Assessment of ultrasound histotripsy-induced damage to ex vivo porcine muscle

Objectives:-Cavitation-based histotripsy uses high-intensity focused ultrasound pulses at a low duty cycle to generate energetic bubble clouds inside tissue to fractionate cells and is a potential noninvasive tumor treatment modality. Aiming at determining therapy efficiency, we experimentally investigated the effects of pulse repetition frequency and lateral scan step size on the degree of damage of histotripsy-induced lesions in porcine muscle tissue. Methods-A single-element spherically focused source (1.1 MHz, 6.34-cm focal length, f/1) was excited to reach the peak compressional and rarefactional pressures of approximately 102 and 17 MPa, respectively. A targeted square of 9 mm wide (lateral to focal plane) was scanned in a raster pattern with the step sizes of 375, 750, 1500, 2250, and 4500 μm. Pulses at each treatment location consisted of 5000 20-cycle sine wave tone bursts with a pulse repetition frequency of 167, 333, or 1000 Hz. Histopathologic examination and image processing were performed to evaluate the tissue damage for each experimental condition. Results-Skeletal myofiber damage was successfully created with our 7 exposure conditions. Three scales for muscle damage were identified through performing quad-tree decomposition to photomicrograph images and then relating decomposition with lesion homogeneity. Conclusions-Using a finer scan step size promoted the lesion homogeneity. Selection of the optimal condition does not depend solely on the comparison of tissue damage. Given the uncertainty on which of the 3 scales for tissue damage allows muscle repair, 2 conditions were identified as optimal: the 1500 μm-333 Hz condition for scale 3 (related to mild damage) and the 750 μm-333 Hz condition for scale 1 (related to severe damage).