Towards the Use of High Intensity Focused Ultrasound to More Precisely Destroy Tumor Tissue
Focused ultrasound is one of the many approaches used to directly kill cancer cells once they have grown to the point at which a tumor can be identified. It involves generating sufficient heat to kill cells, a fairly direct transfer of energy. Pruning back cancerous tissue is helpful, as tumors manipulate the signaling environment to subvert the immune system's ability to destroy cancerous cells, and constantly generate new mutations that ultimately lead to metastasis and the spread of a cancer throughout the body.
Removing tumor tissue in this way is not a cure, however. Curing cancer requires not just the removal of bulk tumors, but also other means that can be deployed to destroy all lingering or metastasized cancerous cells, any small collection of which can start up a tumor once again. The challenge inherent in any mechanical or radiation based removal of tumors is that it is rarely complete enough to prevent recurrence, while the challenge inherent in any small molecule, gene therapy, immunotherapy, or other similar systemically delivered approach is that tumor masses are a different and tougher target than distributed cancer cells.
Ultrasound ablation of tumor tissue has the advantage of avoiding surgery, but the disadvantage of causing just as much collateral damage to tissues as surgery. Today's research materials discuss ways to minimize that damage, by minimizing cavitation, the formation of heated microbubbles that can spread to destroy tissue surrounding the target. Modeling of outcomes in the use of ultrasound ablation is already something of an art form, with a large variation between predicted and actual results, so it is an open question as to how well this additional layer of modeling will work in practice.
Destroying cancer cells with non-surgical ultrasound treatment
Focusing ultrasound energy on a target site in the body to generate heat can burn and destroy the tissue in the site without a surgical procedure. This method is clinically applied to treat uterine fibroids, prostatic hyperplasia, prostate cancer, metastatic bone tumor and other types of tumor to destroy tumor cells using heat. However, there is a potential problem that the surrounding tissue may be burned in the process due to heat diffusion.
In 2019 a research team confirmed the possibility of precisely fractionating target tumor cells, as though it is cut out using a knife, without causing heat damage to any other part of the body by using high-intensity focused ultrasound (HIFU), an ultrasound with an acoustic pressure that is much more powerful than existing ultrasound. In the process of physically destroying the tissue without the use of heat, a boiling vapor bubble is generated at the target site of the HIFU, and it is by the kinetic energy of this primary vapor bubble that the target tumor tissue gets destroyed. However, during the process, cavitation bubble clouds can be subsequently generated between the boiling bubble and the HIFU transducer, leading to unwanted cell destruction. This made it necessary to identify the cause of their formation and to accurately predict the locations of their occurrence.
Results showed that the secondary generation of bubbles was caused by a constructive interference of the backscattered shockwave by the boiling bubble with the incoming incident shockwaves and it is within the range of this interference that the secondary bubbles formed. Based on the images obtained using a high-speed camera, it was found that the area where the interference occurred and the area where the secondary bubbles were generated were closely matched. These findings not only explain the mechanism behind the secondary bubbles formation but also help predict where they will occur, thereby presenting the possibility of destroying target tissue with greater safety and precision.
Boiling histotripsy is a High Intensity Focused Ultrasound (HIFU) technique which uses a number of short pulses with high acoustic pressures at the HIFU focus to induce mechanical tissue fractionation. In boiling histotripsy, two different types of acoustic cavitation contribute towards mechanical tissue destruction: a boiling vapour bubble and cavitation clouds. An understanding of the mechanisms underpinning these phenomena and their dynamics is therefore paramount to predicting and controlling the overall size of a lesion produced for a given boiling histotripsy exposure condition. A number of studies have shown the effects of shockwave heating in generating a boiling bubble at the HIFU focus and have studied its dynamics under boiling histotripsy insonation. However, not much is known about the subsequent production of cavitation clouds that form between the HIFU transducer and the boiling bubble.
The main objective of the present study is to examine what causes this bubble cluster formation after the generation of a boiling vapour bubble. Our results suggest that the formation of a cavitation cloud in boiling histotripsy is a threshold effect which primarily depends (a) the size and location of a boiling bubble, and (b) the sum of the incident field and that scattered by a bubble.