University of Pittsburgh

Whole Organ Therapeutic Ultrasound Delivery and Containment Device

University of Pittsburgh researchers have developed a novel device for whole organ therapeutic ultrasound delivery and containment, designed to improve outcomes in liver transplantation. This technology aims to reduce the incidence of ischemic cholangiopathy by removing microthrombi from the peribiliary vascular plexus during ex vivo machine perfusion.

Description

The device is a containment system that houses the liver within a reservoir of perfusate fluid during ex vivo machine perfusion. Multiple ultrasound probes within the device walls sequentially fire to induce acoustic and inertial cavitation of microbubbles infused into the liver. These microbubbles, filled with perfluorocarbon and smaller than red blood cells, reach all areas of the hepatic microvasculature, including the peribiliary plexus. The cavitation process disrupts microthrombi, restoring microvascular patency and improving post-transplant perfusion. This innovative approach addresses the challenge of ischemic cholangiopathy, a major complication in liver transplantation from donors after circulatory death (DCD).

Applications

• Liver transplantation
• Organ perfusion and preservation
• Reducing ischemic cholangiopathy in DCD liver transplants

Advantages

Reduces the risk of ischemic cholangiopathy by effectively removing microthrombi from the liver's peribiliary vascular plexus.
The use of sonothrombolysis during ex vivo machine perfusion enhances post-transplant perfusion and viability of DCD livers, potentially increasing the number of transplants performed and decreasing deaths on the waiting list. The technology represents a novel mechanical approach to clot disruption, with no apparent injury to the liver, making it a promising solution for improving liver transplant outcomes.

Invention Readiness

The technology has been validated through in vivo studies using a rat model of DCD liver transplantation. Researchers have demonstrated successful resolution of microthrombi from the peribiliary vascular plexus without biochemical or histological injury to the liver. The device design includes multiple ultrasound probes that sequentially fire to prevent sound-wave interference, ensuring complete coverage of the hepatic parenchyma.

IP Status

https://patents.google.com/patent/WO2023192365A1