Welcome back. We continue our coverage of IFMSS 2019 with your host, Doctor Beth Remey, fetal surgeon at Cincinnati Children's Hospital, and myself, Ray Hinkey. Today our focus is on technical and education innovations. We begin with a story about aqueductal stenosis and the return of an old management technique guided by Doctor Steven Emery, director of the Center for Innovative Fetal Intervention at the University of Pittsburgh Medical Center. Aqueductal stenosis is associated with poor neurologic outcomes, and back in the 1980s shunting was attempted because the prognosis was so poor and it was an obvious target because ultrasound was new. You could tell that there was fluid in the brain, and so people tried to shunt the excess fluid, the idea being that If you shunt the excess fluid, you take the pressure off of the brain and you improve neurologic outcomes. That was the plan. So that was attempted and it was a disaster because back in those days, they couldn't make an accurate diagnosis of pressure hydrocephalus. They just saw fluid in the brain, right? So they put shunts in babies that had hydranencephaly and Danny Walker malformation and all other kinds of anomalies. And so all those are in the denominator. So when you look at the numbers, it looks like there's no benefit. But if you actually pull that paper and scrutinize it, you see that the kids who had aqueductal stenosis in. On postnatal evaluation, those kids actually benefited. Nonetheless, IFMSS put a moratorium on shunting in 1986, and there's been just crickets since. There's been very little progress in this diagnosis because people just thought, OK, well we tried shunting, it didn't work. So now the current management is just observe them, get them to near term, 37 weeks, and do assist delivery. But unfortunately the delivery is usually by cesarean section. Sometimes by classical cesarean section because the head is so big, sometimes you even need a vertical skin incision for a baby that, you know, may have serious neurologic impairment. So it's a very unfavorable risk benefit assessment. So I had a patient back in around 2014, and so I proposed to my chairman at the time that we do a You know, a reassessment of this because the world has changed since the 1980s. The technology, you just can't even compare. That's how it started and we set out and published a research agenda. We started an animal model where we generate hydrocephalus in mid-trimester and then put a shunt in and then compare shunted brains to unshunted control. We had to design the shunt from the from scratch from the very beginning. So we've done that and we've tested it and revised it based on our experience with the animal model. We had to generate the animal model that is hydrocephalus that took a long time, but right now we're at the point where we have, we're able to reliably and reproducibly generate hydrocephalus, and we have a shunt device that is. Pretty much near design freeze, and so now that we have that, now we can start looking at efficacy. Did placing the shunt improve the neuroanatomy? And we think that it will, because really what you're, what you're doing is you're just decompressing the intracranial pressure, which will allow the brain to A, continue to develop normally, B, heal from the, the injury that's already occurred. So when, by the time they get to term, their brains are normal as opposed to devastated. How do you feel like this idea has been received in the community? Oh, phenomenal. This is the cool thing. So I presented the research agenda in 2014 at IFMSS, and the people who put the moratorium in 1986 were in the audience. Mike Harrison, Bill Kluwell, you know, and they said, this is awesome. We should, we should do this. We should definitely do this. And then they were just incredibly. Supportive about telling me, OK, this is, this is what we did last time, and, you know, don't do this and try this and think about this, and it's been really, really helpful. So in 5 years you've gotten from concept to an animal model to reproduce and multiple revisions of a shunt that's now you think ready for use. Yes, that's remarkable. It's incredible. Thank you. It's been a lot of work. It's very impressive. That's, that's a very quick timeline for a device development, like a de novo device development, right, because it's not similar to any of the other shunts that we use for fetal indications, right? That was the beauty of it. This new problem allowed us to start from scratch. Just like forget what they tried before. Forget what we're doing for bladder shunts. That's not what we need. We need this thing that has these certain performance characteristics. So we could, we could design, it's, um, it's called purpose designed, which is very unique in fetal medicine. Like what else do we have that has been designed specifically for fetuses? It's always borrowing stuff from other people. The Harrison shunt, the Harrison shunt. Continuing on the theme of product creation, Doctor Jose Piero, director of endoscopic fetal surgery at the Cincinnati Fetal Center, tells us about spina bifida. Spina bifida, these babies usually have a lot of sequela. OK, Paralysis is demonstrated that in utero surgery, prenatally, as soon as possible, makes a difference in these babies, so improve clearly the outcomes. And during the repair in utero, also postnatally, it's very frequent not to have enough skin or dura or the uh recovery of the lesions. So we use consistently many times uh dural patches, dural substitutes, and there is many, many of these materials in the market, but no one is demonstrated to be ideal for this purpose. And nowadays, we innovate with photoscopic approach with minimally invasive fetal surgery. And we need to use these patches through small cannula. So that's a, that's a need to have an ideal patch for this purpose. So in the lab in collaboration with the engineers in Cincinnati, so we decided to do a la ala a la carte patch. So with a lot of properties. So basically we. Doing a blend of two polymers that are FDA cleared already, so in a proportion of blend we can achieve a patch. It can be very thin, can be coiled by temperature in body temperature can be displayed, can be uncoiled automatically, and it's having a lot of good properties biodegradable, it's non-toxic, it's basically spinal cord friendly. So we are doing several publications on that, OK, and hopefully we can put on the market soon, OK, after FDA can approve that and finally proposal sent us to do a clinical trial, and it's an acellular patch. Yes, it's a synthetic patch. It's a PEA PCL, uh, a blend, so it's basically two polymers that disappears around a year or so, so. So you don't need to remove it. You don't need to remove that, and it's totally inert. And for the young investigators and inventors out there, can you just give a timeline of from concept design and, and how long has it taken for you to get to this point where you're ready to apply to the FDA. Important. So we started with this project like almost 3 years ago. So we started with the in vitro testing of all the, the properties of the patch, and once you are completely sure that it's non-toxic, etc. we started the in vivo in rats and now in vivo in large animals, so in fetal, in fetal lambs. And uh, probably we are working with a, a regulatory mark for FDI etc. So probably a product uh from the very beginning to the, uh, to be in the market or to be clinically useful will be like 5 years. Now let's shift gears and discuss developing software to help us perform safer operations. We are joined by Anuk van der Schot, technical physician at Radbon University Medical Center in the Netherlands. Currently we are working on a technique in fetal therapy where uh during twin twin syndrome, uh, laser occlusion of the vascular anastomosis is the way to treat, but this procedure is limited by a very limited field of view. Uh, which makes it very hard for the surgeon to orient and to navigate where the anastomoses are and which anastomosis we have to calculate, so that's why we are trying to make a Google Maps for fetal surgery, um, where we're trying to create a real-time panoramic view of the placental surface on days which the the surgeon can make his decisions. And thereby reducing the risk of complications associated with prolonged surgery time or incomplete surgery. So currently we tested our algorithm by injected placentas and we tried to stimulate the in vivo setup as good as possible. And next step is to bring this technique to the clinical practice. So is the device that's helping make the. Inside of the camera that would go into the uterus or what is what would actually we're just using the visual information of the standard feettoscope, so we don't need extra hardware or sensors or it's just software using the visual information of the feettoscope. You can think of a panoramic view with your camera on your phone, something like that, but then for the feetoscope. So it could potentially work with. Any standard phytoscopy equipment that's in use, yes, and also for other disciplines as well, for example, bronchoscopy or laparoscopy, everything where you're using an endoscope that could be incredible because we are only using the visual information, so that's, I think a very strong point of the of the research. Yeah. Wonderful, thank you. So excited to see what you guys create. We finish our IFMS coverage today with the creation of an innovative way to practice a fetoscopic intervention before heading to the OR. Doctor Gina Miller, assistant professor of gynecology and obstetrics at Johns Hopkins Center for Peotherapy and lead of the fetoscopic spina bifida repair program, tells us more. The problem with feetoscopic spina bifida repair is that there are a lot of technical challenges that go into planning and preparing and team training when it comes for preparation for this type of surgery. And so our approach is to develop essentially a modular system for incorporating 3D printing technology to create patient matched models for practice for each individual case. That helps assist us in determining where the potential challenges are for each individual case within our team, since it's a coordinated effort with two different specialists working side by side, and it allows us to try different materials, try different suturing techniques, and go through that process in a no risk environment. With this process, we've learned that there's a really good visual correlation with the lesion at the time of surgery. There's very high correlation with the number of sutures and how the repair actually goes at the time of surgery. And in order to do a modular system to just do the 3D print of the actual lesion, to go into a standard host model, it's very cheap, it's very efficient. So it's suitable for rapid prototyping for anyone to to really pretty easily incorporate the system into their clinical practice. So what is your lead time from, you know, seeing the patients, making the diagnosis, getting the imaging to actually being able to do the 3D printing? Do your practice and then get to the OR. Sure. So we can take the image from the ultrasound volume. Now the workflow is very much better simplified so that you can go directly from the ultrasound machine to printing software that's printed on a desktop printer in our office. Average print time is a little over half an hour, and then that can go directly into the simulator, which is a desktop model that's also immediately available in our center. And so our turnaround time within the time when you see the patient, counsel them for surgery and schedule them, our surgical rehearsal is done with the core team within the week before surgery. So is it a virtual simulation or an actual it's an actual physical. And what is the material you use to make the physical model? So the rapid print that we use in the office is just a standard ABS filament. It's a hard material. You can also use the Ninja Flex is really nice because it's a soft and more flexible material. The development of the host model, we haven't decided exactly on what the ideal material is, but the prototypes are done in a very low, low fidelity way. But once the standardization of the host as well as the size of each insert is finalized, then the plan is to just generate a really high quality host model. So where are you at in this this process of developing this model? So we're in the process of standardization of the different components of that. And so that is pretty well close to completion, and we've added a few additional features for the host to make the application of the skin covering a little easier and add the instability that we also experience in the OR as a component of the host model as well. So you can really turn that around in very easily within the clinical practice. And fun fact, once this model is created, the authors plan to make the program open source for everyone to use. How exciting is that? That wraps up the IFMS coverage for today, but be sure to stay tuned for part 3, a collection of clinical research findings that will make you think. Have any questions or thoughts about the topics discussed today? Please share them on the Stay Current app, Twitter or Facebook. This chapter is created and edited by Todd Ponsky, Alex Cassar, Alex Gibbons, and myself, Ray Hanney. Remember, knowledge should be free.
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