The rapid development of modern multi-slice computed tomography (MSCT) scanners has provided imaging systems with cone-beam geometry, sub-millimetre slice thickness, and gantry rotation speeds approaching 0.3 seconds per revolution. Clinical MSCT scanners routinely generate volume data sets yet the methods used to quantify spatial resolution remain relatively unchanged from those used to evaluate single slice scanners. In this paper, we describe a method for quantifying the spatial resolution of an MSCT scanner, with cone-beam, geometry using a sphere phantom. By scanning a Teflon sphere embedded in a uniform silicone cylinder, the plane spread function (PlSF) and modulation transfer function (MTF) may be determined. Furthermore, the spatial resolution in the axial and trans-axial directions may be independently quantified, as well as the effects of Azimuthal blur and spiral scanning. To illustrate the utility of the sphere method, the spatial resolution of two commercially available MSCT scanners was measured.© (2006) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.