Pseudo‐extravasation rate constant of dynamic susceptibility contrast‐MRI determined from pharmacokinetic first principles. (8th September 2017)

• Record Type: Journal Article
• Authors: Li, Xin; Varallyay, Csanad G.; Gahramanov, Seymur; Fu, Rongwei; Rooney, William D.; Neuwelt, Edward A.
• Is Part Of: NMR in biomedicine. Volume 30:Number 11(2017:Nov.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-09-08
• Subjects: Ferumoxytol -- gadolinium -- Gjedde–Patlak transformation -- intravascular contrast reagent -- leakage correction -- relative cerebral blood volume; Nuclear magnetic resonance -- Periodicals; Magnetic Resonance Spectroscopy -- Periodicals; 574
• DOI: 10.1002/nbm.3797
• Languages: English
• ISSNs: 0952-3480

Abstract

Abstract : 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) K 2 leakage correction approach, in which the K 2 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 R 2 * 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. Abstract : A new method, similar to Gjedde–Patlak linearization, is proposed to correct the leakage effect of gadolinium (Gd)‐based contrast agent in dynamic susceptibility contrast‐magnetic resonance imaging (DSC‐MRI). Using the DSC data of high‐molecular‐weight, iron‐based, intravascular Ferumoxytol (FeO), the pharmacokinetic interpretation of the new paradigm is empirically validated. Compared with the relative cerebral blood volume (rCBV) color map obtained with FeO (E), Gd rCBV without leakage correction often results in underestimation (B) and Gd rCBV with current correction results in slight overestimation (C); the new method shows an improved result (D).