December 2013

MRgFUS — Looking Beyond Uterine Fibroids
By Kathy Hardy
Radiology Today
Vol. 14 No. 12 P. 28

Bone metastases and movement disorders may prove good targets for focused ultrasound.

Women with painful uterine fibroids who underwent MR-guided focused ultrasound (MRgFUS) since FDA approval of the technique in 2004 can attest to the benefits of this noninvasive outpatient procedure. As word spreads about its effectiveness in women’s health, MRgFUS is finding new potential targets within oncology, such as alleviating bone metastasis pain. In addition, focused clinical trials on brain function are showing some progress in the areas of movement disorders such as Parkinson’s disease and essential tremor.

“There’s a lot going on right now with advanced uses of MR-guided focused ultrasound,” says Lynn Golumbic, marketing director for InSightec, developer of the ExAblate system. “It’s an exciting time for this nonsurgical ‘operating room of the future.’”

MRgFUS is a noninvasive technique combining a high-intensity focused ultrasound beam that heats and destroys targeted tissue with an MRI system, which visualizes patient anatomy and controls the treatment by continuously monitoring the tissue effect. In many cases, focused ultrasound can be performed without anesthesia, hospitalization, or ionizing radiation, allowing a quick return to normal activities and an improved quality of life.

With uterine fibroids, the goal of MRgFUS is to treat as much of the fibroid as possible. This outpatient procedure allows interventional radiologists to target fibroids with high doses of focused ultrasound waves to shrink or destroy the fibroids without damaging surrounding tissue. MRI is used to locate fibroids and establish the proper ultrasound pathway, keeping healthy tissue safe from the ultrasound waves used to attack fibroid tissue. MRI use also is a good way to determine the size of fibroids.

While focused ultrasound is increasingly used in the treatment of uterine fibroids, hysterectomy remains the gold standard for the treatment of these painful growths. According to Anne Roberts, MD, division chief of vascular/interventional radiology and a clinical radiology professor with UC San Diego Health System, much of that is because of reimbursement and insurance coverage issues for the focused ultrasound procedure, which can be costly. Establishing a specific CPT code for MRgFUS could help, but there’s also the matter of the time involved in setting up and completing the procedure, which may tie up a busy MRI suite.

 “MR-guided focused ultrasound is a long procedure,” says Roberts, who also is chair of the ACR’s interventional and cardiovascular imaging commission. “It can take four to five hours to complete the treatment. You have to map the route first, which takes time. If you’re using a clinical machine, not a research machine, your hospital might not want you to tie up the machine for that length of time. So they need to charge enough to recoup any potential lost revenue.”

There’s also the matter of how much time the physician needs to spend on this procedure. “You can’t designate this procedure to a technologist,” Roberts says. “So then you have the issue of a physician dedicating four to five hours sitting at the machine.” She says that by the time a woman is diagnosed with uterine fibroids, the fibroids tend to be large in size and require a significant amount of time to treat.

Other Uses
Treatment time is considerably less with bone metastasis or even with areas in the brain, Roberts says, which could make MRgFUS treatment for conditions in these parts of the body more readily acceptable. “With the bone and brain, these are smaller areas, and the treatment time is less than with uterine fibroids,” she says. “That makes the procedure easier to do and, with more positive results, this will make the procedure more popular.”

Focused ultrasound is making inroads in the oncology world since the October 2012 FDA approval of MRgFUS ablation therapy to alleviate pain caused by metastatic bone tumors for patients who cannot undergo or have not responded to radiotherapy. With bone metastasis pain affecting nerves that are located close to the surface, the standard treatment for such pain is radiation therapy.

ExAblate targets nerves near metastases for ablation, easing pain symptoms, according to the manufacturer’s phase 3 clinical trial data presented to the FDA as part of the company’s premarket approval application. MRI is used to plan and provide continuous guidance for targeting the diseased tissue, noninvasively provides real-time temperature measurement, and monitors treatment outcomes. Patients have reported reduced pain and lasting improvements in well-being and function as well as a decrease in the need for medication.

“Bone metastasis has the real potential for improving the use of this technique on a more widespread basis,” Roberts says.

Joshua E. Meyer, MD, a radiation oncologist at Fox Chase Cancer Center in Philadelphia, says patients with bone metastasis are ideal candidates for MRgFUS because of the accessibility to the nerve endings causing patients considerable pain. “The disease in the bone causes nerves on the outside of the bone to fire, which is what causes patients to suffer from such pain,” he explains. “Because these nerve endings are located on the edge of the bone, we can target and heat up that area, easily burning the area and that area only, which stops the nerves from firing.”

Using MRI to focus the ultrasound energy on the exact area where pain is being generated enables physicians to treat just the area of concern. The fact that there’s bone involved helps this process as well. “Bone is a good absorber of ultrasound energy,” Meyer says. “We can create a big spike of energy at the edge of the bone, but no energy is absorbed beyond that area. That makes MRgFUS a safe and effective treatment for bone metastasis pain.”

Meyer participated in the initial phase 3 study that looked at patients who did not experience favorable outcomes with radiation therapy. With MRgFUS, he says two-thirds of the patients involved in the study saw their pain scores decrease by about 2 points, while their pain medication increased no more than 25%. “We’re getting a good response to MRgFUS for bone metastasis pain,” he says. “MR-guided focused ultrasound works for bone metastasis much as it does for uterine fibroids. MRI allows us to target an area, and the ultrasound provides the treatment. We can then see near real-time feedback to make sure the temperatures were correct and that we treated the right area. And we can do all this without using contrast.”

Radiation Alternative
Meyer adds that side effects from MRgFUS are short lived, with some residual inflammation and soreness in the treated area that lasts only a few days. The standard treatment of radiation and chemotherapy works for some patients but not without its own side effects. It can take two to three weeks after radiation therapy for the patient to feel better, he says.

With the goal of reducing pain, Meyer believes the noninvasive approach is a viable alternative. “Chemotherapy prolongs life, but the patients still have bone pain,” he says. “It doesn’t mean patients will be able to completely eliminate pain medications from their protocol, but they can be reduced. It’s a viable alternative for patients who have not had success with radiation therapy. This is an option with evidence behind it, and it works where other treatments haven’t.”

As in the uterine fibroid treatment scenario, MRgFUS for bone pain requires a certain capital investment, Meyer says, as well as time spent using an MRI machine that facilities may want spent on treating and diagnosing numerous patients. “Adoption is slow,” he says. “Facilities can’t just go out and make large equipment purchases. However, I expect that interest will grow as the word gets out about this technique.”

As word spreads, so too does work in finding more applications for MRgFUS. However, some adjustments may be necessary along the way. For example, a trait that adds to MRgFUS’ success in treating bone metastasis pain can be a hindrance to the technique’s use in treating issues in certain areas of the brain. “Because bone is a good conductor of ultrasound energy, there needs to be a way to get around the scalp and skull when dealing with conditions within the brain [but close to the skull],” says Michael Schwartz, MD, MSc, FRCSC, former division head of neurosurgery at Sunnybrook Health Sciences Centre in Toronto, Canada. “But with MR-guided focused ultrasound, we can treat targets at the center of the brain. Most functional neurosurgery targets are located at the center of the brain, so that makes this technique a good choice.”

According to Golumbic, researchers are taking steps to determine whether transcranial MRgFUS could offer a better and more noninvasive treatment alternative to traditional treatments for Parkinson’s disease, essential tremor, and other movement disorders. Results of a phase 1 trial out of the University of Virginia, recently published in The New England Journal of Medicine, noted that ultrasound can be focused through the scalp and skull with sufficient precision to reduce tremors by creating a small ablation deep in the brain. The 15 study participants, all suffering from essential tremor, saw significant improvement in their dominant hand tremor. Overall, participants reported substantial improvement in their quality of life, with essentially no residual disabilities from their tremor at one year after treatment.

Schwartz is involved in ongoing trials in Canada examining how MRgFUS can be used as an alternative to treatments such as lesioning and deep brain stimulation to treat patients with essential tremor who have not responded to medication. Although often effective, he says traditional treatments come with the risks associated with any open neurosurgical procedure, such as infection. Also, with deep brain stimulation, the process is reversible, meaning that once the stimulation is turned off, the effect goes away.

Faster Response
Gamma knife procedures offer viable alternatives to brain surgery, Schwartz says, but there is the issue of ionizing radiation. In addition, the time it takes to determine whether the procedure was successful can be significant. “To see the effects of gamma knife procedures can take six to 12 months and with the failure rate, you don’t know if the procedure worked until that time has passed,” he says. “With MR-guided focused ultrasound, you can see whether you’ve made an impact immediately.”

With some initial success in MRgFUS treating brain-related issues, Golumbic says researchers are looking into other conditions that stem from the brain, such as neuropathic pain, also referred to as “phantom pain,” and treatment of obsessive-compulsive disorder. “The thinking is if it works in these areas, it could open up the entire psychiatric spectrum,” she says.

Clinicians working in the field see a variety of applications for MRgFUS on the horizon. For example, Roberts says there is the capability for targeted drug delivery, which allows physicians to generate higher toxicities at the targeted volume while sparing the entire body. A nanoparticle could be injected into a tumor and then activated by ultrasound. There also is work under way in the treatment of primary cancers as well as noncancerous issues such as lower back pain.

In the case of MRgFUS applications, as more favorable results are revealed from studies around the world, Roberts believes there is a greater likelihood for adoption and an increased focus on what can be done with this noninvasive technique.

— Kathy Hardy is a freelance writer based in Phoenixville, Pennsylvania. She primarily covers women’s imaging topics for Radiology Today.