By Shruti Vij & Nils Muhlert Functional MRI has been in use for over 25 years. Despite providing us with a breadth of methods developments and exciting findings about how the brain works, there has been a dearth of clinical applications. The OHBM Alpine Chapter has been keenly focussed on ways in which we can translate fMRI and other neuroimaging modalities to the clinic. Founded in 2014, the Alpine Chapter has provide a forum for like-minded brain mappers, both basic scientists and clinicians, throughout Austria, Switzerland, Germany and neighbouring countries to discuss new methods, new projects and to collaborate on programs of research. Here, Shruti Vij spoke to the past and current Chairs, Roland Beisteiner and Christoph Stippich respectively, to find out how the Chapter has developed and its directions for growth. Christoph Stippich, Roland Beisteiner, Shruti Vij at OHBM2018 in Singapore. Shruti Vij (SV): We're here to interview the Chair and Chair elect from the OHBM Alpine chapter. First of all welcome and thank you so much for doing this interview with us. Roland, please let the readers know how the Alpine chapter has developed over the past few years. What has your experience been? Roland Beisteiner (RB): Thank you for the invitation. The Alpine chapter was founded and based on our longstanding tradition of functional imaging in Austria and Switzerland. In 1992 we received our first grant for fMRI in Vienna. We later founded an Austrian society for functional MRI in 2004. So the idea came up to develop this further within the area; we increasingly built contacts with Swiss collaborators. Christoph Stippich was one of the first, very interested colleagues we approached and we soon started to work together. Christoph and I are both clinicians. We both want to implement new methodology for patient care. This is a really exciting field and I believe our methods for human brain mapping are particularly well suited to achieve this goal. Here in OHBM there are many methods and a big, excellent overview about all methodologies, which we could potentially apply to the clinics. In my group, we have always looked out for new technologies and new relevant methods. We’re looking for those that are available and useful for improving patient care and that can be used to tackle the many problems with individual patient diagnostics. Christoph Stippich (CS): Yes after starting our collaboration with Roland and colleagues roughly 10 years ago we extended the Swiss collaborations and in 2014 we got the opportunity to found the Alpine chapter through the OHBM. We are very happy that we got the approval and this has greatly increased collaboration within the area. This was a big help for us, particularly also the clinical collaborations. SV: It’s a great way of incorporating diversity and also making sure those from the Alpine chapter have their own discussion space. Christoph, where do you see the Alpine chapter going in the coming years now you're the chair elect? CS: There are two major directions that we will foster during the next two to four years. One is education, as there’s a large demand to teach people novel neuroimaging methods, how they can be translated into the clinical setting. The other direction is about the harmonization of imaging protocols. Roland and I both come from the purely clinical side. Roland’s a neurologist, I'm a neuroradiologist. We both need advanced and useful diagnostic neuroimaging tools, and that's that we’ve been working on for more than 20 years. The diagnostic application is always in individual patients; group data are helpful, but they don't lead you to an individual diagnosis. So, if someone is really ill, they want medical advice from you on what to do. It’s helpful to have an idea how the brain works in general, but what we’re dealing with is always a patient who will request for a diagnosis or even treatment. SV: You both have interests in using fMRI in the clinical setting. There's a lot of interest in this within OHBM, but also throughout the neuroimaging community. There’s also been an interesting debate on Twitter as to whether this clinical application of fMRI will happen regularly and what form it might take. What are your views about whether fMRI can be ported to the clinical setting to help an individual patient? Do you think it's feasible? RB: I think we still have a long road to improve and use all the possibilities which are in principle available. Currently, for clinical fMRI you typically see pre-surgical applications. This is based particularly on specialized groups and in dedicated centers. It means we do have clinical applications primarily in presurgical and surgical diagnostics. But I think we need to make these methods more usable for pure diagnostics and prognostics in the clinical field. This is certainly possible, but requires a level of methodological improvement, and certainly a good understanding about the peculiarities around a particular group of individual patients. This is, I think, a major issue. CS: My view is that we really have to focus on the individual, and I cannot stress this enough. That means also reference data sets from healthy individuals as well as from various pathological conditions, we need to really standardise how we carry out investigations. Another key point is that it must be applicable in really severely ill patients with neurological or cognitive deficits affecting the functional systems to be investigated. They usually have focal lesions, let's say in epilepsy, in brain tumours or in stroke. So we’re not working with a normal brain structure. The people we may work with might also have difficulty speaking properly and have impairments in other functions. Another problem is translation of established clinical or neuropsychological scales (tests) into functional neuroimaging findings These imaging protocols must be clinically feasible and work within a short scanning time of two to five minutes, and then you have to have very good and robust results from that, they must be validated. The next step is then to integrate this into medically approved systems. Some people are not aware that you cannot simply use any free software for clinical purposes and then, let’s say, apply it into an operation theater. This may lead to medical, ethical and legal issues. You need some transfer and maybe more medically certified software products. This is where the point of harmonization comes into play again. We have to come up with this prospectively and to teach. The whole process has to start from a voluntary basis. You cannot say that's the way we do it. You can just say, this is an option, we can help support and give second opinions and so on, it's always a close interaction with the people who are intending to enter the field. SV: So maybe other people who are interested in doing this kind of research should get in touch with you to learn more about it. One thing that has been at the tips of everybody's mind has been artificial intelligence. And I know, Christoph, that your research has touched on the use of artificial intelligence. How do you feel artificial intelligence is being incorporated into fMRI or brain mapping more generally? CS: Well I’ll say that I'm not a computer guy. I'm not really somebody who understands all the technology (especially the mathematics) behind it. I'm coming from the user side and seeing it critically. So I think what's going to happen - particularly in the fields of radiology and neuroradiology - is that the classical form of a “narrative neuroradiologist” who qualitatively sees some sequences and says, okay, that's that and that, and writes a short descriptive report is going to fade away. It will take a few years in leading centers and maybe half a generation worldwide and then this should be gone. It’ll likely be replaced by some computer assisted systems that help us interpret the images. From these analytics, we can get information, which is not currently available and some is invisible for the “human eye”, helping us to refine our diagnostic tools. It will also help therapeutically, because imaging has been a very quickly evolving field, and has a lot of impact on therapeutic decisions. So I think we can gain much from these computer assisted steps. On the other hand, these methods, especially in artificial intelligence and machine learning, are not made for medical purposes, today. Instead, they come from economics, from the production industry. So we have to go really deeply into it to promote the understanding of basic scientists, of technicians, of developers with the medical field because they really come from another side. If you look into “big data” science and want to learn from these data, then you don't have a great tool for the medical images per se at this stage. We are starting off by looking at already acquired data of varying quality in a retrospective fashion.. And there's a lot of noise in the data. When it comes down to an individual diagnostic case, as I said, you really need precision, you need some quality assurance, you need standards on how we do it, otherwise you will never trust the diagnosis. So there is a big risk of misusing the technologies. And this could cause a lot of harm to the whole field, as well as to an individual patient. This is of utmost importance - to have a feedback loop with the doctors. There's data curation, there's training of systems, and this a lot of work. In fact the “imaging doctors” should take responsibility and play an important role in these processes. In some instances it may take at least a decade until this is a robust clinical tool. And there are many variables influencing it. Let's say there's volumetry, aneurysm segmentations. If you just change little things in there, and then you try to make some analytics of a brain tumor or vascular malformation, you get completely different results. So that needs much knowledge and medical input. SV: You have both clinical expertise by training and a technological or technical kind of mind. How do you balance the two? Has it been hard? CS: I think now we are not per se neuroscientists, we are clinicians. And we had a focus on neuroscience already. So we entered with electrophysiology, using MEG in the mid 90s, and then added many other things, such as fMRI. And that I think, what is very rewarding is that, if you combine clinical work with such research it never gets boring. So it's really interesting, because on the one hand, you have this research approach where we can transform new methodologies into clinical applications: you sit together with a patient and test out how this can be applied, you try to break it down into something usable, and because you’re working in clinical timescales it must be built up in a few minutes, replaced in a few minutes, it must be easy and reproducible. So it's a lot of playing around which makes it fun. On the other hand, if you can use this in diagnostics then you're pioneering from the beginning, and then you roll it out. Furthermore neuroradiology has also a therapeutic arm, which makes the subject even more fascinating. We do invasive catherter maneuvers, and we really treat people intracranially via minimally invasive approaches with stents, coils and other materials – this subdiscipline is called “interventional neuroradiology”. RB: Also, I think it's really a big struggle for clinicians to also do basic, new innovative research. This maybe a general problem within German speaking countries because often, if you have a university Dr position, you are overloaded with routine things. I think it would be a huge improvement, if we would have more clinical research positions, so that young doctors would have the possibility to enter a pure clinical research position, and not feel overloaded by clinical duties. You also have to be aware that this is a disadvantage concerning the competition against basic research groups, your peer researchers. We need more balance, and perhaps need political actions to improve the situation concerning clinical research and research possibilities for clinicians. SV: Is there specific advice you would give to early career researchers? RB: If you are interested in clinical research, really try to understand your specialty, so you understand patients’ diagnoses and diseases, Then you can understand that if you have two patients with the same diagnosis they may vary grossly. This is really a problem, even of course for clinical studies and brain mapping studies. And after that, as I said before, I think we need to improve our job options allowing research after having acquired this clinical background. CS: I would take it a little bit less from the formal side and don't say at the beginning, there needs to be a good pattern. In reality, it's always extra work: you work on the weekends, you work overnight. And it has dramatically improved over the last two decades. But still, it is extra work. If you want to do interesting and really good research, you need the passion, otherwise it will not work out. That's the first step, you have to know what you want, and you have to find the right field. Then, if it's neuroimaging, and you want to do it clinically, then you can select the site. You need to find the right institution. You need to think about mentoring programs, is there dedicated research times, do they have established research groups? This helps you select the right site. Alternatively, you can bring up your own field, and this depends on your personal preferences. So let's say there is a large spectrum of researchers who, coming from one end of this spectrum, may jump on an existing project to quickly promote their own career or, coming from the other end of the spectrum, who want to build up something new from scratch. From my personal perception I may say the latter ones are the ones who are going for a longer duration in research activities and therefore scientifically may achieve more at the end. SV: So is the Alpine chapter having any initiatives in the coming years for Early Career researchers? CS: We have not really established that at the moment. But as I started off this interview, I said we aim to focus on the educational part. And this will lead to some things like that. We are setting up new seminars and courses. We’re also trying to link up with a young clinician-researchers part of an umbrella organization called ‘the Swiss federation of clinical neurosciences’. This is very helpful, so let’s see what this can help us achieve over the next three or four years. SV: Great. I guess last question, is the fun here at OHBM Annual meetings better than the fun at Alpine chapter meetings? RB: Well, I think this is an unfair question. You have to consider that we have meetings of only one to two days, whereas the annual OHBM meeting is five to six days. Also the budget for the annual OHBM meeting is slightly larger [laughs]. But we do have one evening which we use as a social event, a social dinner. If you're able to improve funding for the Alpine Chapter we can easily try to catch up. SV: On that note, I would like to thank you so much for being a part of this interview. I'm sure the community and everybody really enjoyed this interview. And thank you for setting up the Alpine chapter and giving us all this insight. CS: Thanks for the support.
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