PurposeMulticomponent driven equilibrium single pulse observation of T-1 and T-2 (mcDESPOT) is an alternative to established multiecho T-2-based approaches for quantifying myelin water fraction, affording increased volumetric coverage and spatial resolution. A concern with mcDESPOT, however, is the large number of model parameters that must be estimated, which may lead to nonunique solutions and sensitivity to fitting constraints. Here we explore mcDESPOT performance under different experimental conditions to better understand the method's sensitivity and reliability. MethodsTo obtain parameter estimates, mcDESPOT uses a stochastic region contraction (SRC) approach to iteratively contract a predefined solution search-space around a global optimum. The sensitivity of mcDESPOT estimates to SRC boundary conditions, and tissue parameters, was examined using numerical phantoms and acquired in vivo human data. ResultsThe SRC approach is described and shown to return robust myelin water estimates in both numerical phantoms and in vivo data under a range of experimental conditions. However, care must be taken in choosing the initial SRC boundary conditions, ensuring they are broad enough to encompass the true solution. ConclusionResults suggest that under the range of conditions examined, mcDESPOT can provide stabile and precise values. Magn Reson Med 73:161-169, 2015. (c) 2014 Wiley Periodicals, Inc.