Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
What is MR-guided focused ultrasound and what has it traditionally been used for?
It is a new technique that involves focusing 1024 beams of ultrasound through the skull to a focal point in the brain, very much like using the sun and a magnifying glass to burn a hole in a sheet of paper.
We focus these beams through the skull to a very precise location in the brain. This creates heating at that point. In so doing we are able to destroy the tissue at that focal point.
We are using this technique to make very precise lesions non-invasively – without making an incision in the skull – in the brain to improve symptoms in patients with tremor.
So far it has only been used in the brain to treat pain and tremor. It has been used in other parts of the body to treat uterine fibroids and to treat cancer metastases to bone.
Exactly how precise are the lesions that can be made using MR-guided focused ultrasound?
We are talking about focusing the beam to an area that is 1-2mm in diameter. This is very small.
When we are making these lesions in the brain we have to be very precise – if we are off by a few millimeters we would get into serious problems. And so it is essential that we be very precise.
One of the advantages of this technique is that as we are making the lesion we can see it in real-time on the MRI as we are actually performing the procedure in the MRI environment. Thus as we are making the lesion we can see which spot in the brain is being affected and if necessary we can adjust the aim of the lesion so that we move it slightly in one direction or the other if we are not satisfied.
Your recent research examined the application of MR-guided focused ultrasound to the management of essential tremor. What therapies have traditionally been used to treat essential tremor and why is essential tremor often refractory to medical treatment?
The main line of treatment for essential tremor is medication. The medications are not that effective and they are also associated with side effects. Even though they work well in some patients, many of the patients – about a third – end up stopping medication use because they are not well tolerated or they have side effects.
Patients who have severe tremor and do not respond to medicines may consider surgical approaches. The two main operations are called thalamotomy (which involves making a lesion by making a hole in the skull, putting an electrode into the target and burning the cells) and deep brain stimulation. Deep brain stimulation has been used quite extensively for Parkinson’s disease but it also works well for tremor.
Both these operations involve making a hole in the skull and putting a wire or an electrode in the brain. So the difference here is that we do not have to make any holes in the skull so it is considered a non-invasive therapy.
Was MR-guided focused ultrasound an effective approach for treating essential tremor?
As this is a proof-of-principle study, so were only 4 patients in this particular study published in The Lancet Neurology. We are now up to 6 patients and in all patients we have had an 80-90% improvement in the tremor in the opposite hand.
How safe is MR-guided focused ultrasound and how does this compare to previous therapies for treating essential tremor?
The main advantage of this technique is that we do not have to make a hole in the skull and put an electrode in the brain. So this means that we should virtually reduce or eliminate the chances of having bleeding in the brain related to putting an electrode in.
It also means that we should virtually eliminate the occurrence of infection in the brain because we are not opening the skin. It also means that these procedures could be done as an outpatient – so the patient could just come in for the procedure and then go home.
These are all advantages but it is very early on and a very small number of patients have been treated so we will have to study many more patients to be able to develop with a realistic appraisal of the real value and safety of this approach.
What further research needs to be carried out on MR-guided focused ultrasound?
Currently we want to expand the study to involve more patients. A very small number of patients have been treated using this technique so we want to increase the number of patients that might be treated. This is the primary new direction that we are going to take to gain more experience. Other centers in the world will also start and continue along this line of work as well.
Do you think MR-guided focused ultrasound could be used to treat other disorders?
As it is a technique to make focal lesions in the brain, there are other operations that one could envisage either in the realm of movement disorders, Parkinson’s disease, and other forms of tremor. Also in the psychiatric realm, patients with obsessive compulsive disorder (OCD) have been treated with cingulotomy and capsulotomy, and these procedures could be done using the focused ultrasound technique as well.
You have also recently been involved in researching the effects of deep brain stimulation (DBS) in patients with chronic, severe and treatment-resistant Anorexia Nervosa. Please can you give a brief summary of this research?
We have published a paper in The Lancet earlier this month on the first 6 patients with chronic anorexia nervosa treated with deep brain stimulation (DBS). We treated 6 women who had been ill for an average of 18 years (chronic anorexia). These were severely disabled women who had long standing refractory anorexia and had been hospitalized many times.
We found that:
The procedure is reasonably safe.
In 5 out of 6 patients, the operation was able to help improve their depression, anxiety and obsession with looking the way they do.
After 9 months of DBS,3 of the patients were able to obtain a significant weight gain and maintain it.
This is an early approach which could prove to be promising in patients who are suffering with severe anorexia nervosa.
We also found that we were able to change the metabolic activity of the brain. There are areas of the brain that are known to be abnormal in anorexia. We were able to diminish the over-activity in one area of the brain that is shows abnormalities in anorexia.
Also we were able to increase the activity of the parietal lobe in these patients. The parietal lobe is involved in body image processing. So we were able to change the activity of that area of the brain which we find quite interesting.
Do you think non-invasive neurosurgical procedures will play a large part in the future of treating neurological disorders?
The trend is towards making operations smaller, making them less invasive, making them safer, making them faster and moving towards outpatient procedures.
I think that the future of neurosurgery indeed is to move towards non-invasive procedures. It may take a certain amount of time but I think that the trend is, not just in neurosurgery but in all areas of surgery, to make surgery minimally invasive or non-invasive.
We are in a time of tremendous advances in neuroscience and in imaging of the brain. We are able to find new targets; we are able to do operations that were previously not considered or that can now be done more safely and less invasively.
We have a tremendous burden of disease in neuroscience in both neurological and psychiatric disease. We now are much better at identifying which potential targets of the brain could be chosen and which particular patients could be helped. So I think there is hope for many patients with a variety of neurologic and psychiatric illnesses to be treated with these new approaches.
Where can readers find more information?
Our study on MR-guided focused ultrasound can be found in The Lancet Neurology: http://www.thelancet.com/journals/laneur/article/PIIS1474-4422%2813%2970048-6/fulltext
Our study on deep brain stimulation for anorexia nervosa can be found in The Lancet: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2962188-6/abstract
About Dr. Andres Lozano
Andres Lozano, MD, Ph D, FRCSC, FRSC, FCAHS is Professor and Chairman of Neurosurgery at the University of Toronto and holds the R.R. Tasker Chair in Functional Neurosurgery at University Health Network and a Tier 1 Canada Research Chair in Neuroscience.
He is best known for his work in deep brain stimulation (DBS). His team has mapped out cortical and subcortical structures in the human brain and has pioneered applications of DBS for various disorders including Parkinson’s disease, depression, dystonia, anorexia, Huntington’s and Alzheimer’s disease.
Dr. Lozano has over 400 peer-reviewed publications, serves on the board of several international organizations and is a founding member of the scientific advisory board of the Michael J. Fox Foundation.
He has received a number of awards including the Olivecrona Medal and the Pioneer in Medicine Award, has been elected a Fellow of the Royal Society of Canada and the Canadian Academy of Health Sciences and has received the Order of Spain.