Physics

Neuroscience

Image resolution

Nuclear medicine

Mathematics

Parametric statistics

Optics

Statistics

Engineering

Artificial intelligence

Psychology

Medical physics

Sensitivity (control systems)

Electronic engineering

Positron emission tomography

Human brain

Computer science

Neuroimaging

Medicine

Detector

Journal of Nuclear Medicine

1120 null Objectives: null null PET human brain imaging has evolved dramatically, with the availability of a vast array of specific radiotracers, leading to numerous imaging paradigms to measure a wide range of brain targets and to assess neurotransmitter and receptor dynamics. Brain-dedicated PET systems could offer important advantages over currently available whole-body PET systems in terms of sensitivity and resolution. However, state-of-the-art for dedicated brain PET has not progressed beyond the HRRT, designed over 20 years ago. Therefore, there is a compelling need to build next generation human brain PET systems that incorporate significant advances in sensitivity and effective spatial resolution. This is the goal of the NeuroEXPLORER (NX) project.Methods: Experience with >4500 human brain HRRT studies at Yale has shown that sensitivity is a major limiting factor, i.e., radioactivity images are often noisy, and the best possible resolution cannot be achieved due to limited counts. Our experience with the total-body uEXPLORER system at UC Davis has shown that ultra-high sensitivity enables high SNR for short scans and parametric imaging at high spatial resolution with no smoothing. Thus, our primary NX design goals are three-fold. 1) Ultra-high sensitivity, to be achieved by maximizing the coincidence acceptance angle, with a long axial field-of-view (aFOV) together with excellent sensitivity-boosting time-of-flight (TOF). 2) To achieve exceptional image resolution through reduction in the size of detector elements, depth of interaction (DOI) readout, and corrections for inter-crystal scatter (ICS). Significant improvements in spatial resolution are needed to image small structures, reduce the partial volume effect, and measure the input function (IF) in the carotid arteries. 3) Head motion is a critical limit to image resolution and quantification accuracy. Thus, our third NX design goal is continuous motion tracking and correction. null Results: null null The NX design is a cylinder with diameter and aFOV of ~50 cm. The system consists of 5 complete detector rings, each with 20 modules. An additional 6th ring has 3 blocks removed from each side to accommodate shoulders, to place the brain in the center of the aFOV. The 18-mm deep LYSO crystals have an in-plane dimension of 1.5 mm, leading to a simulated resolution of 1.6-1.8 mm. These are organized in micro-blocks of 8 crystals read out by 4 SiPMs with energy resolution null null 10-fold higher effective sensitivity than the HRRT for the brain, with an even greater advantage for the carotids. To provide even higher resolution (~ 1mm) to measure the carotid IF, the NX can support additional ultra-high resolution detector panels. Head motion tracking is performed with a real-time stereovision system using structured light. Initial comparison to the Vicra (which uses a tool mounted on the subject’s head) is underway with existing scanners. To optimize reconstruction and quantification accuracy, high-resolution brain simulations and novel phantom configurations are being designed.Conclusions: A next-generation ultra-high performance human brain PET, the NeuroEXPLORER, has been designed. Following manufacturing and testing, we will apply human imaging paradigms to demonstrate the effectiveness of the NX: 1) showing the dramatic sensitivity increase compared to the HRRT, 2) leveraging high sensitivity to reliably measure uptake in small nuclei, and 3) opening new frontiers of imaging neurotransmitter dynamics. The ultimate goal is a fully functioning and characterized system that dramatically expands the scope of brain PET protocols and applications.Research support: U01EB029811

Design of the NeuroEXPLORER, a next-generation ultra-high performance human brain PET imager