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The goal of this research is to quantitatively compare fatty acid metabolism in the hearts of Wistar-Kyoto (WKY) normal rats and spontaneously hypertensive rats (SHR) as a function of age, and thereby track physiological changes associated with the onset and progression of heart failure in the SHR model. The fatty acid analog, 123I-labeled BMIPP, was used in longitudinal dynamic pinhole SPECT imaging studies performed on two WKY normal rats and two SHRs every seven months for 21 months. In previous work, we addressed issues associated with reconstructing dynamic data acquired with a slowly rotating camera. In this work, we address quantitative effects of limited spatial resolution that result in underestimation of metabolic rate from compartmental models. In particular, blurring of activity between the left ventricular blood pool and surrounding myocardial tissue decreases contrast between blood input and tissue uptake time-activity curves (TACs). Standard compartmental modeling straightforwardly accounts for spillover of blood activity into tissue volumes. However, accounting for spillover of tissue activity into blood volumes is more problematic. Because of tissue spillover, there is no reconstructed voxel that contains a pure blood TAC. Thus, we developed a method to jointly estimate the pure blood input along with compartmental model parameters from B-spline TACs reconstructed directly from dynamic SPECT projection data for 11 studies. Tissue spillover correction improved the contrast between blood input and myocardial uptake curves for all studies and visually improved the fit of the compartmental model for some studies. Estimates of metabolic rate of 123I-labeled BMIPP increased by an average of 72?45% across all 11 studies, compared to estimates obtained without spillover correction. Thus, the tissue spillover correction method resulted in improved quantitative dynamic imaging of fatty acid metabolism in the rat heart, even with slow cam- - era rotation.