Transcript
Okay. My credentials are there. I will introduce each one of the other speakers as we go along. I was asked to tell you news about the functional disorders, what do we have now that we improved the quality of our functional work, what's new, what's in the pipeline. And I have to tell you that Brainlab has inspired with the imaging work mainly with the image fusion that became almost seamless. When I started these, I used to make slides and fused X-rays with the MRI scans and now we have all that seamless. We don't even think about that so we can get any kind of imaging for functional disorders. So that's basically what you will see here.
I will talk a little bit about the first targets, how it got started, our fight against the drugs. You know, we are almost without side effects when we work in the brain specifically. So, the drugs are systemic. So, we have to work on a way of not giving drugs, for instance, for a depressed person that will have a lot of problems, that does not sleep well or sleep too much, not attention or no sexual function. All of these we have to try to decrease for our patients. I will talk a little bit about imagings, new targets. Do we need a target or we can have a USB to the brain? And that's another possible way of treating patients. And then some conclusions.
Well, from the history, we started really to make lesions in the brain by removing the cortex for instance. That's in the 1800s. And now in the 1990s, we are doing neuromodulation. We don't need to do lesions many times. We can use radiation for neuromodulation. We can use ultrasound for neuromodulation. So, we have a technology that is now...as the imaging improve, as you are seeing here, when we used to do a pallidotomy, we used to do electrophysiology to be able to avoid the pyramidal tract in that region. And that changed two pokes in the brain that increased a little bit the risk. We have learned quite a bit. We have learned the speech of each area of the brain. So that helped us. There's electrophysiology that we generated over the years. You see the substantial migraine in yellow is very unique when you arrive in that area.
So that has allowed us to imagine and the artist at UCLA, Dr. Malkasian make all these drawings for me and I am saying to him, "Here, I am stimulating here, I'm stimulating there." And he, a neurosurgeon anatomist was able to draw this. But if you look at this, there's a small imaging in the middle. Well, it looks like that that's what we can see now in each patient of ours. So, and who is providing that to us? It's really the fiber tracking and the ability to isolate. For instance, now we can see the VIM. We can see the VIM which is the target for tremor. We can see GPi, globus pallidus interna. We can see the STN. The nucleus that we use for Parkinson's Disease is stimulation or even lesion these days. Some people are trying that.
So, this is work we were doing with the help of Brainlab software in the 2008, 2007, even before that. So, this kept on improving over the years and more and more dedication in this type of software. Fiber tracking started to show how is the nucleus, but also showing us the noise that you are seeing here. It's someone trying to use their hands and completely frustrated. And now we can do this with a gamma knife or with a focused ultrasound, two competing technologies.
Now we see the fibers arriving to VIM. We see the fibers leaving the VIM and we see this tremor control that we can do with electrical stimulation or with any lesion in that area, precise lesion in that area.
Now how can we use this technology really to avoid complications and to improve our results? And that's basically what we are trying to do with the fiber tracking and gamma knife and we were able to show that we have to move two millimeters in one direction, two millimeters in the other direction. And if you read the paper, you will understand how we are using this technology to improve our targeting.
Now radiosurgery thalamotomy unilaterally, it's really definitely a very good treatment and this is one of the ISRS guidelines. This was promoted a lot by Arjun Sahgal at the time that he was working on this at the ISRS and we summarized this. So, we can say that we have a control of 88% of tremor with unilateral tremor with gamma knife and with very little permanent complication. So, this is a good way of targeting. We can do it with a gamma knife, we can do it with a very nice [inaudible 00:05:59] Novalis if you are using the proper technology with the proper physicist and your Novalis is not treating everything else including prostate. So, you have to be dedicated with this so you do a perfect work with functional disorders.
So, we started to ask where are these fibers coming from? Where are the fibers of each one of these nuclei? They are coming from the cortex, they are coming generally from the brain. For instance, if you look at the globus pallidus interna, you have a diffusion of fibers coming to that direction. If you go for instance with the VIM, you've got a very nice, little track coming in as I showed to you in the previous pictures.
So now these allow us to go with electrical stimulation. What about modulating the brain with radiation? Because the group here, most of you are interested in radiation and not in the stimulation. Well, trying to do precise radiosurgery, we found that surrounding the area of a lesion you can start to see serotonin, you can see glutamate, you can see tyrosine hydroxylase that's a precursor of dopamine for instance. What is the dose that does that? Shall we go to the lab and study that with a little bit more detail? So, we need to do that to be able to start to use this technology in a different way.
Well, it's...we are learning quite a bit now about cognition, about epilepsy, how we're gonna modify these pathways in a way that we can enhance quality of life. This work of Dr. Itzhak Fried is stimulating the entorhinal area. You can for instance enhance videogame. If you put the patient to do spatial tasks, you can improve if you are stimulating that area. If you are making a lesion specifically in the perform path of the hippocampus, you can control seizures. We showed that in the red for instance.
So, there are a lot of things we can do with radiosurgery ahead of the time that's the future to happen. We are already controlling seizures with radiosurgery. And how is really possible to do that in a way that you don't have too many complications? So, we've got to think about that a little bit.
So here it's my daughter that has made that drawing over there. And this is everything she learned from me about the brain. I was surprised. She's an artist and when she drew the brain, I said, "She doesn't know anything." But Brainlab is helping us to unscramble that. We are scrambling that not only with the fiber tracking but also to be sure that these images we see are not distorted. They're not distorted like she thinks. It's distorted in a way that we can be precise. We see that if you see the Dentato-Rubro Thalamic Tract related to tremor, you see that inside of that image that you see here you have apparently no distortion. Red is what is corrected, known to be corrected. But even here you have the two and a half millimeters. And if you are doing a gamma knife work on this, if you are doing Novalis work on this, you may be inside of the pyramidal tract and have a [inaudible 00:09:48] on that. So, it's extremely important that you are not really reaching this tract, the pyramidal tract when you are doing your radiosurgery.
Well, we have also a map, a seven Tesla map with all the segmentation necessary for you to do proper targeting. For instance, in the...this side, you see all the segmentations possible of the basal ganglia. This is because we are doing functional neurosurgery but you have those as well for other applications. So, this segmentation with real...more visualization of imaging allows you that are working with 1.5 Tesla correct the targeting because now you'll have a little bit more information.
Well, what about epilepsy? Epilepsy, we just had a failed trial in treatment of epilepsy with radiosurgery. Why? Because of too much edema. Not the failed trial. We controlled seizures but we were not better than surgery. So, we still have to open the patient's head just because we haven't dominated the doses that we should do. So, this is a proposal of one of our students in Brazil. He said to us...while looking at anatomy and fiber tracking, I told him to study why we don't disconnect that with three very focused lesion in the hippocampus, one in the amygdala and then we disconnect the rest of the hippocampus and through the back. And this decreases the doses that we need to use and decrease the volume that we are doing radiation in the hippocampus. So, when you start with these types of strategies, maybe better strategies than that can be developed. But we can see that as we think about this, as we work on this type of problem, we will have better solutions with that that we had in the past.
Well, fiber tracking again helping us to target. Here we have the Fornix. You know, you see the Fornix, right? Well, here we were targeting the mesial hypothalamus. That's not an easy target to get. And we basically...you can see right here the electrodes that were placed in the mesial hypothalamus. Well, what do we get with that? Well, we take a guy that's waiting 169 pounds, we stimulate it here and in one year or a little bit less, we get him to lose the weight and here you are working with full technology all the way to an operating room with an MRI scan. So, we do...we check what we do, we do tractography at the moment of the surgery, we put the electrode and we check if it's in the proper place. We stimulate and we see where we are. Here the patients in general anesthesia. So, we can ask him, "Are you hungry?" Yet he's not gonna answer. And even if he is not in general anesthesia, he always will say he's hungry. Hungry because we are not gonna get him food before a surgery. So here we see clearly the blood pressure going up when you're in the proper place. So, you have another science to say that and in here we've got the patient that was a mechanic end up getting work well and if you read what he is saying, basically, the therapy was good for him in the bottom here. He had déjà vu, he had a lot of experiences with this stimulation but he's improved his sleeping pattern. He improved his general good feeling. Therefore, he felt that he's looking better, he improved his sexual function and he didn't have any changes in his blood pressure.
So that's what we want. We want to treat people specifically what they need increasing their metabolism in that case and not giving him a drug that will affect his whole system. Well, what about when we are thinking about psychiatric diseases? You know, how can we treat these patients in a way...more focused way? Here we are looking at the, again, fiber tracking trying to compare our patients with morbid obesity with obsessive-compulsive disorder and with Parkinson's Disease. And you see in the middle that you have significant more fibers in OCD. Is that correct? Is the software good enough for us to measure the number of fibers there? Do we have that specificity? If you don't have now, what I found here is not true. I'm sure that the software will be developed for us to have that kind of precision and say to the patient here, "I need to take a little bit of your fibers in the frontal lobe and improve your quality of life and avoid..." What you are seeing here in the right-hand side, you are seeing here the complete destruction of a frontal lobe of a patient with an icepick which destroyed the functional neurosurgeon in the 50s. This was done around 1954. It's not long ago. You are looking at me, I was born in '54. You know, and I'm still lasting. So, I think indeed we have to start to understand very nicely each one of these fibers. And this is the group that we are working in OCD. We are trying to dissect which are the fibers that are important. But not destroying the whole frontal lobe but specifically which is the symptom that that patient has.
Is he measuring things, always is obsessive-compulsive with everything organized or he is washing his hands or he's having bad thoughts? Where is that happening? So, what part of the cortex is dealing with that? So, I asked one of our students to go and look at that mesial frontal, lateral frontal. Still very...not very detailed yet but we start to see here that the mesial frontal is bottom part of internal capsule and as you go laterally, you've got the upper part of the internal capsule. And you start to learn where do we have good results in surgery of OCD. This is a [inaudible 00:16:17] has done this with several cases that were done throughout United States and the world. He got our cases as well. And he found out that where is red, this is where you have the best results, red and yellow. If you go down, you don't get good results in blue.
So, if we look at our patients that we have done the trial of taking only the bottom part of the fibers, then we saw that those patients didn't get good results. But what about the USB to the brain? The trigeminal nerve is a huge wire that goes inside and it's a lot of feeling. So, here's a patient that we completely took her out of depression in a randomized controlled trial just to show that we changed the neurotransmitters in the brain with the stimulation of the frontal lobe, the trigeminal nerve. So, this is one of the pictures of UCLA where we are stimulating with the tape and we did a PET scan showing that you change neurotransmitters in the brain when you are stimulating like that.
So, we don't know anything about the white...the anterior limb of the internal capsule and we know too much about the posterior. So, if you look there in the picture, this is how much we know about the anterior limb of the internal capsule and this is how much we know about the posterior limb of the internal capsule. So, we are in the verge now of learning and learning more what we can do with our frontal lobes. Now to conclude, I would say to you that imaging and stimulation in the brain and techniques of modulating completely our DNA with irradiation, we can in that way start to understand and develop therapies that are focused to the patient preventing them to take a lot of drugs. And that's a romance that is in Portuguese, it's in English, now is also in Spanish in which we just put out this imaging together. Not for you to understand because you understand. It's for the laypeople to understand and to accept the fact that in this day and age we can help them to live better without destroying or without modifying. In other words, accepting the concept of psychosurgery that you saw in the 1954 being done with that kind of results.
Thank you very much. You don't do anything at all and that's the group in Brazil and that's a group at UCLA that worked with me for many years. And this is the guy that I'm preparing to develop new therapies. It's a lot of work to get this done. We are putting a lot of effort in the teaching in Latin America. Arrive there, very, very much work needed to be done for radiosurgery to raise the bar of that. So, we brought it to Brazil and I expect all of you in Rio de Janeiro to help in my quest of improving radiosurgery throughout Latin America. Thank you very much.
I will talk a little bit about the first targets, how it got started, our fight against the drugs. You know, we are almost without side effects when we work in the brain specifically. So, the drugs are systemic. So, we have to work on a way of not giving drugs, for instance, for a depressed person that will have a lot of problems, that does not sleep well or sleep too much, not attention or no sexual function. All of these we have to try to decrease for our patients. I will talk a little bit about imagings, new targets. Do we need a target or we can have a USB to the brain? And that's another possible way of treating patients. And then some conclusions.
Well, from the history, we started really to make lesions in the brain by removing the cortex for instance. That's in the 1800s. And now in the 1990s, we are doing neuromodulation. We don't need to do lesions many times. We can use radiation for neuromodulation. We can use ultrasound for neuromodulation. So, we have a technology that is now...as the imaging improve, as you are seeing here, when we used to do a pallidotomy, we used to do electrophysiology to be able to avoid the pyramidal tract in that region. And that changed two pokes in the brain that increased a little bit the risk. We have learned quite a bit. We have learned the speech of each area of the brain. So that helped us. There's electrophysiology that we generated over the years. You see the substantial migraine in yellow is very unique when you arrive in that area.
So that has allowed us to imagine and the artist at UCLA, Dr. Malkasian make all these drawings for me and I am saying to him, "Here, I am stimulating here, I'm stimulating there." And he, a neurosurgeon anatomist was able to draw this. But if you look at this, there's a small imaging in the middle. Well, it looks like that that's what we can see now in each patient of ours. So, and who is providing that to us? It's really the fiber tracking and the ability to isolate. For instance, now we can see the VIM. We can see the VIM which is the target for tremor. We can see GPi, globus pallidus interna. We can see the STN. The nucleus that we use for Parkinson's Disease is stimulation or even lesion these days. Some people are trying that.
So, this is work we were doing with the help of Brainlab software in the 2008, 2007, even before that. So, this kept on improving over the years and more and more dedication in this type of software. Fiber tracking started to show how is the nucleus, but also showing us the noise that you are seeing here. It's someone trying to use their hands and completely frustrated. And now we can do this with a gamma knife or with a focused ultrasound, two competing technologies.
Now we see the fibers arriving to VIM. We see the fibers leaving the VIM and we see this tremor control that we can do with electrical stimulation or with any lesion in that area, precise lesion in that area.
Now how can we use this technology really to avoid complications and to improve our results? And that's basically what we are trying to do with the fiber tracking and gamma knife and we were able to show that we have to move two millimeters in one direction, two millimeters in the other direction. And if you read the paper, you will understand how we are using this technology to improve our targeting.
Now radiosurgery thalamotomy unilaterally, it's really definitely a very good treatment and this is one of the ISRS guidelines. This was promoted a lot by Arjun Sahgal at the time that he was working on this at the ISRS and we summarized this. So, we can say that we have a control of 88% of tremor with unilateral tremor with gamma knife and with very little permanent complication. So, this is a good way of targeting. We can do it with a gamma knife, we can do it with a very nice [inaudible 00:05:59] Novalis if you are using the proper technology with the proper physicist and your Novalis is not treating everything else including prostate. So, you have to be dedicated with this so you do a perfect work with functional disorders.
So, we started to ask where are these fibers coming from? Where are the fibers of each one of these nuclei? They are coming from the cortex, they are coming generally from the brain. For instance, if you look at the globus pallidus interna, you have a diffusion of fibers coming to that direction. If you go for instance with the VIM, you've got a very nice, little track coming in as I showed to you in the previous pictures.
So now these allow us to go with electrical stimulation. What about modulating the brain with radiation? Because the group here, most of you are interested in radiation and not in the stimulation. Well, trying to do precise radiosurgery, we found that surrounding the area of a lesion you can start to see serotonin, you can see glutamate, you can see tyrosine hydroxylase that's a precursor of dopamine for instance. What is the dose that does that? Shall we go to the lab and study that with a little bit more detail? So, we need to do that to be able to start to use this technology in a different way.
Well, it's...we are learning quite a bit now about cognition, about epilepsy, how we're gonna modify these pathways in a way that we can enhance quality of life. This work of Dr. Itzhak Fried is stimulating the entorhinal area. You can for instance enhance videogame. If you put the patient to do spatial tasks, you can improve if you are stimulating that area. If you are making a lesion specifically in the perform path of the hippocampus, you can control seizures. We showed that in the red for instance.
So, there are a lot of things we can do with radiosurgery ahead of the time that's the future to happen. We are already controlling seizures with radiosurgery. And how is really possible to do that in a way that you don't have too many complications? So, we've got to think about that a little bit.
So here it's my daughter that has made that drawing over there. And this is everything she learned from me about the brain. I was surprised. She's an artist and when she drew the brain, I said, "She doesn't know anything." But Brainlab is helping us to unscramble that. We are scrambling that not only with the fiber tracking but also to be sure that these images we see are not distorted. They're not distorted like she thinks. It's distorted in a way that we can be precise. We see that if you see the Dentato-Rubro Thalamic Tract related to tremor, you see that inside of that image that you see here you have apparently no distortion. Red is what is corrected, known to be corrected. But even here you have the two and a half millimeters. And if you are doing a gamma knife work on this, if you are doing Novalis work on this, you may be inside of the pyramidal tract and have a [inaudible 00:09:48] on that. So, it's extremely important that you are not really reaching this tract, the pyramidal tract when you are doing your radiosurgery.
Well, we have also a map, a seven Tesla map with all the segmentation necessary for you to do proper targeting. For instance, in the...this side, you see all the segmentations possible of the basal ganglia. This is because we are doing functional neurosurgery but you have those as well for other applications. So, this segmentation with real...more visualization of imaging allows you that are working with 1.5 Tesla correct the targeting because now you'll have a little bit more information.
Well, what about epilepsy? Epilepsy, we just had a failed trial in treatment of epilepsy with radiosurgery. Why? Because of too much edema. Not the failed trial. We controlled seizures but we were not better than surgery. So, we still have to open the patient's head just because we haven't dominated the doses that we should do. So, this is a proposal of one of our students in Brazil. He said to us...while looking at anatomy and fiber tracking, I told him to study why we don't disconnect that with three very focused lesion in the hippocampus, one in the amygdala and then we disconnect the rest of the hippocampus and through the back. And this decreases the doses that we need to use and decrease the volume that we are doing radiation in the hippocampus. So, when you start with these types of strategies, maybe better strategies than that can be developed. But we can see that as we think about this, as we work on this type of problem, we will have better solutions with that that we had in the past.
Well, fiber tracking again helping us to target. Here we have the Fornix. You know, you see the Fornix, right? Well, here we were targeting the mesial hypothalamus. That's not an easy target to get. And we basically...you can see right here the electrodes that were placed in the mesial hypothalamus. Well, what do we get with that? Well, we take a guy that's waiting 169 pounds, we stimulate it here and in one year or a little bit less, we get him to lose the weight and here you are working with full technology all the way to an operating room with an MRI scan. So, we do...we check what we do, we do tractography at the moment of the surgery, we put the electrode and we check if it's in the proper place. We stimulate and we see where we are. Here the patients in general anesthesia. So, we can ask him, "Are you hungry?" Yet he's not gonna answer. And even if he is not in general anesthesia, he always will say he's hungry. Hungry because we are not gonna get him food before a surgery. So here we see clearly the blood pressure going up when you're in the proper place. So, you have another science to say that and in here we've got the patient that was a mechanic end up getting work well and if you read what he is saying, basically, the therapy was good for him in the bottom here. He had déjà vu, he had a lot of experiences with this stimulation but he's improved his sleeping pattern. He improved his general good feeling. Therefore, he felt that he's looking better, he improved his sexual function and he didn't have any changes in his blood pressure.
So that's what we want. We want to treat people specifically what they need increasing their metabolism in that case and not giving him a drug that will affect his whole system. Well, what about when we are thinking about psychiatric diseases? You know, how can we treat these patients in a way...more focused way? Here we are looking at the, again, fiber tracking trying to compare our patients with morbid obesity with obsessive-compulsive disorder and with Parkinson's Disease. And you see in the middle that you have significant more fibers in OCD. Is that correct? Is the software good enough for us to measure the number of fibers there? Do we have that specificity? If you don't have now, what I found here is not true. I'm sure that the software will be developed for us to have that kind of precision and say to the patient here, "I need to take a little bit of your fibers in the frontal lobe and improve your quality of life and avoid..." What you are seeing here in the right-hand side, you are seeing here the complete destruction of a frontal lobe of a patient with an icepick which destroyed the functional neurosurgeon in the 50s. This was done around 1954. It's not long ago. You are looking at me, I was born in '54. You know, and I'm still lasting. So, I think indeed we have to start to understand very nicely each one of these fibers. And this is the group that we are working in OCD. We are trying to dissect which are the fibers that are important. But not destroying the whole frontal lobe but specifically which is the symptom that that patient has.
Is he measuring things, always is obsessive-compulsive with everything organized or he is washing his hands or he's having bad thoughts? Where is that happening? So, what part of the cortex is dealing with that? So, I asked one of our students to go and look at that mesial frontal, lateral frontal. Still very...not very detailed yet but we start to see here that the mesial frontal is bottom part of internal capsule and as you go laterally, you've got the upper part of the internal capsule. And you start to learn where do we have good results in surgery of OCD. This is a [inaudible 00:16:17] has done this with several cases that were done throughout United States and the world. He got our cases as well. And he found out that where is red, this is where you have the best results, red and yellow. If you go down, you don't get good results in blue.
So, if we look at our patients that we have done the trial of taking only the bottom part of the fibers, then we saw that those patients didn't get good results. But what about the USB to the brain? The trigeminal nerve is a huge wire that goes inside and it's a lot of feeling. So, here's a patient that we completely took her out of depression in a randomized controlled trial just to show that we changed the neurotransmitters in the brain with the stimulation of the frontal lobe, the trigeminal nerve. So, this is one of the pictures of UCLA where we are stimulating with the tape and we did a PET scan showing that you change neurotransmitters in the brain when you are stimulating like that.
So, we don't know anything about the white...the anterior limb of the internal capsule and we know too much about the posterior. So, if you look there in the picture, this is how much we know about the anterior limb of the internal capsule and this is how much we know about the posterior limb of the internal capsule. So, we are in the verge now of learning and learning more what we can do with our frontal lobes. Now to conclude, I would say to you that imaging and stimulation in the brain and techniques of modulating completely our DNA with irradiation, we can in that way start to understand and develop therapies that are focused to the patient preventing them to take a lot of drugs. And that's a romance that is in Portuguese, it's in English, now is also in Spanish in which we just put out this imaging together. Not for you to understand because you understand. It's for the laypeople to understand and to accept the fact that in this day and age we can help them to live better without destroying or without modifying. In other words, accepting the concept of psychosurgery that you saw in the 1954 being done with that kind of results.
Thank you very much. You don't do anything at all and that's the group in Brazil and that's a group at UCLA that worked with me for many years. And this is the guy that I'm preparing to develop new therapies. It's a lot of work to get this done. We are putting a lot of effort in the teaching in Latin America. Arrive there, very, very much work needed to be done for radiosurgery to raise the bar of that. So, we brought it to Brazil and I expect all of you in Rio de Janeiro to help in my quest of improving radiosurgery throughout Latin America. Thank you very much.