Diffusion-weighted imaging of hyperpolarized [¹³C]urea in mouse liver

Purpose

To compare the apparent diffusion coefficient (ADC) of hyperpolarized (HP) [¹³C,¹⁵N]urea to the ADC of endogenous water in healthy and fibrotic mouse liver.

Materials and Methods

ADC measurements for water and [¹³C]urea were made in agarose phantoms at 14.1T. Next, the ADC of water and injected HP [¹³C,¹⁵N]urea were measured in eight CD1 mouse livers before and after induction of liver fibrosis using CCl₄. Liver fibrosis was quantified pathologically using the modified Brunt fibrosis score and compared to the measured ADC of water and urea.

Results

In cell-free phantoms with 12.5% agarose, water ADC was nearly twice the ADC of urea (1.93 × 10⁻³ mm²/s vs. 1.00 × 10⁻³ mm²/s). The mean ADC values of water and [¹³C,¹⁵N]urea in healthy mouse liver (±SD) were nearly identical [(0.75 ± 0.11) × 10⁻³ mm²/s and (0.75 ± 0.22) × 10⁻³ mm²/s, respectively]. Mean water and [¹³C,¹⁵N]urea ADC values in fibrotic liver (±SD) were (0.84 ± 0.22) × 10⁻³ mm²/s and (0.75 ± 0.15) × 10⁻³ mm²/s, respectively. Neither water nor urea ADCs were statistically different in the fibrotic livers compared to baseline (P = 0.14 and P = 0.99, respectively). Water and urea ADCs were positively correlated at baseline (R² = 0.52 and P = 0.045) but not in fibrotic livers (R² = 0.23 and P = 0.23).

Conclusion

ADC of injected hyperpolarized urea in healthy liver reflects a smaller change as compared to free solution than ADC of water. This may reflect differences in cellular compartmentalization of the two compounds. No significant change in ADC of either water or urea were observed in relatively mild stages of liver fibrosis.

Level of Evidence: 1

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2018;47:141–151.