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Purpose of the Review: Conditions typically prevalent in adults such as hypertension, kidney stones, osteoporosis, and chronic kidney disease are increasing among adolescents and young adults (AYA). The purpose of this review is to describe the association of these conditions to a high salt diet among pediatric patients. Recent Findings: We present animal, human, and 23Na MRI evidence associated with the negative impact of high dietary salt in children. Special focus is placed on novel 23Na MRI imaging which reveals the important concept of a third compartment for sodium storage in soft tissue. Finally, we make recommendations on who should not be on a low salt diet. Summary: A high salt intake predisposes children and AYA to considerable morbidity. We exhort the reader to engage in advocacy efforts to curve the incidence and prevalence of high salt-related life-limiting conditions.

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.

To measure sodium relaxation times and concentrations in human wrists on a clinical magnetic resonance imaging (MRI) scanner with a density-adapted radial sequence. 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. 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. We successfully determined sodium relaxation times and concentrations of the human wrist on a 3T MRI scanner.

Purpose To capture the multiquantum coherence (MQC) 23 Na 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 23 Na 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 T 2 ∗ fast, T 2 ∗ slow, MQC amplitudes, and sodium concentration.

We demonstrated the feasibility of 7 Tesla sodium (23Na) and chlorine (35Cl) MRI of a solitary enchondroma. For this, we established dedicated sequences on a 7-Tesla whole-body system with the following key parameters for 35Cl MRI: TE/TR = 0.35/60 ms, TRO = 5 ms, α = 90°, Δx3 = (6 mm)3, 3 averages, Tacq = 30 min and for 23Na MRI: TE/TR = 0.4/101 ms, TRO = 10ms; α = 90°; Δx3 = (1.9 mm)3, 3 averages, Tacq = 30 min 18 s. The measured apparent Na+ concentration was 255 mmol/l and was approximately 7-fold higher than the apparent Cl– concentration with about 36 mmol/l. Additionally, repeated proton MRI examinations demonstrated constant but subtle growth (≈ 0.65 ml/year) over 14 years. In conclusion, enchondromas obviously have a high contrast-to-noise ratio when compared with the normal bone marrow in 23Na and 35Cl MRI, which may contribute to detection and differentiation in unclear or subtle cases. Key Points: Citation Format

23Na inversion recovery (IR) imaging allows for a weighting toward intracellular sodium in the human calf muscle and thus enables an improved analysis of pathophysiological changes of the muscular ion homeostasis. However, sodium signal-to-noise ratio (SNR) is low, especially when using IR sequences. 23Na has a nuclear spin of 3/2 and therefore experiences a strong electrical quadrupolar interaction. This results in very short relaxation times as well as in possible residual quadrupolar splitting. Consequently, relaxation effects during a radiofrequency pulse can no longer be neglected and even allow for increasing SNR as has previously been shown for human brain and knee. The aim of this work was to increase the SNR in 23Na IR imaging of the human calf muscle by using long inversion pulses instead of the usually applied short pulses. First, the influence of the inversion pulse length (1 to 20 ms) on the SNR as well as on image contrast was simulated for different model environments and verified by phantom measurements. Depending on the model environment (agarose 4% and 8%, xanthan 2% and 3%), SNR values increased by a factor of 1.15 up to 1.35, while NaCl solution was successfully suppressed. Thus, image contrast between the non-suppressed model compartments changes with IR pulse length. Finally, in vivo measurements of the human calf muscle of ten healthy volunteers were conducted at 3 Tesla. On average, a 1.4-fold increase in SNR could be achieved by increasing the inversion pulse length from 1 ms to 20 ms, leaving all other parameters – including the scan time – constant. This enables 23Na IR MRI with improved spatial resolution or reduced acquisition time.

Sodium (23Na) is the most abundant cation present in the human body and is involved in a large number of vital body functions. In the last few years, the interest in Sodium Magnetic Resonance Imaging (23Na MRI) has considerably increased for its relevance in physiological and physiopathological aspects. Indeed, sodium MRI offers the possibility to extend the anatomical imaging information by providing additional and complementary information on physiology and cellular metabolism with the heteronuclear Magnetic Resonance Spectroscopy (MRS). Constraints are the rapidly decaying of sodium signal, the sensitivity lack due to the low sodium concentration versus 1H-MRI induce scan times not clinically acceptable and it also constitutes a challenge for sodium MRI. With the available magnetic fields for clinical MRI scanners (1.5 T, 3 T, 7 T), and the hardware capabilities such as strong gradient strengths with high slew rates and new dedicated radiofrequency (RF) sodium coils, it is possible to reach reasonable measurement times (~10–15 min) with a resolution of a few millimeters, where it has already been applied in vivo in many human organs such as the brain, cartilage, kidneys, heart, as well as in muscle and the breast. In this work, we review the different geometries and setup of sodium coils described in the available literature for different in vivo applications in human organs with clinical MR scanners, by providing details of the design, modeling and construction of the coils.

Sodium handling is a key physiological hallmark of renal function. Alterations are generally considered a pathophysiologic event associated with kidney injury, with disturbances in the corticomedullary sodium gradient being indicative of a number of conditions. This experimental protocol review describes the individual steps needed to perform 23Na MRI; allowing accurate monitoring of the renal sodium distribution in a step-by-step experimental protocol for rodents.This chapter is based upon work from the PARENCHIMA COST Action, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This experimental protocol chapter is complemented by two separate chapters describing the basic concept and data analysis.

Object. The purpose of this work is to reveal the possibilities of low-field 23Na MRI. It was supposed to obtain images of various human organs using the 3D-scanning method, and to do this with minimal hardware modifications of a typical clinical 0,5T scanner. Materials and methods. The proprietary receiving coils, originally intended for registering proton signals (21,1 MHz), were transformed to transceiver ones and tuned to the sodium Larmor frequency of 5,6 MHz. The scanning was carried out by the 3D-gradient echo method with the parameters: TR/TE=44,7/12 ms, FA=45° and isotropic resolution of 6 mm. To increase SNR, apodization in k-space was applied during data processing. Results. 23Na MRI (including volumetric reconstructions) of several human organs – head, breast, heart, joints were obtained with SNR up to 15. Discussion. When developing low-field 23Na MRI, it is advisable to focus on recording only the T2long component (>15 ms). In this case, it is possible to narrow the receiver bandwidth as much as possible and thereby minimize noise. In addition, the requirements for the transmission path are reduced. As a result, for debugging MRI methods, the equipment of a typical clinical scanner, which is supplemented by coils tuned to the sodium NMR frequency only, can be used.

The handling of sodium by the renal system is a key indicator of renal function. Alterations in the corticomedullary distribution of sodium are considered important indicators of pathology in renal diseases. The derangement of sodium handling can be noninvasively imaged using sodium magnetic resonance imaging (23Na MRI), with data analysis allowing for the assessment of the corticomedullary sodium gradient. Here we introduce sodium imaging, describe the existing methods, and give an overview of preclinical sodium imaging applications to illustrate the utility and applicability of this technique for measuring renal sodium handling.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.

Background and purpose To date, treatment response to stereotactic radiosurgery (SRS) in brain metastases (BM) can only be determined by MRI evaluation of contrast-enhancing lesions in a long-time follow-up. Sodium MRI has been a subject of immense interest in imaging research as the measure of tissue sodium concentration (TSC) can give valuable quantitative information on cell viability. We aimed to analyze the longitudinal changes of TSC in BM measured with 23 Na MRI before and after SRS for assessment of early local tumor effects. Methods Seven patients with a total of 12 previously untreated BM underwent SRS with 22 Gy. In addition to a standard MRI protocol including dynamic susceptibility-weighted contrast-enhanced perfusion, a 23 Na MRI was performed at three time points: (I) 2 days before, (II) 5 days, and (III) 40 days after SRS. Nine BMs were evaluated. The absolute TSC in the BM, the respective peritumoral edemas, and the normal-appearing corresponding contralateral brain area were assessed and the relative TSC were correlated to the changes in BM longest axial diameters. Results TSC was elevated in nine BM at baseline before SRS with a mean of 73.4 ± 12.3 mM. A further increase in TSC was observed 5 days after SRS in all the nine BM with a mean of 86.9 ± 13 mM. Eight of nine BM showed a mean 60.6 ± 13.3% decrease in the longest axial diameter 40 days after SRS; at this time point, the TSC also had decreased to a mean 65.1 ± 7.9 mM. In contrast, one of the nine BM had a 13.4% increase in the largest axial diameter at time point III. The TSC of this BM showed a further TSC increase of 80.1 mM 40 days after SRS. Conclusion Changes in TSC using 23 Na MRI shows the possible capability to detect radiobiological changes in BM after SRS.

Purpose To quantify the reliability and agreement of sodium (23Na) MRI in calf muscle and skin of healthy subjects and to measure the smallest real difference (SRD) in each. Subjects and methods Thirty healthy subjects underwent 23Na MRI studies of the calf. A scan-rescan protocol was performed the same day and 1 week later. Relative sodium concentration was measured in the calf muscle and skin and compared between studies. Results A high degree of reliability was confirmed between the scan and rescan tests using linear regression analysis. The Bland-Altman plots indicated high agreement between runs in all regions. The SRD was measured between scans taken the same day and one week later. Correlations were also reported with age, gender and race. Conclusions Reliability and agreement of 23Na MRI in the calf muscle and skin show promise for accurately assessing serial changes in patients.

Functional parameters can be measured with the help of quantitative non-proton MRI where exact relaxometry parameters are needed. Investigation of $$T_{2}^{*}$$ is often biased by strong partial volume (PV) effects. Hence, in this work a PV correction algorithm approach was evaluated that uses iteratively adapted $$T_{2}^{*}$$ -values and high-resolution structural 1H data to determine transverse relaxation in non-proton MRI more accurately. Simulations, a phantom study and in vivo 23Na, 17O and 35Cl MRI measurements of five healthy volunteers were performed to evaluate the algorithm. $$T_{2}^{*}$$ values of grey matter (GM), white matter (WM) and cerebrospinal fluid (CSF) were obtained. Data were acquired at B 0 = 7T with nominal spatial resolutions of (4–7 mm)3 using a density-adapted radial sequence. The resulting transverse relaxation times were used for quantification of 17O data. The conducted simulations and phantom study verified the correction performance of the algorithm. For in vivo measured $$T_{2}^{*}$$ values, the correction of PV effects leads to an increase in CSF and to a decrease in GM/WM (23Na MRI: long/short GM, WM $$T_{2}^{*}$$ : 36.4 ± 3.1/5.4 ± 0.2, 23.3 ± 2.6/3.5 ± 0.1 ms; 35Cl MRI: 8.9 ± 1.4/1.0 ± 0.4, 5.9 ± 0.3/0.4 ± 0.1 ms; 17O MRI: 2.5 ± 0.1, 2.8 ± 0.1 ms). Iteratively corrected in vivo $$T_{2}^{*}$$ values of the 17O study resulted in improved water content quantification. The proposed iterative algorithm for PV correction leads to more accurate $$T_{2}^{*}$$ values and, thus, can improve accuracy in quantitative non-proton MRI.

Purpose 23Na MRI demonstrated increased tissue sodium concentrations in a number of pathologies. Acute atrophy results in muscle fibre volume shrinking that may result in a relative increase of extracellular volume and might affect sodium concentration. Thus, we hypothesized that local unloading of the calf muscles would lead to a decrease in muscle volume and an increase in muscle tissue sodium concentration. Method One lower leg of 12 healthy male subjects was submitted to a 60 day long period of unloading using the Hephaistos orthosis, while the other leg served as control. 23Na MRI and 2D PD-weighted Dixon turbo spin echo were obtained from the control and orthosis leg using a 3T scanner. For quantification, a sodium reference phantom was used with 10, 20, 30, and 40 mmol/L NaCl solution. Result Tissue sodium concentration (TSC) increased as an effect of unloading in the orthosis leg. Relative increases were 17.4 ± 16.8% (P = 0.005) in gastrocnemius medialis muscle, 11.1 ± 12.5 (P = 0.037) in gastrocnemius lateralis muscle, 16.2 ± 4.7% (P < 0.001) in soleus muscle, 10.0 ± 10.5% (P = 0.009) in the ventral muscle group, and 10.7 ± 10.0% (P = 0.003) in the central muscle group, respectively. TSC in the control leg did not significantly change. In the orthosis leg, muscle volume decreased as follows: medial gastrocnemius muscle: −5.4 ± 8.3% (P = 0.043) and soleus muscle: −7.8 ± 15.0% (P = 0.043). Conclusion Unloading atrophy is associated with an increase in muscle sodium concentration. 23Na MRI is capable of detecting these rather small changes.

Alzheimer's & dementia / Translational research & clinical interventions 6(1), e12032 (2020). doi:10.1002/trc2.12032, Published by Wiley, Hoboken, NJ

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.

Purpose:\ud 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.\ud \ud Methods:\ud 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 T*2‐weighted images and venous partial volume estimates were calculated by down‐sampling the finer spatial resolution venous maps from the T*2‐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.\ud \ud Results:\ud 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).\ud \ud Conclusion:\ud 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.

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.

Pediatric glioma response to novel targeted therapy can be heterogeneous on conventional proton (1H) MRI. Sodium concentration, as measured with 23Na MRI in adult brain tumors can provide complementary assessment of tumor proliferation to conventional MRI. However, 23Na MRI pediatric brain tumor studies are lacking. Determine the technical feasibility of performing sodium23Na MRI on pediatric glioma patients. Prospective study of an immunotherapy trial for newly diagnosed and recurrent gliomas (high-grade gliomas, low-grade gliomas, brainstem gliomas) in which participants were imaged with 23Na MRI at 3.0 Tesla. The participants (n=26, 14 males) with median age of 11 years (range = 4–23 years of age) were prospectively evaluated with sodium. 23Na MRI is technically feasible in the pediatric population and can distinguish different types of pediatric gliomas at baseline.

Background In multiple sclerosis (MS), magnetic resonance imaging (MRI) frequently shows ill-defined areas with intermediate signal intensity between the normal appearing white matter (NAWM) and focal T2-hyperintense lesions, termed “diffusely appearing white matter” (DAWM). Even though several advanced MRI techniques have shown the potential to detect and quantify subtle commonly not visible microscopic tissue changes, to date only a few advanced MRI studies investigated DAWM changes in a quantitative manner. The aim of this study was to detect and quantify tissue abnormalities in the DAWM in comparison to focal lesions and the NAWM in MS patients by sodium (23Na) MRI. Methods 23Na and conventional MRI were performed in 25 MS patients with DAWM (DAWM+) and in 25 sex- and age matched MS patients without DAWM (DAWM−), as well as in ten healthy controls (HC). Mean total sodium concentrations (TSC) were quantified in the DAWM, NAWM, normal appearing grey matter (NAGM) and in focal MS lesions. Results In MS DAWM+and DAWM−, TSC values were increased in the NAGM (DAWM+: 44.61 ± 4.09 mM; DAWM–: 45.37 ± 3.8 mM) and in the NAWM (DAWM+: 39.85 ± 3.89 mM; DAWM–: 39.82 ± 4.25 mM) compared to normal grey and white matter in HC (GM 40.87 ± 3.25 mM, WM 35.9 ± 1.81 mM; p Conclusion 23Na MRI is confirmed as a sensitive marker of even subtle tissue abnormalities. DAWM sodium levels are increased and comparable to the abnormalities in NAWM, suggesting pathological changes less severe than in focal lesions comparable to what is expected in the NAWM.

In this pilot study we tested whether a low dose application of a mild diuretic substance such as eplerenone is beneficial in early stages of Duchenne muscular dystrophy using 23Na und 1H imaging, myometry, and clinical testing versus the glucocorticoid gold standard. Two 7-years old patients with DMD were examined on a 3T MRI system. 1H MRI and 23Na density-adapted 3-dimensional radial MRI sequences were performed both before and 1, 3 and 6 months after therapy with eplerenone respectively cortisone. We quantified fatty infiltration on T1-weighted images using subcutaneous fat as reference and fat fraction with a two-point DIXON sequence. Muscle oedema was quantified on STIR images and DIXON water maps with background noise as reference. We quantified Na+ by a muscular tissue concentration sequence with a 51.3mM Na+ with 5% agarose reference tube. A Na+ IR-sequence was used for determination of mainly myoplasmic Na+. Correspondingly myometry of muscles and tendons were assessed. Clinical tests (i.e. 4-steps-test) and blood counts (i.e. K+) were done by a pediatrician. Under eplerenone therapy we detected a reduction of muscular oedema, intracellular-weighted sodium IR signal and muscular sodium concentration. The oedema reduction in the DMD patient receiving eplerenone was more pronounced to the patient with cortisone. Myometric-measured tissue parameters such as muscle stiffness had a more pronounced effect in the child treated with eplerenone after a first increase in muscle stiffness both after eplerenone and cortisone treatment. Clinical abilities during both therapies were mostly constant. Eplerenone might be a possible new therapy option in DMD patients.

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.

This paper offers a critical review of the properties, methods and potential clinical application of sodium (23Na) MRI in human heart. Because the tissue sodium concentration (TSC) in heart is about ~40 µmol/g wet weight, and the 23Na gyromagnetic ratio and sensitivity are respectively about one-quarter and one-11th of that of hydrogen (1H), the signal-to-noise ratio of 23Na MRI in the heart is about one-6000th of that of conventional cardiac 1H MRI. In addition, as a quadrupolar nucleus, 23Na exhibits ultra-short and multi-component relaxation behavior (T1 ~ 30 ms; T2 ~ 0.5–4 ms and 12–20 ms), which requires fast, specialized, ultra-short echo-time MRI sequences, especially for quantifying TSC. Cardiac 23Na MRI studies from 1.5 to 7 T measure a volume-weighted sum of intra- and extra-cellular components present at cytosolic concentrations of 10–15 mM and 135–150 mM in healthy tissue, respectively, at a spatial resolution of about 0.1–1 ml in 10 min or so. Currently, intra- and extra-cellular sodium cannot be unambiguously resolved without the use of potentially toxic shift reagents. Nevertheless, increases in TSC attributable to an influx of intra-cellular sodium and/or increased extra-cellular volume have been demonstrated in human myocardial infarction consistent with prior animal studies, and arguably might also be seen in future studies of ischemia and cardiomyopathies – especially those involving defects in sodium transport. While technical implementation remains a hurdle, a central question for clinical use is whether cardiac 23Na MRI can deliver useful information unobtainable by other more convenient methods, including 1H MRI. Copyright © 2015 John Wiley & Sons, Ltd.

Background: Increase of brain total sodium concentrations (TSC) is present in multiple sclerosis (MS), but its pathological involvement has not been assessed yet. Objective: To determine in vivo the metabolic counterpart of brain sodium accumulation. Materials/methods: Whole brain 23Na-MR imaging and 3D-1H-EPSI data were collected in 21 relapsing-remitting multiple sclerosis (RRMS) patients and 20 volunteers. Metabolites and sodium levels were extracted from several regions of grey matter (GM), normal-appearing white matter (NAWM) and white matter (WM) T2 lesions. Metabolic and ionic levels expressed as Z-scores have been averaged over the different compartments and used to explain sodium accumulations through stepwise regression models. Results: MS patients showed significant 23Na accumulations with lower choline and glutamate–glutamine (Glx) levels in GM; 23Na accumulations with lower N-acetyl aspartate (NAA), Glx levels and higher Myo-Inositol (m-Ins) in NAWM; and higher 23Na, m-Ins levels with lower NAA in WM T2 lesions. Regression models showed associations of TSC increase with reduced NAA in GM, NAWM and T2 lesions, as well as higher total-creatine, and smaller decrease of m-Ins in T2 lesions. GM Glx levels were associated with clinical scores. Conclusion: Increase of TSC in RRMS is mainly related to neuronal mitochondrial dysfunction while dysfunction of neuro-glial interactions within GM is linked to clinical scores.

Background To develop and optimize radiofrequency (RF) hardware for the detection of endogenous sodium (23Na) by 3.0 Tesla (T) MRI in the human prostate. Methods A transmit-only receive-only (TORO) RF system of resonators consisting of an unshielded, asymmetric, quadrature birdcage (transmit), and an endorectal (ER), linear, surface (receive) coil were developed and tested on a 3T MRI scanner. Two different ER receivers were constructed; a single-tuned (23Na) and a dual-tuned (1H/23Na). Both receivers were evaluated by the measurements of signal-to-noise ratio (SNR) and B1 homogeneity. For tissue sodium concentration (TSC) quantification, vials containing known sodium concentrations were incorporated into the ER. The system was used to measure the prostate TSC of three men (age 55 ± 5 years) with biopsy-proven prostate cancer. Results B1 field inhomogeneity of the asymmetric transmitter was estimated to be less than 5%. The mean SNR measured in a region of interest within the prostate using the single-tuned ER coil was 54.0 ± 4.6. The mean TSC in the central gland was 60.2 ± 5.7 mmol/L and in the peripheral gland was 70.5 ± 9.0 mmol/L. Conclusion A TORO system was developed and optimized for 23Na MRI of the human prostate which showed good sensitivity throughout the prostate for quantitative measurement of TSC. J. Magn. Reson. Imaging 2015;42:436–445.

Water properties and salt uptake in Atlantic salmon fillets as affected by antemortem stress, rigor mortis, and brine salting. A low-field 1H NMR and 1H/23Na MRI study.

To evaluate healthy skeletal muscle pre- and post-exercise via 7 T (23)Na MRI and muscle proton T(2) mapping, and to evaluate diabetic muscle pre- and post-exercise via 7 T (23)Na MRI.The calves of seven healthy subjects underwent imaging pre- and post-exercise via 7 T (23)Na MRI (3D fast low angle shot, TR/TE = 80 ms/0.160 ms, 4 mm x 4 mm x 4 mm) and 1 week later by (1)H MRI (multiple spin-echo sequence, TR/TE = 3,000 ms/15-90 ms). Four type 2 diabetics also participated in the (23)Na MRI protocol. Pre- and post-exercise sodium signal intensity (SI) and proton T(2) relaxation values were measured/calculated for soleus (S), gastrocnemius (G), and a control, tibialis anterior (TA). Two-tailed t tests were performed.In S/G in healthy subjects post-exercise, sodium SI increased 8-13% (p0.03), then decreased (t(1/2) = 22 min), and (1)H T(2) values increased 12-17% (p0.03), then decreased (t(1/2 )= 12-15 min). In TA, no significant changes in sodium SI or (1)H T(2) values were seen (-2.4 to 1%, p0.17). In S/G in diabetics, sodium SI increased 10-11% (p0.04), then decreased (t(1/2) = 27-37 min) without significant change in the TA SI (-3.6%, p = 0.066).It is feasible to evaluate skeletal muscle via 3D (23)Na MRI at 7 T. Post-exercise muscle (1)H T(2) values return to baseline more rapidly than sodium SI. Diabetics may demonstrate delayed muscle sodium SI recovery compared with healthy subjects.

Partial (23)Na MRI invisibility in muscle foods is often referred to as an inherent drawback of the MRI technique, impairing quantitative sodium analysis. Several model samples were designed to simulate muscle foods with a broad variation in protein, fat, moisture, and salt content. (23)Na spin-echo MRI and a recently developed (23)Na SPRITE MRI approach were compared for quantitative sodium imaging, demonstrating the possibility of accurate quantitative (23)Na MRI by the latter method. Good correlations with chemically determined standards were also obtained from bulk (23)Na free induction decay (FID) and CPMG relaxation experiments on the same sample set, indicating their potential use for rapid bulk NaCl measurements. Thus, the sodium MRI invisibility is a methodological problem that can easily be circumvented by using the SPRITE MRI technique.

Background: Advanced magnetic resonance imaging (MRI) techniques provide a window into pathological processes in multiple sclerosis (MS). Nevertheless, to date only few studies have performed sodium MRI in MS. Objectives: We analysed total sodium concentration (TSC) in hyperacute, acute and chronic lesions in MS with 23Na MRI. Methods: 23Na MRI and 1H MRI were performed in 65 MS patients and 10 healthy controls (HC). Mean TSC was quantified in all MS lesions with a diameter of >5 mm and in the normal appearing white and grey matter (NAWM, NAGM). Results: TSC in the NAWM and the NAGM of MS patients was significantly higher compared to HC (WM: 37.51 ± 2.65 mM versus 35.17 ± 3.40 mM; GM: 43.64 ± 2.75 mM versus 40.09 ± 4.64 mM). Acute and chronic MS lesions showed elevated TSC levels of different extent (contrast-enhancing lesions (49.07 ± 6.99 mM), T1 hypointense lesions (45.06 ± 6.26 mM) and remaining T1 isointense lesions (39.88 ± 5.54 mM)). However, non-enhancing hyperacute lesions with a reduced apparent diffusion coefficient showed a TSC comparable to the NAWM (37.22 ± 4.62 mM). Conclusions: TSC is not only a sensitive marker of the severity of chronic tissue abnormalities in MS but is also highly sensitive to opening of the blood–brain barrier and vasogenic tissue oedema in contrast-enhancing lesions.

Purpose To examine the effects of the alkylating anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on 23Na MRI and the water apparent diffusion coefficient (ADC) in subcutaneously- (sc-) implanted 9L glioma in rats. Materials and Methods 23Na MRI and 1H water ADC measurements were performed on sham-treated control (N = 6) and BCNU-treated (N = 15) Fisher rats one day before BCNU injection and then one, three, and five days after BCNU injection. Results The BCNU-treated tumors were divided into BCNU-responsive (RBCNU) and BCNU-nonresponsive (NRBCNU) groups depending on the tumor volume changes that occurred after therapy. The pretreatment 23Na MRI signal intensity (SI) and water ADC values were higher in RBCNU tumors compared to NRBCNU tumors. 23Na MRI SI and water ADC increased with tumor growth in control and NRBCNU groups, but these changes were interrupted by BCNU therapy in RBCNU group. Conclusion 23Na MRI and water ADC measurements may be useful for predicting and monitoring response to chemotherapy in some tumors. However, the changes that occurred in 23Na MRI SI and water ADC in sc-implanted 9L tumors are in contrast to previously published results for BCNU therapy of orthotopic 9L tumors. This may have important implications for monitoring therapy response in tumors. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.

Experimental studies demonstrated persistently increased 23Na content in nonviable myocardium post-myocardial infarction (MI). We hypothesized that nonviable myocardium in humans would show elevated 23Na content at all stages of infarct development, and therefore could be imaged with 23Na MRI. Ten patients were examined on days 4, 14, and 90 after infarction, and five of these patients participated in a 12-month follow-up. Double angulated short-axis cardiac 23Na images were obtained with the use of a 23Na surface coil and an ECG-triggered, 3D gradient-echo sequence. 1H T2-weighted imaging (N = 9) was performed on days 4, 14, and 90. Wall motion was assessed by cine MRI, and the infarct size was determined by late enhancement on day 90. The 23Na signal intensity (SI) of infarcted myocardium was expressed as the percentage increase over 23Na SI of noninfarcted myocardium. All of the patients showed an area of elevated SI on 23Na and 1H T2-weighted images that correlated with wall motion abnormalities and late enhancement. 23Na SI was highest on day 4. It then decreased until day 90, but remained elevated (39% ± 18%, 31% ± 17%, 28% ± 13% on days 4, 14, and 90, respectively, P = 0.001). No further decrease was found 1 year after infarction (25% ± 7%, P = 0.89 vs. day 90). 1H T2-weighted SI decreased between days 4 and 14, but on day 90 only six of nine patients had a residual elevated SI. Thus, 23Na SI is elevated in nonviable infarction at all time points following MI, and 23Na MRI may become a suitable technique for imaging nonviable myocardium in humans. Magn Reson Med 52:545–551, 2004. © 2004 Wiley-Liss, Inc.

One of the initiating steps of osteoarthritis is the loss of proteoglycan (PG) molecules from the cartilage matrix. One method for assessing cartilage integrity, therefore, is to measure the PG content or fixed charge density (FCD) of cartilage. This report shows the feasibility of calculating FCD by (23)Na MRI and introduces MRI protocols for human studies, in vivo. (23)Na MRI was used to measure the sodium concentration inside bovine patellar cartilage. The sodium concentration was then converted to FCD (mM) by considering ideal Donnan equilibrium. These FCD measurements were compared to FCD measurements obtained through standard dimethylmethylene blue PG assays. There was a high correlation (slope = 0.89, r(2) = 0.81) between the FCD measurements obtained by (23)Na MRI and those obtained by the PG assays. These methods were then employed in quantifying the FCD of articular cartilage of human volunteers in vivo. Two imaging protocols were compared: one using a birdcage coil, the other using a transmit/receive surface coil. Both methodologies gave similar results, with the average sodium concentration of normal human patellar cartilage ranging from approximately 240 to 260 mM. This corresponds to FCDs of -158 mM to -182 mM.

Background Established imaging methods are still not confident in the determination of stroke onset. Sodium imaging in animal models and lately in humans implicates that the sodium signal intensity within the ischemic lesion increases in a time-dependent fashion. Sodium imaging usually requires a time-consuming change of resonators or magnetic resonance imaging systems. To avoid this, we used a double-tuned 1H/23Na birdcage head coil in combination with a protocol minimizing T1- and T2*-weighting effects for measurement of sodium intensity in acute stroke patients. Methods Multinuclear 1H/23Na data sets were obtained from 16 stroke patients [75 ± 9.9 (standard deviation) years old] 4-130 h after symptom onset. The protocol was acquired on a clinical 3T magnetic resonance imaging site using a double-tuned 1H/23Na birdcage head coil. Sodium signal intensity within the lesion and homologous contralateral side was measured and compared. Results With an acquisition time of the complete magnetic resonance imaging protocol of 22 min, a nonlinear sodium signal intensity increase within the lesion over time after stroke onset was acknowledged. Onset time within six-hours showed an increase of only 8% or less, whereas onset time beyond 8.5 h demonstrated increases of 36% or more reaching a maximum of 170% > 120 h. In addition, some patients showed a difference in sodium signal intensity compared with diffusion weighted imaging lesion. Conclusions The use of a double-tuned 1H/23Na birdcage head coil in a clinical setting ‘allowed sodium intensity measurements’ in a justifiable time also for acute stroke patients, and heterogenous sodium signal intensity in the diffusion weighted imaging lesion might represent differences in tissue damage or repair.

Skin sodium (Na+) storage, as a physiologically important regulatory mechanism for blood pressure, volume regulation and, indeed, survival, has recently been rediscovered. This has prompted the development of MRI methods to assess Na+ storage in humans (23Na MRI) at 3.0 T. This work examines the feasibility of high in-plane spatial resolution 23Na MRI in skin at 7.0 T. A two-channel transceiver radiofrequency (RF) coil array tailored for skin MRI at 7.0 T (f = 78.5 MHz) is proposed. Specific absorption rate (SAR) simulations and a thorough assessment of RF power deposition were performed to meet the safety requirements. Human skin was examined in an in vivo feasibility study using two-dimensional gradient echo imaging. Normal male adult volunteers (n = 17; mean ± standard deviation, 46 ± 18 years; range, 20–79 years) were investigated. Transverse slices of the calf were imaged with 23Na MRI using a high in-plane resolution of 0.9 × 0.9 mm2. Skin Na+ content was determined using external agarose standards covering a physiological range of Na+ concentrations. To assess the intra-subject reproducibility, each volunteer was examined three to five times with each session including a 5-min walk and repositioning/preparation of the subject. The age dependence of skin Na+ content was investigated. The 23Na RF coil provides improved sensitivity within a range of 1 cm from its surface versus a volume RF coil which facilitates high in-plane spatial resolution imaging of human skin. Intra-subject variability of human skin Na+ content in the volunteer population was

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.

The acute affect of voluntary muscle contractions performed by healthy volunteers was evaluated using (23)Na nuclear magnetic resonance (NMR). Three-dimensional gradient-echo (23)Na images, pulse-acquired spectra, and transverse relaxation times were obtained before and after ankle flexion-extension exercise. The muscle sodium concentration was calculated from (23)Na images using a 40 mM NaCl standard and the measured T(2) values. Before exercise the muscle sodium concentration was 26+/-4 mmole/kg wet weight. This agrees closely with literature values, suggesting that muscle Na(+) is fully NMR visible. The (23)Na image intensity increased by 34%+/-7% in the exercised muscle and diminished with a half-life of 30+/-6 minutes. The pulse-acquired spectra, however, did not show any significant change in muscle signal intensity following exercise, but the relative contribution of the slow T(2) component increased. The calculated sodium concentration also did not change significantly after the exercise. We therefore infer that the changes in (23)Na magnetic resonance imaging (MRI) were due to a change in sodium-macromolecular interaction rather than a change in tissue sodium content. We believe that this report represents the first study of (23)Na MRI of skeletal muscle.

Many exciting new variations of MRI have been tested in MR research, but only a few find their way to clinical use. Sodium (23Na) MRI is one of those techniques that at first glance appeared to be very promising. 23Na MRI has the potential to extend MR imaging beyond anatomical imaging by providing information on physiology and cellular metabolism. Signal strength is related to disease specific changes in the tissue. This type of ‘disease specific’ contrast can compensate for the much lower signal to noise ratio of these techniques. The contrast between ischaemic (1) and healthy cardiac tissue and between benign tissue and malignant tumors (2) is based on significant changes in Tissue Sodium Concentration (TSC). For stroke in humans an increase in TSC was recorded of 50%(3). The feasibility of 23Na MRI on human subjects has been demonstrated as far back as 1989 (4) and the image contrast obtainable in stroke(3), cancer and edema (2) has also been demonstrated some time ago. In spite of this, 23Na MRI has yet to find a wider acceptance as a possible clinical tool. The technical difficulty of obtaining 23Na scans can only be part of the reason. If it had been deemed worth it commercially, the MR scanner manufacturers would have found a way to simplify the procedure to almost a push button solution. Apparently, the progression of 23Na MRI from research to clinical use was halted by a failure to create a demand for the great potential of 23Na MRI. Currently 23Na MRI appears to have been rediscovered. Even though the technical advances since the early 90's have been incremental, a threshold has been reached by reducing scan times to the point where the addition of a 23Na MRI to an existing 1H-MRI protocol becomes an option for studies on patients rather than just very patient volunteers. An overview of recent advances in the use of 23Na-MRI for clinical MR research will illustrate the very significant consequences of the reduction of the length of a 23Na scan from more than 45 minutes in earlier attempts to less than 15 minutes at 1.5T. Now 23Na-MRI is no longer a stand-alone modality with 1H-MRI used only as a scout image. Instead, 23Na-MRI is used as an add-on to improve specificity of established 1H-MRI protocols. To understand what kind of information 23Na-MR can and cannot add to an MRI exam we have to explore the properties of this nucleus and what imaging techniques we can use to observe it.

Low signal-to-noise ratio (SNR) has been the main obstacle to multiple quantum-filtered 23Na imaging becoming an important technique for biologic and clinical applications. Through computer simulations and phantom experiments, we show that the SNR in 23Na imaging can be substantially improved by weighted signal averaging. Three-dimensional single quantum and triple quantum (TQ)-filtered 23Na images of an externalized rabbit kidney were collected with this technique. The TQ-filtered image did not show any signal when the animal was alive. However, upon sacrificing the animal, the renal cortex became clearly visible without any significant increase in signal from the medullary region. This increase in TQ-filtered signal in the renal cortex may be caused by an increased concentration of intracellular Na+ in the large intracellular space present herein, compared with the medulla. To our knowledge, this study represents the first example of three-dimensional TQ-filtered 23Na image of a biological sample.

(23)Na magnetic resonance imaging is a promising technique for the noninvasive imaging of renal function. Past investigations of the renal corticomedullary [(23)Na] gradient have relied on imaging only in the coronal plane and on cumbersome calculations of [(23)Na], which require the use of external phantoms. The aim of this study is therefore two-fold: to use an isotropic three-dimensional data set to compare coronal measurements of renal [(23)Na] relative to measurements obtained in planes along the corticomedullary gradients and to investigate cerebrospinal fluid (CSF) (23)Na signal as an internal reference standard, obviating the need for time-intensive [(23)Na] calculations.Nominal isotropic three-dimensional (23)Na MRI data sets were obtained in 14 healthy volunteers before and after a water load. Images were reconstructed in the coronal plane and in planes angled along the direction of the corticomedullary sodium gradients. [(23)Na] values and values of the corticomedullary [(23)Na] gradient were measured by placement of a linear region of interest along corticomedullary gradients in both the coronal/nonangled [(23)Na(non-ang)] and the angled [(23)Na(ang)] image reconstructions. CSF [(23)Na] was also acquired at multiple levels. Ratios of renal (23)Na and CSF (23)Na signal were calculated to construct a semiquantitative parameter, [(23)NaCSF]. Results of water stimulation as measured by [(23)NaCSF] and [(23)Na(ang)] were then compared.Mean values of [(23)Na(ang)] were statistically significantly greater than those of [(23)Na(non-ang)] (P.0001), although these values were linearly correlated (R = 0.553, P.0001) and exhibited similar extents of decreases in absolute terms (P = .2) and in terms of the corticomedullary gradient following the water load. CSF [(23)Na] did not statistically significantly differ at any level after the water load (P.5) but tended to increase in the cranial direction (P.001). [(23)NaCSF] measures demonstrated analogous statistical properties to [(23)Na(ang)] before and after the water load.Assessment of renal corticomedullary [(23)Na] gradients using isotropic data sets with image reconstructions along the gradients is likely more accurate than measurements in the coronal plane. Because CSF [(23)Na] differs based on anatomic levels, such measures are useful as an internal reference only if region of interest placement is consistent. With this caveat in mind, normalization of renal to CSF (23)Na signal provides a feasible, less cumbersome alternative to [(23)Na] calculations in intraindividual studies.

Adjuvant radiochemotherapy (RCHT) improves survival of patients with locally advanced gastric cancer. Conventional three-dimensional conformal radiotherapy (3D-CRT) results in ablative doses to a significant amount of the left kidney, while image-guided intensity-modulated radiotherapy (IG-IMRT) provides excellent target coverage with improved kidney sparing. Few long-term results on IMRT for gastric cancer, however, have been published. Functional magnetic resonance imaging (fMRI) at 3.0 T including blood oxygenation-level dependent (BOLD) imaging, diffusion-weighted imaging (DWI) and, for the first time, (23)Na imaging was used to evaluate renal status after radiotherapy with 3D-CRT or IG-IMRT.Four disease-free patients (2 after 3D-CRT and 2 after IMRT; FU for all patients5 years) were included in this feasibility study. Morphological sequences, axial DWI images, 2D-gradient echo (GRE)-BOLD images, and (23)Na images were acquired. Mean values/standard deviations for ((23)Na), the apparent diffusion coefficient (ADC), and R2* values were calculated for the upper/middle/lower parts of both kidneys. Corticomedullary (23)Na-concentration gradients were determined.Surprisingly, IG-IMRT patients showed no morphological alterations and no statistically significant differences of ADC and R2* values in all renal parts. Values for mean corticomedullary (23)Na-concentration matched those for healthy volunteers. Results were similar in 3D-CRT patients, except for the cranial part of the left kidney. This was atrophic and presented significantly reduced functional parameters (p = 0.001-p = 0.033). Reduced ADC values indicated reduced cell density and reduced extracellular space. Cortical and medullary R2* values of the left cranial kidney in the 3D-CRT group were higher, indicating more deoxygenated hemoglobin due to reduced blood flow/oxygenation. ((23)Na) of the renal cranial parts in the 3D-CRT group was significantly reduced, while the expected corticomedullary (23)Na-concentration gradient was partially conserved.Functional MRI can assess postradiotherapeutic renal changes. As expected, marked morphological/functional effects were observed in high-dose areas (3D-CRT), while, unexpectedly, no alteration in kidney function was observed in IG-IMRT patients, supporting the hypothesis that reducing total/fractional dose to the renal parenchyma by IMRT is clinically beneficial.

23Na MRI changes from the acute to chronic phase were investigated in seven patients with cerebral infarcts. They showed no signal increase during the first 13 h after the stroke and revealed a definite signal increase thereafter. This reached a maximum 45-82 h after stroke and became slightly less marked in the subacute and chronic phases, probably as a result of disappearance of cerebral oedema. In the early acute phase of stroke, 23Na MRI appears to fail to demonstrate Na+ increases in the ischaemic area, due presumably to the invisibility on MRI of intracellular 23Na in the intact brain. The increase more than 13 h after stroke, during which ischaemic cells are likely to die, is presumably because of increased visibility of intracellular 23Na in the dead cells. 23Na MRI is apparently insensitive to early ischaemic changes, but may be useful for assessing the cell viability in the ischaemic brain.

To test the hypotheses that (i) the regional heterogeneity of brain sodium concentration ([Na(+)](br)) provides a parameter for ischemic progression not available from apparent diffusion coefficient (ADC) data, and (ii) [Na(+)](br) increases more in ischemic cortex than in the caudate putamen (CP) with its lesser collateral circulation after middle cerebral artery occlusion in the rat.(23)Na twisted projection MRI was performed at 3 Tesla. [Na(+)](br) was independently determined by flame photometry. The ischemic core was localized by ADC, by microtubule-associated protein-2 immunohistochemistry, and by changes in surface reflectivity.Within the ischemic core, the ADC ratio relative to the contralateral tissue was homogeneous (0.63 +/- 0.07), whereas the rate of [Na(+)](br) increase (slope) was heterogeneous (P0.005): 22 +/- 4%/h in the sites of maximum slope versus 14 +/- 1%/h elsewhere (here 100% is [Na(+)](br) in the contralateral brain). Maximum slopes in the cortex were higher than in CP (P0.05). In the ischemic regions, there was no slope/ADC correlation between animals and within the same brain (P0.1). Maximum slope was located at the periphery of ischemic core in 8/10 animals.Unlike ADC, (23)Na MRI detected within-core ischemic lesion heterogeneity.

Sodium MRI has the potential to differentiate viable and non-viable infarcted myocardium. The accurate quantification of the total sodium content requires imaging techniques with ultra short echo times below 0.5 ms. We present a 3D-radial projection technique which allows the acquisition of ECG-triggered sodium images of the human heart with echo times of 0.4 ms. A 3D-data set of the heart of a volunteer was acquired within less than 18 min on a clinical scanner (1.5 T), achieving a SNR of 10 in the myocardium with an isotropic resolution of 10 mm. This technique provides a tool for clinical studies of ischemic heart diseases.

Background and Purpose — 23 Na MRI may offer new insight into the evaluation of tissue injury. We performed a direct, longitudinal, morphological comparison of 1 H T2 relaxation, 1 H apparent diffusion coefficient (ADC), 23 Na content, and histopathology after cerebral ischemia to address the hypotheses that (a) 23 Na MRI is unique in comparison to 1 H MRI, and (b) accumulation of 23 Na is an unambiguous marker for dead tissue. Methods —Rats underwent 30 minutes of focal ischemia. MRIs of 1 H T2, 1 H ADC, and 23 Na content were acquired from 12 hours up to 1, 2, or 14 days after reperfusion. On excision, brains were stained with triphenyltetrazolium chloride (TTC). Results —In all cases, the region of abnormality increased in size for 2 days. On day 5, both 1 H T2 and ADC temporarily appeared normal despite the presence of TTC-defined infarction. By comparison, the volume of tissue exhibiting abnormally intense 23 Na signal mirrored the TTC-defined infarct at all time points. Conclusions —Regions of high 23 Na content correlate well with the TTC-defined infarct and may be a quantitative in vivo marker for dead tissue. In contrast, the dynamics of the 1 H T2 and ADC make it difficult to interpret these images without additional information because they may appear normal despite infarction. Neither type of 1 H image delineates dead tissue, and none of these methods predicts the potential infarct size at early time points.

Proton magnetic resonance imaging (1H MRI) has emerged as a clinically useful tool for the diagnosis of intraocular tumors. During the last four years 1H MRI characteristics, including spin-lattice relaxation times (T1) and spin-spin relaxation times (T2), have been established for several types of tumors. The introduction of surface coils to the imaging process has significantly improved the quality of intraocular MR images, leading some clinicians to suggest that 1H MR images are preferable to CT scans. Another MRI technique, in which sodium-23 (23Na) is imaged rather than protons, is now under development as tool for intraocular diagnosis. The potential of 23Na MRI depends upon the high concentration and "visibility" of sodium in the vitreous body, and upon the apparent differences in sodium behavior in normal cells vs. tumor cells. The metabolism of normal ocular tissues and intraocular tumors may be probed noninvasively with phosphorus-31 MR spectroscopy (31P MRS). Much progress has been made during the last few years in understanding the appearance of 31P MR spectra of many types of healthy and diseased cells and tissues. Clinical application of this technique to the diagnosis and monitoring of intraocular tumors following conservative treatment will be dependent upon the development of spectroscopy techniques that collect information from the volume of interest (tumor) only.