1 Project Summary 2 3 Neurological and mental health disorders cost the United States more than 800 billion each year. Acquiring both 4 PET and MRI images is critical in characterizing conditions such as brain tumors, epilepsy, Alzheimer’s disease, 5 and depression. Today, most patients must undergo two separate studies on PET/CT and MRI systems to 6 acquire PET and MRI data, which is inconvenient for both the patient and referring physician and leads to 7 software-based image fusion error, extra radiation exposure from the CT scan, and typically weeks of delay to 8 acquire both pieces of information necessary to make informed decisions about the disease treatment. Hybrid 9 PET/MRI can acquire PET and MRI studies simultaneously, avoiding the stated issues with two separate studies. 10 Unfortunately, the access to PET/MRI is limited by the high cost of the commercial permanently-integrated 11 PET+MRI systems, which is about $5M for purchasing the system plus a $1.5-2M room renovation cost. Today, 12 only about 50 integrated PET/MRI systems are installed in the US compared to 13,500 installed MRI systems. 13 Moreover, current whole-body PET/CT and PET/MRI systems are limited in spatial resolution and photon 14 sensitivity achievable for brain imaging. To address these needs, PETcoil is developing a portable TOF-PET 15 system that can be inserted into (and removed from) any MRI system to lower the cost to achieve simultaneous 16 PET/MR brain imaging by up to 10-fold compared to procuring a permanently-integrated PET/MRI system. It can 17 be used with multiple MRI systems for different applications (e.g., clinical and research) or employed as a 18 portable stand-alone system to provide flexible PET imaging capability. Moreover, the PET system will achieve 19 over 3 times higher photon sensitivity and over 4 times finer volumetric spatial resolution compared to state-of- 20 the-art PET/MRI systems. In Phase I, we have developed a partial PET ring of detector modules based on a 21 scalable detector module design and verified its performance and MRI compatibility. In Phase II, we will continue 22 our collaboration with Dr. Craig Levin at Stanford University to develop the full PET insert system (Aim 1), validate 23 the performance and MRI compatibility of the PET insert (Aim 2), and conduct first-in-human pilot studies to 24 validate the clinical image quality acquired with the PET insert (Aim 3). The outcome of Phase II will be the first 25 commercial prototype radiofrequency (RF)-penetrable TOF-PET insert for simultaneous PET/MR and validation 26 of its image quality in clinical pilot studies of neurological disorders. The data collected in the first-in-human study 27 will form the basis of the 510(k) submission of the device. We contend that the proposed PET insert, which allows 28 institutions with at least one MRI system to achieve PET/MRI with up to 10-fold lower cost and superior PET 29 image quality compared to current permanently-integr...