work is collaboration with the Rock Group. Since we met the members of the Rock Group, Kevin, we really progressed in our work. We want to talk about AECC, about the vascular origin, but also about the osseous manifestation and healing of the JOCD. So we talk about first the vascularity, and it's just I will keep it very brief. We know the SOC epiphyseal cartilage is vascular, the articular cartilage is avascular. I actually realized that only after I was board certified in radiology, but now I know it very well. So you see we have these SWI images, this really intricate network we can show. This is in specimen and it was a collaboration with the Rock Group. So the vessels, the so-called epiphyseal cartilage canals, have to come from the periosteum to the secondary ossification center. Arterial and venous vessels are in one epiphyseal canal and they are essential for the development. So we showed here in the specimen how the ossification center gets larger and how the vascularity regresses. So you see the avascular regions, these are absolutely pretty images, very high magnetic field. We could not do this in humans at this point. The vascular watershed areas are critical, and I will explain to you why. We have a lateral peripheral network, a medial peripheral network, a central network, all fed by different arterial supply. So we went further and said, okay, can we trace back the arterial supply of these different networks? And we used a so-called vesselness approach, which then was able to realize that indeed, the trackable, traceable vessels were different in their connectivity. So that's an image of vessel connectivity. We also showed the vessel connectivity and its regression over time. As you can see here very well, at four years of age, the central vascular network is completely regressed, and this is where we actually have the area of latest ossification. So there are two factors coinciding. Vascular regression in an area of the latest to be ossified. So that puts this area at a risk, coming together two risk factors. So therefore, we think that the coincidence of vascular regression and late ossification causes a paucity of vascularity and a high risk in the central area at the notch, and that's where we usually find our medial condyle OCD. Our friends in Vienna, Dr. Tratnik, did this imaging in humans. So they showed the images in humans, and they did it at 7 Tesla. The image of vascular visibility is higher with higher magnetic fields. So now I want to go further, and I want to not go into any further details. So we said epiphyseal cartilage origin. That is how JOCD starts. But then we want to know how does it heal? What is the sequence of events in pathophysiology of healing? And that was something we observed recently and published in Radiology. So we saw this image. We share images. It's yours, Kevin. So our late stage. But we want to recognize early stages. Origin in epiphyseal cartilage. So this is our normal epiphyseal cartilage. We have some problems with vascular disruption at the secondary physis. We have then an area of necrosis, what a lot of you call sickening of the cartilage. And then you see this delay in the ossification front. So then a process, secondary healing, takes place. And you will find peripheral mineralization. And then after peripheral mineralization, you find ossification, osseous bridging, and then at the end you can go both ways. It can heal with a scar sign, or it can become a loose body. So we have shown this in many cases. So this is how it looks. And I would like to make a point for an easily clinically available sequence. It's called T2STAR. We call it the MRI bone window. You see as if you do a CT, all 3D, in all 3D, in a 3D space, and you can, you know if your cartilage is ossified or not. In stage one here, the SHARC2 is nothing in the cartilage. It's very difficult to perceive this in your normal PD and T2 rated images. So this is our stage one. Here, this is the marginal mineralization. It's not yet ossification. It's marginal mineralization. Here you see the T2 rated images. It's dark. It's black. I have no clue what's going on. And then in stage three, now you have ossification and here you can really see the osseous bridging. Again, how do I know is this bridged? Is this not bridged? I have no idea. These are my images which I usually get with my clinical imaging. So one case here. It's a 12-year-old. Again, we have the lesion in the intercondylar area, central aspect, medial femoral condyle. And here you see it heals. Once it's healed and you see the scar sign, yes, our images are sufficient, our normal clinical images. So you pointed out, Ted, the difference of stable and unstable lesions. We really want to know if a lesion is healing or not. We know that 50% of stable lesions don't heal. They need intervention. We often wait very a long time to wait for this moment where it shows healing. I see the follow-ups and sometimes I say, okay, it is a long time. We cannot predict healing easily. I think this experience, and Mark and I worked together for a long time, the time of intervention got really perceivably shorter just because we communicate, we talk about the cases. But we need science to predict if a lesion is healing or not. And ideally, after three months of observation and latest after six months of observation. So that is our goal and this is what drives our work. Again, this is one which healed. How did I know that this would heal here? I mean, there is fluid at the interface. Would I call this unstable? Maybe, maybe not. But as you can see here, it just was healing. So we are missing something which we can measure to predict healing. So we came up with this so-called bone window, which is an easy, accessible clinical tool everybody has on its scanner and can do. So here you can see a beautiful radiograph. So what is going on here? Is this a stable lesion? Is this an unstable lesion? I compare it with my PD. I still don't know what's going on. But now I use my bone window. And if you kind of really train your eyes and look at this area and look at this area, here I see there is osseous bridging, there is ossification, and here we have the peripheral mineralization. If I really use my fantasy, I could say, yes, maybe I even see the peripheral mineralization. But as we know, it's a superimposition. I mean, we see just a flat picture of the entire lesion. And there is lesion heterogeneity as we all know. Sometimes anteriorly it heals, posteriorly it doesn't. So here again, the radiograph better, much better shown here, and that is the healing. I want to kind of get your thoughts one step further. Because you have to realize, based on our observations, you have to go through all stages of healing. You cannot jump. If it heals naturally, it has to first mineralize peripherally the epiphyseal cartilage lesion. It has to then remove the minerals from your cartilage and really start with new de novo bone formation. And then you have the bridging. If you compare this with something which is very familiar to us, bone healing, there are many, many similarities. In bone healing, you have de novo cartilage. You have your gap de novo cartilage, endochondral ossification, that's how we call it. Then initially you see this early mineralization. Then you have to resorb the mineralized cartilage. And after this, you have to then do what is really the callus, the osteoid, the bone formation. All of this happens in OCD too. You have to go through these stages. And then the very last stage is the bone remodeling. So you have to reestablish your marrow. So the fatty marrow is the last thing which comes back into your space. You have to reestablish all vascular supply, very similar to fracture repair. So here you see that when you see the dark signal in your bone marrow, then you know your fatty marrow has not fully reestablished. So let's quickly just go through it one more time. You have your early lesion. You might not find it at this stage. This is cartilage, thickened cartilage. You have your peripheral mineralization. It's just very difficult to see this interface here. And it comes and goes all the way around. And then it starts forming callus. And then it forms callus and heals. So I have two cases, one which healed and the other one which did not heal. So you see this is 7.5 months follow-up. This is 26 months follow-up and later on needed surgery. So how can we predict who will heal and who doesn't heal? So we have out a pilot study which just was published this year. Where we followed non-operative patient and operative patient and did something where we took all of, we have an advantage with these bone windows. We can measure density. So in the 3D volume, we measure bone density and get a number of it. So you see between here and here, the bone density didn't increase. So in a time frame, we have a lack of progression of ossification. So we found that in the non-operative group, here these are all like pre-baseline and follow-up. And there was statistically difference between follow-up and baseline. They had ossification, progressive ossification. We had numbers, we measured it. In the operative patients, you don't have that. It's really hard to perceive with your eye or normal imaging how to measure or assess progressive ossification. So I would like, so that is kind of our goal. And we are not finished yet. We put in an NIH grant, of course, these diseases which are not so frequent, we always get back, pushback from NIH. They don't realize the importance. They don't realize kind of that this might be something which is making a difference in clinical practice. And we have always a reviewer who thinks it's like really bad and not significant. But siblings, genetics, my last, just I touch it. So we imaged siblings of patients who had JOCD, and these siblings were totally clinically normal, nothing. And you can see here, this is early OCD. We followed them months, over months. There is no sign of edema. That is not the ossification variant. The moment we have edema, we don't call it ossification variant. It developed over time. Another case, initially, this is more than ossification variant, but it healed. So our goal is now to really more look into the genetics origin. So we have another clinical seven tesla MRI. We moved, we do all studies of knees on the seven tesla. If there is a free spot, the patient goes on there. And we moved now all of our patient to seven tesla. This is a post-surgical case. Just to show you, 3T, you cannot see the cartilage fissuring. 7T, the resolution is much higher, and you see the cartilage fissuring. And that is part of the resolution, which we increase. So epiphytic cartilage origin, the developmental aspects. Osseous healing recapitulates all stages of endocondral ossification, as known from fracture healing. That's a hypothesis, which I would like people to look into. T2 star bone window helps to assess and predict healing. Strong genetic component is suspected. And if there is one image I would like to keep you, ask you to keep in mind is this bone window and the capability of measure progressive ossification might be something extremely helpful in clinical practice. Thank you.

vascular origin

healing

Juvenile Osteochondritis Dissecans

vascularity

risk factors