Project Summary / Abstract This project will develop a novel molecular imaging technology that combines positron emission tomography (PET) and ultrasound (US) imaging to enable interactive PET and US scanning with real-time visualization of molecular contrast fused with US images. The motivation is to support an unmet clinical need of optimization of personalized patient therapy. Ultrasound imaging is widely used for tissue biopsy. The biopsied tissue samples permits molecular phenotyping and genotyping in order to better understand the pathobiology and to identify druggable target(s) in diseased tissues to tailor the therapeutical regimen. Although the US-buided biopsy is the current practice, its accuracy can be further improved by incorporating the PET tracer signal localization within the target lesions. The proposed technology builds upon a compact PET device that incorporates a robotic arm to interactively scan a patient to acquire images from any organ-of-interest. Fast image reconstruction engine will enable real- time visualization of molecularly targeting agents in organ/lesion for therapy optimization in individualized precision medicine. An unique advantage of this technology is that it combines a compact PET device with any existing clinical US scanner to enable the proposed PET/US imaging capability. These features will support interventions such as image-guided biopsy by overcoming the hurdle due to the size and cost of clinical PET scanners. The outcome of this effort is a new class of compact molecular imaging (MI) technology that can provide anatomic images, physiologic functions (such as speed of blood flow using Doppler US), and molecularly targeted information for a wide range of point-of-care imaging applications. The real-time PET/US imaging capability will disrupt the status quo and stimulate new applications of novel MI agents and MI-guided interventions, analogous to the invention of PET/CT that completely revolutionized the clinical utility of PET. Importantly, the cost of such system will be a fraction of a clinical PET/CT or PET/MR, making it the most affordable hybrid molecular imaging device for deploying novel applications. Thus the proposed technology development will address current unmet clinical needs and make long lasting scientific and societal impacts for years to come.