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Summary:
Neurosurgery for brain tumours and epilepsy requires a delicate balance between removal of sufficient pathological tissue to postpone disease progression/relieve symptoms and limiting resections where damage would cause impairment of important brain function, such as motor ability and language. Neurosurgery has always included stimulation of the exposed brain in patients operated when awake for registration of the neuropsychological and functional responses to localize essential functions. However, direct stimulation requires the patient’s ability to cooperate and is further limited by the growing use of minimally invasive surgery, where the brain surface is no longer exposed. With our new approach, we wish to pave the way to brain mapping that is adaptable to anaesthetized patients and can be used with less invasive surgery techniques. We will first focus on preoperative magnetic resonance (MR) session to map malignant tumour spread as well as areas with essential functions, and will compare findings with positron emission tomography of amino acid uptake to delineate malignancy. Further, an intraoperative MR approach for localizing essential functions will be used to guide the ongoing surgical plan both in patients with brain tumours and epilepsy. Results will be compared to operative and clinical findings and histopathological tissue properties.
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Proejct summary:
Electroceutical therapy is a rapidly expanding therapeutic option used in diverse medical conditions. Our patented device, the fMRI Compatible Electrical Stimulator, can measure the effects of electric stimuli with functional magnetic resonance
imaging (fMRI). Now we want to develop and commercialize our product by generating a regulatory strategy, conducting a market analyses and a Development Plan to support an approval of the product in key markets. Moreover, we will build
an improved control unit of the prototype and conduct clinical pilot studies relevant for two different applications.
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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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- International post doc grant from IRFD
- Staff News, March 2020
- Scholarstipend from DSfN
- Funding from Lægefonden to Lene Donovan
- Grant from Novo Nordisk Foundation
- 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