Majtanik Milan, Gielen Frans, Coenen Volker Arnd, Lehtimäki Kai, Mai Jürgen Konrad
MRX-Brain GmbH, Moritz-Sommer-Str. 4., 40225 Duesseldorf, Germany; Department of Informatics, Heinrich Heine University of Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany.
Medtronic Bakken Research Center, Endepolsdomein 5, 6229 GW Maastricht, the Netherlands.
Neuroimage. 2022 Nov 15;262:119551. doi: 10.1016/j.neuroimage.2022.119551. Epub 2022 Aug 7.
Deep Brain Stimulation (DBS) in the Anterior Nucleus of the Thalamus (ANT) has been shown to be a safe and efficacious treatment option for patients with Drug-Resitant focal Epilepsy (DRE). The ANT has been selected frequently in open and controlled studies for bilateral DBS. There is a substantial variability in ANT-DBS outcomes which is not fully understood. These outcomes might not be explained by the target location alone but potentially depend on the connectivity of the mere stimulation site with the epilepsy onset-associated brain regions. The likely sub-components of this anatomy are fiber pathways which penetrate or touch the ANT region and constitute a complex and dense fiber network which has not been described so far. A detailed characterization of this ANT associated fiber anatomy may therefore help to identify which areas are associated with positive or negative outcomes of ANT-DBS. Furthermore, prediction properties in individual ANT-DBS cases might be tested. In this work we aim to generate an anatomically detailed map of candidate fiber structures which might in the future lead to a holistic image of structural connectivity of the ANT region.
To resolve the various components of the complex fiber network connected to the ANT we used a synthetic pathway reconstruction method that combines anatomical fiber tracking with dMRI-based tractography and iteratively created an anatomical high-resolution fiber map representing the most important bundles related to the ANT.
The anatomically detailed 3D representation of the fibers in the ANT region generated with the synthetic pathway reconstruction method incorporates multiple anatomically defined fiber bundles with their course, orientation, connectivity and relative strength. Distinctive positions within the ANT region have a different hierarchical profile with respect to the stimulation-activated fiber bundles. This detailed connectivity map, which is embedded into the topographic map of the MNI brain, provides novel opportunities to analyze the outcomes of the ANT-DBS studies.
Our synthetic reconstruction method provides the first anatomically realistic fiber pathway map in the human ANT region incorporating histological and structural MRI data. We propose that this complex ANT fiber network can be used for detailed analysis of the outcomes of DBS studies and potentially for visualization during the stimulation planning procedures. The connectivity map might also facilitate surgical planning and will help to simulate the complex ANT connectivity. Possible activation patterns that may be elicited by electrodes in different positions in the ANT region will help to understand clinically diverse outcomes based on this new dense fiber network map. As a consequence this work might in the future help to improve individual outcomes in ANT-DBS.
丘脑前核（ANT）深部脑刺激（DBS）已被证明是药物难治性局灶性癫痫（DRE）患者的一种安全有效的治疗选择。在开放性和对照研究中，ANT常被选用于双侧DBS。ANT-DBS的结果存在很大差异，目前尚未完全了解。这些结果可能不能仅由靶点位置来解释，而可能取决于单纯刺激部位与癫痫发作相关脑区的连接性。这种解剖结构可能的子成分是穿透或接触ANT区域的纤维束，它们构成了一个复杂而密集的纤维网络，目前尚未被描述。因此，对这种与ANT相关的纤维解剖结构进行详细表征，可能有助于确定哪些区域与ANT-DBS的阳性或阴性结果相关。此外，还可以测试个体ANT-DBS病例中的预测特性。在这项工作中，我们旨在生成候选纤维结构的详细解剖图谱，这可能在未来形成ANT区域结构连接性的整体图像。
为了解析与ANT相连的复杂纤维网络的各个组成部分，我们使用了一种合成通路重建方法，该方法将解剖纤维追踪与基于dMRI的纤维束成像相结合，并迭代创建了一个解剖高分辨率纤维图谱，代表了与ANT相关的最重要的纤维束。
用合成通路重建方法生成的ANT区域纤维的详细解剖三维表示包含多个解剖学定义的纤维束，以及它们的走行、方向、连接性和相对强度。ANT区域内不同位置相对于刺激激活的纤维束具有不同的层次特征。这个嵌入到MNI脑地形图中的详细连接图谱，为分析ANT-DBS研究的结果提供了新的机会。
我们的合成重建方法提供了人类ANT区域首个结合组织学和结构MRI数据的解剖学上逼真的纤维通路图谱。我们提出，这个复杂的ANT纤维网络可用于详细分析DBS研究的结果，并可能在刺激规划过程中用于可视化。连接图谱也可能有助于手术规划，并将有助于模拟复杂的ANT连接性。ANT区域不同位置的电极可能引发的可能激活模式，将有助于基于这个新的密集纤维网络图理解临床上多样的结果。因此，这项工作未来可能有助于改善ANT-DBS的个体治疗效果。
