To determine whether analysis of the power spectrum generated from Fourier transform (FT) can detect white matter alignment using clinical scans and to evaluate how tissue coherency changes in patients with advanced multiple sclerosis (MS) using this new method.Brain MR images were acquired using a 3T scanner (GE Healthcare, DISCOVERY MR750, Milwaukee, USA) from a clinical study focusing on the structure and function of corpus callosum. Recruitment included 8 Secondary Progressive MS patients, whose disability score was all equal or above 6 out of 10, and 10 age- and gender-matched healthy controls. MRI protocol included a T2-weighted MR sequence with the following parameters: TE/TR = 82/60 field of view = 240 X 240 mm2, matrix size = 256 X 256. Recently we developed a new technique to evaluate the coherency and anisotropy of tissue structure based on the power spectrum of the FT. This method involves the following steps: 1) Calculating the FT and power spectra of an image; 2) performing logarithmic normalization and intensity thresholding of the power spectrum to preserve information within the upper 80 to 100 percentile; 3) conducting polar conversion of the processed power spectrum and plotting the orientation profile of the image (Fig. 1). To verify the utility of our method, we examined the directionality of corpus callosum as it is the largest interhemispheric white matter structure with highly organized nerve fibers. Regions of interest (ROIs) were drawn in the left, centra and right aspects of both genu and splenium of the structure in axial T2-weighted MRI< with an optimized size of 36 to 49 pixels each (Fig. 2). The distribution of aligning directions (degrees) in each ROI was plotted as a histogram, from which the angular entropy and dominant orientation of individual ROIs were derived and that were used to compare with the visually observed directions of the regions in healthy and to detect changes in anisotropy in patients.Visually, the estimated directions of alignment were approximately 135 (right), 0 (center) and 45 (left) degrees in the genu and 45, 0 and 135 degrees in the splenium of corpus callosum in the image domain (Fig. 2). Using our assessing method, we found that the highest peak of power spectra in the right, center and left areas of genu was at 45, 90 and 135 degrees, which was equal to 135, 0 and 45 degrees respectively in the image domain at the same region. Similarly, in the right, center and left ROIs of the splenium, the spectral peak was at 135, 90 and 45 degrees, equivalent to 45, 0 and 135 degrees in the image (Fig. 3). In patients, corresponding regions showed a similar aligning profile but with reduced orientation strength and increased complexity as measured by angular entropy, suggesting loss of tissue or alignment (p<0.05 as per multi-comparison statistical analysis; Fig. 4). This is most severe in the left and right regions than in the central regions. All ROIs showed a similar trend; however, there was larger variability in the central regions of the genu and the splenium than the other areas. Alterations in tissue microstructures can lead to changes in signal intensity and alignment of image voxels [1]. Assessing tissue anisotropy has been conducted mostly using advanced MRI such as diffusion-weighted imaging, which are not routinely acquired in a clinical setting [2]. In the study, we showed the possibility of obtaining similar structural information using standard T2-weighted MRI. The orientational property in different areas of the corpus callosum calculated using our method showed an extremely high match with the visualized angles of alignment in these regions. Moreover, the loss of white matter anisotropy known in patients with SPMS in detected using this method, even in the lesion free structure such as the corpus callosum [3]. While central ROIs demonstrate relativity large variability, likely due to the position and size of the ROI and needs further confirmation, our overall findings suggest the sensitivity and potential of this image post-processing method. The underlying pathologies of such MRI results may include demyelination, axonal loss and gliosis [4]. Future studies seek to validate current results in large sample size and compared MRI metrics with tissue histopathology.This study suggests the potential of using FT power spectrum in assessing tissue directionality using clinical MRI. This may become an alternative method for determining white matter coherency and can have important clinical implications in improving the utility of clinical scans and in determining injury or repair in patients with MS and other neurological disorder.