Model-free Leakage Index Estimation of the Blood-Brain Barrier Using Dual Dynamic Susceptibility Contrast MRI Acquisition.

Pharmacokinetic K2 mapping from dynamic susceptibility contrast (DSC)‐MRI can be a sensitive technique for evaluating the vascular permeability of the subtly damaged blood‐brain barrier (BBB) in ischemic regions. However, the K2 values of ischemic lesions depend upon the selection of the intact BBB reference region. As previous observations suggest that the ΔR2* curve of pre‐loaded DSC‐MRI is not significantly affected by the extravasation of contrast agent, dual DSC‐MRI acquisitions can be performed to derive the BBB leakage index from the voxel‐wise reference input function for ischemic regions. This study aims to demonstrate the robustness of such model‐free leakage index estimation in ischemic brains. By configuring the relationship between dual ΔR2* curves of the intact contralateral brain, the deviation of the measured ΔR2* curve from the unloaded DSC‐MRI with respect to the non‐deviated ΔR2* curve in the pre‐loaded DSC‐MRI can be quantified as the BBB leakage index. Such model‐free leakage index values from rats with transient middle carotid artery occlusion (tMCAO) (n = 17) and normal controls (n = 3) were evaluated and compared with conventional K2 values with multiple reference regions. Inter‐subject leakage index values were also compared with the corresponding ΔT1 map. Evans‐blue‐stained images were used to validate the leakage index. For the tMCAO group, leakage index values correlated well with ΔT1 (Pearson's r = 0.828). The hyperintense area on the leakage index map matched well with the corresponding Evans‐blue‐stained area (Dice correlation = 0.626). The slopes of the scatter‐plot from the leakage index (0.97‐1.00) were observed to be more robust against changes in the reference region than those from conventional K2 values (0.94‐1.07). In a subtly damaged BBB tMCAO model, model‐free evaluation of vascular permeability using dual DSC‐MRIs would provide a consistent measure of inter‐subject vascular permeability.