Model-Based Optimization of Clinical Deep Brain Stimulation

描述（由申请人提供）：丘脑底核（STN）或内白球（GPi）的深部脑刺激（DBS）是医学上难治性帕金森病（PD）的既定治疗方法。然而，治疗刺激参数的选择主要基于临床直觉，DBS电极的设计并未针对任何一个核进行优化。本生物工程研究基金（PA-06-419）的基本目标是量化DBS在PD患者中的组织激活（VTA）体积。我们最近开发了必要的计算基础设施，以准确预测患者特定的DBS VTA （R21 NS-50449 PI: Mclntyre）。在研究的第一个目标中，我们将为参加NIH赞助的临床试验的每个受试者创建一个患者特异性DBS模型，比较STN DBS和GPi DBS的治疗效果（R01 NS-37959 PI: Vitek）。我们的中心假设是存在一个目标体积的组织，该组织应该被刺激以获得DBS的最大治疗效果，目标VTA的大小和形状对每个核都是特定的。在大量患者群体（60 STN和60 GPi）中对DBS激活的不同解剖结构进行表征，将使我们能够定义刺激治疗和非治疗区域的概率图。这些结果将有助于确定每个细胞核的治疗靶点VTA。在本研究的第二个目标中，我们将利用我们对STN DBS和GPi DBS的目标VTA的定量知识来开发计算机算法，以优化治疗刺激参数设置的临床选择。然后，我们将在20名新患者的队列中前瞻性地测试我们的患者特异性理论最佳刺激参数设置。最后，本研究的第三个目标是设计针对STN和GPi定制的DBS电极。我们将对DBS电极的设计进行逆向工程，使其生成的VTA形状更好地匹配STN或GPi目标VTA的解剖和电约束。从该项目中获得的科学知识将促进DBS治疗PD的临床应用。此外，本研究开发的方法和技术将直接适用于其他疾病如特发性震颤、肌张力障碍、癫痫、强迫症、抑郁症和图雷特综合征的DBS研究。

DESCRIPTION (provided by applicant): Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus inturnus (GPi) represent established therapies for medically refractory Parkinson's disease (PD). However, selection of therapeutic stimulation parameters is primarily based on clinical intuition, and the DBS electrode design is not optimized to either nucleus. The fundamental goal of this Bioengineering Research Grant (PA-06-419) is to quantify the volume of tissue activated (VTA) by DBS in PD patients. We recently developed the computational infrastructure necessary to accurately predict the DBS VTA on a patient-specific basis (R21 NS-50449 PI: Mclntyre). In the first aim of the study we will create a patient-specific model of DBS for each subject enrolled in an NIH sponsored clinical trial comparing the therapeutic efficacy of STN DBS to GPi DBS (R01 NS-37959 PI: Vitek). Our central hypothesis is that there exists a target volume of tissue that should be stimulated for maximal therapeutic benefit from DBS, and the size and shape of the target VTA is specific to each nucleus. Characterization of the different anatomical structures activated by DBS across a large patient population (60 STN and 60 GPi) will allow us to define probabilistic maps of therapeutic and non-therapeutic regions for stimulation. These results will allow definition of the therapeutic target VTA for each nucleus. In the second aim of this study we will use our quantitative knowledge of the target VTA for STN DBS and the target VTA for GPi DBS to develop computer algorithms that optimize the clinical selection of therapeutic stimulation parameter settings. We will then prospectively test our patient-specific theoretically optimal stimulation parameter settings on a cohort of 20 new patients. Finally, the third aim of this study will be to design DBS electrodes that are customized to the STN and GPi. We will reverse engineer the design of the DBS electrode such that they generate a VTA shape that better matches the anatomical and electrical constraints of either the target VTA for STN or target VTA for GPi. The scientific knowledge gained from this project will advance the clinical utility of DBS for PD. In addition, the methodology and technology developed in this study will be directly applicable to the study of DBS in other disorders such as essential tremor, dystonia, epilepsy, obsessive-compulsive disorder, depression, and Tourette's syndrome.