Chapters Transcript Video High Intensity Focused Ultrasound (HIFU) & Essential Tremor All right, we're gonna get started. Is that OK? Everybody ready? All right. So, first of all, thank you for, thank you for coming today. We're going to talk about focus ultrasound. That's we're going to talk briefly about its history, even though it's a new technology. It has been used for other applications. In the past. We'll briefly go over the history of focus ultrasound. We'll talk about two different kinds of focus ultrasound, the high intensity focus ultrasound, which is the main clinical ultrasound. Now we use in neurosurgery and we'll talk about the low intensity focused ultrasound and its potential research and clinical applications. Um I don't have any conflict of interest to disclose in inside is the parent company. They haven't reviewed my presentation. I'm an assistant professor here at us F and Tapa General. We have three functional neurosurgeons. Uh I'm the youngest one recently hired. We have Doctor Beli here with us and we have Professor Smith who was, who is not here with us today. So just to start with the bottom line, uh give you the, the, the summary of the presentation, what we'll be talking about if we get this idea that means we get the whole presentation. First, we're going to talk about that. Lesions in the brain have been used to treat all sorts of neurologic disorders, including essential tremor and Parkinson's disease. We will talk about focused ultrasound. The high intensity low intensity ultrasound, the high intensity ultrasound will deliver high energy ultrasonic beams to a focused area in the brain which can create a lesion. Whereas the low intensity ultrasound creates a micro bubble that is stable and that can be used for all sorts of investigations that will be going, going over briefly. And for now, the high intensity focus ultrasound or HAI is FDA approved for select movement disorders such as essential tremor and Parkinson's disease. So right now, by far, the cases that we do mostly are essential tremor or tremor dominant Parkinson's disease. However, it is approved for Parkinson's disease as well. Not only tremor dominant Parkinson's disease, however, the general Parkinson's disease umbrella is not fully approved by insurance companies yet. So as an outline, we'll start off first with the physical principles of focused ultrasound. We'll talk about the history of ultrasound and the timeline of both the high intensity and the low intensity focus ultrasound. So Hau and Liu, we'll go over the clinical applications, some FDA approved treatments, some investigational treatments. Uh We'll talk about the clinical results, what we expect. We'll discuss the workflow of the day of surgery. We show a few representative cases that we've done here at us F at TG. And we'll end up with a summary. So to understand the difference between high food and food, we need to quickly go over the concept of micro bubble formation, cavitation. As I said, there are two types of two broad categories and it depends on the intensity of the ultrasound wave. So we have the high intensity, the micro bubbles tend to expand and collapse at a certain frequency that can increase friction, generate increased temperature and can cause localized tissue damage or lesioning. Whereas the low intensity focused ultrasound, the micro bubbles are more benign and they can be manipulated to do all sorts of applications that we will discuss. Now in high intensity focused ultrasound. The way I present it to patients is it's much similar to when we were kids, we used to walk around with the lens and try to heat up a leaf when whereby one sun beam is harmless. But if you converge enough of them onto a focal point, you can burn a leaf. And it's very similar in principle to focused ultrasound. If we are able to converge all the ultrasonic waves onto a one point, we can cause an increase in temperature that can be controlled with MRI thermography, this can cause tissue coagulation protein denaturation and it can occur within seconds. This is a representative diagram it can show here in the upper panel demonstration where there is a schematic illustration of stable micro bubble expansion and contraction. And you can see that the micro bubble can tend to expand on contract depending on the phase of the ultrasonic wave. So not only do we have to converge the ultrasound on to a point, but we have to also synchronize the phase of every single beam. And we typically on average say we deliver somewhere around 1000 beam and depend on the amplitude of that fluctuation. We will able to heat up the tissue or control that movement of the micro bubbles to do whatever application we want. Now, if we do it too much, we can have a phenomenon where it can collapse very violently and it can cause tissue damage beyond what we can control. So it's a fine art between creating the micro bubble in the area we want and controlling it expansion and contraction and its subsequent temperature change in order to either create a lesion that's permanent or a transient lesion for testing or brain mapping or to do other applications such as shake up the blood brain barrier or other stuff that we'll talk about later. So, so first, I'm going to talk about the timeline of each starting with Hai. So in terms of history and background, we'll talk about how, how it early started early with animal experiments, how it transitions to humans early on and what's the state of the, the the technology right now? No, I think from my understand, I'm not a physics. But my understanding it's from the dissolved dissolved nitrogen or dissolved air that is in the blood, you inject them and you have different types of, depending on what you need as far as the injection of the micro. Well, as far as those some are nodes uh one type of uh ran. So it's at the 220 kilohertz. Um Yeah, we will show you a few, a few, a few slides, I'll show you. So this is a presentation. So in 1942 Lynn and Putnam uh noted that high frequency short wavelength ultrasound waves can deliver high sonic energy to specific areas of the brain with minimal destruction of surrounding tissue. And they tested it on 37 animals where they delivered hai to different regions of the brain. And they, and they realized that you can create both reversible and irreversible clinical effect. And then subsequently, as you can see here on pathological examination, it showed instantaneous and well consed lesions which you can see here on the right panel on the left panel, it's not, it's not really clear, but it's a picture from 1942. You can see a cat with, with its head inside an ultrasonic transducer. And this is the pathology slide of the cortex of the cat. You can see a very sharp line delineating where the lesion was created. Now during that time period, Will William Fry, who was a physicist at the University of Illinois. Uh he had a strong interest in biophysical research. And during World war two, he worked on the design of ultrasound transducer at the naval uh uh naval lab, Underwater Sound Division in uh in DC. And his ultrasound device included four trans user systems which you can see here in the picture which focused high intensity acoustic beams into an animal and produced a pinpoint lesion without damage to the surrounding tissue. You can see William Fry here in the picture. He passed away at the age of 57 I think from a heart attack. Now, interestingly, his brother Francis Fry and they both worked together early in the 19 fifties and demonstrated that Hai could be used after a craniotomy is made to target, to target deep seated areas in primate brain. Fry also demonstrated a video of high mediated lesioning in a cat brain at the American Association of Neurologic Surgeon back in 1968. That's a picture of him receiving an award at the Society of Therapeutic Ultrasound 20 years ago. Now, Peter Aaron Lindstrom is a Swedish neurosurgeon who in 1954 studied the effects of high food mediated lesioning as an alternative to lobotomy back then, which he used for a variety of neurologic disorders. Whether it's cancer related pain, psycho neurosis, anxiety, depression, or epilepsy. Back then, they used to do the lobotomies either through the nose or it was a very crude procedure that they used to do and he realized maybe if he was, if we were able to avoid penetrating the skull or the dura, he'll be able to avoid those big side effects that they used to see back then. And they also did autopsies on 14 of the 15 patients who had died of cancer subsequently. And they had a satisfactory lobotomy procedure at the time from the focus ultrasound. And they realized also there is minimal disruption to the brain outside the target area. So this was very early on in 1954. Now, in 1950 another famous neurosurgeon Lars Leel, a Swedish neurosurgeon scientist, he designed a specifically adapted frame and ultrasound transducer which you see here on the left picture for the purpose of lesioning. Uh As you, as you can imagine at that time, he realized that it had a lot of limitations. One, it's because he realized it has low accuracy and targeted deep c lesioning. They didn't have good imaging at the time and you needed a craniotomy since the ultrasound beam could not permit visualization through an intact skull. So whoever had to undergo this procedure had to have their bone flap removed to create a window for the ultrasonic wave to go through. And yeah, they had, they didn't have reliable imaging tools at the time. Uh So in order so very impressively, he, he invented the gamma pro se for brain tumors that we still use today. Now, the high intensity ultrasound was found safe for the destruction of brain tumors. These treatments were performed after a creamy through the skin which was placed over the ultrasound window. You can see here on the left panel, a schematic showing the ultrasound wave being generated through the transducer penetrating through the skull window to destroy a tumor, for example. And to the right is a drawing demonstrated Cren we all know what the cran is. I think now going on with the technology up to the 19, late 19 nineties, completely non invasive focus ultra town treatment was realized consisting of a head mounted set of phase a a transducer operating on the real time MRI guidance. So that that did change the game a lot and the software was used at the time also to incorporate to be incorporated in the procedure itself, you know, in order to rectify problems with, you know, with targeting or inaccuracies and to allow phase aberrations due to the skull thickness. So precluding the need to perform a cran simultaneous Mr Thermometry therefore provided real time temperature monitoring during the procedure which enabled the confirmation of the target zone before Li Xiling was performed. And this is pretty much what we do today. So as a timeline, we started off with the animal experiment moved to human with a cry and now we can do it without a cran, we still have to shave the hair at this time. Now, six years ago, it was approved for essential tremor. So vim thalamus, this is probably the largest volume that we do for focus ultrasound. Two years ago, it was approved for Parkinson's disease that is tremor dominant. So same target V I am thalamus for tremor dominant Parkinson's disease. And last year it got approved for unilateral palay for Parkinson's in general. Good candidates for someone for unilateral palay. Ideally, you want them to have asymmetric presentation so that the drug management is easy afterwards. And it's still not approved by insurance company companies here in Florida. Yet we believe hopefully probably by the end of the year, I'd say it would be approved for unilateral pat. Moving on timeline for the low intensity focus ultrasound. This is still an investigational technique at this time. The question is how is it different from the high intensity focus ultrasound? So we spoke about this very briefly. So at the present time, life or low intensity focus ultrasound is being used for a wide array of applications which include, but it's not limited to opening of the blood brain barrier by delivering pulse, ultrasound, micro bubble, enriched cerebral vasculature. You can use that for drug delivery to deliver specific drug to a specific area in the brain. Or if you want to help in the expulsion of toxic substances from the brain such as toxic protein generated by the brain itself under certain neurodegenerative conditions. And there are other investigational applications exist as well. We will probably not discuss in detail. Yes. Yes. People are using it for tumors. So, so what you can do is you can use it. You can use it in combination with high intensity to kill some cells and release DNA material into the blood stream. And then you can collect that blood sample and diagnose the tumor. We call it liquid biopsy. Actually where I trained in Canada, they do it so that can be used potentially, I don't know about TV. But I don't see why not. There are other places you can create a small hole to allow communication if you have obstructive, I think. So a spine is a little bit more difficult at this time because of the way you position the transducer and the way you seal the water over the head. But I don't see why not. I don't see why not. Like down the line. We're also using a her prostate right now. Um So to enable, to help, potentially treat us work, I mean, that would be amazing if you, I I'm pretty sure I talk about it as a corporation. Take this um our two game, right? There's so many people are using it. For example, you can open the blood brain barrier reversibly over a few hours, almost, I mean, less than 24 hours. And you can give chemotherapy, not necessarily at the high dose that we usually give and it would go selectively to areas more than others where you open the blood brain barrier. And some people say if you have a neuro degenerative disease or some some disease secondary to the theoretical collection of abnormal protein, you can use that technology to help clear out those proteins as well. Yeah, we already use that therapy. Would it be more whole brain or could you target a, you usually target the target the area you want? Uh There is no limitation how large it is in theory, but usually you target the area you want, you can give it IV and it can reach the whole brain, but it will penetrate preferentially to the area you want. You could have a thing that went to the track like the stereo tactic kind of, right. So, um we, we've been doing this for a few years job now, held places around the country and right now it's big for. So basically, you know, briefly the, you know, micro bubbles, we lock their head into the frame, the frame on the table for the chance to serve of their head. And then we just use those beams at the low frequency. We just kind of go around the tumor, it opens up the blood vessels all the way around the tumor. Um I think we've done anywhere from 240 CCS to 560 CCS at the moment. So, uh the more we open, the more effective we're gonna be and then there's about a 68 hour window of where we can go ahead and deliver the chemotherapy for the GB M, you know, when you close itself off measuring progress since then. So yeah, it is, we'll be hearing more about it in the next upcoming year. So let's work on this slide. OK. Uh So for focused ultrasound brain applications, I mean, right now, mostly we use it for functional applications, essential tremor, Parkinson's disease, you can use it for brain tumors, metastasis. There are literature about verma gliomas, pituitary Anoma, acoustic neuroma mening. There are some research for epilepsy, amygdala, hippo campy cortical ablation. I don't see why not. It should be very straightforward. Thom is also for epilepsy, tragal neural psychiatric disorders, neuropathic pain, vascular, you know, intracerebral hemorrhage, we will show a few examples, acute ischemic stroke. In theory, you can shrink instead of doing like a like a massive MC A. In fact, you can shrink a part of the brain so that they can avoid Amiran toy, you can hit part of the brain and shrink it gradually before, before the malignant edema kicks in. Um and and other applications, we spoke about targeted drug delivery, blood main barrier opening, hydrocephalus, lamina terminalis, it might be easier than 33 colostomy. Technically for surgery. If you want to target it either endoscopically or, or you know, or stereo tactically, it's harder to access the lamina terminalis. But with focus ultrasound, it's, it's safer because you don't have the, the Basar artery, you don't have the stock, you don't have those structures very close and it's a bigger, bigger area that you can, you can target safely as compared to the third ventricular floor that is moving as well. So that's another application or, or even if you have obstructive hydrocephalus on one vento call, you can do fest of the polo in theory using this technology without an endoscopic procedure. Now, let's compare the advantages of focus ultrasound against standard techniques. So, so let's say for for functional procedure, let's say someone comes in with bad tremor, we have multiple ways we can do it and our team is trained to do to do it in all the ways actually. So we have D BS, we have, we can stick a probe in and do a small lesion with a probe and then take the probe out or we can do stereo tactic radio surgery and create a lesion. And we have focus ultrasound and what are the advantages of focus ultrasound? It first, you need one session, you can achieve, you can achieve results immediately. So you can get immediate clinical benefit, which typically you don't see with SRS, it usually takes time to build up. You have greater precision and accuracy compared to SRS, you can create very sharp margin as opposed to those hazy margins that we see with our ablation. You have real time radiologic evaluation of the thermal lesioning using MRI and it's very accurate it's non invasive or I'd say less invasive. There is no electrode insertion, there's no IP G, there's no generators, extension cables, no secondary tumors, mening with stereotatic radio surgery. And there's in theory, no limitation on the lesion size. What are the disadvantages? Well, disadvantages, let's say for a disease like tremor, essential tremor or Parkinson's that what I tell my patients is, well as the disease progress D BS is able to accommodate that and you're able to manipulate the treatment as needed. Whereas with focus ultrasound, it's a single session thing. Uh So these are the useful summary of the useful mechanism, you know, tissue ablation, thermal ablation drug delivery, you can dissolve clots. So let's say you have a large in inter hemorrhage, there are a lot of centers. What they're doing is research research protocols where they're trying to break down the clot and then aspirated it through a small, small catheter rather than doing those, you know, craniotomies, cran or brain path procedures. You just even for brain path, it's very nice because when you're doing a a tubular procedure, sometimes the clot is too thick and adherent to the tissue. It's, it's a very challenging procedure to do. Uh uh but this could potentially break it down and make it more fluid. So you can aspirate it through a small catheter. Yeah. Uh There are some work on radiation sensitization, drug enhancement. You can coagulate blood vessels like small caroms. There are some studies that have done that uh immune modulation neuromodulation. So you can, you can deliver a treatment that can change function. Uh whether whether or not you create a lesion. Very similar. The non lesion literature might be very similar in principle to the transcranial magnetic stimulation. They can come in for multiple sessions and it can create some changes in the neuron network circuitry and it can cause basal dilation that you can use for other purposes. So these are essentially a brief idea about the principles of focus ultrasound and a brief idea about the timeline where we were and where we are, the high intensity started much earlier than the low intensity. And now it is being used clinically. Whereas the low intensity seems to have a more diverse clinical application and it's more like in its infancy right now. So uh clinical application and essential tremor, we first start with the most common clinical application of of and that is for essential tremor. So as we know, essential tremor is the most common movement disorder. It affects approximately 4%. I say 4% of the population about 40. It's an easy number to remember. And it's characterized as we know by postural and intentional tremor around 8 to 12 Hertz. That's what the books say. Say every time I measure it in clinic, it's like five Hertz. Uh So I don't know how people distinguish it from Parkinson's tremor. Uh uh objectively. Uh it seems to overlap a lot in my, in my experience. Um and the primary treatment is usually medication, it's either, you know, primo or propranolol and medication can treat at least 50% of patients with essential tremor. They will never require any additional procedure and they are happy people. Now, surgical treatment was usually targeting the VM nucleus of the thalamus can be considered if someone is intractable to medical treatment. So treatment options for essential tremor, we have better blockers such as and propranolol. The more effective one is primidone, which is essentially an anti seizure medication, an old anti seizure medication. And there are some anti anxiety medications that can help keeping in mind that anxiety itself can you increase the tremor. And there are surgical intervention, we know DB can mitigate tremor. Now we know focus ultrasound is very effective. I'll show a few examples, we can do a radio frequency tham put a probe in and the probe can usually typically has a temperature probe in it. So we can monitor the temperature but we cannot monitor the spread of the temperature. How far the temperature is spreading, which we can in focus ultrasound and stereo tactic. Radio surgery is also a very effective way to do it. And there are some wearable devices that you can use. This is the color I don't have a lot of experience. Some patients tell me that they tried it by the time they see me, they said it's not working anymore. So I have kind of a biased window that it doesn't work. But there are a lot of patients that I don't see, they never come to my clinic. So I don't know how efficacious this device is and I don't know much about it. To be honest, I know it can vibrate a little bit. I don't know, like stimulate, I don't know how it works. Ok. So for essential tremor, those are the earliest pilot studies where they used Mr guided focused ultrasound temo and those were as early as 2013. There was one proof of concept study. The the that came off the of the the first author is from Toronto from the institute where I worked at. Uh and uh they were able to show at the time 81% reduction in tremor in the dominant hand and 51 reduction in functional uh disability uh as measured by the clinical rating scale for tremor. And that was three months after surgery and that was very early on. So very early on, it was, it was uh it was a successful treatment. Now, later on another study came out where they studied 15 patients and demonstrated the improvement in a tremor, 75% and functional disability by 85. And that's after 12 months. So as people gain more and more experience, it appears that that the tremor control was getting better and better over time from a disability scale, I believe. Now it's probably the numbers are very much close to the RF lesioning and it's all based on how big the lesion can be made safely while still preserving function. So what are the reported adverse effect? So, you know, people can experience numbness or paraesthesia. If the lesion is a little bit poster in the thalamus, you'll be targeting the sensory thalamus. You can have ataxia, you can have taste disturbance, you can have headache, especially from the frame placement. You can have gate disturbance. That's very common. I say to my patients, 1 to 2, 3rd of patients will experience some gate disturbance after ultrasound, especially the 1st and 2nd day after the procedure when the swelling kicks in and it usually dissipates two weeks after the procedure. Vast majority, I'd say maybe 90% of patients, but some patients can have ga disturbances that are persistent afterwards. You can have muscle weakness. If the lesion is not in the right spot, it's very close to the corticospinal tract. So it can cause muscle weakness and it can cause dizziness. And this is what the lesion looks like on MRI. You see post of day one, it's very sharp on post of day seven as the swelling kicks in, it becomes hazy and a month later, it becomes a very sharp cigar shaped lesion council. And this is a very busy slide. I don't know if you can see it. So, so these are these are, you know, the the the various studies that have been ongoing. So people have been using it for thal for tremor. Most of them are thalamotomy, paly, doomy, omy capsulotomy for neuropsychiatric disorder, central lateral Thom tumor ablation and thrombolysis as well. Now, who is suitable for the treatment at least at this time, usually it's confirmed diagnosis of medically refractory, essential tremor or tremor, dominant Parkinson's disease at this time or Parkinson's disease. keeping in mind that we can only do unilateral palay and it's still not approved by insurance. So there's an asterisk to that patients should be 22 years or older for essential tremor or 30 years or older for tremor dominant Parkinson's disease. And they should be able to tolerate the procedure with or without some form of sedation. Of course, they should be able to communicate with us during the procedure. We have to test before we lesion. I'll come to that shortly. And of course, they can fit, they should fit an MRI scanner and they should be able to activate the stop button. Now, the contra indications, uh you know, uh if someone has a device that's not M I compatible right now, patients with DB SI don't offer them focused ultrasound. I don't know if anybody can do it if they have D BS lead on one side. If their skull density is not favorable, it's rare, but it can happen, then we cannot offer them the treatment we want the skull to be uniform. It's my understanding. It's, it's, it's how, how dense the, the skull is compared to the surface area. Is that right? What's? Yeah. So it's uh it's a calculation of someone's coral skull thickness over their thickness, bone marrow pen thickness based on their hand units on AC T scan. So it basically the, the bone marrow Gonzalez phone, if that ratio is low point point five or in Florida, it would be 0.4 then they wouldn't be you. Well, you're applying 1000 over the entire head. So, so, so we're not doing one, we're doing like, you know, 1000 beam all over the head. It's a good question like those caps the salon. Yeah. And it's kind of like that the head close with a membrane that attract the water. So you was compensating for the fact that the strength of the ultrasound of survive by ratio or by you want it to be uniform because if it's not uniform, if it's not uniform, the calculation of the phases and the deflection of the ultrasound is going to be more complicated. Ideally, you want to dense and thin or dense, the more you can sell a bone, the more you have that can sell a bone in the middle, the less this called density ratio, the less predictable where that beam is going to go. And you have thousands of these beams come from here down to the target. And so the reason why you're shaving people bald is so you don't have we as part of that, that pathway and then you go to the skin and the scalp and then if there's too much intervention in the bone, then all the calculations are going to be thrown off and you won't get them. Ultrasound means in the same phase of that particular target. So, what percent of patients I think it's, I think it's very small. I mean, I've seen maybe one or two where we cancel it. Not here, not yet here. I mean, we've been doing it since April was April our first case last year. April. Yeah. So we've been doing it since April and we haven't had a single cancellation. So um we're doing some things where we're testing like um over in Japan, I think like uh giving patients uh some type of calcium or some type of like increase their thickness that we're working on a lot of different things on site at the moment. Um We don't have anything. The reason why it's so important, I think um they were mentioning is that um the skull in this procedure is actually absorbing 80 to 9% of the energy that is transmitted to a patient. So patients skull actually absorbs pretty much all the energy we're giving. So the thinner and more dense someone's skull is it's just that much easier for the energy to pass through that skull and get to the target and focus when someone has a thicker skull, there's a lot more porus our face fraction. Our accuracy is still good, but we don't get enough of that energy past the skull to actually make a lesion in the brain. That's where this ratio comes in handy for us to be able to tell if a patient is going to have a successful treatment or less likely to. Yeah. Thanks, Kevin. And you know, other, other contra indication if someone is on blood. The typically we, we do a lot, I mean, most of these patients are either extremely sick to undergo DB. So they pretty much everybody is on blood thinners. But if they're unable to stop it, I usually don't offer it. And if they have severe cognitive impairment or dementia, usually I sign up for and if they are severely impaired, I usually don't offer it as well. Um So this is what it looks like on the day of procedure. So the patient comes in, we clip their hair completely. The other challenge with hair is it can trap micro bubbles, small bubbles and that can also affect face distortions and the penetration of the ultrasound wave as I understand it. So we shave their head completely. I know they're working on trying to do it without shaving the hair. But right now we do it is a big deal. I've had one patient cancer because we won't. Yeah, maybe it's not that severe and then we do the planning part, you know, basically the planning part, we're trying to align all these beams together to make sure the beam is aligned and the energy changes are aligned in all orientation, whether it's an A P anterior, posterior media, lateral or the dose of ventral orientation, where we want that lesion precisely to be. And then what we do is we do the testing where we deliver a light dose of energy to the area of interest. And we look whether or not the patient is experiencing side effects, is their speech changing? Are they weak on one side? Are they experiencing numbness in their hands or their face? And if they are based on, on the side effect, we can localize where the lesion is and we can move the target. So once, once we move the target, we do the test lesion and we get good results. Typically, when we do the test lesion, you can see almost significant tremor reduction by up to 90% sometimes arrest, but it is reversible. It can come back within a minute or two. Then we are certain that this is the area we want. And that's to me, a huge plus compared to, you know, you can do that with low temperature. But for stereo tactic, radio surgery, you can do that with and then, and then once, once you're confirmed, everything is confirmed, then you deliver the high energy lesion to create it and then you know, take off the frame and the patient can go home. Yeah. Yeah, it takes about two hours and a half, three hours and then they go home. And this is, this is one of our patients that we did, we did the lesion on. You can see you can see how well circumscribed the lesion is this is immediately post up. You do the measurements precisely in the V I am. This patient did fantastic with excellent right side hand control, tremor control. This is another patient we did here at Tampa General. So we use the brain lab software. Sometimes there are Softwares that you can use where you can reconstruct different objects within the brain. You can reconstruct your thalamus internal capsule, anything you want. And this is the picture on the upper corner. You can see a coronal coronal plane showing the vim thalamus in 3D and the sagittal plane in pink. And then on the on the right side, you see an axle image zoomed in and you can see the vim thalamus on both sides. And you can see the target lesion where the omy was made in the axial plane. And this is what it looks on the sagittal plane on the VM thalamus. And this is what it looks on the coronal plane. The lesion is posted up but the the the reformatting of the object was way post up like many months later, just out of interest, we were testing brain lab. So I just doctor B and I said, why don't we test it on one of one of the patients done? And this is what we had this patient actually, interestingly, she also had, had a neck tremor which were excellent control leg, went away. And she also had like a month or two of ipsilateral tremor control, which is very interesting. So she had tremor on both sides but even the same side tremor got better for a period of time. I mean, we knew that it's not going to be sustained. But it was interesting to see what if you could use something like this to deliver stem cells to stem cells have been studied in functional neurosurg for decades. Um There have been several large studies including some that have involved some of our nursing colleagues here at the University of South Florida. Nothing has at this point despite know, some things have proved analyzing but nothing has, has reached the level of to say or where it's led to some kind of. And doctor in Switzerland did studies with people that traumatic the cells that were damaged and put them back and had a so I'm wondering if these are damaged cells, not stem cells, the damaged cells put them somewhere that you know the right. It's OK. I mean, no, I mean, functional neurosurgery, you know, restorative therapy is a big topic. Have really, you know, some, some of there was another study that looked at um stem cell and plants Stanford. And that one, you develop some tantalizing information and intriguing and then it just kind of never you're not side effect. Something else happens. Unfortunately, despite some really interesting data or data again, it's been like repeatedly. But the problem is that without the proper the micro, they don't have the corporate stimulation they all gonna become. And that's the, just a basic, very basic question. You are using ultra, you're using trans and do just to put things in perspective. What is the frequency? What is the, the magnitude which you're using as do? So when you see you're so used to this. So in terms of magnitude and in terms of, can you give me a perspective of? Yeah. Um I just, I'm, I'm Kevin Cala I've been with for three years. I'm a senior outpace specialist. I work with doctor most of the time here and doctor B um so the high frequency system is 650 Kratz. Um I'm not familiar with the other frequencies of the ultra sounds, but this is what we call our middle to high frequency system. So 650 kilohertz is what allows us to be able to focus the ultrasounds enough where we can get that 4 to 6 millimeter accuracy in something frame um without too much of the sound being absorbed by the spot, that's not our happy medium, anything too low like the 2 20 kilohertz system, all that energy passes through the skull way too easily and you can't focus the lesion on the spot is too big. It's uncontrollable. Anything above 650 kier. You have a more focused lesion, but the skull is absorbing too much of the energy. So you won't be able to transmit through the brain and create a lesion. So that's why we use 600 K in order to be able to have a, have a medium of getting past the skull and creating a nice focus. For the second question I have is such high frequency are design is certainly getting lost on the immediate, we've had nothing, no, no issues with hearing loss at the moment. You cannot get this procedure with the cochlear implants and it has nothing to do with their ability to hear or affecting their hearing. It's just solely because the cochlear implants provide too much artifact for the imaging purposes. So we can no longer really see what we're targeting, but we've had no issues with hearing loss or hearing has has people followed it up like uh I haven't came across but the people test hearing before and after, I mean, I've never heard patients complaining we did back in the day. No one's complained of it. And I thought about 700 of these, I've never had anyone come back to say they've had issues of hearing. So it's never been an issue beyond that you have problems with the practice, but it's almost like they don't even. Yeah, no one's had any issue to it. So, what? So for the topic? And I mean, these are a few examples, uh uh of essential tremor patients we've treated together uh, down at uh uh Tampa General. So this is another patient. Uh I think this, this gentleman was left. Yeah, this is a left handed patient came in with really bad tremors, medical management, uh uh problems with alcohol, alcoholism secondary to his tremor. Uh This is his pre operative Archimedes. Spirals you see on the left wasn't able to write a straight line very properly, can barely write his name. And this is two hours after the procedure. Uh That thing changed his life. He wasn't a good D BS candidate. Nothing was working for him. That is another another patient, similar result even worse. You can see the significant atrophy in the brain, you know, enlargement of the ventricles. You can see the lesion in the left VM thalamus on the post op MRI. And you can see how the spiral is significantly improved. Those people are unable to eat, they are unable to drink. They don't like to go out, they don't like to invite people to their house because of their problem. I mean, they like to invite people, they can't do it, they can't use their phone, they can't type and a procedure like this takes about 2.5 hours and can give them their freedom back. Let's see, that is another example. Some people have less tremor than others, but even those patients can benefit as well. This is a patient who had a typical essential tremor, had the procedure done here at Tampa General. And that's another example that patient we did it on New Year's Eve Day, the day 31st of December, we couldn't do the ultrasound for some specific insurance reason. So he came in on the 31st on Saturday and our team was here and he was able to celebrate New Year's at home because his insurance changed in January. So for Parkinson's disease, we can use it as well. 2017 pat in one PD patient suffering from dyskinesia, they improve their boor scores by 60% off medications improved, 55% and the dyskinesia has improved by 70%. This is only one side, the unilateral pado. And then the next year they did tey in tremor, dominant, significant improvement in motor scale resting tremor improvement and in postural tremor. Uh other applications now being studied psychiatric obsessive O CD, uh major depression, chronic neuropathic pain for central lateral temo is being studied, not, not approved yet. The meat pain, 57% at 12 months in eight patients. We know that in a lot of from the lesion in literature though that those patients can tend to recur even after your lesion. So it would be interesting to see what happens to those patients. There are some pilot studies on epilepsy, secondary generalized epilepsy due to subcortical lesion targeting of the anterior thalamic nucleus that we use. Now for D BS to prevent secondary generalization of focal onset epilepsy patients. You can, you can lesion a focal lesion that's causing epilepsy or focal cortical dysplasia in theory or any lesion that you suspect is causing the intractable epilepsy. This should be out in the next few years. I anticipate. We spoke about pulse, low intensity focused ultrasound for opening the blood brain barrier. It's reversible. It can last up to 46 hours after treatment. This is an example for clot lys using micro bubbles, followed by needle aspiration or catheter replacement. Uh Some people are saying that this might be, this might be the future for hemorrhagic stroke or even in theory, an ischemic stroke as well, you can use it. Uh you can provide effective hemostasis while preserving blood flow. Uh If there is a specific area, you want to coagulate, enhance anti tumor immunity, so you can cause you can disrupt the tumor and cause the local release of antigens or even DNA molecules. You can use those, the immune system can identify those antigens. And in theory, it can enhance Antium immunity or if there are DNA molecules can diagnose brain tumors, lymphomas, et cetera. We typically do stereotatic biopsies a lot for diagnosis. For those cases. You can, you can potentially stimulate anti tumor immune response or even with the residual tumors, we spoke about the GB M. Uh and it may suppress remote metastasis. Some people say if you're able to treat the operative, that might be another way because we know with SRS, it can decrease progression, remote metastasis, et cetera. And these are the ongoing trials and investigations for brain tumors. So we have a couple of phase one, phase two trials for recurrent GB M or you know, uh or primary GB M before or GB M before surgery. Uh We have neurogen disease, multi moderate Parkinson's disease or Alzheimer's disease or A LS. Even in A LS, the it seems like they're targeting primary motor cortex. So in conclusion, you know, right now, a high intensity focus ultrasound used for movement disorders, minimally invasive. It's incision, free trans cranial treatment for a variety of diseases. So, thermal and non thermal mechanisms up to date, several clinical trials we saw are being conducted by research institutes worldwide for, for the applications we spoke about thy for essential tumor tremor dominant Parkinson's disease. This is a day procedure. They come in, get treated, they go home the same day we have unilateral palay, especially beneficial for asymmetric parkinson's disease. And we have various applications for life. So we spoke about blood brain barrier for chemo antibiotics as well. That's another way to think about it. Protein, expulsion from the brain, liquid biopsy DNA from tumor cells, treatment of tumor margins, neural network stimulation for a for example. And that's it. Thank you very much. That was wonderful. Thank you very much. Yeah, I mean. Published Created by
