Exploring the Treatment Possibilities and Functionality of High Intensity Focused Ultrasound

Timothy Miller, MD

High intensity focused ultrasound (HIFU) was first therapeutically suggested in 1932 when several clinician researchers discovered the mediums propensity to heat tissue. Nearly 50 years later, the advent of MRI technology led to a renewed interest in HIFU due to the potential for precise spatial guidance via imaging and the development of MR-thermometry, allowing for accurate temperature tracking. The first coupled MR-guided focused ultrasound machine in 2003, set the stage for HIFU to become a useful treatment option with broader applications.

Today, this non-invasive neurosurgical procedure is used to treat essential tremor, Parkinson disease (PD), and high-grade pediatric brain tumors. HIFU, an emerging modality, involves the use of a piezoelectric transducer to deliver high-energy pulses in a spatially coordinated manner, while minimizing damage to tissue outside the target area. Numerous institutions across the globe, including Baptist Health, a major healthcare network located in Florida, have implemented HIFU as a standard neurosurgical practice for the aforementioned conditions.

In a recent interview with NeurologyLive^®, Timothy Miller, MD, director of functional neurosurgery at the Marcus Neuroscience Institute, Baptist Health, sat down to discuss the clinical applications of HIFU as a non-invasive treatment option. Miller, a neurosurgeon himself, emphasized the advantages of HIFU, such as minimal pain, quick recovery, and the absence of infection risks, making it an attractive alternative to deep brain stimulation. Furthermore, he highlighted the importance of understanding patient eligibility, especially for PD subtypes, and shared insights on the learning curve associated with this technology.

NeurologyLive: What have been your experiences with high-focused ultrasound to date?

Tim Miller, MD: Sure. This is a therapy that's indicated for patients with tremor and various types of Parkinson's disease. The main patient cohort is those with essential tremor who have failed medical management, which is defined by the failure of one or two medications over at least a month. There are various reasons patients may fail these medications, either due to inefficacy or side effects. Some of the medications have nasty side effects, and patients don't like them. So, the introduction of high-intensity focused ultrasound (HIFU) has allowed us to treat patients who otherwise might not be treated at all—either because of medication failure or their apprehension to undergo what was previously the alternative: deep brain stimulation. Many patients have, you know, emotional or physical reservations about having electrodes implanted in their brains, with good reason. It's an invasive procedure that carries the pain and risk of infection. HIFU, on the other hand, is relatively painless for most people, or if there's pain, it's only for 20 or 30 seconds, and it has essentially no risk of infection since there are no incisions.

Are the safety and feasibility intangibles what make HIFU so attractive?

Well, no, I think what we'd probably be looking at more is non-inferiority. Essentially, this is a non-inferior method compared to deep brain stimulation, and when you compare invasiveness, it clearly wins out. So, patients are much more likely to consider having this done rather than DBS. The efficacy is great. It's quick, it's immediate. There's no healing period. Patients leave the clinic or MRI center and sometimes go straight to lunch to show off their new, non-shaky hands. So, it can be emotional for those people, in a good way, and of course, we love seeing that.

Does experience matter with this type of therapeutic approach, or is it relatively easy for most clinicians to use?

Yeah, there's obviously a learning curve with this, like with any new technology. The company that developed this technology is very good about training physicians and making sure we’re comfortable. In fact, the first 30 or so cases are proctored by their representatives, who have been with the company for 20 years and have done thousands of these procedures. It's good to have them around for those initial cases to teach us the nuances. But at some point, our understanding takes over, and we can make those nuanced decisions ourselves. There is some patient variability—things like the thickness or density of the skull can affect how we target the small lesion or the energy we use with the ultrasound beam. So, there are intraoperative decisions that need to be made, and the company does a great job of teaching us how to understand these nuances. I've only been doing this for a few months here in Boca, but I trained at Duke and had ongoing training for about eight months before we even started. So by the time we treated our first patient, we were ensuring success, and we've seen that reflected in our outcomes.

For younger residents and medical professionals, what considerations would you give as they begin to learn how to use HIFU?

I think it's important to know the indications and which patients are not eligible. Now that we’ve advertised this quite a bit, we’re getting a lot of referrals from neurologists for patients with Parkinson's disease. There’s a subset of Parkinson's patients that can be treated with HIFU, but it’s a small subset. These are patients with tremor-dominant Parkinson disease, where the tremor is the main issue, without significant gait problems or other symptoms like bradykinesia (slowness of movement) or rigidity, which this therapy doesn't help. So, we need to inform our neurology colleagues that not all patients with Parkinson are suitable candidates. In fact, for patients with Parkinson, I require them to see our in-house neurologists first, so we can work together to decide the best approach. Some of these patients may still be candidates for DBS. Essential tremor, on the other hand, is relatively straightforward. Many primary care physicians manage essential tremor and try medications first, and we accept essentially all essential tremor patients. There’s also a smaller subset of Parkinson's patients with levodopa-induced dyskinesias (LID), who can be treated with HIFU using a different target than we would for tremor. So if neurologists have patients with LID, we're happy to evaluate them for focused ultrasound as well.

Are there any last thoughts on future applications or research to extend this treatment method?

Well, in the neurosurgery world in general, it’s probably too extensive to cover everything, right? There’s a lot of tumor research and many other areas we’re exploring. But with regard to HIFU and targets for deep brain stimulation or ablative procedures, there are ongoing studies. We're looking at anterior capsulotomy for OCD, and there are potential targets for obesity, Tourette's syndrome, and more. These are evolving areas. I think the next big target for this therapy will probably be tumors. We already use heat to treat tumors and conditions like pseudoprogression (radiation-induced necrosis), which currently involves implanting electrodes in the brain and heating up the tumor from the inside out. With ultrasound, we could do it from the outside in, using live thermal imaging—just like we do with HIFU for essential tremor and Parkinson disease. So, I think these are just around the corner, and we will see emerging indications and therapies for focused ultrasound, which will expand the number of patients we can treat.