Histotripsy-induced cavitation cloud initiation thresholds in tissues of different mechanical properties

Histotripsy is an ultrasound ablation method that depends on the initiation and maintenance of a cavitation bubble cloud to fractionate soft tissue. This paper studies how tissue properties impact the pressure threshold to initiate the cavitation bubble cloud. Our previous study showed that shock scattering off one or more initial bubbles, expanded to sufficient size in the focus, plays an important role in initiating a dense cavitation cloud. In this process, the shock scattering causes the positive pressure phase to be inverted, resulting in a scattered wave that has the opposite polarity of the incident shock. The inverted shock is superimposed on the incident negative pressure phase to form extremely high negative pressures, resulting in a dense cavitation cloud growing toward the transducer. We hypothesize that increased tissue stiffness impedes the expansion of initial bubbles, reducing the scattered tensile pressure, and thus requiring higher initial intensities for cloud initiation. To test this hypothesis, 5-cycle histotripsy pulses at pulse repetition frequencies (PRFs) of 10, 100, or 1000 Hz were applied by a 1-MHz transducer focused inside mechanically tunable tissue-mimicking agarose phantoms and various ex vivo porcine tissues covering a range of Young´s moduli. The threshold to initiate a cavitation cloud and resulting bubble expansion were recorded using acoustic backscatter detection and optical imaging. In both phantoms and ex vivo tissue, results demonstrated a higher cavitation cloud initiation threshold for tissues of higher Young´s modulus. Results also demonstrated a decrease in bubble expansion in phantoms of higher Young´s modulus. These results support our hypothesis, improve our understanding of the effect of histotripsy in tissues with different mechanical properties, and provide a rational basis to tailor acoustic parameters for fractionation of specific tissues.