A noninvasive approach for metastatic lymph node ablation using histotripsy tissue fractionation

Lymph node dissection is a widely used surgical procedure to treat and stage metastatic lymph nodes but has substantial side effects, such as lymphedema. Histotripsy is a noninvasive ultrasonic therapy that creates well-demarcated tissue fractionation using high-pressure and short acoustic shockwave pulses. This study investigates the possibility using of histotripsy to ablate lymph nodes noninvasively. Experiments were performed on 6 mixed breed healthy pigs, 11 – 12 weeks old and weighing 31 – 43 kg. Their superficial inguinal lymph nodes were treated in vivo with 5- or 10-cycle histotripsy pulses generated by focused, 1MHz therapy transducers, delivered at 50Hz pulse repetition frequency and peak rarefaction pressure above 21MPa. The treatment was guided by ultrasound imaging probes (either ATL CL15-7 or ATL L12-5) with a commercial ultrasound imaging system, HDI 5000. In one selected case, contrast-specific ultrasound was performed after perimammary injection of Sonazoid (GE Healthcare, Oslo, Norway) to localize the lymph nodes. Anatomical landmarks were then used to identify the same nodes for targeted therapy. The histological results show that, after histotripsy treatment, only the targeted lymph nodes were affected and they had demarcated foci of necrosis with minimal damage to the adjacent and intervening tissue. This in vivo acute study demonstrates the capability of histotripsy to noninvasively generate tissue fractionation within targeted lymph nodes, suggesting that histotripsy has the potential in noninvasive lymph node ablation.