Engineerning Health – Day 1, Pt. 1 – 09:00–10:15

Engineerning Health – Day 1, Pt. 1 – 09:00–10:15

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Good morning, everyone. Warm welcome to this first initiative seminar for the area of advanced engineering health here in Gothenburg. We are hosting you from the RunAn auditorium at Chalmers University of Technology in Gothenburg. I don't know if we have any people joining us from outside of Sweden, but warm welcome to all of you, no matter where you are.

So we who are hosting today are me, Cecilia Berlin and my colleague Martin Fagerström. We will briefly introduce ourselves in a minute, but I want to just say that this room that we're in, RunAn, normally hosts about 450 people. But today, for famous reasons, we are only eight people here. So I actually want to start by saying thank you to our tech staff who are here making this possible today, making sure that we can have this kind of really interesting seminar in spite of an ongoing pandemic. So this is a very interesting, very jam packed day. We have a lot of very exciting researchers who are going to tell you about innovations and steps forward in health.

And today's topic Joining Forces in Healthcare Solutions is very much about how far we can reach when technological competence gets to join medical competence. And just so you have some background on the two people you will be seeing most frequently, but not for the longest duration. Like I said, Cecilia Berlin, and I'm an Ergonomics researcher at Chalmers. I mostly study production ergonomics and Martin, why don't you say some words about yourself? Thank you, Cecilia.

Yes, my name is Martin Fagerström. I work, I'm an associate professor in Solid Mechanics, but I'm here because I'm also the co-director of our area of Advance in Health Engineering. And as Cecilia says, we have two exciting days ahead of us.

They will be long and intense. We start at nine, we end up five both days. We have some breaks in between.

But the longest breaks are the lunches between 12 and one o'clock. We have divided this in four different topics when we talk about the speeches or the presentations. And then we also have two panel discussions.

So for today, we will start with the block pushing the boundaries in diagnostics and treatment, followed by modern treatment focusing on personalized health and health care. And then we will have a panel discussion on how we foster collaboration when we come back tomorrow, we will talk about prevention to keep all of us or most of us out of the hospital. We will talk about restoring health and use solutions for rehabilitation, and then we will conclude with another panel discussion about innovation. But I think that's enough for the schedule. We have four people, four invited guests that are eager to get this show on the road.

So I would like to go directly to them and have an introductory discussion with Ann-Marie Wennberg Lärkö, CEO for Sahlgrenska University Hospital. We have Anita Holmäng, Dean at Sahlgrenska Academy at Gothenburg University. We have Göran Hilmersson, Dean at the Faculty of Science at the University of Gothenburg. And last but not least, we have Stefan Bengtsson the President of Chalmers. So with that, I would like to welcome our our four first guests. And I would like to start with you Ann-Marie.

Currently we are fighting against the global pandemic that I don't think any one of us could have foreseen if we look back, say, one and a half years ago. We're very grateful for all the hard work that all of your employees and other people and other health care providers have put in. So to keep us safe, as safe and healthy as possible. But it's been tough. My question to you is, do you see any silver lining in this? Is there anything that we have learned that we can bring to make us stronger and better for coming challenges? Well, good morning.

Hello, everyone. It's really nice to be here. And as you've been saying, we are right in the middle of the third wave of this pandemic and I'm currently at the hospital. That's why we it's mandatory with the mouth guard.

So that's why I´m talking behind this guard here. And I hope you will hear clearly, Yes. That we have truly seen the importance of clinical research during this pandemic, how it enables new therapeutics that makes a significant difference for the patients. Research, development, education and innovation is the way forward. And we've also seen how digital solutions enable us to meet the patients in new ways. And this is something we believe future health care co-workers, they need to be educated and prepared for this.

And last but not least, we have had to put our entire focus on our main mission and, then we have to put less time on administration, which is actually quite a release. All kinds of specialists have been working together, cross boundary, and that kind of team work is the way to go. Yes, I agree. I think it's really impressive how you have been able to fight this for all of us. But if we try to put aside the covid 19 for a while, what other kind of great challenges do you see that we are facing now to give people better and healthier life? There are many challenges, and we need to use research and development to face these challenges.

The answer to which challenges we should focus on, is to be found among the patients. It is their needs and their must that have to determine our focus, and therefore, it is crucial with a close co-operation between Healthcare, Academy and Industry. Yes, I agree completely.

When you say research, I would like to ask Agneta, we hear a lot about these different challenges, including Covid 19. But how do you see our potential in the region of Västra Götaland? What potential do we have to tackle the challenges today and tomorrow? I think that we are very well equipped in region Västra Götaland with strong universities and healthcare sector, and with a lot of companies and the only pharmaceutical industry of left in Sweden, AstraZeneca. We also have a strong tradition of close and extensive collaboration between many different stakeholders, including academia, care providers and industry, which is, I think the pre-requisite for success. And now, thanks to Chalmers, we can deepen the collaboration with all of us through the newly launched Health Engineering area of Advance, where close dialogue is conducted to develop new forms of collaboration in both research and education. So I'm very happy to say by working together, we are on the go and have a lot of exciting and forward moving development and investments.

Thank you. And another part of Gothenburg University, where we also have a lot of important research, is the Faculty of Science. So Göran you're the Dean of the Faculty of Science, where health and life science is an important focus. Can you give some examples of research that you conduct in this area? Well, thank you and thank you for inviting me here or we being part. I think that national science is the basis of much that is happening both at the technical side and also the medical side. So I would like to say that the essence of what we do as a science faculty is a fundamental understanding of nature and the world around us.

Our research then deals with the structures and mechanisms and from atoms to organisms and also to larger species. And it's multi faced, models and modeling are used. We establish correlations that help to understand the world we live in. And here's science, particularly national science, contributes with new tools, new methods that can be used by others, not the least the technical development and also the medical side applications. The understanding and ability to intervene in biological processes requires, of course, detailed knowledgeable, structure and function across the entire scale and therefore access to modern infrastructures such as Max IV, NMR imaging, mass-spectroscopy, State of the Art lasers, electron microscopy, and other important infrastructures are very important for us, and it puts the fundament for development of new areas.

And in our faculty, for instance, we have machine learning and examples in the physics department, the Volpes research group is doing interdisciplinary collaboration to screen for diseases to see correlations. We have cancer research activities within the faculty. We have antibiotics, we study aging processes through mathematics, and we have a lot of structural biology, membrane proteins, the structure. The structures are needed to understand how we can intervene with them. For instance, developing drugs, medicinal chemistry.

We have research in the area of Parkinson's disease, looking into the chaperons, how they work, put the sensitive proteins in plants, molecular mechanisms, studies of molecular mechanisms, and also genetic mechanisms that are important for many diseases. So we look at these from molecular level, understanding the processes that underlie these diseases or inflammations. So I think that much of what we do is very much related to health, even though we are on the far side, on the fundamental side. But it sounds like sorry, I was interrupting. Go ahead. So I look very much forward to the rest of these two days, symposium or workshop.

I think you what you say spans across a wide range of different disciplines. And also, as you say, many of them are the basis for maybe more medical research or more technical research. And I think that to some extent is quite similar to how we do it at Chalmers, we have a lot of different tools in our toolbox that can be applied to solve medical problems of different sorts. So I would like to go over to Stefan, because we have quite a focus now on health at Chalmers. But why is the combination of engineering and health so important for technical University like Chalmers? Good morning, everyone.

And I would say it is of several reasons. First of all, of course, we clearly see that the healthcare becoming more and more technically advanced, and there's a lot of results coming out of engineering research that probably can be applied to even to continue to develop health care services. So that is one of the reasons our ability to make impact and to contribute in building a better society, which is important for us. Chalmers, of course.

Then, of course, together with colleagues at the Sahlgrenska Academy and the Faculty of Science, we can build also, of course, academic and academic excellence by working together in this important boundary between medicine, science and engineering. So there are also internal driving forces in that sense. So impact and excellence. And the really exciting thing, I think in our collaboration, how it develops here is, of course, it's a lot of research.

But we're also talking education now and I see that there are huge opportunities, and I think it will be more and more important to find various types of hybrid educational programs between medicine, science and the engineering. So there are several reasons for Chalmers to join into this, we have a tradition of working together across various disciplines, internally at our University. But what we're doing now which is so exciting is we are taking now this collaboration across the faculty borders, working with the disciplines that are further away from where we normally act. And and the opportunities are enormous. Yeah.

I think that's quite impressive for this region that we have everything now from Bachelor programs at Chalmers all the way up to a joint graduate school that we will hear about later as a collaboration between Chalmers and Sahlgrenska University Hospital, Sahlgrenska Academy and the Faculty of Natural Sciences. But it also reflects on the medical education post, maybe the new program for educating new doctors. But, Ann-Marie, you have also highlighted this importance of more understanding of technology and innovation for your personnel and for the new doctors that we develop or educate, including new innovation and medic residency program at the hospital. So can you elaborate a little bit more on the view that you see on the need to combine health and engineering? Yeah.

I will do that gladly, because this is something really interesting, I think. And there is so much development going on both within healthcare, engineering and natural sciences. And we cannot have specialists focusing on only their speciality when it is obvious that different fields of science together can create new and better solutions. And I believe in the understanding of each other's fields will make it easier for us to work together, now and in the future. So I'm very hopeful for this program I must say.

And I would also like to take the opportunity to thank the organizer for a fantastic program. I think these two days, and I hope the seminary days will be very fruitful. I think they will. And I also would like to say good luck to all the participants.

Thank you. Yes. So we already talked a lot about the importance of collaboration.

Now we were stressing the technical innovation coupling to medical education. But is there anything you would like to add more? Agneta? Yes. I think with an aging population, the number of people who need assistive devices will increase. And in parallel, cleared demands are being placed on accessibility to healthcare.

And I think that all these challenges require a combination of health and engineering with new approaches to improve the prevention of diseases and injuries and, of course, to promote wellbeing. So I do think that you really need a combination of research in health and engineering to meet tomorrow's health challenges. I couldn't agree more. What do you say Göran? Is there anything you would like to add? I think that is spot on. We have to have to work together more. We are already starting doing it and I think this is the future.

We will be stronger together. We reach longer. So the name of the seminar today is Joining Forces in Healthcare Solutions, which somehow indicates the importance of collaboration. And we've talked about collaboration a lot when it comes to research and education, but there are more levels to this, I think. So what do you say Göran? Do we have are there any more aspects of collaboration that we should be aware of that we shouldn't forget? I am I think not in my mind right now we are working together, and I think possibly we have to strengthen our links and collaboration also with the industrial parts and the region in general, and also what Stefan says in terms of education, we can do more to strengthen collaborations and having our students to work across the different faculties and the universities. Yeah. There is a very interesting and intense discussion on how

we can increase the joint collaboration between our organizations, which I think is very optimistic and it's very exciting. But if this collaboration is so important, Stefan. How do we make sure to foster an environment that we get this kind of collaboration for real between our organizations and also with the surrounding stakeholders? We are building on strong traditions where there are many links between the organizations and also to industry and to other external actors here.

So what we need to do now is to take next step in developing this. And I think important thing here is to facilitate what can we do? Well, we can organize initiative seminars to let people met and understanding that they are sharing common interest or they see opportunities. I think important between our organizations and also with the collaboration with industry and other actors is to have various types of events where we build joint agendas, because if we can build such joint agendas based on needs in the health care and development in the different scientific fields and the also needs in industry and trends and developments observed there, if we can mix this together and building joint agendas. Then, I think we have we have formed a basis for such an environment where we're many, many of our staff will see students as well. We'll see the opportunities and then will take is to the next step. So I would say let´s meet.

Yeah, I think we're all eager to meet also to meet in person. Of course, we cannot do that now. We were hoping to repeat previous successes of the two previous engineering health seminars that have been held before. They have been extremely rewarded for everyone participating, I think not only to listen to new research or exciting presentations, but also to meet, to chat, to have lunch together, and also to sort of find these new ways of working together. Agneta.

So you're the Dean of Sahlgrenska Academy and you and the researchers at Sahlgrenska Academy has a lot of collaboration, for instance, with Chalmers, with the hospital and with Göran and his colleagues at the Faculty of Science. But what in your experience, is the key to success? So what are the key factors for successful research collaboration? I think that Stefan was spot on Let's Meet the very good to summarize it that we cannot should not organize research, but we can facilitate for our researchers with platforms to meet and work together and with support of world class infrastructure and to have shared positions between Chalmers and Sahlgrenska Academy is another way to stimulate collaboration and has found out to be very successful. Another possibility to strengthen our collaboration is to share PhD students and generously supported from region Västra Götaland, we have now started the Gothenburg research goal of health engineering with a dual PhD program, and you will hear more about this initiative later on today. But I hope that this research goal will stimulate collaboration between students and supervisors and also to be attractive for medical and technical oriented PhD student who will have a PhD in medical science and a PhD technical science, I think this is a very good initiative.

Thank you. And I think just comes to mind now, this residency program that we were discussing before on Ann-Marie, I took part in one of those meetings discussing with the residents. When I came to the meeting, it was more, I thought it was more to explain about our area of advance and to explain what we can do.

But I learned a lot in only 15 minutes. And I think we came up with a lot of new ideas for collaboration, of how we can engage students in our joint collaborations. So I think, just want to emphasize to everyone watching that if you get a question to be involved in that residency program, hosting a day, or if you are being asked to give a seminar in the graduate school, the joint graduate school, I think you will get so much back. It's not just you giving information, but you will also get so much back from this fruitful collaboration, this interdisciplinary collaboration. I don't know what you say, Ann-Marie.

I think it goes both ways. Yes, I really do agree with what you're saying. And I myself, I have an experience of this working together, coming together, because you have to go over different boundaries and borders in order to make it happen. So I can just agree a lot with what you say. And the old cliche 1 plus 1 equals 6.

That is really true here. So, Yeah, we have much to gain from this collaboration, and the Sky is the limit, I would say. Yeah, that sounds very positive.

I think so. If we look at today's seminar, you already highlighted that this is maybe one important part of us coming more together. We have a fantastic lineup of speakers. Stefan, this time Chalmers is the host, is there anything you would like to say to address the speakers or the audience? Yes, of course.

I would like to say thank you to all of the speakers, to attending and sharing all of your knowledge to the speakers as well as to the audience. Of course. I hope that you take the opportunity.

I hope that despite of having these digital format that you will have great discussions and that many good ideas will come out of these discussions that could be brought forward in further building collaboration. So thank you to all of you. Also, thank you to the organizers.

And I really look forward following what will be happening during these two days. So thank you, everyone. And good luck with the creative discussions. Yeah, thank you. And I think the lineup is actually a good example of the collaboration that we already have ongoing.

I think we had a fantastic discussion in the program committee with a lot of good, as you can see in the program. Also, a lot of good suggestions for speakers. Many of them couldn't even fit this time.

So we also have a big lineup of runner up for next time. Agneta, many of the speakers are also from Sahlgrenska Academy. Is there anything you would like to add from your side? I think it was frozen for a while. I don't know if you heard the question, Agneta. I can guess what you said, but as many of the speakers are from research groups within Sahlgrenska Academy, I'm very happy.

I'm proud to see that we have a lot of speakers from us, but even more happy to see that there is a combination of speakers from Chalmers and Sahlgrenska on many program items. And I would also like to take the opportunity to thank the organization committee for a fantastic program and all the work you put in to make it so very good and interesting. So I am really looking forward to listen and learn a lot these two days, and I highly recommend you to do the same. Thank you. Thank you.

So we are soon about to announce and introduce our first pair of speakers. But before that, Göran, rumor has it that you will be arranging the next engineering house. Is there anything you would like to first of all, can you confirm? And second, is there anything you would like to say about about this? You should never believe in rumors, but in this case, I can assure you all that this is true.

So we plan on hosting the next Engineering Health seminars and hopefully, I trust that this will be in person, that we will meet in one room and not in hundreds of different rooms. So I look forward to seeing you all and possibly new recruits and new scientists, collaborators, and to meet the in person, person to person so that we can start learning to know each other and therefore by these kind of spontaneous meetings arenas Agneta was talking about can actually function as a seed for new collaborations. So I look very much forward and I'm happy to announce that we will host the next seminar. Thank you.

So we will gladly hand over the organization to you. And I hope that it will be like this time that we all pitch in as good as we did preparing for this seminar. By that I would like to thank you all very much for coming together with me this morning to start this exciting two days seminar. I think we have, as we already said, several times, many very interesting presentations, and also a number of interesting discussions both on collaboration and more on innovation and implementation. So I hope that everyone online will be able to stay tuned as much as possible. So by that, thank you very much.

Stefan, Ann-Marie, Agneta and Göran, I really appreciate the time you took to be here to start this exciting seminar. Thank you. And by that, I would like to hand over to Cecilia, who will introduce the first pair of speakers that we have. Yes, I will without further ado launch us into the next block of topics, which is new technology pushing the boundaries in diagnostics and treatment.

And this block will go on up until lunch. And in between we will have some short breaks. But our first speakers will certainly live up to this pushing the boundaries idea. And I think it's a very interesting research that has provided a very obvious increase in life quality for people who have lost a limb. And we are going to welcome Max Ortiz Catalan and Paolo Sassu. Max is the director of the Center for Bionics and Pain Research, and Paolo is program director of hand transplantations at Sahlgrenska University.

I should say Max is from Chalmers University of Technology, also, they will provide some more details about their background, but I'd like to wish you to a warm Welcome. And as a warm up question, Max and Paolo, where are you joining us from today? Well, right now in the American continent, so it's about two am or something for me, but I'm happy to be giving this presentation. Extra big thanks for making the effort to join us. We really appreciate it. And Paolo, how about you? Easy for me because I'm here in Gothenburg, so I'm fresh. Right, so near, far, wherever you are to take a Cheesy Titanic reference, please go ahead and tell us about your exciting research.

Thank you. Yeah. So I'd like to thank the organization committee for this invitation and we prepare a presentation together with Paolo, with whom we've been collaborating for some time.

And I would like to start saying that I been let me see. I have been collaborating with Sahlgrenska with my group from Chalmers for several years now, initially as the Biomechatronics and Neurorehabilitation Laboratory. And now this has grown into the Center for Bionics and Pain Research, which basically means that we create a way to have a closer collaboration with the hospital. And we have moved all my team from physically from Chalmers into the hospital and now we're also integrating several medical professionals. And the idea of doing this is basically that we can develop and clinical implement technology is to restore human sensori- motor function, and alleviate pain after sensorimotor impairment. And it's very important to highlight this development.

That's something we've been doing, but also the clinical implementation. And this has been thanks to the generous, donation of the Promobilia Foundation and the IngaBritt and Arne Lundbergs Foundation. And the motivation for this is rather clear. The starting point, we want to develop technologies around the patient and involve all the stakeholders.

And the idea of involving all the stakeholders is that we can overcome the barriers for implementing research. So our work doesn't stop when the research grants is over, but we can move forward to clinical practice. And in order to do that, we need to know what is necessary for this to become clinical practice. We have experts from different fields of medicine helping us, giving us their advice as part of the advisory board of the The Center, as well as on the engineering side.

And we also include a few industrial partners. So we can provide devices for these patients that they can take home and their quality of life. And the third motivation for the in the Center is that we can we have brought together all the cutting edge technologies to solve complex cases that are not available pretty much anywhere else in the world.

So the idea with the Center at this point, we have four main branches. We work on Bionic arms and legs, Robotics and Virtual Neurorehabilitation and Pain due to sensorimotor impairment. And you will see it for this presentation is that there are different disciplines such as electronics and medicine and neural engineering, neuroscience, artificial intelligence, virtual reality, and so on that we utilize to develop technologies in all these four applications at the moment. So I think we will start with the biological restoration function after limb loss with Paolo. Yes.

Thank you, Max. I would just like to start saying that I came to Sweden, actually to Gothenburg to, I was recruited by my chief at the time, Anders Nyström and my dear colleague Peter Axelsson to start the hand transplantation program to focus on the this new adventure. So I've never really been interested in developing this field of artificial replacement, let's say after an amputation and Nathan, Max and his team has been extremely inspiring experience because I discovered the new world as our collaboration has been really amazing since the last 4 or 5 years. I think the most important fact is that we've tried really to follow not to parallel lines, but we tried to integrate our work together. Even though I was first interested very much in hand transplantation.

I was extremely happy to work with Max and his development, and he was extremely positive in helping us in many ways with the hand transplantation, especially with the virtual reality training of the patient and the rehabilitation. So it was a really great collaboration. I'll just go through a little bit of a history of hand transplantation. And then we'll talk about our project here at Sahlgrenska very much we move to a great master surgeon, Joseph Murray, who did the first kidney transplantation 1954, what was interesting to see how the scientific community was quite much against transplantation or transplantation was seen as something that would just not happen because of difficulties in immunosuppression and so forth. But thanks to the vision of people that pushed the limits, as many times happens in other fields, this was actually feasible.

The first hand transplantation was done in Ecuador in 1964, and it was pretty much basic immunosuppression. So the hands were rejected two weeks after surgery, and the first successful transplantation, unilateral transplantation was made in 1998 in Lion, France and then in Louisville, USA 1999. And this is the first American patient that I met when I was a fellow. I spent two years in Louisville working with that group.

Transplantation, hand transplantation is really, I would say, safe procedure compared to the most common transplantation, just kidney transplantation. If you look at the patients survival rate, this is still very high at 10 years as well as graft survival rate is still very high compared to other types of transplantation at 10 years, for example. But we do have to remember that all patients are transplanted and hand transplantation patients are the same.

They have to go through immunosuppression for the rest of their lives. So it's a wonderful thing to get one or two hands back, but the drawback is having to take immunosuppression. So why if it's supposed to be so safe? Why we still have so it hasn't become so popular worldwide, well made because it's a highly complex organization. There are still ethical concerns by mainly they don't know much about hand transplantation, and many patients obviously don't want to take immunosuppression, as we see it's extremely high organization because around one patient, we have very many specialties that have to work together, not only hand- surgeons based transplantation of physical therapy, psychology, neurology, pathology, so many figures that have to work with one single patient. Still, even though the World Health Organization say, "Health is a state of complete physical, mental and social well-being..."

An amputated patient is still seen as a healthy person, not necessarily, so for many given immunosuppression to a so called healthy person is somehow wrong or not appropriate. We do have, as I said, the complications and mainly metabolic complications, but also bacterial infections that can happen. But as I said, we can treat them quite well.

And that's why patient survivor rate is very high at 10 years. These are just some examples of transplanted patients around the world and you see how they probably their function is not perfect, but they do have sensation. They have a motor function that allowe them to do most of the daily activities quite well.

So I'm going to give the talk back to Max before showing our protocols. I just wanted to give you a little hint of history and how transplantation has worked in the last few years. Thank you, Paolo. So the challenges that we face when we try to restore a biological limb with an artificial one can be divided more or less in four aspects. One of them is the artificial limb itself.

So we don't have biology anymore, so we need all robotic and arms and legs have been developed for research purposes and also some commercially available with several degrees of freedom that most patients today will use a simple one degree of freedom hand and the main reason is that because we struggle to provide intuitive and reliable control for several robotic joints to patients, and the reliability is mostly due to the use of surface electrodes. Then when it comes to sensory feedback is very much lacking, patients only know what's happening with the prosthesis by looking at them, there is no somatosensation information coming from the prosthesis itself. And then there is another big problem that people don't talk much about, because maybe it's not a sexy to talk about neural engineering. But these prostheses are heavy and they need

to be attached to the body somehow. And the standard technology to do that is a socket that is compressing soft tissues in the stump. Now, a solution for that was developed in Sweden a couple of decades ago with the discovery of osseointegration.

So as you probably know in this audience, osseointegration was discovered in Gothenburg in the 50´s? by Professor P-I Brånemark. First application were dental implants, then after that, Professor Rickard Brånemark and Professor Kerstin Hagberg have been working a lot on using this technology between many other people, of course, this large group of research and clinical implementation. And now there are implants developed to attach prosthesis at the lower limbs or the upper limbs. And there is a spin off company that was created out of this technology Integrum that is located in Gothenburg.

That's one of our collaborators, so that more or less solves the problem of the attachment of the heavy prosthesis to the body. But then we still trying to solve the problem of control. And my group and others around the world have developed technologies and algorithms to decode intention of movement by looking at the electric activity of the body. So we can in principle control every finger of a missing hand and several joints simultaneously, as you can see in the video on the right.

And we made a lot of these work openly available in the first and I think, only platform for decoding motor evolution using by electric signals that were called BioPatRec that has develop over time. We also develop an open source hardware system that allows to record the electric signals. And this has been used a little bit all over the world since it was introduced in 2013 because it can be used as a general human machine interface to control assistive devices. But as I said before, the skin interface is a problem for reliability, so we've been looking at implanted electrodes for several years.

And if you're going to go inside the body, that allows you also to stimulate the nerves superwide sensory feedback. But you can do this outside the nerve, inside the nerve and there are a trade off between using those implanted neural electrodes. And we also done some work to improving or optimizing the way those electrodes work to have a better neural interface. But this idea of using implanted electrodes is by no means new.

It's been used in the 70´s for prosthetic control in the upper limbs and also to provide sensory feedback, so either control and sensory feedback, but this has not been really clinically implemented because of the lack of a stable communication interface between what's implanted and what is outside. So we know we have electrodes that can be used for control from sensory feedback, but that bidirectional communication has been a problem. So a way to solve that will be to use a wireless interface, as it´s been done for Pacemakers and neural stimulators. The problem with prosthesis is that the bandwidth is considerably higher, so this hasn't been realized clinically today. The approach that we take is to use osseointegration because it's already a percutaneous interface and then use that interface as a con-bit of information between implanted electrodes and external prosthesis.

So I started working on this idea in 2009 as part of a master thesis, and it was a project in collaboration with Professor Bo Håkansson at Chalmers and Rickard Brånemark at the hospital and Sahlgrenska Academy and Integrum. So my work in this past years has been to take osseointegration as a technology that allows purely mechanical attachment into a system that prosthesis that allows for communication with implanted electrodes. So a concept that we now call neuromusculoskeletal prosthesis. And this is one of the first patient that was implanted with this system in January 2013. So there you can hear a little bit of the impact that this technology has had in the life of the patient.

And if you can look at the X ray there, you can see that it's all biology approximately. And then you start going distally and then you find the electrodes and then it becomes all robotics. And this is probably one of the most highly human machine interfaces used in clinical practice today. And with my first PhD student, we develop an embedded system that allows to run some of those fancy algorithms that I'll show you in the beginning, but also to provide electric pulses to the nerves to provide sensory feedback.

In both directions. Exactly. This is a world first, the first test of a prosthetic arm that can provide the sense of touch. So if I touch the finger, do you feel it? Yes, I can feel it.

Do you feel it stronger? If I... Yeah, I feel it stronger. When the force increases, the frequency of stimulation increases. So he feels the stronger sensation. Now I feel I have something in my hand. Yes, my hand Magnus.

So for the first time we can have electrodes that can be used for controlling and providing information from the prosthesis that can be used by the patients in the daily life. And as you can hear, the kind of sensations we provide are not as rich as the human experience of touch, but is still good enough for function. And this allow our patient that only has one degree of freedom of control and one sensation in the hand to reach the podium in the last Cybathlon. So this has been, of course, a close collaboration between different parties in medicine and engineering and industry have been involved.

And we've been taking that technology a little bit further by implementing surgical techniques in which we can produce more signals to extract information so the patient can control more degrees of freedom in the prosthesis. One of them is called Targeted Muscle Reinnervation, which is basically a nerve transfer from one of the nerves that was cut because of the amputation to a muscle that has not biomechanical function because there is no joint to act to it. So the surgeons like Paolo can take that nerve and reconnected it to a muscle that is not being used. And then we can put an electrode in that muscle and extract more information. And again, this has been used for several years by patients in their daily activities. From the engineering side, we can show, of course, that is improve function, but there are positive aspects related to the psychology and social relationship of these patients.

They have a better self-esteem, body-image, the social relationships have improved. Their participation in activities has not only increased on amount, but also in the range of activities they can get involved. And because they have this reliably and very integrated prosthetic arm, they also see it as part of the body.

And so that's where we were until recently and now we can pass the word to Paolo on where we are on hand transplantation. Yes, thanks, Max. When I talk about hand transplantation I certainly have to thank all my colleagues that I have had in this project. Let's see if I can get a control of Oh, here it comes. All my colleagues that I really had in this project since the beginning of 2012 and the support of my present chief Karina Reynold But the whole team has been really amazing in participating surgery and helping with the whole project.

And obviously I owe very much to all of them. This is the patient that we've had met many years ago. She had Quadri amputation after sepsis and she'll be using her prosthesis very much since that happened, but she staged several problems. These are just common myoelectrical prosthesis, and that's what we see most commonly in the market. Main concerns that she had were related to showering, brushing her teeth, toileting, putting her lower extremity prosthesis on.

And she's been in the need of help or personal assistant all the time. It's much easier, obviously having one limb amputated, but having 2 or 4 makes things much more difficult, even though we see sometimes very advanced prosthesis in YouTube fields. But the reality, many of these patients, common patients, just use regular prosthesis that do have problems with control ability. And obviously these have no sensation. Sometimes I get even frustrated to watch them. And how difficult it can be even more an easy task a home.

I'm going to show you some little bloody pictures for those who are a little sensitive to blood. So you know. This is good for training, but the patient has done before surgery very intensely to train her muscles and especially to try to recognize the function of these muscles moving each finger and the thumb. Since she's had an application for many years, we tried to and this is done very much with the help of Max team. Maria and Eva has helped very much with the functional MPR to see changes and the plasticity it in the brain. Surgery was done.

We took both hands from a donor from the elbow level, washed everything and we took the arms to another room where we could prepare and dissect all the structures, all panels, nerves, vessels were dissected in one room by my colleagues and then at the same time, the recipients forum was prepared. All the structures were isolated, the bone, tendons and all the rest. You see how many structures we tagged, all the structures here, you can understand how many muscles, tendons, arteries, nervous were isolated during surgery. And then we did the isolation, oesteosynthesis, thanks to a wonderful method developed by our colleague Per Fredriksson to make osteatum of the bone clear and fast in both the recipient and donor. This is the moment where all vessels under microscope were reattached, you see how many peoples are in the room.

And we see here when we release the clamps and the hand becomes pink again and slowly we become from white, more and more pink. And then all the fingers are red and well vascularized. It was very touching moment, I have to say for me and for all my colleagues who were working on it to see a hand again alive, I would say this is the day after surgery, the patient was able to move and control quite well. And it is only two months after surgery where the patient could eat by herself. She has no sensation yet and it will take 5 or 6 months, which for she feels more and more in the fingertips. She already feels some sensation in the palm and she just shows some control of all the fingers.

She has some cloud informacy because intrinsic muscle lack still, but hopefully there will be renovated. What I want to point out again is that here in Gothenburg is the one of the very few centers where we can, thanks to this collaboration between us and Max project, we can really offer the best options available for patients that have had an application of their limbs. And I just see this as a wonderful, wonderful adventures or together. Thanks, Max. Thank you, Paolo.

So as you can see, there is few in our work so far we have had a reliable control, a few degrees of freedom and less than you can have with a biological hand. But we're trying to move forward with again, surgical techniques to improve the amount of joints that the patient can control. So this is a surgical technique called reinneravative peripheral nerve interfaces, in which you can take the nerve that was cut because of the amputation is split in the fascicles.

Take muscle graft, make each of those fascicles innervate muscle graft, and then we can implant an electrode in those muscle grafts, distract more information. So what we're trying to do now and you can see in these videos is some of the work of one of my PhD students, here in Sweden, to regain finger control at a high amputation level. So this is a trans humoral patient and also control of different joints. So this preliminary work because that surgery was

relatively recent. But what we are aiming to is to improve the function by combining surgical techniques with technological solutions. And we have a European project to implement this technology in different amputation levels. So this is below the elbow.

And again, this thanks to the collaboration between all the different partners. We had a surgery done in the first patients about a year ago. And then in this hand, for instance, there are sensors in the thumb and the index finger and the middle finger so she can distinguish how hard or soft those objects are and then sort them accordingly.

Because we're stimulating the nerves, we're looking at different ways so how we can stimulate those nerves to produce different sensations. And we're trying to get those sensations to be functionally relevant in task to improve grasping on them, on the prosthesis. We also look at, that´s for sensory control. We're looking at objective measurements of agency, agency, meaning how strongly do you feel you are in control of something and in this case will be the prosthetic device. And we have a large group of people working on translating this technology from the upper limbs to the lower limbs. And we are in implying the first patient hopefully this year, if things go better with the pandemic.

And the idea is the same, use the most advanced surgical techniques that are available today with engineering technology to restore function, neural control, and sensory feedback in prosthetic legs. So I just going to talk briefly about the work on pain after an amputation is very common to have Phantom sensations. I experienced that myself, I had an accident required to hand surgery during the last summer because I have an axillary block stopping all neural information in my arm. I had the opportunity to experience what a Phantom sensation is, which is common, but very little study. So we have a project to study that further with the hand surgery department.

And that's interesting, but it really becomes a clinical problem when those sensations are painful, and for that we know that it's very common on patients to have Phantom Limb Pain. It normally doesn't go away and then becomes chronic and it's even harder to treat. And if you've ever been in pain, you know that paying demands attention. And for that reason, it has a high impact on quality of life.

It can affect social status, employment, depression and suicides have been reported to patients with severe cases of Phantom Limb Pain. So what we have done with the prosthetic work is very good for curing pain or Phantom Limb Pain, but it is very advanced at the moment is not available all over the world. So it's going to take some time for that to happen.

We're looking at clinical trial of different surgical techniques to see their effect on neuroma pain and Phantom limb pain. But we also develop a non invasive technology for treating Phantom limb pain. So what we do is we have electrodes that are placed on the surface of the skin, as you've seen before in my videos. And we just have basically a computer screen, a webcam that you have in any in any computer nowadays. And what we do is put a marker on the stump.

And with that market, we can do image processing on the computer screen. So we know where we left the mark, and we know that was on the stump. So we can add a virtual arm. And now the patient can control the virtual alarm in the same way they will control the biological and not only do motions with a virtual arm, but also control video games. In this case, the patient is controlling that car by moving his Phantom wrist, he turns the wrist to the left, the car goes left.

When it turns to the right, the car goes right, reflexing the elbow accelerates. And there I think it's about to extend, it breaks. So what we're trying to do, basically, is to engage all the motor neural circuitry that was not used because of the amputation to separate it from the processing of pain. And we have had very successful results with this therapy we done it in the upper limbs one of. my PhD students Eva Lendaro.

We have translated that technology to the lower limbs. We're running currently the largest clinical trial or international clinical trial and Phantom limb pain, then hospitals in eight countries. Beyond that clinical trial, this is also used clinically in different countries around all the corners of the world. So this is now used for a lot of patients around the world.

And what we've seen is that it has some successful results or but we've been trying to find out on why this is the case. I believe that is because, again, we're engaged in the neural circuitry that was not used and separate that from pain and taken advantage of competitive plasticity. And you can read all about that part in an article that I published in Frontiers in Neurology a couple of years ago. And when I was trying to understand why will this work, I realized that the current ideas on the origins of Phantom limb pain we're not really matching the clinical findings that we were observing. So I ended up proposing a new hypothesis for the Genesis of Phantom limb pain that I'm very excited to defend in the first international conference, Phantom Limb Pain, we're organizing and bringing to Gothenborg, where we bring in the experts in the field from the world to talk about this different ideas and treatments. And also we have a collaboration with the hospital to do some brain imaging studies to test the validity of this hypothesis, of the predictions that this hypothesis made.

And we're also looking for neural correlates of Phantom limb pain using EEG. And we developing mathematical and computational models of paint trying to understand the condition better. And although this technology or this treatment that I named Phantom Motor Execution has been rather successfully hasn't been successful for hundreds percent of the patients. And in our aim to have a solution that works for all patients, we have now created a new therapy that is also engaging the sensory system. And for that, we have developed a hardware with one of our students, Mirka Buist.

We trying to optimally stimulate on machanoreceptors, so get that part of the neural circuit engage as well. We're looking at brain modulation to improve this treatment, and we also using some of these technologies for rehabilitation purposes beyond amputations, in cases such as spinal core injuries, where you can see, in this case, the patient can you don't see any movement of the hand of the patient, yet in the screen you can see that he's able to control a virtual limb and we can do this in virtual on augmented reality. And we've seen some interesting and promising results on conversion disorder. And at the moment, as part of another collaboration with a hospital, we are running a clinical trial in chronic stroke patients where we can see the restoration of function even after a year or two, the stroke where you expect very little improvement. So this is some of the new, exciting work that we're doing beyond amputations with, as Paolo mentioned, we're also helping on the rehab of the hand transplantation program.

We are a lot of people who we have some more senior researchers and postdocs and PhD students and master students. And we have visiting students coming from a little bit all over the world. We are incorporating more and more medical professionals into our team, and that was the purpose of creating the Center and moving into the hospital. There are a few documentaries and media articles or popular science done in our work that you can see in our web page.

I'm running a podcast where these are long conversations on Bionics and Pain, where we try to discuss the stuff that sometimes we don't have enough time to discuss scientific conferences, and that will be a very rough presentation. I skipped a lot of the very technical engineering stuff that I figured you might not be so interested, but just give you an overview of the different projects that we have going on at the moment. That's our contact information. And I believe now there's going to be a question session. So that is correct. Thank you.

Very much Max and Paolo, and you may call it rough, Max, but I am continually baffled that this is possible. So this is very cool work you both are doing, and I hope that the question session will be even more enlightening. I forgot to tell the audience before that you can pose questions in the YouTube chat or at an email address that is or at a phone number. I'm hoping maybe our technicians might solve a slide for showing that shortly, but we will be using that all day long. But we already do have some questions, and I want to ask the two of you from a kind of supply and demand perspective, when a patient in need of new hands basically comes to you, what are their options that are easy to offer? Is it that the doctor will primarily propose a prosthesis, or will there be enough hands donated to go around? What's the scenario? Depending on what the patient needs? I can give it a go first, and then you can complement Paolo if you want. The care of patients with amputation is a little bit complicated, because not even in Sweden, we have a dedicated service for people with amputations.

So often what will happen is that they will have their amputation and then they will be seen by a prostethist or rehabilitation therapist. People is different and no amputation is the same. So the possibilities or the options that they can work better for them are not necessarily all the same. So there are some patients are more suitable for different procedures. So the conventional technology, what most people will have is this socket with surface electrodes that, as you saw in the video of that Paolo showed, the function is relatively relatively bad.

So now there are new technologies coming, and we are facing precisely this question on what is the suitable technology for patients and what we do in our clinical trials is inform them on the pros and cons of all the the technologies we offer so they can make an informed decision. Yes, I totally agree. I think the first approach, it's always conventional prosthesis, and then we offer hand transplantation, for example, only for bilateral amputees or Quadri amputees. We don't think it's worthy to take risk within recuperation for people to have only one limb amputated.

So it's always a standard as a routine our patients go through cosmetic or mileage prosthesis, and then if they have problems with that, they will we come to us and they ask if we have solutions that are better than the conventional prosthesis, and then we can have them or try to find a better solution. And something I might add is that even if our technology looks very sophisticated, is by no means a human hand, the sensations are not as rich. The control is not as wonderful as you have with your biological hand and also in hand transplantation say the function is not exactly same.

The sensation is not exactly the same. If somebody loses their hand and they come to us expecting to have something that is equal or even better to their original biological hand is going to be a bit disappointed. So for that reason, it's always important to say, take the the least risky conventional technology first, see if that suffices for the patients. And if not, then they can try some of these more advanced technologies. And if you compare the the prosthetic technology

that we provide with conventional technologies is a huge leap. And we have documented this in qualitative research as well. So they'll say it's not on there between conventional technology and the neuromusculoskeletal prosthesis, but that is when you compare from going to that technology to a neuromusculoskeletal prosthesis. If you go from a biological hand to a prosthesis, we are not there yet. That's interesting to know.

We have some questions that have come in from our audience, and I want to start with one that says, how essential is the AR training before the hand transplant? Or is it enough for the patient to train after the surgery? Like, what difference will it make for them? I can just start a little bit and then Max, if you're a continue, then I would say we don't know yet, but it's in the fact that the patient hasn't used the hand for many, many years and we think that active, even through a virtual image, all muscles making the patient understand how to activate them. And that even before surgery, we help with the pain after surgery. I can say that a patient our patient, you know, a few days after after surgery was already able to identify when I asked the patient, okay. Can you lift your thumb, or can you bend your thumb? She was actually able to identify exactly that muscle that time, and I could move the thumb and that was the same for the other fingers.

Does that depend on the preoperative training, I don't know, but it feels like she was very conscious of what she was doing. So I guess we need more patients to prove that. Max maybe want say some more.

Yeah. So what we see with long term amputations is that most patients will have a Phantom sensation, but that Phantom hand, in this case will be frozen so they can manipulate and by using this augmented and virtual reality will allow them is to start training. Not only it's all circuitry related to control it's on the brain, but also cortical and subcortical.

And what we see with the patients with the treatment of Phantom limb pain and these kind of patients is that they start gaining control over their Phantom, and that also means that they identify the muscles that they need to do. And this is basically because they have a real time feedback on what you're doing. It's very hard to know if you're opening your hand when you don't have a hand.

But when you have a virtual reality system that is responding to your intention of movement, it allows you to find tune that better way so you can achieve the goal. So this training of prior to surgery, we think, is important because it enables the patient to start reusing all of cortical and subcirtical circuits for motor control. So when the hands come in, she can already identify the muscle that is responsible for finger movements and then activate those and therefore they can start producing movement faster. But as Paolo said, this is an equal one.

And we will need to do, say, like a proper randomized trial to test this. But we came in to compare the results of this patient with other hand transplantations in other places to try to give us an idea. The downside of being at the forefront. We don't know yet, but Yeah, I found it fascinating in layman's terms that basically you're rebuilding the brain to prepare it for movement that it can't quite do yet, but we'll be able to soon.

So that's fascinating. We have another question. This one is for Paolo, what can be the survival rate of patients after the implant that you showed the hand implant? Considering the tissue rejection. I show the ones slide saying that survival rates for patient is 96% after 10 years. It's actually if one look at the transplants done since 1999, if you stick only to hand transplantation, we have a very, very high rate patient survival rate.

The problem comes when surgeons try to do a combined, for example, hand and face transplantation or hand and lower extremity transplantations. In those cases, several patients died because the infection of the complicated post opportunity complications. There are many patients done in main China, seven patients that actually lost their hands because they din't have proper treatment after surgery. They were left without or no proper control of immunosuppression. But if we look at those cases done followed properly, particularly in Europe, US, Australia, Taiwan, all those patients actually have shown those who are given immunosuppression in a proper way, they do have very good results.

They do have a very high graft survivor rate, even after 10 years. So it's a very, we said that we do know that our patients can have episodes of rejection. Usually the first episode rejection happens within one year.

The good thing with hand transplantation is that we see the rejection in the skin because the skin is the one that react more. So we can act right away and do even like a local immunosuppression on the skin. So that's very good for us better than kidney or other organs. Well, we can return to early in the presentation. Max, you mentioned that the CBPR had moved from Chalmers to Sahlgrenska. What difference did that make? Like what changes that brought about and how has it helped your operations? Well, we just moved a couple of months ago and this all has happened in the pandemic period.

So it's not that regular time, but we expect that because we are in the hospital now, we can talk a lot more often with a Paolo, for instance, because now the hand surgery department just moved to the next building in the Mölndal hospital. So in the building where we move that´s the R house. There's also a state of the art gate analyzes lab that we who collaborate on our research and lower in prosthetic control. We have spaces dedicated for seeing patients. So I think it's a lot more, it's going to be a lot better for us to be able to have earlier feedback on the development of the technology.

And as you know, by being just chatting in the corridor almost a fika time, you can check ideas earlier and come up with new ideas and make sure that we are doing stuff that is actually relevant for clinicians and patients. So it's a lot of benefits just being in the same place. But we haven't been there so long and it's been during the pandemic, so it's a bit early to have much anecdotes about that yet.

Well, here's hoping for all of us that the immediacy is going to give you some better exchange for sure. I just want to round off with a question for Paolo, actually, how many people are involved in a hand transplant? Like, how big is the team for just one patient to get new hands? If we talk about surgery, we were about 18 surgeons which lasted the surgeries as more or less 18 hours. But then we're obviously anesthesia staff and all the nurses. And there are more people involved obviously, surgery is one day, but then preoperative and postoperative, there are many figures involved, such as a therapists, hand therapists, neurologists that look at nerve functions. Transplant surgeons, obviously, or immunologists because they are the person they look at, the medications, the immunosuppression. So it's a really huge team of people.

That's why there are not many centers in the world that do this. And it's fascinating that we do have this possibility here at Sahlgrenska, recruiting so many people, positive people that work around one vision. So it's a very large amount of people. Yeah, I had that suspicion. So it's good to get confirmed.

It's like a Hollywood production. Almost. Alright. So I wish I had another 15 minutes to ask you more questions, but we do want to provide everyone with a break. So thank you very much for telling us about this fascinating work. And I wish you both a good day and night, I guess.

Or morning for you, Max. So thank you for joining us. Okay. Thank you. Bye.

Okay. So for those of us who are continuing to follow this day, we will now take a 14-ish minute break. So we'll be back at 10:30.

And the general idea from your resident Ergonomist is that if you've been sitting stand up, if you've

2021-05-17 02:50

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