Technological advancements have enabled us to understand the pathophysiology of neurological diseases like never before. Today, we have a much better idea of what goes on in the brain of patients suffering from diseases like Parkinson’s Disease, Essential Tremors, Dystonias, and other movement disorders. Disruption or alterations in neural activity in specific areas of the brain, especially those in the cortico-basal ganglia-thalamo-cortical loop, are most commonly associated with these movement disorders and hence are also the most effective targets for medical and surgical interventions.
Medical treatments for movement disorders, though non-invasive, are seldom disease-modifying. Typically, medical treatments restore a patient’s quality of life for a maximum of 2-5 years with increasing doses of medication. Moreover, there are variants of these movement diseases that do not respond to medical treatments at all. Thus, in such cases, surgical treatment alternatives become important to help patients restore their quality of life. While medical treatments require understanding the underlying pathological process, surgical treatment also requires localising the sweet spot of this pathological activity. Thus, it is only recently, after extensive research, that we have been able to localise movement disorders to specific areas in the brain, some as small as 100 mm3 in size, and thus develop innovative non-invasive treatment alternatives.
Now that we know anatomical targets with therapeutic potential, the challenge is to develop the most effective and safe therapies to target these areas. The most effective and popular approach to accessing and altering the neural activity of specific and deep brain regions is Deep Brain Stimulation (DBS). DBS involves the placement of electrodes in the brain targeting the seat of the pathology to alter the neural activity of specific brain areas/cells. When performed by experts, DBS can achieve a high degree of precision and hence therapeutic effect. Even though it is an invasive procedure with only standard surgical risks, it continues to be the gold standard therapy for pharmaco-resistant and advanced movement disorders. But, efforts are being made to develop novel therapeutic strategies and improve the efficacy with which we access and modulate neural activity in these regions. One such intervention being researched is Focused Ultrasound (FUS).
While focused ultrasound is a non-invasive technique to approach deep brain structures, it often trades off the precision and reversibility offered by DBS. Thus, even experts in the field of neurosurgery have yet to adopt it as a therapeutic alternative. In an attempt to achieve similar precision and some procedural control like DBS, FUS has now been paired with real-time Magnetic Resonance Imaging (MRI), and is called Magnetic Resonance-guided Focused Ultrasound (MRgFUS). In this blog, we will dive deeper into the procedure and its current application in movement disorders.
First, let’s try to understand the technicalities of FUS. FUS uses high-intensity focused ultrasound (HIFU) – ultra-high frequency (220-710 kHz) sonic waves to deliver thermal energy externally. This energy is used to alter the target tissue’s structure, function, or both. This external energy and thus, FUS can be used for thermal ablation, neuromodulation, and drug delivery.
MRgFUS, on the other hand, offers all these therapeutic alternatives with higher precision and procedural control based on real-time monitoring. In a nutshell, the procedure involves real-time magnetic resonance imaging (MRI) and thermometry (measuring the temperature of the brain tissue) throughout the delivery of energy (by FUS). This allows the surgeons to correct the target after unintentional movements by the patient, and also track and limit the damage to surrounding brain tissues. The procedure requires a thorough understanding of FUS physics, expertise in understanding the behavior of brain tissue in response to external energy, and being able to monitor this behavior on MR imaging, which only comes with years of experience.
Over the last few decades, MRgFUS has been explored for its applications in a number of diseases. Here, at Jaslok Hospital and Research Center, Mumbai, MRgFUS is also being used as a non-invasive treatment in fibroid care, specifically for ablative resections of Leiomyoma (or Fibroids) in the Department of Obstetrics and Gynaecology in collaboration with the Interventional Radiology Services team. Jaslok Hospital was one of the first to introduce MRgFUS in Asia (but for non-neurological conditions). While MRgFUS is being explored for its applications in other movement disorders as well, the evidence is not yet strong enough for us to offer the treatment to our patients. Moreover, even though MRgFUS might be a non-invasive alternative, DBS continues to be the gold standard in the field of neuromodulation, especially with the advent of adaptive DBS technologies. And thus, due to the limitations of current MRgFUS technology for neurological conditions, we would like to wait before we introduce it for our patients.
Thus, in an attempt to offer the best to our patients, we will continue to cater to our patients with treatment-resistant Parkinson’s Disease, Dystonia, Essential Tremors, Trigeminal Neuralgia, Epilepsy, Depression, Obsessive Compulsive Disorders, and Tics (or Tourette’s Syndrome), through high-end therapies like Deep Brain Stimulation, Radiofrequency Thermocoagulation, and Vagus Nerve Stimulation in unmatched volumes. In fact, we take pride in being the country’s highest throughput Functional Neurosurgery setup. Soon, we intend to offer MRgFUS for the Essential Tremor, and closely monitor the research in the field for any new treatment alternatives we can offer our patients.
Talking about the procedure of MRgFUS, a patient opting for MRgFUS can expect a pre-workup involving blood tests, safety profile assessment, and an MRI for target localisation. Once the target is identified, the procedure involves the delivery of thermal energy through FUS with continuous monitoring of the target and the temperature of each voxel (small part/portion of the brain tissue) throughout the procedure. The procedure involves three phases, designed to maximise efficacy and minimise any possible adverse effects. Throughout these phases, the patient can expect to experience some sensations, especially as warmth in the head, among others. To comfort the patient, we also have a cooling mechanism in place.
MRgFUS is typically an irreversible procedure, and thus its effects are permanent but not disease-modifying. Similar to DBS, it can slow down the progression of the disease and alleviate symptoms. Unlike Deep Brain Stimulation, there is limited scope to further optimize the treatment once done. After DBS, the stimulation can be optimized with the progression of the disease, but MRgFUS will only have to be repeated with a similar/different target if the disease continues to progress at a fast pace. MRgFUS, on the other hand, does not limit medical diagnostic procedures like MRI, which are limited post-DBS.
Jaslok Hospital and the Department of Functional Neurosurgery are always striving to achieve the highest quality patient care through evidence-based practices. Prof. Dr. Paresh Doshi, the Director of Neurosurgery and Functional Neurosurgery, has over 25 years of experience targeting the deep brain structures for movement disorders, even before the advent of sophisticated techniques like MRI. It is with this experience that we are confident in offering high-precision MRgFUS to our patients with Essential Tremors. Moreover, given his expertise in the field, Prof. Dr. Paresh Doshi also heads the MRgFUS working groups of India, which is a testimony to the team at Jaslok being a leading center in the field.
In conclusion, even though MRgFUS is emerging as an alternative, it is still far from the gold standard – DBS, especially for movement disorders. On the mission to provide the highest quality care to our patients, the Department of Functional Neurosurgery and Jaslok Hospital, Mumbai, still advocate for DBS, while keeping a close eye on the novel developments in MRgFUS. We assure that if and when there would be substantial evidence for the benefits of MRgFUS, we would be among the leading centers in the country to offer neural MRgFUS, purely by virtue of our experience and expertise in neuromodulation and evidence-based practice.
Myths about MRgFUS
It is non-invasive: Yes it does not involve cutting on head, but it destroys brain tissue. Where as Deep brain stimulation makes a cut on the head but does not destroy any brain tissue
It is a novel way of treatment: Lesioning of brain has been performed for more than 50 years. The only difference is the MRgFUS is using a new way of lesioning. Non-invasive lesioning have been performed for Parkinson’s disease and Psychiatric disorders using Gamma Knife or Radiosurgery and minimally invasive lesions have been performed using Radiofrequency lesioning. However, the safety and the titrability benefits of Deep Brain Stimulation has been the reason for the relegating the above as secondary option. The MRgFUS lesioning is no different, it is old wine in new bottle
Facts about MRgFUS
It is effective for Essential tremors. It has been approved for limited purposes to treat Unilateral Parkinson’s disease. It can treat unilateral tremors but is not effective for any advanced Parkinson’s disease patients as it cannot be performed bilaterally.
