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.

NARRATIVE In this proposal, we will be developing, disseminating, and evaluating a web-based software tool that can perform MRI analyses for the diagnostic accuracy of Parkinsonism. Our goal is to leverage our years of experience and algorithm development, to test a prospective cohort of Parkinson’s disease, Multiple System Atrophy, and Progressive Supranuclear Palsy. We expect that at the end of the project, we will have validated a web-based software tool that can use MRIs from different vendors to read, analyze, and predict the diagnosis of different forms of Parkinsonism.