 Hello, so this would be a continuation of my initial lecture, which was where I talked about the WHO classification, the newer WHO classification and the various markers and genetic codes that we have to take into account when we are talking about tumors. Most of that lecture is geared towards how to manage a patient. So that picture was geared towards people who actually treat patients. This is geared towards people who are entirely in a freestanding diagnostic institutions, not so much as a neuro-oncology or cancer center where they're actually directly involved in treatment of patients. So this is something that every neuro radiologist should be able to recognize and general radiologist should have a ballpark of what I'll be talking in the next two sections, where I'll be going along each specific cell line of a tumor and I'll be taking a few examples and talking about how they are presenting what is the most classic picture of that on imaging and what would be the things that we are supposed to tell the clinician when we see that. One of the things that we should be very careful of is the mass effect. See all tumors have masses, they're masses, so they have mass effect. That is one of the hallmarks when you see an abnormal signal on an MR, an abnormal attenuation on a CT, whether there is volume loss or mass effect. If there's volume loss, it's an old injury, it's gliosis, not something we have to be worried about. When you see a mass, it can be anything causing mass effect, but tumors will also be causing mass effect. Mass effect is something that we have to be especially paying more attention to it because this is what immediately kills the patient, not the tumor, the tumor can be treated, if we have time with it, but mass effect is something that can overnight kill the patient, especially when tumors are present in puscia fossa and this is not just for tumors, this is for infections, this is for abscess, this is for hematomas, trauma, subdural collection, sub-epidural collections, anything. If you see something causing mass effect or attenuation, that is something that can kill a patient very, very quickly and you have to be immediately calling the clinician, not letting the patient go home and immediately taking care of the patient, they should not leave the hospital in that situation. So that is something that is when we are talking about tumors, every radiologist and your radiologist, this is something that they should pay special attention to. So going on a step-by-step basis, one of the few things that I want you to remember from this lecture is, do not be obsessed with trying to come up with a histological diagnosis, almost a majority of the time, we find out the exact histologies, even between say WHO one through WHO two and two to three, we find out the correct diagnosis after the biopsy because the tumor may look overall like something and then is actually the most aggressive cell line is a different set of tumor or the genetic cell line is of a different type, like I mentioned in the first lecture. It is the genetic code which trumps the histological appearance. So the correct diagnosis will be maybe completely different of what we are thinking about. To be in the correct ballpark is acceptable. What we have to do as a physician, as a radiologist, our job is not to let a patient who can die or with the aggressive tumor to go home without treatment and not make sure that a patient who has a benign lesion, something what in bones we call as do not touch lesion, something like that in brain, if he has something which is not very aggressive lesion, make sure that the surgeon doesn't get to operate on that, because surgeon's job is to operate, they will operate on anything, our job is to make sure that an unnecessary patient does not go to a surgery. The most important, as I mentioned in the first slide, the most important point that you have to know is that all masses have mass effect and this is what kills the patient quickly and this is what we have to be careful of. That is one point. The other point is if you see a lesion and it does not have mass effect, chances are it is not likely a neoplasm. It is not likely a very aggressive lesion. It is more likely a gliosis or some old pathology which is giving an artifactual appearance of a neoplasm. So just remember that. This is the other thing that I again talked about. The tumors may not be what we see them on imaging. They might turn out to be something completely different because they are histologically named after the most aggressive cell line and also even if they have a completely different histology if the genotype is different, then they will be named after the type cell line. How do we classify tumors? Luckily, we do not have TNM classification but we still have to be talking about what the location, what kind of cell line it is, what kind of histology it is to some extent. We cannot tell the histological diagnosis but we can tell to some extent of where exactly what kind of cell it may be arising from. So we divide it according to the location where it can be intraaxial or arising from the parenchyma or it can be extraaxial and that includes the ventricular system. Something like a colloid cyst or say intraventricular meningioma would still come into an extraaxial lesion. A colloid cyst would not be an intraaxial lesion. Then it may be arising from a bone directly like a metastatic lesion or a bone pathology that is extending and pushing the brain parenchyma and it's intraaxial in location, something like that. And Dural is another location which it can be from the extraaxial. And most of the time it is going to be meningioma but Dural-based metastasis, Dural-based collections something like in leukemia, CLL, you can have collections over there which would be tumors and they're essentially confined within the Dura. So those would be the other extraaxial pathologies. Then this is by location. Once you come into the intraaxial locations we tend to give a kind of a diagnosis which would be along the cell lines. So it may arise from astrocytes so you'll call it a glial tumor or they can arise from pitatory cells. So you will give according to what it may be arising from like a neuroendocrine or a pharyngeal tissue. So pharyngeal tissue would be include macrodinoma, microdenoma, Rathke-Clapsis, craniopharyngeal tumors, those kind. That would be what you would be talking about. If they might arise from ependymol cell line with ependymoma being more so into projecting into the ventricular system, subependymol more so along the parankamal lining. Although keep in mind that subependymol has a better problem than ependymol. Then they may arise from nerve cells such as schwannoma, neurofibroma or they arise from coroed plexus cells. They can be both melanin and benign and accordingly they're termed as papilloma or papillary carcinoma. Then they may be arising from primitive cells like teratoma, dermoid, epidermoid, germinoma. Those would be the things that you would think of if they're arising from cells. And then it may be arising from arachnoid cells or lymphoid cells or pineal gland cells or they may be metastatic in nature or they may be arising from meningiol cells. Now keep in mind that the arachnoid capsules or the meningiol cells do not necessarily have to be entirely located within the deural lining. They can be associated in the ventricular lining. They can be in the PL lining. So all those regions arising from those can still be meningiomas. We have to keep that in mind. So that would be the description for all the tumors arising in the brain panenchyma. And then you tend to give them some sort of diagnosis from what possibly the underlying pathology may be. Then coming out into X triaxial location we talked about if it may be ventricular, a tumor would be a coliopsyst. You can have these deural cystic cirrhosis or other parasitic infections. Or you can have lesions arising from the deural lining which may be meningioma or maybe deural bed monastasis or they may be arising from bone. From the skull base you would have something like a codoma, controsarcoma, plasma cytoma or from any other portion of the calvarium you can have metastatic disease. So once we see a tumor the first thing we have to tell what the location is. We talked about intraaxial and X triaxial. So how do you tell that? So all intraaxial tumors there is no continuity with the bone. There are very rarely any bone changes. I have seen in my entire 15 years of practice one GBM which is extending directly into the bone. Otherwise they're all confined within the brain without any associated bone changes. They cause effacement of CSF spaces. There is no corticometallory buckling which is seen in X triaxial tumors like meningioma where you also have a CSF craft which is present. And gray white distinction is obliterated or involved in intraaxial tumor and vascular supply is generally from anulcarotid artery. When we see a tumor, so now we have decided that it is an intraaxial tumor. Now when we see a tumor, what do we talk of? We have to tell how big is the tumor? What is the extent of the tumor? How many lobes it is involving? Whether it is involving the gray matter, white matter area? Then we have to talk about when we talk about the tumor we have to tell what is the actual viable tumor because a lot of time, a lot of tumor present with cyst and a solid nodule. In most of the things, the solid nodule is the real tumor. The cystic portion is just something which is with the tumor and when they go in surgically, they reset the solid nodule, the cyst involutes most of the time on its own. So we have to tell the enhancing component in an aggressive neoplasm, that is the viable tumor. If the periphery of the cyst is enhancing, then the cyst is also part of the tumor. So you have to tell about that. That also comes into the viable tumor. And if possible, I know the surgeons don't tend to like it, but what are the possible treatment options that you can mention? Because if there's a tumor, say, you're talking about a pituitary lesion and it is coming too close or is almost abutting the optic pathways, then gamma knife radiation therapy from the get go is not something in option. You have to debulk so that there is greater than two millimeter gap between the optic pathways because otherwise, if you heat up the tumor by gamma knife, if you burn the tumor, then that direct heat can be conveyed into the optic pathways and it can cause blindness. So that is something you have to mention some sort of treatment options or things that are not to be done to that patient. Then lastly, I talked about what kills the patient. This is what is the emergency is the mass effect. If the patient is herniating, if the degen is in puscia fossa, the patient can rapidly degenerate and deteriorate. This is something you have to mention. Then how do the tumors spread? They can have direct extension. So they'll spread along the axons, the perivascular space, and if there is a surgery or a biopsy, they can spread along that. So that would be a direct contiguous spread of the tumor. Then you have what is called as a distance spread. Now again, keep in mind, brain tumors rarely ever metastatized. There are some tumors like a coroplexus papillary carcinoma or a medial blastoma, ependymoma. Those kind of tumors do metastatize but they stay confined to the neural axis and they can go down along the spinal cord or superior to the supratentorial region. And they metastatize along the PL or the leptomine gel linings and that is called as the drop metastasis. Then you can have metastasis along the transseptimal lining. This is seen frequently in GBMs where you see one GBM completely disrupting the ependymal lining and then completely opposite side on the brain or a distant area. You see another enhancing agent. So one, it can be a multifocal GBM which is certainly a possibility or it can be a transseptimal spread of a tumor. And then it can extend, say, if a tumor extends up to the PL lining, it can spread along the PL lining and then have another focus or a deposit distant from the original one and that is the spread of the tumor, edema. So tumors cause vasogenic edema. You have to differentiate between vasogenic edema and cytotoxic edema. Cytotoxic edema is something that is like an active edema where a sodium-potassium pump defect is responsible for it. There is ischemia infection toxic metabolic conditions whereas in abrupt insult to a brain, it is generally vasogenic edema such as a trauma tumor hemorrhage. And here in this case, the mechanism is defect in the blood-brain barrier. The edema tends to be extracellular. It responds very well to steroid treatment and cortex is generally spared in edema. So these are the things that overall, interacts on tumors that you're supposed to mention that there it is arising, how much it has spread, what are the things it is involving and the mass effect, the most important being the mass effect. Now let's go along the cell lines. Let's start with the glial tumors or astrocytic tumors. And this is again, we talked about all the genetic markers. We may see, we may feel it to be a certain type of glial tumor. It may come back as a completely different tumor based on its genotype. So keep that in mind. We don't have to be 100% sure. We have to tell them that there is a tumor. It is causing mass effect. These are the locations. These are the possible approaches that can be used. That is our job in your radiology. Now, we talked about the WHO classification. This is more so geared according to how, if I look at a tumor, what do I call it? Now grade one exactly by a WHO classification where they go into those four criteria of gliomas that it doesn't have any of those criteria, it's all fine. It's what the true way should be. But when you're looking at a case and you see a certain kind of tumor, there are certain imaging characteristics that we use to decide that what is grade one, what is grade two. And I'm going to be talking about more so focused according to a clinical approach or sitting on a reading room approach as to how I or in our institution, how we go about talking about tumors. We had talked about that they're classified according to grade one through grade four. So according to me, when I see a tumor which is solid, no necrosis, no enhancement, very minimal peritumoral edema, very minimal or rather a very narrow zone of transition, we call it a grade one tumor. And that being the low grade astrocytoma and other ones being gangloglioma, gangliocytoma, disembryo-pathetic neuroactronomal tumor, those kinds of tumors are generally very, very low grade tumors. So what we'll see is a non-enhancing tumor with a narrow zone of transition, not associated with enhancement. Very frequently, the three I talked about, gangloglioma, gangliocytoma, low grade and astrocytoma involve the mesial temporal lobe. When we see an abnormal signal intensity in the mesial temporal lobe, it can be either a tumor or it can be mesial temporal sclerosis. So mesial temporal sclerosis will have loss of volume. It will have prominent CSF space as it will have a dilated temporal horn. So those are the things that you will look for in mesial temporal sclerosis. Here, it will be exactly the opposite. It will be mass effect. There'll be compression of the temporal horn. There'll be obliteration of the CSF spaces. Overall, it will look like a very bulky appearance as we are looking over here. This was a low grade astrocytoma. All these may still present with seizure epilepsy, but again, we have to differentiate between a tumor and mesial temporal sclerosis. Now, some of these tumors like gangliocytoma can have a small cystic areas, may have a faint enhancement, but by far, these are non-enhancing, low grade tumors confined to the location. They can be anywhere in the brain. These three tend to be along the mesial temporal lobe as opposed to immediately lateral to it. And the lateral aspect of the temporal lobe, temporal parietal region, is the disembroplastic neurotectoral tumor. This is again a low grade neoplasm. It is something which grows very slowly. In fact, it involves both the cortex and the white matter can have a bubbly appearance. It is completely non-enhancing, generally low attenuation on CT and low signal intensity on T1, bright on T2 signal and no enhancement associated. But then very, very infrequently, do they cause any significant mass effect? We'll have a very narrow zone of transition where the subjects and brain will be completely normal. They may present with seizures or headache or maybe incidentally detected. So these, again, grade one tumors, when I look at it, it is going to be a focal lesion with surrounding brain being completely narrow with very little mass effect, low T1, bright T2, low attenuation on CT, absolutely no enhancement associated with it. So this condition lermidiculo disease is kind of a funny thing. It is classified as a tumor. It is also sometimes called as a benign condition, but it tends to grow progressively. It can tend to grow in the significance of that as it is in the posterior fossa where there's not much space. So it can compress the font vertical cause hydrocephalus. It can herniate it and that can suddenly decompensate the patient and kill the patient. Even the hydrocephalus can suddenly decompensate and kill the patient. The classic appearance would be those prominent folia that you see along the cerebellar lining. They are maintained. They are thickly packed over there and they cause distortion of the one side of the cerebellum and they compress the fourth ventricle or the aqueduct of selvius and are associated with restricted diffusion. So this is a dysplastic ganglioncytoma can also have a bubbly kind of appearance. Again, most important thing is it will be associated with very little enhancement. If any, the cerebellar folia will be maintained and it will be kind of involving one side of the cerebellar hemisphere. There's no associated necrosis. There is no significant mass effect. Again, it is confined to a location. There is the suggestion, brain-parent chimer tends to appear completely normal. So it will be a very narrow zone of transition abruptly. The rest of the brain will be completely normal. So we talked about grade one new plasma. Now what makes grade one to grade two on imaging? On grade one to grade two on imaging is basically we start seeing enhancement in that tumor. Otherwise the tumor will be exactly the same. It will be low T1, bright T2, no associated necrosis, no hemorrhage associated with it. But we start seeing enhancement with it and there might be some peritumoral abnormal intensity. So this would be a grade two new plasma. We don't see any necrosis associated with it. There is no associated hematoma associated with it. There is no significant mass effect. In this case, there is no peritumoral edema. There's a very narrow zone of transition, but there is enhancement associated with it on the post contrast T1 on the right. So this would come under grade two tumor by imaging. This is another one, oligodendroclioma. Some people tend to consider this to be a very benign tumor, but oligodendroclioma has a wide range. It can look like a very, very benign tumor confined into the frontal lobe, lower tenuation, narrow zone of transition. Yet at the other extreme, there are three to 5% which shows necrosis and intense enhancement and appear very, very aggressive. When you look at it, you call it a grade three new plasma, but it turns out to be having calcification. And once you see calcification, that tumor is going to be an oligodendroclioma unless proven as something else. By far, if you see a calcification in a tumor, you will consider oligodendroclioma as your primary diagnosis. So these tend to be having a less well circumscribed than the grade one neoplasm, tend to have some peritumoral abdominal signal. They're kind of infiltrative. They're not kind of like a clear margin and they're related with calcifications. This is a case of another case of oligodendroclioma where the first case is in the right frontal, the second in the right right left cases, the left frontal aloe where you have loss of gray white distinction. You have a mass over there low T1, high T2 signal intensity. This may or may not have enhancement associated with it, but will definitely have calcification which will be the hallmark of an oligodendroclioma. Now, not all oligodendrocliomas have calcification about like 30 to 50% of the oligodendrocliomas tend to have calcification. But once you see calcification, it is going to be unless proven by the white liquid endoclioma. This is another example of an atypical oligodendroclioma where I was talking about where they can look as very, very aggressive. So the second and the third cases which we have in the middle and under right, you have intense enhancement associated with it. Now this can, anybody can easily confuse that this is a very poor zone of transition on the second and the third case. It has intense enhancement, significant mass effect. This can be an up and plastics astrocytoma and nobody will be wrong in giving this out as grade three. But this turned out to be like a oligodendroclioma. Now I had talked to you about cystic and solid neoplasm. One of them in a childhood is the polycytic astrocytoma which present as a cyst and a solid non-linear in an adult patient. This is the entity pliomorphic xanthoastrocytoma that gives an identical appearance. You will assist an immural nodule again in which you have the cyst portion which does not have peripheral enhancement. That is not the tumor component. The tumor component is the solid enhancing nodule which is present. If there is enhancement along the periphery then you should consider that the cyst also as being a viable tumor and that might be centered in the crosses or that is a cystic component of a neoplasm. So look for enhancement carefully along the margin. That is what decides. So if you see a cyst and a solid nodule in an adult patient in that these tend to be located in the temporal or inferior frontal lobe, the primary diagnosis should be pliomorphic astrocytoma. Now what makes grade two into grade three? We talked about the cystic lesion but that is not a parasitic astrocytoma or pliomorphic xanthoastrocytoma is not a grade three neoplasm. The cyst is not a tumor. To make it into a grade three neoplasm you should start having central necrosis. So you will have enhancement. You will lose the narrow zone of transition. You'll have significant peritumeral changes. You'll have significant mass effect but the hallmark that we use to convert it into a grade three neoplasm necrosis associated with it. So this is an example of that where you have the second and third slides which showing a low attenuation mass lesion and contrast administration. There is peripheral enhancement. So if you see there is enhancement along the margin of the central necrosis. So this is not just a cyst which is associated with the neoplasm but it actually the necrosis present in the tumor and the periphery is also a viable neoplasm. So this is what we use in WHO three classification that you will have a central necrosis present in the neoplasm. So you will have a wide range of transition. You will have significant peritumeral edema. You may or may not have significant associated with it. This is another case of type three tumor where you have central areas of necrosis. You have peripheral enhancement. You have a wide zone of transition significant peritumeral edema, significant mass effect and T2 hyper intensity, flare hyper intensity, low T1 signal associated with it but you should not have hemorrhage when you are calling the WHO three classification. So you will have necrosis. You will have enhancement which is a step up from grade two neoplasm because you're getting necrosis but you should have hemorrhage. Once you start getting hemorrhage in the tumor we tend to start calling it grade four neoplasm. So everything that the grade three has central necrosis, RAP or significant enhancement, wide zone of transition, edema, abnormal signal, peritumeral signal abnormality but with the presence of hemorrhage we will call it grade four neoplasm. So or GBM or gliomatocysterebra. Now gliomatocysterebra is unusual in the fact that it may or may not have enhancement associated with it. It may or may not have necrosis or hemorrhage associated with it but it is still a grade four neoplasm. In fact, it is one of the most aggressive neoplasm rapidly spreading along the entire cerebral hemisphere involving more than one lobe. Sometimes the entire cerebral hemisphere with significant mass effect and a very, very difficult to treat. Now this one was a GBM. Now we can see necrosis and associated hemorrhage in it. So this was a pre contrast on the right, pre contrast CT. So there is a mass lesion but in the mass lesion that there is hemorrhage. Now when you see it for the first time you don't straight away call it a GBM. You will have to rule out other conditions like vasculopathy, amyloid angiopathy, trauma or venous sinus thrombosis, cortical vein thrombosis as the causes of hemorrhage. Once you have ruled that out and after you do an MR, wait for the tamponade effect to go away and then you do an MR with post contrast imaging and you see enhancement and all those things. Then you call it a tumor. You don't just jump to the UC bleed and this is great for neoplasm. We have to rule out all the other conditions. On the right again, you see a centrally necrotic peripherally enhancing with central area of hematoma along the dorsal posterior aspect. This was another case of GBM. Now look at the peritumoral edema, significant peritumoral edema, significant abnormal attenuation has a distant enhancement of SAS compression on the ventricle causing herniation. Now that is what can kill the patient quickly. The GBM, you still have time to treat it, but the herniation and you can also see the left lateral ventricle is getting dilated so it is being trapped. So these are the things that are emergencies. This patient should not go home. You should hold the patient at your institution or he should go directly to the ER and the surgeon should be aware of this because this patient can rapidly and say it and die. Now, the classic thing about GBM is it crosses midline. Whenever they are close to the corpus callus, they catch the white matter fibers and immediately cross over to the other side. There are other conditions that can cross the midline, but when you see a central necrotic peripheral enhancing neoplasm, this is what you would think of. It would be GBM, no other tumor tends to cross the midline. So these are multiple different cases of a GBM. Central necrosis, crossing the midline, peripheral enhancement, significant peritumoral edema, significant mass effect. So even if in this case you don't see a hemorrhage in it, but it is crossing the midline, then it is still a grade four GBM. It is not going to be grade three or grade two neoplasm. Only GBMs can cross the midline. These are the things that actually cross the midline. So all these will remain in the differential. In a tumor, it is going to be GBM and lymphoma. Then other things that can do that are demyelinating disease, metastasis and infection, all those things. So if you see a central necrotic peripheral enhancing mass and you are thinking of neoplasm, it is going to be between metastasis and GBM. Lymphomas tend to be solid with restricted diffusion and with intense enhancement in sheaths. That would be a classic case. Lymphoma, they tend to have the ventricular lining and they can definitely cross over the midline along the corpus callosum, but these are solid tumors. They generally don't have central necrosis as would be seen with the GBM. The demyelinating disease would be enhancing with restricted diffusion, but focal areas, not with bulky mass effect associated with it. So these are the things that you have to keep whenever you see a lesion along the scallosum crossing the midline. This is what we had talked about initially when I was talking about the GBM, that this is an aggressive form, gliometastase cerebrate. It is a great phoneoplasm. We may or may not see hemorrhage every time, but this is a tumor that spreads along sometimes along the entire cerebral hemisphere. Sometimes it even crosses the midline and goes to the other cerebral hemisphere and there'll be wide zone of transition, low attenuation on CT, T2 flare, signal abnormality. In fact, you would think that there is almost the entire brain is abnormal. And if it would be a child, you would think of something like migrations abnormalities and those kind of things, or what is going on with the brain, but you may or may not see enhancement in it. And once you see for multifocal areas of these, then it is going to be your diagnosis should be gliometastase cerebrate. This is another case of gliometastase cerebrate. You get on the first case, you can see that almost the entire right cerebral hemisphere and portions of the left frontal lobe are involved. It is crossing both along the anterior commissure. It is crossing along the corpus callosum, sphenium of the corpus callosum in the first case. So this is again something like a tumor. It is not having necrosis. There's no clear hemorrhage. This would be still great for gliometastase cerebrate. The same thing in the second case where you have multiple areas of T2 hyperintensity. You have lost your gray white distinction with mass effect and cortical swelling. This tends to grow along the cortical lining. And this would be another case of gliometastase cerebrate. In the third case, you have multiple areas of enhancement separately in the white saloon fissure than in the white peri-atrial region. Now, this would have a differential of either multifocal gliometase cerebrate or it would have a differential of glioblastoma multiforme or gliometase cerebrate. Since there are so many areas involved with mass effect, but there are different locations. So that would be the difference in this condition. Now, one of the things that you have to differentiate when you see a centrally necrotic peripherally-enhancing lesion would be from an abscess as well as a hematoma. All three will give you similar changes where you'll have a central area of non-enhancement, which is a necrosis and then peripheral area of enhancement. A hematoma, as it is involuting, they're on not replaced by hemocidron yet, you will have the identical appearance. But neoplasms tend to have slightly thicker wall and they would not have central areas of restricted diffusion, which will be classically seen in an abscess. One of the things that you have to keep in mind is those micro hematomas, small hematomas, or hemorrhagic metastases may potentially have associated restricted diffusion. So that even more confounds the differential as to whether it is going to be septic emboli or is it like metastases or is it a hematoma or what is it? So, but that is something that you have to keep in mind that small hemorrhagic metastases can have associated restricted diffusion. So this was the first case is a case of an abscess where is this central area of restricted diffusion. The second case, there is no restricted diffusion. This was a case of grade four neoplasm glib-blaster momentiforme. So these are the things we talk about that. How do we go from grade one through grade four? So grade one would be a solid non-enhancing tumor. Grade two, you add minimal amount of enhancement without necrosis. In grade three, you add necrosis to it and on grade four, you add hemorrhage into the necrosis. So that would be overall summary of how we classify glial tumors. So that would be the initial presentation of the tumor. Now we have to talk once we start treating the tumors, once you have treated the tumor, how do we follow up glial tumors? So it all depends upon non-enhancing versus enhancing or WHO one versus WHO two, three and four. What do we look for? So if it was WHO one, the initial tumor was not enhancing, so you can't rely on perfusion imaging or post-contrast imaging for recurrent tumor. What you're looking for, your money images are the T2 images, where T2, it looks like more, like a slightly darker soft tissue, which is new, which is within the area of treatment or T2 hyperintensity, which is generally representing gliosis. So look for that. Look on the, that would be one thing. On the other thing would be ADC. ADC would have, it would be dark, recurrent tumor would be dark on ADC. Contrast imaging is not a reliable thing. So you have to see subsequent studies. And sometimes what happens is you keep seeing the, comparing it to the immediately prior comparison and you say, unchange, unchange, unchange. But if you go back, say four or five studies about maybe like eight or nine months ago and you will see like a significant change in that appearance. So that is another thing that you have to keep in mind that just looking at immediately prior examination, sometimes you cannot perceive the change that is present. Always when you have like eight or nine prior studies, make sure that you compare it to the immediately prior one as well as go back, maybe like six or seven studies and compare it to that. So you see that they're imperceptible to why there has been a change since then, which if you compare to the old examination, we can see. So those are the things that you see in a non-enhancing tumor. In the enhancing tumor, which was like two, three or four type WHO, it becomes relatively easy. What you're looking for is just a new area of enhancement, distant enhancement or within the same area, but a new. All you have to do is differentiate between radiation necrosis versus incans and that you can easily do by CBV perfusion study or you can do by a PET scan. Again, all these threshold for this is about six to eight millimeters of a new lesion for it to be perceived on CBV. Smaller than that, it is difficult. But then what you see is if you feel that there's a new puncture area of enhancement, you can't identify it on CBV. So what you do is a shorter-term follow-up examination, like a one-month follow-up examination until either it includes or it gets bigger where you start suspecting it can be a plasm. So this is what we see for recurrent neoplasm. How do we follow up these studies? So WHO one, there was no initial enhancement. So your baseline exam would be post-surgery to make sure that it's completely removal. After that, you do a one, three, six-month follow-up and then 12-month follow-up and then yearly follow-up for five years. And if it is negative for five years, then you consider to be treated. Now, most of the institution just throw in a CBV because it is difficult to tailor each order exam. So all these patients still come up with perfusion imaging, but ideally, perfusion imaging really does not help in any way or form. In fact, even post-contrast imaging really does not help in any way or form unless the tumor has a more aggressive degeneration. Then you see a sudden, you see a low-grade neoplasm with a new enhancement. That means the patient has degenerated into a grade two, grade three, grade four neoplasm. It is not remaining a grade one neoplasm, but perfusion imaging really does not help in subsequent follow-up WHO one classification. On the other hand, on a W-enhancing region, whether it is two, three, four, what you have to do is always give post-contrast, always do a perfusion imaging because that is what you're looking for. Most of these are treated with radiation also. So you want to differentiate between radiation necrosis versus recurrent neoplasm and a new area of enhancement. So when you operate a patient who has enhancement and within six to eight hours, granulation tissue sets in and it matures around 12 to 24 hours. So if possible, if it is doable, then your first follow-up examination should be less than six hours immediately post-surgery if you can do it to look for any residual enhancement that would identify residual tumor. In fact, at our institution, a lot of tumors, a lot of these patients get intraoperative examination. So they'll resect portion of the tumor, they will do an MR examination, then they will see for any residual enhancement, they'll go after that, and then again, they will do. So he's getting an MR inside the OR while they're taking out the tissue. So that way you can be sure that because the granulation tissue has not set in. Within 12 hours, the granulation tissue is there and if there was a residual tumor, then it gets confusing. Sometimes you can compare it to the pre-op exam and you see enhancement exactly in that location. So this is not granulation tissue, this is residual tumor. But if you can do it within six hours before the granulation tissue sets in, that would be ideal. Otherwise, you do it after 24 hours when the granulation tissue has matured. Then subsequently, the follow-up is the same as with B9, I mean grade one neoplasm that you do it one, three, six, 12 month follow-up and then you already follow-up unless you see a new enhancement, then you closely, decrease the follow-up interval. And this is entirely decided by the clinical services that if we see a punctatory of new enhancement, say at six months, then they would, the next subsequent follow-up, maybe at seven months instead of 12 months. They won't wait for entire six months for subsequent follow-up because they saw a new enhancement and they're worried that they'll be taking a new one. Now these are a few treatment, post-treatment scenarios that I will be talking about. This was a low-grade neoplasm and this is what I was talking about. So if you look at it, one year apart, there was no T2 hyperintensity along the margin. Now there is a new area of T2 hyperintensity which is present along the dorsal medial aspect of the surgical cavity. So this is what we are looking for in a WHO grade one neoplasm. This is a bicarin neoplasm. This is a high-grade neoplasm. This was baseline immediately post-surgery, subsequent examination. If you see, there was some enhancement which was taken as, oh, this would be post-treatment. So we did not treat the patient immediately. He returned after from one month to three months. He returned and that enhancement has significantly grown. So this is what you're looking for a recurrent tumor in a high-grade WHO 234 neoplasm. That new enhancement, new mass effect, new peritumeral edema. Then this is big enough where you will probably see a region imaging also. Now this is a case of radiation necrosis. We see a treated area where there is center necrosis and peripheral enhancement and T2 hyperintensity. Now this can very well be recurrent neoplasm. It can very well be a GBM or an aplastic astrocytoma. But how you differentiate it is by PET scan already, cerebral blood volume, profusion examination. This was a CVV where you see it is completely cold. There is no increased uptake over here. There is no new vascularity. So this is going to be radiation necrosis and recurrent neoplasm. And we have to keep one thing in mind that radiation necrosis in its initial stages can actually grow. There might be associated mass effect. And then over a period of time, it finally endurode. So this was a case where initial study showed six months apart showed there was center necrosis peripheral enhancement, which is taken as radiation necrosis. That really enhancement and center necrosis actually started crossing the middle line, was associated with minimal peritumeral signal abnormality, but not that much mass effect. So even, and the CVV was negative. So it was still taken as radiation necrosis and follow-up examination showed involution of that. This is radiation necrosis in post-gamma knife. So this is what happens if you see it over a period of time. You should not image gamma knife treated lesion in less than one month. Because in the initial stages, the second row was done two weeks after the initial treatment. So it looks as if the tumor has grown. And if you are not aware of what is happening, you may actually go and try to treat it more. So this is post-treatment hemorrhage and enhancement associated with it. It looks as if the lesion has significantly increased. But as the time went, it involuted, it decreased in size and eventually the enhancement had completely resolved. So this is the time period between radiation therapy and when you follow-up examination is important because in the very, very initial stages, it looks as if the overall tumor has worsened and increased size. This is how we did, like I showed you separately on two separate slides, recurrent tumor versus radiation necrosis. This is on the same slide for comparison. In the first row, we have a enhancing lesion with peritumoral edema, which was intense elevation on CBV profusion studies. So this is going to be recurrent tumor as opposed to on the opposite side. In the second row where you have a similar area of enhancement and then necrosis with a gene peritumoral signal abnormality, but that is completely cold on profusion sequence. So this is what as a radiation tumor, necrosis looked like post-treatment examination. This is the effect of Avastin when you start using for separation of the VGEF and new vascularity. So there was a centrally necrotic peripherally enhancing lesion and you started using Avastin. The first study showed the tumor and the signal and the enhancement to involute. But on subsequent studies at a later stage, if you can see on the ADC, there's darkness on the third and bottom slide. So that means despite the medication, the tumor is continuing to grow. And although the lesion itself appears to be somewhat unchanged, in fact, even involuted from the initial study, the tumor actually is rapidly progressing in the underlying area. So this is the major problem that we encountered with Avastin that there is pseudo-response that the tumor is actually growing despite the treatment. As opposed to this is another case where we gave Avastin and the top two are the post-contrast even sequences, the contrast enhancement is completely resolved. So on contrast imaging, and it looks as if the response has been wonderful. But on the flare images, you see that the mass effect, the T2, the extent of the lesion has continued to progress. So this is again a pseudo-response in relation to the Avastin treatment. So this is the flip side of the pseudo-response. This is pseudo-progression. What we were talking about the radiation change. So initial study showed a post-reception cavity with faint enhancement. And if you compare the pre and post contrast even sequences, then those might all be blood by products and not be any real enhancement. So that is when you want to see whether that's true enhancement or not. You compare the pre and post contrast. The blood will be looking inherently T1 bright. And then you come see on the post contrast if there is anything in addition to that even hyper intensity, that is the real enhancement. And that is what we have to worry about. And then at one month apart, it looked as if it had grown, the enhancement is worse. There's a little bit more mass effect, but over a period, this will remain cold on cerebral blood volume. So on perfusion, it was negative. We continue to follow up it and over a six month period, it involuted completely. So pseudo-progression is actually a good response to treatment. It is actually the outcome certain considered to be better if the patient has pseudo-progression because that is the body immune system reacting and it is suppressing the tumor. So that is actually good. So this is what like the, my main second chapter was covering the gliomas because that is by far the most common tumors that you will be encountering in your practice. Our goal should be an outcome, not necessarily that we have to be histologically correct. We don't have to wait for a histological report before we give out a cardiology dictation. It has no purpose of being that accurate. Our job is to treat the patient. And if we can serve our purpose, I think we have done a good service to the patients.