Midline shift (MLS), the amount of displacement of the brain’s midline from its normal symmetric position due to illness or injury, is an important index for clinicians to assess the severity of traumatic brain injury (TBI). In this dissertation, an automated computer-aided midline shift estimation system is proposed. First, a CT slice selection algorithm (SSA) is designed to automatically select a subset of appropriate CT slices from a large number of raw images for MLS detection. Next, ideal midline detection is implemented based on skull bone anatomical features and global rotation assumptions. For the actual midline detection algorithm, a window selection algorithm (WSA) is applied first to confine the region of interest, then the variational level set method is used to segment the image and extract the ventricle contours. With a ventricle identification algorithm (VIA), the position of actual midline is detected based on the identified right and left lateral ventricle contours. Finally, the brain midline shift is calculated using the positions of detected ideal midline and actual midline. One of the important applications of midline shift in clinical medical decision making is to estimate the intracranial pressure (ICP). ICP monitoring is a standard procedure in the care of severe traumatic brain injury (TBI) patients. An automated ICP level prediction model based on machine learning method is proposed in this work. Multiple features, including midline shift, intracranial air cavities, ventricle size, texture patterns, and blood amount, are used in the ICP level prediction. Finally, the results are evaluated to assess the effectiveness of the proposed method in ICP level prediction.