reduction of the required pressure amplitudes, thereby minimizing the adverse effects on healthy tissue.
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.
source : PNAS
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