Web-based Automated Imaging Differentiation of Parkinsonism

摘要 在全球范围内，被诊断为帕金森症的人数有了相当大的增长。 据估计，从1990年到2015年，帕金森氏症的确诊人数翻了一番，超过6例 目前有100万人携带这种诊断，到2040年，将有1200万人和1420万人被诊断出来 患有帕金森症。帕金森病(PD)、多系统萎缩帕金森变异症(MSAP)和 进行性核上性瘫痪(PSP)是帕金森氏症的神经退行性形式，可能很难 诊断是因为他们都有相似的运动和非运动特征，而且每个人都有更高的机会 罹患痴呆症。在帕金森病诊断的前五年，大约58%的帕金森病被误诊，其中 大约一半的误诊是MSA或PSP。由于PD、MSAP和PSP需要独特的治疗方案 而不同的药物，以及测试新药的临床试验需要正确的诊断，有一个 迫切需要临床准备和临床试验准备的标记物用于PD、MSAp和PSP的鉴别诊断。 在过去的十年中，我们开发了扩散成像作为区分帕金森病的创新生物标志物， MSAp和PSP。在本计划中，我们将利用我们丰富的经验来创建一个基于Web的软件工具 它可以处理来自世界任何地方的扩散成像数据。我们将在以下位置传播和测试该工具 帕金森氏症(PD、MSAp、PSP)最大的潜在参与者队列，与 帕金森研究小组。之所以在帕金森研究小组网络中测试这一点，是因为他们是 评估帕金森病第二阶段和第三阶段临床试验的社区。这个基于Web的软件工具 将能够读取原始扩散成像数据，执行质量保证程序，分析 使用经过验证的管道的数据，并提供成像指标和诊断概率。我们将测试 通过在21个地点招收315名受试者(105名PD，105名MSAP，105名PSP)来执行WAID-P 帕金森研究小组。每个站点将进行成像、临床评估、诊断，并将数据上传到 基于Web的软件工具。临床诊断会对诊断算法和成像造成盲目 诊断将与训练有素的神经科医生的运动障碍诊断相比较。我们还将招收一部分 以确定病理确认，并测试算法对患有 尸检诊断。最终结果将是将经过验证的诊断算法传播到 帕金森神经学和放射学社区，并在一个网站上向所有人提供。

SUMMARY Across the globe, there has been a considerable growth in the number of people diagnosed with Parkinsonism. Estimates indicate that from 1990 to 2015 the number of Parkinsonism diagnoses doubled, with more than 6 million people currently carrying the diagnosis, and by year 2040, 12 and 14.2 million people will be diagnosed with Parkinsonism. Parkinson’s disease (PD), multiple system atrophy Parkinsonian variant (MSAp), and progressive supranuclear palsy (PSP) are neurodegenerative forms of Parkinsonism, which can be difficult to diagnose as they share similar motor and non-motor features, and they each have an increased chance of developing dementia. In the first five years of a PD diagnosis, about 58% of PD are misdiagnosed, and of these misdiagnoses about half have either MSA or PSP. Since PD, MSAp, and PSP require unique treatment plans and different medications, and clinical trials testing new medications require the correct diagnosis, there is an urgent need for both clinic ready and clinical-trial ready markers for differential diagnosis of PD, MSAp, and PSP. Over the past decade, we have developed diffusion imaging as an innovative biomarker for differentiating PD, MSAp, and PSP. In this proposal, we will leverage our extensive experience to create a web-based software tool that can process diffusion imaging data from anywhere in the world. We will disseminate and test the tool in the largest prospective cohort of participants with Parkinsonism (PD, MSAp, PSP), working closely with the Parkinson Study Group. The reason to test this in the Parkinson Study Group network, is because they are the community that evaluates Phase II and Phase III clinical trials in Parkinsonism. This web-based software tool will be capable of reading raw diffusion imaging data, performing quality assurance procedures, analyzing the data using a validated pipeline, and providing imaging metrics and diagnostic probability. We will test the performance of the wAID-P by enrolling 315 total subjects (105 PD, 105 MSAp, 105 PSP) across 21 sites in the Parkinson Study Group. Each site will perform imaging, clinical scales, diagnosis, and will upload the data to the web-based software tool. The clinical diagnosis will be blinded to the diagnostic algorithm and the imaging diagnosis will be compared to the movement disorders trained neurologist diagnosis. We will also enroll a portion of the cohort into a brain bank to ascertain pathological confirmation and to test the algorithm against cases with post-mortem diagnoses. The final outcome will be to disseminate a validated diagnostic algorithm to the Parkinson neurological and radiological community and to make it available to all on a website.