Patient-adjustable MRI technology for high-resolution imaging of deep brain stimulation

项目总结/摘要 脑深部电刺激（DBS）是美国食品药品监督管理局（FDA）批准的神经外科手术， 已经成为耐药性帕金森病（PD）的金标准治疗方法， 一种常见的神经退行性疾病，影响的患者数量超过了 被诊断为多发性硬化症、肌肉萎缩症和卢伽雷氏病。DBS也用于治疗 难治性慢性疼痛是一种使人衰弱的疾病，影响着1亿多美国人。尽管 DBS的一般有效性，其潜在的作用机制仍不清楚。不确定性仍然存在 哪些回路受到影响，哪些确切的纤维束需要作为目标，以及最有效的刺激 议定书神经影像学的细致使用，既用于靶点验证，也用于监测治疗诱导的 受影响的大脑网络的功能连接的变化是解释临床症状的重要步骤。 结果，测试新的假设，从而设计增强的治疗方案。在这 在这方面，磁共振成像（MRI）作为一种高分辨率、非侵入性的 成像工具，可以帮助解决这些悬而未决的问题。然而，射频的相互作用 (RF)MRI扫描仪和植入电极的磁场造成了严重的安全隐患， MRI对DBS患者的适用性。因此，DBS患者可用的MRI方法有限， 分辨率，并遭受严重的图像伪影，混淆了受影响的功能连接的研究 大脑网络 该计划开发并验证了针对患者特定需求定制并验证的新型MRI方法 几何形状，这将使MRI承担有关机制和靶向的临床问题， DBS治疗。因此，该项目的具体目标是：（1）开发和验证患者可调整的， 可重新配置的MRI发射线圈，与32通道紧密配合的大脑阵列集成， 射频场和植入电极的不必要的相互作用高达100倍，低于 目前可用的系统，同时提高信噪比（SNR）高达四倍的水平， 皮质结构;（2）开发的方法与全面的电磁验证 模拟和体模实验，以确定成像参数的安全范围并优化临床 成像协议;和（3）设计使用已开发的技术来增强预测的方法 晚期帕金森病患者皮质-纹状体回路功能连接模式的改变。 该项目的近期目标是开发和优化MRI方法，以增强结构和 在FDA批准用于DBS成像的场强下对PD影响的脑网络进行功能成像 并将这些方法用于增强晚期PD患者皮质-纹状体环路的功能定位， 患者研究结果将作为长期目标的出发点， DBS引起的大脑功能结构的变化。

Project Summary/Abstract Deep brain stimulation (DBS) is a Food and Drug Administration (FDA) approved neurosurgical procedure that has emerged as the gold-standard treatment for drug-resistant Parkinson's disease (PD), the second most common neurodegenerative disorder, which affects more patients than the combined number of people diagnosed with multiple sclerosis, muscular dystrophy, and Lou Gehrig's disease. DBS is also used to treat refractory chronic pain, a debilitating condition that affects more than 100 million Americans. Despite the general effectiveness of DBS, its underlying mechanisms of action are still unclear. Uncertainties remain about which circuits are affected, which exact fiber bundles need to be targeted, and the most efficacious stimulation protocol. The meticulous use of neuroimaging, both for target verification and for monitoring treatment-induced changes in the functional connectivity of affected brain networks is an essential step in interpreting clinical outcomes, testing new hypotheses and, consequently, designing enhanced therapeutic protocols. In this regard, magnetic resonance imaging (MRI) appears excellently poised as a high-resolution, non-invasive imaging tool, which could help address these open questions. However, the interaction of the radiofrequency (RF) fields of MRI scanners and the implanted electrodes imposes serious safety hazards that restrict the applicability of MRI for DBS patients. As a result, available MRI methodologies for DBS patients are limited in resolution and suffer from severe image artifacts that confound studies of the functional connectivity of affected brain networks. This program develops and validates novel MRI methodologies tailored and validated for patient-specific geometries, which will bring MRI to bear on the clinical questions regarding the mechanism and targeting of DBS treatment. The specific aims of this project are, therefore: (1) to develop and validate a patient-adjustable, reconfigurable MRI transmit coil, integrated with a 32-channel close-fit brain array, which enables the reduction of the unwanted interaction of RF fields and implanted electrodes up to 100-fold below levels produced by currently available systems, while increasing the signal-to-noise ratio (SNR) up to four times at the level of cortical structures; (2) the validation of developed methodologies with comprehensive electromagnetic simulations and phantom experiments to determine the safe range of imaging parameters and optimize clinical imaging protocols; and (3) devising methodologies which use the developed technology to enhance prediction of altered patterns of functional connectivity of the cortico-striatal loops in advanced Parkinson's patients. The immediate goal of this project is to develop and optimize MRI methodologies to enhance structural and functional imaging of PD-affected brain networks at field intensities that are FDA approved for DBS imaging and to apply these methodologies for enhanced functional mapping of cortico-striatal loops in advanced PD patients. The outcome serves as the launching point for the long-term goal of enabling the study of dynamic DBS-induced changes in the functional architecture of the brain.