InSightec (Tirat Carmel, Israel) reported that a team at the University Children's Hospital Zurich has completed a 10-patient feasibility study testing the use of non-invasive transcranial MR-guided focused ultrasound surgery (MRgFUS) for the treatment of neuropathic pain. According to the company, 10 adult patients diagnosed with chronic neuropathic pain underwent non-invasive deep brain ablation surgery (central lateral thalamotomy) with transcranial MRgFUS and showed improvement in pain scores and reduction of pain medication with no adverse effects at three months follow-up. This is the first study in the world to test non-invasive transcranial focused ultrasound as a treatment modality for functional brain disorders, InSightec noted.
"This study showed that we can perform successful operations in the depth of the brain without opening the cranium or physically penetrating the brain with medical tools, something that appeared to be unimaginable only a few years ago," said Daniel Jeanmonod, MD, a neurosurgeon at the University of Zurich. "By eliminating any physical penetration into the brain, we hope to duplicate the therapeutic effects of invasive deep brain ablation without the side effects for a wider group of patients."
Neurosurgeons currently treat patients with functional neurological disorders such as neuropathic pain or Parkinson's disease by inserting a tiny probe through the cranium and brain to reach and ablate damaged tissue.
For the patient, the procedure really is as simple as it sounds.
Eyal Zadicario, director of Neuro Programs at Insightec, told Medical Device Daily that for the patient, instead of going in for surgery, they are basically going in for an MRI. The patient is sent through an MRI scanner similar to a regular diagnostic MRI scanner, he said, only this scanner has a special ultrasound system integrated into it which can non-invasively ablate tissue inside the brain.
Zadicario said it is an outpatient procedure and no anesthesia is used at all. In the study, he said, the 10 patients were kept under watch in a hospital for 24 hours, but nothing was done to them during that post-procedure monitoring time.
InSightec says that the more traditional invasive treatment works to alleviate pain and other symptoms, however it exposes the patient to complications, including infections, bleeding and damage to surrounding brain tissue, Jeanmonod explained. Also, only patients whose target tissue lies in the clear path of the probe are eligible for the invasive procedure, he said.
"We now have early clinical evidence suggesting that transcranial MRgFUS provides a safe and effective way to non-invasively ablate tissue deep within the brain," said Ernst Martin, MD, director of the Magnetic Resonance Center at the University Children's Hospital Zurich. "While we need to monitor these patients further, we are very encouraged by the results to date and look forward to continuing our research. A non-invasive treatment that reduces the risk of infection and bleeding will fill an unmet need for many patients who currently have run out of treatment options or are unwilling to undergo invasive brain surgery because of the risks associated with it."
According to InSightec, the Swiss research team is planning a larger study for functional brain disorders and expands its clinical research to movement disorders, such as Parkinson's disease and tremor, and to other functional neurological disorders later this year. Additional sites in North America are also expected to initiate clinical research programs in functional brain disorders with transcranial MRgFUS later this year.
Zadicario said there are basically three main advantages to being able to do this procedure noninvasively: Being able to treat tissue in the brain, especially tissue that is deep in the brain, without having to cut through normal healthy tissue to get there; not being concerned with restrictions of getting to the deep brain target as is sometimes the case during the minimally invasive method of doing this procedure; and of course the patient is not at risk of developing the complications associated with surgical intervention such as bleeding or infection.
"When we do it noninvasively under MR guidance ... we basically see the tissue that we treat and treat it," he said. It is a much more accurate method than the surgical method, he noted.
One patient in the study suffered nerve damage from a spinal tumor that led to severe pain and cramps in his right arm. The pain persisted for years and the patient ultimately reported depression and suicidal thoughts because of his condition. Immediately after receiving transcranial MRgFUS treatment on his brain, he reported that the pain had disappeared. A short time later he was able to resume normal activities that his neuropathic pain had prevented him from doing, such as gardening and outings in the country with his family.
According to the company, the ExAblate 400 is the first system to use MR guided focused ultrasound technology that combines MRI – to visualize the body anatomy, plan the treatment and monitor treatment outcome in real time – and high intensity focused ultrasound to target brain tissue non-invasively. MR thermometry allows the physician to control and adjust the treatment in real time to ensure that the targeted area is fully treated and surrounding tissue is spared, InSightec said. The ExAblate 400 is a platform for a variety of transcranial indications, such as brain tumors, functional neurosurgery, stroke and targeted drug delivery, the company noted.
The ExAblate 2000, based on the same technology, was approved by the FDA in 2004 as a treatment for symptomatic uterine fibroids. That system received a CE mark for pain palliation of bone metastases in June 2007.
InSightec is a private company owned by Elbit Imaging (Tel Aviv, Israel), General Electric (Fairfield, Connecticut), MediTech Advisors, and employees. According to the company, it was founded in 1999 "to develop the breakthrough MR guided Focused Ultrasound technology and transform it into the next generation operating room."
"The Neuropathic pain study performed at Zurich demonstrated the feasibility to treat these patients non-invasively without adverse events and with very favorable preliminary efficacy," said Dr. Kobi Vortman, president/CEO of InSightec, in a company statement. "The results of this study set the ground for extensive brain study addressing the areas of functional diseases like Parkinson and Epilepsy, brain tumors and stroke. This technology has the potential to help significant amount of patients while reducing trauma and morbidity. To advance this study InSightec is collaborating with leading neurosurgery and neurology institutes around the world."
Earlier this year the company reported raising $15 million from its existing investors. Elbit invested $7.5 million and another $7.5 million was expected to be invested by its other investors within the next 12 months (Medical Device Daily, March 20, 2009). InSightec said the funds would be used to expand its R&D efforts, for marketing and sales activities, and for general corporate purposes.