ABSTRACT Dynamic positron emission tomography (PET) imaging with tracer kinetic modeling has the potential to enable quantitative characterization of Alzheimer’s disease and related dementias (ADRD) but suffers from invasive blood sampling and limited spatial resolution for imaging small brain vasculature. The high volumetric resolution (~1 mm3) technology being developed under our R01 “High Spatial Resolution Dedicated Head and Neck PET System based on Cadmium Zinc Telluride” can innovatively be applied to improving ADRD imaging efforts. In this ADRD-supplement, we will augment our novel technology for brain imaging and also develop an optimization-derived input function method (ODIF) to enable our scanner to provide accurate dynamic PET imaging of ADRD and offer clinical insight into early detection of ADRD and the quantification of radiotracer concentrations; resulting in imaging that is less invasive and more accurate. Thus far, our scanner from the R01, has demonstrated a depth of interaction <1 mm, high multiple interaction photon event recovery (accuracy >86%), and fully-functional low-noise in-house readout electronics (trigger on energies above 15 keV with electronic noise of 1% FWHM measured by test pulse injecting charge equivalent of 511 keV). These features minimize the spillover and partial volume effects and improve the carotid-derived input function for brain kinetic quantification. The ODIF method will have the potential to further improve the performance of our dedicated system and it can be applied to many existing brain-dedicated scanners and clinical scanners for ADRD imaging. Therefore, our ultra-high resolution and modular design with high packing fraction (~99%) is excellently positioned to improve ADRD imaging as we will add a neck imager to brain-dedicated systems and have high- quality imaging output.