Synopsis

The ability to image sodium is believed to be a powerful tool to understand physiological processes, however have yet to be effectivity translated to clinical realistic usage. Through the use of an efficient k-space trajectory (3D cones) we have undertaken dynamic imaging of the renal sodium distribution pre and post- a furosemide injection. This work shows a decrease in the cortico-medullary sodium gradient over time, as well as being the first renal study on a clinical system with dynamic sodium imaging.

Introduction

Methods

Three Danish domestic pigs were anaesthetised (propofol (0.4mg/kg/h) and fentanyl (8 µg/kg/h)), ventilated, and placed in a 3T MRI scanner (GE 750, WI). T₁ weighted ¹H imaging was performed (8 channel cardiac array, field of view (FOV) = 380mm, reconstruction matrix = 288x288x192, repetition time (TR) = 3ms, echo time (TE) = 1ms, flip angle (FA) = 12 degrees), ²³Na imaging was performed with a pair of Helmholtz loop coils (3D cones readout, respiratory gated, volume excite, FOV = 240mm, TR = 45ms, TE = 0.5ms, flip angle = 60 degrees, NEX = 5, total scan time = 5 minutes, reconstruction matrix = 120x120x120, calibration phantoms = 4% agar, 20, 100 mmolL-1). B₁ maps were acquired to correct for flip angle across the volume (protocol as above, flip angles = 40,80 degrees, NEX = 1) .

Furosemide (0.5 mgkg -1), an acute diuretic, which blocks reabsorption of sodium, potassium and chloride in the distal loop of Henle and abolishes the cortico-medullary osmotic gradient was introduced after a baseline sodium acquisition, and sodium imaging performed in 5-minute blocks for 30 minutes.

Between each imaging block, arterial blood gas samples were acquired to assess for alterations in serum metabolites. Regions of interest were drawn on each kidney using ¹H images, segmenting medullar and cortex (Fig1B). The whole kidney was also segmented by combining both regions previously drawn. Further segmentation of the kidney was performed as previously reported, using 7 layers 7.

Sodium concentration maps were calculated using the calibration phantoms and a region of noise outside of the body (concentration maps pre and 20 post-furosemide seen in Figure 28.

Regions of interest were used to define average sodium concentration values for the kidney, and a linear fit across segmented layers to determine the cortico-medullary sodium gradient.

Temporal alterations in the sodium gradient were assessed by deriving the angle of fit at each time point.

Statistical analysis

Significance was defined at p<0.05. ANOVA and Bonferroni corrected Wilcoxon rank-sum tests were performed to assess for differences between baseline and time point measures of the cortico-medullar sodium gradient angle, serum metabolites, and segmented medullar/cortex sodium concentration.

Results

Kidney segmentation

Segmentation of the kidneys revealed elevated sodium in the medulla, compared to the cortex (90±5vs47±2mmolL^-1,Fig3A, p<0.05). Furthermore, there was a detectable decrease in the medullary, and increase in the cortex, sodium distribution observed 30 minutes post-furosemide (90±5vs70±3mmolL^-1, 47±2vs56±4mmolL^-1, respectively, Fig.3B, p<0.05 in both cases). However, there was no discernible difference in the overall sodium concentration of the whole kidney. The cortico-medullary sodium gradient was observed in all cases (Fig.4A), with a flattening of the gradient observed post-furosemide at all time points (82±1.5vs77.5±1.5 degrees at 20 minutes post-furosemide, Fig.4, p<0.05 in all cases).

Serum metabolites

No significant alterations in serum metabolites were detected during the experiment, p>0.05 in all cases. Serum sodium remained constant throughout each experiment (139±2, mmolL^-1)

Discussion

This study has shown the feasibility of using dynamic quantitative sodium imaging to non-invasively monitor physiological alterations induced by acute diuresis, detecting early alterations in the cortico-medullar gradient.

Further study in to the use of dynamic sodium imaging to assess the glomerular filtration rate may be possible.

A limitation, however, of this work is the lack of tissue validation for sodium concentration results, which would further strengthen the study.

Conclusion

Acknowledgements

References

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