Non-invasive Ultrasonic Tissue Fractionation for Treatment of Benign Disease and Cancer -“Histotripsy”
Ultrasound has been widely known for diagnostic imaging. The most recent studies suggest that it also has potential to be developed as a non-invasive therapy tool. Ultrasound has the ability to focus energy deep within the human body without damaging the overlying tissue. If the energy is sufficient, significant bioeffects (e.g. tissue necrosis and tissue fractionation) can be achieved. This ability of ultrasound is suited perfectly for many types of non-invasive therapy.
For the past five year, our team has been developing a new technique to achieve mechanical fractionation of tissue structure using a number of short (several μsec), high intensity ultrasound pulses. The ultrasound intensity used is hundreds of times higher than regular diagnostic imaging and similar to “lithotripsy” which has been used for breaking down kidney stones. We have called this technique “histotripsy”. “Histo” means soft tissue in Greek, and “tripsy” means breakdown. At a fluid-tissue interface, histotripsy results in localized tissue removal with sharp boundaries, which we use to removal cardiac tissue in treatment of congenital heart disease. In bulk tissue, histotripsy produces mechanical fragmentation of tissue resulting in a liquefied cored with very sharply demarcated boundaries. Histology demonstrates treated tissue within the lesion is fragmented to subcelluar level surrounded by an almost imperceptibly narrow margin of cellular injury. As shown in the pictures on of right, at the lesion boundary, half of the cell is cut off, and the other half is still intact. Histotripsy has vast clinical applications where precise tissue ablation and removal are needed (e.g., tumor treatment).
The mechanism of histotripsy is acoustic cavitation – ultrasound pressure changes form mircobubbles in human body and energetic microbubble activities fragment and subdivide tissue resulting in cellular destruction. Compared to non-invasive thermal therapy, histotripsy has some important advantages including the following: 1) Microbubbles produced at the ultrasound focus, shown as bright spots on ultrasound imaging, allow the operator to see the targeted volume; 2) Energetic microbubble activities can be seen on imaging and provide real-time feedback, so the operator knows what is going on; 3) After treatment, the lesion appears darker on ultrasound imaging, so that the operator knows what has been done; and 4) Histotripsy technique can produce lesions in a very controlled and precise manner. We believe and hope that, in the near future, non-invasive image guided cavitational ultrasound therapy (histotripsy) can be provided to clinicians as a non-invasive surgery tool to significantly improve the quality of currently available surgery and therapy modalities. Current clinical targets are: breast cancer, prostate cancer, several cardiac applications, and various benign diseases including prostatic “BPH” and breast fibroadenoma.
Histotripsy Mechanism – Cavitation Bubble Dynamics
How exactly does the bubble activity result in cellular disruption and tissue fractionation? How can the bubble dynamics be controlled by ultrasound? These are key questions to understand the mechanism of histotripsy. Understanding of the physical mechanism would provide rationale to guide development and optimization of histotripsy for clinical applications. Bubble cloud formation and dynamic activity of individual bubbles within cloud are being studied using high speed imaging and acoustic and optical monitoring.