Cardiorenal sodium MRI at 7.0 Tesla using a 4/4 channel 1 H/23 Na radiofrequency antenna array.

PURPOSE: Cardiorenal syndrome describes disorders of the heart and the kidneys in which a dysfunction of 1 organ induces a dysfunction in the other. This work describes the design, evaluation, and application of a 4/4-channel hydrogen-1/sodium (1 H/23 Na) RF array tailored for cardiorenal MRI at 7.0 Tesla (T) for a better physiometabolic understanding of cardiorenal syndrome. METHODS: The dual-frequency RF array is composed of a planar posterior section and a modestly curved anterior section, each section consisting of 2 loop elements tailored for 23 Na MR and 2 loopole-type elements customized for 1 H MR. Numerical electromagnetic field and specific absorption rate simulations were carried out. Transmission field ( B1+ ) uniformity was optimized and benchmarked against electromagnetic field simulations. An in vivo feasibility study was performed. RESULTS: The proposed array exhibits sufficient RF characteristics, B1+ homogeneity, and penetration depth to perform 23 Na MRI of the heart and kidney at 7.0 T. The mean B1+ field for sodium in the heart is 7.7 ± 0.8 µT/√kW and in the kidney is 6.9 ± 2.3 µT/√kW. The suitability of the RF array for 23 Na MRI was demonstrated in healthy subjects (acquisition time for 23 Na MRI: 18 min; nominal isotropic spatial resolution: 5 mm [kidney] and 6 mm [heart]). CONCLUSION: This work provides encouragement for further explorations into densely packed multichannel transceiver arrays tailored for 23 Na MRI of the heart and kidney. Equipped with this technology, the ability to probe sodium concentration in the heart and kidney in vivo using 23 Na MRI stands to make a critical contribution to deciphering the complex interactions between both organs.

A dual-tuned multichannel bilateral RF coil for 1 H/23 Na breast MRI at 7 T.

PURPOSE: Sodium MRI has shown promise for monitoring neoadjuvant chemotherapy response in breast cancer. The purpose of this work was to build a dual-tuned bilateral proton/sodium breast coil for 7T MRI that provides sufficient SNR to enable sodium breast imaging in less than 10 minutes. METHODS: The proton/sodium coil consists of 2 shielded unilateral units: 1 for each breast. Each unit consists of 3 nested layers: (1) a 3-loop solenoid for sodium excitation, (2) a 3-loop solenoid for proton excitation and signal reception, and (3) a 4-channel receive array for sodium signal reception. Benchmark measurements were performed in phantoms with and without the sodium receive array insert. In vivo images were acquired on a healthy volunteer. RESULTS: The sodium receive array boosted 1.5 to 3 times the SNR compared with the solenoid. Proton SNR loss due to residual interaction with the sodium array was less than 10%. The coil enabled sodium imaging in vivo with 2.8-mm isotropic nominal resolution (~5-mm real resolution) in 9:36 minutes. CONCLUSION: The coil design that we propose addresses challenges associated with sodium's low SNR from a hardware perspective and offers the opportunity to investigate noninvasively breast tumor metabolism as a function of sodium concentration in patients undergoing neoadjuvant chemotherapy.

Corrections of myocardial tissue sodium concentration measurements in human cardiac 23 Na MRI at 7 Tesla.

PURPOSE: To quantify the tissue sodium concentration (TSC) in cardiac 23 Na MRI. To evaluate the influence of different correction methods on the measured myocardial TSC. METHODS: 23 Na MRI of four healthy subjects was conducted at a whole-body 7T MRI system using an oval-shaped 23 Na birdcage coil. Data acquisition was performed with a density-adapted 3D radial pulse sequence using a golden angle projection scheme. 1 H MRI data were acquired at a 3T MRI system to generate a myocardial mask. Retrospective cardiac and respiratory gating were used to reconstruct 23 Na MRI data in the diastolic phase and exhaled state. B0 and B1 inhomogeneity and partial volume (PV) effects were corrected. Relaxation times and TSC of ex vivo blood samples and calf muscle were determined. These values were used in the PV correction to estimate myocardial TSC, which was compared with the measured TSC of calf muscle. RESULTS: Without any correction the measured myocardial TSC was (54 ± 5) mM. The applied correction methods reduced these values by (48 ± 5)% to (29 ± 3) mM, where PV correction had the largest effect (reduction of (34 ± 1)%). Respiratory and cardiac motion gating decreased the concentrations by (11 ± 1)%. With the applied setup, the corrections of B0 and B1 inhomogeneity (reduction of (3 ± 2)%) had negligible influences on TSC values. The resulting myocardial TSC was approximately 1.4-fold higher than the measured TSC of calf muscle tissue of the same healthy subjects ((20 ± 3) mM). CONCLUSION: For quantitative human cardiac 23 Na MRI several corrections are needed and ranked for our setup: PV correction, respiratory and cardiac gating, correction for B1 inhomogeneity effects.

A continuum of T2* components: Flexible fast fraction mapping in sodium MRI.

PURPOSE: Parameter mapping in sodium MRI data is challenging due to inherently low SNR and spatial resolution, prompting the need to employ robust models and estimation techniques. This work aims to develop a continuum model of sodium T2* -decay to overcome the limitations of the commonly employed bi-exponential models. Estimates of mean T2* -decay and fast component fraction in tissue are emergent from the inferred continuum model. METHODS: A closed-form continuum model was derived assuming a gamma distribution of T2* components. Sodium MRI was performed on four healthy human subjects and a phantom consisting of closely packed vials filled with an aqueous solution of varying sodium and agarose concentrations. The continuum model was applied to the phantom and in vivo human multi-echo 7T data. Parameter maps by voxelwise model-fitting were obtained. RESULTS: The continuum model demonstrated comparable estimation performance to the bi-exponential model. The parameter maps provided improved contrast between tissue structures. The fast component fraction, an indicator of the heterogeneity of localised sodium motion regimes in tissue, was zero in CSF and high in WM structures. CONCLUSIONS: The continuum distribution model provides high quality, high contrast parameter maps, and informative voxelwise estimates of the relative weighting between fast and slow decay components.

3D-multi-echo radial imaging of 23 Na (3D-MERINA) for time-efficient multi-parameter tissue compartment mapping.

PURPOSE: This work demonstrates a 3D radial multi-echo acquisition scheme for time-efficient sodium (23 Na) MR-signal acquisition and analysis. Echo reconstructions were used to produce signal-to-noise ratio (SNR)-enhanced 23 Na-images and parameter maps of the biexponential observed transverse relaxation time ( T2*) decay. METHODS: A custom-built sequence for radial multi-echo acquisition was proposed for acquisition of a series of 3D volumetric 23 Na-images. Measurements acquired in a phantom and in vivo human brains were analyzed for SNR enhancement and multi-component T2* estimation. RESULTS: Rapid gradient refocused imaging acquired 38 echoes within a repetition time of 160 ms. Signal averaging of multi-echo time (TE) measurements showed an average brain tissue SNR enhancement of 34% compared to single-TE images across subjects. Phantom and in vivo measurements detected distinguishable signal decay characteristics for fluid and solid media. Mapping results were investigated in phantom and in vivo experiments for sequence timing optimization and signal decay analysis. The T2* mapping results were consistent with previously reported values and facilitated fluid-signal discrimination. CONCLUSION: The proposed method offers an efficient 23 Na-imaging scheme that extends existing 23 Na-MRI sequences by acquiring signal decay information with no increase in time or specific absorption rate. The resultant SNR-enhanced 23 Na-images and estimated T2* signal decay characteristics offer great potential for detailed investigation of tissue compartment characterization and clinical application. Magn Reson Med 79:1950-1961, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Three-dimensional dictionary-learning reconstruction of (23)Na MRI data.

PURPOSE: To reduce noise and artifacts in (23)Na MRI with a Compressed Sensing reconstruction and a learned dictionary as sparsifying transform. METHODS: A three-dimensional dictionary-learning compressed sensing reconstruction algorithm (3D-DLCS) for the reconstruction of undersampled 3D radial (23)Na data is presented. The dictionary used as the sparsifying transform is learned with a K-singular-value-decomposition (K-SVD) algorithm. The reconstruction parameters are optimized on simulated data, and the quality of the reconstructions is assessed with peak signal-to-noise ratio (PSNR) and structural similarity (SSIM). The performance of the algorithm is evaluated in phantom and in vivo (23)Na MRI data of seven volunteers and compared with nonuniform fast Fourier transform (NUFFT) and other Compressed Sensing reconstructions. RESULTS: The reconstructions of simulated data have maximal PSNR and SSIM for an undersampling factor (USF) of 10 with numbers of averages equal to the USF. For 10-fold undersampling, the PSNR is increased by 5.1 dB compared with the NUFFT reconstruction, and the SSIM by 24%. These results are confirmed by phantom and in vivo (23)Na measurements in the volunteers that show markedly reduced noise and undersampling artifacts in the case of 3D-DLCS reconstructions. CONCLUSION: The 3D-DLCS algorithm enables precise reconstruction of undersampled (23)Na MRI data with markedly reduced noise and artifact levels compared with NUFFT reconstruction. Small structures are well preserved.

30 Years of sodium/X-nuclei magnetic resonance imaging.

In principle, all nuclei with nonzero spin can be employed for magnetic resonance imaging (MRI). Special scanner hardware and MR sequences are required to select the nucleus-specific frequency and to enable imaging with "sufficient" signal-to-noise ratio. This Special Issue starts with an overview of different nuclei that can be used for MRI today, followed by a review article about techniques required for imaging of quadrupolar nuclei with short relaxation times. Sequence developments to improve image quality and applications on different organs and diseases are presented for different nuclei ((23)Na, (35)Cl, (17)O, and (19)F), with a focus on imaging at natural abundance.

Optic nerve: separating compartments based on 23Na TQF spectra and TQF-diffusion anisotropy.

We present a triple quantum filtered (TQF) sodium spectroscopy study of an excised bovine optic nerve. By choosing proper experimental parameters, this technique allowed us to independently observe the satellite transitions originating from the various compartments in the tissue. TQF-based diffusion experiments provided further characterization of the compartments in terms of their geometry. As a result, the peak that exhibited the smallest residual quadrupolar splitting, and the largest diffusion anisotropy was assigned to axons. Two other pairs of satellite peaks were assigned to extra-cellular compartments on the basis of either the size of their quadrupolar splitting or the diffusion properties.

Quantitative in vivo 23Na MR imaging of the healthy human kidney: determination of physiological ranges at 3.0T with comparison to DWI and BOLD.

OBJECTIVES: The purpose of this prospective study was to assess the normal physiologic ranges of the renal corticomedullary 23Na-concentration ([23Na]) gradient at 3.0T in healthy volunteers. The corticomedullary [23Na] gradient was correlated with other functional MR imaging parameters--blood oxygenation level dependent (BOLD) and diffusion-weighted imaging (DWI)--and to individual and physiologic parameters--age, gender, estimated glomerular filtration rate (eGFR), body mass index (BMI), and blood serum sodium concentration ([23Na]serum). METHODS AND MATERIALS: 50 healthy volunteers (30 m, 20 w; mean age: 29.2 years) were included in this IRB-approved study, without a specific a priori preparation in regard to water or food intake. For 23Na-imaging a 3D density adapted, radial gradient echo (GRE)-sequence (spatial resolution=5×5×5 mm3) was used in combination with a dedicated 23Na-coil and 23Na-reference phantoms. [23Na] values of the corticomedullary [23Na] gradient were measured by placement of a linear region of interest (20×1 mm2) from the renal cortex in the direction of the renal medulla. By using external standard reference phantoms, [23Na] was calculated in mmol/L of wet tissue volume (mmol/l WTV). Axial diffusion-weighted images (spatial resolution=1.7×1.7×5.0 mm3) and 2D GRE BOLD images (spatial resolution=1.2×1.2×4.0 mm3) were acquired. Mean values±standard deviations for [23Na], apparent diffusion coefficient (ADC) values, and R2* values were computed for each volunteer. The corticomedullary 23Na-concentration gradient (in mmol/l/mm) was calculated along the area of linear concentration increase from the cortex in the direction of the medulla. Correlations between the [23Na] and DWI, BOLD, and the physiologic parameters were assessed with Pearson correlation coefficients. RESULTS: The mean corticomedullary [23Na] for all healthy volunteers increased from the renal cortex (58±17 mmol/l WTV) in the direction of the medulla (99±18 mmol/l WTV). The inter-individual differences ranged from respective cortical and medullary values of 27 and 63 mmol/L WTV to 126 and 187 mmol/L WTV. No statistically significant differences in renal [23Na] were found based on differences in individual or physiologic parameters (age, gender, [23Na]serum, BMI, GFR). No ADC or R2* gradients were identified, and [23Na] did not correlate with these parameters. CONCLUSION: Renal corticomedullary [23Na] values increase from the cortex in the direction of the medullary pyramid, demonstrating wide inter-individual ranges and no significant correlations with age, gender, [23Na]serum, BMI, GFR, ADC, or R2* values. For future clinical evaluations, an approach relying on renal stimulation (e.g. pharmacologically induced diuresis) may be applicable to account for wide inter-individual ranges of normal [23Na].

Quantitative model of NMR chemical shifts of 23Na+ induced by TmDOTP: applications in studies of Na+ transport in human erythrocytes.

The change in the NMR chemical shift of (23)Na(+) induced by the shift reagent TmDOTP was examined under various experimental conditions typical of cells, including changed Na(+), K(+), PO(4)(3-), and Ca(2+) concentrations, pH and temperature. A mathematical model was developed relating these factors to the observed chemical shift change relative to a capillary-sphere reference. This enabled cation concentrations to be deduced quantitatively from experimental chemical shifts, including those observed during biological time courses with cell suspensions containing TmDOTP DOTP, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis (methylenephosphonate) [corrected]. The model was applied to a (23)Na NMR time course in which monensin, a sodium ionophore, was introduced to human erythrocytes, changing the concentration of cations which may bind TmDOTP, and also resulting in cell volume changes. Using the model with experimentally determined conditions, the chemical shift was predicted and closely followed the experimental values over time. In addition to the model, parameter fitting was achieved by calculating the likelihood distribution of parameters, and seeking the maximum likelihood with a Bayesian type of analysis.

Sodium-23 solid-state nuclear magnetic resonance of commercial sodium naproxen and its solvates.

We report on the investigation of sodium coordination environments with solid-state ²³Na nuclear magnetic resonance (NMR) spectroscopy of various hydrates and solvates of sodium naproxen (SN), a commercially available anti-inflammatory drug sold over the counter as Aleve®, among other names. The ²³Na quadrupolar coupling constant is found to change significantly depending on the hydration state, and subtle changes in oxygen coordination environment about the sodium cations were apparent in the NMR spectra. High-resolution double-rotation NMR experiments are also performed on powdered samples to obtain solution-like ²³Na NMR spectra. Our attempts at crystallizing various solvates of SN have led to the characterization of the first crystal structure for the heminonahydrated form. The composition of commercial SN is also investigated and it is shown that Aleve® is composed of approximately 80% monohydrate solvate. Density-functional theory calculations, using the gauge-including projector-augmented-wave formalism, allow for the assignment of ²³Na NMR peaks to specific sodium sites in the reported X-ray crystal structure.

Study of ion translocation by respiratory complex I. A new insight using (23)Na NMR spectroscopy.

The research on complex I has gained recently a new enthusiasm, especially after the resolution of the crystallographic structures of bacterial and mitochondrial complexes. Most attention is now dedicated to the investigation of the energy coupling mechanism(s). The proton has been identified as the coupling ion, although in the case of some bacterial complexes I Na(+) has been proposed to have that role. We have addressed the relation of some complexes I with Na(+) and developed an innovative methodology using (23)Na NMR spectroscopy. This allowed the investigation of Na(+) transport taking the advantage of directly monitoring changes in Na(+) concentration. Methodological aspects concerning the use of (23)Na NMR spectroscopy to measure accurately sodium transport in bacterial membrane vesicles are discussed here. External-vesicle Na(+) concentrations were determined by two different methods: 1) by integration of the resonance frequency peak and 2) using calibration curves of resonance frequency shift dependence on Na(+) concentration. Although the calibration curves are a suitable way to determine Na(+) concentration changes under conditions of fast exchange, it was shown not to be applicable to the bacterial membrane vesicle systems. In this case, the integration of the resonance frequency peak is the most appropriate analysis for the quantification of external-vesicle Na(+) concentration. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012).

23Na double-rotation NMR of sodium nucleotides leads to the discovery of a new dCMP hendecahydrate.

Obtaining definitive information concerning the coordination environment of sodium ions which balance the negative charges found in nucleotides is a challenging task. We show that high resolution 1D and 2D (23)Na NMR spectra of sodium nucleotides obtained in the solid state with the use of double-rotation (DOR) provide valuable structural information. Sensitive spin diffusion homonuclear correlation experiments are used to establish the relative proximities of various pairs of crystallographically distinct Na sites and to assign the spectral resonances. Additionally, the DOR sidebands are simulated to obtain coordination information which is complementary to that obtained using multiple-quantum magic-angle spinning NMR spectra. These experiments led us to discover a new hendecahydrate of deoxycytidine monophosphate (dCMP), the structure of which is confirmed via single-crystal X-ray diffraction. This hydrate crystallizes reproducibly when deuterated water is used exclusively in the preparation process.

Semi-quantitative and simulation analyses of effects of γ rays on determination of calibration factors of PET scanners with point-like (22)Na sources.

The uncertainty of radioactivity concentrations measured with positron emission tomography (PET) scanners ultimately depends on the uncertainty of the calibration factors. A new practical calibration scheme using point-like (22)Na radioactive sources has been developed. The purpose of this study is to theoretically investigate the effects of the associated 1.275 MeV γ rays on the calibration factors. The physical processes affecting the coincidence data were categorized in order to derive approximate semi-quantitative formulae. Assuming the design parameters of some typical commercial PET scanners, the effects of the γ rays as relative deviations in the calibration factors were evaluated by semi-quantitative formulae and a Monte Carlo simulation. The relative deviations in the calibration factors were less than 4%, depending on the details of the PET scanners. The event losses due to rejecting multiple coincidence events of scattered γ rays had the strongest effect. The results from the semi-quantitative formulae and the Monte Carlo simulation were consistent and were useful in understanding the underlying mechanisms. The deviations are considered small enough to correct on the basis of precise Monte Carlo simulation. This study thus offers an important theoretical basis for the validity of the calibration method using point-like (22)Na radioactive sources.

Preparation and biodistribution of radiolabeled fullerene C60 nanocrystals.

The present study describes for the first time a procedure for the radiolabeling of fullerene (C(60)) nanocrystals (nanoC(60)) with Na (125)I, as well as the biodistribution of radiolabeled nanoC(60) ((125)I-nanoC(60)). The solvent exchange method with tetrahydrofuran was used to make colloidal water suspensions of radiolabeled nanoC(60) particles. The radiolabeling procedure with the addition of Na (125)I to tetrahydrofuran during dissolution of C(60) gave a higher radiochemical yield of radiolabeled nanoC(60) particles in comparison to the second option, in which Na (125)I was added after C(60) was dissolved. Using photon correlation spectroscopy and transmission electron microscopy, (125)I-nanoC(60) particles were found to have a crystalline structure and a mean diameter of 200-250 nm. The (125)I-nanoC(60) had a particularly high affinity for human serum albumin, displaying 95% binding efficiency after 1 h. Biodistribution studies of (125)I-nanoC(60) in rats indicated significant differences in tissue accumulation of (125)I-nanoC(60) and the radioactive tracer Na (125)I. The higher accumulation of radiolabeled nanoC(60) was observed in liver and spleen, while accumulation in thyroid, stomach, lungs and intestines was significantly lower in comparison to Na (125)I. In addition to being useful for testing the biological distribution of nanoC(60), the described radiolabeling procedure might have possible applications in cancer radiotherapy.

23Na TQF NMR imaging for the study of spinal disc tissue.

A method for acquiring triple quantum filtered (TQF) (23)Na NMR images is proposed that takes advantage of the differences in transverse relaxation rates of sodium to achieve positive intensity, PI, NMR signal. This PITQF imaging sequence has been used to obtain spatially resolved one-dimensional images as a function of the TQF creation time, tau, for two human spinal disc samples. From the images the different parts of the tissue, nucleus pulposus and annulus fibrosus, can be clearly distinguished based on their signal intensity and creation time profiles. These results establish the feasibility of (23)Na TQF imaging and demonstrate that this method should be applicable for studying human disc tissues as well as spinal disc degeneration.

The application of 23Na double-quantum-filter (DQF) NMR spectroscopy for the study of spinal disc degeneration.

Degenerative disc disease is an irreversible process that leads to a loss of mechanical integrity and back pain in millions of people. In this report, (23)Na double-quantum-filtered (DQF) NMR spectroscopy is used to study disc tissues in two stages of degeneration. Initial results indicate that the (23)Na DQF signal may be useful for determining the degree of degeneration. The spectral analysis reveals the presence of sodium environments with different residual quadrupolar couplings and T(2) relaxation times that we attribute to different regions, or compartments, corresponding to different biochemical regions in the tissue. In general it is found that there are compartments with no residual quadrupolar couplings, compartments with moderate couplings (200 to 1000 Hz), and compartments with couplings ranging from 1500 to 3000 Hz. The results indicate that (23)Na DQF NMR spectroscopy provides a probe of the degenerative state of the intervertebral disc tissues, and might hold potential as a novel diagnostic method for detection of disc degeneration.

Structures of alkali metals in silica gel nanopores: new materials for chemical reductions and hydrogen production.

Alkali metals and their alloys can be protected from spontaneous reaction with dry air by intercalation (with subsequent heating) into the pores of silica gel (SG) at loadings up to 40 wt %. The resulting loose, black powders are convenient materials for chemical reduction of organic compounds and the production of clean hydrogen. The problem addressed in this paper is the nature of the reducing species present in these amorphous materials. The atomic pair distribution function (PDF), which considers both Bragg and diffuse scattering components, was used to examine their structures. Liquid Na-K alloys added to silica gel at room temperature (stage 0) or heated to 150 degrees C (stage I) as well as stage I Na-SG, retain the overall pattern of pure silica gel. Broad oscillations in the PDF show that added alkali metals remain in the pores as nanoscale metal clusters. 23Na MAS NMR studies confirm the presence of Na(0) and demonstrate that Na+ ions are formed as well. The relative amounts of Na(0) and Na(+) depend on both the overall metal loading and the average pore size. The results suggest that ionization occurs near or in the SiO2 walls, with neutral metal present in the larger cavities. The fate of the electrons released by ionization is uncertain, but they may add to the silica gel lattice, or form an "electride-like plasma" near the silica gel walls. A remaining mystery is why the stage I material does not show a melting endotherm of the encapsulated metal and does not react with dry oxygen. Na-SG when heated to 400 degrees C (stage II) yields a dual-phase reaction product that consists of Na(4)Si(4) and Na(2)SiO(3).

Dynamics of 23Na during completely balanced steady-state free precession.

The dynamics of 23Na during completely balanced steady-state free precession (SSFP) have been studied in numerical simulations and experiments. Results from both agree well. It is shown that during SSFP multiple quantum coherences are excited and that their excitation affects the observable signal. The signal response to the sequence parameters (flip angle, TR, and RF pulse phase cycle) shows a structure which can not be described by the Bloch equations. Due to excitation of T31 (s,a), the amplitude ratio of the fast and slowly decaying components deviates from 3:2 and is a function of the sequence parameters. The results shown here represent a basis for the implementation and optimization of 23Na-SSFP imaging sequences.