Pseudo-extravasation rate constant of dynamic susceptibility contrast-MRI determined from pharmacokinetic first principles

Dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI) is widely used to obtain informative perfusion imaging biomarkers, such as the relative cerebral blood volume (rCBV). The related post-processing software packages for DSC-MRI are available from major MRI instrument manufacturers and third-party vendors. One unique aspect of DSC-MRI with low-molecular-weight gadolinium (Gd)-based contrast reagent (CR) is that CR molecules leak into the interstitium space and therefore confound the DSC signal detected. Several approaches to correct this leakage effect have been proposed throughout the years. Amongst the most popular is the Boxerman–Schmainda–Weisskoff (BSW) K₂ leakage correction approach, in which the K₂ pseudo-first-order rate constant quantifies the leakage. In this work, we propose a new method for the BSW leakage correction approach. Based on the pharmacokinetic interpretation of the data, the commonly adopted R₂* expression accounting for contributions from both intravascular and extravasating CR components is transformed using a method mathematically similar to Gjedde–Patlak linearization. Then, the leakage rate constant (K_L) can be determined as the slope of the linear portion of a plot of the transformed data. Using the DSC data of high-molecular-weight (~750 kDa), iron-based, intravascular Ferumoxytol (FeO), the pharmacokinetic interpretation of the new paradigm is empirically validated. The primary objective of this work is to empirically demonstrate that a linear portion often exists in the graph of the transformed data. This linear portion provides a clear definition of the Gd CR pseudo-leakage rate constant, which equals the slope derived from the linear segment. A secondary objective is to demonstrate that transformed points from the initial transient period during the CR wash-in often deviate from the linear trend of the linearized graph. The inclusion of these points will have a negative impact on the accuracy of the leakage rate constant, and even make it time dependent.