Quantitative analysis of uptake and washout of cardiac single photon emission computed tomography (SPECT) radiopharmaceuticals has the potential to provide better contrast between healthy and diseased tissue, compared to conventional reconstruction of static images. Previously, we used B-splines to model time-activity curves (TACs) for segmented volumes of interest and developed fast least-squares algorithms to estimate spline TAC coefficients and their statistical uncertainties directly from dynamic SPECT projection data.