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Dr. Panigrahy is board certified in both Pediatric Radiology and Neuroradiology. He is a Professor of Radiology, Radiologist-in-Chief at Children’s Hospital of Pittsburgh and Vice Chair of Clinical and Translational Imaging Research at UPMC. He has been continuously funded by the NIH since 2009 including both a K23 and current multi-center Ro1. He also has active funding from the Department of Defense, Society for Pediatric Radiology and private foundations. Dr. Panigrahy’s research focuses on applying advanced MR techniques to the study of fetal/neonatal/pediatric brain development and injury in those diagnosed with congenital heart disease and its impact on neuro-developmental across the lifespan.
John Williams: This podcast is for informational and educational purposes only and is not to be considered medical advice for any particular patient. Clinicians must rely on their own informed clinical judgments when making recommendations for their patients. Patients in need of medical advice should consult their personal health care provider. From UPMC Children's Hospital of Pittsburgh, welcome to “That's Pediatrics.” I'm your host, John Williams, professor and chief of the Division of Pediatric Infectious Diseases.
Steph Dewar: And I'm Steph Dewar, associate professor of pediatrics and residency program director here at UPMC Children's Hospital of Pittsburgh. Today, we're excited to welcome Dr. Ashok Panigrahy, who is board-certified in both pediatric radiology and neuroradiology. He's a professor of radiology, radiologist and chief at Children's Hospital in Pittsburgh, and vice chair of Clinical and Translational Imaging Research at UPMC. He's been continuously funded by the NIH since 2009, including both K23 and a current multicenter RO1. He also has active funding from the Department of Defense, the Society for Pediatric Radiology, and private foundations. Dr. Panigrahy's research focuses on applying advanced MR techniques to study brain development in patients with congenital heart disease across the lifespan. Dr. Panigrahy, it is so great to have you here. Thanks for joining us.
Dr. Ashok P: Thank you for having me. This is a real pleasure.
Steph Dewar: Well, we're very excited to get to know about your research here at Children's. I know you clinically are interpreting studies for some of our patients that we have in common, but I'm just curious if you can't tell us a little bit about the other exciting work that you're doing here.
Dr. Ashok P: So my research story actually starts almost over 20 years ago when I was an undergrad in Boston. I had the opportunity to work in the laboratory of Hannah Kinney at Boston Children's, and she was a pediatric neuropathologist. This was also in collaboration with Dr. Volpe, who had just come to Boston Children's in the early '90s to study white matter injury in the newborn. So from very early experience, I was introduced to white matter injury and brain development, particularly in premature infants, but also infants with congenital heart disease because they get similar type of white matter injury.
Dr. Ashok P: And so my early work was being exposed to the neuropathology, and I became interested in imaging through the course of my career. And some of that early work guided the work that I'm doing now, where I'm applying different types of advanced imaging techniques to study this disease across the lifespan in congenital heart disease patients. And it's an interesting topic, also, because the disease itself has changed over the last 20 years because the care of these patients has improved. We're now seeing a soaring population of adult congenital heart disease patients, some of which have risk for dementia and other aspects.
Dr. Ashok P: So, very early on when I was doing the neuropathology studies in the '90s, we were worried about the surgical techniques that we performed in the neonatal period that were resulting in hypoxic-ischemic injury with the brain, and that did not prove to really be the case. And it did take me about 10 years to actually come to that conclusion, but I started to move the direction of my research into understanding other things that could cause abnormal white matter development, including genetics. And when I came here, I started collaborating with Cecilia Lo. She's our chair of Developmental Biology, and whose major research interest is in congenital heart disease also.
Dr. Ashok P: And we had kind of a really interesting experience because she was able to develop some of the first animal models of congenital heart disease with her genetic screens. And I remember the first few times that we started collaborating, I would look at the mouse brains of mice that had hypoplastic left heart syndrome. And it was very interesting because there were areas of the brain that I wouldn't necessarily have thought were abnormal, including the olfactory bulb, hippocampus, cerebellum.
Dr. Ashok P: And when I went back to all the MRIs they had done the 10 years before, I had missed these findings because I was looking for the white matter injury. And so it just goes to show that you can definitely be wrong in your career. And it's really important to, as you're developing and continuing to develop your research, to really think out of the box and recognize that the hypothesis you might have at that time may actually be wrong.
John Williams: That's really an amazing progression. And I'm curious, to start with sort of the pathology, the end result of studying the tissue under a microscope and with various tools, and then to go back to imaging, which you can do while the patient is alive and perhaps under some sedation or anesthesia -- so I'm curious, how good is the imaging now? How good a picture can we get without having to resort to biopsies or other invasive procedures?
Dr. Ashok P: So the imaging has just ... It's just exploded over the last 15 years. And because originally I had thought about going into neuropathology, and then I thought about neurosurgery very briefly, but I think imaging always fascinated me because of the technology development. And that has totally proven to be the case now. We have lots of toys. We have a lot of imaging equipment. We have a lot of techniques, and they just evolve and get faster and more resolution, and we can use different modalities. And really, we can do things very noninvasively. But I do have really strong roots in neuropathology, where I do believe that sometimes you still have to kind of go back to those questions to validate because imaging is still descriptive, and it's noninvasive still, and there's still questions about the resolution and detail we can get down into.
Dr. Ashok P: So, I'm kind of glad that I've come from those roots because it sort of establishes my way of validating my imaging research, and which is important in any new technique that we get or new quantitative method. But the technology is truly soaring. I just recently wrote a grant to image adult patients with congenital heart disease at 7 Tesla, which is a scanner that we have here at UPMC on the adult side. But it's the highest field strength, and if I could show you the images of the hippocampus, it would blow you away.
Steph Dewar: So I'm just very curious about the funding from the Department of Defense. Where do they come off being curious about congenital heart disease?
Dr. Ashok P: Yeah. So I never thought in my life I would ever have a Department of Defense grant when I knew I had a trajectory of children's health. And I was actually introduced to that through my mentor, Cecilia Lo. She was familiar with that funding mechanism. And about seven years ago, the Department of Defense added congenital heart disease to the different topics that they study for the particular mechanism that we apply for. And we were some of the earliest people to even apply for that. And it's a good question why. I think that there are militants themselves who have congenital heart disease who've survived. But there's also military personnel that have family that have children with congenital heart disease, and the cost of taking care of these patients and their long-term issues.
Dr. Ashok P: But I also think that congenital heart disease is a great model, I think, to study the sort of intersection between developmental and destructive events in the brain that are going to have a genetic underpinning, and more so than any other brain disorder that we even know. And I think they like to fund translational type of work, where you can start asking some really interesting questions of tying mechanism to the outcome. And so maybe that's why, but it's always been a question. They still have it in there, so we've been applying constantly. And it is a special way of writing those grants. It's different than NIH, so I've been very thankful to have Cecilia as a mentor.
Steph Dewar: So I find this topic extremely relevant for my career trajectory. As a person who went to medical school in the early-to mid-'80s, the care of patients with congenital heart disease and the outcomes have improved dramatically, where we would offer parents essentially no hope with many congenital heart lesions at that time because the outcomes were so bad. And also the imaging, the changes in the imaging techniques and the clarity, is just so remarkable. So this is just a fascinating intersection where you find your place.
Dr. Ashok P: Yes. I would say that one of the fortunes I have is that I'm involved in recruiting families here in Pittsburgh, where I recruit the mom in the fetal period. So we get to know them very early, and then I recruit them for fetal MRI. And then the baby's born, and we try to do a pre-op MRI and then a post-op MRI if it's safe. So we do look at trajectory. But what's probably even cooler is that we actually really get to know the families. So my coordinators really get to know the families, and we just are there to help them go through this experience. We know maternal stress is an issue with these families, and how that impacts the child's brain development is another area that could be potentially modifiable.
Dr. Ashok P: And then the fact that we see these patients: Now, I do some longitudinal studies, but I also have cross-sectional studies at different ages. But I think what's really important is that the care has improved, but you still see these kids struggle. And they struggle in school, they have ADHD and autism risk, but then it's that transition to adulthood that's hard for some of them. And it's interesting because like in the hypoplastic left heart syndrome, it's very variable. It's like some kids, they just go to college, they're doing great, and others not so good. And some of them are stories where they can't really hold a job as a gas attendant, and their emotional issues don't allow them to develop a long-term relationship. And that affects their cognitive reserve and their ability.
Dr. Ashok P: And so we, as pediatric people, we want the best for our patients. But then you worry, "Well, this person isn't having the best outcome." And I think that's what drove me to write my first adult brain grant. We have to study it, and we have to figure it out. I feel very fortunate that this is the topic that I have landed and focused on, because it's very multifaceted. I probably know pediatric cardiologists better than I even know radiologists because of the multicenter approach and work that I've done. But we also have an amazing heart center here, with just some of the best in the world, I think, taking care of our patients. So I feel very fortunate to be part of that team.
John Williams: Yeah. That's a great point you just made, is that it's a great problem to have, to have such great outcomes for so many of the kids that they're surviving long enough and thriving into adulthood to have these problems. So you just mentioned the multifaceted nature. It sounds like you're working with probably collaborators in psychology, and psychiatry, and neurology, to try and link what you see in the imaging in the brain to these sort of psychosocial outcomes. And then what is your hope, that we can learn interventions?
Dr. Ashok P: It's all about intervention. The latest grant that I just wrote is a 15-center study of 300 babies with transposition that are going to get randomized to dexmedetomidine during surgery and seven days after, versus not. And the primary outcome is going to be brain connectivity at three months of age. And this is ... Everything that I've done from the '90s till now has led to this point. And I think what we're recognizing is all the research that we've been doing in these epoques of time are helping us understand, what are the modifiable risk factors that we could potentially intervene on? And then the imaging can potentially use as a surrogate biomarker or an outcome measure, along with behavior or other measures.
Dr. Ashok P: And so every grant that I'm doing now, I'm thinking of intervention. So we have that dexmedetomidine neuroprotection study. That will be one of the first neuroprotection studies in congenital heart disease. The other potential: I'm interested in exercise, and especially in the Fontan patient. How can we potentially improve neurovascular function in the brain and cognitive reserve in the adolescent patients? And then in every scenario, we know that there's going to be a subset where the bad genetics are not going to lead to the neuroprotection, but some of the patients will be doing okay. So it brings that whole personalized medicine. But this is where my work with Cecilia really comes in. So in the Dex RCT, we're going to be doing a nasal scrape to look at cilia, and she's actually going to do in vitro testing with different anesthetics. So it's that type of work.
John Williams: That's really exciting, though, because you're talking about ways to change how these surgeries you've done to enhance outcomes. Steph and I remember when we were young doctors, the way things were done in the neonatal intensive care unit for very severely premature babies. A lot of those things have changed a lot through research like this that found that there were better ways to take care of babies. And the kids that we used to see with thick, coke-bottle glasses, well, you just don't see that anymore. We know how to mostly prevent that. So this is really groundbreaking research you're talking about.
Steph Dewar: Yeah. This is so exciting to hear about. And I'm just wondering, if you think back to how you ended up in this type of a very exciting career, what advice you might give to that undergrad or that medical student, as to how they could be involved in this type of life-changing research.
Dr. Ashok P: It comes down to mentorship, 100 percent. Five hundred percent. A thousand percent. It's mentorship. I think that's the most important thing. I realize that more and more as I've taken on this vice chair position on the adult side, where I'm trying to help young investigators become translational imaging researchers. I've just realized I lucked out that I just happened to have the right mentors along the way to help me. And the thing that's interesting is that none of those mentors were radiologists. They were Jane Newburger at Boston, who’s a cardiologist; my primary mentor there, Hannah Kinney. Cecilia Lo's in genetics. It just, it doesn't have to be an imaging person, but it's the right mentor, I think, that's critical.
Steph Dewar: So in this day and age with all this technology that we have around us, basically you've brought it down to the human connection and the interpersonal connections that you've made in your career.
Dr. Ashok P: Yes. I think that's what it's about.
Steph Dewar: Well, I really appreciate the time that you've spent with us telling us about the exciting things that are happening here, and learning about all that's going on in Pittsburgh.
Dr. Ashok P: Well, I hope you'll have me come back because I have a lot of other things to talk about in relation to the department and just imaging in general. So maybe you'll have me back.
John Williams: That's a future date.
Steph Dewar: Yes.
John Williams: And also, I believe that we're getting one of these fancy, large, magnet MRIs built here-
Steph Dewar: That's right.
John Williams: ... at UPMC Children's. Correct?
Dr. Ashok P: That's right: 15 Tesla. That's what we're going for.
John Williams: Fifteen Tesla?
Dr. Ashok P: [crosstalk 00:18:39].
John Williams: That seems like a lot of Tesla.
Dr. Ashok P: Yeah. Yes. Very excited.
John Williams: Well, we'll have you back to talk about that.
Dr. Ashok P: OK. Absolutely.
Steph Dewar: Well, great. Thanks for joining us.
Dr. Ashok P: Sure.
Steph Dewar: And I want to thank all of our listeners for finding us. You can find other episodes of “That's Pediatrics” on iTunes, Google Play Music, and YouTube. Be sure to subscribe and keep up with new content. Leave a review and tell us what other topics you'd like our experts to cover. Thanks for listening.
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