Model-Based Optimization of Clinical Deep Brain Stimulation

描述（由申请人提供）：丘脑底核（DBS）或苍白球（GPi）的脑深部电刺激（DBS）代表了医学难治性帕金森病（PD）的既定疗法。然而，治疗刺激参数的选择主要基于临床直觉，并且DBS电极设计未针对任一核进行优化。这项生物工程研究资助（PA-06-419）的基本目标是量化PD患者DBS激活的组织（VTA）体积。我们最近开发了在患者特定基础上准确预测DBS VTA所需的计算基础设施（R21 NS-50449 PI：McIntyre）。在本研究的第一个目标中，我们将为NIH申办的临床试验中招募的每例受试者创建DBS的患者特定模型，以比较DBS与GPi DBS的治疗效果（R 01 NS-37959 PI：Vitek）。我们的中心假设是，存在一个目标体积的组织，应该刺激DBS的最大治疗效益，和目标VTA的大小和形状是特定于每个核。在大量患者人群（60 GPi和60 GPi）中DBS激活的不同解剖结构的表征将允许我们定义治疗和非治疗区域的刺激概率图。这些结果将允许定义每个核的治疗目标VTA。在本研究的第二个目的中，我们将使用我们对DBS的目标VTA和GPi DBS的目标VTA的定量知识来开发优化治疗刺激参数设置的临床选择的计算机算法。然后，我们将在20名新患者的队列中前瞻性测试我们的患者特异性理论上最佳刺激参数设置。最后，本研究的第三个目的是设计针对脑电刺激和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形状能够更好地匹配VTA的解剖学和电气约束条件，无论是用于VTA的目标VTA还是用于GPi的目标VTA。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，本研究中开发的方法和技术将直接适用于DBS治疗其他疾病的研究，如特发性震颤、肌张力障碍、癫痫、强迫症、抑郁症和抽动秽语综合征。

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.