Renal [1-13C]-acetate turnover mapping with hyperpolarized MRI
Emmeli F. R. Mikkelsen1, Thomas S. Nørlinger1, Haiyun Qi1, Ulrich Koellisch2, Rolf F. Schulte3, Michael Pedersen1, Hans Stødkilde-Jørgensen1, and Christoffer Laustsen1

1MRI Research Centre, Aarhus University Hospital, Aarhus N, Denmark, 2Institute of Medical Engineering, Technische Universität München, Munich, Germany, 3GE Global Research, Munich, Germany

Synopsis

Positron Emission Tomography (PET) using carbon-11 acetate has previously been used to reveal the oxidative metabolism in the kidneys. It has been found that renal carbon-11 acetate turnover measured by PET was significantly correlated with renal oxygen consumption and tubular sodium reabsorption measured by an invasive approach. Hyperpolarized MRI is an alternative method to obtain similar intracellular measures of acetate, and the aim of this study was therefore to evaluate the rate constants of hyperpolarized [1-13C]-acetate in rat kidneys. The intrarenal oxygen level was altered by diuretics, and measures of acetate rate constants were calculated before and after injection of furosemide.

Purpose

To measure the intrarenal acetate turnover in response to furosemide using hyperpolarized [1-13C]-acetate.

Methods

Ten female adult Wistar rats (256.0±7.0 g) were included. Blood glucose levels were measured as 7.1±0.7 mmol/L from the tail capillary blood with a Contour blood glucose meter. Tail vein catheterization was performed for administration of hyperpolarized [1-13C]-acetate and furosemide. The animal was anaesthetized with 3% sevoflurane in oxygen as breathing gas. [1-13C]-acetate was polarized in a SpinLab (GE Healthcare). MRI measurements were performed on a 3 T GE HDx scanner (GE Healthcare) equipped with a hydrogen/carbon-RF quadrature transmit/receive-coil (GE Healthcare). A dynamic (120 sec, 1 image/sec) sequence was initiated at start of [1-13C]-acetate injection. A second dynamic scan was performed 20 min after an iv bolus of furosemide (10 mg/ml). Regions-of-interests of left and right kidney parenchyma were manually segmented in order to measure the mean renal activity-curve, and a region inside the abdominal aorta was used to obtain the arterial input curve (AIF). The AIF was then fitted by a gamma variate function (using the nonlinear Levenberg-Marquardt method) for the initial 30 sec after [1-13C]-acetate injection to account for recirculation. Next, graphical analysis, by means of the Patlak plot, was used to estimate the intracellular [1-13C]-acetate conversion rate (k) in units of min-1, using the approximation that the intracellular pharmacokinetics of acetate is considered being monocompartmental and irreversible1.

Results

Hyperpolarized [1-13C]-acetate (fig. 1) accumulated in both kidneys following arterial filling. The acetate turnover or rate constants increased from 2.64 ± 0.78 min-1 to 4.19 ± 1.50 min-1 (paired t-test: p = 0.0021) after administration of furosemide (fig. 2).

Discussion

The rate constants in rat kidneys found in this study was two orders of magnitude larger than those reported with radioactive carbon-11 acetate measured by PET by Juillard et al1. This discrepancy may be explained by the general allometric (log-scale) differences in size and metabolism between pigs and rats. This explanation is supported by the rate constants found in rat myocardium, demonstrating carbon-11 acetate rate constants around 1.5 min-1 2. The increased conversion rate of [1-13C]-acetate following furosemide supports the view that this diuretic drug decreases the intrarenal oxygen consumption (reduction in the sodium reabsorption), thus increasing the cortical blood perfusion.

Conclusion

This study demonstrated the potential of hyperpolarized [1-13C]-acetate MRI as a novel method of assessing renal oxidative metabolism via acetate turnover mapping.

Acknowledgements

Henrik Vestergaard is acknowledged for his laboratory assistance.

References

1. Juillard, L., et al., Validation of Renal Oxidative Metabolism Measurement by Positron-Emission Tomography. Hypertension, 2007. 50(1): p. 242-247.

2. Bentourkia, M., et al., Cardiac studies in rats with <sup>11</sup>C-acetate and PET: a comparison with <sup>13</sup>N-ammonia. Nuclear Science, IEEE Transactions on, 2002. 49(5): p. 2322-2327.

Figures

Figure 1: Examples of [1-13C]-acetate uptake in the aorta and kidneys over time.

Figure 2: The acetate turnover rate (1/min) before and after administration of furosemide. The mean is plotted with SEM.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
3906