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The package dcemriS4 provides a complete set of data analysis tools for quantitative assessment of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Image processing is provided for the ANALYZE and NIfTI data formats as input with all parameter estimates being output in NIfTI format. Estimation of T1 relaxation from multiple flip-angle acquisitions, using either constant or spatially-varying flip angles, is performed via nonlinear regression. Both literature-based and data-driven arterial input functions are available and may be combined with a variety of compartmental models. Kinetic parameters are obtained from nonlinear regression, Bayesian estimation via Markov chain Monte Carlo or Bayesian maximum a posteriori estimation. A non-parametric model, using penalized splines, is also available to characterize the contrast agent concentration time curves. Estimation of the apparent diffusion coefficient (ADC) is provided for diffusion-weighted imaging. Given the size of multi-dimensional data sets commonly acquired in imaging studies, care has been taken to maximize computational efficiency and minimize memory usage. All methods are illustrated using both simulated and real-world medical imaging data available in the public domain.