Histotripsy of rabbit renal tissue in vivo:: Temporal histologic trends

Background and Purpose: Histotripsy is defined as noninvasive, nonthermal, mechanical (cavitational) tissue ablation. We previously demonstrated the predictable acute tissue effects of histotripsy in rabbit kidney and other tissues. We sought to characterize the appearance and natural history of renal tissue after histotripsy. Materials and Methods: Following Institutional Animal Care Committee approval, the left kidneys of 29 rabbits were treated with 60,000 750-kHz, 15-cycle bursts of ultrasound energy from an 18-element phasedarray transducer at a 1-kHz pulse-repetition frequency. The treated kidneys were harvested at 0, 1, 2, 7, 21, or 60 days; fixed in Formalin; then prepared for microscopic analysis with hematoxylin and eosin and trichrome stains. Results: For kidneys harvested acutely (day 0), a contiguous area of finely disrupted tissue was observed containing no recognizable cells or cellular components. Along the boundary of architectural disruption, a border several tubules wide contained cells that were not visibly disrupted but appeared damaged (pyknotic nuclei). At subsequent time intervals, an inflammatory response developed in association with a steadily decreasing area of cellular and architectural disruption. By day 60, only a small fibrous scar persisted adjacent to a wedge of tubular dilation and fibrosis underlying a surface-contour defect. Conclusions: Histotripsy produces mechanical fractionation of cellular and architectural structures. The resultant acellular material appears to be readily reabsorbed within 60 days in the rabbit. This may prove to be a significant advantage for imaging assessment of residual tumor after ablation of renal malignancy.