New U-M-developed technology begins clinical trials
A revolutionary method of tissue ablation has now entered early clinical trials at the University of Michigan. This technology, called histotripsy, was conceived by scientists and clinicians at U-M, and it has the potential to treat a wide variety of disorders.
Histotripsy is a form of focused ultrasound that uses a mechanical process — not heat, like other focused ultrasound modalities — to ablate tissue. The mechanical process of histotripsy creates extreme pressure changes, causing microbubbles to form in the tissue, a process called cavitation.
"When you create very low pressure, dissolved gas and water vapor come out of solution," explains William W. Roberts, M.D., associate professor of Urology and Biomedical Engineering. "These bubbles oscillate, coalesce and collapse, releasing a tremendous amount of energy in a very confined space, which mechanically homogenizes the tissue."
One of the main advantages to histotripsy is its precision. Most other types of ablation — other forms of ultrasound, radiofrequency and microwave — have trouble controlling the spread of heat. With histotripsy, induced pressure can be precisely confined, allowing non-invasive "sculpting" of tissues.
"Additionally, histotripsy can be viewed in real time during the ablative process, because the microbubbles appear bright white on ultrasound imaging," says Roberts. "It's easy to see exactly where the cavitation activity occurs, unlike other ablative modalities whose results cannot be easily imaged until long after the procedure."
First clinical trial: BPH
As a urologist, Roberts was naturally interested in the urologic applications of histotripsy. So benign prostatic hyperplasia (BPH) was chosen as the first disease to be studied with the technology. The traditional surgical treatment of BPH is transurethral resection of the prostate (TURP), which is effective but requires significant time under anesthesia. This is increasingly relevant, as widespread use of medical management for BPH means the current patient population needing TURP is much older and at higher risk for complications than in the past.
Using histotripsy for BPH eliminates prostate tissue and debulks the transition zone in pre-clinical studies. This research showed enough promise for FDA approval of the current pilot clinical trial to evaluate safety in humans.
This trial at the University of Michigan, led by principal investigator John Wei, M.D., has successfully completed enrollment. It is anticipated that a larger multi-center trial and more enrollment opportunities will follow.
"Although initially we are exploring histotripsy as a BPH treatment, it's really a platform technology," explains Roberts. "It could potentially change paradigms for how surgical diseases are treated. Currently, researchers and clinicians are also looking at how histotripsy might be used to treat prostate cancer, small renal masses in the kidney, stone disease, liver cancer, congenital heart syndromes and thrombosis."
Born at the University of Michigan
Histotripsy was conceived at the University of Michigan over 10 years ago, and the initial proof of concept was demonstrated by the Histotripsy Research Group, led by Charles A. Cain, Ph.D., professor of Biomedical Engineering and including Roberts and three other Biomedical Engineering faculty: J. Brian Fowlkes, Ph.D., Zhen Xu, Ph.D, and Timothy L. Hall, Ph.D.
In 2009, the research group realized the need for a commercial partner to further translate histotripsy for clinical use, so a company called HistoSonics was formed. HistoSonics built the human prototype histotripsy system, the Vortx RX, that was approved by the FDA for the pilot human trial.
"This technology and translational research of histotripsy would not be possible without the collaboration and support of many individuals, institutions and foundations," says Roberts. "So it's exciting for everyone, because we believe that histotripsy has the potential to transform many areas of surgical and medical care."
Roberts is on faculty at University of Michigan and is a member of the Histotripsy Research Group. In addition, he also consults for HistoSonics, serves as chairman of its Clinical Advisory Board and is a founder of the company.