Multimodal Imaging of Brain Metabolism

The Multimodal Imaging of Brain Metabolism group combines invasive and non-invasive methods for the in vivo assessment of brain metabolism to study brain function under both healthy and pathological conditions. For this purpose, we use a dedicated small animal positron emission tomography (PET) and µCT scanner, which we combine with laser speckle imaging LSI, RGB reflectometry, rapid sampling microdialysis, and electrophysiological methods. In close collaboration with the in vivo NMR group, we provide a portfolio of cutting-edge in vivo imaging modalities that are also integral to research projects of several other groups at the MPI for Metabolism Research. In addition, we also perform clinical studies using a dedicated brain PET scanner and, in collaboration with the translational neurocircuitry group, MRI.

Our research activities cover three major topics:
(1) defining demand-related regulation of brain energy metabolism
(2) identifying network activations
(3) understanding altered regulation of brain metabolism in pathological conditions.

For the analysis of the demand-related regulation of cerebral energy metabolism in rats, a laser speckle imaging and an oxymetry device were mounted on a PET animal bed (left). Responses in glucose metabolism (middle), blood flow, and blood oxygenation (right) to cortical spreading depressions spontaneously occurring after focal cerebral ischemia were recorded simultaneously.

(1) Demand-related regulation of brain energy metabolism

In the healthy brain, the huge increase in energy demand to repolarize cells after cortical spreading depression (CSD) is used to analyze demand-dependent regulation of energy substrate fluxes. Glucose metabolism can be measured quantitatively using [18F]-fluorodeoxyglucose (FDG) as PET tracer. We combine FDG-PET with laser speckle imaging (LSI), RGB reflectometry, and rapid sampling microdialysis (rsMD) to measure blood flow, oxygen metabolism, and extra-cellular concentrations of glucose and lactate, respectively. Based on these data, we then develop a mathematical model for brain metabolism that predicts the time response of substrate concentrations, glycogen breakdown, oxidative and non-oxidative ATP production, etc. after a stimulus. Such modeling approaches can be instrumental in identifying branches of cerebral energy supply that are most sensitive to failure

DREADDS enable the activation of a distinct group of neurons in the mouse. The characteristic pattern of resulting metabolic changes can be detected using FDG-PET. Projected on a mouse brain atlas, the red and blue areas indicate regions with increased and reduced metabolism, respectively.


(2) Neuronal network activations

Novel methods, such as optogenetics or DREADDs (Designer Receptors Exclusively Activated by Designer Drugs), allow the in vivo activation of distinct cell groups. The Neuronal Control of Metabolism group (Brüning Department) applies these methods to cell populations that are involved in the control of whole-body energy metabolism. Using FDG-PET, we analyze the effect of this controlled activation on regional cerebral glucose metabolism in the entire brain. In close collaboration with the in vivo NMR group, the same activation paradigms are studied using resting state fMRI. Moreover, we correlate metabolic with electrical activation using telemetric recording. In this way, the combination of imaging methods allows for the identification of brain regions and networks that are involved in the control of energy homeostasis.

(3) Brain metabolism in pathological conditions

Another focus of our group is to decode pathophysiological processes that potentially contribute to functional and structural loss in the course of brain injury. Studies are mainly performed in animal models of stroke and, in collaboration with the Departments of Neurology and Neurosurgery at the University Hospital Cologne, in stroke patients. More specifically, using rat models of middle cerebral occlusion, we study interactions of processes like CSD and inflammatory responses in brain tissue at risk near the infarct core. A special emphasis is put on the analysis of the relation between inflammation and metabolism using the PET tracers [15O]-H2O for measuring blood flow, [11C]-PK11195 for measuring inflammation in combination with FDG. Clinically, we have been the first to perform studies on the role of spreading depolarization in patients suffering from malignant hemispheric stroke, and we now have evidence that these depolarizations are involved in secondary infarct expansion not only in experimental stroke models but also in human stroke patients. Finally, to detect secondary growth of infarcts in stroke patients, we initiated a prospective study on infarct progression in relation to CSD occurrence in 2012 for which we use sequential MRI technology (DWI and ADC maps).

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