Myelin water imaging is a promising, noninvasive technique for evaluating white matter diseases such as multiple sclerosis and other leukoencephalopathies (LE), and monitoring myelination in early childhood. Unfortunately, poor image quality and a long acquisition time are major obstacles to practical clinical applications. In this study, a novel postprocessing method with an efficient multi-slice acquisition scheme, called T2 spectrum analysis using a weighted regularized non-negative least squares algorithm and nonlocal mean filter (T2SPARC), is presented to overcome these obstacles and achieve a shorter acquisition time, higher image quality, and large volume coverage. In vivo results from healthy volunteers and a patient with LE showed that the T2SPARC method can generate robust and high-quality myelin water fraction maps of 10 slices within 11 min. This method also yields some useful byproducts such as intra- and extracellular water fraction and long T2 tissue water fraction maps, which can quantify lesions in different brain diseases. Magn Reson Med 70:813–822, 2013. © 2012 Wiley Periodicals, Inc.