Multi-slice CT (MCT) is one of the most recent technical advancements in computed tomography. MCT offers high volume coverage, faster scan speed, and reduced x-ray tube loading. When combined with the helical scan mode, MCT provides even higher volume coverage as a result of the elimination of the inter-scan delays. Similar to the single slice CT, the projection data collected in MCT is inherently inconsistent. To combat projection inconsistency, many image reconstruction algorithms were investigated and developed. Recent studies have shown, however, that the image quality of MCT can be significantly degraded when the data is collected in a tilted helical mode. The degradation can be so severe that it is unacceptable for routine clinical usage. In this paper, we present a detailed investigation to show that the root cause of the image quality degradation is the deviation of the reconstruction iso-center from the gantry iso-center. An analytical model is derived to establish a quantitative relationship between the iso0center shift and other system parameters. The model serves as the mathematical basis for the derivation of a frequency-domain correction algorithm. Detailed performance evaluation is provided in terms of spatial resolution, noise, computational efficiency, and image artifacts.