Characterization of a Transesophageal Focused Ultrasound Transducer for Endoscopic Pancreatic Cancer Ablation

Pancreatic cancer is associated with a poor prognosis mainly due to late diagnosis and limited treatment options. Histotripsy is an image-guided focused ultrasound ablation method with its key features being non-invasive, non-thermal, and non-ionizing. Previous work by our group has demonstrated the feasibility of histotripsy for non-invasively targeting the pancreas through a trans-abdominal approach showing that histotripsy bubble cloud formation and ablation can safely be achieved when there is clear ultrasound visualization. However, when targeting the pancreas, the trans-abdominal approach can be limited by overlying gas in the anterior stomach blocking both imaging and therapy. Here, we proposed the development of endoscopic focused ultrasound (FUS) techniques for applying histotripsy to the pancreas to both overcome gas blockage and provide a higher precision treatment approach. In this study, we developed an endoscopic high-frequency device to evaluate a trans-gastric pancreatic histotripsy approach. First, a custom 3MHz endoscopic histotripsy transducer was designed and simulated based on anatomical and acoustic specifications, featuring 5 rectangular PZT elements geometrically focused at 27 mm for trans-gastric pancreas targeting, with an individual element height of 1.5 cm to remain within esophageal diameter limits. Next, we fabricated two initial prototype 3MHz transducers that had a compact 8 by 2.1 cm overall form factor for endoscopic delivery and a blunt distal tip to facilitate safe esophageal insertion. The prototype transducers were then characterized using hydrophone measurements to evaluate pressure output, high-speed photography to verify bubble cloud generation, and used both in vitro tissue phantoms and ex vivo pancreas tissue to confirm ablation. Results demonstrated sufficient pressure generation, successful cavitation, and ablation in both red blood cell phantoms and excised pig pancreas samples. Finally, the device was assessed in vivo in pigs (n=4) demonstrating successful endoscopic insertion into the stomach from the esophagus under fluoroscopic guidance. Cavitation was also successfully generated in vivo, as confirmed by characteristic audible feedback. Overall, these results represent an important first step towards the development of endoscopic histotripsy as an alternative approach to targeting pancreatic tumors. Endoscopic histotripsy can potentially improve targeting by overcoming gas blockage associated with trans-abdominal approaches and enable higher precision treatments within the sensitive pancreas, with broader applications for pancreatic cancer and other tumor types in anatomically challenging locations.