Pathway targeted deep brain stimulation for Parkinson's disease

描述(申请人提供)：丘脑深部电刺激(DBS)是治疗帕金森氏病(PD)的有效方法。然而，人们对具体的神经通路(S)负责治疗的好处知之甚少。直接刺激超直接通路和/或丘脑底核通路是最有可能成为“靶点”的两个候选通路。因此，该项目的目标是将患者特定的7T成像和神经刺激模型结合在一起，以便能够概率地识别与丘脑DBS患者记录的临床结果指标变化有关的刺激路径。这项研究将依赖于纤维束成像激活模型(TAMS)来指导对30名丘脑DBS患者的临床测试。我们的多学科方法将整合神经成像、神经刺激建模和量化临床结果测量的最新进展，为这些患者定制DBS。第一个目标是在植入手术前获取高分辨率7T磁共振数据。这些图像将提供每个患者无与伦比的解剖特征。第二个目标是为每个受试者创建针对患者的TAM。这些模型将使我们能够在理论上定义集中激活超直接通路或丘脑底核通路的最佳设置。第三个目标将量化或传统临床实践定义的刺激参数所取得的临床结果。这些临床结果将与的预测相结合，创建丘脑底区的概率纤维束成像激活图谱。这项研究的结果将有助于确定最佳的植入位置 DBS电极，并实现刺激参数设置的理论预测，这些参数设置将激活集中在目标通路上和/或避免副作用通路。

DESCRIPTION (provided by applicant): Subthalamic deep brain stimulation (DBS) is an effective for the treatment of Parkinson's disease (PD). However, little is known about the specific neural pathway(s) responsible for therapeutic benefit. Direct stimulation of either the hyperdirect pathway and/or the subthalamopallidal pathway represents two of the most likely candidates as the "target". Therefore, the goal of this project is to combine patient-specific 7T imaging and neurostimulation models together to enable probabilistic identification of the stimulation pathways linked to changes in clinical outcome measures recorded from subthalamic DBS patients. This study will rely on tractography-activation models (TAMs) to guide clinical testing on a cohort of 30 subthalamic DBS patients. Our multi-disciplinary approach will integrate the latest advances in neuroimaging, neurostimulation modeling, and quantitative clinical outcome measures to customize DBS to these patients. The first aim will acquire high- resolution 7T MRI data prior to their implant surgery. These images will provide unparalleled anatomical characterization of each patient. The second aim will create patient-specific TAMs for each subject. These models will enable us to define theoretically optimal settings for focused activation of either the hyperdirect pathway or the subthalamopallidal pathway. The third aim will quantify the clinical outcomes achieved with stimulation parameters defined by either the TAM or traditional clinical practice. These clinical results will be coupled with the TAM predictions to create a probabilistic tractography-activation atlas (PTAA) for the subthalamic region. The results of this study will help identify optimal implantation locations for DBS electrodes, and enable theoretical prediction of stimulation parameter settings that focus activation on the targeted pathways and/or avoid side-effect pathways.