MIRA BIOMEDICAL TECHNOLOGY AND TECHNICAL MEDICINE
top technology for patients
MIRA
Foto: Gijs van Ouwerkerk
Clinical Professor Daniël Saris: ‘Technovolution is the thread running through all my research’ Foto: Gijs van Ouwerkerk
For the last two years, Prof. Daniël Saris has been combining his job as Orthopaedic Surgeon at UMC Utrecht with the position of Clinical Professor of Reconstructive Medicine at MIRA.
MIRA
heads for the future A lot has happened in MIRA’s brief three-year history. ‘Last year, a MIRA book entitled ‘In Sight’ provided a general idea of the research and teaching we carry out here,’ explains Martijn Kuit, Managing Director of MIRA. ‘However, since the publication of this book, so much has happened at MIRA that we’ve had to compile an extra magazine, a copy of which you are now reading. We hope that this update will bring you up to speed on all the latest developments in our institute.’ Growth and excellence. These are the two most important words that Kuit associates with the previous period, in which MIRA has developed from a budding research institute into a respected knowledge centre. ‘Our place in the top-5 of the prestigious EPFL ranking for Biomedical institutes confirms that our chosen approach of linking top-class technological research to clinical expertise and entrepreneurship, is working.’ Growth in every respect ‘Over the past few years, MIRA has attracted numerous top researchers,’ says Kuit proudly. ‘We are using this magazine to present a few of them to you. We have also recently had articles
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published in various renowned scientific journals and our work is resulting in a growing number of spin-offs, which prepare the technologies designed at MIRA for the market (mainly clinical).’ You can read the latest news on the most recent spin-offs on page 8 and 9. MIRA has also secured an increasingly firm position within a number of alliances. ‘A highly significant development for MIRA is the foundation of the Center for Medical Imaging North East Netherlands (CMINEN).’ The parties involved from the very start explain their reasons for doing so on page 12 and 13.
Grateful ‘We are extremely grateful to all those who have helped us to grow over the past few years,’ continues Kuit. Two people in particular have taken the lead. They are MIRA’s Scientific Director Prof. Clemens Van Blitterswijk (read the interview with him and his successor Prof. Vinod Subramaniam at pages 4 and 5), and MIRA’s Medical Director Prof. Peter Vooijs (p. 6 en 7). Kuit concludes: ‘So here at MIRA, we are now heading for the future with great enthusiasm and confidence. But for the time being, we hope that you will enjoy reading this magazine.’
‘As Clinical Professor, it is my job to fortify the links between the technology we are developing at MIRA and the practical situation,’ explains Saris. ‘Being a doctor rather than a technician makes you look at things differently than someone who spends all their time developing technology. You are in a position to see the connection between clinical requirements and the effective application of the technology being developed at the university.’ You need someone to make this connection, continues Saris, because in many cases, technicians assume a clinical need for a specific piece of technology, while in practice, something entirely different is needed. And the reverse is also true, says Saris. ‘There are plenty of clinical problems to which doctors are desperate for a solution, but which technicians are totally unaware of.’ Saris has meanwhile launched a number of research lines at MIRA. They include a project that aims to improve existing cruciate ligament surgical techniques. Saris: ‘This will result in a relatively easy but scientifically interesting improvement to the standard operation used to repair torn cruciate ligaments. In this case, we know that surgeons aren’t queuing up to perform a radically different type of surgery. So we are simply trying to improve the present technique by introducing very minor adaptations, which will probably by accepted and implemented much more readily. The main question in this research is how you can make tendons grow in bone more quickly. The industry is helping us with this, and so we have established a clear link with the Entrepreneurial Professors from MIRA.’ Saris’ second line of research is more fundamental. He and postgraduate researcher Hugo Fernandez are focusing on the regeneration of tendons and connective tissue. ‘One of the things we are doing
is training stem cells by exposing them to various environmental factors or hormones.’ And in a third project, Saris is involved in developing a mould that can be used to place screws in the spine as a safer and more efficient way to straighten it. ‘The project is based on being able to simulate and practise placing the screws before the actual operation. Placing the mould on the spinal column during an operation reduces the risk of touching a nerve in the spinal cord.’ Central theme The thread that runs through all of Saris’ research is the Technovolution concept. ‘Technovolution is survival of the fittest, but in the field of medical technology.’ The only way to find out whether an invention will be a success is to put it into practice. Saris: ‘Technology such as cruciate ligament reconstruction is already fairly well developed; it has already survived. It just needs the odd tweak to make it even more effective.’
Technovolution is survival of the fittest, but in the field of medical technology According to Saris, one of the biggest challenges in his role as Clinical Professor is ensuring that he is sufficiently effective in the one day a week allocated to this job. Saris does this by keeping in constant touch with the research groups in Twente by telephone, e-mail and Skype. ‘It’s also essential to have a postgraduate researcher, a PhD candidate and a few students on hand so that the Reconstructive Medicine desk is manned 24/7.’
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On course for a place in the top 3 In this dialogue, Professor Clemens van Blitterswijk (the current scientific director of MIRA) and Professor Vinod Subramaniam (his successor) discuss the recent successes of MIRA research institute. ‘The course set out by MIRA three years ago is paying off. This is reflected in our institute’s position in the top 5 of the prestigious EPFL ranking.’ We now have to build on this success and conquer the rest of the world. Foto’s: Gijs van Ouwerkerk
‘We were obviously small at first,’ begins Van Blitterswijk. ‘You have to start building up a top institute from within your organization.’ The initial step was to identify demand from the medical field and work out how it corresponded with technologies and research being conducted at MIRA. The next step was to coordinate the various lines of research. MIRA’s ambition is to have the entire chain at its disposal; fundamental and technological research, medical science and market development. According to Van Blitterswijk, this is why MIRA has recently been appointing clinical professors and entrepreneurial professors to work alongside the ‘regular’ professors. MIRA is currently in the middle of what Subramaniam refers to as ‘a quest for excellence’. This includes maximizing the number of research publications in the real top journals. According to the professors, MIRA is on the right track. ‘Our structure is in place, the quality of our publications has improved. Excellence is catching. But in addition to a solid structure, you need a couple of trailblazers with publications in top journals as positive role models. Success generates more success!’ Europe In the meantime, the Twente region recognizes the added value offered by the UT institute and MIRA is steadily gaining a firm national reputation, explains Van Blitterswijk. ‘This didn’t take long,’ he continues. ‘So it’s time for the next step,’ adds Subramaniam: ‘Europe and the rest of the world are calling! 4
We need to forge a path into leading European consortia and make sure that MIRA becomes an ‘essential player’ in the field. Many of our research groups have already made their name in Europe and beyond, but not the institute itself. We now have put MIRA on the international map: the time is ripe.’ At this point it should be said that this will not affect the institute’s regional focus, adds Van Blitterswijk. ‘Regional interests will always be important, even if MIRA secures a better position in the international market. We have a job to do here. The CMI, for example, provides high-quality facilities and job opportunities for the region, and the region has made substantial investments in the CMI. And then there’s the MST, another important partner within the CMI.’ But the CMI is not the only large-scale alliance in which MIRA plays a major role. Van Blitterswijk: ‘MIRA is currently operating in four IMDI Centres of Research Excellence, and is one of the lead partners in three of them: the CMI, the Centre for Care Technology (CCTR) and SPRINT, a centre for rehabilitation and rehabilitation care.’ The centres work as public-private partnerships. In the case of SPRINT, Xsens, for example, is an important partner. Cooperation Subramaniam also sees numerous opportunities for growth in the cooperation between the various research institutes at the University of Twente. ‘Take Nanomedicine, an area where MIRA intersects with MESA+, and which we are keen to explore and
work together on. Or the common ground between MIRA and the CTIT, for example: Telemedicine and bioinformatics. And last but not least, in the healthcare sector you have to contend with ‘governance’, so the link with the UT Institute for Governance and Innovation (IGS) isn’t difficult to understand.’ Van Blitterswijk is quick to stress how important the Technical Medicine programme is to MIRA. ‘This link is a real boon. The programme plays a huge role in embedding our translational research.’ Spin-offs Part of MIRA’s strategy for helping to embed technology into society involves encouraging researchers to bring their research onto the market by means of spin-off companies. Van Blitterswijk: ‘Last year was a top year with six spin-offs. We won’t be able to achieve this figure every year, but that doesn’t matter. We aim to launch an average of three spin-off companies per year. The next step is to generate spin-offs that can grow into companies employing ten people or more.’ In practice, this seems to be a hurdle that many compaßnies are unable to overcome, but to Subramaniam’s mind, a hurdle that shouldn’t be too difficult to remove. ‘The scope of our range of application gives us a massive potential market. It really shouldn’t be a problem if we can develop clinical technology that will work in practice.’ So Twente’s entrepreneurial spirit is flourishing and
MIRA will perhaps be able to reap the benefits of Van Blitterswijk’s new appointment in this respect too. He is set to join the board of Life Sciences Partners (LSP) in Amsterdam, an investment firm with a new investment fund in care innovation. Although Van Blitterswijk will no longer be MIRA’s scientific director, he will still be attached to the institute as professor and head of the Tissue Regeneration group. When asked how big he considers the shoes he is expected to fill to be, Subramaniam smiles before answering: ‘Van Blitterswijk’s way of thinking out of the box and his talent for clever, creative solutions will make him a hard act to follow.’ But Van Blitterswijk responds immediately by saying that this won’t be a problem for his successor. ‘Subramaniam’s passion for excellence is there for all to see. It’s precisely what we need. What’s more, his daughter is called Mira… what more could you possibly ask of a scientific director for this institute!’ Future Taking everything into consideration, the future for MIRA is looking bright. Van Blitterswijk and Subramaniam are positive. When asked where they envisage MIRA to be in another five years, their answer is unanimous: ‘In the top 3 of the EPFL ranking. It’s certainly feasible. We like to set the bar high. Our structure, into which fundamental research, clinical perspective and an entrepreneurial spirit are firmly anchored, gives us the scientific excellence we need to go all the way.’ 5
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‘Technical Medicine fills a gap in the market’
Peter Vooijs has been involved with MIRA (and its predecessors) and the Technical Medicine programme at the University of Twente for more ten years. Initially as an external consultant, later as Scientific Director of the Technical Medicine programme and ultimately as Medical Director of MIRA. According to Vooijs, what makes the job of Medical Director in an institute affiliated to a university of technology so important is the fact that the incumbent directly represents the patients. ‘MIRA stands out because the technology designed here is strongly influenced by demand from the practical field of medicine. This is actually quite rare at a university of technology. Most universities of technology develop technology that scientists think is relevant, but which in many cases has never been actively requested.’ ‘So one of the main roles of the Medical Director is to make certain that the activities at MIRA and in TM do actually revolve around the patients’ interests’, explains Vooijs. ‘We see our patients as clients. As Medical Director, it is your job to safeguard this link. You must also translate questions from the field so that they can be understood by the community in Twente, and you must then inspire the scientists to answer these questions.’ Feats When asked what he considers to be his greatest feat during his period at MIRA, Vooijs thinks long and hard. ‘How long have you got..?’ is his initial reaction. The first thing he mentions is the introduction of the programme in Technical Medicine. ‘It’s a unique concept. There are no programmes like it anywhere else in Europe or America. There was a lot of resistance at first, but the programme is now securely anchored.’ To illustrate this, Vooijs recounts a meeting of medical practitioners that he recently attended. ‘There were a number of people there who a few years ago, had been quite outspoken in their opinion that there was no future for Technical Medicine. During the meeting, these same people were now telling me that it had turned out quite differently from how they had imagined. This just goes to show that Technical Medicine is filling a gap in the market. At first it didn’t exist, and now there’s a clear and present need for Technical Medicine graduates.’ Most medical practitioners have now overcome their initial cold feet, explains Vooijs, and can see the added value of TM students. ‘Doctors were afraid that the TM students would take up valuable time in the operating theatres and get in their way, but these days you hear nothing but positive reports. There are even parties that are considering taking on a TM graduate instead of a doctor. They have the same expertise in certain areas and often cost a lot less. Take writing up a report of a bone scan, for example: a TM graduate is just as good at this as a doctor. And they will be even more valuable once they can register in the BIG [Individual Healthcare Professionals] register. This will do wonders for the general acceptance of TM professionals.’
Professor Peter Vooijs looks back on the progress made by MIRA over the past few years. While talking about his role as Medical Director, he concludes that Technical Medicine has Foto: Gijs van Ouwerkerk
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conquered the Netherlands at a rate of knots.
In great demand Vooijs has also noticed a great and ever-increasing demand for TM professionals in day-to-day practice. ‘I keep hearing that our students have found their feet within fourteen days and are able to join in discussions about the problems and issues facing a department at a professional level. On the whole, our students are outstanding. They are intelligent,
enterprising and capable of working alone. They can also adapt themselves to a wide range of dynamic situations. We recently worked out that 95 percent of our students will have already found a job by their graduation day.’ Those that have not, make a conscious decision to take some time out first, adds Vooijs, to go travelling for example. ‘More than 70 percent of those with a job have a PhD position in a clinical department. This is amazing. We have trouble finding enough students to fill all the PhD positions! They really are in great demand as there are more PhD vacancies than graduates.’ The popularity of Technical Medicine students rubs off onto the research at MIRA, continues Vooijs. ‘The translation into research is automatic here. Someone from Twente supervises every single internship. And there’s always at least one supervisor from Twente involved in every PhD project. This allows our researchers to forge plenty of relevant clinical ties.’ TM nerve centres To stimulate the development of Technical Medicine, Vooijs would like to see so-called TM nerve centres emerge in various hospitals throughout the country. Ideally, a TM nerve centre would comprise a second-year Master’s student, a third-year Master’s student, a PhD candidate, a postgraduate researcher and a staff member, explains Vooijs. ‘To make sure that the staff members are fully prepared for the position, we recently set up the institute for TM fellowships. A fellowship would involve a TM graduate spending two years receiving specific clinical medical training, usually alongside a PhD study. In this way, TM professionals develop expertise that would otherwise not be available in the department, or would only be available in collaborations involving several people. This could now all be rolled into one person. The fellowships are already attracting a great deal of interest.’
‘We see our patients as clients. As Medical Director, it is your job to safeguard this link’ CMI Vooijs considers the second most important feat achieved during his time at MIRA to be the establishment of the CMI. ‘This is a fairly unique development in itself. It is just incredible to set up an institute for imaging together with such a prestigious industrial partner as Siemens, and then watch it operating right up on the frontline of the very latest imaging technology.’ ‘The idea for the CMI first arose during a meal out in Utrecht’, continues Vooijs. ‘I was there with someone from Groningen and someone from Siemens. The CMI is now exactly how we’d imagined during that dinner. We decided immediately that we would go ahead even if we didn’t get the funding. Just because it was such a good plan!’ ‘Vooijs has nothing but praise for the role of Siemens within the partnership. ‘I have to say that the flexibility and participation shown by Siemens have been a very pleasant surprise. I’ve worked with other larger partners before, who will remain nameless, but Siemens is by far the best when it comes to consulting about new developments. Their transparency is so refreshing. I´m really enjoying this partnership!’
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MIRA’s recent successful spin-off companies The essential aim of MIRA’s science is to effectively bring new technologies into clinics. Only then can we positively change the lives of patients. Therefore, we encourage our scientists to bring proprietary technologies and products onto the market. Our staff intensively conducts those with viable ideas. Recently, MIRA’s research results have lead to several inventions with a social and commercial significance. New spin-off companies have been started and existing ones attracted new funding, enabling them to grow. In this article an overview of some recent successful MIRA spin-off companies is given. VyCAP VyCAP is developing a test for the detection of white blood cells at counts of less than 500 cells per millilitre. In comparison, a healthy adult has 4-10 x 106 white blood cells per millilitre.
A single fluorescence image is acquired and the cells are identified using image analysis routines. The first clinical application to be developed is the detection and analysis of cells in cerebrospinal fluid (liquor). For further information: arjan.tibbe@vycap.com
The current methodologies for the analysis and detection of cells present at these low concentrations are time-consuming and require many sample handling steps; steps with a relatively high probability of sample loss, and degradation of sample quality. In addition, the test can only be performed in a laboratory environment and requires highly trained and experienced lab technicians. VyCAP has been developing an all-in-one cartridge that is able to analyse cells present at these concentrations. The cartridge contains a silicon micro-sieve, which concentrates cells from samples ranging from 1–10 millilitres in volume. It also contains all the reagents required to count and identify the collected cells. The smart design of the cartridge makes it possible for all the fluidic handling and sample processing to take place inside the cartridge without the need of external pumps or electrical connections. So the cartridge can be used anywhere without the need for extensive training. After the sample has been processed, the collected cells are counted and identified by a dedicated reader.
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PA Imaging PA Imaging aims to commercialize technology for photoacoustic mammography developed by the Biomedical Photonic Imaging group (BMPI) of MIRA. While BMPI develops the mainframe, the optics and acoustic detection, PA Imaging will initially concentrate on signal acquisition and image reconstruction. Clinical testing will be done at MST Oldenzaal, in a partnership between MST physicians and BMPI researchers. Photoacoustics uses ultrasound generated by short laser pulses to image tissue by the absorption of light by blood. Photoacoustic mammoscopy aims to provide better screening and diagnosis of breast cancer. Compared with X-ray technology, sensitivity and specificity may be improved, and photoacoustics will also be suitable for younger women for which the use of X-rays is inaccurate. Also, photoacoustics will cause less discomfort to the woman as it does not involve harmful radiation or painful breast compression. Furthermore, photoacoustics does not need a contrast agent, as is used in MRI.
Hy2Care Injectable hydrogels for cartilage repair Hy2Care is commercializing a novel concept with the potential to revolutionize the treatment of degenerative cartilage diseases, such as osteoarthritis. Affecting around 1.2 million Dutch people, osteoarthritis is the most common joint disease and is presently incurable. Osteoarthritis results in damage to the articular cartilage surface, which normally provides smooth and pain-free joint movement.
Beeld: Kennispark Twente
Hy2Care’s concept is based on a ’healing plaster’. The plaster used to cover the damaged cartilage surface resembles a two-component adhesive, but is fully compatible with living tissue and can support tissue regeneration. This plaster can be applied using a minimally invasive procedure such as arthroscopy. The plaster provides support to the eroded cartilage surface, thereby facilitating damage repair.
A patient study is currently being performed with our first prototype. Meanwhile, PA Imaging is developing PAM2, which should provide faster imaging. A large patient study using PAM2 is currently in progress, and the researchers involved hope to be able to draw conclusions within 5 years, and to prepare multicentre trials in cooperation with one or many multinationals.
At present, Hy2Care is performing proof-of-concept studies in horse models. Horses frequently suffer cartilage diseases. It is expected that these studies will conclude in 2012, after which preparations for patient studies will commence. The illustration shows a representation of the procedure used to fill up a cartilage defect, involving a double syringe which mixes the two components at the cartilage surface.
NociTRACK NociTRACK has developed unique new medical technology that will lead to large-scale, evidence-based early diagnosis and prevent acute pain from developing into chronic pain. The key medical device is the NociTRACK pain sensitivity monitor. This new mobile, user-friendly, highly automated set-up saves vital time while screening and monitoring a large population of patients at virtually no additional cost. Improved therapy selection methods will mean that fewer pain patients develop chronic pain and that more of them will obtain better and faster pain relief. In this way, NociTRACK will reduce the cost of healthcare and improve the quality of life for a vast number of pain patients throughout the world. NociTRACK is in contact with several clinical partners and hopes to implement NociTRACK in Dutch pain centres.
20MED 20MED Therapeutics is active in the field of controlled drug delivery, developing and operating a portfolio of multifunctional polymer-based carriers for the targeted delivery of small interfering RNAs (siRNAs) and microRNAs (miRNAs) for the treatment of genetic diseases. 20MED was founded following the discovery of innovative and unique polymeric hybrid constructs (hereafter called 20MED nanogels) in the Biomedical Chemistry labs of the University of Twente. These nanogels possess a hitherto unknown combination of properties essential for successful siRNA delivery in clinical applications.
For further information: www.nocitrack.com
Due to their special chemical construction, 20MED nanogels are stable, easy to process, non-toxic nanoparticles that can be supplied in powder form. After being dissolved, they can be easily loaded with therapeutic small RNAs.
Once the nanoparticles have been absorbed by the cells, specific chemical properties of the 20MED nanogel architecture allow the therapeutic payload to escape from endosomes and to be efficiently released into the cytosol. This results in highly efficient transfection and gene silencing. The company’s short-term mission is to further develop and expand this proprietary set of unique polymeric hybrid constructs for RNA application in a diversity of gene related diseases. It also aims to demonstrate their enormous potential for safe and efficient siRNA and miRNA-based gene therapy in a clinical setting. 20MED therapeutics therefore intends to cooperate with biotech and pharma companies that are addressing specific genetic diseases, to meet their existing need for improved gene carrier systems for in vivo application. Screvo Srevo is a rising biotech company that produces a versatile threedimensional (3D) screening system. Screvo’s patented 3D system can be used for a broad range of research activities that include invivo and invitro experiments by increasing the number experimental conditions that can be tested in one animal. This breakthrough technology offers an opportunity to improve the output of preclinical research. Starting with the launch of Verse 3D™ in April 2012, the custom proprietary 3D screening technology aims to significantly reduce systems that fail in late stages of development. This screening device optimizes the invivo environment. With Verse 3D™, it’s possible to screen 36 different conditions in one animal. Conditions can easily be dispensed using standard laboratory equipment in each of the wells and histological analysis can also be performed utilizing standard equipment. In the following years, Screvo aims to be a major contributor in experiment areas, such as in toxicity, tumor cell biology, therapy resistance, cell-cell interactions, spheroid invasion, drug penetration, modeling, concentration gradients, vascularization, cell metabolism, cell migration, and cosmetic ingredients. Overall, the 3D models allow the study of cell-cell and cell-extracellular matrix interactions in native and engineered tissue. For further information: www.screvo.net
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MIRA
From data analysis to data understanding
Professor Christian Beckmann has been working for MIRA as a professor in the NeuroImaging (NIM) group for eighteen months now. He develops tools and techniques to make fMRI data from brain research easier to understand. Applied and theoretical research go hand in hand.
Although Christian Beckmann is a professor in the field of neuroimaging at MIRA, he is actually based in the Donders Institute in Nijmegen. Alongside his job at UT, he is also attached to Imperial College and the University of Oxford in the United Kingdom. Beckmann was originally a mathematician and
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Innovative medical imaging The Center for Medical Imaging North East Netherlands (CMINEN), in short CMI, is the result of a joint initiative
theoretical information specialist, but he has spent the past few years working on brain research. ‘I develop tools and techniques designed to make the data easier to understand. I then apply them when analysing brain data. My main focus is on functional MRI data, which is used to obtain detailed information about oxygen in the brain.’ Interpreting this data is no easy matter, he explains. ‘The volume of data is huge. We’re talking about several hundred images per person, and in every image, we’re looking at 20,000 to 80,000 locations. So you’re looking at a few hundred megabytes of data generated in just a few minutes. In addition, the underlying biophysics and measuring process are highly complex.’
of the University of Groningen (RuG)/
Data understanding So the central thread in all of Beckmann’s research is not data analysis, but data understanding. ‘To my mind, the difference between these two is very important. Many statisticians only explore the theoretical side of this work. If these people don’t put their techniques into practice, they’ll never understand the practical limitations of their method. On the other hand, there are a lot of applied researchers who don´t understand the theoretical limitations of the techniques they are using. This makes it vitally important to ensure that theoretical and applied research goes hand in hand.’ In Beckmann’s research, the theoretical and applied sides of each study are always closely intertwined. ‘This approach – developing and improving tools and techniques, both at theoretical level and in terms of seeing how they function and are applied in practice – fits in perfectly with the Technical Medicine programme,’ says the professor. ‘The complete concept of teaching students in the field of biomedical engineering and combining this with exploratory clinical knowledge is precisely what I do in my own research at NIM.’
state-of-the-art research facilities,
Functional connectivity In his research, Beckmann concentrates on functional connectivity in the brain rather than on structural connectivity. ‘My reason for this is the fact that the connections linking certain areas of the brain can be highly complex. I don’t assume that there are always simple and direct connections. Indirect connections can be just as important.’ Beckmann’s research examines healthy and unhealthy human beings. ‘A lot of our research involves testing healthy adults to get a better understanding of how the brain is organized. We want to know which connections exist, whether these connections are organized into a hierarchy and how the connections evolve over the course of time.’ The data from healthy test subjects enables Beckmann to study break down of connectivity in old age, amongst other things. Beckmann is also exploring the development of babies’ brains, the impact of pharmacological intervention and how conditions such as dementia, ADHD and autism affect the way the brain develops.
University Medical Center Groningen (UMCG), University of Twente (UT), and Siemens Netherlands. The CMI aims to secure a leading global position in innovative medical imaging with groundbreaking research & development, education and valorization. The initiative combines clinical practice and technology, and innovative education in one center. Clinical needs will drive the CMI’s research agenda.
Focus The CMI aims at research and development of minimal to non-invasive medical imaging techniques to improve existing technologies and optimize their integrated use. Using medical technology assessment (MTA) of new and existing imaging techniques to contribute to a higher quality and more affordable healthcare. Oncology, cardiovascular diseases, and neural and neuromuscular diseases are CMI’s major themes. Background Only through innovation the quality of future health care can be improved and the costs be contained. Medical imaging will play a major role in this exercise. Next generation imaging technology will enable the early diagnosis of, for example, cancer and Alzheimer’s disease. This will lead to early interventions that delay or prevent the onset or spread of disease and mitigate its effects. Advances in medical imaging and diagnostics depend on intensive cooperation between clinicians, biologists and engineers. The CMI provides this cooperation of doctors and medical imaging technology experts. It will improve the interpretation and use of medical imaging data and will increase the acceptance of technology’s role in healthcare, through intensive knowledge exchange programs and merged research groups. Aims and objectives The CMI aims to break autonomous trends in healthcare with a negative impact on public health
and costs, by developing systematic pathways for the use and implementation of new and existing imaging devices and biomarkers. Furthermore the CMI will develop low-cost, high-sensitivity tests to exclude disease in order to reduce overexposure to the medical system, and will develop a model of the diagnostic and minimally invasive treatment centers of the future. Economic impact The efforts of the CMI in research and development will significantly decrease mortality rates from cancer and cardiovascular diseases and will substantially improve the quality of life of patients with neurodegenerative diseases. Early treatment can slow down cognitive decline and positively influence movement disorders. The considerable benefits from medical imaging will also reduce costs. Furthermore, it will stimulate clinically driven innovation in medical imaging and will generate new patents and start-ups. The center will involve and support start-ups and small and medium sized enterprises to develop innovative products, which will quickly be released on the market. Finally, with the active involvement of Siemens as a world-leading player in medical imaging, the center will attract international companies to the north-eastern regions of the Netherlands. Ambition The CMI combines established clinical and technological research groups in project teams and will establish a multidisciplinary research institute for all imaging and related non-invasive solutions in healthcare. The research will match current medical imaging technologies and will develop new medical imaging technologies with a focus on oncology, cardiovascular diseases and neural and neuromuscular diseases. Focussing on four ‘enablers’: targeted contrast, navigation technology, medical imaging informatics, and MTA. The CMI will help to realize the vision that, by 2020, individuals with an elevated risk of developing cancer can be identified at an early state and small (pre)malignant lesions can be fully removed through minimallyinvasive intervention. The patient is likely to be cured with less pain, lesser time in hospital care and a shorter recovery period, which will allow for a quicker restart at work.
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MIRA Foto’s: Siemens
Together with MIRA and UMC Groningen, Siemens Healthcare is one of the initiators of the Center for Medical Imaging (CMI). Kees Smaling and Sjaak van der Pouw, CEO and Business Innovation Manager from Siemens Healthcare respectively, explain Siemens’ reasons for embarking on this intensive alliance.
Siemens: ‘CMI must bridge the gap between technology and medical professionals’ The aim of the alliance from Siemens Healthcare’s point of view is to develop new imaging techniques, which will eventually supplement current technology for diagnostics and treatment such as MR and CT, says Smaling: ‘But this is still a very distant goal. In the short term, we are focusing on the phased development of applications for minimally invasive diagnostics using combination technologies.’ Matrix network Siemens first encountered MIRA about two years ago, continues Smaling. ‘Professor Vooijs approached us about the possibility of working together on robotics.’ In the two years that followed, various other parties joined their ranks and the partnership evolved into the CMI. The alliance with a range of different partners is in line with the Siemens innovation strategy, explains Van der Pouw. ‘These days, innovation doesn’t come about in isolation. Siemens is an engineering firm that makes substantial investments in R&D. In global terms, we invest 4.5 billion euros in alliances where Healthcare is one of the leading parties. But not all the innovation is concentrated in our own world-wide R&D centres; nowadays we operate in a matrix network made up of universities, medical practitioners and a range of start-up businesses.’ ‘Doctors tend to focus on the practical potential, but the partnership with Twente enables us to bridge the gap between development, technology and application,’ continues Smaling. And this is what is needed. ‘At present, the medical world is effectively constraining technological progress. This is because of the way medical professionals think. This is how
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I see it: technologists think and doctors act. Doctors are trained to think in short cycles. Which is just as well,’ he hastens to add, ‘because if you’re ill, the last thing you need is a five-year plan. You want treatment and you want it fast.’ Faster pace According to Smaling, the main reason for Siemens joining this alliance is the opportunity to accelerate technological developments. ‘Medical advancement is a lengthy process. You want the cycle to be as short as possible. We hope that the CMI will bridge the gap between technology and medical professionals. New technology will be accepted more readily and, we hope, at a faster pace.’ Van der Pouw adds that the Technology Assessments carried out by UT at an early stage to analyse the potential of technological innovations will play an important role. ‘The other thing that makes this an interesting partnership for us is the fact that the knowledge at MIRA is quite different from the knowledge found in a medical faculty. And by looking beyond the medical world, MIRA has a refreshingly different approach. We are expecting great things from this partnership.’ So what do Smaling and Van der Pouw envisage for the CMI in another ten years? Smaling: ‘That’s difficult to say. I hope that the CMI will be a research centre by then; one with a global reputation for producing good new technology.’ Van der Pouw enlarges: ‘I think we should just state our ambition to make the CMI one of the top 5 medical technology institutes in the world.’
Foto: UMCG
UMCG: patient care will benefit from management of imaging technology Professor Matthijs Oudkerk is Medical Scientific Leader of the CMI and Professor of Radiology at University Medical Center Groningen (UMCG), one of the three founding partners of the CMI. He explains UMCG’s decision to take part in the CMI.
Oudkerk gives two important reasons for UMCG joining the University of Twente and Siemens in the CMI at the very start. ‘We had already noted that the use of instruments in the healthcare sector, including imaging equipment, was insufficiently ‘clinical demand-driven’ and too market-driven.’ For example, producers may develop a new scanner without first listening to the needs and requirements of the specialists expected to work with it. As a result, people are using equipment without being aware of the full extent of its functions! ‘We must work towards a situation whereby imaging equipment is finely tuned to the specific needs of the clinical professionals using it.’ Imaging not fully embedded in hospitals Medical imaging has become an important facet of the healthcare system: it is now used in every specialism. ‘But it is still not fully embedded into the clinics,’ says Oudkerk, ‘which is where the problems start.’ According to the professor, imaging technology is often used where it is not really needed and too many falsepositive diagnoses are made, resulting in unnecessary costs for expensive treatment plans.
‘Not particularly cost effective.’ The CMI arose from the notion that this could be done differently. Twente, Groningen and Siemens formed an alliance whereby the strengths of each individual party were pooled to develop fundamental knowledge of imaging technology. The fact that this is an alliance between two universities and a major industrial partner is in line with the recent trend within society, according to Oudkerk: ‘Research must not only be seen to be socially relevant, it must also help to create jobs. The Hague is a firm advocate of public–private partnerships.’ Managing imaging ‘The CMI promotes a strategy for firm management of imaging technology in treatment plans,’ continues Oudkerk: ‘Clinical requests from specialists are passed to the ‘imaging analyst’ (someone with considerable expertise in image analysis). The first thing that this analyst does is to decide whether imaging will provide an answer to the question posed by the specialist. In other words, imaging will only be used if it is really necessary, and not for cases where a blood test would give the same result.’
By combining various imaging techniques and making an intelligent compilation of the findings, the analyst can make an accurate diagnosis, with a high value in terms of what can be excluded. ‘Much more accurate than is currently the case.’ The specialist can then draw up a treatment plan based on this diagnosis. ‘This obviously requires analysts with an extensive fundamental knowledge of imaging technology. This imaging specialism will evolve from radiology and nuclear medicine,’ says Oudkerk. He is quick to add that these analysts will keep a keen eye on cost efficiency. ‘In concrete terms, they will only use the expensive imaging technology if it is likely to show something that will not show up through other tests.’ Patients will notice results Research in Twente will take place in a pre-clinical research setting, and in Groningen in a clinical research setting. If it were up to Oudkerk, the results from this scientific research would find their way into ‘regular patient care’ as soon as possible. ‘When it comes down to it, the patients are what it’s all about.’
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MIRA
We must work towards creating ‘networks of labs’; this is the best way forward Foto: Universiteit Utrecht
Professor Gert Storm is a new recruit at MIRA. His knowledge and experience in the field of drugs and drug targeting make him a real asset! What’s more, his appointment will serve to reinforce the alliance with Utrecht University.
Storm will be setting up a new group within MIRA, which will explore the area where Targeted Therapeutics meets Nanotechnology (Targeted Nanomedicine). ‘I am determined to get nanomedicine into the clinics,’ explains Storm. Thanks to his past in Biopharmacy, he is well aware that this entails more than ‘just technology’. Originally a ‘chemical biologist’, Storm has held various positions in the United States and the Netherlands, is adjunct professor at the Royal School of Pharmacy in Copenhagen and professor at Utrecht University (where he will continue to work). Alliance It cuts both ways: ‘Utrecht benefits from the experience with nanotechnology and valorization at Twente, while the pharmaceutical expertise from Utrecht is an asset to MIRA and the Technical Medicine programme.’ Storm adds that he would also be happy to teach courses with a pharmaceutical leaning if the curriculum so requires. The primary focus of his research is on drug delivery and targeted carrier systems in cancer and chronic inflammation, such as rheumatism. In future, he may extend his field to include arteriosclerosis and drug delivery to the brain to help investigate typical conditions of old age (for example Parkinson’s and Alzheimer’s). Good imaging technology is vital. Storm already has close ties with the imaging centre in Aachen and the UMCU in Utrecht. According to Storm: ‘The CMI will soon be essential in this respect.’ Trans-institutional ‘In the field of nanomedicine, MESA+ and MIRA complement each other perfectly.’ As far as Storm is concerned, the trans-institutional alliance can be extended even further: the joint proposal for an ERC Synergy Grant submitted by groups working for Albert van den Berg, Dave Blank, Clemens van Blitterswijk and Vinod Subramaniam is a good
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Bringing MIRA’s technologies to the market
MIRA’s Entrepreneurial Professor Fredrik Gustafsson (Sweden, Linköping University) is an authority on ‘stochastic signal processing’. He was recently appointed to chair MIRA’s Biomedical Sensor Fusion group. As founder of three successful companies, Gustafsson will focus on bringing MIRA’s technologies to the market.
parts of the hand, thereby providing useful information to monitor progress in, for example, a rehabilitation process or in sports.
example. ‘Nano-safety is another of the areas that I’d like to explore together with an expert in Budapest. Consider, for example, getting round the side-effects of administering nanomedicines intravenously.’
Xsens ‘I have worked with Xsens for many years now,’ says Gustafsson, ‘and I am delighted to be able to continue this cooperation. We even intend to initiate a PostMaster’s course together, starting this September. Xsens’s Daniël Roetenberg and I will co-host a series of lectures to inspire Master’s and PhD students and even external partners to develop a business plan for their projects, which may eventually lead to a spin-off company.’
The future: opening up labs Storm hopes that within five years, we will see a top research group in Twente which, in addition to acquiring sufficient grants and Vidi subsidies, will also translate research into products for clinical and business practice. When asked whether there is anything that still needs clarification, Storm answers as follows: ‘It is important that as centres of knowledge, we put our facilities and laboratories at each other’s disposal. We must work towards creating a ‘network of labs’; this would be an effective way of facing up to the current restrictions on funding. Why not benefit from each other’s strengths to make ourselves even stronger? This really is the best way forward.’
Applications ‘I have always liked applications,’ Gustafsson admits. Not surprisingly this resulted in his first spin-off company in 2001. ‘We developed a Tyre Pressure Monitor System with a standardized warning symbol in the dashboard. This is now being used in 2 million cars.’ His second spin-off company may become as successful as the first, but in an entirely different market: guitar amplifiers (more specifically: integrating software in the amplifier to create different amplifier sounds, for example Marshall). Finally, Gustafsson and five colleagues at Linköping University have marketed a telephone application that enables indoor navigation by advanced sensor fusion algorithms, using motion sensors, accelerometers and wifi localization. This provides a unique fingerprint of one’s location (for example in a shopping mall). Three completely different companies, with one thing in common: they are all based on signal processing and intelligent software. Gustafsson is joining MIRA part-time alongside his work at Linköping University. His Biomedical Sensor Fusion group will be part of the Biomedical Signals and Systems (BSS) research group of Professor Peter Veltink, and will work closely with MIRA’s spin-off company Xsens, a world leader in 3D motion tracking innovation. Gustafsson will focus on advanced stochastic models to describe the state of the human body. This is based on information provided by sensors to measure for example speed, force, power and temperature. One of the projects he will be working on is called the ‘Power glove’. This ‘glove’, packed with sensors, will be able to measure precisely the movements of all relevant
Entrepreneurial spirit ‘I am amazed by the true entrepreneurial spirit at the University of Twente and MIRA in particular. The way you support spin-offs in all sorts of ways: with courses in starting up a business, funding and experienced coaches for example. In Sweden this would not be possible.’ Future It is difficult to predict where Gustafsson’s research group will be five years from now. ‘Looking, for example, at how Technical Medicine has expanded in such a short time, I’m convinced that MIRA is an exciting and promising place to be,’ Gustafsson concludes.
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MIRA BIOMEDICAL TECHNOLOGY AND TECHNICAL MEDICINE
FOR MORE INFORMATION ABOUT US, VISIT WWW.UTWENTE.NL/MIRA Our visiting address University of Twente MIRA Building Zuidhorst I Drienerlolaan 5 7522 NB Enschede I The Netherlands Our postal address University of Twente MIRA P.O. Box 217 I 7522 NB Enschede The Netherlands