Reproducibility and Optimal Arterial Input Function Selection in Dynamic Contrast-Enhanced Perfusion MRI in the Healthy Brain

Background Dynamic contrast-enhanced MRI (DCE-MRI) has seen increasing use for quantification of low level of blood-brain barrier (BBB) leakage in various pathological disease states and correlations with clinical outcomes. However, currently there exists limited studies on reproducibility in healthy controls, which is important for the establishment of a normality threshold for future research. Purpose To investigate the reproducibility of DCE-MRI and to evaluate the effect of arterial input function (AIF) selection and manual region of interests (ROI) delineation vs. automated global segmentation. Study Type Prospective. Population A total of 16 healthy controls; 11 females; mean age 28.7 years (SD 10.1). Field Strength/Sequence A 3T; GE DCE; 3D TFE T1WI. 2D TSE T2. Assessment The influx constant K-i, a measure of BBB permeability, and V-p, the blood plasma volume, was calculated using the Patlak model. Cerebral blood flow (CBF) was calculated using Tikhonov model free deconvolution. Manual tissue ROIs, drawn by H.J.S. (30+ years of experience), were compared to automatic tissue segmentation. Statistical Tests Intraclass correlation coefficient (ICC) and repeatability coefficient (RC) was used to assess reproducibility. Bland-Altman plots were used to evaluate agreement between measurements day 1 vs. day 2, and manual vs. segmentation method. Results K-i showed excellent reproducibility in both white and gray matter with an ICC between 0.79 and 0.82 and excellent agreement between manual ROI and automatic segmentation, with an ICC of 0.89 for K-i in WM. Furthermore, K-i values in gray and white matter conforms with histological tissue characteristics, where gray matter generally has a 2-fold higher vessel density. The highest reproducibility measures of K-i (ICC = 0.83), CBF (ICC = 0.77) and V-d (ICC = 0.83) was obtained with the AIF sampled in the internal carotid artery (ICA). Data Conclusion DCE-MRI shows excellent reproducibility of pharmacokinetic variables derived from healthy controls. Evidence Level 2 Technical Efficacy Stage 2

Automated summary

This study investigates the reproducibility of DCE-MRI in healthy controls and evaluates the impact of arterial input function selection and manual region of interests delineation versus automated global segmentation. The results show excellent reproducibility of pharmacokinetic variables derived from DCE-MRI in healthy controls.