Identifying Imaging Biomarkers of Deep Brain Stimulation Treatment Outcome in Patients with Movement Disorders

脑深部刺激(DBS)是一种临床神经外科手术，涉及将电极植入大脑中特定的靶区。DBS将自己作为一种成熟的治疗选择，用于治疗各种疾病的症状，包括帕金森氏病(PD)、特发性震颤(ET)、肌张力障碍、抽动症、癫痫和强迫症。DBS在临床应用中取得巨大成功的一个领域是缓解与运动障碍相关的衰弱运动症状。特别是，DBS已被广泛用于治疗PD、ET和肌张力障碍患者，成为药物难治性患者的主要治疗选择。关键是，DBS手术后的疗效与运动症状的改善存在很大差异，导致最佳和次优结果。DBS的广泛变异性可能是由于多种因素，包括神经外科靶区、脑结构和功能的异质性、DBS刺激参数、疾病表型和疾病严重程度。DBS的可变性也严重混淆了这一事实，因为目前还没有完全了解DBS工作的根本机制。目前正在探索的一种可能的途径是通过神经成像来揭示手术后DBS结果的可变性。尤其是磁共振成像(MRI)，这项技术为我们了解大脑变化与大量神经疾病和障碍之间的关系奠定了基础。该项目的具体目的是利用常规收集的术前MRI来确定临床有用的、新的术前生物标志物来预测DBS的疗效。特别是，该项目旨在利用各种先进的神经成像和机器学习分析技术，评估与大脑形态和结构连通性差异有关的数据。各种运动障碍的术前患者数据将在沃尔顿中心NHS基金会信托基金和开放获取的储存库中获得。该项目对改善DBS的临床运动结果具有深远的影响。确定对治疗有最佳反应的患者将有助于未来选择DBS候选人，改善卫生保健系统内的疾病管理。了解和改善反应不佳的患者的结果对于提高生活质量和为疾病管理提供信息也是至关重要的。此外，识别可被证明对生物标志物预测有用的成像方式可以被纳入临床扫描方案。最后，本项目希望补充我们对DBS在不同运动障碍中的可操作性机制的理解。

Deep Brain Stimulation (DBS) is a clinical, neurosurgical procedure, involving the implantation of electrodes to specified target regions in the brain. DBS offers itself as an established treatment option for symptoms across a wide range of disorders, including Parkinson's disease (PD), Essential tremor (ET), Dystonia, Tourette Syndrome, Epilepsy and Obsessive-Compulsive Disorder. An area of clinical application where DBS has seen profound success is in the alleviation of debilitating motor symptoms associated with motor disorders. Specifically, DBS has been used extensively to treat patients with PD, ET, and Dystonia, becoming the primary therapeutic option for pharmacologically refractory patients.Crucially, there is a wide variability in the post-operative efficacy of DBS with relation to the improvement in motor symptoms, resulting in optimal and sub-optimal outcomes. Wide variability of DBS is likely due to a multitude of factors, including the neurosurgically targeted area, heterogeneity of brain structure and function, DBS stimulation parameters, disease phenotype, and disease severity. DBS variability is also critically confounded by the fact that the underlying mechanisms for exactly how DBS works are not fully understood at this current moment in time.One possible avenue being explored to shed light on the variability in post-surgical DBS outcomes is through Neuroimaging. Magnetic Resonance Imaging (MRI) in particular, is a technique that has paved our understanding of the relationship between changes in the brain and a plethora of neurological diseases and disorders. This project is specifically aimed at utilising routinely collected presurgical MRI to ascertain clinically useful, novel preoperative biomarkers to predict DBS efficacy. In particular, the project aims to assess data pertaining to differences in brain morphology and structural connectivity, utilising various advanced neuroimaging and machine learning analysis techniques. Preoperative patient data from a variety of movement disorders will be acquired at the Walton Centre NHS Foundation Trust and from open-access repositories.This project has far-reaching ramifications for improving clinical motor outcomes from DBS. Identifying patients who will be optimally responsive to treatment will aid the future selection of DBS candidates, improving disease management within health care systems. Understanding and improving outcomes for patients who respond sub-optimally is also critical to improve quality of life and inform disease management. Furthermore, identifying imaging modalities that can prove useful for biomarker prediction can be incorporated into clinical scanning protocols. Finally, this project hopes to supplement our understanding of DBS operativity mechanisms across different movement disorders.