Ongoing Projects
Cardiovascular:
Perfusion of the myocardium is compromised in patients with ischemic heart disease. The resulting ischemia causes typical symptoms of chest pain and shortness of breath particularly during exercise where oxygen demand is high. Effective treatment depends on effective diagnostics. To potentially increase availability of effective diagnostics, the project compares the non-invasive diagnostic approaches of PET with 15O-H2O as radiotracer and cardiac MRI with gadolinium contrast by integrated PET/MR. The PET method is widely considered state of the art for perfusion measurements. However, 15O-H2O myocardial perfusion imaging is only available in select PET centers with access to an on-site cyclotron, whereas MRI scanners are ubiquitous in the developed world. If MRI perfusion compares well with 15O-H2O perfusion, more patients will potentially have access to a perfusion study.
Key research methods
- Myocardial perfusion measured by 15O-H2O PET and gadolinium MRI
- Myocardial scar tissue measured as perfusable tissue index by 15O-H2O PET and late enhancement gadolinium MRI
Contact Simon Madsen, PhD student
Main Supervisor: Lars Christian Gormsen, PhD, Clinical Professor
Metabolism:
Polymyalgia rheumatica (PMR) is a common chronic inflammatory disorder characterized by pain of the proximal muscles, general symptoms, and raised inflammatory markers.
Prednisolone remains a cornerstone in the treatment of PMR, but carries significant adverse effects including osteoporosis, diabetes, increased infection risk, and risk of adrenal insufficiency. Therefore, correct diagnosis and adequate monitoring of disease activity is crucial to avoid misdiagnosis and limit treatment duration. PMR remains largely an exclusion diagnosis, and reliable methods to diagnose and monitor the disease are lacking. Therefore, misdiagnosis is a common problem, and patients starting prednisolone prior to proper rheumatological assessment represents a specific diagnostic challenge.
The main objective of this study is to improve the diagnostics and monitoring of polymyalgia rheumatic (PMR). Specifically the objectives are:
- To investigate the diagnostic value of PET/CT for PMR diagnosis at baseline, during prednisolone treatment, and after temporary prednisolone cessation. Clinical diagnosis after 1 year serves as reference and patients not diagnosed with PMR are controls.
- To investigate if PET/CT can be used to monitor treatment response and relapse in PMR.
Contact Andreas Wiggers Nielsen, MD, PhD student, for more information.
Main supervisor: Ellen-Margrethe Hauge, Professor
Co-supervisors: Kresten Krarup Keller, MD, PhD & Lars Christian Gormsen, 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
Contact Mette Louise Gram Kjærulff, MD, PhD Student, for more information
Main supervisor: Lars Christian Gormsen, consultant, professor
Neurology and Neuroscience:
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.
Contact:
Miriam Højholt Terkelsen, MD, PhD-student methoh@rm.dk
Victor Hvingelby, MD, PhD-student au340287@clin.au.dk
Supervisor: Nicola Pavese, MD, Prof. npavese@clin.au.dk
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.
Contact Mie Just, PhD student
Main supervisor: Per Borghammer, PhD, Clinical Professor