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23Na MRI can be used to quantify in-vivo tissue sodium concentration (TSC), but the inherently low 23Na signal leads to long scan times and/or noisy or low-resolution images. Reconstruction algorithms such as compressed sensing (CS) have been proposed to mitigate low signal-to-noise ratio (SNR); although, these can result in unnatural images, suboptimal denoising and long processing times. Recently, machine learning has been increasingly used to denoise 1H MRI acquisitions; however, this approach typically requires large volumes of high-quality training data, which is not readily available for 23Na MRI. Here, we propose using 1H data to train a denoising convolutional neural network (CNN), which we subsequently demonstrate on prospective 23Na images of the calf. 1893 1H fat-saturated transverse slices of the knee from the open-source fastMRI dataset were used to train denoising CNNs for different levels of noise. Synthetic low SNR images were generated by adding gaussian noise to the high-quality 1H k-space data before reconstruction to create paired training data. For prospective testing, 23Na images of the calf were acquired in 10 healthy volunteers with a total of 150 averages over ten minutes, which were used as a reference throughout the study. From this data, images with fewer averages were retrospectively reconstructed using a non-uniform fast Fourier transform (NUFFT) as well as CS, with the NUFFT images subsequently denoised using the trained CNN. CNNs were successfully applied to 23Na images reconstructed with 50, 40 and 30 averages. Muscle and skin apparent TSC quantification from CNN-denoised images were equivalent to those from CS images, with <0.9 mM bias compared to reference values. Estimated SNR was significantly higher in CNN-denoised images compared to NUFFT, CS and reference images. Quantitative edge sharpness was equivalent for all images. For subjective image quality ranking, CNN-denoised images ranked equally best with reference images and significantly better than NUFFT and CS images. Denoising CNNs trained on 1H data can be successfully applied to 23Na images of the calf; thus, allowing scan time to be reduced from ten minutes to two minutes with little impact on image quality or apparent TSC quantification accuracy. [ABSTRACT FROM AUTHOR]

Purpose: Sodium MRI can be used to quantify tissue sodium concentration (TSC) in vivo; however, UTE sequences are required to capture the rapidly decaying signal. 2D MRI enables high in‐plane resolution but typically has long TEs. Half‐sinc excitation may enable UTE; however, twice as many readouts are necessary. Scan time can be minimized by reducing the number of signal averages (NSAs), but at a cost to SNR. We propose using compressed sensing (CS) to accelerate 2D half‐sinc acquisitions while maintaining SNR and TSC. Methods: Ex vivo and in vivo TSC were compared between 2D spiral sequences with full‐sinc (TE = 0.73 ms, scan time ≈ 5 min) and half‐sinc excitation (TE = 0.23 ms, scan time ≈ 10 min), with 150 NSAs. Ex vivo, these were compared to a reference 3D sequence (TE = 0.22 ms, scan time ≈ 24 min). To investigate shortening 2D scan times, half‐sinc data was retrospectively reconstructed with fewer NSAs, comparing a nonuniform fast Fourier transform to CS. Resultant TSC and image quality were compared to reference 150 NSAs nonuniform fast Fourier transform images. Results: TSC was significantly higher from half‐sinc than from full‐sinc acquisitions, ex vivo and in vivo. Ex vivo, half‐sinc data more closely matched the reference 3D sequence, indicating improved accuracy. In silico modeling confirmed this was due to shorter TEs minimizing bias caused by relaxation differences between phantoms and tissue. CS was successfully applied to in vivo, half‐sinc data, maintaining TSC and image quality (estimated SNR, edge sharpness, and qualitative metrics) with ≥50 NSAs. Conclusion: 2D sodium MRI with half‐sinc excitation and CS was validated, enabling TSC quantification with 2.25 × 2.25 mm2 resolution and scan times of ≤5 mins. [ABSTRACT FROM AUTHOR]

Sodium magnetic resonance imaging (MRI) can be used to evaluate the change in the proteoglycan content in Achilles tendons (ATs) of patients with different AT pathologies by measuring the 23Na signal-to-noise ratio (SNR). As 23Na SNR alone is difficult to compare between different studies, because of the high influence of hardware configurations and sequence settings on the SNR, we further set out to measure the apparent tissue sodium content (aTSC) in the AT as a better comparable parameter. Ten healthy controls and one patient with tendinopathy in the AT were examined using a clinical 3 Tesla (T) MRI scanner in conjunction with a dual tuned 1H/23Na surface coil to measure 23Na SNR and aTSC in their ATs. 23Na T1 and T2* of the AT were also measured for three controls to correct for different relaxation behavior. The results were as follows: 23Na SNR = 11.7 ± 2.2, aTSC = 82.2 ± 13.9 mM, 23Na T1 = 20.4 ± 2.4 ms, 23Na T2s* = 1.4 ± 0.4 ms, and 23Na T2l* = 13.9 ± 0.8 ms for the whole AT of healthy controls with significant regional differences. These are the first reported aTSCs and 23Na relaxation times for the AT using sodium MRI and may serve for future comparability in different studies regarding examinations of diseased ATs with sodium MRI. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the feasibility of motion correction for sodium (23Na) MRI based on interleaved acquired 3D proton (1H) navigator images. Methods: A 3D radial density‐adapted sequence for interleaved 23Na/1H MRI was implemented on a 7 Tesla whole‐body MRI system. The 1H data obtained during the 23Na acquisition were used to reconstruct 140 navigator image volumes with a nominal spatial resolution of (2.5 mm)3 and a temporal resolution of 6 s. The motion information received from co‐registration was then used to correct the 23Na image dataset, which also had a nominal spatial resolution of (2.5 mm)3. The approach was evaluated on six healthy volunteers, whose motion during the scans had different intensities and characteristics. Results: Interleaved acquisition of two nuclei did not show any relevant influence on image quality (SNR of 13.0 for interleaved versus 13.2 for standard 23Na MRI and 176.4 for interleaved versus 178.0 for standard 1H MRI). The applied motion correction increased the consistency between two consecutive scans for all examined volunteers and improved the image quality for all kinds of motion. The SD of the differences ranged between 2.30% and 6.96% for the uncorrected and between 2.13% and 2.67% for the corrected images. Conclusion: The feasibility of interleaved acquired 1H navigator images to be used for retrospective motion correction of 23Na images was successfully demonstrated. The approach neither affected the 23Na image quality nor elongated the scan time and can therefore be an important tool to improve the accuracy of quantitative 23Na MRI. [ABSTRACT FROM AUTHOR]

Background: Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) (SLC34A3 gene, OMIM 241530) is an autosomal recessive disorder that results in a loss of function of the sodium-phosphate NPT2c channel at the proximal tubule. Phosphate supplementation rarely improves serum phosphate, hypercalciuria, nephrocalcinosis, 1,25(OH)2 vitamin D (1,25(OH)2D) levels or short stature. Methods: We describe 23Na MRI and the successful use of recombinant human growth hormone (rhGH) and Fluconazole to improve growth (possibly confounded by puberty) and hypercalciuria in a now 12-year-old male with HHRH (novel homozygous SLC34A3 mutation, c.835_846 + 10del.T). Results: The patient had chronic bone pain, hypophosphatemia (0.65 mmol/L[reference interval 1.1–1.9]), pathological fractures and medullary nephrocalcinosis/hypercalciuria (urinary calcium/creatinine ratio 1.66 mol/mmol[480 pmol/L[60–208]. Rickets Severity Score was 4. Treatment with 65 mg/kg/day of sodium phosphate and potassium citrate 10 mmol TID failed to correct the abnormalities.Adding rhGH at 0.35 mg/kg/week to the phosphate therapy, improved bone pain, height z-score from −2.09 to −1.42 over 6 months, without a sustained effect on TmP/GFR. Fluconazole was titrated to 100 mg once daily, resulting for the first time in a reduction of the 1,25(OH)2D to 462 and 426 pmol/L; serum phosphate 0.87 mmol/L, and calcium/creatinine ratio of 0.73.23Na MRI showed normal skin (z-score + 0.68) and triceps surae muscle (z-score + 1.5) Na+ levels; despite a defect in a sodium transporter, hence providing a rationale for a low sodium diet to improve hypercalciuria. Conclusions: The addition of rhGH, Fluconazole and salt restriction to phosphate/potassium supplementation improved the conventional therapy. Larger studies are needed to confirm our findings.

Despite the technical challenges that require lengthy acquisitions to overcome poor signal‐to‐noise ratio (SNR), sodium (23Na) 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 23Na 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 23Na MRI have reduced variability from a FH method over DM. [ABSTRACT FROM AUTHOR]

Introduction: Sodium MRI (23Na MRI) derived biomarkers such as tissue sodium concentration (TSC) provide valuable information on cell function and brain tissue viability and has become a reliable tool for the assessment of brain tumors and ischemic stroke beyond pathoanatomical morphology. Patients with major stroke often suffer from different degrees of underlying white matter lesions (WMLs) attributed to chronic small vessel disease. This study aimed to evaluate the WM TSC in patients with an acute ischemic stroke and to correlate the TSC with the extent of small vessel disease. Furthermore, the reliability of relative TSC (rTSC) compared to absolute TSC in these patients was analyzed. Methodology: We prospectively examined 62 patients with acute ischemic stroke (73 ± 13 years) between November 2016 and August 2019 from which 18 patients were excluded and thus 44 patients were evaluated. A 3D 23Na MRI was acquired in addition to a T2-TIRM and a diffusion-weighted image. Coregistration and segmentation were performed with SPM 12 based on the T2-TIRM image. The extension of WM T2 hyperintense lesions in each patient was classified using the Fazekas scale of WMLs. The absolute TSC in the WM region was correlated to the Fazekas grades. The stroke region was manually segmented on the coregistered absolute diffusion coefficient image and absolute, and rTSC was calculated in the stroke region and compared to nonischemic WM region. Statistical significance was evaluated using the Student t-test. Results: For patients with Fazekas grade I (n = 25, age: 68.5 ± 15.1 years), mean TSC in WM was 55.57 ± 7.43 mM, and it was not statistically significant different from patients with Fazekas grade II (n = 7, age: 77.9 ± 6.4 years) with a mean TSC in WM of 53.9 ± 6.4 mM, p = 0.58. For patients with Fazekas grade III (n = 9, age: 81.4 ± 7.9 years), mean TSC in WM was 68.7 ± 10.5 mM, which is statistically significantly higher than the TSC in patients with Fazekas grade I and II (p < 0.001 and p = 0.05, respectively). There was a positive correlation between the TSC in WM and the Fazekas grade with r = 0.48 p < 0.001. The rTSC in the stroke region was statistically significant difference between low (0 and I) and high (2 and 3) Fazekas grades (p = 0.0353) whereas there was no statistically significant difference in absolute TSC in the stroke region between low (0 and I) and high (2 and 3) Fazekas grades. Conclusion: The significant difference in absolute TSC in WM in patients with severe small vessel disease; Fazekas grade 3 can lead to inaccuracies using rTSC quantification for evaluation of acute ischemic stroke using 23 Na MRI. The study, therefore, emphasizes the importance of absolute tissue sodium quantification. [ABSTRACT FROM AUTHOR]

Quantitative 23Na magnetic resonance imaging (MRI) provides tissue sodium concentration (TSC), which is connected to cell viability and vitality. Long acquisition times are one of the most challenging aspects for its clinical establishment. K‐space undersampling is an approach for acquisition time reduction, but generates noise and artifacts. The use of convolutional neural networks (CNNs) is increasing in medical imaging and they are a useful tool for MRI postprocessing. The aim of this study is 23Na MRI acquisition time reduction by k‐space undersampling. CNNs were applied to reduce the resulting noise and artifacts. A retrospective analysis from a prospective study was conducted including image datasets from 46 patients (aged 72 ± 13 years; 25 women, 21 men) with ischemic stroke; the 23Na MRI acquisition time was 10 min. The reconstructions were performed with full dataset (FI) and with a simulated dataset an image that was acquired in 2.5 min (RI). Eight different CNNs with either U‐Net–based or ResNet‐based architectures were implemented with RI as input and FI as label, using batch normalization and the number of filters as varying parameters. Training was performed with 9500 samples and testing included 400 samples. CNN outputs were evaluated based on signal‐to‐noise ratio (SNR) and structural similarity (SSIM). After quantification, TSC error was calculated. The image quality was subjectively rated by three neuroradiologists. Statistical significance was evaluated by Student's t‐test. The average SNR was 21.72 ± 2.75 (FI) and 10.16 ± 0.96 (RI). U‐Nets increased the SNR of RI to 43.99 and therefore performed better than ResNet. SSIM of RI to FI was improved by three CNNs to 0.91 ± 0.03. CNNs reduced TSC error by up to 15%. The subjective rating of CNN‐generated images showed significantly better results than the subjective image rating of RI. The acquisition time of 23Na MRI can be reduced by 75% due to postprocessing with a CNN on highly undersampled data. [ABSTRACT FROM AUTHOR]

Objective: To measure sodium relaxation times and concentrations in human wrists on a clinical magnetic resonance imaging (MRI) scanner with a density-adapted radial sequence. Materials and methods: Sodium MRI of human wrists was conducted on a 3T MR system using a dual-tuned 1H/23Na surface coil. We performed two studies with 10 volunteers each investigating either sodium T1 (study 1) or sodium T2* (study 2) relaxation times in the radiocarpal joint (RCJ) and midcarpal joint (MCJ). Sodium concentrations of both regions were determined. Results: No differences for transversal of longitudinal relaxation times were found between RCJ and MCJ (T2,s*(RCJ) = (0.9 ± 0.4) ms; T2,s*(MCJ) = (0.9 ± 0.3) ms; T2,l*(RCJ) = (14.9 ± 0.9) ms; T2,l*(MCJ) = (13.9 ± 1.1) ms; T1(RCJ) = (19.0 ± 2.4) ms; T1(MCJ) = (18.5 ± 2.1) ms). Sodium concentrations were (157.7 ± 28.4) mmol/l for study 1 and (159.8 ± 29.1) mmol/l for study 2 in the RCJ, and (172.7 ± 35.6) mmol/l for study 1 and (163.4 ± 26.3) mmol/l for study 2 in the MCJ. Conclusion: We successfully determined sodium relaxation times and concentrations of the human wrist on a 3T MRI scanner. [ABSTRACT FROM AUTHOR]

Background: Lower back pain affects 75%-85% of people at some point in their lives. The detection of biochemical changes with sodium ( 23 Na) MRI has potential to enable an earlier and more accurate diagnosis., Purpose: To measure 23 Na relaxation times and apparent tissue sodium concentration (aTSC) in ex-vivo intervertebral discs (IVDs), and to investigate the relationship between aTSC and histological Thompson grade., Study Type: Ex-vivo., Specimen: Thirty IVDs from the lumbar spines of 11 human body donors (4 female, 7 male, mean age 86 ± 8 years)., Field Strength/sequence: 3 T; density-adapted 3D radial sequence (DA-3D-RAD)., Assessment: IVD 23 Na longitudinal (T 1 ), short and long transverse (T 2s * and T 2l *) relaxation times and the proportion of the short transverse relaxation (p s ) were calculated for one IVD per spine sample (11 IVDs). Furthermore, aTSCs were calculated for all IVDs. The degradation of the IVDs was assessed via histological Thompson grading., Statistical Tests: A Kendall Tau correlation (τ) test was performed between the aTSCs and the Thompson grades. The significance level was set to P < 0.05., Results: Mean 23 Na relaxation parameters of a subset of 11 IVDs were T 1  = 9.8 ± 1.3 msec, T 2s * = 0.7 ± 0.1 msec, T 2l * = 7.3 ± 1.1 msec, and p s  = 32.7 ± 4.0%. A total of 30 IVDs were examined, of which 3 had Thompson grade 1, 4 had grade 2, 5 had grade 3, 5 had grade 4, and 13 had grade 5. The aTSC decreased with increasing degradation, being 274.6 ± 18.9 mM for Thompson grade 1 and 190.5 ± 29.5 mM for Thompson grade 5. The correlation between whole IVD aTSC and Thompson grade was significant and strongly negative (τ = -0.56)., Data Conclusion: This study showed a significant correlation between aTSC and degenerative IVD changes. Consequently, aTSC has potential to be useful as an indicator of degenerative spinal changes., Evidence Level: 2 TECHNICAL EFFICACY: Stage 1., (© 2024 The Author(s). Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To capture the multiquantum coherence (MQC) 23Na signal. Different phase‐cycling options and sequences are compared in a unified theoretical layout, and a novel sequence is developed. Methods: An open source simulation overview is provided with graphical explanations to facilitate MQC understanding and access to techniques. Biases such as B0 inhomogeneity and stimulated echo signal were simulated for 4 different phase‐cycling options previously described. Considerations for efficiency and accuracy lead to the implementation of a 2D Cartesian single and triple quantum imaging of sodium (CRISTINA) sequence employing two 6‐step cycles in combination with a multi‐echo readout. CRISTINA was compared to simultaneous single‐quantum and triple‐quantum‐filtered MRI of sodium (SISTINA) under strong static magnetic gradient. CRISTINA capabilities were assessed on 8 × 60 mL, 0% to 5% agarose phantom with 50 to 154 mM 23Na concentration at 7 T. CRISTINA was demonstrated subsequently in vivo in the brain. Results: Simulation of B0 inhomogeneity showed severe signal dropout, which can lead to erroneous MQC measurement. Stimulated echo signal was highest at the time of triple‐quantum coherences signal maximum. However, stimulated echo signal is separated by Fourier Transform as an offset and did not interfere with MQC signals. The multi‐echo readout enabled capturing both single‐quantum coherences and triple‐quantum coherences signal evolution at once. Signal combination of 2 phase‐cycles with a corresponding B0 map was found to recover the signal optimally. Experimental results confirm and complement the simulations. Conclusion: Considerations for efficient MQC measurements, most importantly avoiding B0 signal loss, led to the design of CRISTINA. CRISTINA captures triple‐quantum coherences and single‐quantum coherences signal evolution to provide complete sodium signal characterization including T2∗ fast, T2∗ slow, MQC amplitudes, and sodium concentration. [ABSTRACT FROM AUTHOR]

Purpose: Sodium MRI shows great promise as a marker for cerebral metabolic dysfunction in stroke, brain tumor, and neurodegenerative pathologies. However, cerebral blood vessels, whose volume and function are perturbed in these pathologies, have elevated sodium concentrations relative to surrounding tissue. This study aims to assess whether this fluid compartment could bias measurements of tissue sodium using MRI. Methods: Density‐weighted and B1 corrected sodium MRI of the brain was acquired in 9 healthy participants at 4.7T. Veins were identified using co‐registered 1H T2∗‐weighted images and venous partial volume estimates were calculated by down‐sampling the finer spatial resolution venous maps from the T2∗‐weighted images to the coarser spatial resolution of the sodium data. Linear regressions of venous partial volume estimates and sodium signal were performed for regions of interest including just gray matter, just white matter, and all brain tissue. Results: Linear regression demonstrated a significant venous sodium contribution above the underlying tissue signal. The apparent venous sodium concentrations derived from regression were 65.8 ± 4.5 mM (all brain tissue), 71.0 ± 7.4 mM (gray matter), and 55.0 ± 4.7 mM (white matter). Conclusion: Although the partial vein linear regression did not yield the expected sodium concentration in blood (~87 mM), likely the result of point spread function smearing, this regression highlights that blood compartments may bias brain tissue sodium signals across neurological conditions where blood volumes may differ. [ABSTRACT FROM AUTHOR]

In multiple sclerosis (MS), experimental and ex vivo studies indicate that pathologic intra- and extracellular sodium accumulation may play a pivotal role in inflammatory as well as neurodegenerative processes. Yet, in vivo assessment of sodium in the microenvironment is hard to achieve. Here, sodium magnetic resonance imaging (23NaMRI) with its non-invasive properties offers a unique opportunity to further elucidate the effects of sodium disequilibrium in MS pathology in vivo in addition to regular proton based MRI. However, unfavorable physical properties and low in vivo concentrations of sodium ions resulting in low signal-to-noise-ratio (SNR) as well as low spatial resolution resulting in partial volume effects limited the application of 23NaMRI. With the recent advent of high-field MRI scanners and more sophisticated sodium MRI acquisition techniques enabling better resolution and higher SNR, 23NaMRI revived. These studies revealed pathologic total sodium concentrations in MS brains now even allowing for the (partial) differentiation of intra- and extracellular sodium accumulation. Within this review we (1) demonstrate the physical basis and imaging techniques of 23NaMRI and (2) analyze the present and future clinical application of 23NaMRI focusing on the field of MS thus highlighting its potential as biomarker for neuroinflammation and -degeneration.

Abstract Purpose The state-of-the-art method to quantify sodium concentrations in vivo consists in a fully relaxed 3D spin-density (SD) weighted acquisition. Nevertheless, most sodium MRI clinical studies use short-TR SD acquisitions to reduce acquisition durations. We present a clinically viable implementation of the Variable Flip Angle (VFA) method for robust and clinically viable quantification of total sodium concentration (TSC) and longitudinal relaxation rates in vivo in human brain at 3 T. Methods Two non-Cartesian steady-state spoiled ultrashort echo time (UTE) scans, performed at optimized flip angles, repetition time and pulse length determined under specific absorption rate constraints, are used to simultaneously compute T 1 and total sodium concentration (TSC) maps using the VFA method. Images are reconstructed using the non-uniform Fast Fourier Transform algorithm and TSC maps are corrected for possible inhomogeneity of coil transmission and reception profiles. Fractioned acquisitions are used to correct for potential patient motion. TSC quantifications obtained using the VFA method are validated at first in comparison with a fully-relaxed SD acquisition in a calibration phantom. The robustness of similar VFA acquisitions are compared to the short-TR SD approach in vivo on seven healthy volunteers. Results The VFA method resulted in consistent TSC and T 1 estimates across our cohort of healthy subjects, with mean TSC of 38.1 ± 5.0 mmol/L and T 1 of 39.2 ± 4.4 ms. These results are in agreement with previously reported values in literature TSC estimations and with the predictions of a 2-compartment model. However, the short-TR SD acquisition systematically underestimated the sodium concentration with a mean TSC of 31 ± 4.5 mmol/L. Conclusion The VFA method can be applied successfully to image sodium at 3 T in about 20 min and provides robust and intrinsically T 1 -corrected TSC maps. [ABSTRACT FROM AUTHOR]

In multiple sclerosis (MS), experimental and ex vivo studies indicate that pathologic intra- and extracellular sodium accumulation may play a pivotal role in inflammatory as well as neurodegenerative processes. Yet, in vivo assessment of sodium in the microenvironment is hard to achieve. Here, sodium magnetic resonance imaging (23NaMRI) with its non-invasive properties offers a unique opportunity to further elucidate the effects of sodium disequilibrium in MS pathology in vivo in addition to regular proton based MRI. However, unfavorable physical properties and low in vivo concentrations of sodium ions resulting in low signal-to-noise-ratio (SNR) as well as low spatial resolution resulting in partial volume effects limited the application of 23NaMRI. With the recent advent of high-field MRI scanners and more sophisticated sodium MRI acquisition techniques enabling better resolution and higher SNR, 23NaMRI revived. These studies revealed pathologic total sodium concentrations in MS brains now even allowing for the (partial) differentiation of intra- and extracellular sodium accumulation. Within this review we (1) demonstrate the physical basis and imaging techniques of 23NaMRI and (2) analyze the present and future clinical application of 23NaMRI focusing on the field of MS thus highlighting its potential as biomarker for neuroinflammation and -degeneration. [ABSTRACT FROM AUTHOR]

Abstract A novel magnetic resonance imaging (MRI) acquisition and reconstruction method for obtaining a series of dynamic sodium 23Na-MRI acquisitions was designed to non-invasively assess the signal variations of brain sodium during a hand motor task in 14 healthy human volunteers on an ultra high field (7T) MR scanner. Regions undergoing activation and deactivation were identified with reference to conventional task-related BOLD functional MRI (fMRI). Activation observed in the left central regions, the supplementary motor areas and the left cerebellum induced an increase in the sodium signal observed at ultra short echo time and a decrease in the 23Na signal observed at long echo time. Based on a simple model of two distinct sodium pools (namely, restricted and mobile sodium), the ultra short echo time measures the totality of sodium whereas the long echo time is mainly sensitive to mobile sodium. This activation pattern is consistent with previously described processes related to an influx of Na+ into the intracellular compartments and a moderate increase in the cerebral blood volume (CBV). In contrast, deactivation observed in the right central regions ipsilateral to the movement, the precuneus and the left cerebellum induced a slight decrease in sodium signal at ultra short echo time and an increase of sodium signal at longer echo times. This inhibitory pattern is compatible with a slight decrease in CBV and an efflux of intracellular Na+ to the extracellular compartments that may reflect neural dendritic spine and astrocytic shrinkage, and an increase of sodium in the extracellular fraction. In conclusion, cerebral dynamic 23Na MRI experiments can provide access to the ionic transients following a functional task occurring within the neuro-glial-vascular ensemble. This has the potential to open up a novel non-invasive window on the mechanisms underlying brain function. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Under the hypothesis that increased extracellular sodium induces sustained neuronal excitability with the onset and progression of migraine, this study evaluates dynamic in vivo Na fluxes in the brain of a preclinical rodent analogue of migraine. Ultra-high field Na magnetic resonance imaging (MRI) at 21.1 T has demonstrated potential to quantify sodium concentrations with good spatial and temporal resolution after the onset of central sensitization. Sprague-Dawley male rats with implanted intraperitoneal lines were studied by MRI before and after an in situ injection of 10 mg/kg of nitroglycerin (NTG) vs vehicle and saline controls. Slice-selective Na images were acquired using a multislice free induction decay-based chemical shift imaging sequence with resolution of 1.1 × 1.1 × 3 mm for a 9-minute acquisition. A total of 27 repeated scans were acquired over 1 hour of baseline scanning and longitudinally up to 3 hours after injection. Increases of Na MRI signal in the brainstem, extracerebral cerebrospinal fluid, and cisterna magna were evident almost immediately after NTG injection, gaining significance from controls in 36 minutes. The cerebellum and third ventricle also showed sustained trends of increased Na, with the former gaining significance at over 2 hours after NTG injection. The data provide evidence of an early change in sodium concentration, markedly in posterior fossa cerebrospinal fluid and brainstem regions. Further study of fluctuations of sodium concentration and their modulation with treatments could help understand the dynamic features of migraine, locate a putative migraine generator, and guide development of therapeutic measures to correct the disturbance of sodium homeostasis. [ABSTRACT FROM AUTHOR]

Purpose: To investigate and to reduce influences on the determination of the short and long apparent transverse relaxation times ( T 2 , s *, T 2 , l *) of 23Na in vivo with respect to signal sampling. Methods: The accuracy of T 2 * determination was analyzed in simulations for five different sampling schemes. The influence of noise in the parameter fit was investigated for three different models. A dedicated sampling scheme was developed for brain parenchyma by numerically optimizing the parameter estimation. This scheme was compared in vivo to linear sampling at 7T. Results: For the considered sampling schemes, T 2 , s * / T 2 , l * exhibit an average bias of 3% / 4% with a variation of 25% / 15% based on simulations with previously published T 2 * values. The accuracy could be improved with the optimized sampling scheme by strongly averaging the earliest sample. A fitting model with constant noise floor can increase accuracy while additional fitting of a noise term is only beneficial in case of sampling until late echo time > 80 ms. T 2 * values in white matter were determined to be T 2 , s * = 5.1 ± 0.8 / 4.2 ± 0.4 ms and T 2 , l * = 35.7 ± 2.4 / 34.4 ± 1.5 ms using linear/optimized sampling. Conclusion: Voxel‐wise T 2 * determination of 23Na is feasible in vivo. However, sampling and fitting methods have to be chosen carefully to retrieve accurate results. Magn Reson Med 80:571–584, 2018. © 2018 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

Blood clotting is a fundamental biochemical process in post-hemorrhagic hemostasis. Although the varying appearance of coagulating blood in T1 - and T2 -weighted images is widely used to qualitatively determine bleeding age, the technique permits only a rough discrimination of coagulation stages, and it remains difficult to distinguish acute and chronic hemorrhagic stages because of low T1 - and T2 -weighted signal intensities in both instances. To investigate new biomedical parameters for magnetic resonance imaging-based characterization of blood clotting kinetics, sodium imaging and quantitative susceptibility mapping (QSM) were compared with conventional T1 - and T2 -weighted imaging, as well as with biochemical hemolysis parameters. For this purpose, a blood-filled spherical agar phantom was investigated daily for 14 days, as well as after 24 days at 7 T after initial preparation with fresh blood. T1 - and T2 -weighted sequences, a three-dimensional (3D) gradient echo sequence and a density-adapted 3D radial projection reconstruction pulse sequence for 23Na imaging were applied. For hemolysis estimations, free hemoglobin and free potassium concentrations were measured photometrically and with the direct ion-selective electrode method, respectively, in separate heparinized whole-blood samples along the same timeline. Initial mean susceptibility was low (0.154 ± 0.020 ppm) and increased steadily during the course of coagulation to reach up to 0.570 ± 0.165 ppm. The highest total sodium (NaT) values (1.02 ± 0.06 arbitrary units) in the clot were observed initially, dropped to 0.69 ± 0.13 arbitrary units after one day and increased again to initial values. Compartmentalized sodium (NaS) showed a similar signal evolution, and the NaS/NaT ratio steadily increased over clot evolution. QSM depicts clot evolution in vitro as a process associated with hemoglobin accumulation and transformation, and enables the differentiation of the acute and chronic coagulation stages. Sodium imaging visualizes clotting independent of susceptibility and seems to correspond to clot integrity. A combination of QSM and sodium imaging may enhance the characterization of hemorrhage. [ABSTRACT FROM AUTHOR]

Purpose A multinuclei imaging setup with the capability to acquire both sodium (23Na) and proton (1H) signals at 9.4 Tesla is presented. The main objective was to optimize coil performance at the 23Na frequency while still having the ability to acquire satisfactory 1H images. Methods The setup consisted of a combination of three radio frequency (RF) coils arranged in three layers: the innermost layer was a 27-channel 23Na receive helmet which was surrounded by a four-channel 23Na transceiver array. The outer layer consisted of a four-channel 1H dipole array for B0 shimming and anatomical localization. Transmit and receive performance of the 23Na arrays was compared to a single-tuned 23Na birdcage resonator. Results While the transmit efficiency of the 23Na transceiver array was comparable to the birdcage, the 23Na receive array provided substantial signal-to-noise ratio (SNR) gain near the surface and comparable SNR in the center. The utility of this customized setup was demonstrated by 23Na images of excellent quality. Conclusion High SNR, efficient transmit excitation and B0 shimming capability can be achieved for 23Na MRI at 9.4T using novel coil combination. This RF configuration is easily adaptable to other multinuclei applications at ultra high field (≥ 7T). Magn Reson Med 75:906-916, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

• 23Na MRI enables the quantification of tissue sodium concentration (TSC). • TSC quantification is primarily performed based on external reference phantoms. • Internal references have the potential to simplify 23Na MR imaging. • CSF and the vitreous humor as internal references on 50 stroke patients. • Quantification based on the vitreous humor provided most robust results. [ABSTRACT FROM AUTHOR]

Abstract: This study addresses the spatial relation between local Na+ and K+ imbalances in the ischemic core in a rat model of focal ischemic stroke. Quantitative [Na+] and [K+] brain maps were obtained by 23Na MRI and histochemical K+ staining, respectively, and calibrated by emission flame photometry of the micropunch brain samples. Stroke location was verified by diffusion MRI, by changes in tissue surface reflectivity and by immunohistochemistry with microtubule-associated protein 2 antibody. Na+ and K+ distribution within the ischemic core was inhomogeneous, with the maximum [Na+] increase and [K+] decrease typically observed in peripheral regions of the ischemic core. The pattern of the [K+] decrease matched the maximum rate of [Na+] increase (‘slope’). Some residual mismatch between the sites of maximum Na+ and K+ imbalances was attributed to the different channels and pathways involved in transport of the two ions. A linear regression of the [Na+]br vs. [K+]br in the samples of ischemic brain indicates that for each K+ equivalent leaving ischemic tissue, 0.8±0.1Eq, on average, of Na+ enter the tissue. Better understanding of the mechanistic link between the Na+ influx and K+ egress would validate the 23Na MRI slope as a candidate biomarker and a complementary tool for assessing ischemic damage and treatment planning. [Copyright &y& Elsevier]

23Na magnetic resonance imaging and the delayed gadolinium-enhanced magnetic resonance imaging methods to investigate cartilage can be used to determine the fixed charge density of cartilage. The methods give results that differ by a factor of 2. In this study, we use Monte Carlo simulations on a model system of cartilage and find that the difference originates from the Coulombic intermolecular interactions between the ions in the cartilage, and in the synovial fluid. Those interactions are neglected in the standard Donnan analysis that generally is adopted to evaluate magnetic resonance imaging data. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: A low-field (LF) 1H NMR T2 relaxation and 23Na/1H MRI study was performed on Atlantic salmon to study the effect of ante-mortem handling stress and rigor mortis on muscle water properties and subsequent post-rigor salting. Compared to rested fish, exhausted fish exhibited a more rapid and stronger development of rigor mortis. This resulted in significant differences in post-rigor water-holding capacity and salt uptake. By LF NMR T2 relaxation analysis significant differences in water distribution according to (1) ante-mortem handling, (2) fillet location, and (3) brine salting were detected. Furthermore, 23Na MRI revealed differences between the two treatments in fillet salt distribution, where the salt penetration in exhausted fillets was more pronounced. By combining 1H and 23Na MR images, the salt diffusion and distribution seemed to be highly affected by the distribution of fat. [Copyright &y& Elsevier]

Abstract: The effect of sodium chloride (NaCl) diffusion into meat was investigated. Proton and sodium magnetic resonance imaging were used to determine the diffusion behaviour of brine (NaCl) in porcine Longissimus dorsi and semitendinosus. NaCl diffusion was visualized through images and diffusion coefficients were determined to be in the range 3–7×10−10 m2 s−1, which is in agreement with values reported in the literature. The diffusion coefficient was found to increase during curing, suggesting microstructural changes in the meat. A supplementary experiment proved that the diffusion behaviour of sodium chloride in regions of meat with connective tissue/fat is distinctive from regions with pure myofilament tissue, as anticipated. Apparent diffusion coefficient (ADC) maps showed that meat microstructures shrunk when cured with 20% (w/w) NaCl brine. ADC across (⊥) the main muscle fiber direction decreased more than ADC along (‖) the main muscle fiber direction. The greater shrinkage in the direction across muscle fibers suggests that the curing induced shrinkage of the transverse structures rather than reduction in longitudinal structures. [Copyright &y& Elsevier]

Abstract: The effects of 5-fluorouracil (5FU, 150 mg/kg, ip) on subcutaneously implanted radiation-induced fibrosarcoma (RIF-1) tumors were monitored by in vivo 1H MRI to evaluate the water apparent diffusion coefficient (ADC), by single-quantum (SQ) and triple-quantum-filtered (TQF) 23Na MRI to evaluate compartmental Na+ content and by positron emission tomography (PET) to evaluate 2-[18F]fluoro-2-deoxy-d-glucose (FDG) uptake in the tumor. The MRI experiments were performed on untreated control and treated mice once before and then daily for 3 days after treatment. The PET experiments were performed on separate groups of age- and tumor-volume-matched animals once before and then 3 days after treatment. Tumor volumes significantly decreased in treated animals 2 and 3 days posttreatment. At the same time points, in vivo MRI measurements showed an increase in both total tissue SQ 23Na signal intensity (SI) and water ADC in treated tumors while control tumors showed no change in these parameters. TQF 23Na SI and FDG uptake were significantly lower in treated tumors compared with control tumors 3 days after 5FU treatment. The correlated increases in total tissue 23Na SI and water ADC following chemotherapy reflect an increase in extracellular space, while the lower TQF 23Na SI and FDG uptake in treated tumors compared with control tumors suggest a shift in tumor metabolism from glycolysis to oxidation and/or a decrease in cell density. [Copyright &y& Elsevier]