Abstract: In this proposed research project, we seek to develop an advanced brain SPECT system that offers a unique hyperspectral imaging capability substantiated by an excellent energy resolution (e.g., <2.5 keV at 140 keV and <3.5 keV at 250 keV) across a wide energy range (25-600 keV), and at the same time deliver a 1- mm spatial resolution and a very high sensitivity to allow detailed visualization of multi-tracer uptakes in various brain regions. This device could potentially have a transformative impact on brain research by allowing for microscopic, multi-functional assessment of brain functions under various experimental conditions. This proposed research project will integrate the disruptive high-performance 3D CZT imaging-spectrometer technologies with a novel synthetic compound eye (SCE) camera design, as well as an innovative iterative image reconstruction method using deep-learning based priors, to develop a next-generation clinical brain SPECT imaging system with transformative spatial resolution and imaging sensitivity unattainable previously. The long-term objective is to apply this innovative imaging system to human brain SPECT studies using a collection of various SPECT radiotracers, and develop and advance physiological parametric imaging methodologies, in order to investigate the long-standing issues in neurobiology and improve our understanding of the interplay and relationship among cerebral blood flow and perfusion, brain tissue oxygenation, neuronal cell metabolism, and brain cell tracking under different cognitive challenges and biophysical conditions in healthy and in disease. We would envision the proposed system to serve as a unique imaging platform to significantly advance our understanding of neural cell biology and regional brain functions in response to various cognitive, behavioral, and physiological challenges by employing these unprecedentedly innovative SPECT imaging methodologies in order to assess all relevant quantitative physiological measurements that will be interpreted in an integrated fashion and synergistically so that new perspectives in brain research unattainable previously can be formulated.

Project Narrative This proposed research project will integrate the disruptive high-performance 3D CZT imaging-spectrometer technologies with a novel synthetic compound eye (SCE) camera design, as well as an innovative iterative image reconstruction method using deep-learning based priors, to develop a next-generation clinical brain SPECT imaging system with transformative spatial resolution and imaging sensitivity unattainable previously. The long- term objective is to apply this innovative imaging system to human brain SPECT studies using a collection of various SPECT radiotracers, and develop and advance physiological parametric imaging methodologies, in order to investigate the long-standing issues in neurobiology and improve our understanding of the interplay and relationship among cerebral blood flow and perfusion, brain tissue oxygenation, neuronal cell metabolism, and brain cell tracking under different cognitive challenges and biophysical conditions in healthy and in disease. We would envision the proposed system to serve as a unique imaging platform to significantly advance our understanding of neural cell biology and regional brain functions in response to various cognitive, behavioral, and physiological challenges by employing these unprecedentedly innovative SPECT imaging methodologies in order to assess all relevant quantitative physiological measurements that will be interpreted in an integrated fashion and synergistically so that new perspectives in brain research unattainable previously can be formulated.