Imaging Biomarkers for Parkinson's Disease using 7 Tesla MRI

描述(申请人提供)：帕金森氏病(PD)是最常见的严重运动障碍，影响超过1%的60岁以上的成年人。仅在美国，每年与PD相关的总成本估计就超过60亿美元。随着老年人在人口中所占比例的增加，帕金森病对我们的医疗保健系统构成了越来越大的负担。帕金森病的早期症状与黑质多巴胺神经元的选择性丢失有关，但帕金森病的病因尚不清楚。虽然运动表现的早期治疗通常是相当成功的，但疾病继续进展，非运动表现的发展增加了残疾。一种正在获得越来越多关注的策略是开发神经保护性疗法，以减缓或阻止进展。神经保护的应用将在疾病的早期应用具有最大的益处。这就需要越来越灵敏的方法来检测和描述帕金森病的病理特征。成像为帕金森病患者或有风险的患者提供了在体评估的新机会。在过去的二十年里，人们进行了大量的磁共振成像研究，以检测与帕金森病相关的脑深部核团的形态变化。不幸的是，这些MR研究的结果一直是有争议和不一致的，主要是因为MRI分辨率的限制。最近7T磁共振成像技术的进步使我们能够以显著提高的对比度和分辨率成像大脑深部核团；因此，我们能够表征和量化帕金森病患者这些结构的病理变化。这项建议的主要目标是开发和评估以下方法：(1)使用7T磁共振成像对脑深部核团的病变进行量化和表征，以及(2)通过连续的MRI扫描确定量化变化的可靠性。这一建议的基本原理是基于这样一个事实，即高分辨率7T磁共振成像使大脑深部核团的可靠分割和量化成为可能，并潜在地允许表征结构随时间的变化。这些信息最终将有助于促进我们对帕金森病进展的了解，并有助于开发新的方法来监测新疗法的效果。这项拟议的研究具有创新性，因为我们应用了新的7T磁共振成像和分割技术，可以量化与帕金森病相关的脑深部核团形态的变化。我们的中心假设是，MR将允许对PD病理进行精确的体内结构分析，这将与临床表现密切相关。这项建议的具体目的是评估和比较：(1)7T磁共振成像的帕金森病患者脑深部结构的测量可靠性(观察者之间和观察者内部)；(2)通过横断面研究，评估帕金森病患者和对照受试者脑深部结构的差异。第二个探索性目标是测量特定的结构变化(和疾病进展)，以确定未来纵向研究所需的样本量。与公众健康相关：随着7T磁共振图像提供的图像对比度和分辨率显著提高，我们将开发和优化磁共振成像技术，以允许可靠地测量帕金森病患者的深部大脑结构。这将有助于我们加深对帕金森病疾病进展过程中结构-功能关系的理解。

DESCRIPTION (provided by applicant): Parkinson's disease (PD) is the most common serious movement disorder and affects over 1% of adults older than 60 years of age. In the United States alone, the total annual costs related to PD are estimated to exceed 6 billion dollars. With the increasing proportion of elderly in the population, PD represents a growing burden on our health care system. The early symptoms of PD are associated with a selective loss of dopamine neurons in the substantial nigra but the etiology of PD is unknown. Although early treatment of motor manifestations is usually quite successful, the disease continues to progress and the development of non-motor manifestations adds to disability. One strategy that is gaining increasing attention is the development of neuroprotective therapies that would slow, or halt progression. The application of neuroprotection would have maximal benefit applied early in the disease. This requires increasingly sensitive methods of detection and characterization of PD pathology. Imaging offers new opportunities for in vivo assessment of patients with PD, or at risk. In the past two decades, a number of MR imaging studies have been performed to detect changes in the morphology of deep brain nuclei associated with PD. Unfortunately, the results of these MR studies have been controversial and inconsistent, primarily because of MRI resolution limitations. Recent technical advances in 7T MR imaging now allows us to image deep brain nuclei with significantly improved contrast and resolution; thus, we are able to characterize and quantify pathological changes in these structures in PD. The primary objective of this proposal is to develop and evaluate methods for: (1) quantification and characterization of pathological changes in deep brain nuclei using 7T MRI and (2) determine the reliability of the quantification of changes over time through serial MRI scans. The rationale for this proposal is based on the fact that high resolution 7T MR imaging makes both reliable segmentation and quantification of deep brain nuclei possible as well as potentially permitting characterization of structural changes over time. This information ultimately will help advance our understanding of the progression of PD and contribute to the development new methods to monitor the effects of new therapies. This proposed research is innovative in that we have applied new 7T MR imaging and segmentation techniques which can quantify changes in deep brain nuclei morphology in association with PD. Our central hypothesis is that MR will permit a precise in vivo structural analysis of PD pathology that will correlate closely with clinical manifestations. The specific aims of this proposal are to evaluate and compare: (1) the measurement reliabilities (between and within observers) of deep brain structures in PD patients imaged with 7T MR; and (2) the differences in the deep brain structures between PD and control subjects through a cross- sectional study. A secondary exploratory aim is to measure specific structural changes (and disease progression) over time to determine the sample size required for a future longitudinal study. PUBLIC HEALTH RELEVANCE: With the significantly improved image contrast and resolution offered by 7T MR images, we will develop and optimize MR imaging techniques to allow for reliable measurement of deep brain structures in patients with Parkinson disease. This will help advance our understanding of the structure-function relationships in the disease progression of Parkinson disease.