Reply:

Abstract

W e appreciate the comments from Drs Lim and Moon on our article entitled, "Dynamic Contrast-Enhanced MRI Reveals Unique Blood-Brain Barrier Permeability Characteristics in the Hippocampus in the Normal Brain," and appreciate the opportunity to respond.The first comment is focused on the permeability model used in dynamic contrast-enhanced (DCE)-MR imaging postprocessing. In our study, we used a commercially available software, Olea Sphere (Olea Medical, La Ciotat, France), using the extended Tofts permeability model to postprocess the acquired DCE-MR imaging data into blood-brain barrier permeability (BBBP) parameters of K trans and VE. The authors suggest the use of the Patlak model combined with long scan times of 10-30 minutes 1 to improve the contrast-to-noise ratio for K trans , thereby improving the detectability of subtle BBB permeability changes.Different theoretic models have been proposed for DCE-MR imaging data analysis, including the Tofts and extended Tofts models, the adiabatic tissue homogeneity model, the 2CX model, the distributed capillary adiabatic tissue homogeneity model, and the gamma capillary transit time model. 2 The model used in our study, while less robust as indicated by the authors, is readily integrated in the clinical setting and is thus more practical from a clinical standpoint compared with the other aforementioned models. The Tofts model and other models have previously been shown to overestimate K trans , and variability in K trans values across different models is a known issue affecting all models. 2,3 Most important, even if absolute K trans values may have been overestimated in our study, all subjects were analyzed with the same model conditions; therefore, our conclusions regarding relative region-based changes in K trans remain valid.While there are certain inherent disadvantages to the Tofts and Kermode model in detecting subtle BBBP changes, our study nevertheless revealed statistically significant region-specific BBBP differences in healthy subjects. Most important, the purpose of our study was to compare the BBBP in different brain regions in healthy subjects and not to optimize permeability models or parameters. We used a commonly used commercial software and found statistically significant results on an intraindividual level.Although we mentioned in our Materials and Methods section that 80 cine phases were performed, we did not explicitly state that the acquisition time was 11 minutes 14 seconds. The benefits of extending the acquisition time in clinical practice may be limited by considerations such as patient tolerability, cost, and renal clearance of gadolinium-based contrast agents. 4 The authors additionally requested details of the acquisition protocol based on a consensus recommendation on BBB permeability imaging in small-vessel disease. 4 Given that our findings are specific to young healthy volunteers without small-vessel disease, we did not consider that the referenced consensus guideline applied in this study; however, in our Materials and Methods sect...