Ultrasonic Histotripsy for Tissue Therapy

Abstract

Hepatocyte transplantation has been considered and investigated as a promising and alternative method to liver transplantation for treating liver-based metabolic disorder in newborns over the past two decades. Although some clinical trials have been conducted and shown clinical benefits and outcomes, it is difficult to deliver and achieve a desired level of integration and transplantation of hepatocytes in the liver parenchyma. To overcome this problem, this work introduces an alternative method to a portal-infused-hepatocyte cell transplantation. To improve the level of engraftment of transplantable hepatocytes, these are injected directly into cavities generated by ultrasonic histotripsy. Histotripsy is an extracorporeal noninvasive technique which has been recently developed using high intensity focused ultrasound (HIFU) for inducing tissue fractionation with no coagulative necrosis. The exact mechanisms for the tissue fractionation are not well understood yet; but the possible mechanisms are thought to be a combination of nonlinear wave propagation effect, explosive bubble growth and ultrasonic atomization. The main objectives of this work are to demonstrate the feasibility of this new cell therapy and evaluate and distinguish between the different types of cavitation activity for either a thermally or a mechanically induced lesion. In the present work, numerical studies on the bubble dynamics (the Gilmore-Akulichev bubble model coupled with the Khokhlov-Zabolotskaya-Kuznetsov equation) and both ex- and in vivo liver experiments are conducted with histological analysis (haematoxylin and eosin stain). The numerical and the experimental results suggest that (a) the acoustic emissions emitted during the thermal ablation and the histotripsy exposure can be distinguished both numerically and experimentally and (b) the proposed cell therapy may potentially form an effective and safe clinical treatment for replacing and correcting disordered hepatocytes, although the transplantation was not conducted in this work.