A stone’s throw from recovery

In a vast basement lab at the Center for Industrial and Medical Ultrasound (CIMU), an arm of UW’s Applied Physics Lab, Vera and Tatiana Khokhlova pose beside their research poster. They stand a collegial, professional distance apart, looking like any pair of senior and junior colleagues who are experts in their field and proud of their work.

It turns out this mother-daughter team is the latest in a long line of physicists tracing its roots back to Russia and Moscow State University, where both earned PhDs. Together, they collaborate on research that has the potential to transform care for kidney stone and tumor patients using ultrasound technology, which leverages high-frequency sound waves to mechanically liquify harmful tissue. “Like a little blender,” says Tatiana, the daughter, “but small.”

The Khokhlovas work closely with CoMotion, UW’s collaborative innovation hub and commercialization office, to translate their findings from the lab to the clinic. Some of this happens through UW spinoff SonoMotion. Over 10 years, SonoMotion has raised $38M to develop a noninvasive platform to treat kidney stones in a variety of clinical settings, on fully awake patients. It’s now conducting further clinical studies on human subjects and it has reached “breakthrough” status from the US Food and Drug Administration, a designation that enables accelerated regulatory review.

“The experts at CoMotion will help you every step of the way if you want to set up your own company, or they will support licensing agreements with outside companies,” Vera says. “They protect our rights as investigators,” she adds. CoMotion also helped recruit industry veteran Oren Levy as SonoMotion CEO and co-founder.

The team has filed dozens of disclosures with CoMotion over the years, contributing to the more than 9,700 total disclosures received from UW innovators since 1983. This figure reflects decades of collaboration with academic researchers and more than 280 spinoffs. “What a marvelous milestone,” says François Baneyx, UW’s Vice Provost for Innovation and director of CoMotion. “And what a testament to the incredible creativity of our researchers, and their appetite to make the world a better place through the translation of their discoveries to the marketplace.”

Physics runs in the Khokhlov family. All four of Tatiana’s grandparents were physicists, and her paternal grandfather was a leader in nonlinear acoustics at Moscow State University (MSU). “In our family, you either love science or you hate it,” says Tatiana, who realized she loved it from a young age. She got to know members of CIMU on summer visits to the US in childhood and conferences in Moscow, and was hired as a postdoctoral fellow at UW decades later. She is currently a research associate professor in UW Medicine’s Department of Gastroenterology.

Though the pair’s areas of expertise overlap, they say, Vera tends to take a more theoretical approach while Tatiana enjoys hands-on work and testing in experimental model systems. They say they enjoy a collegial relationship, though “sometimes we yell,” Tatiana says with a laugh. But that’s mostly about the work—and nobody else seems to hear it.

“You would hardly know that they are mother and daughter,” says CIMU founder and former director Larry Crum, who adds that this relation surprises colleagues they meet at conferences and such. “They maintain that sort of scientific culture when they work together.”

Back at the CIMU lab, Vera and Tatiana show off “Bob,” a mannequin with a plastic torso containing a jelly-like, stone-riddled model kidney implanted into its back. They take Bob (purchased with the support of a $50K award from the CoMotion Innovation Gap Fund) on the road with them to industry meetings and conferences so doctors can try out their novel kidney-blasting device.

Most people know about ultrasound’s applications in imaging fetal development, vital organs, and injuries; the technology is also routinely used to break up harmful tissue, like kidney stones and tumors, through heating. Like how a magnifying glass focuses sunlight onto a single point, a curved ultrasound transducer—the handheld component of the ultrasound machine—can focus acoustic waves on a designated point inside the body.

Thermal destruction has drawbacks, not least the presence of its remnants. “Nearby tissue can also suffer heat damage,” says Vera, senior principal engineer at CIMU and Tatiana’s mother. “It’s dense and desiccated, and it takes a while for the body to resorb it.”

CIMU’s engineers are working on a next-generation approach that applies acoustic waves to mechanically liquify tissue. The method—histotripsy, first described about 20 years ago—enables more precise destruction without damage to healthy tissue. It also offers the advantage of real-time monitoring through conventional ultrasound imaging.

Boiling histotripsy, a specialized form of this method developed by the Khokhlov team, uses high-intensity ultrasound to create vapor-filled bubbles in tissue, then acoustic waves are directed to pop the bubbles and mechanically destroy the tissue itself, blasting it into tiny pieces that are quickly reabsorbed by the body.

The team is also exploring how this method can be deployed to destroy complex, three-dimensional tissues like tumors, collaborating with scientists at UW’s Fred Hutchinson Cancer Center. A key advantage, across applications, is that the device is fairly compact and does not require special equipment, only minor modifications to existing clinical systems for thermal ablation.

This work piqued the interest of NASA, which contributed funds as part of its effort to address astronauts’ disproportionately high risk of kidney stones, largely a result of weightlessness and its effects on bone metabolism. The technology, with additional funding from the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases and the US Department of Defense’s Surgical Research Institute, has been tested in early feasibility studies at the International Space Station and in early clinical studies at UW Medicine.

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Note: An earlier version of the article misstated the number of innovations disclosed to CoMotion since 1983. As of December 31, 2023, the number of disclosures is just over 9,700.