Multiple reference tissue method for contrast agent arterial input function estimation

A precise contrast agent (CA) arterial input function (AIF) is important for accurate quantitative analysis of dynamic contrast-enhanced (DCE)-MRI. This paper proposes a method to estimate the AIF using the dynamic data from multiple reference tissues, assuming that their AIFs have the same shape, with a possible difference in bolus arrival time. By minimizing a cost function, one can simultaneously estimate the parameters and underlying AIF of the reference tissues. The method is computationally efficient and the estimated AIF is smooth and can have higher temporal resolution than the original data. Simulations suggest that this method can provide a reliable estimate of the AIF for DCE-MRI data with a moderate signal-to-noise ratio (SNR) and temporal resolution, and its performance increases significantly as the SNR and temporal resolution increase. As demonstrated by its clinical application, sufficient reference tissues can be easily obtained from normal tissues and subregions segmented from a tumor region of interest (ROI), which suggests this method can be generally applied to cancer-based DCE-MRI studies to estimate the AIF. This method is applicable to general kinetic models in DCE-MRI, as well as other CE imaging modalities.