In this paper, a fully automatic and computationally efficient midsagittal plane (MSP) extraction technique in brain magnetic resonance images (MRIs) has been proposed. Automatic detection of MSP in neuroimages can significantly aid in registration of medical images, asymmetric analysis, and alignment or tilt correction (recenter and reorientation) in brain MRIs. The parameters of MSP are estimated in two steps. In the first step, symmetric features and principal component analysis (PCA)-based technique is used to vertically align the bilateral symmetric axis of the brain. In the second step, PCA is used to achieve a set of parallel lines (principal axes) from the selected two-dimensional (2-D) elliptical slices of brain MRIs, followed by a plane fitting using orthogonal regression. The developed algorithm has been tested on 157 real T 1 -weighted brain MRI datasets including 14 cases from the patients with brain tumors. The presented algorithm is compared with a state-of-the-art approach based on bilateral symmetry maximization. Experimental results revealed that the proposed algorithm is fast (<1.04 s per MRI volume) and exhibits superior performance in terms of accuracy and precision (a mean z-distance of 0.336 voxels and a mean angle difference of 0.06).2 of 23 misalignment of brain MRIs. A general phenomenon in brain MRI scanning is that many neuroimaging scanners produce tilted and distorted brain images. The tilt of the head is not always detectable, due to many reasons such as the health conditions, immobility of patients, imprecision of the data calibration systems, and the inexperience of the technicians. Consequently, the slices of the brain MRIs are no more alike within the same orientation, at either the axial or coronal level [15]. Disoriented and misaligned brain MRIs can betray visual inspection and prevalently yield erroneous clinical perception [16]. In summary, assessment of brain MRIs for any anomaly based on cross-referencing of brain hemispheres (left and right), either by a human expert or computer-based software could be affected by false geometrical representation. Consequently, it is essential to correct the tilt and realign the brain MRIs data before further analysis.Manual misalignment correction is extremely time-consuming and laborious to perform on a huge scale. It also demands an urbane knowledge of brain anatomy. Therefore, it is neither sufficient nor efficient. Alignment or tilt correction of brain MRIs is tantamount to realigning the MSP with the center of the image matrix or image coordinate system [14]. If the MSP is computed precisely, the orientation problem of the MRI volume can be resolved. Thus, the tilt of the head volume can be assessed and adjusted. An ideal MSP can be defined as a virtual geometric plane passing through the interhemispheric fissure (IF) [17], about which the three-dimensional (3-D) anatomical structure of the brain (such as the ventricles, anterior/posterior commissures, corpus callosum, thalamus) exhibits maximum bilateral symmetry [18].Previously, ...