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White matter lesions have been always challenging for general as well as neuroradiologits. Any disease process in the brain or body can affect white matter, making it very difficult to pinpoint the diagnosis. However the application of the proper algorithmic approach, pattern of distribution, and study of the morphology of these lesions makes it possible to limit the differential diagnosis and, many times, pinpoint specific diagnosis. Advancement of various imaging techniques predominately in MR (MR spectroscopy, MR perfusion, diffusion tensor imaging (DTI). functional MR) along with PET has further improved our understanding of these disease processes. However, most of these techniques are new and not well understood by every physician. This issue will cover the topics necessary to master these techniques.