Validity of perfusion parameters obtained using the modified Tofts model: a simulation study.

The two-compartment Tofts model (2CTM) has had widespread use in research and clinical practice. It assumes there is no broadening associated with the bolus transit through the capillary bed of the tissue under study. This assumption is often violated, with consequences that are hard to predict intuitively. The two-compartment exchange model is a generalization of 2CTM obtained by dropping the zero-broadening hypothesis, making it suitable for estimating the impact of violating this assumption. Using data simulated on the basis of the two-compartment exchange model, the correspondence between the hemodynamic parameters serving as input for the two-compartment exchange model and the parameters resulting from fitting the data with the 2CTM was investigated. The influence of tissue type and experimental setup was studied. Generally, a large tissue and setup dependent bias of the 2CTM fitting results with respect to the two-compartment exchange model input was observed. Extreme caution is needed when interpreting 2CTM data.