Key: KJ = Karl Johnson s.l. = sounds like

Transcription

1 Key: KJ = Karl Johnson s.l. = sounds like KJ: Good afternoon everybody. I m Karl Johnson from Birmingham Children s Hospital. My area is with paediatric bone marrow, which in many ways is a tiny subject, in many ways is a massive subject. If we were histopathologists we d have the whole day and the whole week looking at different sorts of marrow and I m sure you ll know the slide on the left is Gaucher s and the one on the right is Leukaemia. But if you have to image those then there s probably no a huge amount of difference between them. I think that s the bottom line, is that we talked about the non-specific nature of imaging and when you get down to marrow effectively it doesn t really matter what s going on in the cells. The MRI pictures are somewhat similar, so we have to be aware the limitations of MRI. I have to say that we have a very large leukaemic practice at Birmingham Children s Hospital. We favour really image primarily make the diagnosis that s still non blood types and stuff like that. It s really basically what is available and then remember the marrow is part of bone and I m going to avoid anything that s got skeletal appearances. Because effectively that s a different talk altogether and you read the literature and still now the primary diagnosis of most bone tumours is done on the plain film. If you get abnormal features, what does the playing field look like? It goes back to original comments, so I m going to avoid primary based tumours, which again are affecting the marrow. What am I going to do? Very briefly, because you ve heard a lot about sequences today, talk about sequence selection. Talk about normal development variance because you think once you understand the normal development of marrow and the potential pitfalls in that I think imaging marrow becomes quite easy cause effectively it ll either be dark on T1 or bright on T2-weighted images and briefly mention the pathology. And that s broken down in proliferation depletion, replacement, vascular changes which I m going to avoid because again, this is a separate subject and miscellaneous. Basically it s what s going on in the cells and I m going to give you some examples. It is an overview of the type of pathologies that affect rather than all the pathologies. Otherwise as I say we d be hear all the time. The MRI feature s been non-specific and I d be giving you a lecture about [unclear 02:06] and this, that and the other and all those things that I didn t quite understand even when I Googled them. That s where we re going to go with today. But first, what is marrow? We talk about red and yellow marrow and fatty haemopoietic marrow. Basically it s a distinction made on fat content and there are two types. The fatty marrow is what most of us have got and then red marrow is where we produce our blood cells in times of crisis or in early age. Distribution varies between us all, depending on how athletic we are, where we live. If we all lived in the Andes we d probably have more red marrow but it varies between one another but it should be symmetrical. It should follow normal patterns. As long as it follows those normal patterns and is symmetrical you can probably say it s probably going to with normal. Red marrow is composed of haemopoietic cells, basically they produce our red cells. The supporting stroma and all the other things that produce white blood cells and neutrophils and all those things. Basically all the precursors of our blood film, and within that there are scattered fat cells. Now, that is important because the amount of scattered fat cells will vary between this audience and therefore will vary our MRI appearances but hopefully we ll all have normal MRI appearances. Even though if we re to do the same sequences we ll all

2 have slightly different appearances, because it s the amount of scattered fat cells and those other supporting cells in there, and a rich vascular supply. Whereas yellow marrow has all the same as before but the fat is overwhelmingly greater, so again the vast majority of time you will have been imaging fat. How do we choose our sequences? You can do lots and lots of sequences for marrow but in my own personal experience we do the marrow because we re doing something else. And while you might choose your best marrow sequences they may not be the best sequences to imaging the other pathologies. In a way, even though I m going to give you well this is the best way to image marrow, I appreciate that in the reality of life we may not get those sequences because of the demands on our magnet time and what else we re imaging. T1 is the bottom line, so if you want to look at marrow, T1 and probably the best way of looking at it would be a coronal sequence. It s good for differentiating red and yellow marrow. Yellow marrow, cause it s fat, it s going to be white and anything else is going to be off-white. STIR [s.l. excellent 04:16] as we know for oedema but remember certainly on STIR and imaging everything that glistens is not gold. Just because you re seeing high signal you can t say that s oedema. It basically is high signal on the STIR and you have to put in the context. And that s very important to remember that not everything that s high signal on marrow imaging is necessarily pathological. It would go back to our red and yellow marrow and what we re looking at there. As I say, we don t always need to intend image of marrow concerns. We may not get the sequences we like. As I ve alluded to, yellow marrow is isointense so it s [unclear 04:50] T1. Since we re invariable doing the muscles and the fat around the bones we ve got a good marker for it. Low signal or STIR because of that fat is not very difficult. If you give contrast it will differentiate between pathological processes. And that will again be accentuated on STIR if that s that. Pathology typically has a greater enhancement than normal fatty [unclear 05:15]. If you do see a high signal sequence on your STIR images and you re not sure if it s pathological or not, if you give Gadolinium and if it enhances it increases the likelihood it will be pathological, but it s not an absolute. If it doesn t enhance chances are it s most likely going to be part of the benign spectrum of marrow change. If you re unsure again, look at the other side. If it s bilateral and symmetrical and it doesn t enhance chances are it s going to be a benign process. Just to show you an example really, this child do imaging for a fractured scaphoid. Basically this is normal fatty marrow. It s all very low signal. You can see the fracture line and the oedema around it. You can see the oedema here. Due to point out again that even though this is oedema and this is basically free water, it s very high signal, probably similar to CSF if we do a image of the cord. There is again high signal at the end of the metaphysis here. Again, it s not as high signal as CSF but that probably reflects some residual red marrow at the end of the metaphysis. Again, depending on the signal sequence and depending on how pathological those changes are. Just another example, child who incidentally had JA, but want to illustrate that you do get enhancement low on the end of metaphysis with contrast. And where you ve got pathological change on the STIR images you also get contrast enhancement, but again I ve not been imaging the marrow per se but you can make observations about the marrow during this process. Obvious example, child using STIR images you can see the obvious fracture line, the tibial fracture, the huge amount of oedema, STIR is great for showing oedema. But again, remember that not everything that s bright on the STIR image in marrow isn t necessarily pathological. Red marrow, typically signal intensity is equal or greater than muscle [unclear 06:55] T1 and T-rated images. In neonates it might be slightly different because the neonatal marrow s very, very vascular. Typically red marrow is higher than muscle but lower than CSF. That s

3 important to remember that it s bright, but it s not always really bright as water. Again, red marrow remains hyper intense on the STIR images and yellow marrow will be saturated out. Again, shows you example, these are children with normal changes and hopefully appreciate that this is normal haemopoietic marrow and it s of high signal on the STIR weighted images around the metaphysis. That s normal, similarly on the T1- weighted images it s a relatively high signal around the metaphysis there. Those are normal appearances, so that high signal that we re seeing on the knee image there is just normal marrow. We talked about doing whole-body STIRs and when we first started doing this we did a use of turbo STIR. You be careful that, depending on where you child is in the magnet and what sort of sequence was used during, that not all STIRs are the same and depending on how you fat suppress. And depending how the degree of contrast that you get and just to show really, the best is to show you that on the left-hand side this is our standard STIR sequence. But on the right-hand image it is a turbo STIR, so again the degree of contrast is less and the degree of fat saturation is less. Be careful how you interpret it, because again the contrast you get and this conspicuousness of any lesion will be altered by how you get it. Smaller children, the edge of field again, fat saturation may be limited and again the signal to noise ratio and the contrast can be limited where the child is in the magnet. Be careful that we don t over- and under-interpret signal change within the marrow because of technical factors related to it. A brief [unclear 08:42] to diffusion weighted imaging. It is coming in. Have to admit before when I knew I had to give this talk they kept saying, Oh, do some diffusion, do some diffusion. And the radiographer s are trying their very best and the images were relatively poor because you ve got relatively low signal to noise because bone is predominantly fat. There s not as much water coming back. Any small amount of movement artefact will affect it and then I spoke to our physicist who then defined some better sequences. Effectively the use a sequence using five different B values and they specifically look at tissues. This is done by a research team looking at osteosarcomas and looking at the diffusion changes in osteosarcoma. And it does have an effect. They restricted diffusion if the child responds to treatment, but it is coming in. I don t think it s standard practise but I think it s now part of standard research practise. Most magnets you can do it and I think in a few years time we ll be aware. What I m trying to do now is get my own road map of what normal marrow should look like on diffusion weighted image. I think it will be useful in differentiating between ischemic change and infected change. Maybe we can start to reduce the amount of contrast we should be using. That s the way I m thinking it s going but at the moment it s still with the research group but I think in a few years time we ll need to get a better idea of what normal marrow looks like. Occasionally you can show nice examples. This was diffusion imaging done for the body tumour work and this is a child who s had radiotherapy. That s where he got the change within the signal within the marrow and the lower [unclear 10:05] can appreciate on the diffusion image being done for the body tumour that you can appreciate differences. Diffusion will be useful and it might be useful, certainly in looking for tumour necrosis, looking for avascular necrosis and looking at how we assess some of these pathologies. But at the moment I think it s important that we try and find the techniques and move forward. That s where I personally am at the moment. I m trying to get a new roadmap of normal diffusion in children. That s how we d approach it. What should we be looking for? It s always important to know what normal is before we start and as and when we are born basically the majority of our skeleton is red marrow because we need to replace our foetal haemoglobin with normal adult haemoglobin. Red marrow

4 occupies the whole of the ossified skeleton. It will then start to disappear and it retreats 10:55] centrally so that by adulthood we ve got limited amount of red marrow within us. But we ve got the propensity to turn our yellow marrow back into red marrow if we re put under stress. And it goes in a similar pattern. It retreats in a way, sorry, just to show you this is what normal red marrow looks like in a young baby. You can see that the signal intensity of the marrow is similar to that of a muscle. This is all red marrow in a two-month-old baby. This is what normal red marrow looks like. It begins at the apendice skeleton and progressed centrally. The long bones diaphysis go first, then the distal metaphysis, then the proximal metaphysis. You may still get some islands of red marrow left behind and the last metaphysis to change will be the proximal humeri and the proximal femurs about ten years of age. In the epiphysis changes occur within six months of ossification, so that s the way you should go. Just to show, it s a really good example. The changes are bilateral and they should be symmetrical and they should follow that pattern. Depending where you are, if you ve got changes in the distal metaphysis, which you think are red marrow, then you should expect to see similar changes in the proximal metaphysis because that follows on. If you ve got changes and you think oh, maybe that s just red marrow in the distal metaphysis, but the proximal metaphysis looks normal then you have to think again. You ve got to make sure that you understand that pattern of the way it changes and put that into context. Again, just to show some examples within the arm. Again, it s very difficult to get really nice pictures of red marrow in the young babies cause even though the [unclear 12:329] said by one year of age in my personal experience it changes very, very quickly. I think we do a lot of marrow imaging, so a lot of imaging of neonates, babies under six months of age for congenital dislocation, hip. We ve had surgery and the surgeon wants to know if the hips in place. Most of the time at six months of age they ve all converted to yellow marrow, so even though the literature said about one year of age in my personal experience it s a lot quicker than that. Therefore a lot of the imaging I do, the marrow s already gone fatty by that stage, but you can appreciate again it s relatively low signal, the T1-weighted images and as we get older it changes. But you can appreciate on the image, on the far right, it can be slightly patch so you can get these small islands of red cells left behind. Again, around the knee joint you ve got residual amount of marrow changes and don t be confuse those with pathological changes. What they say is that they should fan out from the metaphysis and the physis like a flame. It should be perpendicular to the long length, to the axis of the physis like a flame extending out from the metaphysis. If you have that flame type of appearance, if you can appreciate that, that is normal. These are patchy normal changes that visit your marrow and again, around the proximal femurs again extends down from the physis like a flame and these are normal changes. Not to be confused with pathology. Within the foot and also within the hand as well you can get, certainly on STIR and T2-weighted images, a patchy high signal change. These are residual little pockets of red marrow. People call them marrow oedema and it s one of those controversial areas. As I said before, everything that s bright, glitters is gold. They could be oedemas but basically these are normal small patches of normal signal. These aren t to be confused with pathology. Sometimes if you put a child in a cast and the bones become osteopenic this is really quite accentuated as the bone becomes osteopenic you get an accentuation. Because you re losing bone substance the patchiness can get accentuated. It can be accentuated by osteopenia with these patchy changes well recognised, certainly in the foot and now I think also in the hand as being normal variant. Again, not to be confused with pathology. In the spine, again the change is slightly slower than the appendix skeleton.

5 T1 version while you compare that to the disc and typically hypotension after about a year. Again, that s what the literature said. In my own personal experience I think things move a lot quicker than that. Isointense with the disc being one to five years of age and hyper intense after five years of age. Don t forget that there is a central vessel within the virtual body and that can affect the change. You often see changes around the vessel, which are slightly distinct from those around the rest of the body. That s just because this is close to the vessels running into the virtual body. Be careful that you don t over-interpret. The disc is here and this is the un-ossified cartilage. Again, you should be concurring disc with virtual body there. These are young babies where full of haemopoietic marrow and low signal and as you get older they get higher signal and changes. Again, these changes are around the vessel coming in are to be expected in their normal variants. That s the normals and then just to briefly, I ll show you some pathological processes. Pathology is proliferation, depletion, replacement and miscellaneous and it s proliferation of cells within the marrow, depletion of those cells and replacement of those cells. The examples I m going to show you are the ones that I see more commonly. It s not a complete list and it s just to give you an example of a way to approach potential marrow imaging. But as I say, I think primarily the haematologist will do a blood test and then they ll do a triphide and if they re then a bit confused they ll send it for MRI. We re left with those that they really can t understand. In my personal experience I m given the difficult ones. I m in at the deep end all the time. Leukaemia. Basically it s a malignancy of haemopoietic cells, infiltration and replacing the cells by malignant ones. Children it s more likely to be in the long bone. The [unclear 16:42] are variable and basically you can have a child with quite severe leukaemic changes and the MRI will be normal. Similarly I think it s most importantly they can present with musculoskeletal symptoms and certainly within the last twelve months through the orthopaedics and haematology section at the children s hospital in Birmingham we ve had three cases of Leukaemia that have presented to those. While I would say we can t offer service to the haematologist primarily making the diagnosis we can offer a service to the children by saying actually not all bone pain, just because it s normal does it mean to say that it s not fully significant. I always think about Leukaemia and those haematological malignancies when you ve got a child and you re not sure why they ve got the bone and joint pains. That s what I would say in terms of the importance of that. What we re looking for is abnormal distribution of red marrow. It signals change on the T1-weighted images. It s taken away a normal fatty marrow to single chains and it s either abnormal distribution of what appears to be normal red marrow. Or abnormal signal from that red marrow in a normal position or abnormal signal in a normal distribution. Basically we re replacing the fatty cells with leukaemic deposits and they re hyper intensive on the T1-weighted images and the T2 signal change is more variable. Depending on what s in those leukaemic deposits so it s really loss of high signal on the T1 and a variable signal on the T2 s. Two examples, obviously they were T2-weighted on the left-hand side and this high signal change in the marrow and on the T1-weighted, on the left on the other side is low signal change. These are leukaemic deposits within the spine there. Elsewhere in the body it can be very variable. As I say basically it s abnormal signal, abnormal distribution and not what you expect. It can be extremely variable. Again, further examples and again, more examples again but in a way what they represent is the fact that Leukaemia can be extremely variable. But if I was to put these slides into a talk about infection, osteomyelitis or CMO or LCH it d be exactly the same. I m not making the diagnosis I m just saying actually there s something wrong with the child. If they ve got joint pain we know why

6 they ve got joint pain and they need to investigate it but obviously that s all part of working in an MDT and making sure the appropriate sort of specialists are involved. But this is what Leukaemia looks like but the imaging would be compatible with many other pathological processes as we alluded to already this morning. The other thing to look at and be aware of is yellow to red reconversion and the example I m going to show you is Sickle Cell Disease. As I was coming down on the train I thought actually what I should have done is put a picture of Lance Armstrong up because effectively he would have had yellow to red conversion. He took lots of EPO and cheated. I probably should say, I m not... [unclear 19:32]. And effectively what we re looking at is the ability of the body to change from yellow to red marrow under duress. Athletes can get it. If you go and live in Peru, as I say, your marrow will change but the example that I m going to give is Sickle Cell Disease because I work in an area with a large Afro-Caribbean community and Sickle Cell is very common depending on where you work or depending on the instance of this. For those who don t work in an with lots of Sickle, it s basically hereditary condition where we re basic replacing normal theta haemoglobin with haemoglobin S, and that causes just distortion of the blood vessel. It can be homozygous, which is HBSS or it can be heterozygous or there can be various traits. There s various different things that can be linked with a thalassemic gene. There s a various degree of different haemoglobin type genetic changes, but what we re looking for is that Sickle Cell. It s blood carrying capacity is reduced. It s more likely to clot your capillaries. It s more likely to cause infarction. It s more likely to cause long-term complications. If the child becomes stressed with the amount of oxygen they re getting is reduced or they have a concomitant illness that can accentuate the problem and cause a crisis effectively. The loss of blood swells to an end organ and the child suffers from that. From a marrow point of view, what we get is our normal basic low signal on T1, cause effectively we re putting haemopoietic marrow, replacing our fatty marrow. There may be a low signal within that due to infarction and typically in the long bones. Typically this is what you d expect. Again, these are T1-weighted images. You d expect the marrow to be coming back as very fatty but you can see it on the leg there, it is all very, very low signal. This is due to replacement. And again further examples again. Lots of low signal changes. This is a STIR-rated image, now you can appreciate the signal change here and again what you ve got an infarced within the femoral head, which is not uncommon in Sickle Cell Disease. Times I m called upon, it s not really to make the diagnosis Sickle. That s done from a blood test. It s basically is it crisis or is it infection? When we say crisis effectively you ve got ischemia, you ve got inflammatory change because the bone is becoming necrotic and lack of blood supply or are they getting [unclear 21:50] infection? The problem is that they ve increased this infection or else increase of crisis. You ve got crisis, more likely to get infection. If you re infected you re more likely to get crisis and what we re looking for is oedema, [unclear 22:00] reaction and soft tissue changes which can occur in both. If this slide had put up three quarters of an hour ago, said this is acute osteomyelitis you d all go yeah, yeah, it s a good example. But what this is, is crisis. This is basically the large amount of soft tissue swelling, a large amount of subcutaneous changes and I hope you can appreciate there is farctions within the bone as well as oedema within the bone. But you get the [unclear 22:23] elevation, you get the collections. How do I know it s crisis? Basically the child s put on the drugs they give for this and oxygen and in about two days later they were better, so they responded clinically. They also were started on antibiotic, but the antibiotic were only given about 24 hours at which point the child had responded. Initially, it was ooh, I can t make the decision

7 and I think as a radiologist I think it s very difficult to, but basically because you ve got such extensive changes the decision was made to treat them as both and clinically that the way the child responded was this was just a crisis. Obviously if the child had not responded then the antibiotics would have carried on and the child would probably have had further [unclear 23:06] to make sure there was no abscess collection developing. It s a nice example. Unfortunately I don t think I can tell you anything that you d say ah, this differentiates between the two. There are one or two case supports in the literature that says diffusion weighted imaging might be able to show you that, but I think they just show that you re getting infarctions within the bone rather than saying you re definitely getting infection in the bone. That is an area that we need to look at but this is what it looks like. Don t say that everything we look at is definitely infection and everything we see is definitely crisis. The spine-age on the bottom was again another child with crisis. This actually was infection. They had a large epidural abscess there just to show you that you can get both together. Just to finish off we re talking about replacement and this is a child who had [unclear 23:49] stimulating factors. This is a child who had Leukaemia or a malignancy, was treated and basically was given drugs to stimulate the marrow. You can get those patchy changes which are heterogenic. That s proliferation and looking at depletion and the commonest thing we see will be [unclear 24:06] infarction. She s deaf and loss of the cellular elements and what you see there is a serpiginous border and it s like geographic changes within the bone. And you get the double line, which is decreasing the intensity of the periphery due to the dead bone. And then adjacent to it you get increasing intensity because you ve got this granulation tissues trying to form, trying to repair it. You can also get periphery enhancement of infarced, because again it s a response to the necrosis. And once seen, never forgotten really. Those are classical examples of bone infarcs. Again there s this serpiginous irregular edge. It s low signal around the edge. You can get associated oedema and signal changes because of the inflammatory change around it. these are classical infarcs. Again, it s knowing the history. The majority of the bone infarcs that I image of children have been on high dose steroids for a long time because of malignancy. And it s a well recognised cause of bone pain in the child who s in remission rather than having a relapse of the primary malignancy. It s basically a consequence of the treatment that they re on. If you image children who have been on long-term chemotherapy, chances are one in five you re going to pick up significant bone infarcs, and again just examples. The important thing is to recognise is a) is it in epiphysis? Is it affecting the cartilage? Have you got cartilage loss? Cause that s it, once your cartilage is gone you re in a different ball game. You ve got early osteoarthritis. You ve got problems. If it s within the marrow and the child s growing, if you follow these up they get smaller, they do have oedema, what would use? The body is very good at adapting to it so it s trying to give somebody the prognostic indicator and monitoring it so you know why the child s getting the pain. The other area to see is round the femoral epiphysis and again it s that classical double rim sign around the epiphysis. But as you can see on the post-contrast images, you can get enhancement around the edges there. These are all examples of Perthes Disease, which again is infarction process but again enhancement is not common. And certainly Perthes Disease we give contrast and try and assess if we can give some degree of [unclear 26:13] indicator. Cause if you get the peripheral enhancement around the edges here there s meant to be a better sign than if you lose the stuff in the middle. It s an area where you can log the degree of marrow change. Other areas where with loss, and this is a child with Myelofibrosis and the way to put this is it s sort of two pathological process going at the same time. You ve

8 got low signal change here, which is basically the fibrosis within the marrow, which is the primary problem. In response to that the body is converting all its fatty marrow into haemopoietic marrow and trying to produce more red blood cells. The body is trying to act against the primary process and this is Myelofibrosis where you ve got fibrotic changes within the marrow. This is early changes. We ve got follow up. Unfortunately this child s degree of low signal change got worse as the fibrosis got worse. This is just [unclear 26:58] Myelofibrosis. Again, diagnosis typically made on trephine, rather than by radiologists. You ll often see this change in children who ve had radiotherapy and radiotherapy changes could occur within a couple of weeks of radiotherapy. You get this mottled change within the marrow but after about four or five weeks or certainly after six weeks you get fatty replacements. The normal haemopoietic cells are destroyed by the radiotherapy and yet fatty replacements. Typically if you re imaging children who ve had brain tumours, who ve had radiotherapy you re obviously see very high signal change in the marrow due to fatty replacement within the marrow and that s not uncommon within the radiation field. This is a worse example. This is basically complete necrosis following radiotherapy and chemotherapy and basically once you ve got cell death it just becomes low signal on all sequences. Replacement, in an adult world the commonest replacement would be metastasis and again low signal change on the T1-weighted images. It s very non-specific. This is metastasis. Luckily in paediatric practice metastasis are relatively common but if you know the primary diagnosis then you see signal change. It suggests metastasis. We now do a lot more whole-body STIR and whole-body T1 s looking for metastatic disease rather than bone scans. It depends on the availability of magnet and your work with your oncologist. Osteopetrosis, again it s a diagnosis made from the plain film but if you do MRI and this child has [unclear 28:24] MRI not for any other reason but because you ve basically got scoliosis and loss of normal marrow. Everything s low signal on any means you ve got a T2-weighted image, but again we wouldn t normally image that marrow. It s just a nice example to show that this is what happens if you lose all your normal cellular components. This is to go right back to the beginning is Gaucher s Disease and again just replacement, loss of normal signal by abnormal accumulation of cells. Again, very non-specific but just reflects the primary process. Miscellaneous, I ve only got one example and this is LCH. Basically again it s very non-specific. The diagnosis typically made from plain film and the history. It is quite a lot to see in the marrow. I think once you understand the normal variation, then I think it s easy to say is this abnormal or not? If you think it s abnormal, you re typically going to say what s wrong with the patient? What s their blood count? If necessary you need to go and biopsy because I think MRI is quite non-specific. What we can try and do is avoid them biopsy and things like infarcs and normal areas but sometimes we can t really give any more differential and it s back down to the collusions with the other tests. Thank you very much.