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The Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) was established as a research center in January 2006 based on a 40 mio DKK grant from the Lundbeck Foundation. The center was officially inaugurated February 9, 2006.

In November 2009 and again in October 2010, the Lundbeck Foundation extended the original 5-year term with additional funding to Cimbi, enabling first a 1-year extension of Cimbi and secondly a 4-year continuation of the center. In total, the Lundbeck Foundation generously supported Cimbi with 80 mio DKK.

cimbi logo wide LF 634x150Cimbi was founded on a collaboration between a number of research institutions in Copenhagen. These institutions formed the core of Cimbi and all the research activities in Cimbi involved one or more of these institutions. The core institutions were distributed among the Copenhagen University Hospitals, the Technical University of Denmark and the University of Copenhagen. Furthermore, a number of other Danish and international institutions were associated with Cimbi as collaborators in one or more subprojects. The institutions involved in Cimbi research therefore spanned many scientific fields and provided the strong foundation needed to carry out the diverse activities undertaken in Cimbi.

The institutions involved in Cimbi were:

  • Neurobiology Research Unit (NRU), Copenhagen University Hospital, Rigshospitalet. NRU has been at the heart of Cimbi with a long history of research within receptor brain imaging, receptor binding, cellular characterization and quantification, tracer validation, kinetic modelling and data analysis. Furthermore, NRU housed the management of Cimbi and was the contact point between Cimbi and the Lundbeck Foundation.
  • Danish Research Centre for Magnetic Resonance, (DRCMR), Copenhagen University Hospital, Hvidovre. DRCMR was the first centre in Denmark to conduct MRI research and still plays a leading role in the Danish MR community. DRCMR provided Cimbi with MRI resources and expertise in fMRI, brain morphology and diffusion tensor imaging.
  • Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, who provided the Cimbi basis for cold chemistry facilities and expertise in organic syntheses.
  • Department of Applied Mathematics and Computer Science (DTU Compute),the Technical University of Denmark. DTU Compute has a long history of research in mathematical modelling and advanced signal processing, especially within the field of medical imaging.
  • PET and Cyclotron Unit, Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital, Rigshospitalet was a key player in terms of providing the entire infrastructure for radiochemistry, PET- and MR-PET scanner facilities as well as the expertise within the field.
  • Unit of Medical Psychology, Department of Public Health, University of Copenhagen. Health psychology, neuropsychology and developmental psychology
  • Research Unit for Affective Disorders, Department of Psychiatry, Copenhagen University Hospital, Rigshospitalet. Epidemiological and clinical expertise in affective disorders
  • Department of Psychology, University of Copenhagen. Neuropsychology and social cognition
  • The Neuroscience, Cognition & Learning Consortium, Learning Lab Denmark. Cognitive neuroscience expertise
  • Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen. Genetic polymorphism
  • Section of Biostatistics, Faculty of Health Sciences, University of Copenhagen. Databases, biostatistics
  • Rotman Institute-Baycrest Centre and University of Toronto, Canada. Modelling expertise
  • Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden. Databases of receptor imaging data in humans (PET and autoradiography), radiochemistry expertise
  • Institute of Medicine, Research Center Jülich, Germany. Postmortem human material, neuroreceptor autoradiography, PET-scanning, connectivity expertise
  • Department of Pharmacology, Oxford University, United Kingdom. Neuropharmacology expertise, in vitro facilities for tracer development
  • MRC Cognition and brain sciences unit, University of Cambridge, United Kingdom. Cognitive neuroscience and functional imaging expertise
  • Neuroscience and Psychiatry Department, University of Manchester, United Kingdom. Cognitive neuroscience and functional imaging expertise
  • Center of Excellence for Stress and Mental Health, San Diego Veteran's Affairs Healthcare System, USA. MRI and fMRI expertise
  • Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard University, Boston, US. MRI and fMRI expertise

 

Research aim

The overall aim of Cimbi was to uncover basic questions regarding interindividual differences in behavior and personality in healthy people with a particular emphasis on phenotypical variations that are likely to be causally related to variations in the serotonergic transmitter system. Individual differences in trait effect and personality are for a large part genetically determined and they are critical in shaping complex human behavior, social interplay and also in overcoming challenges from the ever-changing environments. Such individual differences may also serve as important predictors of vulnerability to neuropsychiatric disorders, including depression, anxiety and memory disorders.

Neuroimaging studies, including molecular, structural and functional MRI studies have been used to uncover the neural substrates of interindividual variability with a particular emphasis on the serotonergic transmitter system. At the same time, genetic variation has been considered as an important component substantially adding to interindividual variability.

In the first life cycle of Cimbi (Cimbi-I, 2006-10) we have demonstrated a number of relevant and meaningful associations. These studies illustrated the predictive links between genetic or trait-like behaviors (e.g., trait neuroticism) on one hand and regional brain structure, activation and serotonergic markers on the other hand. Such correlation studies were useful and informative, and they provided us with neuroimaging biomarkers of disease susceptibility and suggested causal links.

In the second operative period of the Center (Cimbi-II, 2011-2015) we focused on longitudinal and interventional studies in order to better address causal relationships and to substantiate the predictive value of brain imaging as biomarkers. Specifically, Cimbi-II operated with five interacting themes of relevance for the serotonergic transmitter system: Mood and Emotions, Biorhythms, Affective Cognition, Brain Development, and Decision-making. In addition, two platforms were included, one for radioligand development and validation, and another for data analysis.

 

Management

The members of the Cimbi-II steering group were:

  • Professor Gitte Moos Knudsen who was the center director. She was based at the Neurobiology Research Unit (NRU) at Rigshospitalet.
  • Professor Hartwig R. Siebner who was based at the Danish Research Centre for Magnetic Resonance (DRCMR) at Hvidovre Hospital.
  • Professor Lars Kai Hansen who was based at the Department of Informatics and Mathematical Modelling at the Technical University of Denmark (DTU).
  • Professor Terry L. Jernigan who was based at the Department of Cognitive Science at University of California, San Diego (UCSD).
  • Professor Sven Frøkjær who was based at the Faculty of Health and Medical Sciences (former FARMA) at University of Copenhagen.
  • Chief Medical Officer Jannik Hilsted who was based at Rigshospitalet.

The Cimbi center manager was:

  • Peter S. Jensen who was based at the Neurobiology Research Unit (NRU) at Rigshospitalet.

In the first life cycle of Cimbi (Cimbi-I, 2006-10), the Cimbi steering group had a management meeting once a month. In the second lifecycle of Cimbi (Cimbi-II, 2011-15), the Council of Investigators (COI) group meetings replaced the monthly steering group meetings and the role of the steering group became more withdrawn, primarily taking care of broader issues like economy and strategy. In Cimbi-II the steering group only had one scheduled meeting a year, right after the annual meeting.

The Council of Investigators (COI) group consisted of the senior researchers and postdocs with the daily responsibility for the different projects within Cimbi. The COI group met once a month to mutually inform about status in all projects and also discuss practical and scientific aspects.

Besides the members of the steering group and the center manager, the members of the COI group included:

  • Olaf B. Paulson, Professor, NRU who is former leader of NRU and DRCMR.
  • Vibe Frøkjær, PhD, NRU who has been responsible for the Cimbi-II themes: "Mood and Emotions" and "Affective Cognition" (together with Gitte Moos Knudsen)
  • Patrick Fisher, PhD, NRU who has been responsible for the Cimbi-II theme: "Biorhythms".
  • Kathrine Skak Madsen, PhD, DRCMR who has been responsible (together with William F. C. Baaré) for the Cimbi-II theme: "Brain Development".
  • William F. C. Baaré, PhD, DRCMR who has been responsible (together with Kathrine Skak Madsen) for the Cimbi-II theme: "Brain Development".
  • Julian Macoveanu, PhD, DRCMR who has been responsible for the Cimbi-II theme: "Decision Making".
  • Hanne D. Hansen, PhD, NRU who has been responsible for Cimbi-II platform I: "Radioligand Development".
  • Claus Svarer, PhD, NRU who has been responsible (together with Carsten Stahlhut) for Cimbi-II platform II: "Data Analysis".
  • Finn Aarup Nielsen, PhD, DTU who has been responsible (together with Claus Svarer) for Cimbi-II platform II: "Data Analysis".

 

Research output

Since 2006 Cimbi has generated 375 peer-reviewed publications. See the full publication list here. On top of that, a total of 44 Cimbi-related PhD-students have successfully defended their theses.

Systematically characterizing a PET radioligand: The full [11C]SB207145 story

Here we are sharing with you how Cimbi has completed a set of studies aimed at systematically characterizing a PET radioligand known as [11C]SB207145, which binds to the serotonin type 4 receptor (5-HT4R). From the determination of how to quantify the signal from [11C]SB207145 PET scans to initial evidence that it may also represent a proxy for inter-individual differences in brain serotonin levels, the collaborative effort across research groups within Cimbi underscore its abilities to move biomedical research forward. Read the entire story here.

From molecule to man: The full Cimbi-36 story

Developed through medicinal chemistry, radiochemistry, and animal studies, 2012 was the year where our first “Cimbi”-compound, [11C]Cimbi-36, was taken into humans and tested in healthy volunteers. This milestone builds on several years of development and represents a huge achievement for the center. Read the entire story here.

 

Cimbi Closing Sympoisum in 2015

When Cimbi came to conclusion of its funding period from the Lundbeck Foundation, the 10-year (2006-15) long initiative was celebrated at an excellent 3-day closing symposium in September 2015, supported by and held at the Royal Danish Society for Sciences and Humanities. The symposium consisted of exciting lectures from a beautiful cocktail of international speakers and Cimbi-affiliated researchers. A few photos from the symposium are shown below.

Samletbillede

Photos from the 3-day Cimbi Symposium 2015 in the Royal Society for Sciences and Letters.

After 2015, the branding of Cimbi has been well-established and there has been at least be three lines of research that have carrried on, namely 1) the nomenclature of radioligands developed within the framework 2) the Cimbi database and 3) the Cimbi biobank. The established Cimbi database/biobank are internationally recognized as unique and will continue to constitute a valuable resource for researchers within and outside of Denmark, e.g. for new hypothesis driven studies. In 2016 we published an inventory of the database in Neuroimage and we contiously receive requests for access to data from several researchers. All future requests for use of data from the database will be assessed efficiently by a small group of people, collectively covering most of the modalities represented within the database. Importantly, this will ensure due credit and acknowledgement to Cimbi researchers. You can read more about the Cimbi Database and Cimbi Biobank here.