Eight years ago, focused ultrasound pioneer Larry Crum, PhD, transitioned away from directing the department that houses the focused ultrasound efforts at the University of Washington (UW), but under the leadership of Tom Matula, PhD, it has continued to grow into a powerhouse for researching and commercializing focused ultrasound technologies.
“I am in the process of disentangling myself from professional activities in anticipation of retirement,” said Dr. Crum. “Tom has been running the show for the past 8 years, and it is flourishing with new ideas, new projects, new grants, and industry support.” Tom laughs, saying, “Larry continues to mentor young staff, engage in scientific debates, and provide professional and personal wisdom to us all.”
A part of the Applied Physics Laboratory, the Center for Industrial and Medical Ultrasound (CIMU) is home base for focused ultrasound research at UW. It is staffed with about 20 engineers, physicists, mathematicians, and technicians whose mission is to:
- Perform fundamental physical and bioengineering research
- Develop instruments, techniques, ideas, and products
- Foster research collaborations between UW faculty and industry
- Develop joint projects with other ultrasound research teams and regulatory institutes
- Spin off companies for technology transfer
- Educate and train students and technicians
More clinically oriented, the ultrasound-based Washington Molecular Imaging and Therapy (uWAMIT) center uses ultrasound for imaging, diagnosing, and treating diseases. It is an interdisciplinary institute, comprised of collaborative faculty from CIMU, bioengineering, and radiology who collaborate to discover, develop, translate, and commercialize molecular imaging and therapy technologies. Their work is centered on:
- Using easily available, low cost, and real-time ultrasound for molecular-level diagnoses
- Detecting early stage cancers with cancer-specific molecular probes
- Attaching specific molecular probes to chemotherapies and delivering them in targeted areas
- Mediating targeted gene transfer for the treatment of genetic diseases
- Developing and creating efficient manufacturing processes for molecular probes, contrast agents, nanoparticles, and biomarkers
The aim of both the CIMU and the uWAMIT is to take developments from basic research and commercialize them to create healthcare solutions that are used in medical practice. “We are translational and more focused on therapy than imaging--but we do include imaging,” said Tom Matula. “We are the only group like us.” For example, the group at uWAMIT is working to personalize medicine by creating a shift from diagnosing symptomatic patients to detecting the disease before symptoms appear. Ideally their molecular imaging and therapy technologies will identify high-risk individuals, to confirm disease onset and pinpoint its location, and then deliver the molecular therapy treatment that is specific to that individual’s disease. Their emphasis on commercialization also makes them unique in academia.
Scientists refer to the “Valley of Death” as the place where discoveries from university researchers get lost or are prevented from evolving into healthcare companies or products. To fend off these losses, uWAMIT and CIMU specifically work to commercialize their developments by:
- outlining the clinical outcomes and constraints that can develop into opportunities
- aligning their internal research ives with clinical unmet need (i.e., clinical market opportunities)
- partnering with existing companies to pursue new market opportunities
- connecting the opportunities to innovation and research projects
- positioning themselves to develop new companies and license existing technology
Focused ultrasound companies that have recently spun off from UW include Mirabilis, SonoMotion, and Matchstick Technologies.
Using an ultrasound guidance platform, Mirabilis was spun off to use focused ultrasound as a treatment for uterine fibroids. Although they will eventually pursue other indications, the company has successfully completed initial clinical trials with an exceptionally quick treatment time as compared to other systems (less than 10 minutes).
SonoMotion is a company that provides treatment options to manage or treat kidney stones. Their technology using ultrasound propulsion to move kidney stones was invented at UW, and it is currently in clinical trials. They discovered that “pushing” a kidney stone from the lower pole of the kidney to the uretropelvic junction could facilitate its passing. The company is also working with CIMU to develop burst wave lithotripsy to remove small kidney stones before they become painful.
DNA fragmentation is the goal of Matchstick Technologies, a newly formed company that is using focused ultrasound to break up DNA or chromatin for laboratory analysis. The company’s current strategy is to manufacture and sell the device, and provide the fragmentation service on a subscription basis.
Many other CIMU inventions that have been licensed by FUS companies are providing important revenue to the research enterprise at UW.
Q & A with Tom Matula, PhD, about FUS at the University of Washington
To learn about the ongoing work within these centers, we interviewed Dr. Matula to gain a high-level overview of the many ways that FUS research is integrated into the Seattle campus.
Q. How many total staff in each position?
We currently employ about 20 full time staff plus students, who rotate through on cyclic funding schedules that last 4 to 5 years. We currently have two visiting scholars from China. Yujing Zong is from Xi’an (the origin of the terra cotta warriors), and Wang Gong, MD, is visiting from Chongqing. Dr. Gong is an ultrasound imaging clinician. Prof. Vera Khokhlova and Oleg Sapozhnikov split time between UW and Moscow State University.
Q. Who are your key investigators?
Some of our more senior principal investigators include Mike Bailey, PhD, Andy Brayman, PhD, Larry Crum, PhD, Joo-Ha Hwang, MD, PhD, Vera Khokhlova, PhD, Oleg Sapozhnikov, PhD, Pierre Mourad, PhD, Yak-Nam Wang, PhD, and Wayne Kreider, PhD. All of the members of our team are listed on the CIMU website.
Q. Who are your internal and external collaborators? Who else at UW do you work with?
Because we’re a soft-money group that relies on grants and contracts to fund our work, we’re a very collaborative group, and the list is large! In terms of clinical departments, our biggest partners are Radiology (Norm Beauchamp, Chair) and Urology (Hunter Wessells, Chair). We collaborated with radiologist Peter Eby, MD on a breast cancer immunology study. Radiologists Wayne Monsky (interventional) and Manjiri Dighe (body imaging) are looking at using FUS to treat intravascular blood clots and as a way to monitor other therapies and improve diagnostic capabilities. Urologist George Schade, MD and Adam Maxwell, PhD are studying the use of histotripsy to treat renal cell carcinoma (kidney cancer). With Gastroenterology, we work with Dr. Tatiana Khokhlova, PhD, to study HIFU-enhanced release of biomarkers and immune response. We also work with Karol Bomsztyk, MD, a nephrologist interested in chromatin biomarkers associated with kidney disease. In Bioengineering we work with Matt O’Donnell, PhD and ex-dean of Engineering, on ultrasound imaging projects, and we recently recruited a collaborator from Cyprus: Mike Averkiou is setting up a new laboratory and will work on drug delivery in the liver (a separate project from Dr. Hwang’s). We also have several collaborators in molecular imaging and therapy, including Suzie Pun PhD, and Xiaohu Guo, PhD in Bioengineering, and Lilo Pozzo in Chemical Engineering. To help us vet our technologies, we work regularly with Connie Bourassa-Shaw, who runs the Buerk Center for Entrepreneurship, and CoMotion, the UW technology transfer office.
We also collaborated with Philips to determine the feasibility of using the Sonalleve clinical MR-HIFU system for boiling histotripsy. Accurate characterization of the system was performed using acoustic holography and nonlinear modeling methods, showing its capability to generate high-amplitude shock waves at the focus. We also continue to work with GE on various imaging modalities, and Mirabilis Medica in support of their goal to treat uterine fibroids. We work with the major metrology centers and experts worldwide involved in developing standards for ultrasound therapies within the International Electrotechnical Commission (IEC), American Institute of Ultrasound in Medicine, and Acoustical Society of America.
Q. Which FUS applications and biomechanisms are being investigated?
Our current focus is on ablation, histotripsy, imaging, and cellular fragmentation.
Q. What are some of your projects at CIMU?
- Boiling histotripsy — fractionating tissue volume, producing holes in connective tissue, inducing immune response, enhancing the release of biomarkers for diagnostics, developing ultrasound and MRI methods for guiding and monitoring the treatment
- Urology — kidney cancer, lithotripsy, and stone propulsion
- Gastroenterology – liver cancer
- Radiology — intravascular blood clots, therapy monitoring, improving diagnostics, breast cancer
- Drug Delivery — liver disease, pancreatic cancer
- Neurology – multiple sclerosis
Histotripsy Focus Feature (April 2014)
New Research Will Assess FUS and ThermoDox as a Combined Treatment for Pancreatic Cancer (May 2012)
Induction of an Immune Response to Breast Cancer with MRgFUS- Peter Eby (2010 video)