Acoustic Waveform Optimization for Improved Mild Hyperthermia in Cancer Therapy

Mild hyperthermia (MHTh) is a procedure that involves mildly (≤ 6°C) heating a tumor to enhance the efficacy of standard-of-care cancer treatments such as chemotherapy and radiation therapy. Generating MHTh with ultrasound (US) has seen increased use in the clinic because it is noninvasive and relatively low-cost. However, current US-MHTh systems face significant challenges including difficulty in generating uniform and localized MHTh in large target volumes (i.e., tumors), especially in deep heterogeneous tissues. In this study, we use a ring array US transducer to generate acoustic fields in large arbitrarily shaped targets by optimizing the transmission radiofrequency (RF) waveforms that drive ring array transducer elements. We present a novel methodology based on an inverse wave propagation model to generate the arbitrary pressure fields that account for tissue acoustic properties, depth, and the shape of the tumor. In silico and in vitro studies validated the efficacy of the methodology to generate arbitrary pressure fields and subsequently extend them as periodic transmissions to generate MHTh. These results demonstrate the feasibility of using a ring array US transducer with the proposed waveform optimization to enable more uniform and localized MHTh generation in arbitrary shaped targets in deep heterogenous tissues.