Prostate cancer accrues 180,000 new cases in the United States of America annually, and remains the second most common cause of cancer death in men. The standard approach for treating prostate cancer is whole gland therapy, including surgical resection or radiation therapy. Treatment co-morbidities from whole gland therapy occur in 42% of cases and can significantly reduce patient quality of life. For these reasons, several studies have recently concluded that prostate cancer is being dramatically over-treated. The objective of these studies is to generate data using an ultrasound-activated agent for both image-guidance and enhancement of tumor liquefaction with therapeutic ultrasound. Therapeutic ultrasound has been used for non-invasive prostate ablation extensively outside the United States, and was approved for use in the United States in December 2015 by the U.S. Food and Drug Administration (FDA). Histotripsy is a form of therapeutic ultrasound which liquefies tissue mechanically into acellular debris through ultrasound-induced bubble clouds. Ultrasound-triggered phase shift emulsions (UPEs) are encapsulated metastable liquid droplets that can be transitioned to microbubbles by histotripsy. These microbubbles can be utilized for both diagnostic ultrasound contrast and enhancement of the histotripsy therapy. We have loaded the UPE liquid core with an MR contrast agent (Gd2O3). Strong T1 contrast occurs once the UPE is transitioned, enabling multimodal imaging of the liquefaction zone. More information can be found here.
Histotripsy is a noninvasive focused ultrasound therapy that employs the mechanical action of bubble clouds to liquefy tissue. Pre-clinical studies have demonstrated histotripsy efficacious for acute clot ablation. Chronic deep vein thrombi are stiffer than acute thrombi, which will modulate the bubble cloud activity. The Specific Objective of this study was to determine the relationship between medium stiffness and bubble cloud activity necessary for liquefaction. Tissue-mimicking agarose phantoms with elastic moduli ranging from 10 to 150 kPa were exposed to histotripsy pulses of 5-ms duration and peak negative pressures of 12-24 MPa. Bubble cloud emissions mapped with passive cavitation imaging were correlated with the phantom liquefaction zone using receiver operator characteristic analysis. The strength of bubble emissions necessary for liquefaction was extracted for each phantom stiffness. Strong bubble cloud emissions were observed on passive cavitation imaging for all phantoms. No change was observed with phantom stiffness in the emission power necessary for liquefaction. Further, there was no indication of changes in the strength or location of bubble cloud emissions with phantom stiffness. The Key Outcome from this study is a fixed threshold acoustic power mapped with passive cavitation imaging can be utilized for predicting liquefaction of acute and chronic thrombus.