深腦刺激系統應用於帕金森氏病之 模擬、分析與控制

Abstract

近年，台灣人口老化的問題日趨嚴重。隨著人口高齡化，國人對於多重慢性疾病日趨重視，帕金森氏病即是一個典型的例子。臨床上，深腦刺激系統常用於治療帕金森氏病。進行深腦刺激時，選擇適當刺激位置及適當刺激參數以達到最佳刺激效果是關鍵的議題。基於此動機，本論文進行最佳刺激位置的選擇及最佳刺激參數的調整，以期加強目前現有深腦刺激系統之功效。最佳刺激位置的選擇是利用全身麻醉的患者於正中神經刺激下，視丘下核之神經訊號進行分析，並找出與運動相關的神經位置。分析結果顯示，視丘下核之神經訊號於正中神經刺激下，神經訊號的種類及功率譜密度的變化皆較未刺激前之訊號有顯著的變化，此變化可作為選擇刺激電極放置位置的特徵，此分析方式亦可解決臨床上深部腦刺激系統中刺激電極在空間中自由度選擇較小之限制；最佳刺激參數的調整則需先建構深腦刺激系統於大腦環境之模型，利用此模型使用有限元素分析方式進行刺激量的估測，再透過此估測量應用最佳化理論進行刺激參數的調整。此外，我們更進一步地透過臨床實驗探討刺激參數與病人肢體反應的關係。實驗結果顯示，患者使用此方法所得之刺激參數進行深腦刺激，確實可以達到最佳刺激效果、最小刺激副作用及最低電池消耗量的目標。透過此刺激位置選擇及刺激參數調整的研究，提供深腦刺激系統更完善的系統功能，也得以增強現有刺激系統的效用及更進一步地改善帕金森氏症患者的生活品質。

The problem of aging population becomes more and more serious in Taiwan. Accompanying with aging population, multi-chronic diseases, such as Parkinson’s disease (PD), have received much attention. In clinical practices, deep brain stimulation system is often utilized for PD treatment. In deep brain stimulation, how to select suitable stimulation location and parameters for better therapy efficiency are very critical. Based on these motivations, the dissertation is dedicated to exploring the selection of optimal stimulation location and the adjustment of optimal stimulation parameters for improving the DBS system. The optimal stimulation location is selected via analyzing the neuronal activities in the subthalamic nucleus of a patient with PD in general anesthesia with median-nerve stimulation and identifying the neurons related to motor control. The analysis shows that spiking patterns and power spectrum density of neuronal activities vary evidently with median-nerve stimulation. The variety can be taken as features to determine the stimulation electrode location. The approach also addresses the challenge of limited spatial freedom in deep brain stimulation system. In addition, a computerized model of brain-electrode interface is established for optimal stimulation parameters adjustment. Through the model, the amount of stimulation region can be estimated by finite element analysis and further utilized to determine stimulation parameters via the optimization scheme. Moreover, the relationship between stimulation parameters and patient’s clinical motor response is explored in vivo test. The experimental results show that patients treated with adjusted stimulation parameters can achieve the goals of maximizing therapy benefit, minimizing side effects and minimizing power consumption of the battery. Through the study of selecting optimal stimulation location and adjusting optimal stimulation parameters, it provides the DBS system more complete functions for increasing the DBS efficiency and further improving the life quality of PD patients.