Transcript
My name is Diana Horvath from Stuttgart, from Germany, and I'm from the Neurological Department. So I'd like to show you the diagnostic follow-up of brain metastasis using contrast clearance analysis. Identifying response patterns earlier. MRIs like these, we see very often. Nearly every day. We see a ring enhancement lesion after surgery, and radiotherapy, which shows a strong enhancement two months later, and some solid aspect in other months later. So, what is it? Is it tumor or is it treatment effect? Thank you.
And conventional MRI, like seeing on this slide here on T1 images, is often is not enough to differentiate tumor progression from treatment effect. But treatment responses assessment maps or the TRAM, or so-called now contrast clearance analysis, like shown on these slides with the solid blue tumor helps us to differentiate between these two entities, and helps all the involved third party department to find best treatment for patient. Oops, that was the wrong direction, sorry. But how does it work? So, we make standard T1 images, five minutes after using...after injection normal dose of contrast agent. At this one, the early T1, and we make a second one 60 to 100 minutes later. It's the early T1 scan. You don't have to put another contrast dose.
It's just the first one you have, and you make the scan just 60 to 100 minutes later, and substrate the first one, the early T1 from the late one, from the second one, and get these TRAMS or contrast clearance analyses. And you see on this slide the green-gray matter that is very slight and homogenous T1 signal intensity over time. But in other regions, where there is a ruptured blood-brain barrier, you can see an accumulation of contrast agent over time, or a clearance of contrast agent, whether cut off by 55 minutes. And this helps us to differentiate in blue the solid tumor or some morphological active tumor, for the red one, which is the therapy-induced effect.
So, this is another example. This is the first, the early T1. You see maybe these, in this area, at [inaudible 00:03:33.272], this is high signal at the early one, and a low signal at the later T1 after Gd, and these are these blue areas in this example. This is a tumor, and the red one, where we see some slight enhancement in the early one, but the stronger one after 60 or 70 minutes, this is the necrosis on the other area. So, this is the problem with the normal MRI and the perfusions. There are nearly 20 errors we make perfusions with calculating cerebral blood volume. You see these examples here below. And it really helps, but the problem is the intensified antiangiogenetic therapy in the last years make a few false-negative perfusions. So, especially for small lesions, we can miss the target in the perfusion. Whereas contrast clearance analysis has high-specificity, and high-sensitivity, and higher image resolution, helping us to detect if even metastasis during follow-up.
So, let me now show three examples of our data. In Stuttgart we had...we made the last year since we have the contrast clearance analysis. This is a 45-year-young woman with brain cancer in September 16, and she had the metastasis nearly one year later. The brain metastasis here on the right side, temporal occipital, and she underwent brain surgery and VMAT radiotherapy with total doses of 30 Gy. Showing here on the right side, the MRI after surgery. You see some bleeding over there near the resection hole. And the next T1, the normal T1 sequences showing no pathological enhancement, even in the perfusion.
And we might, at the end of the radiotherapy, the first MRI, seeing this ring-enhancing lesion, and one month later just the same one. But what happens five months after radiotherapy? You see this different enhancement on this side with some perifocal edema, and two months later, bam, we have this lesion with a strongly enhancement, with strong perifocal edema. So, it was a little bit hard to say is it now a reoccurrence, or is it a treatment response? So, seeing...looking at the T1...Yeah, looking at the T1 here in this area, and the perfusion, we have some more weight or low cerebral blood volume. But making the contrast clearance analysis it helps us to say, this whole lesion, this one, this solid one, it has to be a recurrence, and this border is maybe necrosis.
So, at that time she underwent a second surgery. You see here the maps after the second surgery. This is the T1 without contrast agent and the T1 after contrast agent. And what is now this one? You see here, this very slight enhancement, it was hard to say, is it now a rest of the second metastasis or what? So, we made, after surgery, this second time the contrast clearancing. It's not solid tumor. It seems to be only the necrosis after first therapy. The second patient is a 63-year-old man with non-small cell lung carcinoma, having nearly one year later, this bizarre lesion on the right side parietal, with contrast enhancement.
And being a solitary lesion, we decided to make a stereotactic brain...a stereotactic radiotherapy with a total dose of 27 Gy in three single doses of 9 Gy. This is the volume you see for the...I have to say for the first radiation. And two months later, after radiotherapy, we see here the initial pictures, the initial T1, and this is after radiosurgery. But what is this one? We have here a second lesion, and looking at the slice maps, after a stereotactic needle biopsy, we see this lesion on the trajectory of the needle. And looking to the first CT after the stereotactic biopsy, it's just really on this trajectory, but we weren't sure at that moment is it just a reaction tissue or what is it?
So, we made another MRI, one month later, seeing this second lesion getting bigger, making a perfusion with a high cerebral blood volume at this side. And you see here, this was the first...the lesion, the new lesion, and this is one month later with it getting really bigger with some perifocal edema. At that moment we made the contrast clearance analysis, and we see on this side, the first therapied metastasis, and this new lesion with blue area, with solid new metastasis on the trajectory. So, I should get another of the second radiotherapy. On this area, you see here the actual, the second volume. And this is, for example here, the first one he made. So, last time we saw him it was two weeks after radiotherapy, and we saw him in our emergency room with headache. But he doesn't seem to have any complications or a new lesion. This is the last CT we have from him.
And third patient is a 55-year-old man with a malignant melanoma in 14. And has this metastasis on the same time, on the left side temporal occipital. He underwent surgery and VMAT with a 54 Gy. This is the VMAT. And we see two months later another micro-metastasis on the cerebral side here on the left. And this, where she went stereotactic radiotherapy, and it was well done. Both metastases has no recurrent. But two months later he has the third metastasis on the lenticular nucleus. And this should make us some headache the next three years. These metastases were also stereotactic radiotherapied, and we see after seven months and nine months after radiation, a little bit stronger enhancement on T1, with first edema, which is normal, and then it's getting a little bit smaller.
So, what happened after? Ten months after radiation, we have a really strong enhancement with a huge perifocal edema, and at that time we made a single voxel spectroscopy. Seeing what? We see some lipids on this side, but not very much. The choline peak is not as high as we see it at metastasis. But we can't be really sure what this spectroscopy shows because we see this very inhomogeneous baseline. And we made also the perfusions, so it is showing, yes, a low cerebral blood volume at this time. So, we said, it doesn't look like a recurrence, but we have to make some other controls. And we made it for 14 and 17 months after radiation, seeing first this getting bigger, the lesion, and the perfusion is just the same. It doesn't show a real elevated cerebral blood volume. So, which was a necrosis 17 months after radiotherapy.
And this was also showed by the second spectroscopy made now with a...sorry, with a very high lipid, and showing this necrosis at this time. But nearly two year after the radiation, we see a total different aspect of this lesion. It's kind of bigger, and the contrast enhancement you see, it's totally different from the last one we had. So, having a positive B-RAF mutation here, we first get chemotherapy with no MRI effect one month later. So, he underwent surgery. We see the patient after surgery, but unfortunately, he get here an ischemia on this area, on this surgery area. So, the next control it was five months later, and we see a kind of strong T1 enhancement, and it was just too strong for ischemia five months later.
So, being uncertain about this lesion, we made the next control four months later. Seeing the T1 lesion here getting smaller, and at that time, we made the contrast clearance analysis. And we see here, the perifocal necrosis, and only a very little spot of blue area. Three months later, the T1 gets smaller, and even the blue area gets smaller at that time, and even the last control we had, it was this one with a further small lesion, a small blue area in this region. So, we see, with contrast clearance analysis, it's a huge support for us in diagnosis to differentiate recurrence from treatment effect. Thank you very much.
And conventional MRI, like seeing on this slide here on T1 images, is often is not enough to differentiate tumor progression from treatment effect. But treatment responses assessment maps or the TRAM, or so-called now contrast clearance analysis, like shown on these slides with the solid blue tumor helps us to differentiate between these two entities, and helps all the involved third party department to find best treatment for patient. Oops, that was the wrong direction, sorry. But how does it work? So, we make standard T1 images, five minutes after using...after injection normal dose of contrast agent. At this one, the early T1, and we make a second one 60 to 100 minutes later. It's the early T1 scan. You don't have to put another contrast dose.
It's just the first one you have, and you make the scan just 60 to 100 minutes later, and substrate the first one, the early T1 from the late one, from the second one, and get these TRAMS or contrast clearance analyses. And you see on this slide the green-gray matter that is very slight and homogenous T1 signal intensity over time. But in other regions, where there is a ruptured blood-brain barrier, you can see an accumulation of contrast agent over time, or a clearance of contrast agent, whether cut off by 55 minutes. And this helps us to differentiate in blue the solid tumor or some morphological active tumor, for the red one, which is the therapy-induced effect.
So, this is another example. This is the first, the early T1. You see maybe these, in this area, at [inaudible 00:03:33.272], this is high signal at the early one, and a low signal at the later T1 after Gd, and these are these blue areas in this example. This is a tumor, and the red one, where we see some slight enhancement in the early one, but the stronger one after 60 or 70 minutes, this is the necrosis on the other area. So, this is the problem with the normal MRI and the perfusions. There are nearly 20 errors we make perfusions with calculating cerebral blood volume. You see these examples here below. And it really helps, but the problem is the intensified antiangiogenetic therapy in the last years make a few false-negative perfusions. So, especially for small lesions, we can miss the target in the perfusion. Whereas contrast clearance analysis has high-specificity, and high-sensitivity, and higher image resolution, helping us to detect if even metastasis during follow-up.
So, let me now show three examples of our data. In Stuttgart we had...we made the last year since we have the contrast clearance analysis. This is a 45-year-young woman with brain cancer in September 16, and she had the metastasis nearly one year later. The brain metastasis here on the right side, temporal occipital, and she underwent brain surgery and VMAT radiotherapy with total doses of 30 Gy. Showing here on the right side, the MRI after surgery. You see some bleeding over there near the resection hole. And the next T1, the normal T1 sequences showing no pathological enhancement, even in the perfusion.
And we might, at the end of the radiotherapy, the first MRI, seeing this ring-enhancing lesion, and one month later just the same one. But what happens five months after radiotherapy? You see this different enhancement on this side with some perifocal edema, and two months later, bam, we have this lesion with a strongly enhancement, with strong perifocal edema. So, it was a little bit hard to say is it now a reoccurrence, or is it a treatment response? So, seeing...looking at the T1...Yeah, looking at the T1 here in this area, and the perfusion, we have some more weight or low cerebral blood volume. But making the contrast clearance analysis it helps us to say, this whole lesion, this one, this solid one, it has to be a recurrence, and this border is maybe necrosis.
So, at that time she underwent a second surgery. You see here the maps after the second surgery. This is the T1 without contrast agent and the T1 after contrast agent. And what is now this one? You see here, this very slight enhancement, it was hard to say, is it now a rest of the second metastasis or what? So, we made, after surgery, this second time the contrast clearancing. It's not solid tumor. It seems to be only the necrosis after first therapy. The second patient is a 63-year-old man with non-small cell lung carcinoma, having nearly one year later, this bizarre lesion on the right side parietal, with contrast enhancement.
And being a solitary lesion, we decided to make a stereotactic brain...a stereotactic radiotherapy with a total dose of 27 Gy in three single doses of 9 Gy. This is the volume you see for the...I have to say for the first radiation. And two months later, after radiotherapy, we see here the initial pictures, the initial T1, and this is after radiosurgery. But what is this one? We have here a second lesion, and looking at the slice maps, after a stereotactic needle biopsy, we see this lesion on the trajectory of the needle. And looking to the first CT after the stereotactic biopsy, it's just really on this trajectory, but we weren't sure at that moment is it just a reaction tissue or what is it?
So, we made another MRI, one month later, seeing this second lesion getting bigger, making a perfusion with a high cerebral blood volume at this side. And you see here, this was the first...the lesion, the new lesion, and this is one month later with it getting really bigger with some perifocal edema. At that moment we made the contrast clearance analysis, and we see on this side, the first therapied metastasis, and this new lesion with blue area, with solid new metastasis on the trajectory. So, I should get another of the second radiotherapy. On this area, you see here the actual, the second volume. And this is, for example here, the first one he made. So, last time we saw him it was two weeks after radiotherapy, and we saw him in our emergency room with headache. But he doesn't seem to have any complications or a new lesion. This is the last CT we have from him.
And third patient is a 55-year-old man with a malignant melanoma in 14. And has this metastasis on the same time, on the left side temporal occipital. He underwent surgery and VMAT with a 54 Gy. This is the VMAT. And we see two months later another micro-metastasis on the cerebral side here on the left. And this, where she went stereotactic radiotherapy, and it was well done. Both metastases has no recurrent. But two months later he has the third metastasis on the lenticular nucleus. And this should make us some headache the next three years. These metastases were also stereotactic radiotherapied, and we see after seven months and nine months after radiation, a little bit stronger enhancement on T1, with first edema, which is normal, and then it's getting a little bit smaller.
So, what happened after? Ten months after radiation, we have a really strong enhancement with a huge perifocal edema, and at that time we made a single voxel spectroscopy. Seeing what? We see some lipids on this side, but not very much. The choline peak is not as high as we see it at metastasis. But we can't be really sure what this spectroscopy shows because we see this very inhomogeneous baseline. And we made also the perfusions, so it is showing, yes, a low cerebral blood volume at this time. So, we said, it doesn't look like a recurrence, but we have to make some other controls. And we made it for 14 and 17 months after radiation, seeing first this getting bigger, the lesion, and the perfusion is just the same. It doesn't show a real elevated cerebral blood volume. So, which was a necrosis 17 months after radiotherapy.
And this was also showed by the second spectroscopy made now with a...sorry, with a very high lipid, and showing this necrosis at this time. But nearly two year after the radiation, we see a total different aspect of this lesion. It's kind of bigger, and the contrast enhancement you see, it's totally different from the last one we had. So, having a positive B-RAF mutation here, we first get chemotherapy with no MRI effect one month later. So, he underwent surgery. We see the patient after surgery, but unfortunately, he get here an ischemia on this area, on this surgery area. So, the next control it was five months later, and we see a kind of strong T1 enhancement, and it was just too strong for ischemia five months later.
So, being uncertain about this lesion, we made the next control four months later. Seeing the T1 lesion here getting smaller, and at that time, we made the contrast clearance analysis. And we see here, the perifocal necrosis, and only a very little spot of blue area. Three months later, the T1 gets smaller, and even the blue area gets smaller at that time, and even the last control we had, it was this one with a further small lesion, a small blue area in this region. So, we see, with contrast clearance analysis, it's a huge support for us in diagnosis to differentiate recurrence from treatment effect. Thank you very much.