Current cone-beam CT systems acquire full field-of-view projections in which x-ray scatter degrades the contrast of soft-tissue in the reconstructed images. The objective of this work was to simulate volume-of-interest (VOI) imaging, which reduces scatter and dose to the patient through beam collimation, to investigate the improvements in soft-tissue visibility on the Gamma Knife Icon. The results indicated that as field size decreased, contrast and noise increased, leading to only modest improvements in the contrast-to-noise ratio when using the same initial photon fluence. A reconstruction framework called the interior virtual method was adapted to suppress truncation-induced artifacts and noise in the VOI image. In this framework the projection data were extrapolated using a cosine function, an intermediate image was reconstructed analytically, and virtual projections of the intermediate image were created for iterative reconstruction. The framework supports high quality VOI reconstruction and can allow clinicians to optimize dose for soft-tissue visualization.