Armin Michael Nagel

BACKGROUND: Potassium-enriched table salt lowers blood pressure (BP) and reduces cardiovascular mortality. Whether these beneficial effects stem from reduced Na ⁺ intake, increased K ⁺ intake, or both is unknown. We tested the hypothesis that oral potassium chloride (KCl) supplementation lowers body Na ⁺ content and BP in patients with essential hypertension (EH) or hyperaldosteronism, independent of salt intake. METHODS: Between February 2024 and February 2025, we conducted a single-arm, prospective, longitudinal study with nonrandomized oral KCl intervention in 40 participants with hypertension. All received personalized (blood K ⁺ -adjusted) KCl supplementation (SPAN-K tablets, potassium chloride 600 mg; Aspen Pharmacare Australia Pty, Ltd) for 6 to 9 weeks. After the intervention, participants completed a routine diagnostic workup and were classified with EH or hyperaldosteronism. Primary end point: baseline muscle Na ⁺ surplus in hyperaldosteronism. Secondary end point: interventional muscle Na ⁺ mobilization and BP reduction. RESULTS: Seventeen participants were diagnosed with EH, and 23 with hyperaldosteronism. At baseline, patients with hyperaldosteronism showed higher muscle Na ⁺ content (24.67±2.93 versus 22.48±3.37 mmol/L tissue volume, P =0.023; primary end point). Oral KCl increased 24-hour urine K ⁺ excretion without altering 24-hour urine Na ⁺ . KCl supplementation successfully eliminated the muscle Na ⁺ surplus in the hyperaldosteronism group (−1.90 mmol/L tissue volume [95% CI, −3.20 to −0.60]; P =0.005; secondary end point), lowered blood Na ⁺ /K ⁺ ratios in both groups (EH, −5.34 [95% CI, −7.69 to −2.99]; P =4.6×10 ^-5 ; hyperaldosteronism, −7.02 [95% CI, −9.04 to −5.01]; P =2.1×10 ^-8 ), and reduced systolic BP (EH, −8.33 mm Hg [95% CI, −14.55 to −2.12]; P =0.010; hyperaldosteronism, −7.35 mm Hg [95% CI, −12.69 to −2.01]; P =0.008). To account for early study termination, a conservative significance threshold of α=0.025 was implemented, which all end points crossed. CONCLUSIONS: Oral KCl supplementation mobilizes intracellular Na ⁺ stores, corrects pathological Na ⁺ /K ⁺ distribution, and lowers BP across hypertension phenotypes. This safe, targeted approach warrants consideration as a scalable public health strategy for cardiovascular disease prevention. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06569589.

Purpose: To evaluate the repeatability of an extended multiparametric 7 T MRI protocol for voxel‐wise tissue characterization combining morphological, CEST, QSM, QTI, and Sodium contrasts. Methods: A repeatability study was performed in 12 volunteers without diagnosed neurological disease on a 7 T MRI system, using a comprehensive acquisition protocol with a combined acquisition time of 45:24 min, from which 45 contrast maps were derived. Quantitative repeatability was assessed using region‐based and voxel‐wise analyses. Precision and reliability were evaluated using the coefficient of variation (CV), repeatability coefficient (%RC), and intraclass correlation coefficient (ICC). Voxel‐wise agreement between scan–rescan images was assessed using Pearson correlation coefficients. Results: Across contrasts spanning morphological, CEST, QSM, QTI, and ²³ Na imaging, %RC was below 20% for 20 contrasts, with mean CV below 5% for most. Repeatability was highest for MP2RAGE T ₁ maps and QTI MD (CV ≈ 1%–2%; ICC up to 0.86) and lowest for ²³ Na imaging (ICC < 0.6). CEST contrasts were highly repeatable at low saturation power but more variable at higher power (CV up to ≈8%). QSM contrasts showed moderate ICC (0.46–0.82). Voxel‐wise correlations exceeded r = 0.8 for most contrasts, confirming preserved spatial patterns across repeated scans. Conclusion: Multiparametric 7 T MRI enables reproducible voxel‐wise characterization of brain tissue across a wide range of contrasts. Despite variability in specific contrasts, the overall high repeatability and strong voxel‐wise agreement support the feasibility of voxel‐wise imaging approaches for quantitative brain imaging and provide a foundation for future applications in clinical research and neuroscience.

Purpose: Chemical exchange saturation transfer (CEST) MRI offers unique metabolic insights for imaging of cancer, stroke, or neurodegeneration. However, the rapid expansion of CEST preparation schemes and evaluation techniques creates a bottleneck; novel methods often remain complex prototypes requiring offline processing, preventing clinical adoption. Methods: To bridge this gap, we propose a hybrid sequence and reconstruction framework. This approach combines a flexible, pTx‐enabled preparation block using the open‐source Pulseq standard with a closed‐source snapshot readout, and an interchangeable ONNX‐based neural network for online post‐processing. Results: We validated this framework at 7 T using three distinct applications: deepWASABI for B0 and B1 prediction, a protein CEST approach for B1‐corrected CEST mapping, and semi‐solid MT MRF for quantifying magnetization transfer rates and semi‐solid proton volume fractions. By utilizing closed‐source readouts, we leverage advanced proprietary image reconstructions essential for high‐resolution whole‐brain coverage. Simultaneously, the integrated ONNX network processes contrast‐weighted images directly at the scanner to generate parameter maps online. Conclusion: This hybrid architecture eliminates complex compilation steps, allowing deployment by simply copying Pulseq and ONNX files. By enabling push‐button execution and immediate clinical data storage, this platform significantly accelerates the development, evaluation, and dissemination of advanced CEST MRI methods and forms a blueprint for scaling any magnetization‐prepared MRI approach at any system.

Sodium MRI can be used in musculoskeletal imaging to assess tissue composition because sodium concentration is related to glycosaminoglycan (GAG) content. In tendinopathy, the GAG content is elevated, resulting in a high signal in sodium MRI. Because biochemical changes typically precede structural alterations, sodium MRI may be a useful indicator for detecting early tendon matrix changes associated with tendinopathy. Quantitative sodium concentration determination has only been applied to Achilles tendons but not yet to smaller tendons, such as the patellar tendon. Due to its smaller diameter, the patellar tendon is more susceptible to partial volume artifacts, making accurate sodium concentration quantification more challenging. However, partial volume correction (PVC) may help overcome these difficulties. In this study, we determined the apparent tissue sodium concentration (aTSC) in seven patients with patellar tendinopathy and 20 healthy controls using clinical 3 T MRI with a density‐adapted 3D radial MR‐sequence. Sodium images were corrected for partial volume effects using an in‐house developed PVC, called the estimated single target correction (eSTC). Additionally, ¹ H T ₂ * values were calculated for comparison, as they are sensitive to structural alterations. Sodium relaxation times were determined in three healthy controls, resulting in a T ₁ of 30.2 ± 0.4 ms and a biexponential T _2s * of 0.7 ± 0.2 ms and T _2l * of 13.0 ± 0.1 ms. The short component p _s accounted for 35.7% ± 2.1% of the transversal relaxation. aTSC values were 35.4 ± 10.1 mM in tendinopathy patients and 21.6 ± 3.9 mM in healthy controls. ¹ H T ₂ * values were 5.4 ± 1.9 ms and 2.8 ± 0.3 ms, respectively. Differences between patients and controls were significant for both parameters. These findings support the suitability of sodium MRI for quantitative assessment of the patellar tendon and demonstrate its potential for visualizing biochemical changes associated with patellar tendinopathy.

Background: Lung surveillance in cystic fibrosis (CF) relies on chest radiography (CR) despite cumulative radiation. Low-field MRI may be a radiation-free alternative for children and young adults. Methods: We prospectively compared 0.55 T MRI and CR in 28 same-day examinations of 22 people with CF (mean age 13 ± 5 years). Three raters scored the disease with the MRI CF score and a modified Chrispin–Norman score, expanded from two to three zones per hemithorax to match the six MRI lobes. Analyses used per-examination values averaged across the raters (Wilcoxon tests, intraclass correlation coefficients, ICC). Results: MRI yielded higher global scores (median 8.2 vs. 6.7, p = 0.002) and higher centrilobular opacity scores (p = 0.005, adjusted p = 0.03). Air trapping was also higher on MRI (p = 0.025) but not after correction for multiple comparisons (adjusted p = 0.12). The other categories did not differ. Both correlated inversely with FEV1 (p < 0.001), without a significant modality-by-FEV1 interaction (p = 0.08). Interobserver agreement was higher for MRI (ICC = 0.93) than CR (0.82), difference 0.12 (95% bootstrap CI 0.06 to 0.18). The findings held in a per-participant sensitivity analysis. Conclusions: 0.55 T MRI is a feasible, radiation-free alternative to CR in CF, yielding higher modality-specific scores and more consistent interobserver agreement. Because the instruments were only category-mapped and no CT reference was available, higher scores do not establish superior lesion detection.

Purpose: Most sites develop and use custom coils for 7 T body MRI since no standard pTx body coil exists, leading to diverse coil designs differing in transmit element type, layout, and number of receive channels. This study investigates and compares eight existing coils, including one remote body coil array and seven local arrays, regarding their transmit and receive performance. Methods: Phantom measurements were conducted with all coils on the same 7 T scanner, using the same phantom and imaging protocol. Transmit performance was compared in terms of B ₁ ⁺ efficiency and coverage. Receive performance was compared in terms of SNR, coverage, noise correlation, and g‐factors. Results: Mean B ₁ ⁺ efficiency ranged from 2.02 to 4.33 μT/√kW across configurations, lowest for the remote array and highest for an 8Tx8Rx local array. Central SNR ranged from 278 to 1072, increasing with receive element count and peaking for an 8Tx32Rx configuration. HF‐excitation‐coverage ranged from 34 to 384 mm, and HF‐receive‐coverage from 135 to 384 mm, with the remote array combined with a local 32Rx array achieving highest coverage. Acceleration performance improved with increasing receive element count in the corresponding direction. An 8Tx16Rx and an 8Tx32Rx arrays performed best in LR‐/AP‐direction and the 32Rx array in HF‐direction. Conclusion: No existing local pTx coil provides universally optimal performance, as each design offers different advantages in either B ₁ ⁺ efficiency, coverage, SNR, or acceleration. Among the local arrays, the 8Tx32Rx array (C5) might represent a reasonable compromise with respect to the parameters evaluated in this study, as it exhibits the highest central SNR, high coverage, and acceleration.

Purpose: To study the impact of mesoscopic magnetic susceptibility heterogeneity on chemical shift‐encoded (CSE) proton density fat‐fraction (PDFF) quantification in muscular dystrophies, a subgroup of neuromuscular disorders. Theory and Methods: In MRI, extramyocellular lipid deposits induce orientation‐dependent Larmor frequency variations due to microstructural anisotropy, resulting in spatially varying frequency shifts between fat and water and increased transverse relaxation rates. A newly developed PDFF quantification method accounting for resonance shifts and dual R ₂ * rates was applied on standard 6‐point CSE acquisitions of Duchenne ( n = 15), Becker ( n = 31), and facioscapulohumeral ( n = 30) muscular dystrophy patients, and control subjects ( n = 40). The impact of frequency shifts, decay functions, and lipid models on PDFF estimation was systematically assessed. Results: Accounting for resonance shifts resulted in large PDFF quantification differences compared to a reference method (−3.8% [−14.8%, 7.2%]), significantly improved fitting quality (Bayesian Information Criterion (BIC) difference ≥ 10), and reduced fat/water separation artifacts, confirming predictions by numerical simulations. Bias and variability due to the lipid model were reduced to less than 1%. Fitting quality in high R ₂ * regions was further improved using a dual relaxation model with linear/quadratic decay (BIC difference ≥ 2). Sensitivity to change was improved on the tested cohorts (SRM increased by 0.18). DTI‐estimated angular dependencies reflected theoretical and numerical predictions for elongated axially symmetric lipid deposits. Conclusion: The proposed approach improvements could enhance the PDFF quantification reliability in neuromuscular disorders studies and support more accurate monitoring of myosteatosis.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cysts from different nephron segments, yet their origin remains inaccessible to in vivo imaging. Building on ex vivo studies that cyst sodium concentration ([Na⁺]) may reflect tubular origin, we developed a non-invasive ²³ Na magnetic resonance imaging (MRI) approach at 7 Tesla to phenotype ADPKD cysts in vivo based on cyst sodium. In nephrectomized ADPKD kidneys, cyst fluid [Na ⁺ ] closely matched ²³ Na MRI signal intensities, revealing two distinct cyst phenotypes: serum-like high-[Na ⁺ ] cysts and low-[Na ⁺ ] cysts. High-[Na ⁺ ] cysts expressed the proximal tubular marker sodium-glucose cotransporter-2, whereas low-[Na ⁺ ] cysts expressed markers of distal tubules and collecting ducts. The vasopressin V2 receptor (V2R), the therapeutic target of tolvaptan, was detected exclusively in low-[Na ⁺ ] cysts, linking sodium phenotype to therapeutic target expression. In vivo, ²³Na MRI enabled classification of 2,299 cysts in 20 ADPKD patients. High-[Na ⁺ ] cysts were 1.8-fold more frequent overall. Anatomical cyst localization did not predict sodium phenotype, underscoring the need for functional imaging rather than structural inference. Patients exhibited marked interindividual variation in cyst composition, with low-[Na ⁺ ] cysts comprising 4.6% to 83.9% of all cysts. Given the exclusive expression of V2R in low-[Na ⁺ ] cysts, this heterogeneity may influence disease progression and therapeutic responsiveness. These findings establish ²³Na MRI as a non-invasive method to phenotype ADPKD cysts in vivo and provide a functional imaging approach with potential relevance for stratifying patients and guiding future therapeutic interventions.

To evaluate the repeatability and consistency of rapid quantitative ²³ Na MRI of the human calf, an acquisition‐weighted stack‐of‐stars (AW‐SOSt) sequence was implemented on a 7T MRI system and used for all measurements. Three variants, differing only in nominal in‐plane spatial resolution (2.5, 5.0, and 7.5 mm) and corresponding acquisition times (8:04, 4:02, and 2:41 min), while maintaining a constant slice thickness of 15 mm, were employed for imaging the calf skeletal muscle. Quantitative consistency across resolutions and repeatability was evaluated in simulations and consecutive measurements of 10 healthy volunteers. The apparent tissue sodium concentration (aTSC) was determined using a postprocessing pipeline consisting of a B ₀ , B ₁ , relaxation, and partial volume correction (PVC). Deviations of the determined aTSC from simulated ground truth were below 6.0%. The simulated coefficient of variation (CV) improved with decreasing spatial resolution from 1.1% to 0.9%. The in vivo findings matched the simulation results. The CV improved with increasing voxel size, decreasing from 2.7% at 2.5‐mm resolution to 2.0% at 7.5‐mm resolution. Measurements remained highly consistent across different in‐plane resolutions, with a small increase in aTSC (≈0.2 mM) observed as a difference between lower resolutions (7.5 mm) and the highest resolution (2.5 mm). All applied protocols showed good repeatability and high consistency between the protocols. aTSC quantification using low‐resolution ²³ Na MRI showed improved repeatability, whereas in vivo measurements showed no effect on quantitative accuracy. This study demonstrates that low‐resolution ²³ Na MRI with short acquisition times combined with PVC could be a practical alternative to commonly used “high‐resolution” techniques with long acquisition times for quantifying aTSC in calf muscle tissue.

Purpose: Spin density‐weighted (SDW) and inversion recovery (IR) ²³ Na MRI provide different sodium contrasts with complementary information. Therefore, the aim was to develop a time‐efficient sequence scheme capable of providing both contrasts by acquiring SDW and IR ²³ Na MRI data within a single sequence without additional measurement time. Methods: In the developed pulse sequence, the conventional 180° inversion pulse was divided into two successive 90° pulses, with an additional readout inserted between them. The sequence was initially evaluated in simulations and phantom measurements. Afterwards, it was applied in calf muscle measurements of six healthy volunteers to assess its practical feasibility and signal characteristics. All ²³ Na measurements were acquired at 7 T and compared to standard SDW and IR sequences. Results: The interleaved SDW/IR sequence yielded image quality and contrast comparable to standard SDW and IR sequences. Phantom experiments showed slightly higher remaining T ₁ ‐weighting in the interleaved sequence compared with standard SDW, resulting in only minor changes in image contrast. Fluid suppression was effective across all IR approaches, though efficiency decreased modestly with longer effective inversion pulse lengths. Spin dynamic simulations for IR ²³ Na MRI indicated slightly increased sensitivity to fluid suppression artifacts arising from B ₀ inhomogeneities in the interleaved sequence. In vivo calf muscle measurements did not reveal significant differences in the mean muscle signal between the interleaved SDW/IR sequence and the corresponding standard sequences. Conclusion: The proposed interleaved sequence enables simultaneous acquisition of ²³ Na SDW and IR contrasts, thereby reducing overall scan time and eliminating the need for co‐registration.