Summary of Gjertrud's 1-year project:
Developing drugs for treatment of brain disorders is challenging, time consuming and costly. PET neuroimaging has evolved as a useful tool for investigating the interactions between a drug and its target receptor in the human brain. Although PET is frequently used for drug development, the experimental framework and methodologies used to analyze the acquired data are inefficient, often leading to biased outcomes and high variability. With improved analytical techniques it will be possible to modify the experimental setup so that the number of PET scans can be reduced without sacrificing statistical power.
Current analytical tools require that at least two scans, one at baseline and one after administration of the drug, are acquired for each research subject. We aim to improve the utility of PET for drug development by establishing methods that enable within-scan challenges, in which the drug is administered during an ongoing scan. Such a setup circumvents the issue of biological fluctuations between scans, while also reducing costs and lowering the total radiation exposure. However, in order to employ this experimental design a new class of pharmacokinetic models must be developed, because current models are adequate only for separate scans. In this project, we plan to develop new mathematical models that describe the pharmacokinetics of the PET ligand before, during and after administration of a drug competing for the same receptor. We will validate these models using simulation experiments and real PET data.
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Hormonal sensitivity and brain function: Do oral contraceptives distort serotonergic brain architecture and does discontinuation restore it?
Women who use oral contraceptives face an increased risk of developing depressive episodes. We do not know why. Recent cross-sectional findings from our group raises the question if oral contraceptives distort serotonergic brain architecture, which may critically disturb brain function and increase risk of depressive symptoms at least in hormone sensitive women. Using frontier molecular brain imaging techniques and a longitudinal design including baseline, and on-/off states of oral contraceptive use, we here propose to directly illuminate serotonergic brain signatures of using oral contraceptives and determine its reversibility in healthy young women who are first time users. We anticipate that this work will critically advance our understanding of how changes in sex-hormone milieu increase susceptibility for depressive episodes and provide novel preventive and therapeutic opportunities, which holds grand potential to protect mental health.
Neuroimaging of brain pulsations and its impact on human brain disease
Naturally occurring pulsations in the brain are physiologically very important and may be essential for clearance of brain waste products. The novel neuroimaging tool magnetic resonance encephalography (MREG) enables the investigation of these pulsations non-invasively in humans. We propose to exploit this novel tool to understand the outcome measures and apply it in a brain disorder. The first aim is thus to provide deeper mechanistic insight into MREG outcomes and investigate the extent to which MREG detected brain pulsations are linked to intracranial pressure in healthy controls. Subsequently, we aim to probe the diagnostic potential of MREG in a group of patients with idiopathic normal pressure hydrocephalus (iNPH), treatable with shunt. iNPH is a neurodegenerative disease which is underdiagnosed and undertreated because current diagnostics poorly predicts who will benefit from shunting. We will assess patients before and after treatment to evaluate the predictive value of MREG.
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We have set up a firm procedure for how to bring patients and volunteers safely into the building and to the scanners, and this procedure has been approved by all relevant parties, including the Director of Diagnostic Center, the Head of Department of Neurology, staff from Department of Radiology and a hygiene nurse. We are looking very much forward to being able to continue our interesting research projects.
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Welcome to the following new faces who will join NRU in March:
Volunteer/Bachelor's student Ajla Sabitovic (Medicine).
Interns Miriam Demattia and Natasha Christiansen (both Neuroscience & Neuroimaging). Miriam will be working with Mikael in the lab and Natasha with Patrick.
Ajla 
Natasha 
Also welcome back to Dorte Zilstorff, MD, who will join us for two months.
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Congratulations to prof. Jens D. Mikkelsen for receiving 140.000 DKK from Danish Society for Neuroscience (DSfN) in a scholarstipend for molecular biomedicine student Clara Madsen, who will be conducting a project entitled 'Synaptic vesicle glycoprotein 2A (SV2A) used as a novel biomarker of synaptogenesis in an animal model of cerebral palsy (CP)'
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Congratulations to Lene Donovan for receiving 45.000 DKK from Lægefonden (A.P. Møller) for the project 'Effects of psilocybin on pig brains'.
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- Bias and fairness in medicine
- NRU research in Deadline on DR2
- Best master's thesis of the year award to Søren Vinther Larsen
- Vibe Frøkjær appointed as Clinical Research Associate Professor
- Martin Nørgaard receives Carlsberg Foundation Internationalisation Fellowship
- Grant from the Research Fund of the Mental Health Services - Capital Region of DK
- NRU Christmas Symposium 2019
- Travel stipend from the Lundbeck Foundation
- The new NRU brain research 3T MR
- Melanie Ganz in the BIDS Steering Group