Ongoing projects
This study aims to understand the early stages of Parkinson's by using multiple imaging techniques like MRI and PET scans of individuals at high risk, mainly in patients with isolated rapid eye movement sleep behavior disorder (iRBD). The goal is to identify early signs of disease progression and understand how different brain regions are affected over time.
We hypothesize that pathological processes in Parkinson's are temporally related and coexist in multiple brain areas during the prodromal stage. By using state-of-the-art imaging and statistical methods, we aim to elucidate these relationships and potentially identify patterns that can predict the progression to Parkinson's.
The project involves studying MRI and PET scans to detect changes in brain blood flow, neuroinflammation, dopaminergic and cholinergic functions in high-risk individuals over a three-year period. By combining data from different imaging techniques and long-term clinical follow-up, we aim to understand the relationships between various brain changes and predict the progression to Parkinson's and related diseases.
The findings of this study could lead to the discovery of early progression-biomarkers of iRBD patients and help predict clinical progression and identify new treatment targets for Parkinson's.
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Andreas Baun, PhD student
Supervisor: Nicola Pavese, MD, Prof.
Humans maintain steady physiological conditions through dynamic, self-regulating multi-organ interactions with energy-consuming systemic feedback loops that orchestrate organs to respond to perturbations. This is known as homeostasis. Dynamic whole-body PET/CT imaging has the potential to detect deviations in the balanced metabolic state using the radioactive glucose analogue 18F-FDG.
This study aims to explore variations in the inter-organ glucometabolic correlation in diabetes and lymphoma patients in comparison to a healthy control group. Applying correlation analyses and metabolic connectivity frameworks, metabolic alterations caused by diabetes and lymphoma can be quantified, making it possible to evaluate if the alterations can be indicative of the diseases and if the effects can be separated on a group-level and individual level.
Figure 1: Group abnormality maps created with connectome analysis from a group of patients without diabetes (left) and a group of diabetes patients (right) when compared to a control group of patients without diabetes
Key Research Methods:
- Organ glucose uptake measured with [18F]-FDG whole-body dynamic PET
- Connectome analysis using inter-organ correlations
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Marius Eldevik Rusaas, PhD student
Main Supervisor: Ole Lajord Munk, PhD, Professor
Ketone bodies are produced in the liver as an alternative fuel when blood glucose levels are low, as can be seen with various types of diet. In a previous study, we observed that the ketone bodies act as a kind of “super-fuel” for the heart and improve cardiac energy utilization. The overall purpose of the study is to investigate whether three weeks of intermittent fasting (fasting every other day) results in a more pronounced “metabolic shift” towards the use of ketone bodies for cardiac energy production than three weeks of Western diet (no restrictions). In addition, we will investigate the effect of fasting-induced ketosis on insulin resistance, and brain perfusion. The results of the study will contribute to knowledge about cardiovascular diet and can potentially have a decisive effect on which dietary recommendations should be given to obese people, as well as other people at risk for cardiovascular disease.
Key research methods
- Myocardial and cerebral perfusion measured by 15O-H2O
- Myocardial oxygen consumption and energy utilization measured by 11C-acetate
- Myocardial metabolism of fatty acids, ketone bodies, and glucose measured by 11C-palmitate, 11C-hydroxybutyrate, and 18F-FDG, respectively
- Skeletal muscle mRNA and protein expression of key ketolytic enzymes
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Mette Louise Gram Kjærulff, MD, PhD Student
Main supervisor: Lars Christian Gormsen, Clinical Professor, Department Chair
This study aims to assess the effect of Spinal Cord Stimulation (SCS) on the cholinergic nervous system and the glucose metabolism in the brain of patients with Parkinson’s disease (PD) and gait problems. Furthermore, this is a feasibility study that investigates the safety of this treatment and the effect on clinical gait performance of the participants.
Gait problems are common in PD and are often resistant to other treatments, including medicine. SCS has been found to improve gait, such as freezing of gait, in a small number of patients with PD. The mechanism of action is, however, unclear, and the treatment does not seem to work well in all candidates. Recently it has been implicated that cholinergic dysfunction in PD caused by degeneration of brainstem locomotor regions (such as the pedunculopontine nucleus) is involved in the control of movement initiation and body equilibrium. The cholinergic PET tracer 18FEOBV targets the vesicular acetylcholine transporter which is specific to cholinergic pre-synaptic terminals. 18F-deoxyglucose (18F-FDG) PET is a marker of regional cerebral glucose metabolic rate (by the marker of synaptic activity).
With this double-blind, randomised, placebo-controlled study, we aim to shed light on the mechanism of action of SCS with 18FEOBV and 18F-FDG PET scans. We also aim to identify imaging biomarkers at baseline that could be predictive of a favourable or a negative outcome of SCS and improve patient selection.
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Miriam Højholt Terkelsen, MD, PhD student
Main supervisor: Nicola Pavese, MD, Prof.
This PhD-study investigates the distribution and burden of alpha-synuclein pathology in post-mortem human brains from patients with Parkinson’s disease (PD) and incidental Lewy body disease using immunohistochemical (IHC) methods. The post-mortem brains used in this study was collected in 1945-1982 and are part of the Danish Brain Collection (previously located in Risskov).
Neuropathological studies have shown a brainstem-predominant pattern of alpha-synuclein pathology and a limbic system-predominant pattern. Brains from the Danish Brain Collection have both hemispheres conserved in a fixative making it possible to perform bilateral IHC analyses.
We aim to explore the symmetry/asymmetry aspect of PD by investigating the alpha-synuclein distribution bilaterally.
Here, we hypothesize that brainstem-predominant cases will show a symmetrical spreading pattern representing PD cases, where pathology originates in the autonomic nervous system, whereas limbic system-predominant cases will show an asymmetrical spreading pattern representing PD cases, where pathology originates within the brain in a single site, i.e. unilaterally.
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Contact Mie Just, PhD student
Main supervisor: Per Borghammer, PhD, Clinical Professor