Magnetic Resonance Imaging on Sodium Nuclei: Potential Medical Applications of <Superscript>23</Superscript>Na MRI

Sodium is a key element in a living organism. The increase of its concentration is an indicator of many pathological conditions. ²³Na magnetic resonance imaging (MRI) is a quantitative method that allows to determine the sodium content in tissues and organs in vivo. This method has not yet entered clinical practice widely, but it has already been used as a clinical research tool to investigate diseases such as brain tumors, breast cancer, stroke, multiple sclerosis, hypertension, diabetes, ischemic heart disease, osteoarthritis. The active development of the ²³Na MRI is promoted by the growth of available magnetic fields, the expansion of hardware capabilities, and the development of pulse sequences with ultra-short echo time.     

Na and H NMR Microimaging of Intact Plants

²³Na NMR microimaging is described to map, for the first time, the sodium distribution in living plants. As an example, the response of 6-day-old seedlings of Ricinus communis to exposure to sodium chloride concentrations from 5 to 300 mM was observed in vivo using ²³Na as well as ¹H NMR microimaging. Experiments were performed at 11.75 T with a double resonant ²³Na–¹H probehead. The probehead was homebuilt and equipped with a climate chamber. T₁ and T₂ of ²³Na were measured in the cross section of the hypocotyl. Within 85 min ²³Na images with an in-plane resolution of 156 × 156 μm were acquired. With this spatial information, the different types of tissue in the hypocotyl can be discerned. The measurement time appears to be short compared to the time scale of sodium uptake and accumulation in the plant so that the kinetics of salt stress can be followed. In conclusion, ²³Na NMR microimaging promises great potential for physiological studies of the consequences of salt stress on the macroscopic level and thus may become a unique tool for characterizing plants with respect to salt tolerance and salt sensitivity.     

In vivo K, Na and H MR imaging using a triple resonant RF coil setup

The maintenance of a gradient of potassium and sodium ions across the cell membranes is essential for the physiological function of the mammal organism. The measurement of the spatial distribution of pathologically changing ion concentrations of ²³Na and ³⁹K with magnetic resonance imaging offers a promising approach in clinical diagnostics to measure tissue viability. Existing studies were focused mainly on ²³Na imaging as well as spectroscopy with only one post-mortem study for ³⁹K imaging. In this paper a triple resonant RF coil setup for the rat head at 9.4 T is presented for imaging of both nuclei (²³Na and ³⁹K) and the acquisition of anatomical proton images in the same experiment without moving the subject or the RF coil. In vivo MR images of ³⁹K and ²³Na in the rat brain were acquired as well as anatomical proton images in the same scanning session.     

Combined imaging biomarkers for therapy evaluation in glioblastoma multiforme: correlating sodium MRI and F-18 FLT PET on a voxel-wise basis

We evaluate novel magnetic resonance imaging (MRI) and positron emission tomography (PET) quantitative imaging biomarkers and associated multimodality, serial-time-point analysis methodologies, with the ultimate aim of providing clinically feasible, predictive measures for early assessment of response to cancer therapy. A focus of this work is method development and an investigation of the relationship between the information content of the two modalities. Imaging studies were conducted on subjects who were enrolled in glioblastoma multiforme (GBM) therapeutic clinical trials. Data were acquired, analyzed and displayed using methods that could be adapted for clinical use. Subjects underwent dynamic [¹⁸F]fluorothymidine (F-18 FLT) PET, sodium (²³Na) MRI and 3-T structural MRI scans at baseline (before initiation of therapy), at an early time point after beginning therapy and at a late follow-up time point after therapy. Sodium MRI and F-18 FLT PET images were registered to the structural MRI. F-18 FLT PET tracer distribution volumes and sodium MRI concentrations were calculated on a voxel-wise basis to address the heterogeneity of tumor physiology. Changes in, and differences between, these quantities as a function of scan timing were tracked.     

Sodium T2*-weighted MR imaging of acute focal cerebral ischemia in rabbits

Changes in T2*-weighted tissue sodium (23Na) signal following acute ischemia may help to identify necrotic tissue and estimate the duration of ischemia. Sodium signal was monitored in a rabbit model of acute (0-4 h) focal cerebral ischemia, using gradient echo 23Na MR images (echo time = 3.2 ms) acquired continuously in 20-min intervals on a 4-Tesla MRI. 2,3,5-Triphenyl-tetrazolium chloride staining was used to identify regions of necrosis. In necrotic tissue, average 23Na image signal intensity decreased by 11% +/- 8% during the first 40 min of ischemia followed by a linear increase (0.19%/min) to 25% +/- 14% greater than baseline after 4 h of ischemia. The time course of 23Na signal change observed in necrotic tissue following focal ischemia in this rabbit model is consistent with an initial decrease in 23Na T2* relaxation time followed by an increase in tissue sodium concentration and provides further evidence that tissue 23Na signal may offer unique information regarding tissue viability that is complementary to other MR imaging techniques.     

Characterization of sodium cations in zeolite omega by solid-state23Na NMR spectroscopy

Sodium cations localized at crystallographically distinct cation sites in the hydrated zeolite omega were characterized by various solid-state²³Na NMR techniques, such as²³Na MAS,¹H-²³Na CP/MAS,²³Na quadrupolar nutation and variable temperature NMR spectroscopy. In the²³Na NMR spectrum of zeolite omega two signals were identified, a low-field Gaussian line at ca. ?3 ppm (its quadrupole coupling constant was estimated approximately on the order of magnitude of 0.2 MHz) and a high-field quadrupole pattern with an isotropic chemical shift of ?8 ppm and a quadrupole coupling constant of 2.3 MHz. The former signal is attributed to sodium cations in the 12-ring channels and the latter one to sodium cations in gmelinite cages of zeolite omega. The variable temperature NMR experiments reveal the interactions between the sodium cation and the adsorbed water molecules in zeolite omega. The sodium cations in the 12-ring channels are highly hydrated and so mobile as to average the¹H-²³Na dipole interaction. Hence, these sodium cations give no contribution to the¹H-²³Na cross polarization process. By contrast, the sodium cations in the gmelinite cages are less hydrated and more rigid. They are closely bonded not only to the adsorbed water molecules but also to the lattice oxygen of the gmelinite cages, which leads to an effective¹H-²³Na polarization transfer.     

Noninvasive (1)H and (23)Na nuclear magnetic resonance imaging of ancient Egyptian human mummified tissue

Historic mummies are a unique example of the human desire for immortality. Therefore, it is not surprising that modern diagnostic imaging has been widely applied to study them. Yet, magnetic resonance imaging (MRI) of such old remains has never been successfully achieved in a noninvasive way without rehydration. Furthermore, the impact of artificial mummification as done in ancient Egypt by natron (a blend of NaCl, Na(2)CO(3), NaHCO(3) and NaP(2)SO(4)) on human tissue with a particular focus on the sodium spatial distribution has never been addressed. Here, we show for the very first time completely noninvasive (1)H and (23)Na imaging of an ancient Egyptian mummified finger by nuclear magnetic resonance (NMR). Protons could be visualized by NMR only in the tissue close to surface and sodium primarily in the bone, while computer tomography images both, soft tissue and bone but does not distinguish between different chemical elements. The selective enrichment of sodium in the bone may by due to postmortem incorporation of (23)Na into the tissue by natron-based mummification because our reference measurement of a historical finger not subjected to artificial mummification showed no sodium signal at all. Our results demonstrate not only the general feasibility of nonclinical MRI to visualize historic dry human tissues but also shows the specific (1)H and (23)Na spatial distributions in such mummy tissue, which is particularly interesting for archeology and may open up a new application for MRI.     

Graphene Nanosheets Suppress the Growth of Sb Nanoparticles in an Sb/C Nanocomposite to Achieve Fast Na Storage

Presently, graphene incorporation is one of the most effective strategies to develop superior electrode materials for sodium‐ion batteries (SIBs). Herein, it is excitingly found that an incorporated graphene nanosheet in the preparation processes can not only completely protect all the Sb nanoparticles in an Sb/C composite from being inactivated, but also suppresses their growth to undesirable micrometer size. While there are still many exposed Sb particulates on the surface of pristine Sb/C microplates, the graphene‐incorporated Sb/C/G nanocomposite consists of uniform Sb nanoparticles of 20–50 nm, all of which have been protected by and wrapped in the mixed carbon network. When used as anode materials for SIBs, the Sb/C/G nanocomposite exhibits the best Na‐storage properties in terms of the highest reversible capacity (650 mA h g^?1 at 0.025 A g^?1), fastest Na‐storage ability (290 mA h g^?1 at a high current density of 8 A g^?1), and optimal cycling performance (no capacity decay after 200 cycles), in comparison to pristine Sb/C and pure Sb. It is further revealed that the much enhanced performance should originate from the improvement of Na‐storage kinetics and increase of electronic conductivity via comparing the electrochemical impedance spectra, and cyclic voltammetry profiles, as well as the polarization variation along with current densities.     

Ion implantation in III–V compounds

In this work we studied the effect of electron and proton irradiation on the depth distribution of sodium in commercial soda-lime glasses. Samples have been irradiated at different energies and fluences.

The ²³Na (ρ, α) ²⁰Ne nuclear reaction has been used to determine the sodium profiles. No detectable changes in the sodium concentration profiles have been introduced during the measurements, the proton fluences and doses needed in this type of analysis being very low.

The obtained results support the hypothesis that the driving force for Na diffusion is mainly connected to the build-up of an electric field whose direction is determined by the projectile charge, while Na mobility changes because of the local temperature increase due to the beam power dissipation.     

<Superscript>17</Superscript>O and<Superscript>23</Superscript>Na nuclear quadrupole double resonance of sodium formate and sodium acetate

The¹⁷O and²³Na nuclear quadrupole resonance spectra of powdered sodium formate and sodium acetate have been determined at room temperature by proton-¹⁷O and proton-²³Na double resonance. All¹⁷O sites have been found to be chemically equivalent. The nonzero value of the asymmetry parameter of the electric field gradient tensor at the¹⁷O site shows that the electron density distribution is not cylindrically symmetric around the C−O bond axis.     

Practical design of a 4 Tesla double-tuned RF surface coil for interleaved 1H and 23Na MRI of rat brain

MRI is proving to be a very useful tool for sodium quantification in animal models of stroke, ischemia, and cancer. In this work, we present the practical design of a dual-frequency RF surface coil that provides (1)H and (23)Na images of the rat head at 4 T. The dual-frequency RF surface coil comprised of a large loop tuned to the (1)H frequency and a smaller co-planar loop tuned to the (23)Na frequency. The mutual coupling between the two loops was eliminated by the use of a trap circuit inserted in the smaller coil. This independent-loop design was versatile since it enabled a separate optimisation of the sensitivity and RF field distributions of the two coils. To allow for an easy extension of this simple double-tuned coil design to other frequencies (nuclei) and dimensions, we describe in detail the practical aspects of the workbench design and MRI testing using a phantom that mimics in vivo conditions. A comparison between our independent-loop, double-tuned coil and a single-tuned (23)Na coil of equal size obtained with a phantom matching in vivo conditions, showed a reduction of the (23)Na sensitivity (about 28 %) because of signal losses in the trap inductance. Typical congruent (1)H and (23)Na rat brain images showing good SNR ((23)Na: brain 7, ventricular cerebrospinal fluid 11) and spatial resolution ((23)Na: 1.25 x 1.25 x 5mm(3)) are also reported. The in vivo SNR values obtained with this coil were comparable to, if not better than, other contemporary designs in the literature.     

Monitoring chemotherapeutic response in RIF-1 tumors by single-quantum and triple-quantum-filtered (23)Na MRI, (1)H diffusion-weighted MRI and PET imaging

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

23Na and (1)H NMR microimaging of intact plants

(23)Na NMR microimaging is described to map, for the first time, the sodium distribution in living plants. As an example, the response of 6-day-old seedlings of Ricinus communis to exposure to sodium chloride concentrations from 5 to 300 mM was observed in vivo using (23)Na as well as (1)H NMR microimaging. Experiments were performed at 11.75 T with a double resonant (23)Na-(1)H probehead. The probehead was homebuilt and equipped with a climate chamber. T(1) and T(2) of (23)Na were measured in the cross section of the hypocotyl. Within 85 min (23)Na images with an in-plane resolution of 156 x 156 micrometer were acquired. With this spatial information, the different types of tissue in the hypocotyl can be discerned. The measurement time appears to be short compared to the time scale of sodium uptake and accumulation in the plant so that the kinetics of salt stress can be followed. In conclusion, (23)Na NMR microimaging promises great potential for physiological studies of the consequences of salt stress on the macroscopic level and thus may become a unique tool for characterizing plants with respect to salt tolerance and salt sensitivity.     

<Superscript>23</Superscript>Na spin-lattice relaxation in powder Rochelle salt

The temperature dependence of ²³Na spin-lattice relaxation in the polycrystalline Rochelle salt was studied by NMR within the range from 235 to 320 K covering both Curie points. The spin-relaxation time t ₁ versus temperature curve showed noticeable dips near the phase transitions against the background of the regular decrease in the relaxation time upon increasing temperature. The dips observed were ascribed to critical contributions to sodium spin-lattice relaxation caused by the slowdown of the correlation time for one of two relaxation modes in the Rochelle salt. The ²³Na NMR parameters were also measured for the melted Rochelle salt. This article was submitted by the authors in English.     

MR imaging of teeth using a silent single point imaging technique

Magnetic resonance imaging (MRI) of teeth is an emerging application area which is still in development. Previous investigations did not fully focus on potential in vivo applications. Using ¹H and ³¹P MRI, we obtained ex vivo microimages of teeth with a silent single point imaging (SPI) technique. ¹H Images with an in-plane resolution of 310×310 μm² were obtained. Utilizing sine-shaped gradient ramps significantly reduced the sound pressure level of the experiment to that of background noise. ¹H magnetic resonance spectroscopy (MRS) was used to characterize the major components in the observed resonance. The spin–spin (T₂) relaxation times of water in enamel and dentin differed by at least one order of magnitude. Three-dimensional surface reconstruction of the data allowed for complete visualization of the tooth’s surface while volume reconstruction displayed the internal geometry. PACS 82.56.Na; 83.85.Fg; 87.61.-c; 87.19.-j; 43.50.Cb     

Parallel imaging with 3D TPI trajectory: SNR and acceleration benefits

Three-dimensional (3D) twisted projection imaging (TPI) trajectory has a unique advantage in sodium (²³Na) imaging on clinical MRI scanners at 1.5 or 3 T, generating a high signal-to-noise ratio (SNR) with a short acquisition time (∼10 min). Parallel imaging with an array of coil elements transits SNR benefits from small coil elements to acquisition efficiency by sampling partial k-space. This study investigates the feasibility of parallel sodium imaging with emphases on SNR and acceleration benefits provided by the 3D TPI trajectory. Computer simulations were used to find available acceleration factors and noise amplification. Human head studies were performed on clinical 1.5/3-T scanners with four-element coil arrays to verify simulation outcomes. In in vivo studies, proton (¹H) data, however, were acquired for concept–proof purpose. The sensitivity encoding (SENSE) method with the conjugate gradient algorithm was used to reconstruct images from accelerated TPI-SENSE data sets. Self-calibration was employed to estimate coil sensitivities. Noise amplification in TPI-SENSE was evaluated using multiple noise trials. It was found that the acceleration factor was as high as 5.53 (corresponding to acceleration number 2×3, ring-by-rotation), with a small image error of 6.9% when TPI projections were reduced in both polar (ring) and azimuthal (rotation) directions. The average noise amplification was as low as 98.7%, or 27% lower than Cartesian SENSE at that acceleration factor. The 3D nature of both TPI trajectory and coil sensitivities might be responsible for the high acceleration and low noise amplification. Consequently, TPI-SENSE may have potential advantages for parallel sodium imaging.     

A reference agent model for DCE MRI can be used to quantify the relative vascular permeability of two MRI contrast agents

Dynamic Contrast Enhancement (DCE) MRI has been used to measure the kinetic transport constant, K^trans, which is used to assess tumor angiogenesis and the effects of anti-angiogenic therapies. Standard DCE MRI methods must measure the pharmacokinetics of a contrast agent in the blood stream, known as the Arterial Input Function (AIF), which is then used as a reference for the pharmacokinetics of the agent in tumor tissue. However, the AIF is difficult to measure in pre-clinical tumor models and in patients. Moreover the AIF is dependent on the Fahraeus effect that causes a highly variable hematocrit (Hct) in tumor microvasculature, leading to erroneous estimates of K^trans. To overcome these problems, we have developed the Reference Agent Model (RAM) for DCE MRI analyses, which determines the relative K^trans of two contrast agents that are simultaneously co-injected and detected in the same tissue during a single DCE-MRI session. The RAM obviates the need to monitor the AIF because one contrast agent effectively serves as an internal reference in the tumor tissue for the other agent, and it also eliminates the systematic errors in the estimated K^trans caused by assuming an erroneous Hct. Simulations demonstrated that the RAM can accurately and precisely estimate the relative K^trans (R^Ktrans) of two agents. To experimentally evaluate the utility of RAM for analyzing DCE MRI results, we optimized a previously reported multiecho ¹⁹F MRI method to detect two perfluorinated contrast agents that were co-injected during a single in vivo study and selectively detected in the same tumor location. The results demonstrated that RAM determined R^Ktrans with excellent accuracy and precision.     

Isotope shift and HFS ofD 1 lines in Na-22 and 23 measured by saturation spectroscopy

High resolution saturation spectroscopy was applied to measure the relative isotope shift of theD ₁ lines in radioactive²²Na against²³Na in vapour cells. The result,δν=758.5(7) MHz, combined with other known values, indicates that the field shift is negligible in sodium isotopes. The hyperfine coupling constant of the² P _1/2 level in²²Na was found to be 37.0(1) MHz. A frequency offset locking technique is described which renders an accurate frequency calibration and achieves a long-term frequency stabilization.     

Electron-stimulated desorption of sodium atoms initiated by their reverse motion

This paper reports on the first measurement of the yield and energy distributions of sodium atoms in electron-stimulated desorption at T = 160 K from sodium layers adsorbed on tungsten with a gold film atop. The Na atom yield has a resonant pattern with an appearance threshold of 30 eV, which can be attributed to exciton excitation in the Na 2p level. The Na yield is associated with the formation of a semiconducting Na _x Au _y film at T ∼ 300 K and sodium and gold coverages in excess of one monolayer. Sodium atoms are desorbed through Auger neutralization of Na²⁺ ions in their reverse motion toward the surface and is limited by the resonant ionization of Na atoms as they pass through the adsorbed layer of Na⁺ ions. The energy distributions of Na atoms are bell shaped with a maximum at about 0.56 eV.     

NMR Studies of Heat-Induced Transitions in Structure and Cation Binding Environments of a Strontium-Saturated Swelling Mica

In this work, we combine ²⁷Al, ²⁹Si, ¹⁹F, and ²³Na magic-angle spinning (MAS) nuclear magnetic resonance (NMR) to characterize the structure and interlayer cation environments in a strontium-saturated member of the swelling mica family before and after a heat-induced collapse of the interlayer space. The ²⁷Al and ²⁹Si MAS NMR demonstrate that the sample consists mainly of swelling mica, though the composition does not match the ideal structural formula. Aluminum NMR also shows that a portion of the aluminum shifts from a tetrahedral to an octahedral coordination environment upon heating. Changes in the ²⁹Si and ¹⁹F NMR after heating are consistent with a structural rearrangement of the tetrahedral sheet to permit the binding of larger cations in the ditrigonal cavity. The ²³Na MAS NMR results indicate the presence of three unique sodium environments before and after heating. The heat-invariant resonance is consistent with the presence of sodium carbonate. The other two resonances are associated with interlayer sodium and reflect a migration of sodium to a dominantly anhydrous ditrigonal binding structure with heating. Quantitative elemental analysis and NMR data presented here suggest strontium is bound deep within the ditrigonal cavity of the collapsed micas. Authors' address: Karl T. Mueller, 104 Chemistry Building, Penn State University, University Park, PA 16802, USA