Investigation Of The Mechanical Response And Cavitation Erosion At The Focus During Focused Ultrasound Ablation Surgery

Focused ultrasound ablation surgery（FUAS）can treat a variety of benign and malignant tumors,which has advantages of no ionization,few side effects,and non-invasiveness.However,there are still some problems to be solved and explored.Firstly,inter-patients’variations and tissue heterogeneity affect the efficacy and efficiency of FUAS.Due to the low sensitivity and specificity of sonography,it is challenging to quantitatively monitor the treatment process of FUAS.Meanwhile,the high-intensity irradiation causes significant acoustic radiation force and cavitation in the biological tissues in the focal region.The acoustic radiation force deforms and displaces the biological tissues,and the bubble collapse leads to complex physical effects,such as localized high temperature,high pressure,and high-speed microjet,which result in the mechanical damage to the biological tissues.In this thesis,FUAS-induced mechanical response and acoustic cavitation in the focal region is investigated.A method that is based on ultrasound-stimulated-vibro-acoustography（USVA）is proposed to monitor FUAS treatment;a viscoelastic model is established for the sound velocity and sound absorption coefficient relevant to the viscoelasticity of biological tissue.The coagulative necrosis was predicted by the acoustic parameters of biological tissue while the mechanical erosion was quantitatively assessed by the acoustic cavitation,microjet impact and velocity inversion models.Firstly,the thermal,mechanical,and biological mechanisms of FUAS are introduced,the challenges and difficulties faced are explained,and the research objectives are proposed:（1）the theoretical model of the mechanical response of biological tissues and its relationship with the USVA signal characteristics;（2）correlation and inversion method between the biological tissue’s viscoelasticity and spatial distribution of sound velocity and absorption coefficient;（3）quantitative relationship between cavitation erosion near a solid interface and microjet.Next,the Voigt model of the medium viscoelasticity is combined with the Navier-Stokes equation of fluid motion for the relationship between the acoustic radiation force and the displacement field of the biological tissue.In the k-space,the Green’s function of the longitudinal wave displacement in the viscoelastic medium is convolved with the acoustic radiation force in the both time and space as the mechanical response of the biological tissue and the mechanism of the USVA source.In the dual-frequency confocal ultrasonic transducer,the characteristics of the acoustic radiation force field in the focal region are studied.The radiation performance（i.e.,the dynamics,radial width,longitudinal depth,and side lobe distribution of each harmonic in the acoustic radiation force field）of the two structures（I:equal radiation area,II:8 spherical sectors）are compared.The simulation and measurement results show that the 8-spherical sectors structure has higher localization.And,the acoustic radiation force of the fundamental frequency and the second harmonic are proportional to,the nonlinearity and attenuation coefficient.The larger the linear focusing gain,the smaller and sharper the main lobe of the acoustic radiation force.Moreover,the frequency difference has little effect on the longitudinal depth,radial width,and maximum amplitude of the acoustic radiation force field of corresponding to each harmonic,irradiation time for the temperature rise no more than 1°C,and mechanical index.Thirdly,the displacement field of the USVA is analyzed.It is found that linear superposition is valid for the one-dimensional line source,the two-dimensional surface source,and the three-dimensional volume source and the interference of the frequency difference signal from the parametric array and nonlinear scattering effect is too little to be considered.The radiated sound field of the three-dimensional USVA source is established by the Rayleigh integration.The influences of the medium elastic modulus,the geometries of the USVA source,and the nonlinearity on the USVA field are analyzed.The relationship between USVA amplitude and the biological tissue’s elastic modulus is found.The spatial resolution and signal-to-noise ratio under varied nonlinearities are quantitatively analyzed.Therefore,with the increase of the intensity but the decrease of the irradiation time,the signal-to-noise ratio and the sensitivity of FUAS monitoring can be improved.Fourthly,the frequency-domain Helmholtz equation obtained by combining the Voigt viscoelasticity model with the Navier-Stokes equation is used for inversing the biological tissue’s viscoelasticity,and then according to the Kramers-Kronig relationship,the sound velocity and absorption coefficient are constructed.The performance of the inversion model is quantified by the compression modulus（viscosity）contrast,contrast transfer efficiency,contrast-to-noise ratio（CNR）,and root mean square error（RMSE）.The inversion errors between the inversed sound speed and absorption coefficient and the actual are small,for example?（f）=0.11 f^1.9 and?（f）=0.12 f^1.9for the actual and inversed frequency-dependent acoustic absorption coefficient,respectively.At the lower frequencies,the dispersion effect is negligible.In addition,the diffraction effect only affects the displacement propagation,but not the viscoelasticity.Namely,changes to force source distribution due to the biological tissue heterogeneity and variation will not affect the inversion of viscoelasticity.Fifthly,cavitation erosion experiments are carried out using a copper plate in a spherical cavity focused ultrasonic transducer.Under the assmption of（1）the effect of fusion between cavitation bubbles on the bubble collapse is ignored and（2）the dimension of the microjet is equal to that of the maximum bubble which is not affected by gravity and buoyancy,the cavitation threshold,the initial radius of the cavitation bubbles,and microjet velocity are determined.Combining the nonlinear propagation Westervelt equation and the high strain rate Johnson-Cook（J-C）constitutive model,a microjet impact model of multiple cavitation bubbles is constructed to describe cavitation erosion,and a continuous impact mode of the microjet is proposed using with the equivalent acting time.By analyzing the morphological characteristics of cavitation pits,the relative errors of cavitation pit depths at the hydrostatic pressure of 3,6,and 10 MPa are 4.02%,3.34%,and 1.84%,respectively;and the relative error of the dynamic change of the cavitation pit morphology under the hydrostatic pressure of 10 MPa is 7.33%,which show the reliability of the model and the rationality of the assumptions.The experimental and simulation results show that the greater the hydrostatic pressure,the greater the cavitation erosion pit depth,the cavitation erosion pit diameter,the cavitation erosion pit-to-microjet diameter ratio and the cavitation erosion intensity,but the smaller the cavitation erosion pit diameter-to-depth ratio.Under the continuous ultrasonic irradiation,the cavitation erosion became more intense.Finally,according to the analogy with the nanoindentation test,a microjet velocity inversion model is built to evaluate the cavitation intensity by using the morphological features of cavitation pits（i.e.,cavitation pit diameter and depth）at different hydrostatic pressures.The lower and upper limits of the corresponding microjet velocity errors are5.98%and 0.11%,6.62%and 9.14%,6.54%and 5.42%at the hydrostatic pressure of 3MPa,6 MPa,and 10 MPa,respectively.The inversion results show that if and only if the cavitation pit diameter-to-microjet diameter ratio is close to 1,the microjet velocity inversion model can work effectively.In summary,this thesis systematically studies the mechanical response and acoustic cavitation characteristics of focused ultrasound ablation surgery as a theoretical basis for monitoring FUAS.Although there are still many shortcomings,it shows a novel approach of investigating FUAS mechanism,dose distribution,and therapeutic evolution.This work has good scientific and application potential.