The Impact of Arterial Input Function Determination Variations on Prostate Dynamic Contrast-Enhanced Magnetic Resonance Imaging Pharmacokinetic Modeling: A Multicenter Data Analysis Challenge, Part II

This multicenter study evaluated the effect of variations in arterial input function (AIF) determination on pharmacokinetic (PK) analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data using the shutter-speed model (SSM). Data acquired from eleven prostate cancer patients were shared among nine centers. Each center used a site-specific method to measure the individual AIF from each data set and submitted the results to the managing center. These AIFs, their reference tissue-adjusted variants, and a literature population-averaged AIF, were used by the managing center to perform SSM PK analysis to estimate K(trans) (volume transfer rate constant), v(e) (extravascular, extracellular volume fraction), k(ep) (efflux rate constant), and τ(i) (mean intracellular water lifetime). All other variables, including the definition of the tumor region of interest and precontrast T(1) values, were kept the same to evaluate parameter variations caused by variations in only the AIF. Considerable PK parameter variations were observed with within-subject coefficient of variation (wCV) values of 0.58, 0.27, 0.42, and 0.24 for K(trans), v(e), k(ep), and τ(i), respectively, using the unadjusted AIFs. Use of the reference tissue-adjusted AIFs reduced variations in K(trans) and v(e) (wCV = 0.50 and 0.10, respectively), but had smaller effects on k(ep) and τ(i) (wCV = 0.39 and 0.22, respectively). k(ep) is less sensitive to AIF variation than K(trans), suggesting it may be a more robust imaging biomarker of prostate microvasculature. With low sensitivity to AIF uncertainty, the SSM-unique τ(i) parameter may have advantages over the conventional PK parameters in a longitudinal study.