Histotripsy in focused ultrasound surgery: Mechanical ablation of tissue using controlled acoustic cavitation.

Abstract

This research has investigated non-invasive tissue ablation techniques in ultrasonic surgery that are mediated primarily by the mechanical effects of controlled acoustic cavitation, thereby de-emphasizing the role of thermal coagulation during treatment of diseased tissues. This approach is referred to as histotripsy, in which soft tissues are broken apart by mechanical agitation, in analogy to established lithotripsy procedures whereby renal stones are similarly comminuted. During histotripsy, cavitation microbubbles are formed endogenously in the treatment volume due to the intense rarefactional pressures (> 20 MPa) incurred. The actions of these microbubbles can impart severe yet highly localized mechanical damage to surrounding cellular architecture. The primary goal of this research was to investigate acoustic methods to control these powerful cavitation effects in order to produce therapeutic soft tissue lesions with minimal thermal invasiveness to surrounding collateral structures. Toward this end, an acoustic pulsing scheme was developed to actively sustain cavitation activity through the use of short-duration (e.g., 15 mus), high-intensity (e.g., 40 kW/cm<super>2</super> I_SPPA) pulses delivered at low repetition frequencies (e.g., 0.17 kHz). This approach maintained the microbubble population during treatment without producing significant temperature elevations (e.g., DeltaT = 5&deg;C). Cavitation-mediated damage morphology in porcine myocardium and renal parenchyma consisted of well-circumscribed, 0.5-1 cm<super>3</super> voids containing homogenized tissue slurry. Standard histological staining revealed extremely fine pulverization that often bisected single cells. This type of damage morphology offers particular advantages over thermal ablation in applications where diseased or impeding tissue must be physically removed, not merely treated and left <italic>in situ</italic>. In general, the ability to sustain effective cavitation during histotripsy was strongly influenced by acoustic pulse conditions, as measured by four specific metrics: (i) the prevalence of homogenate within the lesion; (ii) the Young's modulus following treatment; (iii) the degree of spatio-temporal variability in acoustic backscatter; (iv) the duration of light scattering from bubble surfaces inside the lesion, measured using fiber-optic techniques. Consistent trends were observed in the behavior of all four metrics as acoustic input conditions were adjusted, lending supportive evidence that the histotripsy process can be controlled through application of rationally-based pulsing strategies designed to manage resident microbubble activity.