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26:56Yeah, there have been huge advancements in pediatric brain tumors. It's really one of the most exciting fields right now because of how many things have really moved forward in the field. And so we know so much more about the biology of these tumors and the genetic underpinnings to them and can really drill down with each individual tumor to find out what the molecular change has been in the cells that is driving tumor growth. And that's really helped us understand them and opened up a whole new field of individual treatments. And so, you know, every tumor is different. In some tumors, we've discovered that there may be a cell of origin that the child is born with.

27:34A lot of tumors, we don't understand why some kids are getting them and some don't. Some may have familial implications and some may have environmental. We don't understand everything, but we're learning more and more every day, and we know so much more about the individual genetics of the tumor. Could we get to a point within our lifetimes where there is some sort of screening for kids when they're born or in their early days that helps identify what they could be susceptible to, and then we could allow for different treatments ahead of that to prevent it actually from happening? Definitely. I think so.

28:08And it may not be for every tumor, but I think we're already getting close to that for certain diagnoses where we know specific things that we can potentially screen for, and we're finding certain germline mutations that are familial, hereditary. So yeah, I think we may get to that point where screening is better for all tumors, but we're very close for certain types of tumors. Is there differences in boys and girls when it comes to either tumors or what impacts? For some. Yeah. Yeah. For some diagnoses and some have, you know, greater percentages with boys and some with girls. It really just depends on the diagnosis and many, many it's equivalent.

28:47I am also curious about like, you guys seem to certainly take a family approach and you have to when it's kids. Like what's involved when you've got specific therapies and it's not, it's leading up to the surgery or whatever the treatment is. No, the treatment of these kids takes a village. We have a huge multidisciplinary team. We have neurosurgeons, neuro-oncologists, neurologists, the neuropathologists, geneticists, neuroradiologists, and we also have the rehabilitation experts with physical occupational therapy, the neuropsychologists, and endocrinologists. I mean, there are so many different expertise fields that are required to take care of these kids because brain tumors really affect every single aspect of their life and have the potential to affect every aspect of their physical and neurodevelopment.

29:33And so, you know, we are really fortunate here to have so much expertise that we're able to really individualize the team needed for each specific child. Thank you so much. This is heavy stuff. Thank you so much. Really appreciate it. Dr. Alyssa Baer, Director of Neurosurgical, Oncology and Co-Director of the Brain Tumor Center at Boston Children's Hospital. This is Bloomberg. Stay with us. More from Bloomberg Business Week Daily coming up after this.

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32:43Let's get back to our adept look and conversations about the work that's being done at Boston Children's Hospital. That's where Carol and I are this afternoon. We kick off this hour with Dr. Ellen Grant. She's director of fetal neonatal neuroimaging and developmental science here at Boston Children's Hospital. Here she leads a 70-person neuroimaging and computational science center that's working to develop tools to better detect and understand brain physiology and development, all with the goal to improve cognitive, behavioral, and neurological outcomes, not just in fetuses, but in infants and toddlers.

33:15And then of course, ultimately, as they get older. Dr. Grant joins us on site here at Boston Children's Hospital. Dr. Grant, welcome. How are you? Great. Good. Thank you. Thanks so much for having me. Thanks for joining us. Brain imaging in children, if we have a better understanding of the brain and fetal development and for babies and toddlers, what will that allow us to understand? What does it prevent? What does it treat? Well, everything begins in utero pretty much. So your life is an arc from infancy or when you're conceived through to adulthood. So the more we can understand the early development, the more we can start to understand how we make sure children are on the right trajectory.

33:48So the goal is to characterize brain development very early on. So we tell at the very earliest point when to start to deviate from a normal trajectory so we can get things back on track early as possible. And ideally, we want in future to be able to prevent diseases from happening, not just try to deal with them and try to correct them later on when the damage is partly done. So how early can we do it today and detect that there's something wrong? How early realistically do you think we can get it to? Yeah. We start looking at fetuses at about 11, 15 weeks, something around there at the earliest, closer to around 18 weeks.

34:21We start to characterize brain development, you know, 18, 19 weeks or so. So it begins quite early when we start to see and look at early brain development. Well, you and your team did a study a few years ago that gave you results to argue for earlier MRI during pregnancy. Is that study enough to actually change the standard of care? Well, we do use it early here at Boston Children's. So when there's an indication, we do it as early as we can to better characterize the entire fetus. Because it's not just the brain, it's the body it's attached to, too. So we want to understand not just the brain development, but how that brain is developing in the context of the other organ systems.

34:57So we can do that. Because it doesn't necessarily run hand in hand. Like, it can be very different, right? In terms of what's going on with brain development versus the rest of the system, they can disconnect? No. They're intimately connected. So that's what we want to understand. So let's say, for example, we deal with a lot of congenital heart disease here. That has effects on brain development. We deal with congenital diaphragmatic hernias. That has effects on brain development. So everything that's happening in the fetus, whether it's a brain or not, has the potential to have subtle effects on brain development.

35:29Why do kids? I mean, kids do need specialized tools for brain imaging. Talk to us about that one way. That's the whole reason that I came to Boston Children's, is industry is not interested in fetuses and twins and young children. So it's really hard to get devices that are built specifically for these age frames. So that's why I brought a team of technical people. So they're engineers, physicists, computer scientists, data scientists that help to either develop the devices or come up with better ways to analyze the data that we get with an eye on trying to understand pediatric disorders. So for example, we want to monitor and we're developing optical devices for the NICU to monitor cerebral blood flow.

36:10But the heart rate of a neonate is 150. So we have to sample at a much higher rate than you would in an adult to get the same information. So we have to build specifically devices to the physiology. And then if you think of a head of a premature baby, it's very, very small. So I can't take a probe that we use in adults and just put it on a preterm. So we have to develop the devices to fit the size of the infants. I want to just go, and I feel like we touched on this earlier. I mean, we are Bloomberg Business Week. We are Bloomberg and very entrenched in financial markets. And I feel like the more I've been doing this, money just follows everything.

36:46Money is why people do things or don't do things. Is that really it? Is it just the market? I hate to even make it that way. The market size. And so you don't have medical equipment companies building the things because they just don't think the market size is big enough? That is a big problem. And I think that's where we're trying to get into more of a business perspective. Like if we do a small startup that starts to answer those questions, then a bigger company might buy it. But if we stay in the research realm, then it's sometimes really hard to go that last mile and get something into clinical practice.

37:16So how do you do that? How do you cross that? So what do you do? Yeah, this is what we're strategizing on right now is trying to figure out how we do those small startups, get industry interested. Right. And a lot of things we're doing right now, actually, one of the projects we're working on is, you know, AI strategies, right? And if we can get enough data on infants or fetuses and so on, we can start to build models that predict not just group outcomes, but we want to get to individual outcomes because that's what parents care about, right? So if we can figure out, get those models together.

37:47So that's what we're working on now is trying to create these AI models that are specialized for pediatrics and hoping to do startups around that particular concept. I have to ask one more question. Are venture capitalists interested? I don't know because we haven't really talked to any that I've heard about, but I think they always want something that's almost ready. So we're hoping to see a little bit further along. Yeah, a little bit further along. Okay, interesting. Can what we learn and what you understand through imaging about the brain's development be applied to how adult brains are treated?

38:17Everything in adult life has a genesis in infants, right? We were all there once. Yeah, yeah, exactly. And some of the ways the adult brain response is more prominent in a pediatric brain. So in some disorders, they go to pediatric models to see a physiology that's more prominent in neonates or infants but also occurs in adults. You know, in doing the research and the prep for our interview with you, there is a picture of a physician or a therapist doing some what I think is called therapeutic hypothermia to a brand new baby's head. And my understanding is that oxygen deprivation around birth is one of the leading reasons that you actually see babies come into the NICU.

39:05Yes, that is one of the main reasons, yes. And the therapy for this is as simple as? Yeah, you cool them down or at least keep them normal. Yeah, at least keep them normal thermic. Because when they have injuries, sort of the whole physiological response to an injury is to have a fever. And that is detrimental. So we want to keep them cool so that they don't set off these cascades of brain injury. And that's partly why we built this one device because we want to be able to monitor through the NICU stay and optimize management. But it's interesting, we don't even know what the right blood pressure for a newborn is.

39:39So this is why we wanted to have a probe that could measure cerebral blood flow to the brain, because there is no way to monitor whether there's enough brain or oxygen getting to the brain with the tools that we have right now. I feel like we never even talk about blood pressure when it comes to infants, right? Yeah. We just don't. But you need to know. Yeah. You did your residency and fellowship in the 1990s. Curious how imaging has changed since then. Oh, my gosh. Where do you think, how will it improve in the next, I don't know, 10 years? I don't know what's a smart benchmark. Yeah, yeah. When I was in training, MR was just starting, and it was very slow.

40:11So where we've come now is the acceleration acquisition is just incredible. What used to take us an hour to do, we can do in 10 minutes now. So the speed, the speed of acquisition is huge. We're also developing a lot of analysis that we can do after the images are acquired to give us more quantitative metrics. because the whole thing in medicine to get past the qualitative read of a radiologist, which is helpful, but we want to put more numbers on it so we can have a more dynamic range on how we describe each child. And therefore, we can get into better precision medicine and outcome prediction.

40:46So we're getting more to that quantitative aspect of imaging now, and not just brain, but all body parts, of course, and down to fetal age. Is it for kids, too, every case is very personal and individual? Or are there trends and things that you can help in so that one case can help another? Is there a body of knowledge that gets built off of this? Yes, there's a body of knowledge that gets built off of this. But this is where we come back to AI. I only can remember so much. You know, even though I've been in practice for a long time, things fall out. Joy of the craft. So this is where I'm really excited about AI because I can, you know, mine our databases to find where's an individual child just like that one I'm treated now.

41:28What did they respond to? What worked for them? And how are these two similar? So I combine the databases to start to come up with individual outcome prediction, which is what we're doing right now with databases we've got from some of the major trials for hypothermia. And so we can use this large database to try to take individual outcomes. You can say, well, I have a newborn with this pH that had these, you know, and I'm a mother of this age and put in features. and they could give you from that database an outcome prediction. So working on that and also working on making data more available to parents because I think a lot of parents are very frustrated with trying to read the literature, even if you're using ChatGPT or OpenAuth.

42:08It's really hard. It's really hard. And then you get group statistics. And then where does my kid fit in between the 25 % to 75 % good outcome or something like that? To get chatbots that can work with some of our databases. So anybody can talk to a physician, so to speak, to give the answers that they want. That's pretty remarkable because I just think about the tone of these chatbots and if there's a way that they can be – we talked earlier this week about what a challenge it can be for people to actually interact with them in a quote-unquote normal way. But is there a way for them to actually be empathetic and work with patients, work with parents, work with families?

42:55And forgive us, we've got about 40 seconds. Yeah, yeah. No, we're working on that, but I can't tell you all the secrets because we're going to start on that. Wait, you can't. You can't wait. No, you can go longer than that. Can I ask you something? When you guys do use AI in chatbots, do you have hallucinations? Like do the AI hallucinations? Or how do you, especially when you're dealing with medical prevention, there's a lot of safeguards we put around that. So we have, again, this is sort of more the secret sauce that I can't talk about yet, but there are ways to constrain chatbots to give you reasonable answers that are statistically sound.

43:29All right, so when you can, will you come back? Yes, I will. Okay, good stuff. So appreciate it. Dr. Ellen Grant, Director of Fetal Neonatal Neuroimaging and Developmental Sciences here at Boston Children's Hospital. Thank you again. You're listening to the Bloomberg Business Week Daily Podcast. Catch us live weekday afternoons from 2 to 5 p.m. Eastern. Listen on Apple CarPlay and Android Auto with the Bloomberg Business app. Or watch us live on YouTube. We are live from Boston Children's Hospital where we're speaking with some of the nation's leading doctors on matters related to health, health policy, innovation, medical care, and everything that has to do with health.

44:04Carol, a fixture at my high school and college was torn ACLs. Volleyball, lacrosse, soccer, field hockey. a torn ACL, surgery to reconstruct it, then weeks on crutches, months of recovery, and oftentimes it was girls, not boys, who tore their ACL. Which I find interesting. I guess I would have thought it was the other way around. Girls and women tear their ACLs at a higher rate than men and boys. This is Dr. Martha Murray's world. She's orthopedic surgeon in chief for Boston Children's Hospital. She joins us here in Boston, where we are at Boston Children's Hospital. Dr. Murray, welcome. How are you?

44:34I'm good. Thank you so much for having me. Nice to have you. So you've got this background in material science and engineering. It's not typical for a surgeon. We're going to talk about your innovation in ACL surgery in just a minute. But on the boys versus girls, men versus women, why do ACL tears affect women more than men? Well, it's a really interesting question, and it's been one of much debate for the last few decades. And there have been things like, well, it must be a hormone cycle, or it's the shape of women's hips and their valgus angles to their knees. but a really interesting study came out very recently from the Harvard School of Public Health as well as Harvard University with Dr.

45:09Danielson and Dr. Richardson where they actually showed that the studies that say that women tear their ACL more frequently than men were often based when the women's teams were smaller than the men's teams. And the way they calculated exposures was the number of practices or games you played in, not necessarily your playing time. So if you're a man who's on a hockey team versus a woman who's on a hockey team, the women's teams were smaller so those women were playing more so they were planting it and hockey that's a bad example soccer would be better but if the team is smaller the women are going to be planting and pivoting and playing much more time per game or practice so more stress more use more stress more use more time so maybe it's not maybe women and all things equal maybe women and men don't have a different rate of torn acl correct when when they corrected for unit of exposure so kind of game time playing rather than just a game.

45:59The injury rates look very similar. Wow. That's totally different than what? I mean, is this the standard now? I mean, do you think this is it? It's relatively new work that's coming out, but it resonates with most of us who take care of women and men on their athletic teams. Yeah. I want to ask about your background, material science and engineering. I know Tim said not typical for a surgeon, but I think it's a really smart combination. I have a doctor a foot doctor, same thing, engineering. And like, he doesn't just deal with my foot. He thinks about, okay, what are you doing? What else is going on in your body?

46:33Tell me about that mix and why it's kind of unique and smart and ties things together. Well, for me, it was actually of necessity, right? So I was an engineering graduate student and a friend of mine came into a party one night on crutches, as Tim was saying, and who had torn his ACL. And I said, oh, are they going to go sew it back together? And he was a med student. He was like, you stupid engineer. We can't sew it back together. You have to take it out and replace it with a graft of tendon that they're going to take from the back of my leg, and then it's all this rehab. And I thought, that seems kind of excessive, right?

47:04Like, that's a lot to have to go through. And so I spent the next six months or so in the medical school library just reading everything I could about why didn't the ACL heal. And I realized nobody really had figured out why it didn't heal. They tried it, sewing back together, didn't work, so then went to grafts. And we've been doing grafts for 50 years, and nobody really asked why doesn't it heal. And so for me then, there was no biomedical engineering at that time, And so my choices were to continue on with my project, which was developing airplane wings that were invisible to radar. And I thought, well, that's a really cool project, but I really want to figure out this ACL thing.

47:36And my advisor was like, well, I guess you could go to medical school. This is a Netflix series in the making. Okay, well, the advisor obviously had an impact, and your friend obviously had an impact. But fast forward, you know, 30 years plus, and you have actually invented a new way to treat ACL tears, the bear method. you did figure out that there's a reason why ACLs don't heal like an MCL would actually heal. Why is that? Well, it's really interesting. So both the medial collateral ligament and the anterior cruciate ligament are ligaments. When you look at them under the microscope, they look very similar.

48:08But interestingly, when the MCL tears, you can go in a brace, and at about six weeks, that ligament will heal fine in your back playing soccer. In contrast, the ACL, when it tears, even if we try to sew it back together, it doesn't heal. And so we wondered why. And so we did a series of studies where we looked and we compared the two tissues and their response to injury. And what we found was that actually the response to injury was very similar in the two ligaments. So the tissue and the cells in the tissue were doing exactly what they were supposed to do in both tissues. But the difference was in the MCL, when it tears, the ends bleed, and that blood clots and forms what we call a hematoma between the two torn ends of the ligament.

48:42And then in contrast, in the ACL, because it lives in this fluid environment of the joint, The ends bleed, but instead of making a clot or hematoma between the torn ends of the ligament, the blood disperses through the fluid of the joint. And so the two ends never have that scaffolding, that biologic scaffolding, to hold them back together. So once we discovered that, then it was a fairly logical step to say, is there some way we could immobilize the blood in between those two torn ligament ends and get that biologic signal where it needs to be to encourage healing of the ACL? And that's really what bridge-enhanced ACL repair, or BEAR, is.

49:14So the magic is kind of the sponge that we've developed that can absorb the patient's blood. You can place that blood-laden sponge in between the torn ends of the ACL, sew the ACL back together. But now you have the biology plus the sutures and the repair, and the ligament will heal. So what is done in terms of numbers or percentage with the method that you pioneered, what you invented, versus actual reconstruction and using other ligaments? That's a great question. So this is still fairly new. So we got FDA approval for this product in 2020, and so it's only been in practice for a few years now.

49:51There are studies coming out of Children's here, which is where we did the first studies, of course. But now other centers are coming along and doing follow-on studies, and those results are starting to come out. And it's very exciting to watch it grow. I'm also curious. You mentioned, like, FDA approval. Like, the approval process, is it a smart one? Is it the right one in terms of making sure that what's being done and studied the R &D, that it's safe for when it's finally done on patients? Or is it preventing things from maybe put into use sooner? I'm just curious where you guys weigh in. You're in it.

50:23You're in it every day. Yeah, I think it's a delicate balance. But I would say in our personal experience, the FDA was an amazing partner. So we were able to get into an early adoption program where they actually met with us and helped us and put together a panel of experts that would help us figure out how to make this the safest possible product and the most effective product before we went to patients. And we found their advice incredibly valuable. There was a lot of conversation and back and forth. And just having them, it felt like it was a team effort because we were in alignment. I mean, as a physician, I was going to be shaking the hands of these patients and my partners were, and we wanted to make sure things were as safe as possible.

50:57So they helped us with that. Do we have data yet on long-term impact or long-term outcomes yet when it comes to the Bayer procedure? Yeah, our longest data that we have is at about six years, and it's only in the small number of patients in those first studies that we did. But the reason that we want to study it longer term is because, as you may know, many of these patients will develop arthritis early in life, and as a pediatric orthopedic surgeon, I want to make sure we have a procedure that's going to last my patients for 60 or 70 years, not have the knee break down in 10 or 20 years. And so we're very interested in this arthritis question with Bayer.

51:33And in our preclinical studies, we were able to see that arthritis was actually much less in the subjects that we treated with an ACL repair with the sponge versus a reconstruction. So we're interested in seeing if that same thing plays out in patients. And the early data suggests that it is true. But again, that's very early data on small numbers of patients. So we're excited to see how that pans out. We're talking with Dr. Martha Murray. She's orthopedic surgeon-in-chief for Boston Children's Hospital. That's where we are, Tim and me, on this Friday. Preventive care. Like, so much of what we talk about often when we're doing interviews is preventive care.

52:09And I feel like the whole health community has been thinking about this for a long time. So what's the preventive care so that as much as we don't want you unemployed, like, how do we think about taking better care if we're living longer? Like, how do we think about this? So there's a couple questions on that. So one is how do we help our teenagers reduce their risk of injury? And I think the main thing for that for our athletes when they're in it. Because we push kids when they're younger. I think a lot of parents really push kids. So some things we can do to help them is help them work on strengthening in addition to just play time.

52:38And another thing is cross-training. So not playing the same sport all year round or playing the same sport every day. Giving their body a chance to rest and heal between exposures to sport. It's as simple as that. I think so. Wow. Does ACL tear happen more in kids than adults? And if yes, is it because kids are the ones who are playing sports and we're just sitting at computers? I think that's probably part of it. Again, it gets to this exposure question. How many times do you plant and change direction? And so the peak of ACL Andrews is really the high school athlete because everybody's playing a sport.

53:09And so we see a lot of them there. I want to ask you about social media and all of us sitting on phones or sitting in front of screens. Like, I just, I keep thinking that we're going to one day, I don't know whether it's 50 years from now, we're going to have a neck that basically goes over there. Or maybe not because we're going to have glasses on and that's how. Like, how do you think about this digital world? You're laughing, but. Can you surgically remove my phone from my hand? That's what Carol wants to know. But I do think about what it's doing to us. Well, look at it. Not just on mine. I've got the ACL fix for you.

53:35I don't know if I can fix this social media problem. But physically, like, I'm just thinking, like, how, you know, kids are in their phones constantly and stuff and, like, the shape. Like, do we need to be thinking about what this is doing kind of to our spine and different things? I think so. But I also think things come in cycles, right? And we see now if you walk down the street, you see everybody's on their phone. I think we're going to five years from now, we're going to look back at that and say, why are we doing that? You know, maybe we'll start looking up at the sky more. I hope so. Yeah, that's what I hope, too.

54:04Yeah, I mean, gosh, that's like you're opening up. You know, I know. I just I look around on the subway and just everybody and I'm just thinking the curvature and I don't know, whatever. What's the next thing you're working on or that you're excited about? I'm really excited about a product that we're working on for rotator cuff injuries. And it's a product that's injectable so that potentially... That's great. Yeah, you can have an ultrasound of your shoulder, see where the tear is, and then inject the product into the tear maybe in an office visit. So that's what we're working on, but very early days on that.

54:30Again, a challenge with pediatric patients as well? No, this is more adults, but we thought if we could make this work for a ligament, maybe we could try it for the rotator cuff tendon. And the nice thing about the rotator cuff is it is accessible by ultrasound and injection. And it's a pretty easy model for us to study. If we can make that injectable work there, then there's lots of other places we could apply it. Meniscus, other things. Did you ever figure out the invisible airplane wings? No. Not too late. Social media, invisible airplane wings, ACL. You guys are killing me. Well, we are glad you ended up going into pediatric orthopedic surgery.

55:03Is there another career like you're going to add on after this? You could do it. You could do it. I'll try. This was so much fun. Yeah, it was fun. Thank you guys very much. Dr. Martha Murray, she's orthopedic surgeon chief for Boston Children's Hospital. This is the Bloomberg Business Week Daily Podcast. Available on Apple, Spotify, and anywhere else you get your podcasts. Listen live weekday afternoons from 2 to 5 p.m. Eastern on Bloomberg.com, the iHeartRadio app, TuneIn, and the Bloomberg Business app. You can also watch us live every weekday on YouTube. and always on the Bloomberg Terminal.

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