MULTIMODAL MRI TO PREDICT DBS MOTOR AND COGNITIVE OUTCOMES IN PARKINSON’S DISEASE

多模态 MRI 预测帕金森病的 DBS 运动和认知结果

• 批准号: 10705789
• 负责人: Melanie A Morrison
• 金额: $ 66.6万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-19 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10705789
• 关键词: Address; Area; Basal Ganglia; Brain; Brain imaging; Clinical; Cognitive; Data; Deep Brain Stimulation; Development; Diffusion Magnetic Resonance Imaging; Effectiveness; Electrodes; Ensure; Equilibrium; Functional Magnetic Resonance Imaging; Ganglia; Globus Pallidus; Goals; Image; Implant; Individual; Intervention; Iron; Location; Magnetic Resonance Imaging; Maps; Measures; Modeling; Motor; Operative Surgical Procedures; Outcome; Parkinson Disease; Pathologic; Patient-Focused Outcomes; Patients; Performance; Pharmaceutical Preparations; Play; Positioning Attribute; Postoperative Period; Predisposition; Radar; Reporting; Resources; Risk; Role; Severity of illness; Structure; Structure of subthalamic nucleus; Symptoms; Techniques; Thalamic structure; Therapeutic; Tissues; Treatment Efficacy; brain surgery; burden of illness; candidate selection; clinical predictors; cognitive ability; connectome; density; experience; feature selection; improved; model building; motor symptom; multimodality; neuroregulation; neurosurgery; novel; outcome prediction; patient population; patient subsets; patient variability; pragmatic implementation; predictive modeling; prognostic; prognostic tool; response; screening; side effect; symptomatic improvement; tool

PROJECT SUMMARY/ABSTRACT Implantable deep brain stimulation (DBS) is a second-line surgical neuromodulation for Parkinson's disease (PD) that can provide significant relief of motor symptoms when medications become less effective, however there are currently no reliable predictors of therapeutic efficacy. While the gold standard suggests that a patient will benefit from DBS if their motor symptoms respond to PD medications with at least 30% improvement, the pre- dictive accuracy of this criteria is variable across studies, and has been disproportionately evaluated in the con- text of only one of two common brain targets for PD. A lack of reliable prognostic criteria to predict overall out- comes with DBS, including risk for cognitive side-effects in balance with motor symptom improvement, has led to variable patient outcomes. Some not considered candidates by the gold standard have been reported to re- spond well to DBS, while others have experienced limited benefit despite strong candidacy and well positioned electrodes. With over 4000 DBS surgeries performed in the US for PD each year, there is an increasing demand for better prognostic tools and streamlined approaches to inform optimal candidate and brain target selection. We aim to address this unmet need by leveraging advanced MRI techniques for improved prediction of patient outcomes after one year of DBS. Previous studies have shown that measures of brain connectivity derived from functional MRI (fMRI) and diffusion tensor imaging (DTI), can be used to predict motor symptom response to DBS. Brain iron accumulation in the basal ganglia, a marker of PD severity derived from susceptibility contrast on T2* MRI, has also shown promise for predicting DBS motor outcomes. However, practical implementation of the results from previous studies in the pre-operative setting is limited by the use of normative connectomes, post-operative electrode coordinates, and less sensitive susceptibility techniques for prediction, along with out- come data from only one of two brain targets for PD. To overcome these limitations, we will use patient-specific pre-operative MRI data to predict outcomes for both PD targets. Specifically, we propose a novel multivariate approach that incorporates fMRI and DTI with quantitative susceptibility mapping (QSM), a superior susceptibility technique to T2* MRI, to enhance prediction accuracy. By using complimentary features of disease burden that are highly relevant to DBS effects on brain connectivity and individual basal ganglia structures, we expect that our approach will improve upon the current gold standard. In 100 patients with PD undergoing DBS, we aim to: 1) evaluate the impact of 3T MRI on clinical prediction of motor outcomes, 2) identify MR and clinical features most relevant for predicting overall versus individual motor and cognitive outcomes, and 3) investigate additional variance in patient outcomes explained by post-operative targeting accuracy. The results will provide a framework in which DBS outcomes can be reliably predicted at the patient and symptom level to inform candidate and target selection, and even therapeutic settings. In this way, we can ensure that resources are geared toward patients most likely to benefit from DBS.

项目总结/摘要 植入式脑深部电刺激（DBS）是治疗帕金森病（PD）的二线手术神经调节 当药物变得不那么有效时，它可以显著缓解运动症状，然而， 目前还没有可靠的疗效预测指标。虽然黄金标准表明， 如果患者的运动症状对PD药物有反应，至少改善30%，则可从DBS中获益， 这一标准的准确性在不同的研究中是可变的，并且在条件中进行了不成比例的评估， PD的两个常见大脑目标之一的文本。缺乏可靠的预后标准来预测总体的预后- 伴随DBS，包括认知副作用的风险与运动症状的改善相平衡， 病人的治疗效果据报道，一些不被黄金标准视为候选人的人重新- 对星展银行的资助很好，而其他银行尽管有很强的候选资格和良好的定位，但受益有限 个电极每年在美国进行的PD DBS手术超过4000例，需求不断增加 更好的预后工具和简化的方法，以告知最佳的候选人和脑靶点选择。 我们的目标是通过利用先进的MRI技术来改善对患者的预测， DBS一年后的结果。以前的研究表明，大脑连接的测量来自于 功能磁共振成像（fMRI）和扩散张量成像（DTI），可用于预测运动症状反应， DBS基底神经节中的脑铁蓄积，一种源自易感性对比的PD严重程度标志物 在T2* MRI上，也显示出预测DBS运动结果的前景。然而，实际执行 在手术前环境中的先前研究的结果受到使用标准连接体的限制， 术后电极坐标，以及用于预测的不太敏感的敏感性技术，沿着， 数据来自帕金森病的两个大脑目标之一。为了克服这些局限性，我们将使用患者特异性 术前MRI数据预测两个PD目标的结局。具体来说，我们提出了一种新的多元 该方法将fMRI和DTI与定量易感性绘图（QSM）相结合，具有上级的易感性 T2* MRI技术，以提高预测准确性。通过利用疾病负担的互补特征， 与DBS对大脑连接和个体基底神经节结构的影响高度相关，我们预计， 我们的做法将改进现行的金本位制。 在100例接受DBS的PD患者中，我们的目的是：1）评价3 T MRI对临床预测的影响， 运动结果，2）识别与预测整体与个体运动最相关的MR和临床特征 和认知结果，以及3）调查术后解释的患者结局的其他差异 瞄准准确性。这些结果将提供一个框架，在该框架中，可以可靠地预测DBS结局。 患者和症状水平，以告知候选人和目标选择，甚至治疗设置。通过这种方式， 我们可以确保资源用于最有可能受益于DBS的患者。