Reliability assessment of sodium ( 23 Na) MRI at 7.0 T in healthy human calf muscle and preliminary results on tissue sodium concentrations in subjects with Addison’s disease

doi:10.21203/rs.3.rs-1497516/v1

Download PDF

Research Article

Reliability assessment of sodium ( 23 Na) MRI at 7.0 T in healthy human calf muscle and preliminary results on tissue sodium concentrations in subjects with Addison’s disease

https://doi.org/10.21203/rs.3.rs-1497516/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Objectives: To determine the relaxation times of the sodium nucleus, and to investigate the reliability of quantitative, in vivo TSC measurements using sodium magnetic resonance imaging (²³Na-MRI) in human skeletal muscle and explore the discriminatory value of the method by comparing TSCs between healthy subjects and patients with Addison’s disease.

Materials and Methods: In this prospective study, ten healthy subjects and five patients with Addison’s disease were involved. ²³Na-MRI data sets were acquired using a density-adapted, three-dimensional radial projection reconstruction pulse sequence (DA-3DPR) with a modification for the relaxation times measurements. Differences in TSC between muscle groups and between healthy participants were analyzed using a nonparametric Friedman ANOVA test. An interclass correlation coefficient (ICC) was used as the reliability index.Wilcoxon rank sum test was used for evaluation of differences in TSC between study participants.

Results: The mean T₁ in the gastrocnemius medialis (GM), the tibialis anterior (TA), and the soleus (S) was 25.9±2.0ms, 27.6±2.0ms, and 28.2±2.0ms, respectively. T₂^*_mono values were GM, 12.0±0.9ms; TA, 12.8±0.7ms; and S, 12.9±2.0ms. In healthy volunteers, TSC values in the GM were 20.0±1.0mmol/L, 14.1±0.9mmol/L in TA, and 12.8±0.8mmol/L in S, and were significantly different (p=0.0005). The ICCs for GM, TA and S were 0.784, 0.818, 0.807, respectively. In patients with Addison’s disease, TSC in GC, TA, and S were 10.2±1.0mmol/L, 8.4±0.6mmol/L, and 7.2±0.1mmol/L, respectively.

Conclusions: TSC quantification in a healthy subject’s calf at 7.0 T is reliable; the technique is able to distinguish sodium level differences between muscles and between healthy subjects and Addison’s disease patients.

sodium magnetic resonance imaging

tissue sodium concentration

calf muscle

Addison’s disease

Over the last two decades, clinical research has demonstrated that biochemical information on disease progression and treatment efficacy may be obtained with a non-invasive metabolic imaging modality called sodium magnetic resonance imaging (²³Na-MRI) [1]. The method enables quantification of tissue sodium concentration (TSC), which has been demonstrated to be a useful imaging marker for the investigation of different pathological conditions in almost every part of the human body [2]. Currently, the number of preclinical and clinical ²³Na-MRI studies at 7.0 T is increasing, mainly because of the substantial gain in signal-to-noise ratio (SNR) at ultra-high fields [3–7]. An optimal SNR substantially improves image quality and reduces a patient’s scan time, thus confirming TSC as a marker for disease diagnosis and monitoring. However, an accurate sodium concentration quantification at ultra-high fields is challenging and depends on many factors, such as relaxation times (T₁ and T₂^*) of the tissue of interest. Unfortunately, the knowledge about sodium relaxation times at 7.0 T of the muscle is still limited [8].

Sodium (²³Na) is the primary cation in the human body and its concentration is connected to the physiological state of a cell and early changes in human homeostasis. Body hormonal imbalance or certain diseases, such as diabetes mellitus, hypertension, and acute heart failure, may cause an increase or a decrease of the sodium concentration in blood and manifest as conditions known as hypernatremia or hyponatremia [9, 10]. Changes of ²³Na concentrations in the calf muscle, on the other hand, may be closely related to the molecular pathophysiology of the muscle tissue, which also may be common in rare diseases, such as muscle channelopathy [11] and dystrophy [5, 12–14]. Addison’s disease is another rare disorder characterized by impaired production of the steroid hormones cortisol and aldosterone, which may affect the sodium and potassium ion equilibrium (electrolyte imbalance) in the tissue [15]. Similar to the above-mentioned rare diseases, in subjects with Addison’s disease, sodium concentration level disturbances in a tissue may be potentially assessed using ²³Na-MRI.

To be used as a reliable tool for different diagnostic and research investigations, this method requires an evaluation of repeatability and reproducibility, which should establish sodium tissue concentration assessments with sufficiently high accuracy.

The purpose of our study was to determine the relaxation properties of sodium nuclei in healthy calf muscle, and second, to perform reproducibility and repeatability tests of the sodium quantification measurements applicable in lower leg muscle investigations at 7.0 T. Further, we aimed to investigate whether regional differences in TSC of muscle are detectable and to explore the feasibility and discriminatory value of this method in patients with Addison’s disease.

All measurements were performed between July 2020 and June 2021 and were approved by the local research ethics committee. Written, informed consent was obtained from all participants in the study. All methods were performed in accordance with the Declaration of Helsinki.

Hardware

MRI was performed on a whole-body 7.0 T MR scanner with a 70 mT/m gradient amplitude and a 200 mT/m/ms slew rate (Magnetom, Siemens Healthcare, Erlangen, Germany). Study participants were scanned in the supine, feet-first position. A dual-tuned sodium and proton knee coil (14 ²³Na channels and a single ¹H channel; Stark Contrast, Germany) was used.

Phantoms

A cylindrical phantom made of poly methyl methacrylate (PMMA) filling completely the knee coil was filled with a mixture of agar (4%) (Agarose, Sigma-Aldrich, USA) and a saline solution of 61.6 mmol/L, and was used for field mapping and corrections. The local transmitter B₁⁺ field was mapped with a phase-sensitive method that applies a pulse combination of nominal flip angles of α_x = 180° about the x-axis and α_y = 90° about the y-axis [16]. External B₀ field inhomogeneity correction was achieved by generating a data set with two different TEs; the first data set was acquired for off-resonance map calculations due to the resultant phase differences of two different echo times, and, in a second step, the data set was reconstructed multiple times with the corresponding off-resonance for each pixel to correct for B₀ inhomogeneity. Sequence parameters are presented in Table 1. The correction factors derived from the cylindrical phantom were applied on in vivo data similar to previous work [17].

A set of calibration phantoms was made of 4% agar and saline solution with four different sodium concentrations: 15.4, 30.8, 46.2, and 61.6 mmol/L, doped with 1% nickel sulfate. Concentration phantoms were attached to the inner side of the coil and were used for calibration curve derivation. To match the T₁ value of the phantom and muscle tissue, we added 2.9 g/L copper sulfate to the mixture.

Imaging protocol

All ²³Na multi-channel data sets were acquired using a density-adapted, three-dimensional radial projection reconstruction pulse sequence (DA-3DPR) [18]. For T₁ relaxation time measurements, a modified DA-3DPR with an inversion recovery (IR) pulse was included and five different inversion times (IT) were used. T₂^* mapping was performed employing the same DA-3DPR sequence with 20 different echo times (TE).

A proton (¹H) double echo steady state (DESS) sequence was acquired for partial volume effect (PVE) correction. Sodium imaging was performed using DA-3DPR followed by noise-only scans (no radio frequency [RF] power). More details on the sequences used can be found in Table 1.

Study participants

Tenhealthy subjects were recruited.In four of ten participants, relaxation time measurements were performed. Reliability tests were performed in all ten participants and planned in such a way that subjects underwent three lower leg muscle MRI examinations organized as two separate visits with an interval of seven to eightdays in between. The group was divided in two sub-groups arbitrarily. The first half of the subjects received two MRI scans during the initial visit and one MRI scan during the repeat visit. The second half of the subjects received one MRI on the first visit and two MRIs on the second visit. Between the two scans, during one visit, the subject left the scanner for a five-minute-long break. Volunteers were placed in a similar position according to anatomic landmarks from proton (¹H) morphological imaging for the next scan. The order of the number of measurements for the two sessions was randomly determined. In addition, five participants with a diagnosis of Addison’s disease were scanned. Demographic data on study participants are shown in Table2.

Image reconstruction and inhomogeneity correction

Sodium images were reconstructed using an adaptive combining method (ADC) implemented in three dimensions to combine the complex images of the individual coils, with an interpolation factor of two and an overlap of eight pixels [19, 20]. SNR maps were calculated using a multiple replica approach [21]. Images were multiplied with correction factors obtained from actual measurements and compared to images corrected with a homogeneous phantom correction map. The accuracy of the applied method was evaluated on a set of agar phantoms with different sodium concentrations comparing prepared sodium concentrations of calibration phantoms with the concentrations calculated after image corrections were applied [22].

PVE corrections

The anatomical information necessary for PVE correction was obtained with a DESS sequence with the parameters mentioned above. Two packages of the Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (v6.0, Analysis Group, FMRIB, Oxford, UK) were used: the FMRIB's Linear Image Registration Tool (FLIRT) for the image registration and the FMRIB's Automated Segmentation Tool (FAST) for the image segmentation [23]. PVE calculation was performed according to a method proposed by Niesporek et al. [24], based on the geometric transfer matrix (GTM) method for PVE correction. The structural information was used in combination with a simulated point spread function (PSF) to calculate the corresponding region-spread functions (RSF) via convolution.

Relaxation time calculations

T₁ and T₂^* relaxation time maps were derived by fitting the ²³Na signal evolution to a mono-exponential function (T₁) or a bi-exponential function (fast T₂^* and slow T₂^* components) using IDL software (version 6.3, Research Systems, Boulder, CO, USA).

TSC assessments

Sodium data sets from every volunteer were reconstructed using an in-house-written MATLAB (R2020b, MathWorks Inc., Natick, MA) script. ²³Na-MRI images were co-registered offline to the corresponding DESS image for each volunteer and analyzed on an Aliza (Aliza Medical Imaging & DICOM Viewer, Bonn, Germany). A quantitative assessment of ²³Na-concentration was performed on manually drawn region of interests (ROIs) that covered the gastrocnemius medialis (GM), the tibialis anterior (TA), and the soleus (S) and were placed by two readers in consensus. Values for ²³Na-concentration in millimoles per liter (mmol/L) were calculated according to the formula (1) taking sodium signal intensity from selected ROIs:

$$\left[{Na}_{in vivo}\right]=\frac{{I}_{in vivo}^{corr}}{{I}_{phan}^{corr}}\left[{Na}_{ref}\right]$$

Where $\left[{Na}_{in vivo}\right] and \left[{Na}_{ref}\right]$and $\frac{{I}_{in vivo}^{corr}}{{I}_{phan}^{corr}}$ is the ratio of corresponding signal intensities corrected for relaxation time differences between muscle tissue and phantoms. ${I}_{in vivo}^{corr}$ was derived from ²³Na images which were previously corrected for PVE, and B₀ and B₁⁺ inhomogeneity.

Statistical analysis

Statistical analysis was done using IBM SPSS Statistics for Windows, version 22.0 (IBM, Armonk, NY). Metric data are described by means (mean ± SD) and normal distribution of measured values was tested using the Shapiro Wilks test. For categorical data, absolute frequencies and percentages are presented. Differences in TSC between the muscle regions were tested using a nonparametric Friedman ANOVA test. To investigate which pairs of muscles were significantly different in terms of TSC, we used a pairwise Wilcoxon signed-rank test with Bonferroni correction of P-values to compensate for multiple comparisons. Wilcoxon rank sum test was used for evaluation of differences in TSC between healthy volunteers and patients. A P value less than 0.05 was considered statistically significant.

The reliability of measurements was estimated with an intra-class correlation coefficient (ICC) using a two-way random-effects model [25]. Based on the 95% confident interval of the ICC estimate, values less than 0.5, between 0.5 and 0.75, between 0.75 and 0.9, and greater than 0.90 were indicative of poor, moderate, good, and excellent reliability, respectively. Differences between three measurements (M1, M2, M3) were assessed using Bland-Altman plots.

Relaxation time measurements

In the subgroup of four healthy volunteers (age: 25 ± 4 years), the mean T₁ and T₂^* relaxation times were measured, calculated, and summarized in Table 3. The mean T₁ in GM, TA, and S were: 25.9 ± 2.0 ms, 28.2 ± 2.0 ms, and 27.6 ± 2.0 ms, respectively. T₂^*_mono values were as follows: GM: 12.9 ± 0.9 ms; TA: 12.8 ± 0.7 ms; and S: 12.9 ± 2.0 ms (Table 3) (Fig. 1). The mean short component of T₂^*, T₂^*_short were GM: 3.6 ± 2.0 ms; TA: 3.2 ± 0.5 ms; and S: 3.0 ± 1.0 ms, and the mean long component of T₂^*, T₂^*_long, were GM: 10.8 ± 0.5 ms; TA: 10.6 ± 0.8 ms; and S: 10.8 ± 0.9 ms, respectively (Fig. 2).

Reliability tests

For the first measurement, the mean TSC values for GM, TA, and S were: 19.9 ± 0.5 mmol/L, 14.0 ± 0.5 mmol/L, and 12.7 ± 0.7 mmol/L, respectively. For the second scan, we found TSC of 19.9 ± 0.6 mmol/ for GM, 13.8 ± 0.6 mmol/L for TA, and 12.7 ± 0.5 mmol/L for S. The third exam for GM, TA, and S found TSC values of 19.8 ± 0.5 mmol/L, 13.7 ± 0.5, mmol/L and 12.4 ± 0.8 mmol/L, respectively. ICC analysis showed a good reliability for each group of muscles individually. The ICC for the gastrocnemius medialis was 0.784 (CI 95%, lower bound = 0.468, upper bound = 0.951), for the tibialis anterior, the ICC was 0.818 (CI 95%, lower bound = 0.435, upper bound = 0.948), and, for the soleus, the ICC was 0.807 (CI 95%, lower bound = 0.435, upper bound = 0.948). Bland-Altman diagrams showing results of reproducibility tests are provided in Fig. 3.

TSC quantification of the calf muscles

Ten healthy subjects, five men and five women (age: 30 ± 6 years, body mass index (BMI), 21.1 ± 1.0 kg/m²) were involved in reliability tests. The mean SNR of sodium images of the human calf was 16 ± 3. Before corrections were applied, the mean TSC values for GM, TA, and S were 22.7 ± 0.7 mmmol/L, 17.8 ± 1.0 mmol/L, and 16.4 ± 0.9 mmol/L and, respectively. After all corrections were applied, the mean TSC of three measurements were: gastrocnemius medialis: 19.9 ± 0.1 mmol/L; tibialis anterior: 13.8 ± 0.2 mmol/L; and soleus: 12.6 ± 0.02 mmol/L (Table 4).

Nonparametric Friedman test showed a significant difference between TSC values for all three types of muscles (P = 0.0005). There was a difference between gastrocnemius medialis and soleus muscle (P = 0.018) and between gastrocnemius medialis and tibialis anterior (P = 0.018). A difference between the soleus and tibialis was found as well (P = 0.018).

In participants with Addison’s disease (age: 41 ± 10 years, BMI: 22.5 ± 1.0 kg/m²) the mean TSC measured in the gastrocnemius medialis was 10.2 ± 1.0 mmol/L. In the tibialis anterior and soleus, measured TSC values were 8.4 ± 0.6 mmol/L and 7.2 ± 0.1 mmol/L, respectively (Table 4).

A significant difference in TSC values was found between healthy volunteers and patients for all three muscles: P = 0.0007, P = 0.0027 and P = 0.0007 for GM, TA and S, respectively (Fig. 4).

Tissue sodium concentration can be considered a useful parameter for biochemical investigations of muscular pathologies. At present, TSC values reported in the literature indicate substantial differences between individual reports of this parameter assessed in human calf muscle. This is most probably due to the lack of established MRI quantification protocols available and different quantification methodologies applied. Our study was performed at 7.0 T MRI and involved ten healthy subjects and included relaxation time measurements, TSC quantification, and repeatability and reproducibility tests. Relaxation time measurements demonstrated no substantial differences in T₁, T_2mono, T_2long, and T_2short of three different muscle types. Sodium concentration quantification in healthy participants showed significant differences in TSCs in three different parts of the calf muscle (gastrocnemius medialis, tibialis anterior, and soleus) (P = 0.0005). In healthy participants, reliability tests showed good reliability of sodium concentration quantification in three different regions of the calf muscle (ICC = 0.784–0.948). In addition, we examined and quantified TSCs in the calf muscle of five subjects with a diagnosis of Addison’s disease and found substantially lower TSC values compared to those in healthy participants. This finding is in line with our expectation and the choice of AGS as a model for ²³Na⁺ imbalances. Glucocorticoids and mineralocorticoids play a major role in the regulation of sodium balance. Interestingly, these differences could be observed despite adequate hormone substitution therapy in patients with adrenal insufficiency. Whether ²³Na-MRI might play a useful role in the clinical evaluation of adequate treatment should be evaluated in future trials,

The relaxation T₁ times of ²³Na of the healthy human lower leg muscle at 3.0 T reported in the literature were about 29 ms [26]. Measurements of relaxation times of the ²³Na nucleus of lower leg muscle measured at 7.0 T showed values that were slightly different from those obtained on 3.0 T scanners. The short and long components of T₂^* at 3.0 T were reported to be 0.7 ± 0.1 ms and 13.2 ± 0.2 ms, respectively [27].

Moreover, because of different physiological and pathological contributions (edema, volume regulation, etc.) to the sodium concentration, the ²³Na-MRI measurements in patients may be potentially confounded by T₁ and T₂^* relaxation effects, and consequently, the values can actually deviate from the values measured in healthy tissue [14].

Quantitative TSC values of the lower leg muscle determined noninvasively with ²³Na-MRI in healthy male subjects are in good agreement with the results obtained invasively by chemical analysis in patients who require extremity amputation [28]. TSC values reported in the literature are in the range of 13.0 to 25.0 mmol/L [29]. Gast et al. recently reported TSC after B₀ corrections for the gastrocnemius medialis, assessed at two sites, as 17.0 ± 2.2 mmol/L for site ≠ 1 and 16.2 ± 1.3 mmol/L for site ≠ 2. For the tibialis anterior, TSC at two sites were 14.3 ± 1.3 mmol/L and 13.7 ± 1.2 mmol/L, respectively. For the soleus, TSC values were 18.1 ± 1.4 mmol/L and 17.5 ± 1.0 mmol/L, respectively [3], confirming significant differences in TSC between GM, TA, and S muscle (p < 0.0005). Recently, Ahlulail et al. reported substantially higher TSC values after using T₂* corrections and found the highest concentrations of sodium in the soleus muscle (34.1 ± 2.2 mmol/L) compared to GM (25.0 ± 2.8 mmol/L) and TA (25.3 ± 2.1 mmol/L) [27]. This discrepancy in the highest sodium content found in different muscles reported in the literature need to be further investigated using standardized protocols and applied on a larger group of subjects.

Reliability investigations of ²³Na-MRI in lower leg [4, 27, 29] or in upper leg muscle [30] have been already reported in the literature; however, measurement conditions for different research centers may be different (i.e. external magnetic field strength, coils, etc.), and reliability may vary from one to another investigation site. Therefore, we performed our own tests to demonstrate the reliability of quantification methodology applied in this study.

Our study has some limitations. First, our population group was too small to have an appropriate analysis of sex- and age-related differences in TSC. Sodium relaxation times in Addison’s and healthy subjects muscle tissue may be different as well. Moreover, it is known that ²³Na concentration in the calf of women can be hormonally dependent, which makes standardization of quantification more challenging [31]. Second, our healthy participants were slightly younger than the Addison’s disease patients. Therefore, studies that would include a larger population group still need to be performed. In addition, the image post-processing procedure is time-consuming and further development of the image reconstruction methods are necessary. However, all evaluations were performed in post-processing, so this did not influence the participant’s scanning time. A short acquisition time is extremely important if measurements have to be performed on patients to reduce potential motion artefacts and keep discomfort to a minimum. The application of sodium magnetic resonance fingerprinting (²³Na-MRF) would enable much faster data acquisition for relaxation time measurements [32, 33].

Sodium concentrations in the tissue may be reliably assessed using ²³Na-MRI at 7.0 T. The technique is quantitative and sensitive enough to distinguish differences in sodium levels between heathy and pathological tissue. Early metabolic changes in the tissue may be evaluated with ²³Na-MRI. This might provide information on the effectiveness of glucocorticoid and mineralocorticoid replacement therapy in adrenal insufficiency and could be a useful parameter with which to evaluate ongoing treatment.

Ethical Approval:

Institutional Review Board of Medical University of Vienna approval was obtained.

Written informed consent was obtained from all subjects (patients) in this study. All methods were performed in accordance with the Declaration of Helsinki.

Consent for publication

Not applicable.

Availability of data and materials

The datasets generated and/or analysed during the current study are not publicly available due their size and complexity but are available from the corresponding author on reasonable request.

Competing interests

Not applicable.

Funding

This study has received funding by FWF Der Wissenschaftsfonds (KLI 917).

Authors' contributions

O.Z. conception and design of the work, data the acquisition, analysis, interpretation of data; manuscript drafting; H.B. data acquisition, analysis; J.V. data acquisition, analysis; P.S. data interpretation; manuscript revision; P.W. data interpretation; M.K. data interpretation; manuscript revision; M.K data interpretation; manuscript revision; S.T. data interpretation; manuscript revision; V.J. conception and design of the work, data acquisition, analysis, interpretation of data.

Acknowledgements

Not applicable.

Madelin, G., et al., Sodium MRI: methods and applications. Prog Nucl Magn Reson Spectrosc, 2014. 79: p. 14-47.
Zaric, O., et al., Frontiers of Sodium MRI Revisited: From Cartilage to Brain Imaging. J Magn Reson Imaging, 2020: p. e27326.
Gast, L.V., et al., Combined imaging of potassium and sodium in human skeletal muscle tissue at 7 T. Magn Reson Med, 2021. 85(1): p. 239-253.
Gerhalter, T., et al., Assessing the variability of (23) Na MRI in skeletal muscle tissue: Reproducibility and repeatability of tissue sodium concentration measurements in the lower leg at 3 T. NMR Biomed, 2020. 33(5): p. e4279.
Gerhalter, T., et al., Quantitative (1)H and (23)Na muscle MRI in Facioscapulohumeral muscular dystrophy patients. J Neurol, 2020.
Utzschneider, M., et al., Towards accelerated quantitative sodium MRI at 7 T in the skeletal muscle: Comparison of anisotropic acquisition- and compressed sensing techniques. Magn Reson Imaging, 2021. 75: p. 72-88.
Utzschneider, M., et al., Accelerated quantification of tissue sodium concentration in skeletal muscle tissue: quantitative capability of dictionary learning compressed sensing. MAGMA, 2020. 33(4): p. 495-505.
Madelin, G., A. Jerschow, and R.R. Regatte, Sodium relaxation times in the knee joint in vivo at 7T. NMR Biomed, 2012. 25(4): p. 530-7.
Kopp, C., et al., 23Na magnetic resonance imaging-determined tissue sodium in healthy subjects and hypertensive patients. Hypertension, 2013. 61(3): p. 635-40.
Hammon, M., et al., 23Na Magnetic Resonance Imaging of the Lower Leg of Acute Heart Failure Patients during Diuretic Treatment. PLoS One, 2015. 10(10): p. e0141336.
Weber, M.A., et al., 7-T (35)Cl and (23)Na MR Imaging for Detection of Mutation-dependent Alterations in Muscular Edema and Fat Fraction with Sodium and Chloride Concentrations in Muscular Periodic Paralyses. Radiology, 2016. 280(3): p. 848-59.
Weber, M.A., et al., Sodium (23Na) MRI detects elevated muscular sodium concentration in Duchenne muscular dystrophy. Neurology, 2011. 77(23): p. 2017-24.
Gerhalter, T., et al., (23) Na MRI depicts early changes in ion homeostasis in skeletal muscle tissue of patients with duchenne muscular dystrophy. J Magn Reson Imaging, 2019. 50(4): p. 1103-1113.
Kushnir, T., et al., In vivo 23Na NMR studies of myotonic dystrophy. Magn Reson Med, 1997. 37(2): p. 192-6.
Liamis, G., H.J. Milionis, and M. Elisaf, Endocrine disorders: causes of hyponatremia not to neglect. Ann Med, 2011. 43(3): p. 179-87.
Morrell, G.R., A phase-sensitive method of flip angle mapping. Magn Reson Med, 2008. 60(4): p. 889-94.
Zaric, O., et al., Tissue Sodium Concentration Quantification at 7.0-T MRI as an Early Marker for Chemotherapy Response in Breast Cancer: A Feasibility Study. Radiology, 2021: p. 201600.
Nagel, A.M., et al., Sodium MRI using a density-adapted 3D radial acquisition technique. Magn Reson Med, 2009. 62(6): p. 1565-73.
Walsh, D.O., A.F. Gmitro, and M.W. Marcellin, Adaptive reconstruction of phased array MR imagery. Magn Reson Med, 2000. 43(5): p. 682-90.
Benkhedah, N., et al., Evaluation of adaptive combination of 30-channel head receive coil array data in 23Na MR imaging. Magn Reson Med, 2016. 75(2): p. 527-36.
Minarikova, L.e.a. Adaptive combine reconstruction of sodium MRI data of breast and knee at 7 T: optimization and comparison to sum-of-square reconstruction. in Proc. Intl. Soc. Mag. Reson. Med. 25 (2017). 2017.
Zaric, O., et al., Quantitative Sodium MR Imaging at 7 T: Initial Results and Comparison with Diffusion-weighted Imaging in Patients with Breast Tumors. Radiology, 2016. 280(1): p. 39-48.
Jenkinson, M., et al., Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage, 2002. 17(2): p. 825-41.
Niesporek, S.C., et al., Partial volume correction for in vivo (23)Na-MRI data of the human brain. Neuroimage, 2015. 112: p. 353-363.
Koo, T.K. and M.Y. Li, A Guideline of Selecting and Reporting Intraclass Correlation Coefficients for Reliability Research. J Chiropr Med, 2016. 15(2): p. 155-63.
Nagel, A.M., et al., 3 Tesla sodium inversion recovery magnetic resonance imaging allows for improved visualization of intracellular sodium content changes in muscular channelopathies. Invest Radiol, 2011. 46(12): p. 759-66.
Alhulail, A.A., et al., Fast in vivo (23) Na imaging and T 2 * mapping using accelerated 2D-FID UTE magnetic resonance spectroscopic imaging at 3 T: Proof of concept and reliability study. Magn Reson Med, 2021. 85(4): p. 1783-1794.
Kopp, C., et al., (23)Na magnetic resonance imaging of tissue sodium. Hypertension, 2012. 59(1): p. 167-72.
Dyke, J.P., et al., Reliability and agreement of sodium ((23)Na) MRI in calf muscle and skin of healthy subjects from the US. Clin Imaging, 2018. 52: p. 100-105.
Milani, B., et al., Exploring a new method for quantitative sodium MRI in the human upper leg with a surface coil and symmetrically arranged reference phantoms. Quant Imaging Med Surg, 2019. 9(6): p. 985-999.
Wang, P., et al., Sex differences in sodium deposition in human muscle and skin. Magn Reson Imaging, 2017. 36: p. 93-97.
Kratzer, F.J., et al., Sodium relaxometry using (23) Na MR fingerprinting: A proof of concept. Magn Reson Med, 2020. 84(5): p. 2577-2591.
Kratzer, F.J., et al., 3D sodium ((23) Na) magnetic resonance fingerprinting for time-efficient relaxometric mapping. Magn Reson Med, 2021.

Table 1

Imaging parameters of imaging sequences used in this study

Measurement	TR (ms)	TE (ms)	Matrix size	In-plane resolution (mm³)	FA (°)	Slice thickness (mm)	Inversion Time (ms)	Number of projections	Pulse duration (ms)	Acquisition time (min:s)
B₀ mapping	139	0.60/1.60	128×128	4.0×4.0	90	4.0	/	4000	1.0	9:16
B₁⁺ mapping	150	1.0	128×128	4.0×4.0	90	4.0	/	4000	2.0	10:00
T1 relaxation time	253-370	0.80	128×128	6.5×6.5	90	6.5	3.0-120	2600	1.5	64:03
T2* relaxation time	65	0.4-5.0	128×128	5.8×5.8	90	5.8	/	9000	0.68	48:45
Proton imaging	9.32	2.55	320×320	0.5×0.5	20	1.0	/	/	/	3:08
Sodium imaging	100	0.55	128×128	2.5×2.5	90	10.0	/	10000	0.5	16:40

B₀, external field; B₁⁺, local transmitter field; FA, flip angle; IT, inversion time; T1, longitudinal relaxation time; T2*, transverse “observed” relaxation time; TE, echo time; TR, repetition time

Table 2

Demographic data on participants involved in the study

Subject number	Age	Gender	Diagnosis	BMI	Laterality
1	27	Male	Healthy	19.7	Right
2	20	Male	Healthy	20.1	Right
3	26	Female	Healthy	21.9	Right
4	28	Female	Healthy	20.5	Right
5	32	Male	Healthy	22.5	Left
6	35	Male	Healthy	23.0	Left
7	34	Female	Healthy	20.8	Left
8	25	Female	Healthy	19.9	Left
9	36	Male	Healthy	21.0	Left
10	40	Female	Healthy	22.0	Right
11	33	Male	Addison’s disease	22.3	Right
12	30	Female	Addison’s disease	23.8	Right
13	49	Female	Addison’s disease	22.9	Right
14	54	Female	Addison’s disease	21.0	Right
15	40	Male	Addison’s disease	22.6	Right

Table 3

²³Na relaxation time values T₁[ms], T_2mono[ms], T₂^*_short [ms], and T₂^*_long [ms] of the different regions of human calf muscle presented as means ±SD

Subject number	Muscle type	T₁ [ms]	*T₂^_mono [ms]**	*T₂^_short [ms]**	*T₂^_long [ms]**
1	gastrocnemius	28.5±0.5	14.0±0.5	3.4±0.2	10.5±0.5
	tibialis anterior	29.4±1.0	12.5±0.3	3.1±0.2	10.1±0.4
	soleus	28.9±0.3	14.2±0.3	2.5±0.8	10.9±0.2
2	gastrocnemius	24.1±2.0	12.6±0.2	2.5±0.3	10.3±0.3
	tibialis anterior	25.4±0.3	13.7±0.8	3.0±0.4	10.9±0.2
	soleus	26.0±0.2	12.7±0.3	4.0±3.0	10.0±0.6
3	gastrocnemius	24.4±3.0	11.9±0.2	2.7±0.1	11.3±0.8
	tibialis anterior	26.4±0.4	12.2±0.2	2.6±0.3	9.9±0.4
	soleus	27.7±0.8	11.0±0.2	2.6±0.1	12.0±0.5
4	gastrocnemius	26.4±0.9	13.0±2.0	5.6±0.2	11.1±0.8
	tibialis anterior	29.0±2.0	12.7±0.5	3.9±2.0	11.6±0.2
	soleus	30.1±0.9	13.4±2.0	4.5±0.6	10.3±0.6

Table 4

Tissue sodium concentration (TSC) determined after external (B₀) and local (B₁) field inhomogeneity corrections and partial volume effect (PVE) in healthy subjects in different muscle regions and during three imaging sessions (measurements), M1, M2, and M3

Subject number↓ Muscle type→	TSC [mmol/L] - M1			TSC [mmol/L] - M2			TSC [mmol/L] - M3
Subject number↓ Muscle type→	GM	TA	S	GM	TA	S	GM	TA	S
1	20.2±0.8	13.4±0.7	12.2±0.8	21.0±0.8	13.2±0.2	12.7±0.3	20.0±0.3	13.2±0.2	12.8±0.3
2	20.5±0.9	13.7±0.9	12.9±0.9	20.8±0.4	14.0±0.8	12.5±0.2	20.5±1.0	13.2±1.0	12.7±1.0
3	19.9±0.2	14.6±1.0	13.2±0.4	19.8±0.6	14.8±1.0	13.0±1.0	19.6±2.0	14.6±0.8	12.6±0.7
4	20.8±0.5	14.0±0.4	12.5±0.9	20.5±1.0	14.5±0.6	12.8±0.9	20.0±0.8	13.9±0.9	13.1±0.7
5	20.0±0.8	14.9±0.2	13.1±1.0	19.6±0.8	14.0±0.5	12.2±0.2	19.4±1.0	13.5±0.5	12.5±0.2
6	19.5±1.0	13.8±1.0	13.9±0.5	20.0±2.0	13.1±0.1	13.5±0.5	20.8±0.9	13.7±0.7	13.4±0.4
7	19.9±0.9	13.5±0.5	12.9±1.0	19.6±1.0	13.6±0.6	12.7±0.7	19.7±0.6	13.3±0.6	12.0±0.5
8	19.5±0.8	13.7±1.0	12.1±0.4	19.5±0.9	13.0±0.7	11.7±0.8	19.4±2.0	13.5±0.1	11.1±0.3
9	19.0±0.2	14.1±0.7	11.5±0.8	19.5±1.0	14.2±0.6	12.6±0.2	19.0±0.5	13.5±0.4	11.0±0.6
10	19.8±0.5	14.4±0.8	12.2±0.2	19.0±0.7	14.0±0.2	12.9±1.0	19.8±0.9	14.3±1.0	12.8±1.0
11*	9.6±0.6	7.7±0.7	7.2±0.8
12*	10.7±0.8	8.0±0.8	7.1±1.0
13*	11.1±0.8	9.0±1.0	7.1±2.0
14*	10.8±0.9	8.8±2.0	7.4±0.5
15*	8.8±1.0	8.7±0.9	7.3±0.4

G, gastrocnemius; M1, M2, M3, the first session, the second, and the third imaging session, respectively; S, soleus; TA, tibialis anterior; TSC, tissue sodium concentration; *Addison’s patient

No competing interests reported.

Download PDF

Editorial decision: Major revision
20 Jun, 2022
Reviews received at journal
15 Jun, 2022
Reviews received at journal
14 Apr, 2022
Reviewers agreed at journal
12 Apr, 2022
Reviewers agreed at journal
08 Apr, 2022
Reviewers invited by journal
07 Apr, 2022
Editor assigned by journal
04 Apr, 2022
Editor invited by journal
04 Apr, 2022
Submission checks completed at journal
04 Apr, 2022
First submitted to journal
28 Mar, 2022

You are reading this latest preprint version

Reliability assessment of sodium ( 23 Na) MRI at 7.0 T in healthy human calf muscle and preliminary results on tissue sodium concentrations in subjects with Addison’s disease

Status:

Version 1

Abstract

Figures

Introduction

Materials And Methods

Hardware

Phantoms

Imaging protocol

Study participants

Image reconstruction and inhomogeneity correction

PVE corrections

Relaxation time calculations

TSC assessments

Statistical analysis

Results

Relaxation time measurements

Reliability tests

TSC quantification of the calf muscles

Discussion

Conclusion

Declarations

References

Tables

Additional Declarations

Status:

Version 1