ABSTRACT: NAPS2 NEUROIMAGING CORE The Neuroimaging Core of the North American Prodromal Synucleinopathy Consortium on RBD, Stage 2 (NAPS2) will ensure that state-of-the-art techniques are applied and that innovative analytic techniques are used. The Neuroimaging Core will be directed by leaders in brain imaging in neurodegenerative diseases with extensive experience supporting the imaging needs of multi-site projects. Many of the Core leaders have collaborated with NAPS investigators on prior research in RBD and synucleinopathies. The prior experience and collaborations within the Neuroimaging Core team will ensure a smooth transition of imaging support for NAPS2. Prior imaging studies of RBD are few and have generally been small, retrospective, or single-site investigations. We provide preliminary data to support all of the imaging modalities that will be utilized in the protocol and demonstrate the soundness of the methods proposed. We will prospectively collect and evaluate multimodal MRI and DaTscan imaging data in over 300 participants with RBD longitudinally, at two time points, with innovative methods to support the Project and advance the field. There are several innovative aspects of this Core, including the use of: 1) multi-shell and multi-band imaging acquisition protocols for collection of high resolution dMRI and rs-fMRI data in reasonable acquisition time, harmonized across multiple sites, 2) quantification of iron load with multi-echo gradient echo (GRE) MRI using quantitative susceptibility mapping and R2* relaxometry, 3) quantification of neuromelanin volume in locus coeruleus and substantia nigra pars compacta using a magnetization transfer contrast neuromelanin-sensitive MRI (NM-MRI) approach with automated image processing and high reproducibility, and 4) DaTscan quantitative analysis using semi-automated processing to provide standardized and harmonized region-to-background and z-score data. The Neuroimaging Core aims are to: 1) establish and maintain harmonized MRI and DaTscan SPECT acquisition protocols at the participating sites, 2) operate a standardized quality control program for MRI and DaTscan, including ongoing image quality monitoring, rating and maintenance, and 3) supply processed cross-sectional and longitudinal data on serial MRIs and DaTscans for the Project focused on predicting phenoconversion, and share these data with the research community. This latter aim includes providing cross-sectional and longitudinal data to the Laboratory of Neuroimaging (LONI) for sharing with outside investigators. All images will be anonymized and directly downloadable from the LONI website. Language will be developed on the NAPS2 and LONI websites to guide outside investigators interested in these data. This clinical dataset will be freely downloadable along with the images for researchers who do not require genetic information for their analyses.