Gender Differences in Sodium Deposition in Muscle and Skin

Ping Wang^1,2, Muge Serpil Deger³, Hakmook Kang⁴, T. Alp Ikizler³, Jens M. Titze⁵, and John C. Gore^1,2

¹Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, United States, ²Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United States, ³Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States, ⁴Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, United States, ⁵Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States

Synopsis

Sodium ions play a vital role in cellular homeostasis and electrochemical activity throughout the human body. Previous studies have measured muscle and skin sodium contents in vivo in humans using MRI and have shown characteristic changes with age and as a result of pathological changes. In this study, we found significant gender differences in sodium deposition between muscle and skin, with male has higher sodium content in skin than in muscle, while female has higher muscle sodium than skin sodium. This observation seems to be more reliable with the increase of age.

Introduction

Sodium is the most abundant cation in the human body, and is vital for cellular function and integrity.^1,2 Normally, the intracellular space accounts for 80% of tissue volume with a sodium concentration of 10 – 15mM, against an extracellular volume fraction of 20% with a sodium concentration of 140 – 150mM. This relatively stable concentration difference is primarily maintained by the sodium-potassium Na⁺/K⁺-ATPase pump, which pumps sodium out of cells while pumping potassium into cells. Leaky cell membranes or impaired Na⁺/K⁺ exchange kinetics potentially change the cytosolic total tissue sodium, making sodium a biomarker of a wide range of disease states.^3-5 Previous studies have measured muscle and skin sodium contents in vivo in humans using MRI and have shown characteristic changes with age and as a result of pathological changes.^6,7 Following an earlier preliminary observation,⁸ we investigated whether there are significant gender differences in sodium deposition between muscle and skin based on a cohort of 20 males and 18 females. Our results indicate that age-matched males appear to have higher sodium accumulation in skin than in muscle, whereas women tend to have greater muscle than skin sodium. This gender-relevant sodium deposition is statistically significant, and this difference in distribution seems to be more reliable with increasing age.

Methods

Thirty-eight subjects (20 males, ages 25-79, median age 51; 18 females, ages 38-66 years, median age 53) were recruited in this study. Imaging was performed on a Philips Achieva 3.0T MR scanner (Philips Healthcare, Cleveland OH, USA) with a 23Na quadrature knee coil (Rapid Biomedical GmbH, Rimpar, Germany). Four calibration phantoms (NaCl aqueous solutions of 10mM, 20mM, 30mM, and 40mM) served as reference standards and were scanned together with subject’s calf muscles. Subject’s left lower leg was scanned with the skin closely in contact with the hard surface (a concave cover) of the phantom holder. Figure 1 shows the sodium coil, phantoms/holder, and the subject’s setup. MR scans primarily included a proton mDixon scan and a sodium scan which have the same isocenter. The mDixon provides a high resolution anatomical image for muscle ROI definition. Sodium imaging was performed using an optimized 3D Gradient-echo sequence, FOV = 192 x 192 x 210mm³, voxel size = 3 x 3 x 30mm³, 7 slices, TR/TE/FA = 130ms/0.99ms/90°, bandwidth = 434Hz/pixel, acquisitions: 26, scan time = 15min54sec. As shown in Figure 2, the muscle ROIs include five regions (anterior compartment - red, peroneus - green, soleus - blue, medial gastrocnemius - cyan, and lateral gastrocnemius - gold) which were drawn on the mDixon images, skin ROI (purple) and phantom ROIs (red circles) were drawn on the sodium image directly. To investigate the possible gender relevance to sodium deposition between muscle and skin, sodium differences between muscle and skin were computed for each subject (ΔTSC = TSC_muscle - TSC_skin). Then a Wilcoxon rank sum test was applied to the ΔTSC series of males and females to examine if they were significantly different. In addition, a scatter plot was used to depict the relationship between ΔTSC and age.

Results

Table 1 summarizes the TSC in muscle and skin for males and females, along with age information and ΔTSC. Notably, the majority of the males have higher TSC in skin than in muscle, which is opposite to females whose muscle TSC is greater than skin TSC. The Wilcoxon rank sum test confirms the gender difference in sodium deposition between muscle and skin is significantly different (P < 0.05). Figure 3 plots the correlation between sodium difference (ΔTSC = TSC_muscle - TSC_skin) and age for males and females. It appears that younger subjects have smaller ΔTSC (and are also more variable especially for males), and the absolute value of ΔTSC tends to increase with the increase of age, which tends to be true for both males and females.

Discussion

Our results show there are different patterns of sodium accumulation in muscle and skin for men and women, a difference that appears to increase with age. The MRI method used is able to unambiguously differentiate sodium in muscles of the leg and skin and quantify spatial differences in concentration with good precision and spatial resolution. These findings are relevant to the interpretation of sodium measurements that potentially may be used to follow changes over time in, for example, patients with hypertension or chronic kidney disease.

Conclusion

Significant gender difference in sodium deposition between muscle and skin was found, with male has higher sodium content in skin than in muscle, while female has higher muscle sodium than skin sodium. The observation seems to be more reliable with the increase of age.

Acknowledgements

No acknowledgement found.

References

1. Madelin G, Lee J, Regatte R, et al. Sodium MRI: methods and applications. Prog Nucl Magn Reson Spectrosc. 2014; 79:14-47.

2. Constantinides C, Gillen J, Boada F, et al. Human skeletal muscle: sodium MR imaging and quantification-potential applications in exercise and disease. Radiology. 2000; 216(2):559-68.

3. Ouwerkerk R, Morgan R. 23Na MRI: From Research to Clinical Use. J Am Coll Radiol. 2007; 4(10):739–741.

4. Boada F, Gillen J, Shen G, et al. Fast three dimensional sodium imaging. MRM. 1997; 37(5):706-715.

5. Inglese M, Madelin G, Oesingmann N, et al. Brain tissue sodium concentration in multiple sclerosis: a sodium imaging study at 3 tesla. Brain. 2010; 133(3):847-857.

6. Kopp C, Linz P, Wachsmuth L, et al. (23)Na magnetic resonance imaging of tissue sodium. Hypertension. 2012; 59(1):167-172.

7. Kopp C, Linz P, Dahlmann A, et al. 23Na magnetic resonance imaging-determined tissue sodium in healthy subjects and hypertensive patients. Hypertension. 2013; 61(3):635-640.

8. Wang P, Nockowski C, Gore J. In vivo sodium T1 and T2 measurements in human calf at 3T. 23rd ISMRM. Toronto, Canada. 2015; p 705.

Figures

Figure 1. (A) Lower part of the 3T sodium knee coil and the calibration standards inside a phantom holder. A concave cover with a hard smooth surface is used to cover the phantoms/holder during imaging. (B) During imaging the skin is in direct contact the surface of the cover.

Figure 2. (A) mDixon water image with five muscle subgroups labeled. (B) Muscle regions are overlaid on sodium image (with vessel pixels excluded from ROI) which has been interpolated to the resolution of the mDixon image. Skin ROI and phantom ROIs are drown on sodium image.

Figure 3. Scatter plot of ΔTSC = (TSC_muscle – TSC_skin) versus age for male group (blue) and female group (pink), |ΔTSC| appears to increase with the increase of age for both males and females, although the ΔTSC of male tends to be more variable.

Table 1. Summary of sodium concentration in muscle and skin for male and female groups. Sodium difference (ΔTSC) between muscle and skin was computed for the use of Wilcoxon rank sum test to examine the gender relevance of sodium distribution (in muscle and skin), significant difference is reached P-value < 0.05.

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

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