Modeling and Simulation of Microdialysis in the Deep Brain Structures

Sammanfattning: Microdialysis is a method for monitoring of the local biochemical environment in a region of interest. The method uses a catheter, mimicking the function of a blood capillary, to sample substances from the surrounding medium through diffusion. A recent application for microdialysis is the sampling of neuroactive substances in the deep brain, or basal ganglia, during deep brain stimulation (DBS) for patients with Parkinson’s disease. The basal ganglia consist of nuclei interconnected by chemical synapses, and it is hypothesized that the levels of neurotransmitter substances around the synapses are affected by DBS treatment. In order to relate the microdialysis data to their anatomical origin and to the effects of DBS, it is suitable to estimate the tissue volume which is sampled during a microdialysis experiment. In this thesis, the maximum tissue volume of influence (TVImax) for a microdialysis catheter was simulated and evaluated using the finite element method (FEM), to allow interpretation of biochemical data in relation to anatomical structures.A FEM model for simulation of the TVImax for a microdialysis catheter placed in grey brain matter was set up, using Fick’s law of diffusion. The model was used to investigate the impact of the analyte diffusion coefficient (D), the tissue tortuosity (λ) and the loss rate constant (k) on the size of the TVImax by regression analysis. Using relevant parameter intervals, the radius of the TVImax of a neurotransmitter was estimated to 0.85 ± 0.25 mm. A microdialysis experiment on calf brain tissue showed agreement with the regression model. A heterogeneous anisotropic FEM model based on diffusion tensor imaging (DTI) showed that the radius of the TVImax may vary by up to 0.5 mm as a consequence of local tissue properties, which was reasonable in relation to the 95% confidence interval from the regression estimation. The TVImax was simulated and patient-specifically visualized in relation to MRI images for four patients undergoing microdialysis in parallel to DBS. The size of the TVImax showed to be relevant in relation to the basal ganglia nuclei, and the obtained microdialysis data indicated that the biochemical response to DBS depends on the catheter position. The simulations of the TVImax were combined with patient-specific DBS electric field simulations, for further interpretation of the results in relation to the effects of DBS.In conclusion, simulations and visualizations of the TVImax allowed relating microdialysis data to its anatomical origin. Detailed knowledge about the parameters affecting the microdialysis sampling volume is valuable for the current application as well as other applications related to the migration of analytes in tissue.