Mechanical dyssynchrony (MD) occurs when different regions of the heart wall contract out of phase, often leading to congestive heart failure (CHF). Cardiac resynchronization therapy (CRT) is a medical intervention for CHF that resynchronizes the heart, reducing MD. However, CRT provides no clinical benefit in 20-50% of recipients. Single-photon emission computed tomography (SPECT) radionuclide angiography (RNA) is an imaging technique that is capable of quantifying MD by accurately assessing cardiac wall motion. In this thesis, new methods of quantifying MD with SPECT RNA were developed and evaluated as a means to predict response to CRT. Novel Fourier-analysis (FA) amplitude values were compared to left ventricular (LV) scar size in the lateral wall to determine whether they can serve as surrogate markers for predicting response to CRT. Moderate but significant correlations were shown to exist between amplitude- and scar-based parameters. Lateral wall amplitude analysis was equivalent to lateral wall scar analysis for predicting response to CRT, but there were indications that amplitude may also be partly complementary to scar.Novel MD parameters were developed using FA amplitude parameters and by developing novel clustering algorithms. These novel MD parameters were evaluated alongside pre-established FA phase-based parameters in both global and segmental regions for their ability to predict CRT response. In both FA and cluster analysis, several septal wall parameters were significantly predictive of CRT response. Based on the area under a receiver operating characteristic curve (AUC), there was an indication of improved predictive ability using cluster analysis (AUC=0.82) over scar analysis (AUC=0.73) and FA (AUC=0.78), but differences were not significant in the small test population. Novel amplitude-based FA parameters and cluster analysis approaches provide promising tools for the assessment of MD and the prediction of CRT response with SPECT RNA.