Endoscopic high-intensity focused US: technical aspects and studies in an in vivo porcine model (with video)

Abstract

Background High-intensity focused ultrasound (HIFU) is becoming more widely used for non-invasive and minimally invasive ablation of benign and malignant tumors. Recent studies suggest that HIFU can also enhance targeted drug delivery and stimulate an anti-tumor immune response in many tumors. However, targeting of pancreatic and liver tumors using an extracorporeal source is challenging due to the lack of an adequate acoustic window. The development of an endoscopic ultrasound (EUS)-guided HIFU transducer has many potential benefits including improved targeting, decreased energy requirements and decreased potential for injury to intervening structures. Objective To design, develop and test an EUS-guided HIFU transducer for endoscopic applications. Design A pre-clinical, pilot characterization and feasibility study. Setting Academic research center. Patients Studies were performed in an in vivo porcine model. Intervention Thermal ablation of in vivo porcine pancreas and liver was performed with EUS guided focused ultrasound through the gastric tract. Results The transducer successfully created lesions in gel phantoms and ex vivo bovine livers. In vivo studies demonstrated that targeting and creating lesions in the porcine pancreas and liver are feasible. Limitations This is a pre-clinical, single-center feasibility study with a limited number of subjects. Conclusion An EUS-guided HIFU transducer was successfully designed and developed with dimensions that are appropriate for endoscopic use. Feasibility of performing EUS-guided HIFU ablation in vivo has been demonstrated in an in vivo porcine model. Further development of this technology will allow endoscopists to perform precise therapeutic ablation of peri-lumenal lesions without breaching the wall of the gastric tract.

Thermal therapy of pancreatic tumours using endoluminal ultrasound: Parametric and patient-specific modelling

“…In practice, it could be beneficial to distend the stomach or duodenum lumen to stretch and thin the luminal wall. This would be particularly important in the presence of folds or rugae, which could cause an increase in effective wall thickness or harbor air bubbles that could impact acoustic transmission and increase localized heating [25]. Distension of the lumens may be achievable either through filling the stomach or small intestines with water, through endoscopic manipulation, or by incorporating large distensible balloons onto the applicator that would be inflated once the applicator was positioned [69].…”

“…In addition to size, the proximity of pancreatic tumors to sensitive anatomy, such as ducts, bowel, or significant vasculature, limits volumetric tumor coverage for ablation and imposes the need for highly accurate placement and manipulation of the applicator to ensure that energy is directed precisely towards target tissues. Integrating the applicator with an endoscope may provide sufficient control for positional accuracy [25]. Image-guidance techniques, incorporating MRI or ultrasound guidance, could also be employed to verify positioning, monitor treatments, and permit feedback control [25,71,72].…”

“…Integrating the applicator with an endoscope may provide sufficient control for positional accuracy [25]. Image-guidance techniques, incorporating MRI or ultrasound guidance, could also be employed to verify positioning, monitor treatments, and permit feedback control [25,71,72]. While the PI feedback control scheme employed herein permitted conformal lesion formation, more advanced schemes incorporating pilot/boundary-control points or model predictive control could further improve targeting and reduce undesirable thermal exposure [52,73].…”

“…Specific applicator configurations for placement in the upper gastrointestinal (GI) tract have been applied clinically for endoluminal ablation of esophageal and biliary tumors [22,23]. An endoscope with a miniature spherically-focused transducer at the tip has also been developed and experimentally validated to create ablation lesions in porcine pancreas and liver under endoscopic ultrasound guidance [24,25]. …”

Endoscopic Ultrasound and Related Technologies for the Diagnosis and Treatment of Pancreatic Disease - Research Gaps and Opportunities

“…74 Clinical translation of these methods awaits the development of a high-intensity focused US endoscope. 75 …”