The goal of this project is to develop radionuclide molecular imaging technologies using a clinical pinhole SPECT/CT scanner to quantify changes in cardiac metabolism using the spontaneously hypertensive rat (SHR) as a model of hypertensive-related pathophysiology. This paper quantitatively compares fatty acid metabolism in hearts of SHR and Wistar-Kyoto normal rats as a function of age and thereby tracks 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 metabolic pinhole SPECT imaging studies performed every seven months for 21 months. The uniqueness of this project is the development of techniques for estimating the blood input function from projection data acquired by a slowly rotating camera that is imaging fast circulation and the quantification of the kinetics of 123I-BMIPP by fitting compartmental models to the blood and tissue time-activity curves. 1. Introduction Hypertrophic cardiomyopathy is a condition in which the heart muscle becomes thick, forcing the heart to work harder to pump blood. Under normal conditions the heart uses glucose (~30%), fatty acids (~60%), and lactate (~10%) as primary energy sources, in addition to amino acids and ketone bodies [1–3]. In the case of cardiac hypertrophy, however, there is an increase in cardiac mass and a switch to a reliance on glucose metabolism. To be able to detect and interpret the early onset of this change, there is the need to develop methodology for sensitive predictors for early detection, prognosis and to follow the response to therapy for hypertrophic cardiomyopathy. In clinical settings, the abnormalities of fatty acid metabolism in hypertrophic cardiomyopathy can be recognized by the decreased uptake in single-photon emission computed tomography (SPECT) images [4]. It has also been demonstrated that compartmental analysis and dynamic SPECT imaging make it possible to detect abnormalities of fatty acid utilization earlier than SPECT imaging, with the potential to provide an even earlier prediction of the onset of cardiac hypertrophy [5]. There is a need to develop technology for imaging small animal models on clinical SPECT systems that could easily be translated to the clinic for diagnosis and management of patients with cardiac hypertrophy. However, the challenge is to perform compartmental analysis of dynamic studies in small animals with pinhole SPECT using slowly rotating gantries (slow camera rotation with 1？s per view) when the recirculation time in the animals is
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