By Joy Polefrone, PhD, Focal Drug Delivery Program Director

Inspired by the FUS Foundation’s symposia in 2008 and 2010, the Sapienza University of Rome organized the 1^st European Symposium on Focused Ultrasound Therapy. Held from September 22-23, the meeting was a great success with more than 200 people present. Program content was excellent and covered current and future applications of both MR-guided and ultrasound-guided focused ultrasound technology. The agenda included three invited presentations by FUS Foundation staff members and spotlighted some of our funded researchers as well. 

From my perspective, key takeaways from the meeting included:

• MR-guided focused ultrasound research and development is robust in Europe and is receiving a tremendous amount of government funding, especially in the Netherlands and the United Kingdom
• The field of ultrasound-guided focused ultrasound has advanced solidly and is now being used to treat prostate, thyroid and liver cancer and for pain palliation as well.
• Multi-disciplinary, multi-institutional, public-private collaboration is of great interest – an initial discussion was held to develop a European Working Group to facilitate the adoption of both MR-guided and ultrasound-guided applications.
•  The European community holds the FUS Foundation in high regard and has asked us to facilitate the formation of its new Working Group. Further details are now being planned and will be announced in coming months.

Day one highlights:

• Brain applications - Key presentations from the FUS Foundation’s Brain Program described research on intracerebral hemorrhage and essential tremor, given by University of Virginia clinician-researchers Stephen Monteith, MD and W. Jeffrey Elias, MD, respectively.
• Breast cancer - Presenters included researchers from Japan, Italy and Germany, with planned research discussed by the team of Professor Willem Mali, MD at UMC Utrecht.
• Bone tumors - Presentations covered focused ultrasound for pain palliation, back pain, osteoid osteoma, and excitingly, the application of focused ultrasound to achieve tumor control, which was presented by Alessandro Napoli, MD, PhD of La Sapienza.
• Abdominal tumors - Applications in patients were described by leaders in the field, including Wladyslaw Gedroyc, MD from St. Mary’s Hospital who discussed treatment with MR-guided focused ultrasound.
• Technology discussions - Falko Busse of Philips Healthcare discussed the company’s new HIFU platform recently launched at CIRSE (see article above). Franco Orsi, MD of the European Insititute of Oncology in Milan discussed his experience with ultrasound-guided focused ultrasound. The technological challenges and solutions for respiratory gating and motion tracking were presented by Rares Salomir, PhD, of the University of Geneva in Switzerland.

Day two highlights:

• Prostate cancer – Discussions touched on various focused ultrasound modalities and addressed some of the more contentious issues, including treatment of patients with low-risk cancer as well as the basis of focal therapy. Presentations also included an MR-guided approach as well as data from the groups in Italy involved in a treat-and-resect study using this technique.
• Uterine fibroids – Mathias Matzko, MD described his clinical experience with MR-guided FUS in Germany, followed by presentations on efficiency improvement and volumetric ablation from groups in France and Germany respectively. Advances or improvements in treatment were covered, including presentation of treatment results with FUS for adenomyosis and early results on fertility preservation from the team in Spain.
• Drug delivery – Marcel Arditi from Bracco offered a very informative presentation on the many approaches and applications of microbubbles and therapy. Joy Polefrone, PhD of the FUS Foundation, described drug dose painting with the combination of temperature sensitive liposomes and MR-guided HIFU by the team at the NIH. She also discussed the FUS Foundation’s Focal Drug Delivery Program.
  
  FUSF-funded researcher Nathan McDannold, PhD of the Brigham and Women’s Hospital  presented exciting results in the use of focused ultrasound combined with microbubbles to safely open the blood brain barrier repeatedly over many weeks in a large animal model. He showed both safety and maintenance of functional capacity, all of which are critical for moving this work into a clinical setting.
  
  Andreas Melzer, MD of Dundee University described a planned approach for treating multiple indications with focused ultrasound and drug delivery using MR-compatible advanced robotics, active beam steering for targeting moving organs and a combination of MR-guided focused ultrasound and PET for molecular imaging guided focal therapy. Such an approach would truly be a treatment suite of the future.
• Organization and networking - An afternoon session centered on adoption and collaborative research projects, with lively discussions around developing a successful center and the utility of a registry for uterine fibroids.

By Neil Glossop, FUS Foundation Consultant

Held in Munich, Germany from September 10 to 14, the 2011 meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) brought together researchers and clinicians in interventional applications from all over the world. The strength and commitment of this community was signified by the number of delegates in attendance – 6,164, a new record – and the number of abstracts submitted – 1,413.

Sonalleve platform was introduced at CIRSE by Philips Healthcare

A key event related to focused ultrasound was the Philips Healthcare users meeting and the official launch of the company’s new Sonalleve platform. The updated system fully integrates Ingenia, the new digital broadband MR system recently introduced by Phillips. The data acquisition and imaging capabilities of the Ingenia are so advanced that they can be compared to the transition from analog box televisions to the new generation of digital flat screen platforms.

In redesigning the Sonalleve, Philips also addressed customer feedback received during the system’s first two years of clinical experience.

What’s new about this MR system?

Rather than the image signal traveling from the receiver coil into a spectrometer (a.k.a. large computer) for processing in the room next door, the Ingenia platform digitizes the signal from the MR directly in the coil on the patient table, and sends the data to be reconstructed as an image via a fiber optic cable. For those who don’t speak MR-lingo, this is something similar to going from dial-up to broadband internet access in both speed and image content quality. In addition to that, the Ingenia comes with a 70 cm wide magnet bore for more patient comfort.

What’s new in the HIFU platform?

Now that the magnet comes with a wider bore and imaging data is being captured in the MR table, adjustments had to be made to the architecture of the focused ultrasound system to enable compatibility with the new MR system. While they could have simply made the architectural changes, Philips made many updates to the platform based on user feedback, which include improvements for the patient, physician and the technology.

Importantly, the new table is more comfortable for fibroid treatments and other applications, including adenomyosis and bone metastasis, which were both cleared for use under the CE mark on this new platform in addition to fibroids.

The physician user-interface has been improved for better treatment planning, improved workflow and optimization of cooling time for fibroid treatments to enhance user efficiency and ease. Lastly, the focused ultrasound technology has been advanced with the addition of a Philips-designed transducer that offers a longer focal length, increased treatment window and treatment depth, as well as scaling up the integrated receiver coil in the focused ultrasound platform, which will allow for improved resolution.

The FUS Foundation-funded clinical trial at the University of Virginia attained a new milestone this month when its principal investigator, W. Jeffrey Elias, MD, presented preliminary study findings at the Congress of Neurological Surgeons meeting in Washington, DC.

Dr. Elias and his team during ET procedure

Results to date show that the study’s first 10 patients had a 78 percent improvement in tremor scores in their hand, as assessed with the Clinical Rating Scale for Tremor (CRST). Their functional activities scores improved by 92 percent, as measured in the ‘Disability’ subsection of the CRST. Elias said that outcomes and complications were comparable to other procedures for tremor, including stereotactic thalamotomy and deep brain stimulation.

“So far, this noninvasive treatment has been life-changing for patients,” said Elias, who is Director of Stereotactic and Functional Neurosurgery at UVA. “All now have improved ability to use their dominant hand to perform tasks that they couldn’t do before treatment, such as writing legibly, drinking and eating without spilling, and buttoning clothes. It has been exciting to see their immediate improvements.”

The study is using magnetic resonance imaging to guide and monitor the delivery of focused ultrasound to tremor-causing nerve cells in the thalamus, a region deep within the brain known to be an effective target for ET and other movement disorders. The treatment goal is to reduce tremor in a patient’s dominant hand.

Most study participants have had ET for decades, Elias reported. As part of the study’s inclusion criteria, all had previously taken at least two medications that failed to control their tremor. Despite the severity of their disability, patients had opted to cope with symptoms rather than undergo invasive surgical procedures.

Conducted under an FDA-approved protocol, the single-arm, non-randomized, phase 1 study began in February 2011 and is expected to treat 15 patients before concluding. All patients are being followed for three months.  If final results prove successful, Elias anticipates launching a larger, pivotal trial to study the overall safety and long-term efficacy of MR-guided focused ultrasound in treating medication-refractory ET.

Funding for the study is being provided by the Focused Ultrasound Surgery Foundation, which is also underwriting a parallel study at the University of Toronto in Canada. Foundation Chairman, Neal Kassell, MD, says the study’s success could lead to other new treatments. “By demonstrating that MR-guided focused ultrasound can treat tissue deep in the brain with great precision and accuracy, we hope to open the door to treating Parkinson's disease, epilepsy and brain tumors. Much work remains to be done, but the path forward is clear,” he observed.

Kassell added, “Because the brain poses more complex technical challenges than other organs, success in treating ET will spur advancements in developing new focused ultrasound therapies for the breast, liver, pancreas and prostate, which are less complicated to treat.”

Currently, MR-guided focused ultrasound is an FDA-approved therapy for uterine fibroids; it is approved in Europe and elsewhere for the treatment of uterine fibroids and pain associated with bone metastasis. Around the world, clinical trials are treating prostate, breast, bone and uterine tumors.

Study details

The UVA study marks the first step in determining if MR-guided focused ultrasound is a safe and effective treatment for ET and if it offers potential benefits beyond current surgical options. The study has enrolled patients who are 18 to 80 years old and who have taken at least two medications that do not control their tremor. Participants, who are followed for three months after treatment, receive assessments for general health, neurological status and tremor measurements. The study is also tracking data about device or procedure-related side effects that occur within three months of treatment.

Study treatments are performed using the ExAblate Neuro, an investigational device manufactured by InSightec, Ltd. The device consists of a specially designed table with a helmet-like unit that contains phased array focused ultrasound transducers. Treatments are planned with the precision of MR imaging and then monitored with MR thermography, which provides real-time tracking of focused ultrasound delivery. The entire process is noninvasive and does not involve ionizing radiation.

During the study, a series of focused ultrasound pulses are administered through a patient’s intact scalp and skull to a precisely targeted spot in the thalamus. Patients receive no anesthesia and remain awake, providing feedback to clinicians after each pulse. Under the UVA study protocol, only one side of the brain is being treated – known as a unilateral thalamotomy – resulting in single hand tremor control.

All study treatments have been performed at the state-of-the-art UVA Focused Ultrasound Center, which was established by a public-private partnership of UVA, the Commonwealth of Virginia, the Focused Ultrasound Surgery Foundation and InSightec, Ltd.