Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Department of Electrical Engineering, University of Michigan, Ann Arbor, MI, USA.
Neuroimage Clin. 2021;29:102518. doi: 10.1016/j.nicl.2020.102518. Epub 2020 Dec 3.
Motor outcomes after subthalamic deep brain stimulation (STN DBS) for Parkinson disease (PD) vary considerably among patients and strongly depend on stimulation location. The objective of this retrospective study was to map the regions of optimal STN DBS for PD using an atlas-independent, fully individualized (N-of-1) tissue activation modeling approach and to assess the relationship between patient-level therapeutic volumes of tissue activation (VTAs) and motor improvement.
The stimulation-induced electric field for 40 PD patients treated with bilateral STN DBS was modeled using finite element analysis. Neurostimulation models were generated for each patient, incorporating their individual STN anatomy, DBS lead position and orientation, anisotropic tissue conductivity, and clinical stimulation settings. A voxel-based analysis of the VTAs was then used to map the optimal location of stimulation. The amount of stimulation in specific regions relative to the STN was measured and compared between STNs with more and less optimal stimulation, as determined by their motor improvement scores and VTA. The relationship between VTA location and motor outcome was then assessed using correlation analysis. Patient variability in terms of STN anatomy, active contact position, and VTA location were also evaluated. Results from the N-of-1 model were compared to those from a simplified VTA model.
Tissue activation modeling mapped the optimal location of stimulation to regions medial, posterior, and dorsal to the STN centroid. These regions extended beyond the STN boundary towards the caudal zona incerta (cZI). The location of the VTA and active contact position differed significantly between STNs with more and less optimal stimulation in the dorsal-ventral and anterior-posterior directions. Therapeutic stimulation spread noticeably more in the dorsal and posterior directions, providing additional evidence for cZI as an important DBS target. There were significant linear relationships between the amount of dorsal and posterior stimulation, as measured by the VTA, and motor improvement. These relationships were more robust than those between active contact position and motor improvement. There was high variability in STN anatomy, active contact position, and VTA location among patients. Spherical VTA modeling was unable to reproduce these results and tended to overestimate the size of the VTA.
Accurate characterization of the spread of stimulation is needed to optimize STN DBS for PD. High variability in neuroanatomy, stimulation location, and motor improvement among patients highlights the need for individualized modeling techniques. The atlas-independent, N-of-1 tissue activation modeling approach presented in this study can be used to develop and evaluate stimulation strategies to improve clinical outcomes on an individual basis.
接受丘脑底核（STN）深部脑刺激（DBS）治疗的帕金森病（PD）患者的运动结果差异很大，并且强烈依赖于刺激位置。本回顾性研究的目的是使用无图谱依赖、完全个体化（N-of-1）组织激活建模方法为 PD 绘制 STN DBS 的最佳刺激区域，并评估患者水平的组织激活治疗体积（VTA）与运动改善之间的关系。
使用有限元分析对 40 名接受双侧 STN DBS 治疗的 PD 患者的刺激诱导电场进行建模。为每位患者生成神经刺激模型，包括其个体的 STN 解剖结构、DBS 导联位置和方向、各向异性组织电导率和临床刺激设置。然后对 VTA 进行基于体素的分析，以绘制最佳刺激位置。测量并比较了 STN 中相对于 STN 更具刺激性和刺激性较小的特定区域的刺激量，这是根据其运动改善评分和 VTA 确定的。然后使用相关分析评估 VTA 位置与运动结果之间的关系。还评估了 STN 解剖结构、活性接触位置和 VTA 位置方面的患者变异性。将 N-of-1 模型的结果与简化的 VTA 模型的结果进行了比较。
组织激活建模将刺激的最佳位置映射到 STN 质心内侧、后方和背部的区域。这些区域向尾状核下的内区（cZI）延伸。在背腹和前后方向上，具有更优和更劣刺激的 STN 之间的 VTA 位置和活性接触位置存在显著差异。治疗性刺激在背侧和后侧方向上明显扩散更多，为 cZI 作为重要的 DBS 靶点提供了额外证据。通过 VTA 测量的背侧和后侧刺激量与运动改善之间存在显著的线性关系。这些关系比活性接触位置与运动改善之间的关系更稳健。患者之间的 STN 解剖结构、活性接触位置和 VTA 位置存在很大差异。球形 VTA 建模无法重现这些结果，并且往往会高估 VTA 的大小。
需要准确描述刺激的扩散情况，以优化 PD 的 STN DBS。患者之间的神经解剖结构、刺激位置和运动改善的高度变异性突出了对个体化建模技术的需求。本研究中提出的无图谱依赖的 N-of-1 组织激活建模方法可用于开发和评估刺激策略，以改善个体的临床结果。
