Figure 2.

Gadobutrol Permeability Derived from Voxel-wise T₁ mapping: (A) To derive the Gadobutrol concentration [Gd] in the bladder mucosa using the Eq. (1), we first estimated the T₁ relaxation rate constant or relaxivity (r₁) of Gadobutrol at 9.4 T by the linear fitting of the reciprocal of the water T₁ relaxation time or T₁ water relaxation rate (1/T₁) measured in the serial two fold dilutions of [Gd] 2 mM at 37 °C. Linear fitting generated the regression equation: y = 3.576x + 0.1975 with the coefficient of determination (R²) of 0.999 and r₁ value of 3.576 L/mmol/s for Gadobutrol at 9.4 T. In contrast to the linear relationship between T₁ water relaxation rate of the phosphate buffered saline (PBS) vial (blank) supplemented with ascending concentrations of Gadobutrol from 0.1-2 mM [Gd], the non-linearity between [Gd] and signal intensity is illustrated by the doubling of [Gd] from 1 to 2 mM producing only a minor change in the signal intensity of T₁ weighted images acquired at TR/TE of 640/14 ms. (B) Compared to control group, the post-contrast T₁ relaxation time computed from 20 pixels in ROI of mucosa* was significantly shorter in WAS group (*p < 0.005, two-way ANOVA followed by Sidak’s test) and T₁ relaxation time was further shortened upon PS exposure (0.5 mL of 1%w/v) for 30 min. (C) Higher mucosal permeability in WAS group is indexed by a significantly higher ingress of Gadobutrol derived from the non-invasive, quantitative measurement of increased T₁ water relaxation rates (n = 5; *p < 0.001, two-way ANOVA and Sidak’s test) which is doubled from the respective pre-PS levels by PS exposure in both groups. (D) Bladder wall depth of instilled Gadobutrol penetration was evaluated by measuring the spatial separation between U and L on post-contrast and post-protamine T₁ maps. The penetration depth of Gadobutrol after PS in WAS group was significantly larger than in the control group *p < 0.05. All values are expressed as Mean ± SD.