PROJECT SUMMARYThis grant deals with Emission Computed Tomography (ECT) defined broadly as three-dimensional imaging of molecules or cells that have been labeled so that they emit light high-energy photons or charged particles without significant alteration of their biological function.The labeling can use radionuclides or light-emitting molecules so the emissions can benuclear decay products including electrons positrons and high-energy photons or visible ornear-infrared photons. The main application of ECT and the focus of this grant is molecularimaging in clinical medicine and biomedical research. The basic premise of the proposedresearch is that common theoretical and computational challenges recur in all forms of ECT. Five Specific Aims are proposed. Aim 1 will provide dedicated parallel computing systemsand associated algorithms optimized for image science as applied to ECT. The systems willcombine field-programmable gate arrays (FPGAs) with a cluster of graphics processing units(GPUs) and fast interconnects. Aim 2 is on imaging the radiance a function that describes any radiation field in terms of sixvariables: 3 spatial coordinates 2 variables specifying direction of flux and an energy orwavelength. We give particular attention to photon-processing detectors which use advancedstatistical methods to estimate as accurately as possible some subset of the six radiancevariables for each detected photon or particle. Tools will be developed for analyzing all stepsin the imaging chain in terms of radiance. Aim 3 deals with a critical but often neglected issue in imaging: null functions which arecomponents of an object that make no contribution to the image data. We will developmethods to compute these invisible components and determine how they influence the abilityto extract information from ECT images. Aim 4 relates objects of interest in molecular imaging to the underlying physiology of thepatient or animal subject being imaged. New mathematical tools never before used in biologyor medicine will be applied to the analysis and optimization of ECT systems. Aim 5 will develop task-based measures of image quality which are crucial to any rigorousscience of imaging. We will develop the theory and computational tools needed to assessimage quality of ECT systems in terms of therapeutic efficacy as well as diagnostic efficacyand we will develop algorithms to search efficiently for configurations of ECT systems that areoptimal in terms of task performance.