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The assessment of tissue perfusion by dynamic contrast-enhanced (DCE) imaging involves a deconvolution process. For analysis of DCE imaging data, we implemented a regression approach to select appropriate regularization parameters for deconvolution using the standard and generalized singular value decomposition methods. Monte Carlo simulation experiments were carried out to study the performance and to compare with other existing methods used for deconvolution analysis of DCE imaging data. The present approach is found to be robust and reliable at the levels of noise commonly encountered in DCE imaging, and for different models of the underlying tissue vasculature. The advantages of the present method, as compared with previous methods, include its efficiency of computation, ability to achieve adequate regularization to reproduce less noisy solutions, and that it does not require prior knowledge of the noise condition. The proposed method is applied on actual patient study cases with brain tumors and ischemic stroke, to illustrate its applicability as a clinical tool for diagnosis and assessment of treatment response.