Focused ultrasound | Congress 2026

Historically, Dr.  Martínez has trained at many different centers, most notably Queen Square, Grenoble, France, which is the birthplace of neuromodulation, and more recently the Madrid CINAC Hospital, which is a research hospital essentially devoted to neuroscience and specifically Parkinson's disease, where he has developed the [00:01:00] high-intensity focused ultrasound program.

Thank you so much for joining us today,  Raúl.

Raúl Martínez Fernández: It is my pleasure. Thanks to you for the invitation.

 Mitra Afshari: Wonderful. Let's get started. So there has been really incredible progress just over the last 5 to 10 years in the field of MRI-guided focused ultrasound. This technology has really brought us back to the era of lesional therapy but a gentler form of lesional therapy, right? As a DBS provider as well, your perspective on the utility and the gaps when it comes to focused ultrasound is really invaluable.

What was previously reserved as a therapy mainly for essential tremor patients has now expanded to Parkinson's disease. What was previously reserved for treatment of just tremor has now expanded to the treatment of other symptoms of PD, like bradykinesia, rigidity, dystonia, with novel targets as well.

Let's start first with the treatment of essential tremor. There's a lot of [00:02:00] exciting stuff happening in Parkinson's disease, but we don't want to forget about essential tremor, right? How has the focused ultrasound procedure been improved for essential tremor patients, and can you comment on improvements made with respect to side effects?

Raúl Martínez Fernández: If I go back to the first meeting that we had as focused ultrasound users, it was in Chicago, 2016. We were just 20, 25 researchers, 25 sites. And the main point there, in my view, was that the community was still refractory to go back to ablation. Because, as you said, ablation is an old procedure, and now we're in the DBS era.

So that was a barrier that we had to overcome. And the way to overcome this barrier has been providing evidence. I think that in essential tremor, that ablation of the thalamus, of the VIM, is perhaps the treatment with the better risk-to-benefit ratio that we have at the moment in terms of efficacy and [00:03:00] as compared to invasiveness and safety.

I'm still, as you said, a DBS user, which is a great treatment, excellent, it changed the life of thousands of patients worldwide. So I'm not saying that focused ultrasound is better than DBS. I'm just saying that it's a new tool and that in a

percentage of patients may be a better option than DBS.

I see both procedures as complementary. Over the years, several studies, randomized control studies, long-term follow-up studies, have shown that if you do a proper ablation of the VIM of the thalamus, you may have a sustained benefit on tremor, initially unilateral and then bilateral treatments, with a very reasonable safety profile despite it is a lesion.

If the lesion is well located and has the proper size, most side effects are either transient, minimal, or mild. So overall, I think what has been important is to provide evidence, to overcome this feeling of going back to something that was, [00:04:00] perhaps, too invasive or dangerous for our patients.

That has been the most important job over the years.

 Mitra Afshari: When it comes to reducing side effects, you really think for essential tremor and focused ultrasound thalamotomies, it's really just been a learning curve of perfecting the lesion in order to reduce side effect profiles?

Raúl Martínez Fernández: Absolutely. If you compare the first trials with the trials that we have now, in the last studies, they showed that side effects, again, they are mostly mild or transient, and it has been improved with experience, with the evidence from different groups, because this is collaborative, we need the experience of people who are starting to do it, and also the technique itself has developed. We know how to use it better, but we also have new tools like neuroimaging during the treatment has improved a lot, and that has helped to do proper lesions. So yeah, I think there has been an improvement in both technical and clinical application that has led to better results in terms of safety but also in terms of efficacy.

The efficacy that we had [00:05:00] at the beginning was lower than the efficacy that we have at the moment. Any technique, particularly those that involve complicated procedures, require a learning curve, and I think now we do it better than we did 10 years ago.

 Mitra Afshari: Wonderful. Let's turn to Parkinson's disease. As you mentioned, tremor was the initial indication for focused ultrasound, specifically thalamic focused ultrasound. And so now we're exploring focused ultrasound pallidotomies, subthalamotomies, and pallidothalamic tractotomies in Parkinson's disease.

So, can you bring us up to speed with that literature? Many of these studies have been performed by yourself and your colleagues in Spain.

Raúl Martínez Fernández: Essential tremor is a relatively simple condition, and PD is much more complex. And as such the clinical phenotypes of the patients are very different. Also we have different targets or neurosurgical targets that can be approached, and each specific [00:06:00] target has a specific clinical effect.

We are learning, we still don't know properly, but we are learning how to apply a specific procedure, a subthalamotomy or a thalamotomy or tractotomy, in a specific phenotype of patient. What is the most appropriate target for each patient? Also considering that we have DBS ... so what technique is better, either FUS or deep brain stimulation in this specific patient? And if we select FUS, ultrasound, what is the most appropriate target?

To summarize it in brief, we can say that VIM thalamotomy is very effective for tremor-dominant PD, although we have encountered some relapses that we are learning how to avoid them, but that can happen. The subthalamic nucleus may be the most effective target to improve parkinsonism, rigidity, bradykinesia and tremor. Pallidotomy and tractotomy, they improve both to some extent.

They improve parkinsonism and [00:07:00] also motor complications like dyskinesia or dystonia. So considering this, we have a scenario where we have different tools, different approaches, and we have to understand in a given patient what does this patient need? Is it tremor? Is it dyskinesia, or is it bradykinesia?

Depending on that, and based on the evidence that we have gathered over the years, that is, in my opinion, when everything started, patient selection. And that is one of the critical points that we have to define.

 Mitra Afshari: Absolutely. And just taking it one step further.

As you mentioned, it can be quite complex trying to figure out the right treatment for the right patient, but then the patient changes over time, right? What's your current take on performing DBS in the STN nucleus following focused ultrasound of the STN? For instance, in a patient where the benefit has not been as durable, where the symptoms have progressed on that same side.

Have you done some of these cases? I know historically [00:08:00] there's been fear of going back into that site, right?

 What is your take on that? I believe there's some new literature coming out on that as well. 

Raúl Martínez Fernández: That's a very important question. What happens if there's partial effect or relapse or progression of the patient? I can tell you that if you have a proper lesion, proper size covering the target, in all the areas and sub-areas that are necessary, even if you cannot modulate, like in DBS, the effect of a well-located lesion is permanent.

Having said that, the disease can progress, particularly on the other side, and you have to decide what to do in that case. If you have a relapse or a partial effect on the treated side, that means that you have not covered the whole target. And that also means that there is a place for either a re-treatment with FUS or for placing an electrode.

We have some experience on that, and it is feasible. You have a patient, in both situations, you have a patient that you have treated unilaterally. The treatment has been insufficient with FUS, and then you can place an electrode there. That has been done, [00:09:00] and it's feasible.

There's a very recent publication by a Japanese group of one case report. Perhaps you were referring to that one. So, as long as there are clinical symptoms of parkinsonism, there is STN, which is still with beta activity and firing, so you can place there an electrode.

On the other side, you have a patient, you have done subthalamotomy or thalamotomy.

And you have a good effect on the treated side, but the other side has progressed. What do we do there? You can consider also ablation, but first, it's not approved regulatorily speaking, and second, there is not enough evidence to use it regularly. I think we need more evidence to be sure that can be done and to which patients.

We have some preliminary experience, 6 patients, very positive or positive, but we don't have enough experience to say that bilateral lesions can be done. But if they can't, then we can place an electrode on the other side, and that has been done as well. So again, I go back to this thought of being complementary.

[00:10:00] It's not, in my view, FUS versus DBS. It's FUS and DBS or DBS and FUS. They are complementary, and they can help each other at a given moment in a given patient. Also an important thing, the degree of invasiveness of each therapy is different.

Overall, FUS is a lesion, so we cannot say that it's non-invasive. I don't consider the technique non-invasive, but globally it's less invasive than DBS. So perhaps one approach may be considering FUS in either more frail patients with higher fragility or early patients, meaning not as much affected.

We can consider perhaps doing a focal incisional lesion there, and if in the evolution these patients progress, we can repeat the lesion or we can do the other side. Then at that point, we can maybe consider placing an electrode. So again, we have to think about the tools we have to treat PD and learn how to use them appropriately at each time point and each [00:11:00] patient.

 Mitra Afshari: Wonderful. What's your take on where we're headed with focused ultrasound in Parkinson's disease? So tomorrow at the Congress, we'll be hearing from Dr. Robert Chen from the University of Toronto on how alternative strategies like focused ultrasound and transmagnetic stimulation can be used to modulate, truly modulate, neural networks outside of the typical motor networks.

What's your take on where we're headed in that regard?

Raúl Martínez Fernández: I think we have so many possibilities. Focused ultrasound can be used as an ablative procedure, and that is, in my view, invasive. Globally less invasive that an intervention in the brain, but is still invasive. But it can also be used in a neuromodulation modality, and that is low-intensity focused ultrasound, and that is non-invasive.

That I agree. You can have side effects, though, if you don't apply the proper parameters. But if you do the right things, that is non-invasive, and that is non-invasive neuromodulation. And the main advantage of that, and I know that Professor Chen has been working on that, the main [00:12:00] advantage is that you have access to deep brain structures.

As compared to TMS, which usually has cortical effect, with focused ultrasound, you have very high partial specificity, and in deep brain structures like the GPi, the STN, or even other regions if it's non-invasive, you can consider impacting on limbic regions of the STN or the GPi

to see what are the emotional effects of the technique. You can even map the STN or another nuclei neuromodulating the area and seeing the clinical effects, both in terms of motor, non-motor modification. So I think it is still something we are learning how to do it, but if neuromodulation with ultrasound energy, low-intensity focused ultrasound neuromodulation, if we're able to control it I think that this opens a lot of opportunities particularly in research more than in clinical practice, but clinical as well, but particularly in research.

You can explore any network that we want. We can modify any [00:13:00] network that we know and to see what happens in those brains. 

 Mitra Afshari: Absolutely. And lastly, Dr.  Martínez, beyond symptomatic motor benefit for Parkinson's disease, what other ways has focused ultrasound been used in Parkinson's disease and other neurological disorders?

You were going in that direction in terms of limbic networks, cognitive networks. Can you give us a little bit of a taste of some of the studies that are being done right now?

Raúl Martínez Fernández: Not in ablation. Ablation has been confined to the motor area of any nuclei because we cannot ablate, we cannot lesion the limbic system because then you have permanent side effects, so you have to be careful with that, but with neuromodulation. There is not much evidence at the moment because, again, neuromodulation has been the newcomer.

Ablation has been done with FUS for 12 or 15 years, but neuromodulation has just started, so there is not a lot of evidence on that. What I expect to be able to impact on [00:14:00] those cognitive and limbic networks in patients who have neuropsychiatric conditions like Gilles de la Tourette syndrome, psychiatric diseases, or even a patient with Parkinson's disease who's apathetic or who's psychotic or has cognitive impairment.

How I envision it is this research is trying to modulate those networks to understand if there is any way to improve, in a non-invasive manner, is any way to improve those symptoms, and also to understand what happens to those networks in a pathological and recover condition, or more physiologic condition.

In neuromodulation, there is not much evidence. There's some evidence with healthy subjects, with psychiatric disorders, and it seems that there's a clinical effect, a clinical benefit, although anything which is non-invasive is going to be transient. The effect is going to be transient.

It's not going to persist unless you repeat the procedure over and [00:15:00] over.

 Mitra Afshari: If it's a more lower intensity neuromodulatory, it will require repetitive ...

Raúl Martínez Fernández: Yeah. This is what we believe at the moment. We don't have experience to conclude that, but that is what I would expect. Yes.

 Mitra Afshari: This was a really nice review of a very complex and evolving topic. Thank you for being here. I can imagine this is a very exciting time for you as a researcher, and I want to congratulate you on all the wonderful work you're doing, and thank you for educating us today on the MDS podcast.

It's really been a pleasure.

Raúl Martínez Fernández: It's been a pleasure as well. Thank to you for the invitation. Thank you. [00:16:00]