HIFU vs LIFU in Neurodegenerative Disorders

[Dr. Jacob Fleming]
Let's dive right in. What the heck is HIFU, first of all?

[Dr. Bhavya Shah]
HIFU, everybody calls it HIFU, it's a high-intensity focused ultrasound. It's important to note it's called focused ultrasound, and high-intensity and low-intensity, there's different applications depending on the duty cycle that you're using and things like that, so focused ultrasound, high-intensity applications, and low-intensity applications. It's the ability to focus ultrasound waves onto a single point and use it to change how neurons behave if you're using low-intensity and then ablate tissue or destroy tissue if you're using high-intensity with applications in the brain and outside of the brain, obviously.

[Dr. Jacob Fleming]
Very cool. Obviously, we immediately contrast this to the ultrasound that the rest of us radiologists or other interventional proceduralists are used to for diagnostic purposes. This is actually using the same underlying physics but for therapeutic purposes.

[Dr. Bhavya Shah]
Yes, therapeutic ultrasound is a great way to refer to it, too.

[Dr. Jacob Fleming]
Excellent. Let's start. Before we dive a little bit further, your training and your pathway in your career so far has really been wrapped up in this, and I always like to hear a little bit of the background from our guests first, so tell us a little bit about your life and your training and how everything has led up to where you are with this right now.

[Dr. Bhavya Shah]
Sure. When I was in Boston as a radiology resident, I was working on applications for nerve regeneration in a lab at the Brain and Cognitive Sciences at MIT. Now, how are we going to deliver these nanoparticles to the brain was always a question. Open surgery means you have to cut through tissue to get to your target, and then, vascular approaches aren't really going to work for what we're trying to do here. Focused ultrasound really stuck out to me as I was reviewing the literature and things.

Then I got accepted to the T32 fellowship at Stanford and was exposed to focused ultrasound. I think it really invigorated my passion for what we could do with this stuff. Especially as radiologists, people who are trained to use images to treat patients, I think this offers us an ability to use advanced imaging to target discrete tissues in the brain, either to ablate them thermally or with low-intensity focused ultrasound to deliver drugs or even do things such as liquid biopsies, which we'll talk about.

[Dr. Jacob Fleming]
That's really amazing. Can you tell us a little bit more about your experience with the T32 fellowship?

[Dr. Bhavya Shah]
Yes. The T32 fellowship is a two-year training program. 16 months of that is really dedicated to research and any subjects you really want to undertake. The reason there are so many options when you go into one of these T32 training programs, especially at a place as rich with resources as Stanford, the focused ultrasound, there was just something about it that was more than just diagnostic applications. I've always had an interventional bent to things and so it just seemed to make sense for me.

[Dr. Jacob Fleming]
Excellent. From there, building on your work with the T32 fellowship, how did you get started in your career and then work toward this?

[Dr. Bhavya Shah]
At Stanford, they were doing some of the original clinical trials to look at essential tremors. This idea that you could target a specific thalamic nucleus in the brain to treat essential tremor or tremor-dominant Parkinson's disease was really brought forth at the University of Virginia by Jeff Elias, who's a neurosurgeon there. They were doing a clinical trial multi-center and Stanford was one of the sites. I remember while I was training there, one of the questions that kept coming up is we can't see this target on high-resolution imaging. We can't see it on the best imaging that we have so we were resorting to indirect or landmark-based approaches.
As a fellow and people are telling you, "Hey, this is a problem. Go find a solution," you're constantly, it's always running in the back of your head like, "How am I going to find this target?" and so I started working in tractography and things like that.

[Dr. Jacob Fleming]
Awesome. Let's just dive in and talk a little bit more about the specifics of it. You're, obviously, at UT Southwestern right now. You came in, as you started your early career, practicing as a neuroradiologist. Obviously, this was a particular interest to you and so I take it you knew that this is something that was going to be a major focus for you in your career, right?

[Dr. Bhavya Shah]
Yes, absolutely. Early on, when I went with Joe Maldjian and Neil Rofsky, they were really looking for somebody from our end to take us by the horns and really lead the program and make it what we could do it. That was really my whole reason for coming here or being hired to come here. Previously, I was working as a neuroradiologist at the VA. I just started a medical device company and I was spending three days a week reading spine MRI and routine brain MRIs and working on my company. As soon as that company took off on its own and didn't really need me so much for the chief scientific officer part of it, I spent all this time training. I always had passion for focused ultrasound, and to hear that Joe and Neil were looking for somebody to lead the program, it just fit.

[Dr. Jacob Fleming]
Right place at the right time.

[Dr. Bhavya Shah]
Exactly.

[Dr. Jacob Fleming]
That's great. You had that itch. You knew you needed to be doing something else. When I was a first-year resident, I think things were starting to get off the ground and so it's been cool to see this unfold and see the volume go up and the success. Tell us about the journey so far getting this program started.

[Dr. Bhavya Shah]
It's definitely been a journey. I think as most things, when we talk about medical technology, cost is a pretty significant burden. When this technology was getting FDA approved and other sites were picking it up and we wanted to purchase it, there's always limitations on how much money a hospital system can put into equipment. We got really lucky and Bill Dauer and Marc Diamond really spoke to me a little bit about focused ultrasound technology.

I was working with Marc on some preclinical experiments looking at Alzheimer's disease with focused ultrasound, and he introduced me to Bill. Bill's really been really instrumental in getting this technology here. He's the director of the O'Donnell Brain Institute at UT Southwestern. He really liked the idea. He supported the idea. Our movement disorder section also really supported the idea. We got the money from a donor to get the equipment, and then once we got the equipment, we just started rolling.

[Dr. Jacob Fleming]
Fantastic. I want to jump off from that. This is a predominantly IR podcast so there's a bunch of equipment nerds listening. Let's talk equipment. What all is involved in this operation?

[Dr. Bhavya Shah]
You either need a 1.5 Tesla or a 3 Tesla MRI scanner, and you need a 1024 array transcranial ultrasound transducer. That transducer has its own components, a water circulating tank, equipment that comes with the kit, and then, obviously, a stereotactic head frame that you have to place on the patient before you do the procedure to keep their head still. Those are the big components. Really big components is really that transducer. Right now there's only one company who makes a FDA approved transducer to do HIFU. The other is the 1.5T or 3T MRI. Those are the big pieces.

[Dr. Jacob Fleming]
Got you. This ultrasound unit is totally different than typical one we just got in the department using to do the DVT studies or for guided procedures.

[Dr. Bhavya Shah]
Yes. This doesn't even look like an ultrasound unit. It looks like those old school perm devices where you go and put that thing on your head. It looks exactly like that. It's a helmet. When you open that helmet up, you can find that there are 1024 phased array ultrasound transducers. That's what really makes it possible as a phased array technology.

Focused ultrasound in the brain isn't new, the Fry brothers at Springfield, Illinois. The problem was that we didn't really have the technology to image what we were doing and so they'd have to do a craniotomy and then use focused ultrasound. In fact, Lars Leksell even built a frame for it. He built a focused ultrasound stereotactic frame. It's been there. I think with the advent of technology imaging phased array ultrasound transducers, it really changed the game, allowed us to deliver ultrasound across an intact skull.

[Dr. Jacob Fleming]
That's really incredible. I love hearing that history that it was an open surgical technique, and now, like I said-- Would you consider this basically a non-invasive technology? Is that how you would describe this?

[Dr. Bhavya Shah]
A lot of people say it's non-invasive. I actually think it is pretty invasive because you are targeting deep structures of the brain. I think another way of maybe saying it is incisionless because you're not making any holes or making any incisions. I think that's more appropriate because deep thalamic nuclei is pretty invasive in my opinion.