23Na Magnetic Resonance Imaging Research Articles

Quantitative 23Na magnetic resonance imaging in the abdomen at 3T.

To assess the feasibility of sodium-23 MRI for performing quantitative and non-invasive measurements of total sodium concentration (TSC) and relaxation in a variety of abdominal organs. Proton and sodium imaging of the abdomen was performed in 19 healthy volunteers using a 3D cones sequence and a sodium-tuned 4-rung transmit/receive body coil on a clinical 3T system. The effects of B1 non-uniformity on TSC measurements were corrected using the double-angle method. The long-component of 23Na T2* relaxation time was measured using a series of variable echo-times. The mean and standard deviation of TSC and long-component 23Na T2* values were calculated across the healthy volunteer group in the kidneys, cerebrospinal fluid (CSF), liver, gallbladder, spleen, aorta, and inferior vena cava. Mean TSC values in the kidneys, liver, and spleen were similar to those reported using 23Na-MRI previously in the literature. Measurements in the CSF and gallbladder were lower, potentially due to the reduced spatial resolution achievable in a clinically acceptable scan time. Mean long-component 23Na T2* values were consistent with previous reports from the kidneys and CSF. Intra-population standard error was larger in smaller, fluid-filled structures due to fluid motion and partial volume effects.

Sodium quantification in skeletal muscle: comparison between Cartesian gradient-echo and radial ultra-short echo time 23Na MRI techniques

BackgroundClinical magnetic resonance imaging (MRI) studies often use Cartesian gradient-echo (GRE) sequences with ~2-ms echo times (TEs) to monitor apparent total sodium concentration (aTSC). We compared Cartesian GRE and ultra-short echo time three-dimensional (3D) radial-readout sequences for measuring skeletal muscle aTSC.MethodsWe retrospectively evaluated 211 datasets from 112 volunteers aged 62.3 ± 12.1 years (mean ± standard deviation), acquired at 3 T from the lower leg. For 23Na MRI acquisitions, we used a two-dimensional Cartesian GRE sequence and a density-adapted 3D radial readout sequence with cuboid field-of-view (DA-3D-RAD-C). We calibrated the 23Na MR signal using reference tubes either with or without agarose and subsequently performed a relaxation correction. Additionally, we employed a six-echo 1H GRE sequence and a multi-echo spin-echo sequence to calculate proton density fat fraction (PDFF) and water T2. Paired Wilcoxon signed-rank test, Cohen dz for paired samples, and Spearman correlation were used.ResultsRelaxation correction effectively reduced the differences in muscle aTSC between the two acquisition and calibration methods (DA-3D-RAD-C using NaCl/agarose references: 20.05 versus 19.14 mM; dz = 0.395; Cartesian GRE using NaCl/agarose references: 19.50 versus 18.82 mM; dz = 0.427).Both aTSC of the DA-3D-RAD-C and Cartesian GRE acquisitions showed a small but significant correlation with PDFF as well as with water T2.ConclusionsDifferent 23Na MRI acquisition and calibration approaches affect aTSC values. Applying relaxation correction is advised to minimize the impact of sequence parameters on quantification, and considering additional fat correction is advisable for patients with increased fat fractions.Relevance statementThis study highlights relaxation correction’s role in improving sodium MRI accuracy, paving the way for better disease assessment and comparability of measured sodium signal in patients.Key points• Differences in MRI acquisition methods hamper the comparability of sodium MRI measurements.• Measured sodium values depend on used MRI sequences and calibration method.• Relaxation correction during postprocessing mitigates these discrepancies.• Thus, relaxation correction enhances accuracy of sodium MRI, aiding its clinical use.Graphical

Hardware and Software Setup for Quantitative 23Na Magnetic Resonance Imaging at 3T: A Phantom Study.

Magnetic resonance (MR) with sodium (23Na) is a noninvasive tool providing quantitative biochemical information regarding physiology, cellular metabolism, and viability, with the potential to extend MR beyond anatomical proton imaging. However, when using clinical scanners, the low detectable 23Na signal and the low 23Na gyromagnetic ratio require the design of dedicated radiofrequency (RF) coils tuned to the 23Na Larmor frequency and sequences, as well as the development of dedicated phantoms for testing the image quality, and an MR scanner with multinuclear spectroscopy (MNS) capabilities. In this work, we propose a hardware and software setup for evaluating the potential of 23Na magnetic resonance imaging (MRI) with a clinical scanner. In particular, the reliability of the proposed setup and the reproducibility of the measurements were verified by multiple acquisitions from a 3T MR scanner using a homebuilt RF volume coil and a dedicated sequence for the imaging of a phantom specifically designed for evaluating the accuracy of the technique. The final goal of this study is to propose a setup for standardizing clinical and research 23Na MRI protocols.

The effects of semaglutide, empagliflozin and their combination on the kidney sodium signal from magnetic resonance imaging: A prespecified, secondary analysis from a randomized, clinical trial

AimsTo evaluate the effect of treatment with semaglutide and empagliflozin on the cortico-medullary sodium gradient (MCR; medulla/cortex ratio), urine sodium/creatinine ratio (UNACR), and estimated plasma volume (ePV) and to compare the MCR between persons with and without type 2 diabetes. MethodsUsing the 23Na magnetic resonance imaging (23Na-MRI) technique, we investigated the effects of 32 weeks of treatment with semaglutide, empagliflozin or their combination on MCR in 65 participants with type 2 diabetes and high risk of cardiovascular disease. The participants were recruited from a randomized, controlled interventional trial and further characterized by UNACR and ePV. In addition, in a cross-sectional design, we compared MCR by 23Na-MRI in 12 persons with type 2 diabetes and 17 matched controls. Data from the interventional trial were analyzed using a single, multivariate linear mixed model strategy for repeated measurements. Data from the cross-sectional study were analyzed by fitting a linear regression model adjusted for age and sex. ResultsCompared to placebo, semaglutide, but not empagliflozin, significantly decreased the MCR (−9 %, 95%CI (−18, −0.06)%, p = 0.035 and −0.05 %, 95%CI(−0.15, 0.05)%, p = 0.319, respectively). The UNACR decreased in the semaglutide group(−35 %, 95 % CI(−52, −14) %, p = 0.003) but not in the empagliflozin group (7 %, 95 % CI(−21, 44)%, p = 0.657), whereas the ePV decreased in the combination group. The MCR was not different between persons with and without type 2 diabetes. Conclusion23Na magnetic resonance imaging can identify drug induced changes in the MCR in persons with type 2 diabetes, and 32 weeks of semaglutide decreases the MCR in such persons. There is no difference in the MCR between persons with and without type 2 diabetes. Trial number and registryEUDRACT 2019-000781-38, clinicaltrialsregister.eu.

Abstract 13395: Dapagliflozin Reduces Myocardial Sodium Content and Correlates With Reverse Cardiac Remodeling in Nondiabetic Patients With Heart Failure and Preserved Ejection Fraction (Dapa-Sodium)

Introduction: Myocardial sodium overload is a major determinant of adverse cardiac remodeling in heart failure (HF). Sodium tissue content by 23Na magnetic resonance imaging (23Na-MRI) has been validated in human studies. SGLT-2 inhibition blocks sodium reabsorption in renal proximal tubular cells with remarkable cardiovascular outcomes in HF due to mechanisms not yet fully understood. Hypothesis: SGLT-2 inhibition will decrease myocardial sodium content and it will correlate with reverse remodeling in HFpEF. Aim: To determine whether Dapagliflozin leads to decreased myocardial sodium content and reverses pathological hypertrophy in HFpEF. Methods: Prospective, single-center, open-label study of sixty nondiabetic outpatients with HFpEF underwent baseline 23Na-MRI and initiated with dapagliflozin 10 mg once daily according to GDMT. Absolute changes in myocardium relative sodium signal intensity (rSSI) and left ventricular mass index (LVMi) were analyzed from baseline and at 3-month follow-up with 23Na-MRI. Results: All patients exhibited significantly high baseline myocardium rSSI [0.32 (0.28, 0.34)]; 66% above median [0.24 (0.20, 0.27), P = 0.004], decreasing -30% to [0.27 (0.22, 0.30), P<0.001] at 3 months with Dapagliflozin therapy. These changes were correlated with a significant reduction in LVMi of -13 g/m 2 [from 84 g/m 2 (72, 120) to 71 g/m 2 (63, 95), P<0.001]. Conclusions: Dapagliflozin reduces myocardial sodium content and reverses pathological hypertrophy in patients with HFpEF. These findings suggest that SGLT-2 inhibition acts directly on cardiomyocytes and explains the cardioprotective effects demonstrated though large randomized trials.

Skin sodium content as a predictor of blood pressure response to renal denervation

Patients with treatment resistant hypertension (TRH) are known to have elevated sodium (Na) content in muscle and skin. Renal denervation (RDN) emerged as an adjacent therapeutic option in this group of patients. This analysis aimed at evaluating whether tissue Na content predicts blood pressure (BP) response after RDN in patients with TRH. Radiofrequency-device based RDN was performed in 58 patients with uncontrolled TRH. Office and 24-h ambulatory BP were measured at baseline and after 6 months. To assess tissue Na content Na magnetic resonance imaging (Na-MRI) was performed at baseline prior to RDN. We splitted the study cohort into responders and non-responders based on the median of systolic 24-h ambulatory blood pressure (ABP) reduction after 6 months and evaluated the association between BP response to RDN and tissue Na content in skin and muscle. The study was registered at http://www.clinicaltrials.gov (NCT01687725). Six months after RDN 24-h ABP decreased by −8.6/−4.7 mmHg. BP-Responders were characterized by the following parameters: low tissue sodium content in the skin (p = 0.040), female gender (p = 0.027), intake of aldosterone antagonists (p = 0.032), high baseline 24-h night-time heart rate (p = 0.045) and high LDL cholesterol (p < 0.001). These results remained significant after adjustment for baseline 24-h systolic BP. Similar results were obtained when the median of day-time and night-time ABP reduction after 6 months were used as cut-off criteria for defining BP response to RDN. We conclude that in addition to clinical factors including baseline 24-h ABP Na-MRI may assist to select patients with uncontrolled TRH for RDN treatment.

Multiple quantum filtered nuclear magnetic resonance of 23Na+ in uniformly stretched and compressed hydrogels.

Stretching or compressing hydrogels creates anisotropic environments that lead to motionally averaged alignment of embedded guest quadrupolar nuclear spins such as 23Na+. These distorted hydrogels can elicit a residual quadrupolar coupling that gives an oscillation in the trajectories of single quantum coherences (SQCs) as a function of the evolution time during a spin-echo experiment. We present solutions to equations of motion derived with a Liouvillian superoperator approach, which encompass the coherent quadrupolar interaction in conjunction with relaxation, to give a full analytical description of the evolution trajectories of rank-1 (T^1±1), rank-2 (T^2±1), and rank-3 (T^3±1) SQCs. We performed simultaneous numerical fitting of the experimental 23Na nuclear magnetic resonance (NMR) spectra and rank-2 (T^2±1) and rank-3 (T^3±1) SQC evolution trajectories measured in double and triple quantum filtered experiments, respectively. We estimated values of the quadrupolar coupling constant CQ, rotational correlation time τC, and 3 × 3 Saupe order matrix. We performed simultaneous fitting of the analytical expressions to the experimental data to estimate values of the quadrupolar coupling frequency ωQ/2π, residual quadrupolar coupling ωQ/2π, and corresponding spherical order parameter S0*, which showed a linear dependence on the extent of uniform hydrogel stretching and compression. The analytical expressions were completely concordant with the numerical approach. The insights gained here can be extended to more complicated (biological) systems such as 23Na+ bound to proteins or located inside and outside living cells in high-field NMR experiments and, by extension, to the anisotropic environments found in vivo with 23Na magnetic resonance imaging.

High tissue-sodium associates with systemic inflammation and insulin resistance in obese individuals

Background and aimsHigh sodium intake is associated with obesity and insulin resistance, and high extracellular sodium content may induce systemic inflammation, leading to cardiovascular disease. In this study, we aim to investigate whether high tissue sodium accumulation relates with obesity-related insulin resistance and whether the pro-inflammatory effects of excess tissue sodium accumulation may contribute to such association. Methods and resultsIn a cross-sectional study of 30 obese and 53 non-obese subjects, we measured insulin sensitivity determined as glucose disposal rate (GDR) using hyperinsulinemic euglycemic clamp, and tissue sodium content using 23Na magnetic resonance imaging. Median age was 48 years, 68% were female and 41% were African American. Median (interquartile range) BMI was 33 (31.5, 36.3) and 25 (23.5, 27.2) kg/m2 in the obese and non-obese individuals, respectively. In obese individuals, insulin sensitivity negatively correlated with muscle (r = −0.45, p = 0.01) and skin sodium (r = −0.46, p = 0.01). In interaction analysis among obese individuals, tissue sodium had a greater effect on insulin sensitivity at higher levels of high-sensitivity C-reactive protein (p-interaction = 0.03 and 0.01 for muscle and skin Na+, respectively) and interleukin-6 (p-interaction = 0.024 and 0.003 for muscle and skin Na+, respectively). In interaction analysis of the entire cohort, the association between muscle sodium and insulin sensitivity was stronger with increasing levels of serum leptin (p-interaction = 0.01). ConclusionsHigher muscle and skin sodium are associated with insulin resistance in obese patients. Whether high tissue sodium accumulation has a mechanistic role in the development of obesity-related insulin resistance through systemic inflammation and leptin dysregulation remains to be examined in future studies.Clinicaltrials.gov registration: NCT02236520.

Annals for Hospitalists - March 2023

Annals for Hospitalists - March 2023

Variability by region and method in human brain sodium concentrations estimated by 23Na magnetic resonance imaging: a meta-analysis

Sodium imaging (23Na-MRI) is of interest in neurological conditions given potential sensitivity to the physiological and metabolic status of tissues. Benchmarks have so far been restricted to parenchyma or grey/white matter (GM/WM). We investigate (1) the availability of evidence, (2) regional pooled estimates and (3) variability attributable to region/methodology. MEDLINE literature search for tissue sodium concentration (TSC) measured in specified ‘healthy’ brain regions returned 127 reports, plus 278 retrieved from bibliographies. 28 studies met inclusion criteria, including 400 individuals. Reporting variability led to nested data structure, so we used multilevel meta-analysis and a random effects model to pool effect sizes. The pooled mean from 141 TSC estimates was 40.51 mM (95% CI 37.59–43.44; p < 0.001, I2Total=99.4%). Tissue as a moderator was significant (F214 = 65.34, p-val < .01). Six sub-regional pooled means with requisite statistical power were derived. We were unable to consider most methodological and demographic factors sought because of non-reporting, but each factor included beyond tissue improved model fit. Significant residual heterogeneity remained. The current estimates provide an empirical point of departure for better understanding in 23Na-MRI. Improving on current estimates supports: (1) larger, more representative data collection/sharing, including (2) regional data, and (3) agreement on full reporting standards.

The role of machine learning in developing non-magnetic resonance imaging based biomarkers for multiple sclerosis: a systematic review

BackgroundMultiple sclerosis (MS) is a neurological condition whose symptoms, severity, and progression over time vary enormously among individuals. Ideally, each person living with MS should be provided with an accurate prognosis at the time of diagnosis, precision in initial and subsequent treatment decisions, and improved timeliness in detecting the need to reassess treatment regimens. To manage these three components, discovering an accurate, objective measure of overall disease severity is essential. Machine learning (ML) algorithms can contribute to finding such a clinically useful biomarker of MS through their ability to search and analyze datasets about potential biomarkers at scale. Our aim was to conduct a systematic review to determine how, and in what way, ML has been applied to the study of MS biomarkers on data from sources other than magnetic resonance imaging.MethodsSystematic searches through eight databases were conducted for literature published in 2014–2020 on MS and specified ML algorithms.ResultsOf the 1, 052 returned papers, 66 met the inclusion criteria. All included papers addressed developing classifiers for MS identification or measuring its progression, typically, using hold-out evaluation on subsets of fewer than 200 participants with MS. These classifiers focused on biomarkers of MS, ranging from those derived from omics and phenotypical data (34.5% clinical, 33.3% biological, 23.0% physiological, and 9.2% drug response). Algorithmic choices were dependent on both the amount of data available for supervised ML (91.5%; 49.2% classification and 42.3% regression) and the requirement to be able to justify the resulting decision-making principles in healthcare settings. Therefore, algorithms based on decision trees and support vector machines were commonly used, and the maximum average performance of 89.9% AUC was found in random forests comparing with other ML algorithms.ConclusionsML is applicable to determining how candidate biomarkers perform in the assessment of disease severity. However, applying ML research to develop decision aids to help clinicians optimize treatment strategies and analyze treatment responses in individual patients calls for creating appropriate data resources and shared experimental protocols. They should target proceeding from segregated classification of signals or natural language to both holistic analyses across data modalities and clinically-meaningful differentiation of disease.

Grey-matter sodium concentration as an individual marker of multiple sclerosis severity

Objective: Quantification of brain injury in patients with variable disability despite similar disease duration may be relevant to identify the mechanisms underlying disability in multiple sclerosis (MS). We aimed to compare grey-matter sodium abnormalities (GMSAs), a parameter reflecting neuronal and astrocyte dysfunction, in MS patients with benign multiple sclerosis (BMS) and non-benign multiple sclerosis (NBMS). Methods: We identified never-treated BMS patients in our local MS database of 1352 patients. A group with NBMS was identified with same disease duration. All participants underwent 23Na magnetic resonance imaging (MRI). The existence of GMSA was detected by statistical analysis. Results: In total, 102 individuals were included (21 BMS, 25 NBMS and 56 controls). GMSA was detected in 10 BMS and 19 NBMS (11/16 relapsing-remitting multiple sclerosis (RRMS) and 8/9 secondary progressive multiple sclerosis (SPMS) patients) (p = 0.05). On logistic regression including the presence or absence of GMSA, thalamic volume, cortical grey-matter volume and T2-weighted lesion load, thalamic volume was independently associated with BMS status (odds ratio (OR) = 0.64 for each unit). Nonetheless, the absence of GMSA was independently associated when excluding patients with significant cognitive alteration (n = 7) from the BMS group (OR = 4.6). Conclusion: Detection of GMSA in individuals and thalamic volume are promising to differentiate BMS from NBMS as compared with cortical or whole grey-matter atrophy and T2-weighted lesions.

Comprehensive Account of Sodium Imaging and Spectroscopy for Brain Research

Sodium (23Na) is a vital component of neuronal cells and plays a key role in various signal transmission processes. Hence, information on sodium distribution in the brain using magnetic resonance imaging (MRI) provides useful information on neuronal health. 23Na MRI and MR spectroscopy (MRS) improve the diagnosis, prognosis, and clinical monitoring of neurological diseases but confront some inherent limitations that lead to low signal-to-noise ratio, longer scan time, and diminished partial volume effects. Recent advancements in multinuclear MR technology have helped in further exploration in this domain. We aim to provide a comprehensive description of 23Na MRI and MRS for brain research including the following aspects: (a) theoretical background for understanding 23Na MRI and MRS fundamentals; (b) technological advancements of 23Na MRI with respect to pulse sequences, RF coils, and sodium compartmentalization; (c) applications of 23Na MRI in the early diagnosis and prognosis of various neurological disorders; (d) structural-chronological evolution of sodium spectroscopy in terms of its numerous applications in human studies; (e) the data-processing tools utilized in the quantitation of sodium in the respective anatomical regions.

Extended Ischemic Recovery After Implantation of Human Mesenchymal Stem Cell Aggregates Indicated by Sodium MRI at 21.1T.

Extended therapeutic application remains a significant issue in the use of stem cell therapies to treat ischemic stroke. Along these lines, neurological recovery in a rodent model of ischemic stroke was evaluated following implantation of human mesenchymal stem cell aggregates (hMSC-agg), labeled with micron-sized particles of iron oxide, directly into the lateral ventricle contralateral to the ischemic lesion hemisphere. Longitudinally, disease progression and response to hMSC-agg therapy were assessed by 1H and 23Na magnetic resonance imaging (MRI) at 21.1T to investigate cellular localization, migration, and recovery over an extended timeframe. MRI provides quantifiable metrics of tissue status through sodium distributions in addition to traditional proton imaging. Quantitative 23Na MRI revealed a significant decrease of sodium concentrations following hMSC aggregate implantation, indicating recovery of homeostasis. This result correlates positively with extended neurological recovery assessed by behavioral analysis and immunohistochemistry. These findings demonstrate the potential of implanted hMSC aggregate therapy to provide extended treatment for ischemic stroke, as well as the robustness of MRI for monitoring such approaches. This method potentially can be translated to a clinical setting for the assessment of extended cell therapy efficacy.

Relaxation-weighted 23Na magnetic resonance imaging maps regional patterns of abnormal sodium concentrations in amyotrophic lateral sclerosis.

Objectives:Multiparametric magnetic resonance imaging (MRI) is established as a technical instrument for the characterisation of patients with amyotrophic lateral sclerosis (ALS). The contribution of relaxation-weighted sodium (23NaR) MRI remains to be defined. The aim of this study is to apply 23NaR MRI to investigate brain sodium homeostasis and map potential alterations in patients with ALS as compared with healthy controls.Materials and Methods:Seventeen patients with ALS (mean age 61.1 ± 11.4 years, m/f = 9/8) and 10 healthy control subjects (mean age 60.3 ± 15.3 years, m/f = 6/4) were examined by 23NaR MRI at 3 T. Regional sodium maps were obtained by the calculation of the weighted difference from two image data sets with different echo times (TE1 = 0.3 ms, TE2 = 25 ms). Voxel-based analysis of the relaxation-weighted maps, together with 23Na concentration maps for comparison, was performed.Results:ROI-based analyses of relaxation-weighted brain sodium concentration maps demonstrated increased sodium concentrations in the upper corticospinal tracts and in the frontal lobes in patients with ALS; no differences between ALS patients and controls were found in reference ROIs, where no involvement in ALS-associated neurodegeneration could be anticipated.Conclusion:23NaR MRI mapped regional alterations within disease-relevant areas in ALS which correspond to the stages of the central nervous system (CNS) pathology, providing evidence that the technique is a potential biological marker of the cerebral neurodegenerative process in ALS.

Hemodialysis Patients with Cardiovascular Disease Reveal Increased Tissue Na+ Deposition

Background: The relationship between Na⁺ balance and cardiovascular disease (CVD) in hemodialysis (HD) patients is not yet fully understood. We hypothesized that HD patients co-diagnosed with CVD show increased tissue Na⁺ accumulation compared to HD patients without CVD. Methods: In our observational study, 52 HD patients were divided into a group with (23 subjects) or without (29 subjects) a positive history of cardiovascular events. We used ²³Na-magnetic resonance imaging (²³Na-MRI) at 3.0 Tesla to quantify Na⁺ content in skin and muscle of both groups directly before and after HD. Additionally, total body fluid distribution was determined by bioimpedance spectroscopy (BIS) and laboratory parameters were assessed. Results: Compared to HD patients without CVD, ²³Na-MRI detected an increased Na⁺ content in skin (21.7 ± 7.3 vs. 30.2 ± 9.8 arbitrary units (a.u.), p < 0.01) and muscle tissue (21.5 ± 3.6 vs. 24.7 ± 6.0 a.u., p < 0.05) in patients with previous CVD events. Simultaneously measured fluid amount by BIS, includingexcess extracellular water (1.8 ± 1.7 vs. 2.2 ± 1.7 L, p = 0.44), was not significantly different between both groups. Tissue Na⁺ accumulation in HD-CVD patients was paralleled by a higher plasma concentration of the inflammation marker interleukin-6 (5.1, IQR 5.8 vs. 8.5, IQR 7.9 pg/mL, p < 0.05). Conclusion: In our cohort, HD patients with CVD showed higher tissue Na⁺ content than HD patients without CVD, while no difference in body water distribution could be detected between both groups. Our findings provide evidence that the history of a cardiovascular event is associated with disturbances in tissue Na⁺ content in HD patients.

Tissue Sodium Storage in Patients With Heart Failure: A New Therapeutic Target?

Preclinical data suggest sodium deposited (without water) in tissues may lead to aberrant remodeling and systemic inflammation, independently of fluid overload in patients with heart failure (HF). Tissue salt storage can be measured noninvasively and quantitatively with 23Na-magnetic resonance imaging. We aimed to investigate the possibility that patients with HF complicated by renal dysfunction are subject to higher tissue sodium concentration exposure than patients with chronic kidney disease alone. We conducted an exploratory study including 18 patients with HF, 34 hemodialysis patients (with no meaningful renal clearance of sodium), and 31 patients with chronic kidney disease, with glomerular filtration rate matched to the patients with HF. Every patient underwent 23Na-magnetic resonance imaging of the calf, to quantify tissue sodium and allow comparison among the 3 patient groups. There were no differences in age, sex, and body mass index between groups. Median (interquartile range) skin sodium content in HF (31 [23-37] mmol/L) was very high and indistinguishable from skin sodium content in hemodialysis patients (30 [22-35] mmol/L), P=0.6. Patients with HF exhibited significantly higher skin sodium content than matched estimated glomerular filtration rate chronic kidney disease patients (22 [19-26] mmol/L), P=0.005. Median muscle sodium content in patients with HF was significantly higher than in patients with chronic kidney disease, P=0.002. There was no relationship with estimated glomerular filtration rate in patients with HF. We report a significant correlation between skin sodium and urinary sodium (P=0.04) but no correlation with muscle sodium. Patients who were assessed as being volume depleted (sodium excretion fraction <1%) had lower skin sodium content than patients with sodium excretion fraction >1% (P=0.03). We have demonstrated that patients with HF characteristically have very high levels of skin sodium storage, comparable to well-characterized extreme levels seen in patients with end-stage kidney disease requiring hemodialysis. 23Na-magnetic resonance imaging may allow precision medicine in the management of this challenging group of patients with HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03004547.

What can 7T sodium MRI tell us about cellular energy depletion and neurotransmission in Alzheimer's disease?

The pathophysiological processes underlying the development and progression of Alzheimer's disease (AD) on the neuronal level are still unclear. Previous research has hinted at metabolic energy deficits and altered sodium homeostasis with impaired neuronal function as a potential metabolic marker relevant for neurotransmission in AD. Using sodium (23 Na) magnetic resonance (MR) imaging on an ultra-high-field 7 Tesla MR scanner, we found increased cerebral tissue sodium concentration (TSC) in 17 biomarker-defined AD patients compared to 22 age-matched control subjects in vivo. TSC was highly discriminative between controls and early AD stages and was predictive for cognitive state, and associated with regional tau load assessed with flortaucipir-positron emission tomography as a possible mediator of TSC-associated neurodegeneration. TSC could therefore serve as a non-invasive, stage-dependent, metabolic imaging marker. Setting a focus on cellular metabolism and potentially disturbed interneuronal communication due to energy-dependent altered cell homeostasis could hamper progressive cognitive decline by targeting these processes in future interventions.

An approach to evaluation of the point-spread function for 23 Na magnetic resonance imaging.

Despite the technical challenges that require lengthy acquisitions to overcome poor signal-to-noise ratio (SNR), sodium (23 Na) magnetic resonance imaging (MRI) is an intriguing area of research due to its essential role in human metabolism. Low SNR images can impact the measurement of the point-spread function (PSF) by adding uncertainty into the resulting quantities. Here, we present methods to calculate the PSF by using the modulation transfer function (MTF), and a 3D-printed line-pair phantom in the context of 23 Na MRI. A simulation study investigated the effect of noise on the resulting MTF curves, which were derived by direct modulation (DM) and a method utilizing Fourier harmonics (FHs). Experimental data utilized a line-pair phantom with nine spatial frequencies, filled with different concentrations (15, 30, and 60 mM) of sodium in 3% agar. MTF curves were calculated using both methods from data acquired from density-adapted 3D radial projections (DA-3DRP) and Fermat looped orthogonally encoded trajectories (FLORET). Simulations indicated that the DM method increased variability in the MTF curves at all tested noise levels over the FH method. For the experimental data, the FH method resulted in PSFs with a narrower full width half maximum with reduced variability, although the improvement in variability was not as pronounced as predicted by simulations. The DA-3DRP data indicated an improvement in the PSF over FLORET. It was concluded that a 3D-printed line-pair phantom represents a convenient method to measure the PSF experimentally. The MTFs from the noisy images in 23 Na MRI have reduced variability from a FH method over DM.

Ode to Salt: Commentary on “Skin Sodium Accumulates in Psoriasis and Reflects Disease Severity”

"Skin Sodium Accumulates in Psoriasis and Reflects Disease Severity" (Maifeld etal., 2021) showed that skin sodium ion (Na+) is increased in patients with a PASI > 5. Na+ concentration as well as its content were increased in these patients, supporting the proposed mechanism that increased Na+ concentrations enhance IL-17 expression from CD4+ cells. These data initially were generated using a noninvasive technique, sodium (23Na) magnetic resonance imaging, and then were verified using 23Na spectroscopy and atomic absorption spectrometry in ashed-skin biopsies in humans and also using mouse models of psoriasis. These findings suggest a novel pathologic mechanism for psoriasis development and target for treatment.