Clinical application of pharmacokinetic analysis as a biomarker of solitary pulmonary nodules: Dynamic contrast-enhanced MR imaging

The purpose of this study is to evaluate perfusion indices and pharmacokinetic parameters in solitary pulmonary nodules (SPNs). Thirty patients of 34 enrolled with SPNs (15-30 mm) were evaluated in this study. T1 and T2-weighted structural images and 2D turbo FLASH perfusion images were acquired with shallow free breathing. B-spline nonrigid image registration and optimization by π² test against pharmacokinetic model curve were performed on dynamic contrast-enhanced MRI. This allowed voxel-by-voxel calculation of k_ep, the rate constant for tracer transport to and from plasma and the extravascular extracellular space. Mean transit time, time-to-peak, initial slope, and maximum enhancement (E_max) were calculated from time-intensity curves fitted to a gamma variate function. After blinded data analysis, correlation with tissue histology from surgical resection or biopsy samples was performed. Histologic evaluation revealed 25 malignant and five benign SPNs. All benign SPNs had k_ep < 1.0 min ^-1. Nineteen of 25 (76%) malignant SPNs showed k_ep > 1.0 min^-1. Sensitivity to diagnose malignant SPNs at a cutoff of k_ep = 1.0 min^-1 was 76%, specificity was 100%, positive predictive value was 100%, negative predictive value was 45%, and accuracy was 80%. Of all indices studied, k_ep was the most significant in differentiating malignant from benign SPNs.