This work aims to establish a theoretical framework for the modeling of bubble nucleation in histotripsy. A phenomenological version of the classical nucleation theory was parametrized with histotripsy experimental data, fitting a temperature-dependent activity factor that harmonizes theoretical predictions and experimental data for bubble nucleation at both high and low temperatures. Simulations of histotripsy pressure and temperature fields are then used in order to understand spatial and temporal properties of bubble nucleation at varying sonication conditions. This modeling framework offers a thermodynamic understanding on the role of the ultrasound frequency, waveforms, peak focal pressures, and duty cycle on patterns of ultrasound-induced bubble nucleation. It was found that at temperatures lower than 50 °C, nucleation rates are more appreciable at very large negative pressures such as -30 MPa. For focal peak-negative pressures of -15 MPa, characteristic of boiling histotripsy, nucleation rates grow by 20 orders of magnitude in the temperature interval 60 °C-100 °C.

High-intensity focused ultrasound (HIFU) is a promising treatment modality for the non-invasive ablation of pathogenic tissue in many organs. Optimal treatment planning strategies based on high-performance computing methods are expected to form a vital component of a successful clinical outcome in which healthy tissue is preserved and accurate focusing achieved. The practical application of the algorithms informing these strategies depends on the ability to produce fast and accurate full-wave patient-specific simulations, with minimal computational overheads. For realistic clinical scenarios, all simulation methods which employ volumetric meshes require several hours or days to run on a computer cluster. The boundary element method (BEM) is an effective approach for modelling the wave field because only the boundaries of the hard and soft tissue regions require discretisation. A multiple-domain BEM formulation with a novel preconditioner for solving the Helmholtz transmission problem (HTP) is presented in this paper. Numerical experiments are performed to solve HTP in multiple domains comprising: i) human ribs, an abdominal fat layer and liver tissue, ii) a human kidney and a perinephric fat layer, exposed to the acoustic field generated by a HIFU array transducer. The time required to solve the equations associated with these problems on a single workstation is of the order of minutes. These results demonstrate the great potential of this new BEM formulation for rapid and accurate HIFU treatment planning.