Finnish Infrastructures for Functional Imaging (FIFI) is a distributed, Finnish national-level large-scale research infrastructure providing open access services in functional in vivo imaging of humans and animals. FIFI aims to guarantee that cutting-edge imaging technology is widely available for research and development projects both in academia and industry to enhance the science and to exploit the biomedical imaging infrastructures to the fullest.
The established infrastructures forming the FIFI consortium serve more than 700 users annually (20% external, 15% foreign), and the research results in more than 300 publications per year, about 40% of them in high-impact journals (IF > 5). Over the past 5 years, the research success of 9 Finnish Centres of Excellence, 10 Academy Professors and 11 ERC grant holders has critically depended on these infrastructures. The community of trained functional imagers is rapidly expanding, and we are actively contributing to that expansion. The FIFI infastructures support 10 graduate schools and they have facilitated training of altogether ~300 PhDs and numerous postdoctoral researchers.
The host organizations of the currently affiliated FIFI infrastructure partners include (in alphabetical order): Aalto University, Hospital District of Helsinki and Uusimaa, Turku University Hospital, University of Eastern Finland, University of Helsinki, University of Turku, and Åbo Akademi University. New partners may be included based on international recognition, complementary expertise to existing partners, and established open access practices.
Recent developments in modern techniques of biomedical imaging have led to a shift in the focus of biomedical research areas towards imaging, as well as to commercial innovations and growing business opportunities worldwide. The techniques are applicaple in basic, preclinical and clinical research settings of both animals and humans, in which their importance is well recognized. In high-level scientific research, however, carefully organized utilization scheme of these very expensive techniques must be formed and followed in order to achieve best possible results cost-efficiently as well as to keep the methods accessible to national and international user groups also in the future.
The Finnish participation in European level biomedical operations, Euro-BioImaging (EuBI), was initially activated within Biocenter Finland (BF) in 2010-2012 through a platform that focused on molecular and cellular imaging. The latest plan for the Finnish Participation in Euro-BioImaging (EuBI) ESFRI Initiative to Strengthen Imaging Infrastructures in Europe is included in Finland's strategy and roadmap for research infrastructures 2014-2020 by the Academy of Finland and Ministry of Education and Culture. In this plan, the Finnish bioimaging research scene was successfully organized into a format that corresponds to the European-level vision of bioimaging. The Finnish EuBI consortium is headed and coordinated by Professor John Eriksson at Åbo Akademi University; the vice-coordinator is Academy Professor Riitta Salmelin at the Aalto University.
An important component of the current plan of the reorganization of the Finnish imaging scene is to bring Finnish national spearhead in vivo imaging under a single coordinated open-access infrastructure, Finnish Infrastructures for Functional Imaging (FIFI). Thus, FIFI integrates the Finnish in vivo functional imaging nodes that, together, cover translational research from preclinical animal to clinical human imaging. Parts of FIFI are former partners of the Biocenter Finland consortium; the collaboration continues. FIFI mirrors and complements the Biocenter Finland. Together, they aim to keeping bioimaging in Finland at the competitive edge also in the future.
An essential component of understanding the operation of the human mind, brain and body is to unravel the underlying neural and molecular mechanisms. Functional imaging techniques provide the means of investigating those mechanisms in basic, preclinical and clinical research settings, in humans and animals, with resolution ranging from synaptic signalling to dynamic interactions of cell populations at the whole-organ level. Finnish researchers have made internationally influential contributions in development and innovative use of especially the magnetoencephalography (MEG), magnetic resonance imaging (MRI) and positron emission tomography (PET) methods. These spearhead methodologies also form the core of FIFI.
NEUROIMAGING infrastructure: MEG, MRI, fMRI, EEG, nTMS, nTMS-EEG, MEG-fMRI, MEG/MRI, NIRSI, nTMS-others.
Kuopio Biomedical Imaging Unit: µMRI, fMRI, µPET, µSPECT/CT, EEG, ultrasound, optical.
Turku PET Centre: PET, MRI, fMRI, µPET, SPECT, CT, EEG, ultrasound, optical, PET/MRI, PET/CT.
Biomedicum Imaging Unit: TPEF, 3PEF, SHG, THG, IVIS.
|The Brain Research Unit (BRU) at Aalto University (now part of NEUROIMAGING infrastructure) is a world-renowned pioneer and developer of MEG for time-sensitive imaging of sensory, motor and cognitive human brain functions since the early 1980's. The world's 1st whole-scalp neuromagnetometer became operational at BRU in 1992. Furthermore, the first 3T human whole-body MR scanner in Nordic countries (2002), dedicated fully for functional magnetic resonance imaging (fMRI) research, was commissioned at the AU Advanced Magnetic Imaging (AMI) Centre.||Kuopio Biomedical Imaging Unit (Kuopio-BIU) has pioneered biomedical MRI applications since the early 1990's; one of the first 9.4T small animal MRI systems in Europe was installed there in 1995. BIU is an international leader in developing, e.g., spin-lock-based MRI contrast and has gained international recognition through application of novel MRI methodology in search of biomarkers for epileptogenesis and gene therapy.|
|Turku PET Centre (TPC) is one of the largest molecular imaging research units in Europe and one of the most productive units in multimodal molecular imaging in metabolic and brain research. TPC started tracer development activities in the 1970's and in vivo imaging in the 1980's. It was the first centre in Europe to synthesise F-18-FDG, the most commonly used tracer today.||Biomedicum Imaging Unit at the University of Helsinki is a core facility that provides expertise and modern equipment for light microscopy and optical in vivo imaging. The preclinical small animal imaging modalities include multiphoton microscopy and whole body fluorescence and bioluminescence imaging.|
In our distributed network of major established Finnish large-scale research infrastructures, we offer state-of-the-art approaches for in vivo functional imaging that include, among others, (i) tracking macroscopic current flow in neuronal populations via the associated electromagnetic field (MEG; electroencephalography, EEG), (ii) exploiting magnetic properties of molecules in the brain and body (MRI; functional MRI, fMRI), (iii) using radioligands to map the distribution and kinetics of target-specific tracer molecules (PET; single-photon emission computed tomography, SPECT), (iv) measuring how absorption/reflection of light (optical techniques), sound (ultrasonic techniques) or X-rays (computed tomography, CT) is influenced by functional changes in the studied system, and (v) inducing neuronal currents (navigated transcranial magnetic stimulation, nTMS) and measuring the behavioural, neural and motor effects.
The strong scientific expertise and innovation within the FIFI consortium is an essential component of the successful use and further development of the research infrastructures. The coverage of research topics from basic science through preclinical to clinical research, continuous interactive development of methods and applications, and the complementary emphasis on neuroimaging, molecular imaging and translational imaging among the partners benefit the research of the FIFI user base as a whole. Multimodality, through insightful combination of the various methods, is the next major step in functional imaging world-wide; this view is shared by the FIFI partners.
Finnish researchers are internationally influential contributors in development and innovative use of magnetoencephalography (MEG), magnetic resonance imaging (MRI) and positron emission tomography (PET). FIFI brings together the key developers of these Finnish spearhead methodologies of in vivo imaging. The cost of state-of-the-art in imaging instrumentation and supporting infrastructure, even in a single imaging modality, let alone with the increasing need for multimodal imaging, is in the order of millions of euros. Furthermore, the efficient use of such instruments requires considerable methodological expertise (e.g., MEG physics and analysis, MRI physics/pulse sequence programming, image analysis, PET tracer synthesis and data analysis) that cannot be mastered by all user groups.
FIFI brings together a critical mass of synergistic and complementary high-level expertise for concerted national-level planning of infrastructure upkeep and development, services, user training and future investments. FIFI and BF consortia importantly mirror and complement each other and, through efficient division of labour and good synergy, cover the entire bioimaging field from cellular through animal to human imaging.
To use our expertise and infrastructures, check detailed information from the corresponding websites. Current partner infrastructures of the FIFI consortium:
NEUROIMAGING (NI) collaboration: Aalto NeuroImaging (ANI) and the BioMag Laboratory, governed by Aalto University, University of Helsinki, and Hospital District of Helsinki and Uusimaa
Turku PET Centre (TPC), formed by University of Turku, Åbo Akademi University, and Turku University Hospital
Kuopio Biomedical Imaging Unit (Kuopio-BIU), formed by University of Eastern Finland
Biomedicum Imaging Unit (Helsinki-BIU), formed by University of Helsinki
Prospective partners and close collaborators:
Jyväskylä Centre for Interdisciplinary Brain Research (CIBR), formed by University of Jyväskylä
The FIFI consortium has a Coordinating Group with one representative from each of the partner infrastructures and a named (part-time) director. The Coordinating Group will meet at least twice a year, alternating with governing board meetings of the partner infrastructures.
Other actively involved operative personnel:
Web page comments to: Tolvanen Tuomas
Jeltsch M, Jha SK, Tvorogov D, Anisimov A, Leppänen VM, Holopainen T, Kivelä R, Ortega S, Kärpanen T, Alitalo K.
Abstract: Hennekam lymphangiectasia–lymphedema syndrome (Online Mendelian Inheritance in Man 235510) is a rare autosomal recessive disease, which is associated with mutations in the CCBE1 gene. Because of the striking phenotypic similarity of embryos lacking either the Ccbe1 gene or the lymphangiogenic growth factor Vegfc gene, we searched for collagen- and calcium-binding epidermal growth factor domains 1 (CCBE1) interactions with the vascular endothelial growth factor-C (VEGF-C) growth factor signaling pathway, which is critical in embryonic and adult lymphangiogenesis. By analyzing VEGF-C produced by CCBE1-transfected cells, we found that, whereas CCBE1 itself does not process VEGF-C, it promotes proteolytic cleavage of the otherwise poorly active 29/31-kDa form of VEGF-C by the A disintegrin and metalloprotease with thrombospondin motifs-3 protease, resulting in the mature 21/23-kDa form of VEGF-C, which induces increased VEGF-C receptor signaling. Adeno-associated viral vector–mediated transduction of CCBE1 into mouse skeletal muscle enhanced lymphangiogenesis and angiogenesis induced by adeno-associated viral vector–VEGF-C. These results identify A disintegrin and metalloprotease with thrombospondin motifs-3 as a VEGF-C–activating protease and reveal a novel type of regulation of a vascular growth factor by a protein that enhances its proteolytic cleavage and activation. The results suggest that CCBE1 is a potential therapeutic tool for the modulation of lymphangiogenesis and angiogenesis in a variety of diseases that involve the lymphatic system, such as lymphedema or lymphatic metastasis.
Pihko E, Nevalainen P, Vaalto S, Laaksonen H, Mäenpää H, Valanne L, and Lauronen L.
Abstract: Cerebral palsy (CP) is characterized by difficulty in control of movement and posture due to brain damage during early development. In addition, tactile discrimination deficits are prevalent in CP. To study the function of somatosensory and motor systems in CP, we compared the reactivity of sensorimotor cortical oscillations to median nerve stimulation in 12 hemiplegic CP children vs. 12 typically developing children using magnetoencephalography. We also determined the primary cortical somatosensory and motor representation areas of the affected hand in the CP children using somatosensory-evoked magnetic fields and navigated transcranial magnetic stimulation, respectively. We hypothesized that the reactivity of the sensorimotor oscillations in alpha (10 Hz) and beta (20 Hz) bands would be altered in CP and that the beta-band reactivity would depend on the individual pattern of motor representation. Accordingly, in children with CP, suppression and rebound of both oscillations after stimulation of the contralateral hand were smaller in the lesioned than intact hemisphere. Furthermore, in two of the three children with CP having ipsilateral motor representation, the beta- but not alpha-band modulations were absent in both hemispheres after affected hand stimulation suggesting abnormal sensorimotor network interactions in these individuals. The results are consistent with widespread alterations in information processing in the sensorimotor system and complement current understanding of sensorimotor network development after early brain insults. Precise knowledge of the functional sensorimotor network organization may be useful in tailoring individual rehabilitation for people with CP.
Harno H, Haapaniemi E, Putaala J, Haanpää M, Mäkelä JP, Kalso E, and Tatlisumak T.
Abstract: We describe the frequency, duration, clinical characteristics, and radiologic correlates of central poststroke pain (CPSP) in young ischemic stroke survivors in a prospective study setting. A questionnaire of pain and sensory abnormalities and EQ-5D quality-of-life questionnaire were sent to all 824 surviving and eligible patients of the Helsinki Young Stroke Registry. Patients (n = 58) with suspected CPSP were invited to a clinical visit and filled in the PainDETECT, Brief Pain Inventory, and Beck Depression Inventory questionnaires. Of the included 824 patients, 49 had CPSP (5.9%), 246 patients (29.9%) had sensory abnormality without CPSP, and 529 patients (64.2%) had neither sensory abnormality nor CPSP. The median follow-up time from stroke was 8.5 years (interquartile range 5.0–12.1). Patients with CPSP had low quality of life compared to those with sensory abnormality without CPSP (p = 0.007) as well as to those with no sensory abnormality and no CPSP (p < 0.001). Forty (82%) of the patients with CPSP had concomitant other pain. CPSP was associated with moderate (p < 0.001) and severe (p < 0.001) stroke symptoms, but there was no difference in age at stroke onset or subtype of stroke according to the TOAST classification between the groups. Stroke localization was not correlated with CPSP. Late persistent CPSP was found in 5.9% of young stroke survivors and was associated with concomitant other pain, impaired quality of life, and moderate or severe stroke symptoms.
Salminen-Vaparanta N, Vanni S, Noreika V , Valiulis V , Móró L, and Revonsuo A.
Abstract: One way to study the neural correlates of visual consciousness is to localize the cortical areas whose stimulation generates subjective visual sensations, called phosphenes. While there is support for the view that the stimulation of several different visual areas in the occipital lobe may produce phosphenes, it is not clear what the contribution of each area is. Here, we studied the roles of the primary visual cortex (V1) and the adjacent area V2 in eliciting phosphenes by using functional magnetic resonance imaging-guided transcranial magnetic stimulation (TMS) combined with spherical modeling of the TMS-induced electric field. Reports of the subjective visual features of phosphenes were systematically collected and analyzed. We found that selective stimulation of V1 and V2 are equally capable of generating phosphenes, as demonstrated by comparable phosphene thresholds and similar characteristics of phosphene shape, color, and texture. However, the phosphenes induced by V1 stimulation were systematically perceived as brighter than the phosphenes induced by the stimulation of V2. Thus, these results suggest that V1 and V2 have a similar capability to produce conscious percepts. Nevertheless, V1 and V2 contribute differently to brightness: neural activation originating in V1 generates a more intense sensation of brightness than similar activation originating in V2.
Kujala J, Sudre G, Vartiainen J, Liljeström M, Mitchell T, and Salmelin R.
Abstract:Animal and human studies have frequently shown that in primary sensory and motor regions the BOLD signal correlates positively with high-frequency and negatively with low-frequency neuronal activity. However, recent evidence suggests that this relationship may also vary across cortical areas. Detailed knowledge of the possible spectral diversity between electrophysiological and hemodynamic responses across the human cortex would be essential for neural-level interpretation of fMRI data and for informative multimodal combination of electromagnetic and hemodynamic imaging data, especially in cognitive tasks. We applied multivariate partial least squares correlation analysis to MEG–fMRI data recorded in a reading paradigm to determine the correlation patterns between the data types, at once, across the cortex. Our results revealed heterogeneous patterns of high-frequency correlation between MEG and fMRI responses, with marked dissociation between lower and higher order cortical regions. The low-frequency range showed substantial variance, with negative and positive correlations manifesting at different frequencies across cortical regions. These findings demonstrate the complexity of the neurophysiological counterparts of hemodynamic fluctuations in cognitive processing.
The established FIFI infrastructures can offer measurement hours for external users. Short research plan and an ethics statement (for human and animal research) is required. Each site offers training and may require participation in courses for safety and basic skills for operating the local infrastructure. Infrastructure personnel assists the users upon request and the infrastructures offer the best possible complementary measurement capabilities, such as physiological and behavioural monitoring and responses devices and stimulation systems, when needed. We aim to streamline online reservation and user documentation systems, as well as common scientific and financial reporting policies, from initially separately operated infrastructure sites to across all FIFI partners.
The annual upkeep costs of the FIFI infrastructure are about 12 M€ in total and the number of support personnel approximately 100. In the established infrastructures, the funding comes primarily through stakeholders (users 60-75%, host institutes 25-40%). Within FIFI, we aim to equalize the overall funding structure as much as possible across the infrastructures, and enhance its transparency. All host institutes prioritize life sciences in their current strategies and are committed to supporting their imaging infrastructures.
FIFI has made its own internal roadmap for critical upgrades and new investment needs until 2020. For example, cutting-edge preclinical and translational research requires 14T MRI device for animal as well as a 7T MRI (the first one in Finland) for human studies. The optimal placement of new infrastructure is determined on a national level by location of knowhow and users in agreement with all the involved parties.
The FIFI partners provide a wide selection of regularly organized training courses: MEG introduction (NI), fMRI school (NI), MRI safety (NI, Kuopio-BIU), TMS training (NI), PET basics (TPC), BioNMR workshops (Kuopio-BIU), optical live brain imaging (Helsinki-BIU) and others. FIFI partners also provide training through contribution to university curricula. Within FIFI, we aim to coordinate the training courses into an entity that can be offered, e.g., as part of graduate studies.
New partners may be included based on international recognition, complementary expertise to existing partners, and established open access practices and common principles of operation, outlined above. For further information or questions on practical matters, please contact the Coordinating Group members or operative personnel of FIFI.
Espoo: AMI Centre's MRI safety course; Announced soon
Espoo: Aalto TMS user and safety course; Tue 28.4.2015, 09:00-15:00
Kuopio: 17th Kuopio Bio-NMR Workshop; April 16-17, University of Eastern Finland
Kuopio: XXXVII Finnish NMR Symposium; April 15-16, University of Eastern Finland
Espoo: Aalto TMS user and safety course; Thu 26.3.2015, 09:00-15:00
Espoo: AMI Centre's MRI safety course; Thu 5.3.2015, 08:30-13:00
Espoo: Aalto TMS user and safety course; Fri 13.2.2015, 09:00-15:00
Espoo: AMI Centre's MRI safety course; Wed 4.2.2015, 08:00-12:00