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_i (mean intracellular water lifetime). All other variables, including the definition of the tumor region of interest and precontrast T₁ 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_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_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 microvascula-ture. With low sensitivity to AIF uncertainty, the SSM-unique_i parameter may have advantages over the conventional PK parameters in a longitudinal study.