Sodium triple quantum MR signal extraction using a single-pulse sequence with single quantum time efficiency.

PURPOSE: Sodium triple quantum (TQ) signal has been shown to be a valuable biomarker for cell viability. Despite its clinical potential, application of Sodium TQ signal is hindered by complex pulse sequences with long scan times. This study proposes a method to approximate the TQ signal using a single excitation pulse without phase cycling. METHODS: The proposed method is based on a single excitation pulse and a comparison of the free induction decay (FID) with the integral of the FID combined with a shifting reconstruction window. The TQ signal is calculated from this FID only. As a proof of concept, the method was also combined with a multi-echo UTE imaging sequence on a 9.4 T preclinical MRI scanner for the possibility of fast TQ MRI. RESULTS: The extracted Sodium TQ signals of single-pulse and spin echo FIDs were in close agreement with theory and TQ measurement by traditional three-pulse sequence (TQ time proportional phase increment [TQTPPI)]. For 2%, 4%, and 6% agar samples, the absolute deviations of the maximum TQ signals between SE and theoretical (time proportional phase increment TQTPPI) TQ signals were less than 1.2% (2.4%), and relative deviations were less than 4.6% (6.8%). The impact of multi-compartment systems and noise on the accuracy of the TQ signal was small for simulated data. The systematic error was <3.4% for a single quantum (SQ) SNR of 5 and at maximum <2.5% for a multi-compartment system. The method also showed the potential of fast in vivo SQ and TQ imaging. CONCLUSION: Simultaneous SQ and TQ MRI using only a single-pulse sequence and SQ time efficiency has been demonstrated. This may leverage the full potential of the Sodium TQ signal in clinical applications.

Comparison of triple quantum (TQ) TPPI and inversion recovery TQ TPPI pulse sequences at 9.4 and 21.1 T.

PURPOSE: Both sodium T1 triple quantum (TQ) signal and T1 relaxation pathways have a unique sensitivity to the sodium molecular environment. In this study an inversion recovery time proportional phase increment (IRTQTPPI) pulse sequence was investigated for simultaneous and reliable quantification of sodium TQ signal and bi-exponential T1 relaxation times. METHODS: The IRTQTPPI sequence combines inversion recovery TQ filtering and time proportional phase increment. The reliable and reproducible results were achieved by the pulse sequence optimized in three ways: (1) optimization of the nonlinear fit for the determination of both T1-TQ signal and T1 relaxation times; (2) suppression of unwanted signals by assessment of four different phase cycles; (3) nonlinear sampling during evolution time for optimal scan time without any compromises in fit accuracy. The relaxation times T1 and T2 and the TQ signals from IRTQTPPI and TQTPPI were compared between 9.4 and 21.1 T. The motional environment of the sodium nuclei was evaluated by calculation of correlation times and nuclear quadrupole interaction strengths. RESULTS: Reliable measurements of the T1-TQ signals and T1 bi-exponential relaxation times were demonstrated. The fit parameters for all four phase cycles were in good agreement with one another, with a negligible influence of unwanted signals. The agar samples yielded normalized T1-TQ signals from 3% to 16% relative to single quantum (SQ) signals at magnetic fields of both 9.4 and 21.1 T. In comparison, the normalized T2-TQ signal was in the range 15%-35%. The TQ/SQ signal ratio was decreased at 21.1 T as compared with 9.4 T for both T1 and T2 relaxation pathways. The bi-exponential T1 relaxation time separation ranged from 15 to 18 ms at 9.4 T and 15 to 21 ms at 21.1 T. The T2 relaxation time separation was larger, ranging from 28 to 35 ms at 9.4 T and 37 to 40 ms at 21.1 T. CONCLUSION: The IRTQTPPI sequence, while providing a less intensive TQ signal than TQTPPI, allows a simultaneous and reliable quantification of both the T1-TQ signal and T1 relaxation times. The unique sensitivities of the T1 and T2 relaxation pathways to different types of molecular motion provide a deeper understanding of the sodium MR environment.

Sodium MRI of the Lumbar Intervertebral Discs of the Human Spine: An Ex Vivo Study.

BACKGROUND: Lower back pain affects 75%-85% of people at some point in their lives. The detection of biochemical changes with sodium (23Na) MRI has potential to enable an earlier and more accurate diagnosis. PURPOSE: To measure 23Na 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 23Na longitudinal (T1), short and long transverse (T2s* and T2l*) relaxation times and the proportion of the short transverse relaxation (ps) 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 23Na relaxation parameters of a subset of 11 IVDs were T1 = 9.8 ± 1.3 msec, T2s* = 0.7 ± 0.1 msec, T2l* = 7.3 ± 1.1 msec, and ps = 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.

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

OBJECTIVES: 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. MATERIALS AND METHODS: 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 3 T 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. RESULTS: 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. DISCUSSION: 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.

Combining sodium MRI, proton MR spectroscopic imaging, and intracerebral EEG in epilepsy.

Whole brain ionic and metabolic imaging has potential as a powerful tool for the characterization of brain diseases. We combined sodium MRI (23 Na MRI) and 1 H-MR Spectroscopic Imaging (1 H-MRSI), assessing changes within epileptogenic networks in comparison with electrophysiologically normal networks as defined by stereotactic EEG (SEEG) recordings analysis. We applied a multi-echo density adapted 3D projection reconstruction pulse sequence at 7 T (23 Na-MRI) and a 3D echo-planar spectroscopic imaging sequence at 3 T (1 H-MRSI) in 19 patients suffering from drug-resistant focal epilepsy who underwent presurgical SEEG. We investigated 23 Na MRI parameters including total sodium concentration (TSC) and the sodium signal fraction associated with the short component of T2 * decay (f), alongside the level of metabolites N-acetyl aspartate (NAA), choline compounds (Cho), and total creatine (tCr). All measures were extracted from spherical regions of interest (ROIs) centered between two adjacent SEEG electrode contacts and z-scored against the same ROI in controls. Group comparison showed a significant increase in f only in the epileptogenic zone (EZ) compared to controls and compared to patients' propagation zone (PZ) and non-involved zone (NIZ). TSC was significantly increased in all patients' regions compared to controls. Conversely, NAA levels were significantly lower in patients compared to controls, and lower in the EZ compared to PZ and NIZ. Multiple regression analyzing the relationship between sodium and metabolites levels revealed significant relations in PZ and in NIZ but not in EZ. Our results are in agreement with the energetic failure hypothesis in epileptic regions associated with widespread tissue reorganization.

Multi-nuclear sodium, diffusion, and perfusion MRI in human gliomas.

PURPOSE: There is limited knowledge about the associations between sodium and proton MRI measurements in brain tumors. The purpose of this study was to quantify intra- and intertumoral correlations between sodium, diffusion, and perfusion MRI in human gliomas. METHODS: Twenty glioma patients were prospectively studied on a 3T MRI system with multinuclear capabilities. Three mutually exclusive tumor volumes of interest (VOIs) were segmented: contrast-enhancing tumor (CET), T2/FLAIR hyperintense non-enhancing tumor (NET), and necrosis. Median and voxel-wise associations between apparent diffusion coefficient (ADC), normalized relative cerebral blood volume (nrCBV), and normalized sodium measurements were quantified for each VOI. RESULTS: Both relative sodium concentration and ADC were significantly higher in areas of necrosis compared to NET (P = 0.003 and P = 0.008, respectively) and CET (P = 0.02 and P = 0.02). Sodium concentration was higher in CET compared to NET (P = 0.04). Sodium and ADC were higher in treated compared to treatment-naïve gliomas within NET (P = 0.006 and P = 0.01, respectively), and ADC was elevated in CET (P = 0.03). Median ADC and sodium concentration were positively correlated across patients in NET (r = 0.77, P < 0.0001) and CET (r = 0.84, P < 0.0001), but not in areas of necrosis (r = 0.45, P = 0.12). Median nrCBV and sodium concentration were negatively correlated across patients in areas of NET (r=-0.63, P = 0.003). Similar associations were observed when examining voxel-wise correlations within VOIs. CONCLUSION: Sodium MRI is positively correlated with proton diffusion MRI measurements in gliomas, likely reflecting extracellular water. Unique areas of multinuclear MRI contrast may be useful in future studies to understand the chemistry of the tumor microenvironment.

Assessment of sodium (23Na) brain MRI at 3T - preliminary results.

Purpose: The purpose of this work was to establish a database of tissue sodium concentration (TSC) in the normal brain of healthy volunteers. Tissue sodium concentration can be used as a sensitive marker of tissue viability in stroke or radiation therapy monitoring. Material and methods: Thirty-seven volunteers were scanned with a 23Na protocol in the span of one year; within this group, 29 studies were of acceptable quality. The study was approved by the Local Bioethics Committee. Data were acquired during a single magnetic resonance (MR) scanner session. The single scanner session consisted of 23Na 3D radial gradient echo (GRE) acquisition, MPRage, SPACE-FLAIR, and Resolve-DTI. MPRage images were segmented to obtain masks of the grey matter (GM), white matter (WM), and cerebrospinal fluid (CSF), which were registered to the sodium image space for image analysis. Images were transformed into TSC maps - a signal calibration curve obtained from the reference phantom of known sodium concentration and known relaxation time. Results: The collected data were analysed in 2 different ways: volunteers were divided by sex and by age. No significant differences in TSC were found between sexes. In all comparisons there was a significant difference in TSC between younger and older volunteers. In healthy volunteers mean TSC were as follows: GM 33.21 ± 4.76 mmol/l, WM 28.41 ± 4.03 mmol/l and for CSF 41.3 ± 6.69 mmol/l. Conclusions: This preliminary work is a base for further work with sodium imaging in brain lesions. The entirety of the col-lected data will be useful in the future as a baseline brain TSC for comparison to values obtained from pathologies.

Simultaneous 3D acquisition of 1 H MRF and 23 Na MRI.

PURPOSE: To develop a 3D MR technique to simultaneously acquire proton multiparametric maps (T1 , T2 , and proton density) and sodium density weighted images over the whole brain. METHODS: We implemented a 3D stack-of-stars MR pulse sequence which consists of interleaved proton (1 H) and sodium (23 Na) excitations, tailored slice encoding gradients that can encode the same slice for both nuclei, and simultaneous readout with different radial trajectories (1 H, full-radial; 23 Na, center-out radial). The receive chain of our 7T scanner was modified to enable simultaneous acquisition of 1 H and 23 Na signal. A heuristically optimized flip angle train was implemented for proton MR fingerprinting (MRF). The SNR and the accuracy of proton T1 and T2 were evaluated in phantoms. Finally, in vivo application of the method was demonstrated in five healthy subjects. RESULTS: The SNR for the simultaneous measurement was almost identical to that for the single-nucleus measurements (<2% change). The proton T1 and T2 maps remained similar to the results from a reference 2D MRF technique (normalized RMS error in T1 ≈ 4.2% and T2 ≈ 11.3%). Measurements in healthy subjects corroborated these results and demonstrated the feasibility of our method for in vivo application. The in vivo T1 values measured using our method were lower than the results measured by other conventional techniques. CONCLUSIONS: With the 3D simultaneous implementation, we were able to acquire sodium and proton density weighted images in addition to proton T1 , T2 , and B1+ from 1 H MRF that covers the whole brain volume within 21 min.

Quantitative 23 Na-MRI of the intervertebral disk at 3 T.

Monitoring the tissue sodium content (TSC) in the intervertebral disk geometry noninvasively by MRI is a sensitive measure to estimate changes in the proteoglycan content of the intervertebral disk, which is a biomarker of degenerative disk disease (DDD) and of lumbar back pain (LBP). However, application of quantitative sodium concentration measurements in 23 Na-MRI is highly challenging due to the lower in vivo concentrations and smaller gyromagnetic ratio, ultimately yielding much smaller signal relative to 1 H-MRI. Moreover, imaging the intervertebral disk geometry imposes higher demands, mainly because the necessary RF volume coils produce highly inhomogeneous transmit field patterns. For an accurate absolute quantification of TSC in the intervertebral disks, the B1 field variations have to be mitigated. In this study, we report for the first time quantitative sodium concentration in the intervertebral disks at clinical field strengths (3 T) by deploying 23 Na-MRI in healthy human subjects. The sodium B1 maps were calculated by using the double-angle method and a double-tuned (1 H/23 Na) transceive chest coil, and the individual effects of the variation in the B1 field patterns in tissue sodium quantification were calculated. Phantom measurements were conducted to evaluate the quality of the Na-weighted images and B1 mapping. Depending on the disk position, the sodium concentration was calculated as 161.6 mmol/L-347 mmol/L, and the mean sodium concentration of the intervertebral disks varies between 254.6 ± 54 mmol/L and 290.1 ± 39 mmol/L. A smoothing effect of the B1 correction on the sodium concentration maps was observed, such that the standard deviation of the mean sodium concentration was significantly reduced with B1 mitigation. The results of this work provide an improved integration of quantitative 23 Na-MRI into clinical studies in intervertebral disks such as degenerative disk disease and establish alternative scoring schemes to existing morphological scoring such as the Pfirrmann score.

Gender differences in cell volume fraction (CVF): a structural parameter reflecting the energy efficiency of maintaining the resting membrane potential.

The cell volume fraction (CVF) of the human brain is high (~82%) and is preserved across healthy aging while the brain declines in volume. These two observations, supported by several independent techniques, suggest that CVF is an important structural parameter. A new biophysical model is presented that incorporates CVF into the Goldman equation of classical membrane electrophysiology. The Goldman equation contains few structural constraints beyond two compartments separated by a semipermeable membrane supporting ion gradients. As potassium is the most permeable ion in the resting state, the resting membrane potential is determined by the potassium ion gradient. This biophysical model indicates that the sodium-potassium ion pumps use less energy at high CVF to maintain the resting membrane potential, explaining the high value of CVF and its conservation with healthy aging. CVF is measured to be statistically significantly higher in the brains of males compared with females, suggesting a structural requirement for higher energy efficiency in the larger male brain to support the greater number of neurons and synapses. As CVF can be measured in humans using quantitative sodium MRI and has potential implications for brain health, CVF may be a quantitative parameter that is useful for assessment of brain health, especially in patients with diseases such as dementia and psychiatric disease that do not have anatomical correlates detectable by clinical proton MRI.

Compressed Sensing in Sodium Magnetic Resonance Imaging: Techniques, Applications, and Future Prospects.

Sodium (23 Na) yields the second strongest nuclear magnetic resonance (NMR) signal in biological tissues and plays a vital role in cell physiology. Sodium magnetic resonance imaging (MRI) can provide insights into cell integrity and tissue viability relative to pathologies without significant anatomical alternations, and thus it is considered to be a potential surrogate biomarker that provides complementary information for standard hydrogen (1 H) MRI in a noninvasive and quantitative manner. However, sodium MRI suffers from a relatively low signal-to-noise ratio and long acquisition times due to its relatively low NMR sensitivity. Compressed sensing-based (CS-based) methods have been shown to accelerate sodium imaging and/or improve sodium image quality significantly. In this manuscript, the basic concepts of CS and how CS might be applied to improve sodium MRI are described, and the historical milestones of CS-based sodium MRI are briefly presented. Representative advanced techniques and evaluation methods are discussed in detail, followed by an expose of clinical applications in multiple anatomical regions and diseases as well as thoughts and suggestions on potential future research prospects of CS in sodium MRI. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 1.

Quantitative sodium magnetic resonance imaging in food: Addressing sensitivity issues using single quantum chemical shift imaging at high field.

According to various health organizations, the global consumption of salt is higher than recommended and needs to be reduced. Ideally, this would be achieved without losing the taste of the salt itself. In order to accomplish this goal, both at the industrial and domestic levels, we need to understand the mechanisms that govern the final distribution of salt in food. The in-silico solutions in use today greatly over-simplify the real food structure. Measuring the quantity of sodium at the local level is key to understanding sodium distribution. Sodium magnetic resonance imaging (MRI), a non-destructive approach, is the ideal choice for salt mapping along transformational process. However, the low sensitivity of the sodium nucleus and its short relaxation times make this imaging difficult. In this paper, we show how sodium MRI can be used to highlight salt heterogeneities in food products, provided that the temporal decay is modeled, thus correcting for differences in relaxation speeds. We then propose an abacus which shows the relationship between the signal-to-noise ratio of the sodium MRI, the salt concentration, the B0 field, and the spatial and temporal resolutions. This abacus simplifies making the right choices when implementing sodium MRI.

Evaluation of Sodium Relaxation Times and Concentrations in the Achilles Tendon Using MRI.

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.

Combined imaging of potassium and sodium in human skeletal muscle tissue at 7 T.

PURPOSE: To validate the feasibility of quantitative combined potassium (39 K) and sodium (23 Na) MRI in human calf muscle tissue, as well as to evaluate the reproducibility of the apparent tissue potassium concentration (aTPC) and apparent tissue sodium concentration (aTSC) determination in healthy muscle tissue. METHODS: Quantitative 23 Na and 39 K MRI acquisition protocols were implemented on a 7 T MR system. A double-resonant 23 Na/39 K birdcage RF coil was used. Measurements of human lower leg were performed in a total acquisition time of TANa = 10:54 min/TAK = 8:06 min and using a nominal spatial resolution of 2.5 × 2.5 × 15 mm3 /7.5 × 7.5 × 30 mm3 for 23 Na/39 K MRI. Two aTSC and aTPC examinations in muscle tissue were performed during the same day on 10 healthy subjects. RESULTS: The proposed acquisition and postprocessing workflow for 23 Na and 39 K MRI data sets provided reproducible aTSC and aTPC measurements. In human calf muscle tissue, the coefficient of variation between scan and re-scan was 5.7% for both aTSC and aTPC determination. Overall, mean values of aTSC = (17 ± 1) mM and aTPC = (85 ± 5) mM were measured. Moreover, for 39 K in calf muscle tissue, T2∗ components of T2f∗ = (1.2 ± 0.2) ms and T2s∗ = (7.9 ± 0.9) ms, as well as a residual quadrupolar interaction of ωq¯ = (143 ± 17) Hz, were determined. The fraction of the fast component was f = (58 ± 4)%. CONCLUSION: Using the presented measurement and postprocessing approach, a reproducible aTSC and aTPC determination using 23 Na and 39 K MRI at 7 T in human skeletal muscle tissue is feasible in clinically acceptable acquisition durations.

Tissue Sodium Concentration within White Matter Correlates with the Extent of Small Vessel Disease.

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.

Microstructural correlates of 23Na relaxation in human brain at 7 Tesla.

23Na provides the second strongest MR-observable signal in biological tissue and exhibits bi-exponential T2∗ relaxation in micro-environments such as the brain. There is significant interest in developing 23Na biomarkers for neurological diseases that are associated with sodium channel dysfunction such as multiple sclerosis and epilepsy. We have previously reported methods for acquisition of multi-echo sodium MRI and continuous distribution modelling of sodium relaxation properties as surrogate markers of brain microstructure. This study aimed to compare 23Na T2∗ relaxation times to more established measures of tissue microstructure derived from advanced diffusion MRI at 7 â€‹T. Six healthy volunteers were scanned using a 3D multi-echo radial ultra-short TE sequence using a dual-tuned 1H/23Na birdcage coil, and a high-resolution multi-shell, high angular resolution diffusion imaging sequence using a 32-channel 1H receive coil. 23Na T2∗ relaxation parameters [mean T2∗ (T2∗mean) and fast relaxation fraction (T2∗ff)] were calculated from a voxel-wise continuous gamma distribution signal model. White matter (restricted anisotropic diffusion) and grey matter (restricted isotropic diffusion) density were calculated from multi-shell multi-tissue constrained spherical deconvolution. Sodium parameters were compared with white and grey matter diffusion properties. Sodium T2∗mean and T2∗ff showed little variation across a range of white matter axonal fibre and grey matter densities. We conclude that sodium T2∗ relaxation parameters are not greatly influenced by relative differences in intra- and extracellular partial volumes. We suggest that care be taken when interpreting sodium relaxation changes in terms of tissue microstructure in healthy tissue.

Radiofrequency excitation-related 23 Na MRI signal loss in skeletal muscle, cartilage, and skin.

PURPOSE: To assess the sodium MRI signal loss resulting from typically used RF excitation pulses in human skeletal muscle, patellar cartilage, and skin. METHODS: A double flip-angle experiment was performed 3 times on the knees of 5 healthy volunteers with prescribed ω1 = γB1 of 1.67 kHz, 0.333 kHz, and 0.167 kHz. This was done to search for ω1 -dependent increased rates of sodium-23 central resonance flipping known to result from residual quadrupole splitting (ωQ ), as this flip-angle effect is associated with signal loss. This study facilitated in vivo regression of Gaussian-distributed residual quadrupole splitting SD (ωQ(SD) ) as well as T2fast and T2slow . Signal loss predicted from simulation was then compared with images acquired using 90° RF pulse lengths of 0.5 ms, 0.25 ms, and 0.15 ms. RESULTS: Sodium-23 central resonance flipping was significantly greater than prescribed (44% cartilage, 23% skin, 9% muscle) using ω1 = 0.167 kHz, but only 4% cartilage, 5% skin, and 2% muscle using ω1 = 1.67 kHz. Regression yielded ωQ(SD) = 420 ± 50 Hz for cartilage but no significant ωQ(SD) for skin or muscle. This points to rapid biexponential relaxation as the cause of the flip-angle effect for skin/muscle. The T2fast(60%) /T2slow(40%) values were 1.6 ± 0.8 ms/16.1 ± 2.5 ms for muscle, 2.7 ± 0.9 ms/18.4 ± 2.5 ms for cartilage, and 0.4 ± 0.1 ms/9.3 ± 1.7 ms for skin. Simulation predicted signal loss of 6% ± 3%, 3% ± 1%, and 2% ± 1% for muscle, 16% ± 3%, 6% ± 1%, and 3% ± 1% for cartilage, and 26% ± 7%, 15% ± 4%, and 10% ± 3% for skin when using 90° RF pulse lengths of 0.5 ms, 0.25 ms, and 0.15 ms, matching experiment. CONCLUSION: High-power (short) RF pulses are necessary to reduce excitation-related signal loss, particularly for sodium-23 imaging of cartilage and skin.

Venous contribution to sodium MRI in the human brain.

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 1 H 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.

Simultaneous proton magnetic resonance fingerprinting and sodium MRI.

PURPOSE: The goal of this work is to demonstrate a method for the simultaneous acquisition of proton multiparametric maps (T1 , T2 , and proton density) and sodium density images in 1 single scan. We hope that the development of such capabilities will help to ease the implementation of sodium MRI in clinical trials and provide more opportunities for researchers to investigate metabolism through sodium MRI. METHODS: We developed a sequence based on magnetic resonance fingerprinting (MRF), which contains interleaved proton (1 H) and sodium (23 Na) excitations followed by a simultaneous center-out radial readout for both nuclei. The receive chain of a 7T scanner was modified to enable simultaneous acquisition of 1 H and 23 Na signal. The obtained signal-to-noise ratio (SNR) was evaluated, and the accuracy of both proton T1 , T2 , and B1+ and sodium density maps were verified in phantoms. Finally, the method was demonstrated in 2 healthy subjects. RESULTS: The SNR obtained using the simultaneous measurement was almost identical to single-nucleus measurements (<1% change). Similarly, the proton T1 and T2 maps remained stable (normalized root mean square error in T1 ≈ 2.2%, in T2 ≈ 1.4%, and B1+ ≈ 5.4%), which indicates that the proposed sequence and hardware have no significant effects on the signal from either nucleus. In vivo measurements corroborated these results and demonstrated the feasibility of our method for in vivo application. CONCLUSIONS: With the proposed approach, we were able to simultaneously acquire sodium density images in addition to proton T1 , T2 , and B1+ maps as well as proton density images.

Localized B0 shimming based on 23 Na MRI at 7 T.

PURPOSE: To validate the feasibility of localized B0 shimming based on B0 maps acquired with sodium (23 Na) MRI. METHODS: A localized B0 shimming routine based on a constrained regularized algorithm in combination with 23 Na MRI data acquired with a 3D density-adapted radial readout scheme was implemented on a 7T MR system. Measurements were performed using a dual-tuned 23 Na/1 H head coil. The quality of B0 maps reconstructed from 23 Na images and the resulting shim values was examined depending on the acquisition duration between 10 minutes and 15 seconds to examine clinical applicability. The B0 shimming based on 23 Na B0 maps was performed both for phantom and human head of 6 healthy volunteers, and the resulting B0 homogeneity was compared with the vendor-provided 1 H MRI-based gradient-echo brain shimming routine. RESULTS: The proposed 23 Na MRI-based shimming routine showed a reduction in B0 variation comparable to the vendor-provided shim both in phantom and in vivo measurements. Within the examined multicompartment phantom, the B0 variations could be reduced by up to 77% using the 23 Na MRI-based shim. In human head, B0 variations were reduced by approximately 50% using an acquisition time of 15 seconds for the 23 Na B0 maps and only 1 iteration of B0 shimming. CONCLUSION: The 23 Na MRI-based localized B0 shimming is possible at 7 T within clinically acceptable acquisition durations (< 1 minute). It was shown that using the proposed 23 Na MRI-based shimming approach, the 23 Na image quality at ultrahigh field strength can be strongly improved.