PROJECT SUMMARY—Imaging Core (Core E) Brain imaging plays a critical role in research and care of dementia. The Imaging Core of this PPG on frontotemporal dementia (FTD) has facilitated scientific discovery since its initiation in 2002. Brain imaging has been used by this PPG to characterize different forms of FTD, support diagnosis, and advance knowledge about a variety of brain functions that are particularly affected in FTD, including executive control, social and emotional behavior, speech, and langauge. To achieve these goals, we have used a variety of imaging modalities including structural MRI; diffusion MRI (dMRI); task-free functional MRI (tf-fMRI); and FDG, amyloid, and tau PET. Over the last few years, this core has also focused on the development of longitudinal processing pipelines for multiple imaging modalities to facilitate tracking disease over time. In the next cycle of the PPG, the Imaging Core will continue to support novel uses of brain imaging to validate new assessments of emotion and language (in Project 1: Language and Emotions); develop biological markers of specific proteinopathies (Project 2: Molecular Biomarkers); understand the factors that influence caregiver health (Project 3: Caregiver Health); and understand cognitive resilience, variation in rates of decline, and develop a new clinical trials meaure (Project 4: FTD Heterogeneity). All of these projects will utilize cross-sectional and longitudinal imaging data generated by this core, in particular structural MRI, dMRI, and tf-fMRI. To support this work, the Imaging Core will pursue the following aims: Aim 1: Collection and archiving of images and maintainenance of an image database. We will collect and manage the following MRI sequences in patients with the behavioral variant of FTD; the nonfluent, semantic, and logopenic variants of primary progressive aphasia; corticobasal syndrome; progressive supranuclear palsy-Richardson’s syndrome; and Alzheimer’s diseas;, and in controls: MP-RAGE, FLAIR, dMRI, ASL-perfusion tf-fMRI, and T2-weighted MRI. We will also acquire 18F-PI2620 and 18F-Florbetaben PET scans in patients for whom clinical features and blood biomarkers for AD are inconsistent. Aim 2: Extraction of imaging data to create cross-sectional estimates of structure, function, and molecular pathology. We will generate regional estimates of volume and structural connectivity coinciding with the baseline visit for each participant. Aim 3: Creation of longitudinal MRI-based change data. We will generate regional estimates of volume and structural connectivity coinciding with each visit in each participant, and voxelwise maps of longitudinal change in volume and white matter integrity. Aim 4: Data archiving and analytical consultation. We will work with PPG investigators and staff and other researchers at our center to incorporate imaging data into their analyses.