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The Current State of Focused Ultrasound Indications: Essential Tremor, Parkinson's & Bone Metastases

Author Caleb Solivio covers The Current State of Focused Ultrasound Indications: Essential Tremor, Parkinson's & Bone Metastases on BackTable MSK

Caleb Solivio • Feb 29, 2024 • 37 hits

High-intensity focused ultrasound (HIFU) continues to have growing therapeutic potential as a non-invasive medical treatment. This article delves into the specific conditions and patient groups suited for HIFU, particularly emphasizing its utility in essential tremor, Parkinson’s disease, and bone metastases. However, as HIFU gains traction, it becomes increasingly important to outline the conditions for which HIFU is indicated as well as the best patient-candidates for such a treatment. Additionally, and just as important, is the topic of which clinicians will use HIFU. While radiologists, with their in-depth imaging expertise, emerge as obvious frontrunners, Dr. Bhavya Shah maintains that HIFU belongs to a multidisciplinary field that prioritizes patient care.

This article features excerpts from the BackTable MSK Podcast. We’ve provided the highlight reel in this article, but you can listen to the full podcast below.

The BackTable MSK Brief

• High-intensity focused ultrasound (HIFU) is FDA-approved for treating essential tremor and specific symptoms of Parkinson's disease.

• Four-tract tractography is a method that uses advanced structural imaging, validated with cadaver studies, that can increase the precision of HIFU.

• Outside of neurodegenerative disorders, HIFU has potential in bone conditions, such as painful bone metastases and facet diseases, as bone has an intrinsic property to absorb ultrasound energy.

• Radiologists, due to their expertise in imaging, are pivotal in the application of HIFU therapies but the interdisciplinary nature of HIFU requires collaboration across multiple medical specialties.

Focused Ultrasound Indications: Essential Tremor, Parkinson's & Bone Metastases

Table of Contents

(1) Focused Ultrasound for Essential Tremor & Parkinson’s Disease

(2) Focused Ultrasound for Painful Bone Metastases

Focused Ultrasound for Essential Tremor & Parkinson’s Disease

High-intensity focused ultrasound is useful in patients as a non-invasive treatment option for neurodegenerative disorders. Specifically this technology is salient for patients with essential tremor or tremor-dominant Parkinson's disease. Additionally, HIFU can be employed for other Parkinson's motor symptoms like bradykinesia, rigidity, and dyskinesias. The efficacy of this treatment comes from its precision, derived from a technique called four-tract tractography. This technique increases accuracy by identifying optimal treatment target zones and steering clear of critical brain tracts.

[Dr. Jacob Fleming]
You mentioned a couple of different clinical scenarios, essential tremor, Alzheimer's, are those the primary clinical issues we're seeing? What kind of clinical issues are you seeing in the clinic in treating these patients?

[Dr. Bhavya Shah]
The focused ultrasound technology or high-intensity focused ultrasound is currently FDA-approved for a couple of things, essential tremor, tremor-dominant Parkinson's disease. Those are patients who have a very specific type of Parkinson's disease in which their main symptom is tremor. Number three is also other motor symptoms in the setting of Parkinson's disease such as bradykinesia, rigidity, dyskinesias, things like that. Depending on what you're doing, the target is different. For essential tremor and tremor-dominant Parkinson's disease, the target has historically been considered the ventral intermediate nucleus of the thalamus, or some people, for the tremor-dominant Parkinson's disease, would consider even the ventral oralis posterior nucleus.

For Parkinson's disease, the target in the United States as FDA-approved is the globus pallidus internus, which is in contrast to some of the clinical trials that are coming out of Europe, in which they're targeting the subthalamic nucleus. Just, I think, last week there was a paper published in the New England Journal of Medicine looking at HIFU pallidotomy in the United States, multi-site clinical evaluation of how well it worked. Similarly, in the Journal of Neurology, maybe two or three weeks ago, the Europeans published their experience with the STN. I think without really getting into the nitty gritty, it's pretty obvious that the reductions in these motor symptoms are not as great as people had initially anticipated, although there is some effect and there is still a pretty significant adverse effect profile.

[Dr. Jacob Fleming]
Interesting. I understand that part of the reason that speaking to one of our colleagues, Fabricio Feltrin, shout-out to Fabricio. He's a great fellow, research fellow, and now attending at UT Southwestern. He's been very involved with this as well. He says part of the reason that your patients have such good improvement in a lot of cases has to do with the workup and using the MR tractography. Can you talk about that whole part of the pre-procedure aspect?

[Dr. Bhavya Shah]
Yes, absolutely. A shout-out to Fabricio as well. He's probably one of the best fellows I've ever worked with and he's a fantastic attending.

There's so many different ways to target the part of the brain that you're talking about. Let's talk about essential tremor because I think that's going to be the most straightforward way of thinking about this. The ventral intermediate nucleus is the target, but people can't see it on any kind of high-resolution imaging so they're relying on landmark or indirect-based methods. They identify key structures in their brain, like the anterior commissure and posterior commissure, and they make measurements from this and say, approximately, this is where they think the target is.

The great thing about focused ultrasound is before you treat, meaning, that before you ablate a part of the brain, you can use low-intensity focused ultrasound to stimulate what you think is the target. Then if you go and examine the patient in real-time, you can see that their tremor is getting better and you can also ask if they're having any side effects. If their tremor is getting better and they're not having side effects, it means you're in a great spot. You may not be in a great spot and patient's tremor might not have gotten better or they might have some side effects, in which case, you're going to have to move and search around looking for the target.

To get around this, we use this method called four-tract tractography that I developed here. Basically, we started in cadavers, maybe when I was recruited, so four or five years ago, that we obtained through the World Body Program. These people had passed, but they had donated their bodies to science. We were able to acquire them right after they'd passed so no fixation, no formaldehyde, nothing like that. We would get them on the scanner in the middle of the night and we'd run really high-resolution, 32, 64, 128 direction DTI, advanced structural imaging, such as this Fast Gray Acquisition T1 Inversion Recovery, and then we would process these different tractography things.

Meanwhile, we would take the patient's brain and we would put it in a 3D-printed slicing guide. The slicing guide, the whole purpose of it was to hold the brain like it is held anatomically, but in a specific plane known as the anterior commissure, posterior commissure plane. We would then slice through the brain at two-millimeter sections from the front to the back and then register these images of the MRI back to the path using block-face photography. Then we would dissect down in micron sections and identify white matter tracts so we're entering and leaving the thalamus.

We were looking at a couple of things. Number one, anytime you say DTI out loud, someone says distortion, huge gradients, lots of distortion. We're in the central part of the brain so we wanted to make sure that that wasn't going to be the case. Number two, people talk about biomarkers all the time. Imaging biomarkers are one of those things where just because you can identify it, is it really there? We wanted to show that, "Yes, it's really an anatomic structure that you can identify and it's pretty high likely what you're looking at.

The third thing we want to do, the reason we ran so many DTI scans, was because we wanted to use something that's clinically relevant. Radiology, sometimes we get really excited that we can make pretty pictures and then we have 256 directions, but no clinical protocol can support that. We wanted to drive it down to as little as possible so we were using 32 directions. At the same time this was going on, people in functional neurosurgery, neurosurgeons were reporting that the improvement of the patient's tremor, and essential tremor, didn't really matter how close you were to the VIM. What really mattered was how close you were to the white matter tract, the dentato-rubro-thalamic tract.

What tract they were looking at and what tract you should prospectively target, nobody really seemed to understand that. That's what we did. We came back and said, "Look, there are two components to the DRTT, a decassating and a non-decassating component. From histology and pathology and all the anatomic studies that have ever been done, we know that the decassating DRTT goes into two nuclei, the VOP and the VIM, and the non-decassating only goes into the VIM. If you're targeting at the posterior margin of those two, you're pretty much hitting VIM.

We did a lot of this preliminary work in cadavers. It really proved that what we were looking at was what we could see, and then it became translating into FDA-approved software for treatment. We started using Brainlab and processing this. Ever since then, we've been using this approach four-tract tractography to identify the targets, the decassating and the non-decassating DRTT, and also, identify tracts that we want to avoid, the medial lemniscus, which is primary sensory for the whole body, and also, the corticospinal tract, which is your primary motor tract. You want to stay away from those. That's how we've developed our protocols.

A lot of people tell me, "we've done tractography and it doesn't work." I think that that is a fair criticism because it depends on who's doing your tractography. One of my friends, he's a neurosurgeon, and he's like, "We gave the radiologist the protocol and they did it and they made the tracts." I would say to that, that's probably not going to work even without seeing the tracts because if you're the treatment physician, you should be making your tracts and looking at them yourself and making sure they make sense.

[Dr. Jacob Fleming]
It's definitely one of the advantages of you being the diagnostician and the treater.

[Dr. Bhavya Shah]
Yes, absolutely, and I think that's important. The other thing is, I think that protocols vary greatly and having a really good understanding of the anatomy is really essential. That being said, we've expanded. We've shared our approach with UCSF, Mayo Clinic in Rochester, University of Colorado, and Duke, and they seem to be getting the same tracts that we're getting, and the same responses so I think it's working out.

Listen to the Full Podcast

Transcranial Focused Ultrasound for Tremor: Next Generation Image-Guided Therapy for the Brain with Dr. Bhavya Shah on the BackTable MSK Podcast)
Ep 16 Transcranial Focused Ultrasound for Tremor: Next Generation Image-Guided Therapy for the Brain with Dr. Bhavya Shah
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Focused Ultrasound for Painful Bone Metastases

Outside of the neurodegenerative and movement disorder realm, HIFU also extends to other conditions such as painful bone metastases and facet diseases. This is, in part, due to the unique capacity of bone to absorb ultrasound energy. When applied to painful bony metastases, HIFU specifically targets and eradicates the periosteal nerve responsible for the pain. By heating the bone, not only is the sensory input that triggers pain removed, but there's potential to address the tumor itself, offering promising implications for managing benign bone tumors.

[Dr. Jacob Fleming]
You've just really opened my mind to the possibilities of focused ultrasound and it's clear that this is going to be really big over the next few years. There's going to be a lot of interest in this from a lot of different specialties. My question to you is, how do you see radiologists best staying at the forefront of this treatment and being not just involved with the basic science and the imaging but actually as the treating physicians? How do you see that?

[Dr. Bhavya Shah]
Well, I think that's really important. I think radiology has changed over the years and we've learned some hard lessons. I think number one is patient engagement. We have to be willing to engage patients and the patients are the most important thing. They're the reason we are doing any of the things that we're doing. That's the reason that any of us took the jobs that we took. We have to remember that. We have to work to understanding that whatever we do, we're trying to do it to improve the standard of care for patients.

Number two, we have to realize that we are a key component of a multidisciplinary team. In the brain, that is so critical. It is important to have people with different perspectives, different experiences. Even though they clash, even when they say, "Hey, Bhavya, I've done tractography. It doesn't work," or, "I've looked at perfusion imaging. It doesn't work," really understand why it hasn't worked for them and what they have done or they haven't done. I think having that multidisciplinary team is really important because--

The O'Donnell Brain Institute, one of its core principles is to get people out of boxes. "I'm a neurosurgeon. I'm a neuroradiologist. I'm a neurologist." Well, we think that going forward, the most evolved way of thinking about this is who's doing what that's in the best interest of the patient and letting them do that. Then I would say that for radiologists who are interested in this technology, I think, it is very imaging-heavy. I just gave grand rounds at University of Colorado and that was a question that came up. "Hey, Bhavya, I'm really interested in this. What can we do? How how can I be involved?"

Well, all of this technology is image-based therapy. I think there's a very strong argument to be made that when you're doing precise lesioning of the brain or other parts, having really advanced, not cursory knowledge, but really deep knowledge of what advanced imaging can offer you, what its limitations are, what you can do with it, is critical.

[Dr. Jacob Fleming]
Yes, absolutely. Especially in your applications, the people you are working very closely with, the other physicians, neurosurgeons, and neurologists, they're extremely adept at imaging. Especially at UT Southwestern world-class physicians we're working with. You, actually, I remember you impressed this upon me when I was a first year resident, is don't settle for fuzzy descriptions of things. If it's Broca's the area where you're seeing a lesion, describe it there. The neurosurgeon may see a report with a vague description, they have the benefit of the patient in front of them, and they say, "Oh, I think this may be actually affecting Broca's area," for example.

I think about that a lot because when we're just looking at from the diagnostic aspect, we can sometimes be a little bit hamstrung and it's easy to describe things, we can easily be way too specific sometimes. It's of debatable utility but I think it's really important in our training that we have the most in-depth, eloquent descriptions of the anatomy. Then that becomes second nature to us. I couldn't agree anymore with what you said. I think that, clearly, this is going to be a multidisciplinary and interdisciplinary effort going forward. I think that's one of the many values that radiology brings is just having that extremely specific understanding of the anatomy and also how the imaging, especially the tractography, like you talked about, is being used for this.

[Dr. Bhavya Shah]
I think that's critical. I think that the training is an important and a critically important part of that.

Podcast Contributors

Dr. Bhavya Shah discusses Transcranial Focused Ultrasound for Tremor: Next Generation Image-Guided Therapy for the Brain on the BackTable 16 Podcast

Dr. Bhavya Shah

Dr. Bhavya Shah is a practicing neuroradiologist with UT Southwestern in Dallas, Texas.

Dr. Jacob Fleming discusses Transcranial Focused Ultrasound for Tremor: Next Generation Image-Guided Therapy for the Brain on the BackTable 16 Podcast

Dr. Jacob Fleming

Dr. Jacob Fleming is a diagnostic radiology resident and future MSK interventional radiologist in Dallas, Texas.

Cite This Podcast

BackTable, LLC (Producer). (2023, June 21). Ep. 16 – Transcranial Focused Ultrasound for Tremor: Next Generation Image-Guided Therapy for the Brain [Audio podcast]. Retrieved from https://www.backtable.com

Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.

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