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Transcript
I'm going to talk about both fibertracking and its use in SRS, as well as some cranial nerve imaging that we've done at our institution. These are my disclosures.
So as we all know, stereotactic radiosurgery is a field that's been enabled by advancements in technology and increased precision. So we've gone from the era of whole brain radiation and conventional radiation. And with advances in anatomical or structural MRI, we've been able to go into this era of stereotactic radiosurgery, and we believe that with connectivity-based and network-based imaging and fibertracking, we're going to go into a new era of stereotactic radiosurgery.
So, this is an example of using structural imaging advancements. So comparing 3-Tesla to 7-Tesla structural MRI showing the increased signal to noise ratio, and increased contrast to noise ratio that that affords us. However, what we don't get from that is patient-specific connectivity information. So for that, what we do at our institution is connectivity-based imaging using DTI and tractography that Dr. Konin [SP] and Expert Lee already went into, so I don't need to go into the physics behind that. But essentially, we're using MRI sequences that are sensitive to the diffusion of water along axons. And we use that information for both to determine the orientation of those axons, and then we can then use that information using either deterministic or probabilistic algorithms to then define targets and seeds to define connectivity or structural connectivity between structures in the brain.
As shown here at the bottom, you can see connectivity from the thalamus to the motor cortex. So, other groups, like this group in Pittsburgh, has used high-definition fiber tractography to actually delineate cranial nerve fibers. This is an example of using this technique to localize trigeminal nerve fibers, as well as central fibers from the trigeminal nerve, such as the spinal trigeminal tract, as seen here. So, we had a patient that presented it with this Meckel's Cave tumor. We previously performed radiosurgery on the tumor itself. The patient had tumor-associated trigeminal nerve pain that did not respond to radiosurgery, the patient was not a good surgical candidate. So we used probabilistic tractography to better delineate the trigeminal nerve on that side. It was very difficult to actually see the nerve without the tractography. So after doing this, we used this in our radiosurgery planning suite, and we treated the trigeminal nerve using this method. And the patient had a pretty good outcome after three months, with good relief of his pain.
Also, from the same group, they showed that you can use optic pathway delineation using high-density fibertracking, as shown here to delineate the optic tracts, the chiasm, and then the optic radiations. And then using this, they then used this in the setting of a hypothalamic glioma that was displacing the optic apparatus inferiorly, as you can see here. And what they found intraoperatively was that it corroborated what they saw with the fibertracking method. So, can we use this for radiosurgery thalamotomies? Ninety-percent of these patients, as we know, do respond to radiosurgery for either tremor predominant PD or central tremor. However, it's not used as often as you would expect, given the success rate. And why not? As we know there's two major limitations. One, we can't really treat bilaterally using this technique. And number two, the complication rate from radiosurgical thalamotomy is slightly higher compared to DBS.
So how can we improve this? Well, we could address this complication rate by trying to improve our targeting. And while we can use direct anatomical imaging and better structural imaging, this will not, even if we can visualize the target with this imaging, will not necessarily tell us what the function of that area is in the brain. So what we really want to know is what is the connectivity of that area, and is that area functionally connected in a clinically relevant fashion?
So, why does connectivity and why do networks matter? Dr. Konin has already talked about this. This is a paper by Michael Fox that kind of touched on this topic and showed that really if you look at these targets for various disorders, regardless of where the actual anatomical location of the target was, it could be very, you know, in disparate locations depending on whether you're doing invasive or non-invasive neuromodulation, the underlying theme was that the network does matter. The connectivity explains the efficacy of these targets, and that that information, that connectivity information, should be used to guide refinements of neuromodulation targets.
So using an approach, and Dr. Konin kind of talked about the Oxford Group that initially did the segmentation of the thalamus based on his connectivity, different cortical areas, as you can see in the bottom-right panel, we use a technique to look at our placement of DBS electrodes for essential tremor in a retrospective fashion. So these are patients who had undergone bilateral DBS for tremor, and we subsequently took all of our thalamic voxels and characterized them based on their connectivity, different cortical areas. And what we found was a little bit interesting. We found that actually, if you looked at the voxels that were within the area of stimulation, and were effective, they were actually associated with voxels that are highly connected to the premotor cortex.
And you can see here we were able to see, for example, in this case, in most of these cases, you have bilateral stimulation, and you can see the yellow is the area that's most highly connected to our precentral or premotor area. There was one patient on one side that did not have good efficacy, and you can see that the DBS electrode was not located in that voxel. The other finding from this research was that if you looked at the overlap between the most connected voxel across all of the subjects, there was only a 60% overlap. So, this shows us that there's a high degree of variability from patient to patient. So, each voxel in each patient is not going to be connected in the same way. And so that was used in a retrospective fashion, and what our group is trying to do is to use that prospectively for thalamic targeting, for deep brain stimulation.
Now, we then moved on and done some cases of SRS for the thalamotomies for both essential tremor and tremor-predominant PD. This is a patient who had tremor-predominant Parkinson's Disease. And, we identified the thalamus, in the region of thalamus that's highly connected to motor cortex that's shown here in the blue up here, and we're able to delineate that. This was using probabilistic tractography. And, what we did was use our Frameless Novalis System with a 140 Gy point dose. And using this, we did do some safety constraints with a 20% isodose for the internal capsule border and then using our Z-plane as three millimeters above AC-PC. And using this, this is a patient that, as you can see, we followed with MRI, and you can see the thalamotomy lesion on MRI that's stable with time. And at 22 months out, the patient had essentially no tremor in the right-upper extremity following this technique.
So, the other question is, can we use deterministic tractography for targeting? The case that I showed you, we primarily used probabilistic tractography. But, as you can see here, this is a patient with stats plus DBS for tremor, and we compared using probabilistic tractography with a 50% threshold and overlaid that on the Brainlab deterministic algorithm, and we showed fairly good overlap between those two segmentations. The purple being the probabilistic segmentation, and the white is the deterministic... Sorry, the other way around. The white is the probabilistic and the purple was deterministic in these examples. This is another patient, showing again at various levels of probabilistic thresholding, 30%, 40%, and 50%. There's a fairly good overlap between the deterministic and the probabilistic segmentation of the thalamus.
So, our workflow is to use the Brainlab segmentation to segment the motor cortex and the thalamus, and then we use Brainlab tractography to identify motor cortex tracts intersecting with the thalamus. We placed a 140 Gy isodose, and again, we used the 20% isodose line on the medial border of the capsule, and then the Y is centered on the motor tractography intersection with the thalamus, and the Z is three millimeters above the AC-PC plane. And again, this is a frameless technique that we use at our institution.
So then the question is, can we use this for other diseases? Another group at our institution has shown that. We looked at patients that were targeted for pain, for intractable pain, so we're targeting PVG and sensory thalamus here. And, we went back and we looked at the contact placements and looked at the clinical efficacy. So, this was a series of five patients, and most of the patients, four of the five patients had good clinical success. One of those is shown here in the top-left, and showing good overlap between the contact and the area that was delineated using tractography. In this case, it was probabilistic tractography to define the sensory thalamic area. However, one of the patients had a poor clinical outcome. And in that case, the DBS contact was shown to be slightly medial to the tractography-identified area.
So in conclusion, the brain is a functional organ that functions at the level of connectivity. Diseases of the brain affect networks. Therefore, therapies of the brain should also modulate networks. Diffusion tensor imaging and tractography enhances our current structural understanding of the brain to identify the proper networks for targeting, and we believe that integrating diffusion targeting will enhance the efficacy and safety of radiosurgery. Thank you.
So as we all know, stereotactic radiosurgery is a field that's been enabled by advancements in technology and increased precision. So we've gone from the era of whole brain radiation and conventional radiation. And with advances in anatomical or structural MRI, we've been able to go into this era of stereotactic radiosurgery, and we believe that with connectivity-based and network-based imaging and fibertracking, we're going to go into a new era of stereotactic radiosurgery.
So, this is an example of using structural imaging advancements. So comparing 3-Tesla to 7-Tesla structural MRI showing the increased signal to noise ratio, and increased contrast to noise ratio that that affords us. However, what we don't get from that is patient-specific connectivity information. So for that, what we do at our institution is connectivity-based imaging using DTI and tractography that Dr. Konin [SP] and Expert Lee already went into, so I don't need to go into the physics behind that. But essentially, we're using MRI sequences that are sensitive to the diffusion of water along axons. And we use that information for both to determine the orientation of those axons, and then we can then use that information using either deterministic or probabilistic algorithms to then define targets and seeds to define connectivity or structural connectivity between structures in the brain.
As shown here at the bottom, you can see connectivity from the thalamus to the motor cortex. So, other groups, like this group in Pittsburgh, has used high-definition fiber tractography to actually delineate cranial nerve fibers. This is an example of using this technique to localize trigeminal nerve fibers, as well as central fibers from the trigeminal nerve, such as the spinal trigeminal tract, as seen here. So, we had a patient that presented it with this Meckel's Cave tumor. We previously performed radiosurgery on the tumor itself. The patient had tumor-associated trigeminal nerve pain that did not respond to radiosurgery, the patient was not a good surgical candidate. So we used probabilistic tractography to better delineate the trigeminal nerve on that side. It was very difficult to actually see the nerve without the tractography. So after doing this, we used this in our radiosurgery planning suite, and we treated the trigeminal nerve using this method. And the patient had a pretty good outcome after three months, with good relief of his pain.
Also, from the same group, they showed that you can use optic pathway delineation using high-density fibertracking, as shown here to delineate the optic tracts, the chiasm, and then the optic radiations. And then using this, they then used this in the setting of a hypothalamic glioma that was displacing the optic apparatus inferiorly, as you can see here. And what they found intraoperatively was that it corroborated what they saw with the fibertracking method. So, can we use this for radiosurgery thalamotomies? Ninety-percent of these patients, as we know, do respond to radiosurgery for either tremor predominant PD or central tremor. However, it's not used as often as you would expect, given the success rate. And why not? As we know there's two major limitations. One, we can't really treat bilaterally using this technique. And number two, the complication rate from radiosurgical thalamotomy is slightly higher compared to DBS.
So how can we improve this? Well, we could address this complication rate by trying to improve our targeting. And while we can use direct anatomical imaging and better structural imaging, this will not, even if we can visualize the target with this imaging, will not necessarily tell us what the function of that area is in the brain. So what we really want to know is what is the connectivity of that area, and is that area functionally connected in a clinically relevant fashion?
So, why does connectivity and why do networks matter? Dr. Konin has already talked about this. This is a paper by Michael Fox that kind of touched on this topic and showed that really if you look at these targets for various disorders, regardless of where the actual anatomical location of the target was, it could be very, you know, in disparate locations depending on whether you're doing invasive or non-invasive neuromodulation, the underlying theme was that the network does matter. The connectivity explains the efficacy of these targets, and that that information, that connectivity information, should be used to guide refinements of neuromodulation targets.
So using an approach, and Dr. Konin kind of talked about the Oxford Group that initially did the segmentation of the thalamus based on his connectivity, different cortical areas, as you can see in the bottom-right panel, we use a technique to look at our placement of DBS electrodes for essential tremor in a retrospective fashion. So these are patients who had undergone bilateral DBS for tremor, and we subsequently took all of our thalamic voxels and characterized them based on their connectivity, different cortical areas. And what we found was a little bit interesting. We found that actually, if you looked at the voxels that were within the area of stimulation, and were effective, they were actually associated with voxels that are highly connected to the premotor cortex.
And you can see here we were able to see, for example, in this case, in most of these cases, you have bilateral stimulation, and you can see the yellow is the area that's most highly connected to our precentral or premotor area. There was one patient on one side that did not have good efficacy, and you can see that the DBS electrode was not located in that voxel. The other finding from this research was that if you looked at the overlap between the most connected voxel across all of the subjects, there was only a 60% overlap. So, this shows us that there's a high degree of variability from patient to patient. So, each voxel in each patient is not going to be connected in the same way. And so that was used in a retrospective fashion, and what our group is trying to do is to use that prospectively for thalamic targeting, for deep brain stimulation.
Now, we then moved on and done some cases of SRS for the thalamotomies for both essential tremor and tremor-predominant PD. This is a patient who had tremor-predominant Parkinson's Disease. And, we identified the thalamus, in the region of thalamus that's highly connected to motor cortex that's shown here in the blue up here, and we're able to delineate that. This was using probabilistic tractography. And, what we did was use our Frameless Novalis System with a 140 Gy point dose. And using this, we did do some safety constraints with a 20% isodose for the internal capsule border and then using our Z-plane as three millimeters above AC-PC. And using this, this is a patient that, as you can see, we followed with MRI, and you can see the thalamotomy lesion on MRI that's stable with time. And at 22 months out, the patient had essentially no tremor in the right-upper extremity following this technique.
So, the other question is, can we use deterministic tractography for targeting? The case that I showed you, we primarily used probabilistic tractography. But, as you can see here, this is a patient with stats plus DBS for tremor, and we compared using probabilistic tractography with a 50% threshold and overlaid that on the Brainlab deterministic algorithm, and we showed fairly good overlap between those two segmentations. The purple being the probabilistic segmentation, and the white is the deterministic... Sorry, the other way around. The white is the probabilistic and the purple was deterministic in these examples. This is another patient, showing again at various levels of probabilistic thresholding, 30%, 40%, and 50%. There's a fairly good overlap between the deterministic and the probabilistic segmentation of the thalamus.
So, our workflow is to use the Brainlab segmentation to segment the motor cortex and the thalamus, and then we use Brainlab tractography to identify motor cortex tracts intersecting with the thalamus. We placed a 140 Gy isodose, and again, we used the 20% isodose line on the medial border of the capsule, and then the Y is centered on the motor tractography intersection with the thalamus, and the Z is three millimeters above the AC-PC plane. And again, this is a frameless technique that we use at our institution.
So then the question is, can we use this for other diseases? Another group at our institution has shown that. We looked at patients that were targeted for pain, for intractable pain, so we're targeting PVG and sensory thalamus here. And, we went back and we looked at the contact placements and looked at the clinical efficacy. So, this was a series of five patients, and most of the patients, four of the five patients had good clinical success. One of those is shown here in the top-left, and showing good overlap between the contact and the area that was delineated using tractography. In this case, it was probabilistic tractography to define the sensory thalamic area. However, one of the patients had a poor clinical outcome. And in that case, the DBS contact was shown to be slightly medial to the tractography-identified area.
So in conclusion, the brain is a functional organ that functions at the level of connectivity. Diseases of the brain affect networks. Therefore, therapies of the brain should also modulate networks. Diffusion tensor imaging and tractography enhances our current structural understanding of the brain to identify the proper networks for targeting, and we believe that integrating diffusion targeting will enhance the efficacy and safety of radiosurgery. Thank you.