An extended reference region model for DCE-MRI that accounts for plasma volume

The reference region model (RRM) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides pharmacokinetic parameters without requiring the arterial input function. A limitation of the RRM is that it assumes that the blood plasma volume in the tissue of interest is zero, but this is often not true in highly vascularized tissues, such as some tumours. This study proposes an extended reference region model (ERRM) to account for tissue plasma volume. Furthermore, ERRM was combined with a two-fit approach to reduce the number of fitting parameters, and this was named the constrained ERRM (CERRM). The accuracy and precision of RRM, ERRM and CERRM were evaluated in simulations covering a range of parameters, noise and temporal resolutions. These models were also compared with the extended Tofts model (ETM) on in vivo glioblastoma multiforme data. In simulations, RRM overestimated K^trans by over 10% at v_p  = 0.01 under noiseless conditions. In comparison, ERRM and CERRM were both accurate, with CERRM showing better precision when noise was included. On in vivo data, CERRM provided maps that had the highest agreement with ETM, whilst also being robust at temporal resolutions as poor as 30 s. ERRM can provide pharmacokinetic parameters without an arterial input function in tissues with non-negligible v_p where RRM provides inaccurate estimates. The two-fit approach, named CERRM, further improves on the accuracy and precision of ERRM.