PurposeTo evaluate whether a non-linear blood ΔR2*-versus-concentration relationship improves quantitative cerebral blood flow (CBF) estimates obtained by dynamic susceptibility contrast (DSC) MRI in a comparison with Xe-133 SPECT CBF in healthy volunteers. Material and MethodsLinear as well as non-linear relationships between ΔR2* and contrast agent concentration in blood were applied to the arterial input function (AIF) and the venous output function (VOF) from DSC-MRI. To reduce partial volume effects in the AIF, the arterial time integral was rescaled using a corrected VOF scheme. ResultsUnder the assumption of proportionality between the two modalities, the relationship CBF(MRI)=0.58CBF(SPECT) (r=0.64) was observed using the linear relationship and CBF(MRI)=0.51CBF(SPECT) (r=0.71) using the non-linear relationship. DiscussionA smaller ratio of the VOF time integral to the AIF time integral and a somewhat better correlation between global DSC-MRI and Xe-133 SPECT CBF estimates were observed using the non-linear relationship. The results did not, however, confirm the superiority of one model over the other, potentially because realistic AIF signal data may well originate from a combination of blood and surrounding tissue.