Not all glioma cells can be visualized during brain tumor resection, making it difficult for a neurosurgeon to achieve maximal resection. Constantinos G. Hadjipanayis, MD, PhD, reviews the current techniques and technologies that are available to help optimize tumor resection. Later, he provides guidance on when a surgeon should stop removing brain tumor.
Chapters (Click to go to chapter start) Extent of resection for glioblastoma and why it’s not enough Challenges during brain tumor resection surgery and how intraoperative mapping and DTI (diffusion tensor imaging) help Visualization technologies (microscopes, fluorescence-guided surgery, etc.) and their role in optimizing tumor resection Raman spectroscopy Intraoperative imaging When should we stop removing tumor? Q&A/Discussion professor of neurosurgery and oncological sciences here at Mount Sinai. He's the director of neurosurgical oncology and the director of the brain tumor nanotechnology lab. A lot of his recent research has been in the study of magnetic hypothermia for the treatment of glioblastoma as well as in fluorescence guided surgery. And his talk today is going to focus on surgical judgment which has come up as sort of a discussion point in when to stop when you have continued fluorescence. Looking forward to hearing that. Okay thank you peter. Um just share my screen. Sorry I lost my voice a little bit last night but hopefully it'll carry through here. Can you all see this? Okay. I'm gonna put it on the presentation. Okay looks good. So I think you know this is a topic that uh is quite interesting to me and I know you know our group as well as kind of talked about this several times and it kind of builds off a discussion we had recently at the double N. S. In philadelphia. We had a panel of neurosurgeons from around the country. Here are my disclosures. I do have a financial conflict with Five A Les. I'm also a synaptic um consultant and the other disclosures are not related here. So I'd like to talk a little bit about high grade glioma specifically glioblastoma and some of the considerations that we have in terms of how we respect those tumors and then dive into visualization of these tumors and then understand how we use our surgical adjuncts to help us see the tur better but also localized function better. And then finally kind of dive into some newer concepts and paradigms that we're exploring for possible treatment of residual tur that may allow for safer um maximum and maybe even super maximum resection. And then end with, you know, the concept of when we should stop removing tumor. And I have a case that I wanted to highlight at the end really for the residents. So, you know, I think that the extent of her section story for glioblastoma and high grade gliomas is has been published quite well over the years. And I, you know, the landmark article that started out was in um Uh 2001, the J. & S. by Lacroix At all. And that really kind of highlighted the fact that if you took out 98% or more of the contrast enhancing, tumor. you could actually, you know, really impact survival of the patient and their outcome. And and then there's been studies, you know, through the years kind of looking at different gradations of that concept in terms of really looking at what percentage does make a difference. And and that those numbers while they're kind of variable, they are used now and how we judge patients for surgery. Of course there's other factors we look at two in terms of age functional status and pathology, but, you know, I think we kind of adopted those types of principles in our practice routinely now. But we can all say that if we could take out as much of the tumo are safely as possible that we can impact patient survival. And and the the other point that's important is that if we take out as much as the tumor safely, it also allows for chemo radiation or a german therapies to work more effectively. And that's something that's also been looked at through the years. Well, when we look at our current paradigm, we really respect and focus on respecting the contrast enhancing portion of the tumor as you see here. But the question is is that enough? And we know that it's not enough because we know that outside of that contrast enhancement are you are cells that are growing and infiltrating the surrounding brain. So as you see here on the right hand side, the red dots correspond to the cancer cells kind of spreading through the white matter pathways and sub cortical regions of the brain. And this is something that, you know, walter dandy taught us, you know, 100 years ago where you could take out a whole hemisphere and then some way or another, those infiltrating cells can cause a recurrence. Uh But we do know that if we can go past the contrast enhancing border, we could impact survival and that's part of the basis of the talk today. Um And we know that there's cancer cells there because there are studies where people actually biopsied those areas around contrast enhancing tumor specifically Pat kelly, who was the leader at N. Y. U. For a number of years that was really his claim to fame. But you know, how do we see those tumors better? Um And then the question is how do we respect those tumor cells outside of the contrast enhancing portion without hurting our patients? So we know that poor functional outcomes after surgery really devastate glioblastoma patients. And this is a study out of the University of florida by Miriam romans group about five years ago. And you can see that if people have um definitely you know, if they have deficits after surgery, the survival curves really separate out and these are already people who have limited survival. So if you're going to take away function and someone who already has a terminal condition that is really not a good thing. And that's something that's been shown in a number of other studies, including you know, some guidelines that have come out. So how do we balance the good where we maximally respect tomo and even perform possible supra maximal resection with the bad where we want to prevent postoperative neurologic deficits. And that's the conversations we have daily at our conferences. Well the other conversation that's now becoming more important in these decisions is higher level executive function and this is what the brain connect um is all about now and there's a lot of attention now and how we can understand higher level cognitive function of the brain and when our residents call us and say, well the patient's neurologically intact after a large brain tumor resection. You know, I pause because I know they're not neurologically intact. In fact, There's probably 90% of our patients who have cognitive impairment that come to us and probably that or more who have further deficits on a higher level after surgery. And then the question is, well, how do we kind of prevent that? And as you see these networks on the right, I'm just showing you the what we call the D. M. N. Network, the default mode network and then the central executive network ce and these are networks that are kind of created and executive function. Higher level cognitive domains. You can see they're well connected, you know, all throughout the brain. So so is there a window we can go in through two brain tumors based on how these connect homes are patterned in our brain that can help us understand how to minimize these types of deficits which actually can be very disabling in our brain tumor patients. That's the story of evolution. But it is kind of an exciting story. You know, it really was born out of the the human brain mapping project that was published in 2016. So, you know, I think that's something that, you know, we are going to explore with the glioma connect um project. Well, going back to the concept of super maximum reception those. This is an editorial that. No and I just it's impressed. You'll see it probably in the next week or two through J. And S. Uh And it's really a an editorial about a paper for the Miami group where they looked at super maximum resection of eloquent gbm. Um And you know immediately you think to your mind was that a double edged sword? I mean are you going after all the tumor in an eloquent G. B. M. And hurting the patient? Well it so happened in the series of 102 patients with left hemispheric eloquent newly diagnosed GBM. They were able to um really spare neurologic function. They had no differences in rates of complications. Uh Their patients all returned back to preoperative baseline and they used a lot of Cortical sub cortical mapping type approaches during their surgery. And almost three quarters of their patients to really identify those pathways and then push the resection as far as they can. And in this case these tumors um You know they respected the contrast enhancing tumor and then they were able to perform a lumpectomy or lesion ectomy of the contrast enhancing tumor and the flare signal surrounding the tumor. Some of the discussions we have daily include molecular markers of gliomas and we're not going to touch on these too much. There are new guidelines that came out in 2021. The normal players that we talk about all the time or MGMT methylation status I. D. H mutation status. You know whether the patient has a one P. 19 Q co deletion. We know that poor prognostic factors in high grade glioma patients are really the E G fr amplified tumors specifically with the E G F. R. V. Three mutation, those with P 10 deletion tURk promoter mutations, the C. D. K. And two A. B mutations. And then of course the H three K. 27 mutations. And you know the question is we don't have that data typically upfront and surgery although there are um some interesting avenues in terms of imaging now and computer based uh learning algorithms where we may be able to dice out whether tumors E. Jafar expressing or not based on some of that and that's an exciting area. But you know should we not be as aggressive with our receptions for tumors such as Allah goes and eloquent areas which are sensitive to german therapies more so than you know, tumors that are astrocytes aromas and not as sensitive And then should we be more aggressive for the tumors that are MGMT and methylated? I mean these are some of the questions that we have but we don't have the answers for quite yet. We're moving in that direction. Well there are other challenges as well in terms of intra operative visualization and you know this is a slide that I've shown before and. You know this is after resection of the tumor and the navigation system shows you're outside of the contrast enhancing border. We know that there's been shift and brain uh movement with the craniotomy and tumor resection. So the navigation is kind of inaccurate. We look over to the left with white light can see some quarter of white matter and you know, you think you've done a good job taking out the tumor. And of course we have other modalities now with intra operative ultrasound and even inter operative them really well. You know, there's still that difficulty seeing the border and there's still that difficulty of understanding where those functional pathways are to avoid. Um you know, I think we always want to take out the tumor safely. So this is a technique that, you know, I think is now gold standard for people for patients with brain tumors and especially eloquent brain brain tissue, where we utilize multiple different mapping methods. And this is a paper from the UCSF group published last year. And you know, I love this illustration because it kind of highlights what we can do. And you know, to the right of this illustration, you can see there's um a bipolar handheld device or a monopoly Oler where we stimulate the the white matter pathways here and you can see it's the the internal capsule kind of right there and really kind of get as close as possible to those areas that are functional without hurting a patient based on the stimulation parameters that you're using and, you know, the manipulators, one that kind of gives us a little bit more cushion in terms of separation between those white matter pathways versus the probe. And then if you want to get really, really close, we use the bipolar hand piece which which can, you know, take you even closer for your receptions and and then of course you have the direct cortical stimulation as you see here uh and other mapping techniques. But you know, the combination of mapping and something like what we'll talk about in a second is fluorescence guided surgery can really be powerful because your understanding where the white matter pathways are and your delineating the tur. Um of course there are limitations with these approaches. They're they're tools. They're not for everybody. And um you know, we don't need to do awake craniotomy As much anymore. We we used to do so many more weight craniotomy. He's 10 or so years ago. But now with our mapping techniques, except for direct language mapping, we don't need to do an awake craniotomy for those patients. Um and you can see here this is kind of a nice illustration in a review. It was published a few years back, you could see that the motor pathways are on the right and you've stimulated those with whatever technology you're using. And then to the left, you can see the fluorescence guided surgery. So you could delineate the tumor and then you can discover where those functional pathways are to help guide your surgery. Well the other thing that that we have done in addition to others is understand how DT can be used for surgical planning. Well, you know, D. T. I. Is quite powerful and there's various iterations of that that have come to fruition. Um And you know the way that works is it captures the difference in water diffuse civility and and brain tissue. And then the tract ah graffiti algorithms exploit that to visualize those white matter pathways. And you know, this is synaptic system that we have and we use for all our patients and my patients at at Sinai. And you could parse out what track you want to look at in terms of the corona radio, to the cortical spinal tracts. Even down to the argument physical assaults uh and other types of fibers such as the optic radiation. So it's quite nice and it's quite helpful. But the question is, is that really a quantity quality quantitative analysis or is it more of a qualitative analysis? So you know then then the question is is DTC track topography accurate. Well right now, if you look at D. T. I. With large tumors that are endemic to this. There is no question that the adama uh and the surrounding tumor infiltration can really obscure the accuracy of D. T. I remember. So DT is based on the flow of water. So if you have a deem a president, which is basically uh um Visa genic adama, that flow of water can be disrupted and the track topography then becomes quite inaccurate. So can you model the diffusion MRI scan data To separate out the edema from the two in tumour infiltration? Um and you know, complex that those white matters with fiber crossings on an overlay of an M. R. I. Scan. So that's something that we're actually teaming up with the pen group. So raggedy verma is A D. T. I. Expert at Penn and she and I and others are working on a new diffusion tensor imaging modeling to to really understand the location of non enhancing tumor, the so called surrounding white matter pathways. Uh and take into account the edema and those infiltrating tumor cells. So how do you do that? Well, you know what what um what was just discussed was great. I mean, it was a great uh presentation on M. R. I. And this kind of piggybacks on that a little bit. So currently track typography is based on what's called single shell Vauxhall acquisitions. And you know, I'm not going to get into the physics of that because I, you know, that's out of my expertise. But now with newer generation M. R. I scans, you can obtain what's called multi shell diffusion MRI scan images. So those types of images then allow for better accounting of the water based imaging in relationship to the tur. Uh And then these types of images algorithms can be made to allow for overlay of the white matter pathways onto those images. So the question is will this allow us to um understand where those DT white matter pathways are better in these adam entous tumors and also kind of identify the surrounding white matter pathways because that would help us if we want to adopt this whole super a total or super maximum reception paradigm which as I started with the presentation is where we are heading because the contrast enhancing resection model is not where we're going to be, it's just it's outdated and we know that if we could take out more tumor it's better but we don't want to hurt our patients. So we're putting together a grant with pen and it's going to include a pilot study for inclusion of high grade glioma patients for super maximum section. And you know, we will incorporate navigation, direct electrical stimulation and fluorescence guided surgery with this new D. T. I. Modeling uh that will be developed and and it's a neat concept because we're partnering with sin Aptiva. So there's there's an industry component only in that they're incorporating it into their neuro navigation platform. The the DT technology and software is really being developed depends. So we're going to be applying it to patients. Uh And what are we gonna do? Well we're gonna we're gonna use it to evaluate patients and there's a group of neurosurgeons who are also going to be using the conventional approach. Uh And we're going to be able to look at deficits and patients with different scales including the united stroke scale and nano scores to really understand how neurologic function can be impacted pre and post surgery utilizing this new planning algorithm. So the concept is we would lay this overlay this under navigation in the synaptic system in hopes that we can identify those pathways better in hopes that we could respect better and more safely. So stay tuned for that. That's what we're getting ready to uh submit that here in the summer. Um I'm going to switch gears a little bit from the D. T. I. Concept to more of the visualization concept and you know our microscope is our workhorse. I mean that's something that we all are comfortable with. I mean it's really revolutionize revolutionize neurosurgery and really allowed us to advance in all aspects of neurosurgery without question. But you know now we have some newer visualization devices right? We have you know a device where we can activate by voice. So these are you know some tools that we have. I mean certainly you know the magnification the voice control features are fun but the really important part of that is how well can you see with these types of devices and you know the exact scope is really kind of helped me with my practice and I think it's really helped me see better and what I do in our brain to our population. And we've incorporated the track topography in that in that algorithm as you know. Uh And as as I just mentioned, we're going to try to make that better but there are still challenges with the X. A. Scope. I mean here's a view of the X. A. Scope for a high grade glioma patients. So you see this darkest tumor highlighted by the blue arrows. Okay. And it's quite apparent the visualization is quite nice, very clear panoramic view but the cancer cells are all the way out here. So you know, that's definitely something that you know is challenging and you know, we have published outcome studies. Now this is something that one of our medical students, actually two of our medical students at the time, Rebecca and Nikita and then Alex our resident and then Gabrielle, an MD PhD student at Sinai help put together with thomas. Didn't even acknowledge Tommy's at UW. Now we've put together this this series, you know, looking at outcomes of GBm patients that just underwent resection with the X. A scope. Now there was no control group with a conventional microscope but our results were quite similar to the microscope. So you know, our extent of resection was was very compatible with the microscope. And you know, our our complication rates were equally compatible or maybe less compared to the historical literature. Uh and we were able to look at um you know the six month progression free survival Which was 86% in in our patient case series of 26 patients. This is a retrospective study. But you know, these are the types of studies we need to kind of publish on new technology to really understand, you know, are they making a difference? Are they equally effective? If they're not then why should we be using them? So I'm not gonna go into too much here because we've we've kind of beat this one to death here in china. You guys all know, you know the fluorescence guided surgery story quite well and it's it's it's pretty much standard of care and most centers now actually not by all neurosurgeons. But at most centers this is an option now provided for the neurosurgical resection of tumors. And it's really based on the administration of a pro drug or floor for in this case five L. A. Which accumulates in the tumor tissue. And then we use a specific wavelength of light to excite that floor for or metabolites. We could visualize the tumor. I mean this is the paper we published now 11 years ago. Um And that same illustration I showed to you before where you know we have that sub cortical white matter area, the navigation. I don't have it here but on the prior slide shows them outside of the contrast enhancing area while we turn on the blue light. And then lo and behold it it you know avidly flores is violet red. And that's because with five L. A. We can get tissue to take up the five L. A. Outside the contrast enhancing border and metabolize it to the protocol for night. And that's been something that's been shown over and over in multiple studies. And of course walter steamer was really the pioneer with this technology and published the landmark Randomized study in 2006, which really hammered home the fact that he could almost double the rate of complete resection of patients and really make a dent in progression free survival in six months. It was a study that had a lot of question marks. You know, it wasn't powered for overall survival. There are other things that kind of um tainted the study. But listen, we have not had a randomized study since. Like this. So this is going to go down as one of the few randomized studies for high grade gliomas in terms of surgical resection. And of course we owe that to walter steamers effort. Now we've done a significant part of the work in the US in terms of a multi center study first ever. And that was published this past year and our own resident Alex cooper and our own faculty member ray Young really helped put this together And it was a multi center study that I started and Isabel was part of that and we had you know 15 other sites around the country. And we also were able to confirm you know the diagnostic rate of five L. A. Is quite high in patients. And we were able to do safe surgery and our patients and really show that um you know five L. A. Is quite helpful in detecting the tumor at multiple centers throughout the U. S. And you know I think that the UAE fluorescence guided surgery for tumors. I think that's pretty well answered now. I mean I think we could see tumors better delineate the brain tissue around the fluorescent tumor. And it's really the only way to get real time image guidance in resection of tumors. And we know we could potentially respect more of the tumor. So there are other floor floors out there and we're not going to go into them too much here. Flora scene is one that's used in a number of sites and it really relies on breakdown of the blood brain barrier. There is a window of time where you could use that. I. C. G. Is another one. And there's some other floor floors that are targeted. Now coming into play with more advanced clinical trials that target E. G. Fr And in one instance the blaze 100 agent which is based on a toxin um can target chloride channels in gliomas. But if you see on the on the lower table this is a paper Alex put together a review for us. You can see that you know I. C. G. And and florists and have been around for quite some time and they're really used for ophthalmological indications. And five is really the only one that has been approved for gliomas and removal of gliomas in terms of Fgs and safety. This is something that's also been kind of established that using fluorescence guided surgery while can result in more neurologic deficits upfront at six weeks. Those deficits balance out in our US study really confirmed that. Well there are other technologies that are now coming into play with restaurants that are quite interesting and this is out of the B. And I group utilizing vocal laser endo microscopy. Um And this is kind of an interesting concept that's based on the use of floor scene and an endoscope type type device where you could see in real time uh tumor cells on the right. They are black and white. You could see blood vessels and and you know this could help push the envelope for resection obviously if we could have it in color that would be better. But we are able to see tumor cells at the cellular level vessels around there. This could help us push the envelope as well. But again remember we still need functional data in terms of white matter pathway uh function with direct electrical stimulation. This is a technology that I just presented at the double N. S. Um using a handheld probe and Raman spectroscopy is another technology which I think is going to have a role and how we detect residual tumor tissues. So this utilizes a near for a laser that basically emits from the tip of a handheld and then excites the molecules and the vibrational patterns of those molecules then provides a signature. So if you look at this lower right hand side, the ramen spectrum could detect proteins, lipids, nucleic acids, carbohydrates. I mean it's pretty amazing what level it can detect and and the changes in those those um molecules can provide a signature in terms of tumor non tumor in a label free manner. So so this is a device we've been using for probably 1-2 years now in our cases and we're doing it for brain mets and gliomas. And we're actually collecting data with the McGill group in Canada who really introduced this study this technology years ago and we're developing machine based learning algorithms. I mean this is, you know, just a case in the O. R. Where we um basically use it to buy And we collect tissue after we get the measurement. It takes about 2-3 seconds and then we get corresponding tissue samples where we then correlate the roman signal with the historic pathology. So we can look at Marcel burden diagnosis of the tumor based on the roman spectrum that's that's collected uh and and this is done at two independent centers uh with us here. So it's an exciting device that that I think is going to have some, some merit. And how we move forward to the surgery. This is going to be just another tool where we can, you know, scan the cavity and see if we can detect tissue. And what the company is doing. It's called reveal is they're developing this display where you're going to touch the tissue you want to inspect. And it's going to say whether your signal quality is good and that's going to say tumor or no tumor. and they're working on the threshold of 15% of tumor cells, which I find fascinating in our study now, we've been using 90%, which is pretty high. But you can imagine if you can get down to a 15% threshold of that could be quite powerful. And then if it can tell you what tomo you're operating on it, it'll say good signal tumor, no tumor. And then what, you know, whether it's a glioma, whether it's a meningioma, whether it's a brain metastases or what have you. And that's based on some computer based learning that they are developing and I'm not going to get into the details here. But you can see that sensitivity and specificity is quite high for this device based on the McGill training data. And then even in the testing data was quite nice. So, you know, we've been able to kind of reproduce those results at a separate center separate surgeons, separate pathologists to really highlight the fact that this is is pretty diagnostic actually overall. So the workflow would be you would do your de bulking, you could do fluorescence guided surgery, intra operative ultrasound. You know, you could use the the new track typography type navigation. Use this device to scan the resection cavity in real time. It's nondestructive, it's just a light, get the data you do. You have and then just determine whether you want to push forward. So that's an exciting avenue that we're able to leave. There will be a multi center study coming out with that next year. Um I'm going to talk just briefly here about inter operative imaging because I think it's important, you know the M. R. I. Is something that you know has been discussed over and over for use in patients. And you know, there's definitely I think a role for intra operative imaging from that aspect, whether it's M. R. I. Or ultrasound sound because I think, you know, seeing residual tumor allows us to go back and respect that. So I think there is a role when you start looking at it in comparison to other technologies. There's not a lot of difference though between five billion I. M. R. I. Four high grade gliomas. I think if you look at you are such as low grade gliomas and other types. I do think the Imrie has the upper hand and I think that's why we're even exploring it. So I'm gonna finish off here with a novel concept that we're pushing along too in terms of utilizing five A. L. A. For what we call inter operative therapy. It's called photodynamic therapy. So patients are going through five L. A. Fluorescent got its surgery. We're able to visualize the tur resect it better. And then it so happens that if you excite five L. A. With a 635 nanometer light that allows you to kill the cancer cells. So this is a new paradigm that you know it has been around for some time with other floor floors and now being pushed along with five A. L. A. And it so happens that if you use ultrasound at a specific ah low intensity focused ultrasound not not high foods, I guess we should call it lo fu. You can also excite the the prototype warfarin which is a metabolite of five L. A. And kill the cancer cells. So we published this article last year and the french group finished their 10 The 1st 10 patients ever where they did the inter operative five photodynamic therapy. And you can see here. Um Well here's the illustration I want to show you here. Um So the concept is you resect the tumor and then you put a balloon in the cavity and then the balloon is expanded. And then what you do is you put um a laser fiber in there. So here's here's the illustration um to showcase kind of what we're talking about here. So the balloon gets expanded. There's a laser fiber in there. The laser fiber illuminates the balloon and then the time and power results in the energy deposition in the cavity. So it's it's in this case in the in the trial that we did, which is a phase one Was 200 jewels. We did not treat any patients that sign that this was all done. And uh the University of lil in France. Uh and this is Nicholas reigns one of my colleagues in the University of Louisville in France. You can see he's wearing, they're all wearing their goggles and they put the balloon in and they illuminate the cavity. So you know, we um are going to be doing this study hopefully later this year. But if you look at the results in the 1st 10 patients that they were treated, they're not bad. And if you look at the median progression free survival for newly diagnosed patients, 17.3 months and the overall survival was 23.1 months. And let me tell you something, the majority of those patients were MGmT Ian methylated. So it's a very small sample size to draw definitive conclusions and the the dose that was used was low and they're now doing it what's called the dose indigo study where they're bumping that dose up with longer light administration during surgery. But I think it's something that needs to be explored more. Here's the concept of sonar dynamic therapy. So this is cartoon showcasing a similar concept but using focused ultrasound not the light. And this is being done out of uh the B. And I my my close colleague not Orson I is really leading the way with this with the phase 01 uh called uh so knowledge since uh and the only difference with this one is they're giving the five L. A. I. V. Instead of orally. Which is interesting. But in this study they are basically treating half the tur with sonar dynamic therapy to see what kind of treatment response they're getting. These are patients who may have inoperable tumors. And then they basically just get the I. V. Five L. A. They may have had a biopsy before and then they get through these treatments with sonar dynamic therapy. So what kind of slow things down here towards the end and just really kind of go back to the concept when should we stop removing tur. Well I think we need to utilize all our tools and technology at our disposal and really balance extent of resection with function and I don't think one technology um can be relied on to perform the best surgery. I think we have to use multiple technologies and really understand how intra operative imaging visualization can help us make real time decisions to push the envelope. And we are making those decisions. So the tools and the technologies are not making those decisions for us. Write a fool with a tool. Yeah. You know the saying right, a fool with a tool is still a fool. So you know the technology is assisting us in our decision making And you know, postoperative deficits and patients is a zero sum game if more tumors removed. So you know what I tell the residents is I'm not going to push the envelope if the patient's gonna have a deficit in a patient who already has a limited survival. So that again the good with the bad. Uh and then the whole concept of higher order executive function is something that we need to understand moving forward and that's something that's getting more and more attention and patients are going to want to know about this moving along in our field. So the balance is good, Maximum safe resection or super maximum resection. And of course the baddest postoperative neurologic deficits. Um I'm going to close it up here with a case here at the end. This is the case we did a few months ago, it was a delta flight attendant. She was working on a flight from the uh J f from actually was from Nigeria to JFK and she developed right upper extremity weakness gait difficulty over a month. She had intermittent word finding difficulties. We go back here. She was taken to a local hospital and then transferred us for further care. She had continued right upper extremity weakness despite steroids. So she had a fixed deficit. So here's the tumor. Um So you know obviously we're concerned about the tumor being involved with the surrounding motor fibers. So here's the track topography and you can see the blue represents the cortical spinal tracts and that kind of is hugging that post your part. Now what do we talked about before? The edema? Really kind of obscure some of the T. So while there's no blue right next to the tumor, we know that the edema may cause inaccuracies here. So I I know that the the the tracks are right on the tuber because the patient also has a fixed deficit after steroids. So you know that is helpful. But at the same time we have to understand its limits. So she got five L. A. And we did the resection of the tumor. And then we used the extra scope and then switched over for fluorescence imaging with the the conventional microscope. We did motor mapping and we were able to excite the face, arm and leg In the post resection cavity of four million amps. And this was what we saw at that point. So there was residual fluorescence. This was along the post your margin of the and then you can see the resection cavity there. So the question is when do we stop? Right? The the urges man. I'm gonna get that fluorescence out. I'm gonna take that tumor. So I'm a better surgeon. And the patient's gonna do better. Well, no, that's not the answer. The answer is you stimulated that area at four million amps and there were cortical spinal tracks there and the patient has a deficit on steroids. So for me, I elected to stop and this is what happened. So there was a little rind of contrast there. You can see on that back part and laterally. Um She woke up with a dense right hemi presents. Her speech is fine and then her her motor function went back to normal over the course of several days. And then she's been able to ambulance. Normally she has no motor deficits and her quality of life has been spared for the most part except she's going through adjuvant treatments. You know, she has fatigue and so forth from radiation, radiation treatments and chemotherapy. So a couple of things that we just want to make sure we know is patients with deficits despite steroids are set up for worsening deficits with surgery. So pay attention to that if they get better with steroids that tells us that the edema caused the weakness. It wasn't the tur um You have to use all your tools, you know to to really understand where the tumor um is located and surrounding uh functional pathways. I think. Um You can't respect all the fluorescent tumor tissue in those areas in certain cases. And going back to the point we have to balance the good with the bad. Someone with a poor performance status post op is going to have a greater poor prognosis. So it's just not acceptable. So you know I have some other cases but I think we're going to stop there and happy to answer any questions. Thank you. Thank you doctor. All right. Thanks. Dr Rogers class. That was a great overview of the current adjective therapies we have. Um in terms of interoperable technologies. One thing that was a really hot topic at the C. N. S. I was hoping to pick your brain about the role of liquid biopsy and helping identify tumors before we get to the operating room. You grampa Great point with using new advance memory sequences to help predict different methylation says, and different potential um tumor mutations. I'm curious To hear your thoughts on the role of liquid biopsy or some limitations. And how do you think in the next 5 to 10 years that will be incorporated into a normal workflow of managing these tumors. Yeah, I think that's a great point Alex. I do think there's a lot of work being done with liquid biopsies and we've made a lot of progress before. It was very difficult to detect cells reliably in the blood because of all the different surrounding noise with proteins and other things in the blood. But now with technology we've been able to isolate ourselves better in lower numbers. So I think that's going to have a role and it's going to help give us more data in addition to the computational algorithms being developed for imaging that we have before we go to the O. R. Uh You know, the other concept is you know with roman spectroscopy is you know, I I didn't talk about this but the video system also may be able to provide that to during surgery. So we tried that out a couple of years ago. We've been trying to get into the O. R. But you know, Todd, Holland and dan origin are now moving into the realm of you know potentially diagnosing E. G. Fr status in the O. R. Uh and a couple other molecular markers. So it's it's advancing. I mean I think we're going to have more and more information and I think we still have to make those decisions um with that information at the end of the day. Thanks. I really enjoyed the talk. Cost is it's it's I assure that the residents understand this is the sort of talk you can give if you spent a career in scientific training um thinking broadly the range of topics that were discussed and very concisely presented. It's not easy to do. Um It takes I think it takes almost a lifetime of of thinking about it to condense it like this. Um and really represents what I what I think is academic neurosurgery um you know, every single almost every single case that you can, the cost just does is either enrolled in a study or he's thinking about something new many times multiple things. Um And I think this is what makes the department successful. We hope we see it in the work that raj and Jack presented and what's happening to the vascular team with multiple studies. So, you know, I'm really impressed with what is going on. If there was one area where I would like to have heard more. Um it's on what you think the future of ultrasound will be for diagnosis because as the resolution improves, that is something that is obtainable in real time. It can now be linked to the navigation with some of the newest deforming integrated software that brain labs coming out with. So I wonder how that's going to add to your I. M. R. I. And your fluorescence Costas. Yeah. You know that's a great point. The the Europeans, specifically the Italians. Uh I'm drawing a blank now fred Frederico um Anyhow, yeah, their group and actually they're going to be having whole session at the E and S on this where they're going to have a day symposium and educational seminar where you can have a hands on approach. But yeah, the the ultrasound technology is advancing with the corporation of of novel um imaging during surgery. So so you're going to overlay your M. R. I. Scan. But there are certain things with the ultrasound that you can detect now and then going back and incorporating that with brain lab for example can can really highlight um some of the margins of the tumor that normally you couldn't see with ultrasound because of the resolution. So you know they're also overlaying you know white matter tract photography surrounding the ultrasound in ways that are going to be quite powerful. So yeah stay tuned for that one. Um You know that that hasn't quite hit us well yet but it's on its way. And the Europeans are already doing a lot of this stuff with the more advanced ultrasound techniques. Yeah it only makes sense what's this? I wanted to I wanted to ask you about the workflow um for the for the photodynamic therapy because I'm sure that there's a way and at the moment I think they're inflating the balloon in the O. R. And sitting and waiting while you illuminate. But I'm sure there's gotta be a way to basically leave a balloon catheter in their post operatively and treat for hours or days even. And then pull it almost like a DVD or the way we do convection enhanced delivery in the brain stem. Yeah. Yeah. So so that's a concept that has been discussed. Um Remember the light will photo bleach the floor for. So the longer the lights there the longer the photo bleaching effect occurs and then that whole killing effect kind of goes away. Um, but the question is, could you stare tactically implant something like that and then kind of leave it in for a few hours and then kind of remove it later. So you don't have to have a craniotomy. Yeah. So, so there there are all these different techniques being developed for that. The Europeans. Um, there's two camps now there's the balloon camp which the french are leading and then the Germans are leading the interstitial photodynamic therapy camp where they're basically doing a bunch of burr holes and stereo tactic placement of laser fibers in the tumor. So they could put anywhere from 5 to 8 laser fibers in the tumor and then they basically illuminate for whatever time they want to and then they take them out. They claim that it's safe. I one of my critiques as well. The US we're not going to want to do eight, you know, different burrow holes, little burrow holes and placement of a laser fiber. We we will take the patient to the or we will put a balloon in. But you know, maybe for the inoperable tumors, like the lamest tumors where you're using light. Um, you know, lit is what we've been trying to do for some of those inoperable tumors. But the heat causes side effects that are sometimes scary. Whereas with this, could the light be a safer approach. I mean, you could argue with with stereo E. G. We can we put in 2025. So I mean with a robot you could easily put in 10 15 20 laser fibers safely if you plan it and then you can treat these deep tumors without the heat effect on. It's a cool concept. Yeah I mean and and then the question is could you start treating tumors like D. I. P. G. Tumors? You know where you know then then you know the risk kind of goes up a little bit. But I certainly think that's an approach that could be looked at thanks comments or questions. So cost is if you were to equipped a new O. R. Now with what you think is going to get us to the next 5 to 10 years and you had an unlimited amount of space and all the all the resources you need. What would you put in that Oar? Well while we talked about some of the limitations with intra operative MRI I still think there's a role for it for sure because there's going to be newer techniques with interrupt operative memory that we can capitalize in and around the O. R. Time. So I think that's an important one. And then you know there's tumor types that we still need the inter operative memory to be helpful with. I think the ramen spectroscopy handheld. It's something that's going to be incorporated. I think the video system will be at the back table. It'll be a back table type device. You know where we get little tissue specimens put them in the device and we'll get color images. Um You know I think um fluorescence guided surgery is here to stay. So you know the the new visualization devices are all have are all incorporating this the exa scopes and other things coming out. So I mean there's headlamps to we didn't even talk about that are now being used. So those are kind of the big ones. I think the mapping though still is the gold standard for functional white matter pathways. But I'm hopeful that these newer um D. T. I. Techniques will help you know overlay better track biography that we can rely on better. So those are some of the big ones. You know. The ultrasound concept also can be applied to the O. R. Not only for visualization and diagnosis but therapy. You know we we may be able to oblate tumors with a handheld device using ultrasound. We already used the Coosa for tumors. But can you imagine if you just had a a probe that um didn't make any noise? Didn't vibrate that basically admitted an ultrasound wave. And we could use that to respect us and and not um interfere with blood vessels. You know that would be kind of neat or nerves. You know some some type of Device that could differentiate between the two. I agree to that. I would add uh you know, the whole vascular access suite, you know, the the modern or of the near future I think should be thought of as a brain interventional sweep on one end really emphasizing trans vascular access. That then allows us to then move directly into transcranial access and on the other side focusing on the imaging, the navigation and the evaluation of tissue. Well, when we can get there in the next five years, I think there will be an opportunity for us to upgrade. So look forward to it. Any other comments questions. All right.