A method for pharmacokinetic modelling of dynamic contrast enhanced MRI studies of rapidly enhancing lesions acquired in a clinical setting

Abnormal microcirculation is a feature of many neoplastic and non-neoplastic diseases. Physiological variables that characterize tissue microcirculation ( capillary permeability and the volume of the extravascular extracellular fluid) are altered in pathological states. Pharmacokinetic analysis of dynamic contrast enhanced MRI (DCE-MRI) has found a widespread use in the assessment of abnormal microcirculation due to the direct link between the contrast agent kinetics and underlying microcirculatory properties. A representation of temporal variation of contrast agent concentration in blood plasma (C-p(t)) is central to this analysis. In clinical applications of DCE-MRI, signal intensity curves derived from rapidly enhancing lesions often display a sigmoid shape during the initial phase of contrast uptake and rapid arrival at the equilibrium phase. In this work, the features of two principal methods for pharmacokinetic analysis of DCE-MRI which allow for theoretical representation of C-p(t) are examined and combined to improve analysis of this particular class of DCE-MRI curves. The proposed method allows the representation of the initial sigmoid part of the enhancement profiles whilst retaining a realistic representation of C-p(t) based on previously published measurements obtained in healthy volunteers. The results of the computer simulations indicate that in rapidly enhancing lesions, with the transfer constant K-trans greater than 0.1 min(-1), the DCE-MRI acquisition can be restricted to 5 min post-injection and a mono-exponential representation of C-p(t) decay is sufficient. Furthermore, non-ideal bolus delivery can be represented as a short constant rate infusion when the tissue under investigation exhibits a sigmoid pattern of contrast uptake.