Using serial CT scans, this project aims to develop a clinical research tool that analyzes changes in vertebral density in spines involved with metastatic disease. Tracking of total vertebral body and tumor volume alone was investigated. A program was developed to semi-automate the segmentation of the region of interest followed by image registration to superimpose the segmentation onto spatially aligned serial scans. Based on analysis of a simulated metastatic vertebra, generating a voxel distribution histogram from the vertebral body best quantified density in serial scans. This quantification method may improve clinical decision-making and treatment options for patients with vertebral metastases. To develop a clinical research tool to serially track tumor involvement in vertebrae with metastatic disease by quantifying changes in CT attenuation. Segmentation of the vertebral body and analysis of the voxel distribution within the region provides the most accurate method of quantifying changes in tumor involvement for the metastatic spine. A quantitative method to assess the progression or regression of disease may improve clinical decision–making and treatment options for patients with spinal metastases. The vertebral body segmentation was more accurate at tracking tumor involvement (voxel distribution histogram: 96.8% +/− 0.75% accuracy, mean density error: 4.7% +/− 0.8%) than segmenting the tumor volume alone (voxel distribution histogram: 86.1% +/− 3.6% accuracy, mean density error: 14.1% +/− 4.8%). A program was developed to semi-automatically segment the total vertebral body and tumor volume alone from CT scans of metastatically involved vertebrae. Image registration through user-defined landmarks and surface matching was used to spatially align serial scans, and the initial segmentation was superimposed with the aligned scans. Changes within the segmentation between CT scans were tracked using mean density and a voxel distribution histogram. A cadaveric vertebra with a simulated tumor was scanned at five orientations with 20° offsets to determine the accuracy of the methods. Error primarily resulted from unavoidable re-sampling during alignment of the scans.