This month’s featured focused ultrasound researcher, Urvi Vyas, PhD, has made important contributions in the area of ultrasound beam propagation. Realizing that many newsletter readers may not be familiar with this process, we asked, Matthew Eames, PhD, a biomedical engineer and Senior Project Engineer for the FUS Foundation Brain Program, to provide an explanation. Here’s what he wrote:

Ultrasound beam propagation through the different tissues of the body is roughly analogous to the bending of light as it passes through different materials. As an example, consider the accompanying photo of straws placed in glasses of water. You’ll quickly notice that, in the photo, the submerged portions of the straws do not line up with the portions above the waterline. This is because the speed of light in water is different from that in air, and as we look through the water’s surface, we perceive distortions in the image of submerged objects. The lenses of cameras, telescopes, and reading glasses all capitalize on the difference in speed of light between air and the lens material in order to focus or magnify images.

Matthew Eames, PhD

With clinical ultrasound, the different tissues of the body – primarily muscle, fat, and bone – have different speeds of sound that bend, defocus, and distort the ultrasound beam as it propagates through the body. This can have a great impact on the formation of diagnostic images or on the delivery of therapy. The distorted ultrasound propagation caused by a layer of fat or the irregular surface of the skull is something that must be corrected for or taken into consideration in order to ensure accurate diagnosis or treatment.

Imagine standing at either end of a conference table from someone you know.  It would be easy to recognize them.  Now imagine something placed between you – a wall of glass block, for example – that altered the path of light.  Now it is significantly harder to identify the other person.  This glass block is analogous to a layer of fat or the irregular surface of the skull in the context of ultrasound and is something that must be corrected for or taken into consideration when delivering therapy or interpreting diagnostic images.

Researcher interview: Urvi Vyas, PhD, Stanford University

A highlight of the FUS Foundation’s 2010 International Symposium on MR-guided Focused Ultrasound was the presence of our Young Investigators, ten early-career scientists selected to present their work during oral or poster sessions. The spirit and enthusiasm of these individuals provided a special spark that energized the entire symposium.

During a recent interview, one of those Young Investigators – Urvi Vyas, PhD – provided an update on her focused ultrasound activities. The excitement and positive expectancy with which she spoke were truly inspirational. 

Vyas, who is now a post-doctoral fellow at Stanford University, earned her PhD in bioengineering at the University of Utah. Professionally, her main interests are ultrasound beam propagation and MR-guided focused ultrasound surgery. Like many of the unsung heroes in the field of focused ultrasound, she is working behind the scenes to address technical issues and challenges that will make new patient treatments possible.  

After completing her undergraduate degree in bioengineering at Shree Govindram Institute of Technology and Science in India, Vyas joined Utah’s bioengineering program where she helped develop an NIH-funded focused ultrasound system for breast cancer. That project enabled her to learn from three individuals she describes as mentors: ultrasound expert Douglas Christensen, PhD, MR leader Dennis Parker, PhD, and biothermal specialist Robert Roemer, PhD.

“I think this is an exciting field because you need so many people to come together to make a system work. You need temperature measurements. You need the ultrasound to work. You need to control the ultrasound. Not only that, you need to control the heating and so you need somebody that knows the bioheat transfer equation,” Vyas observes.

Focused ultrasound system for the breast

In creating a focused ultrasound system for the breast, the Utah team had to break new ground in a number of areas: measuring temperature in the breast, planning patient treatments and designing a transducer. “Where I came in was the ultrasound part of all of this,” says Vyas.

She worked on developing fast simulations for ultrasound beam propagation. “We went from a time scale of a couple of hours to simulate one beam propagation pattern to a few seconds. This was on a grad student laptop, so this was really exciting. Once we had that working, we could then design patient-specific treatment plans. We’d take an MR image of the patient and then design a treatment plan that would fit this particular patient,” she explains.

After helping to reduce treatment planning time, Vyas got involved in designing an ultrasound transducer for the breast. “We designed various configurations and figured out that the side-shooting transducer would work best for the breast,” she says.

Inverse problem-solving

Her next task was using fast beam propagation simulation to solve an inverse problem. “In the forward problem, I can simulate where the beam is going to be. I can also do the inverse problem. I can see the temperature and figure out what the tissue properties for this particular person are because it’s very hard to measure acoustic properties of a human being without cutting the human being open,” she says.

Solving the inverse problem lead to a first-time in vivo study in which the Utah team demonstrated that the acoustic properties of muscle could be measured noninvasively with focused ultrasound. This work qualified Vyas for the FUS Foundation’s Young Investigator Award and for an award from the Society for Thermal Medicine.

At Stanford, Vyas is working with Kim Butts Pauly, PhD, a leader in MR thermometry. Her energies are now being directed to correcting trans-cranial phase aberration. “When you put the ultrasound beam through the skull, there are a lot of aberrations because of the skull having different thicknesses,” Vyas explains. “The plan is to use the acoustic radiation force imaging and figure out how to better correct these aberrations in the brain.”

Although the clinical applications of this approach have not yet been determined, Vyas hopes it will be widely useful. “I think what we want to do is give the field a very efficient, fast way of doing phase aberration correction and just share it with everybody,” she says.

Vyas is inspired by the thought of patients benefitting from her work. “When you’re in a lab typing code on a computer, you don’t realize what it may lead to,” she says. Attending the FUS Foundation’s recent Brain Workshop gave her a glimpse of the impact her work could have on patients. There, she heard doctors talking about treatment envelopes based on simulations she helped develop. “These treatments are going to be in clinics really soon, and it’s very exciting,” she exclaims.

Philips Healthcare is about to begin the next leg of its journey toward FDA approval of its Sonalleve MR-guided focused ultrasound system as a treatment for uterine fibroids, benign tumors that affect 20-50 percent of pre-menopausal women over 30 years old. 

Like many conditions related to female reproduction, uterine fibroids are not widely and openly discussed, yet they have a substantial toll on health and workplace productivity. Women with large fibroids often experience significant pain, menorrhagia, pressure and bloating as well as bowel and urinary problems and impaired fertility. It is estimated that more than half of the 600,000 hysterectomies performed in the U.S. annually are due to uterine fibroids. From an employer’s perspective, the prevalence of uterine fibroids equates to increased absenteeism, lost productivity and added healthcare expenditures. Hysterectomies, for example, require a four to six-week recovery period.

Intent on providing a noninvasive, outpatient, quick-recovery therapeutic option to Americans with uterine fibroids, Philips will soon launch a Phase II/III study to assess the safety and efficacy of the Sonalleve system. Although patient recruitment is pending, the study – Philips Pivotal Clinical Trial for MRI-HIFU of Uterine Fibroids – is now posted on clinicaltrials.gov. It is expected to enroll 224 women between 18 and 50 years old at four sites in the U.S. and at two other sites in Canada and Korea.

During the Philips trial, patients will be randomly assigned to treatment or control groups. Those in the treatment group will receive focused ultrasound therapy; control group participants will undergo a simulated treatment in which no therapeutic ultrasound doses are delivered. Participants will be followed for 12 months.

The pivotal trial was preceded by a Phase I/II pilot clinical trial that assessed the safety and capabilities of the Sonalleve system in treating uterine fibroids. Launched in 2009, the pilot study was designed to treat 11 patients at two U.S. sites – the National Institutes of Health in Bethesda, MD and St. Luke’s Episcopal Hospital in Houston, TX.

Philips has been marketing its Sonalleve MR-HIFU Uterine Fibroid Therapy System outside the U.S. since receiving CE marking in December 2009. The system is now installed in more than 40 sites worldwide. If Phillips’s quest for FDA approval is successful, the Sonalleve will become the second MR-guided focused ultrasound system available for commercial use in the U.S., joining InSightec’s ExAblate system as a noninvasive clinical option for the treatment of uterine fibroids.

The FUS Foundation’s Research Award Program has received a major funding boost from a $1 million commitment recently made by the Robertson Foundation.

“We are delighted and honored to gain the support of the Robertson Foundation and are completely aligned with its targeted, disciplined, results-oriented approach to philanthropy,” says FUS Foundation Chairman Neal Kassell, MD. “This funding will enable us to advance our mission by investing in highly worthy and promising research projects in the field of focused ultrasound.”

The Robertson Foundation was established in 1996 by Tiger Management founder Julian H. Robertson, Jr., his wife Josie, and their family.  Medical research is one of four principal areas it supports.

“Focused ultrasound is an exciting new technology,” says Julian Robertson.  “We are pleased to support research into this noninvasive medical therapy which has huge potential”.

About the Research Awards Program

Since 2007, the FUS Foundation’s Research Awards Program has provided more than $2 million in funding for 23 investigator-initiated projects ranging from preclinical research to pilot clinical trials using focused ultrasound. Treatments under investigation have included essential tremor, neuropathic pain and functional brain disorders, as well as tumors of the breast, liver and pancreas.

The Research Awards Program is designed to fill a funding void by providing “seed money” for highly promising focused ultrasound studies. It enables researchers to compile the preliminary data needed to apply for more substantial grants – from government agencies and other sources— that are needed to move their work toward clinical reality. Awards are typically $100,000 for a 12-month period.

In recent months, the Research Awards Program has taken steps to increase its effectiveness and impact by adopting two funding tracks. The first encompasses preclinical and pilot clinical studies that promise to lead to the development of unmet clinical needs or treatments that are superior to current therapies. The second covers high-risk, early-stage, proof-of-concept projects that are unlikely to receive funding from other sources but that, if successful, could have a profound impact on the advancement of the field of focused ultrasound.