FUSF research award recipient: Natasha Rapoport, Ph.D., University of Utah, Salt Lake City, USA

Natasha Rapoport, Ph.D.

Russian-born Natasha Rapoport, Ph.D., a research professor of bioengineering at the University of Utah, knows something of pain and trauma. Her physician father, Yakov, was jailed in 1953, wrongly accused in an infamous, yet fictitious “Doctor’s Plot” to assassinate Stalin. Natasha was 14 when she opened the door and her beloved papa was whisked away to be manacled and interrogated. Yakov Rapoport survived, and both father and daughter later wrote memoirs. Yakov has died, and Natasha has traded the Moscow forests for Salt Lake’s desert. But she carries on the family scientific tradition in a quest to make currently fatal pancreatic cancer a chronic, or even curable, disease.

Rapoport is the recipient of a $100,000 research award from the FUS Foundation to study the mechanisms of ultrasound action and its role in delivering cancer drugs to tumors. Her project will combine results from two powerful imaging modalities, MRI and RFP (red fluorescent protein), to study in vivo how the cancer drug paclitaxel is delivered by ultrasound to effectively kill pancreatic cancer cells.

“My goals and the goals of the Foundation are so much alike,” she said. “I want to see my development getting into clinical trials and hopefully into clinical practice.”

Her research began a decade ago when she realized that ultrasound enhances drug release from microscopic nanoparticles called polymeric micelles.

“When you encapsulate a drug in nanoparticles, you can target it to the tumor,” Rapoport said. “This is because the blood vessels in tumors are much more permeable than in normal tissues. This is the Achilles heel of the tumor, which allows drug-loaded nanoparticles to get through into tumor tissue without penetrating into normal tissue. Then we focus ultrasound in the tumor to release the drug from nanoparticles.”

But there are so many problems treating pancreatic cancer. The disease is often asymptomatic and discovered too late. And drug diffusion over the tumor is challenging. Plus, Rapoport said, it is common for pancreatic cancer cells to quickly become resistant to drug treatment.

However, Rapoport has found a potential solution, and if she’s successful, perhaps, one day, inoperable pancreatic tumors could be shrunken and made operable. “We inject paclitaxil loaded nanodroplets and they accumulate in the tumor,” Rapoport explained. “The accumulation is enhanced by focused ultrasound, which increases the gaps between endothelial (blood vessel wall) cells. When we sonicate these nanodroplets (irradiate them with ultrasound) they convert into microbubbles and when they convert they release their drug load.” Ultrasound is known to enhance diffusion and help to overcome all biological barriers for a drug to hit its target inside cancerous cells.

In past experiments on mice with pancreatic tumors, she discovered that large tumors regress significantly during treatment with ultrasound-mediated drug delivery under MRI guidance while smaller tumors die and don’t appear to recur after completion of treatment.

“This grant will allow me to find the best ultrasound parameters and optimal nanoparticle parameters for translating to larger preclinical models and then, hopefully, to humans,” Rapoport said. “If we keep getting the results that we’ve obtained in mice, then I think we may get permission to move to clinical trials, at first for compassionate use.”

Interview with Wladyslaw Gedroyc, M.D., St. Mary’s Hospital, London, England

The Focused Ultrasound Surgery Foundation has awarded a $232,808 research award to Wladyslaw M. Gedroyc, M.D. of St. Mary’s Hospital in London for a two-year randomized clinical trial comparing MR-guided focused ultrasound with radiofrequency ablation in the treatment of back pain caused by facet joint disease.

The clinical trial marks the next step in Gedroyc’s pioneering efforts to develop a noninvasive treatment for facet joint disease that provides more complete and longer lasting pain relief than current therapies. He and his team at St. Mary’s Hospital have already conducted a non-randomized pilot clinical trial in which MR-guided focused ultrasound was used to treat 17 patients suffering from extreme back pain caused by facet joint osteoarthritis. Post-treatment assessments show the technology is safe and effective.

“The follow-up data that we have collected is very promising, with up to 60 percent reduction in pain and a similar level of reduction in the level of disability, as measured by NRS and Oswestry Disability Index scores,” Gedroyc says.

The start date of the clinical trial will be determined following the approval of the study protocol by the ethics committee at St. Mary’s Hospital.

Gedroyc says, “It is difficult to estimate how many people suffer from facet joint disease because chronic back pain is large mish-mash of many pathologies. One of the big problems is that people are often treated for facet disease when they may have other problems of the back.” 

For this reason, the studies at St. Mary’s only recruit patients who have demonstrated a definite response to a previous facet intervention. “By a ‘facet intervention’ I mean something like a local anesthetic or steroid injection close to the facet join, or a joint injection of steroids, or possibly a radiofrequency ablation of the nerves around there,” Gedroyc explains. Radiofrequency ablation, he says, is the current gold standard for facet joint treatment.

The new technique uses MR-guided focused ultrasound to destroy nerve structures in degenerative facet joints. “We simply heat up the facet joints with focused ultrasound in a noninvasive manner so that we destroy the nerve bundles along the posterior aspect of the facet joint,” Gedroyc says. “We believe these nerve bundles are instrumental in causing pain from facet joint disease.”

If clinical trials are successful, he adds, “It means that we will have created a method of treating facet joints with an entirely noninvasive modality. No radiation will be involved. Just an MR scan using focused ultrasound. So, the patient would come in, lie down on the table, we would treat probably three facet joints on each side, and they will walk out. And we anticipate that we could do this in about half an hour or so. If it is long-lasting, then we have a huge potential for improving the way patients are treated, requiring no more injections.”

Key developments and information related to the randomized clinical trial at St. Mary’s will be covered in future issues of this newsletter.

The last ten years have been challenging for Billy R. Williams of Fort Valley, Virginia. The former Pentagon employee, who survived the 9/11 terrorist attack, has suffered from essential tremor, a progressive and debilitating neurological disorder.

Medications controlled his tremor for a while, but eventually the shaking became so severe that Williams found it impossible to do anything with his dominant right hand. He was unable to button his shirt, eat without spilling or fill in a crossword puzzle. An avid golfer, he even needed help teeing up his ball. Referred to the University of Virginia for evaluation, he learned about various treatment options and ultimately agreed to participate in a new clinical trial. Funded by the FUS Foundation, the study is assessing the safety and initial efficacy of noninvasive MR-guided focused ultrasound as a treatment for essential tremor.

On February 25, 2011, Williams became the first essential tremor patient in the world to receive MR-guided focused ultrasound therapy, and the results were dramatically positive.

Study Information
Click here for study information posted on the National Institutes of Health website. Patient inquiries can be directed to UVA Neurosurgery Clinical Trials at 434-243-1435 or by emailing  This e-mail address is being protected from spambots. You need JavaScript enabled to view it.

Click here to read FUS Foundation newsletter coverage of this study >

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As a researcher, Nathan McDannold, Ph.D. is on a quest to improve the delivery of drugs to the brain. “Most drugs don’t actually get into the brain when you inject them into the body or if a person takes a pill because of the blood-brain barrier,” he explains. “It places a big limitation on what drugs you can use.”

In preclinical studies a decade ago, McDannold and his colleagues made an important discovery: the blood-brain barrier (BBB) could be temporarily disrupted without causing damage. Doing so involved the use of pulsed, low power ultrasound combined with small microbubbles filled with a contrast agent for ultrasound imaging.

Since then, McDannold’s goal has been to translate this discovery into safe and effective patient therapies that not only treat brain disorders but also precisely target where drugs are delivered. He is now investigating the use of MR-guided focused ultrasound in opening the BBB. The approach has so far proven successful and safe in large animal models.

Encouraging research has also been performed by Eun-Joo Park, Ph.D., a research fellow on McDannold’s team. “She looked at treating breast cancer metastases in the brain using Herceptin,” McDannold explains. “A lot of patients get breast cancer, and they respond well to drugs. But when it metastasizes to the brain, they don’t respond to the drugs very well anymore. So, we hope that by disrupting the blood-brain barrier in the tumor and around it, we can get drugs into the brain and help these patients.”

McDannold envisions many brain disorders benefitting from focal drug delivery. “There are some results in animals showing that we can actually clear out some of the plaques that are formed in Alzheimer’s. There are other applications for diseases like Parkinson’s or multiple sclerosis, potentially,” he observes. “This stuff is really wide open for us to look at. We’re just sort of scratching the surface and developing the technology that will enable a lot of other research.”