| Objectives: Histotripsy is a well-controlled ultrasonic tissue ablation technology that mechanically and progressively fractionates soft tissue using cavitation. Significant ultrasound backscatter reduction occurs as the tissue in the treated volume is increasingly fractionated. This paper studies the quantitative correlation between the degree of histotripsy-induced tissue fractionation and the backscatter reduction. Method: A total of 55 lesions were produced in vitro using histotripsy in porcine kidneys. Histotripsy treatment consisted of high intensity (19 MPa peak negative pressure), short duration (15 cycles), 1 MHz ultrasound pulses delivered at 100 Hz pulse repetition frequency. Different degrees of tissue fractionation were generated by varying the number of pulses from 100 to 2000 pulses per treatment location (i.e., 3.75 to 75 pulses/mm3). RF imaging data of the treated tissue were recorded using a 10 MHz linear array imaging probe with a diagnostic ultrasound system. Ultrasound backscatter amplitude of the treated tissue was defined as the median of the pixel intensities within a 4? mm2 region-of-interest (ROI) in the treated area. Backscatter reduction of the treated tissue was calculated by the difference between the post-treatment and pre-treatment backscatter amplitude in ROI. The degree of tissue fractionation was assessed by the percentage of intact cell nuclei within the treated area via histological evaluation. The degree of tissue fractionation was then correlated to the backscatter reduction from the corresponding lesion. Results: All pulse numbers resulted in significant backscatter reduction in the treated tissue (p<0.001; Student’s t-test). As the number of pulses increased from 100 to 2000 pulses per treatment location, the backscatter amplitude reduced from 0 dB to -16 dB (R2=0.87). Correspondingly, the percentage of intact nuclei in the treated area decreased exponentially from 100% to 0% (R2=0.96). Regression analysis showed a strong correlation between the degree of tissue fractionation and the level of backscatter reduction (R2=0.93). Discussion and Conclusions: The strong correlation between tissue fractionation and backscatter reduction suggests that the backscatter reduction can provide quantitative image-based feedback for tissue fractionation. As tissue fractionation should be related to the cell death, backscatter reduction may be a potential real-time feedback parameter for histotripsy, allowing the prediction of local clinical outcomes, i.e. when a tissue volume has been sufficiently treated. |