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Using explainable AI, genetics and neuroimaging to target the glymphatic system

The glymphatic system is a brain-wide perivascular clearance pathway which facilitates the clearance of Amyloid-beta, a pathological hallmark of Alzheimer’s disease, from the brain. It is regulated by the sleep-wake cycle. The function of the glymphatic system relies highly on the water channel aquaporin 4 (AQP4), which is expressed by the AQP4 gene. Identifying genetic variants of risk with respect to the function of the glymphatic system and the role of sleep on its function, and defining genetically stratified groups to identify suitable candidates for future studies will aid in the investigation of a link between sleep and neurodegeneration. However, the effects of single genetic variants are typically very small. Additionally the interaction between genes or single nucleotide polymorphisms (SNPs), as well as gene-environment interactions might impede the declaration of single genetic variants as statistically significant.

SleepLess Project: Imaging synaptic plasticity in therapeutic sleep deprivation for major depression

Patients with major depression benefit from therapeutic sleep deprivation. The causality of this clinically effective therapeutic measure is unknown and the underlying molecular mechanisms remain elusive. We hypothesize that prolonged wakefulness is associated with an increase in synaptic strength, and that the synaptic dysregulation is affecting long term potentiation in patients with major depression. The aim of the project is to examine the synaptic basis of the antidepressant effect of therapeutic sleep deprivation by Positron Emission Tomography (PET) imaging of the synaptic vesicle protein 2A (SV2A) as a measure of synaptic density in patients and healthy subjects as well as animal models of depression. Since both anesthesia and sleep are subject to compromise biologically valid outcomes when studying the synaptic basis of therapeutic sleep deprivation, we developed a fully quantitative PET imaging method for awake animals.

Attenuation correction and image reconstruction for hybrid MRI/PET

In cooperation with the Institute of Aerospace Medicine of the German Aerospace Center (DLR), we operate a hybrid MRI/PET scanner within [:envihab], a research facility to explore the effects of extreme environmental conditions on humans. Combined Positron Emission Tomography (PET) and magnetic resonance imaging (MRI) using hybrid PET/MRI scanners offers unique chances to contribute to a better understanding of processes in basic brain research and to improve the understanding of pathophysiological mechanisms of neurological and psychiatric diseases. While PET provides metabolic information, MRI can provide anatomic information as well as information about physiological parameters, water diffusion, metabolite concentrations etc. Simultaneous acquisition of MRI and PET data correlates the data of the two complementary modalities both spatially as well as temporally and allows multifunctional and multiparametric imaging.

Phantom development for hybrid MRI/PET

Phantom measurements for PET/MRI hybrid imaging, which combines MRI soft tissue morphological imaging with PET functional imaging, are of strong interest for improving, tuning and analyzing the performance of the scanners and can be used as a ground truth for method development and evaluation in attenuation and motion correction, image reconstruction and general image quality assessment. However, creating multimodal phantoms for use in simultaneous acquisition of PET and MRI remains challenging. The image contrast in PET is caused by radiotracer distribution, and in MRI by proton relaxation times. The materials used in one modality might produce strong artifacts in images from the other modality, or might even be completely invisible.

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Teaching experience 2

Workshop, University 1, Department, 2015

This is a description of a teaching experience. You can use markdown like any other post.