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Focused Ultrasound · UF Health MedEd Cast

• 0:03
  Melanie (Host): Welcome to UF Health MedEdCast with UF Health Shands Hospital.
• 0:07
  I'm Melanie Cole.
• 0:08
  And today, we're highlighting focused ultrasound.
• 0:11
  Joining me is Dr.
• 0:12
  Justin Hillyard.
• 0:13
  He's a neurosurgeon and an associate professor at the University of
• 0:17
  Florida College of Medicine, and he practices at UF Health Shands Hospital.
• 0:22
  Dr.
• 0:22
  Hillyard, it's a pleasure to have you join us today.
• 0:24
  And as we've heard a little more and more about focused ultrasound, it's generated
• 0:30
  pretty much excitement in neurosurgery.
• 0:32
  It represents something patients almost can't believe is possible, Doc.
• 0:37
  targeting these deep in the brain areas without making an incision.
• 0:41
  So for colleagues who may not yet fully understand where this technology
• 0:46
  fits in, can you start by explaining a little bit about what focused
• 0:51
  ultrasound actually is and why it's such a breakthrough in neuroscience?
• 0:57
  Justin D Hilliard, MD: Yeah, thanks, Melanie.
• 0:57
  You're right.
• 0:58
  Focused ultrasound is an incredible, therapy, and it's being used for
• 1:04
  the treatment primarily of essential tremor, but, in the future also for
• 1:09
  perhaps aspects of Parkinson's disease.
• 1:11
  But for today, I'm gonna focus on, perhaps our conversation on essential tremor.
• 1:16
  And essentially, it uses ultrasound technology.
• 1:21
  It uses 1,024 tiny ultrasound transducers that are lined on a
• 1:26
  special helmet that direct, ultrasound waves at a very specific region of
• 1:32
  the brain in the thalamus that's implicated with tremor circuitry.
• 1:37
  And that ultrasound energy converts to heat in the brain,
• 1:40
  and the heat creates an ablation.
• 1:42
  It, it disrupts the tremor circuitry, thereby reducing, usually on the
• 1:48
  order of 70 to 80%, the magnitude of an individual's tremor.
• 1:53
  Melanie (Host): Wow, isn't that amazing?
• 1:54
  It's really an exciting time in your field, Dr.
• 1:56
  Hillyard.
• 1:57
  So when people hear ultrasound, they usually think imaging, not treatment.
• 2:02
  Justin D Hilliard, MD: Yes.
• 2:02
  Melanie (Host): Walk us through a little bit of the science
• 2:05
  of how it works inside the
• 2:06
  brain.
• 2:07
  Justin D Hilliard, MD: Yeah.
• 2:08
  So you're right.
• 2:08
  The ultrasound really just refers to a wavelength of, emission, And so,
• 2:14
  the most common ultrasound that we're used to thinking about in the medical
• 2:17
  field might be an echocardiogram or maybe, know, for obstetrics.
• 2:23
  So this uses the same wavelength, but it uses, instead of just a single transducer
• 2:27
  that you might put on somebody's heart, it uses 1,024 transducers, like I said, lined
• 2:32
  on a helmet that are each sending a little bit of energy that at the focal point
• 2:38
  accumulates to a large amount of energy at the, motor nucleus of the thalamus.
• 2:45
  And where all of the ultrasound energy comes together at the focal point,
• 2:49
  thus the focused part of focused ultrasound, you create an increase
• 2:54
  in temperature to about the mid 50 degrees Celsius held for a few seconds.
• 2:59
  That creates a lesion, an ablation in the brain that completely dis-disrupts,
• 3:03
  the tremor circuitry there.
• 3:05
  And so, practically speaking, a candidate for focused
• 3:08
  ultrasound comes to the office.
• 3:11
  They undergo two imaging modalities to, discern whether or not they're an
• 3:15
  appropriate candidate for this therapy, a CT scan and an MRI of their brain.
• 3:21
  The MRI of the brain is what I use to identify the region in the thalamus that
• 3:25
  we want to target the ultrasound waves to.
• 3:27
  The CT scan is used to assess the geometry of the individual's skulls.
• 3:32
  About 15% of people in North America will have a skull that absorbs or reflects
• 3:38
  so much of the ultrasound energy that I can't get enough to the brain to
• 3:41
  cause the temperature increase to cause the change that we're looking for.
• 3:44
  So this is a screening tool, that I'm able to use before the person
• 3:49
  goes into the scanner to know just the physics of the machine.
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  Will the physics of this person's skull, the geometry of their skull
• 3:56
  allow enough energy to pass through to achieve the target temperature that we
• 4:00
  need in order to, reduce their tremor?
• 4:03
  So when they come to clinic, we get those two images.
• 4:06
  I run the CT scan through a computational model, and this is true,
• 4:09
  this isn't specific to UF Health.
• 4:10
  This is anywhere in the country that you go for focused ultrasound,
• 4:13
  people are running the exact same, computational model.
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  It's part of the manufacturer's software package, and it, basically
• 4:21
  calculates a number, above which we can give the energy, to a sufficient
• 4:26
  degree to raise the temperature and below which, the skull will absorb
• 4:30
  or reflect too much of the energy.
• 4:32
  So that's sort of a little bit of nuts and bolts, but if you'd like, I can take
• 4:35
  you through, the treatment day itself.
• 4:38
  Melanie (Host): Before you get into the day of, when we think of focused
• 4:43
  ultrasound and how it first gained national attention in the treatment
• 4:46
  of essential tremor as you're speaking about, what made tremor such an ideal
• 4:51
  early application for this technology?
• 4:54
  Justin D Hilliard, MD: That's a great question, Melanie.
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  You know, one of the aspects of tremor that made this a good application,
• 5:00
  early on is that it's something that is immediately noticeable.
• 5:04
  So, when I'm talking about giving energy first, usually takes between
• 5:08
  four to eight doses of energy in order to reduce the tremor.
• 5:10
  Well, I'm not turning the machine on full blast to begin with.
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  First, I'm starting off on real low doses of energy, and I can observe in real
• 5:19
  time between doses of energy whether their tremor is getting better or not,
• 5:22
  or whether I might be, the patient might be experiencing a side effect.
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  And so the immediacy of the patient's symptoms in someone with tremor is part
• 5:33
  of what made it a good first disease to be able to treat with ultrasound technology.
• 5:40
  Melanie (Host): So once you've done your patient selection and assumed that
• 5:44
  criteria, walk us through that day.
• 5:47
  Justin D Hilliard, MD: So, on the day of the procedure, the patient and I,
• 5:49
  we would meet in the preoperative area.
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  And the first step that I have to do, or anyone who's doing focused ultrasound,
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  I have to do a complete head shave.
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  And it's not my preference again, this is universally done.
• 5:59
  But the reason is because the ultrasound waves can reflect off the
• 6:03
  hair in a manner that's unpredictable.
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  And we need to be able to precisely predict where those
• 6:08
  ultrasound waves are gonna end up.
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  So shave the head, and then we need a, a way to keep the patient's
• 6:13
  head still during the procedure.
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  So that's done by placing the patient in a frame.
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  The frame is held in place with four pins.
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  Prior to placing those pins, I give four injections of numbing medicine.
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  It stings for a minute or two.
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  We all know what that's like.
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  Gets nice and numb, and then they have the frame in place.
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  As you mentioned, Melanie, it's called focused ultrasound, but it's done
• 6:33
  in conjunction with an MRI machine.
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  So we go to the r- room where we have the MRI machine, we have
• 6:37
  the focused ultrasound unit.
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  We lay the patient down on the MRI table, get them padded under their knees,
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  under their shoulders, under their neck.
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  The head frame that I just placed attaches directly to the MRI table,
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  and then the ultrasound unit, it looks like a helmet, and it comes down and
• 6:52
  connects to the head frame that I placed.
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  The patient goes into the MRI machine.
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  I get an image And then I start to deliver the energy.
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  Again, four to eight doses, 20 seconds each generally, each dose a
• 7:05
  little bit higher than the last dose.
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  And the patient typically will experience a headache or a spinning
• 7:10
  sensation as I'm giving that energy.
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  Between doses, I'm evaluating the patient, seeing their tremor improve, sometimes
• 7:17
  making minor adjustments to where I've targeted based on the, MRI and based
• 7:23
  on the patient's feedback on how their symptoms are improving or whether they're
• 7:27
  experiencing any side effects before I turn the machine all the way up, so to
• 7:31
  speak, to deliver that final dose of energy that creates the permanent, change.
• 7:36
  Once that's completed, you're looking at about 60 to 90 minutes in total.
• 7:40
  we get the patient out of the head ring to the recovery area.
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  They spend about 30 minutes there before they're ready to leave the hospital.
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  The following day, I get an MRI to evaluate how their brain is reacting
• 7:52
  to what we just did, and that sort of dovetails into side effects and recovery
• 7:56
  that I can talk about if you'd like.
• 7:58
  Melanie (Host): let's speak about recovery and, for patients with
• 8:01
  medication refractory tremor.
• 8:03
  How do the outcomes compare, Dr.
• 8:04
  Hillyard, with more traditional interventions like deep brain stimulation?
• 8:10
  Justin D Hilliard, MD: definitely wanna get into that.
• 8:11
  For thoroughness, let me talk about recovery, and then I'll
• 8:14
  pivot and, I'll make a comparison to deep brain stimulation or DBS.
• 8:18
  So we're targeting a four-millimeter spot in the brain, in the thalamus
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  and, and the brain, that part's gonna be permanently changed.
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  It's gonna be ablated.
• 8:27
  The surrounding brain tissue is gonna be irritated.
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  You're gonna get some cerebral edema around, the lesional site, and that
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  edema impacts normal regions of the brain that affect other functions.
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  There are four domains that are commonly impacted: speech, dysarthria,
• 8:42
  and some word-finding difficulties.
• 8:45
  sensation, numbness, tingling, paresthesias, rarely a change in taste.
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  Coordination, clumsiness with the hand, and then balance, feeling
• 8:55
  like the person's leaning to one side or that they don't have,
• 8:59
  quite as good power in their leg.
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  The edema is at its worst within the first week, and then it
• 9:04
  begins to slowly dissipate.
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  Takes about two to three months for the edema to resolve entirely.
• 9:10
  About 10% of patients will have a mild to moderate permanent side
• 9:13
  effect, 90% no permanent side effect.
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  You can't get anyone through the procedure without a temporary side effect.
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  If you're doing it right and you're creating a durable lesion, the surrounding
• 9:24
  brain, it's gonna react to what you did.
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  So I tell patients I want them to have a cane, potentially even a
• 9:29
  walker available for their balance.
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  I don't want to turn a good outcome of tremor relief into a new problem,
• 9:34
  a broken hip, you know, a subdural hematoma hitting their head, et cetera.
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  if you counsel patients correctly, which I try to do, I try to emphasize the
• 9:41
  recovery aspect, people know what to expect, and they're, and they're safe.
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  And it's, it's okay that there's a recovery.
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  There are with most things in medicine, right?
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  You have a knee replacement, it's no surprise that you're gonna be
• 9:51
  using a walker for a couple weeks.
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  You know, you have cataract surgery, it's no surprise that, you might need
• 9:57
  to, keep your eye covered or something like that for a period of time.
• 10:00
  So if people know what to expect, then, the recovery is generally smooth.
• 10:05
  Comparing outcomes to deep brain stimulation, I do both.
• 10:09
  I do focused ultrasound, and I do deep brain stimulation.
• 10:12
  And so whenever I'm seeing a patient, I'm thinking about which one should I do?
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  Which one do I think would be best for this patient?
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  And there are a number of considerations between that that we can get
• 10:21
  into, but focusing on outcomes.
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  Deep brain stimulation, it's the gold standard for
• 10:27
  treatment of essential tremor.
• 10:29
  Focused ultrasound, it's a great therapy, but DBS is the gold standard.
• 10:33
  Why?
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  Because of the flexibility, that it provides over time, being able
• 10:37
  to increase the stimulation and kind of keep up with the tremor.
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  Generally speaking, you're looking at about an 80% to 90%
• 10:44
  reduction in tremor with DBS.
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  With focused ultrasound, it's right there with it.
• 10:48
  It's about 70% to 80%, okay?
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  So about 10% less.
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  When you look at durability five years out with focused ultrasound,
• 10:56
  it wanes to about a 45% reduction.
• 10:59
  With DBS, it hangs in there a little bit better.
• 11:02
  You're, you're around 60% to 70% out at five years.
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  So somebody who's relatively young, relatively healthy, I would steer them
• 11:11
  toward deep brain stimulation or DBS.
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  For somebody who's older, maybe getting into their late 70s, 80s, even 90s,
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  I've treated patients with focused ultrasound, that's the more ideal therapy.
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  Less surgical risk, no risk of infection.
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  You're not worried about wound healing, outpatient procedure,
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  no general anesthesia.
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  Somebody with a multitude of medical comorbidities, maybe they've had, uh,
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  multiple heart attacks, maybe they have stents in place, maybe they're diabetic.
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  that may be somebody that I'm less inclined to do DBS on because the,
• 11:45
  the risk of surgical complication.
• 11:47
  Melanie (Host): Well, thank you for explaining that.
• 11:50
  Now, Dr.
• 11:51
  Hillyard, as exciting as this is, we're seeing these applications
• 11:54
  expanding into Parkinson's disease, other movement disorders, even
• 12:00
  possibly over the next several years, psychiatric disease, epilepsy.
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  I mean, they're talking about this for so many indications.
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  Where's the field headed?
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  What are the most promising indications that you would be most excited about?
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  Justin D Hilliard, MD: absolutely right, Melanie.
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  The, the, the future is quite bright for the utility of focused ultrasound
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  in a host of, diseases beyond movement disorders, like you mentioned, including
• 12:26
  epilepsy and, I'm gonna pivot for a minute and make a distinction between
• 12:31
  something called high-intensity focused ultrasound, which is what
• 12:33
  you and I have been talking about, and low-intensity focused ultrasound.
• 12:37
  So some of the most exciting research that I think is-- that's on the
• 12:41
  horizon and that UF is participating in, is the use of low-intensity
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  focused ultrasound to disrupt what's called the blood-brain barrier.
• 12:49
  That's, uh, a protective mechanism that our body has to shield our
• 12:55
  brain from chemicals and substances that might get into our blood.
• 12:59
  But with certain diseases, we want to disrupt the blood-brain barrier so
• 13:04
  that we can preferentially deliver an immunologic therapy or a pharmaceutical
• 13:09
  therapy and deposit a high concentration of that drug in a specific brain region.
• 13:13
  For example, in Alzheimer's disease, there are several exciting immunologic,
• 13:18
  therapies right now that have shown some promise, but it's hard to get
• 13:22
  the concentration of that medicine in the particular areas of the brain,
• 13:26
  that you need to create a big effect.
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  You can take a patient, potentially, this is the research that's being done,
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  the hypothesis, you could take a patient to low-intensity focused ultrasound.
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  It's a different frequency of ultrasound waves.
• 13:40
  It disrupts the blood-brain barrier temporarily for about 24 hours.
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  As soon as you disrupt it, you co-administer an immunologic, and it has
• 13:50
  the potential to preferentially deposit in the region of the brain that you
• 13:53
  just disrupted the blood-brain barrier.
• 13:55
  This is the area that I am perhaps most excited about in terms of evolving
• 14:00
  indications, but I think we're a couple years out, from things like that.
• 14:05
  Melanie (Host): Wow.
• 14:05
  So Dr.
• 14:06
  Hilliard, this really changes the concept of what surgery can look like.
• 14:10
  And for other neurosurgeons and even referring physicians, how has this
• 14:17
  technology altered the way you're thinking about interventions in the
• 14:21
  brain, and where do you see this headed in the next five to 10 years?
• 14:26
  Justin D Hilliard, MD: some of the things that I'm excited about, other areas of
• 14:28
  research that might be, you know, within the timeline of five to 10 years out
• 14:33
  are things like incisionless biopsies.
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  So for a neurosurgeon, some of the most treacherous biopsies that we have to
• 14:40
  do are deep-seated lesions in the brain that are relatively inaccessible and
• 14:45
  high risk, where we have to drill a hole, insert a cannula several inches
• 14:51
  through normal brain before we get to the brain tumor or the lesion that
• 14:55
  we're worried about is a brain tumor.
• 14:58
  And, inserting that cannula, that little, piece of metal to, to, uh,
• 15:02
  get a biopsy, we can cause a hemorrhage and can cause somebody who has a
• 15:06
  bad problem and make it even worse.
• 15:09
  With low-intensity focused ultrasound, there's potential to disrupt the
• 15:12
  blood-brain barrier around these tumor cells or this, you know, deep-seated
• 15:16
  lesion in the brain, which would hypothetically allow some of the DNA of
• 15:21
  that tumor to leak into the bloodstream that you could then do a peripheral
• 15:25
  blood draw, analyze fragments of the tumor DNA from that blood work,
• 15:32
  and be able to tell the patient, "This is the type of tumor you have.
• 15:35
  Here are its mutations.
• 15:36
  Here's how we're gonna treat it," without ever having to make an incision.
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  that's probably the area that I, would be most excited about in terms of changing
• 15:45
  how we're treating, people currently.
• 15:49
  I don't think focused ultrasound is gonna replace things
• 15:51
  like deep brain stimulation.
• 15:52
  There's, again, I, I think DBS, it's the gold standard for the treatment of
• 15:56
  many movement disorders and so forth.
• 15:59
  But for the right patient, focused ultrasound is, is a phenomenal therapy.
• 16:04
  Melanie (Host): Well, it certainly sounds like that.
• 16:06
  And Dr.
• 16:06
  Hillyard, as we wrap up, for referring physicians, what's most
• 16:11
  important for them to understand about when to consider referral
• 16:14
  for focused ultrasound evaluation?
• 16:17
  Justin D Hilliard, MD: so right now, I am using focused ultrasound for
• 16:21
  the treatment of essential tremor.
• 16:23
  So we've talked about some exciting things, Melanie, and
• 16:25
  but I think it is best suited for essential tremor, and that's what
• 16:28
  its FDA, labeled for right now.
• 16:30
  It also has an FDA label for Parkinson's disease, but I, I h-
• 16:34
  vast, vast majority of patients, I think, are still better served with
• 16:37
  DBS who have Parkinson's disease.
• 16:38
  So for referring physicians who have essential tremor patients, it's important
• 16:43
  that they've failed medical management.
• 16:45
  That is defined as failure of two first-line medical agents like
• 16:50
  primidone or propranolol, who are having a tremor that is significantly
• 16:55
  impairing their quality of life, their ability to feed themselves,
• 16:58
  to, to drink from a cup, to, write.
• 17:03
  I don't expect my primary care colleagues to understand the nuances of, you
• 17:09
  know, movement disorders, neurology.
• 17:12
  So if, if you have a patient that you've tried a couple of medications
• 17:15
  on and they failed, I'm happy to review the referral and, and to evaluate
• 17:20
  the patient here at UF and help, you know, partner with you to see if the
• 17:24
  patient would be a reasonable focused ultrasound candidate or, potentially
• 17:29
  a deep brain stimulation candidate.
• 17:31
  A lot of people are afraid of brain surgery, Melanie, and when they have
• 17:34
  an opportunity to come and meet our team here under the, you headline
• 17:38
  of focused ultrasound, they realize, "Hey, actually, when I've heard some
• 17:42
  of the relative advantages of DBS, maybe that's not such a bad way to go."
• 17:46
  And so anyone that I'm receiving in the office, I'm trying to think
• 17:50
  about what is the modality that's best, to treat this patient.
• 17:55
  Melanie (Host): Great information.
• 17:56
  Dr.
• 17:57
  Hillyard, thank you so much for joining us today and really sharing your incredible
• 18:02
  expertise on this amazing technology.
• 18:04
  Thank you again.
• 18:06
  And to learn more about this and other healthcare topics at UF
• 18:09
  Health Shands Hospital, please visit innovation.ufhealth.org.
• 18:13
  And to listen to more podcasts from our experts, please
• 18:16
  visit ufhealth.org/medmatters.
• 18:19
  That concludes today's episode of UF Health MedEdCast with
• 18:23
  UF Health Shands Hospital.
• 18:24
  I'm Melanie Cole.