Quantitative Brain Sodium MRI Depicts Corticospinal Impairment in Amyotrophic Lateral Sclerosis.

Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that mainly affects the upper and lower motor neurons. Recent sodium (23Na) MRI studies have shown that abnormal sodium concentration is related to neuronal suffering in neurodegenerative conditions. Purpose To use 23Na MRI to investigate abnormal sodium concentrations and map their distribution in the brains of study participants with ALS as compared with healthy control subjects. Materials and Methods Twenty-seven participants with ALS (mean age, 54 years ± 10 [standard deviation], eight women) and 30 healthy control subjects (mean age, 50 years ± 10; 16 women) were prospectively recruited between September 2015 and October 2017 and were examined by using conventional proton MRI and sodium MRI at 3 T. Voxel-based statistical mapping was used to compare quantitative whole-brain total sodium concentration (TSC) maps in participants with ALS with those in control subjects and to localize regions of abnormal elevated TSC. Potential overlap of abnormal elevated TSC with regions of atrophy as detected with 1H MRI also was investigated. Results Voxel-based statistical mapping analyses revealed higher sodium concentration in motor regions (bilateral precentral gyri, corticospinal tracts, and the corpus callosum) of participants with ALS (two-sample t test, P < .005; age and sex as covariates). In these regions, mean TSC was higher in participants with ALS (mean, 45.6 mmol/L wet tissue ± 3.2) than in control subjects (mean, 41.8 mmol/L wet tissue ± 2.7; P < .001; Cohen d = 1.28). Brain regions showing higher TSC represented a volume of 15.4 cm3 that did not overlap with gray matter atrophy occupying a volume of 16.9 cm3. Elevated TSC correlated moderately with corticospinal conduction failure assessed with transcranial magnetic stimulation in the right upper limb (Spearman ρ = -0.57; 95% confidence interval: -0.78, -0.16; P = .005; n = 23). Conclusion Quantitative 23Na MRI is sensitive to alterations of brain sodium homeostasis within disease-relevant regions in patients with amyotrophic lateral sclerosis (ALS). This supports further investigation of abnormal sodium concentration as a potential marker of neurodegenerative processes in patients with ALS that could be used as a secondary endpoint in clinical trials. © RSNA, 2019 Online supplemental material is available for this article.

Tissue sodium content in patients with type 2 diabetes mellitus.

BACKGROUND: Tissue sodium content by 23Na magnetic resonance imaging (MRI) has been found to be increased in arterial hypertension. We analyzed whether tissue sodium content is increased in patients with type-2 diabetes (T2DM). METHODS: Patients with T2DM were compared to those with primary hypertension. Patients with T2DM were off any antidiabetic and hypertensive patients off any antihypertensive therapy for at least 4 weeks. Skin and muscle sodium content was assessed non-invasively with a 3.0 T clinical MRI system (Magnetom Verio, Siemens Health Care, Erlangen, Germany) in each patient. RESULTS: In patients with T2DM (N = 59) we observed significantly greater muscle sodium content (diabetes: 20.6 ±â€¯3.5 vs hypertension: 16.3 ±â€¯2.5 mmol/l, p < 0.001) and skin sodium content (diabetes: 24.5 ±â€¯7.2 vs hypertension: 20.6 ±â€¯5.7 mmol/l, p = 0.01) than in those with primary hypertension (N = 33). When potential confounders (age, body mass index, gender, systolic and diastolic blood pressure, estimated glomerular filtration rate) were entered in a covariance analysis, both skin sodium content (p = 0.037) and muscle sodium content (p < 0.001) were still clearly elevated. CONCLUSION: Patients with T2DM have greater skin and muscle sodium content. These are the first known data to demonstrate increased tissue sodium content in patients with T2DM, measured by 23Na magnetic resonance imaging. Since tissue sodium content is related to organ damage, therapeutic intervention should aim at reducing tissue sodium content.

(39) K and (23) Na relaxation times and MRI of rat head at 21.1 T.

At ultrahigh magnetic field strengths (B0 ≥ 7.0 T), potassium ((39) K) MRI might evolve into an interesting tool for biomedical research. However, (39) K MRI is still challenging because of the low NMR sensitivity and short relaxation times. In this work, we demonstrated the feasibility of (39) K MRI at 21.1 T, determined in vivo relaxation times of the rat head at 21.1 T, and compared (39) K and sodium ((23) Na) relaxation times of model solutions containing different agarose gel concentrations at 7.0 and 21.1 T. (39) K relaxation times were markedly shorter than those of (23) Na. Compared with the lower field strength, (39) K relaxation times were up to 1.9- (T1 ), 1.4- (T2S ) and 1.9-fold (T2L ) longer at 21.1 T. The increase in the (23) Na relaxation times was less pronounced (up to 1.2-fold). Mono-exponential fits of the (39) K longitudinal relaxation time at 21.1 T revealed T1 = 14.2 ± 0.1 ms for the healthy rat head. The (39) K transverse relaxation times were 1.8 ± 0.2 ms and 14.3 ± 0.3 ms for the short (T2S ) and long (T2L ) components, respectively. (23) Na relaxation times were markedly longer (T1 = 41.6 ± 0.4 ms; T2S = 4.9 ± 0.2 ms; T2L = 33.2 ± 0.2 ms). (39) K MRI of the healthy rat head could be performed with a nominal spatial resolution of 1 × 1 × 1 mm(3) within an acquisition time of 75 min. The increase in the relaxation times with magnetic field strength is beneficial for (23) Na and (39) K MRI at ultrahigh magnetic field strength. Our results demonstrate that (39) K MRI at 21.1 T enables acceptable image quality for preclinical research. Copyright © 2016 John Wiley & Sons, Ltd.

[Functional MRI 2.0. ²³Na and CEST imaging]. / Funktionelle MRT 2.0. ²³Na- und CEST-Bildgebung.

In recent years the purely morphological magnetic resonance imaging (MRI) has been increasingly flanked by so-called functional imaging methods, such as diffusion-weighted imaging (DWI), to obtain additional information about tissue or pathological processes. This review article presents two MR techniques that can detect physiological processes in the human body. In contrast to all other functional MR imaging techniques, which are based on hydrogen protons, the first technique presented (X-nuclei imaging) uses the spin of other nuclei for imaging and consequently allows a completely different insight into the human body. In this article X-nuclei imaging is focused on sodium ((23)Na) MRI because it currently represents the main focus of research in this field due to the favorable MR properties of sodium. The second MR technique presented is the relatively novel chemical exchange saturation transfer (CEST) imaging that can detect exchange processes between protons in metabolites and protons in free water. The first part of this article introduces the basic technical principles, problems, advantages and disadvantages of these two MR techniques, whereas the second part highlights the potential clinical applications. Examples illustrate several potential applications in neuroimaging (e. g. stroke and tumors), musculoskeletal imaging (e. g. osteoarthritis and degenerative processes) and abdominal imaging (e. g. kidneys and hypertension). Both techniques inherently contain an incredible potential for future imaging but are still on the threshold of clinical use and are currently under evaluation in many university centers.

A flexible nested sodium and proton coil array with wideband matching for knee cartilage MRI at 3T.

PURPOSE: We describe a 2 × 6 channel sodium/proton array for knee MRI at 3T. Multielement coil arrays are desirable because of well-known signal-to-noise ratio advantages over volume and single-element coils. However, low tissue-coil coupling that is characteristic of coils operating at low frequency can make the potential gains from a phased array difficult to realize. METHODS: The issue of low tissue-coil coupling in the developed six-channel sodium receive array was addressed by implementing 1) a mechanically flexible former to minimize the coil-to-tissue distance and reduce the overall diameter of the array and 2) a wideband matching scheme that counteracts preamplifier noise degradation caused by coil coupling and a high-quality factor. The sodium array was complemented with a nested proton array to enable standard MRI. RESULTS: The wideband matching scheme and tight-fitting mechanical design contributed to >30% central signal-to-noise ratio gain on the sodium module over a mononuclear sodium birdcage coil, and the performance of the proton module was sufficient for clinical imaging. CONCLUSION: We expect the strategies presented in this study to be generally relevant in high-density receive arrays, particularly in x-nuclei or small animal applications. Magn Reson Med 76:1325-1334, 2016. © 2015 Wiley Periodicals, Inc.

Sodium-23 MRI of whole spine at 3 Tesla using a 5-channel receive-only phased-array and a whole-body transmit resonator.

Sodium magnetic resonance imaging ((23)Na MRI) is a unique and non-invasive imaging technique which provides important information on cellular level about the tissue of the human body. Several applications for (23)Na MRI were investigated with regard to the examination of the tissue viability and functionality for example in the brain, the heart or the breast. The (23)Na MRI technique can also be integrated as a potential monitoring instrument after radiotherapy or chemotherapy. The main contribution in this work was the adaptation of (23)Na MRI for spine imaging, which can provide essential information on the integrity of the intervertebral disks with respect to the early detection of disk degeneration. In this work, a transmit-only receive-only dual resonator system was designed and developed to cover the whole human spine using (23)Na MRI and increase the receive sensitivity. The resonator system consisted of an already presented (23)Na whole-body resonator and a newly developed 5-channel receive-only phased-array. The resonator system was first validated using bench top and phantom measurements. A threefold SNR improvement at the depth of the spine (∼7cm) over the whole-body resonator was achieved using the spine array. (23)Na MR measurements of the human spine using the transmit-only receive-only resonator system were performed on a healthy volunteer within an acquisition time of 10minutes. A density adapted 3D radial sequence was chosen with 6mm isotropic resolution, 49ms repetition time and a short echo time of 540µs. Furthermore, it was possible to quantify the tissue sodium concentration in the intervertebral discs in the lumbar region (120ms repetition time) using this setup.

Sodium MRI of the human heart at 7.0 T: preliminary results.

The objective of this work was to examine the feasibility of three-dimensional (3D) and whole heart coverage (23)Na cardiac MRI at 7.0 T including single-cardiac-phase and cinematic (cine) regimes. A four-channel transceiver RF coil array tailored for (23)Na MRI of the heart at 7.0 T (f = 78.5 MHz) is proposed. An integrated bow-tie antenna building block is used for (1)H MR to support shimming, localization and planning in a clinical workflow. Signal absorption rate simulations and assessment of RF power deposition were performed to meet the RF safety requirements. (23) Na cardiac MR was conducted in an in vivo feasibility study. 3D gradient echo (GRE) imaging in conjunction with Cartesian phase encoding (total acquisition time T(AQ) = 6 min 16 s) and whole heart coverage imaging employing a density-adapted 3D radial acquisition technique (T(AQ) = 18 min 20 s) were used. For 3D GRE-based (23)Na MRI, acquisition of standard views of the heart using a nominal in-plane resolution of (5.0 × 5.0) mm(2) and a slice thickness of 15 mm were feasible. For whole heart coverage 3D density-adapted radial (23)Na acquisitions a nominal isotropic spatial resolution of 6 mm was accomplished. This improvement versus 3D conventional GRE acquisitions reduced partial volume effects along the slice direction and enabled retrospective image reconstruction of standard or arbitrary views of the heart. Sodium cine imaging capabilities were achieved with the proposed RF coil configuration in conjunction with 3D radial acquisitions and cardiac gating. Cardiac-gated reconstruction provided an enhancement in blood-myocardium contrast of 20% versus the same data reconstructed without cardiac gating. The proposed transceiver array enables (23)Na MR of the human heart at 7.0 T within clinical acceptable scan times. This capability is in positive alignment with the needs of explorations that are designed to examine the potential of (23)Na MRI for the assessment of cardiovascular and metabolic diseases.

Multinuclear MR and multilevel data processing: an insight into morphologic assessment of in vivo knee articular cartilage.

RATIONALE AND OBJECTIVES: Quantitative assessment of knee articular cartilage (AC) morphology using magnetic resonance (MR) imaging requires an accurate segmentation and 3D reconstruction. However, automatic AC segmentation and 3D reconstruction from hydrogen-based MR images alone is challenging because of inhomogeneous intensities, shape irregularity, and low contrast existing in the cartilage region. Thus, the objective of this research was to provide an insight into morphologic assessment of AC using multilevel data processing of multinuclear ((23)Na and (1)H) MR knee images. MATERIALS AND METHODS: A dual-tuned ((23)Na and (1)H) radio-frequency coil with 1.5-T MR scanner is used to scan four human subjects using two separate MR pulse sequences for the respective sodium and proton imaging of the knee. Postprocessing is performed using customized routines written in MATLAB. MR data were fused to improve contrast of the cartilage region that is further used for automatic segmentation. Marching cubes algorithm is applied on the segmented AC slices for 3D volume rendering and volume is then calculated using the divergence theorem. RESULTS: Fusion of multinuclear MR images results in an improved contrast (factor >3) in the cartilage region. Sensitivity (80.21%) and specificity (99.64%) analysis performed by comparing manually segmented AC shows a good performance of the automated AC segmentation. The average cartilage volume (23.19 ± 1.38 cm(3); coefficient of variation [COV] -0.059) measured from 3D AC models of four data sets shows a marked improvement over average cartilage volume (23.24 cm(3); COV -0.19) reported earlier. CONCLUSIONS: This study confirms the use of multinuclear MR data for cartilage morphology (volume) assessment that can be used in clinical settings.

[Bilateral 23Na MR imaging of the breast and quantification of sodium concentration]. / Bilaterale 23Na-MR-Bildgebung der Mamma und Quantifizierung der Natriumkonzentration.

A novel setup for (23)Na MRI, which allows bilateral imaging of the breast, is presented. For this purpose a figure-eight receive-only (23)Na surface coil was developed. For our experiments on three samples with NaCl solutions of different sodium concentrations and two female subjects we used an asymmetric birdcage coil in transmit mode and the developed surface coil for receiving the signal at 3T. Imaging of the samples showed the applicability of the employed normalization method for measuring the distribution of sodium concentration. In a sample of concentration [Na(+)]=51mM we achieved SNR=70 at a nominal isotropic resolution of 2,5mm (TR=66ms, TE=0,6ms, TA=20min). Furthermore we showed that by means of this setup it is possible to quantify the sodium concentration in breast tissue (TSC) of a female subject with an accuracy of 23% (TR=150ms, TE=0,5ms, TA=45min).

Iterative 3D projection reconstruction of (23) Na data with an (1) H MRI constraint.

PURPOSE: To increase the signal-to-noise ratio (SNR) and to reduce artifacts in non-proton magnetic resonance imaging (MRI) by incorporation of a priori information from (1) H MR data in an iterative reconstruction. METHODS: An iterative reconstruction algorithm for 3D projection reconstruction (3DPR) is presented that combines prior anatomical knowledge and image sparsity under a total variation (TV) constraint. A binary mask (BM) is used as an anatomical constraint to penalize non-zero signal intensities outside the object. The BM&TV method is evaluated in simulations and in MR measurements in volunteers. RESULTS: In simulated BM&TV brain data, the artifact level was reduced by 20% while structures were well preserved compared to gridding. SNR maps showed a spatially dependent SNR gain over gridding reconstruction, which was up to 100% for simulated data. Undersampled 3DPR (23) Na MRI of the human brain revealed an SNR increase of 29 ± 7%. Small anatomical structures were reproduced with a mean contrast loss of 14%, whereas in TV-regularized iterative reconstructions a loss of 66% was found. CONCLUSION: The BM&TV algorithm allows reconstructing images with increased SNR and reduced artifact level compared to gridding and performs superior to an iterative reconstruction using an unspecific TV constraint only.

Sodium quantification in the spinal cord at 3T.

PURPOSE: Sodium channels are involved in neuronal function and therefore methods to assess tissue sodium concentration in vivo are exceptionally appealing. Recently there has been a renewed interest for brain sodium magnetic resonance imaging (MRI), thanks to higher magnetic field strength scanners. However, sodium measures in the spinal cord are lacking due to major technical challenges. Here we propose for the first time a clinically feasible non-invasive method for quantifying sodium in the spine using magnetic resonance spectroscopy. METHODS: Sodium spectra from the cervical cord were collected using image selected in vivo spectroscopy (∼14 min scan time) and quantified using a reference phantom. RESULTS: The sodium magnetic resonance spectroscopy measures provided in vivo concentration estimates of 31.2±2.4 mM. Repeat scans showed good reproducibility with a coefficient of variation of <6%. CONCLUSION: Proposed here for the first time is a fast non-invasive technique to quantify total sodium in the spinal cord in vivo. This newly proposed technique has a great potential for translation into clinic, thanks to its simplicity.

Assessment of the renal corticomedullary (23)Na gradient using isotropic data sets.

RATIONALE AND OBJECTIVES: (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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Simultaneous single-quantum and triple-quantum-filtered MRI of 23Na (SISTINA).

The low MR sensitivity of the sodium nucleus and its low concentration in the human body constrain acquisition time. The use of both single-quantum and triple-quantum sodium imaging is, therefore, restricted. In this work, we present a novel MRI sequence that interleaves an ultra-short echo time radial projection readout into the three-pulse triple-quantum preparation. This allows for simultaneous acquisition of tissue sodium concentration weighted as well as triple-quantum filtered images. Performance of the sequence is shown on phantoms. The method is demonstrated on six healthy informed volunteers and is applied to three cases of brain tumors. A comparison with images from tumor specific O-(2-[18F]fluoroethyl)-L-tyrosine positron emission tomography and standard MR images is presented. The combined information of the triple-quantum-filtered images with single-quantum images may enable a better understanding of tissue viability. Future studies can benefit from the evaluation of both contrasts with shortened acquisition times.

Hyperkalemic periodic paralysis and permanent weakness: 3-T MR imaging depicts intracellular 23Na overload--initial results.

PURPOSE: To assess whether myoplasmic ionic sodium (Na+) is increased in muscles of patients with hyperkalemic periodic paralysis (HyperPP) with 3-T sodium 23 (23Na) magnetic resonance (MR) imaging and to evaluate the effect of medical treatment on sodium-induced muscle edema. MATERIALS AND METHODS: This study received institutional review board approval; written informed consent was obtained. Proton (hydrogen 1 [1H]) and 23Na MR of both calves were performed in 12 patients with HyperPP (mean age, 48 years±14 [standard deviation]) and 12 healthy volunteers (mean age, 38 years±12) before and after provocation (unilateral cooling, one calf). 23Na MR included spin-density, T1-weighted, and inversion-recovery (IR) sequences. Total sodium concentration and normalized signal intensities (SIs) were evaluated within regions of interest (ROIs). Muscle strength was measured with the British Medical Research Council (MRC) grading scale. Five patients underwent follow-up MR after diuretic treatment. RESULTS: During rest, mean myoplasmic Na+ concentration was significantly higher in HyperPP with permanent weakness (40.7 µmol/g±3.9) compared with HyperPP with transient weakness (31.3 µmol/g±4.8) (P=.004). Mean SI in 23Na IR MR was significantly higher in HyperPP with permanent weakness (0.83±0.04; median MRC, grade 4; range, 3-5) compared with HyperPP without permanent weakness (0.67±0.05; median MRC, grade 5; range, 4-5) (P=.002). Provocation reduced muscle strength in HyperPP (before provocation, median MRC, 5; range, 3-5; after provocation, median MRC, 3; range, 1-4) and increased SI in 23Na IR from 0.75±0.09 to 0.86±0.10 (P=.004). Spin-density and T1-weighted sequences were less sensitive, particularly to cold-induced Na+ changes. 23Na IR SI remained unchanged in volunteers (0.53±0.06 before and 0.54±0.06 after provocation, P=.3). Therapy reduced mean SI in 23Na IR sequence from 0.85±0.04 to 0.64±0.11. CONCLUSION: 23Na MR imaging depicts increased myoplasmic Na+ in HyperPP with permanent weakness. Na+ overload may cause muscle degeneration developing with age. 23Na MR imaging may have potential to aid monitoring of medical treatment that reduces this overload.

Presynaptic regulation of quantal size: K+/H+ exchange stimulates vesicular glutamate transport.

The amount of neurotransmitter stored in a single synaptic vesicle can determine the size of the postsynaptic response, but the factors that regulate vesicle filling are poorly understood. A proton electrochemical gradient (Δµ(H+)) generated by the vacuolar H(+)-ATPase drives the accumulation of classical transmitters into synaptic vesicles. The chemical component of Δµ(H+) (ΔpH) has received particular attention for its role in the vesicular transport of cationic transmitters as well as in protein sorting and degradation. Thus, considerable work has addressed the factors that promote ΔpH. However, synaptic vesicle uptake of the principal excitatory transmitter glutamate depends on the electrical component of Δµ(H+) (Δψ). We found that rat brain synaptic vesicles express monovalent cation/H(+) exchange activity that converts ΔpH into Δψ, and that this promotes synaptic vesicle filling with glutamate. Manipulating presynaptic K(+) at a glutamatergic synapse influenced quantal size, indicating that synaptic vesicle K(+)/H(+) exchange regulates glutamate release and synaptic transmission.

Cartilage quality assessment by using glycosaminoglycan chemical exchange saturation transfer and (23)Na MR imaging at 7 T.

PURPOSE: To compare a glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging method, which enables sampling of the water signal as a function of the presaturation offset (z-spectrum) at 13 points in clinically feasible imaging times, with sodium 23 ((23)Na) magnetic resonance (MR) imaging in patients after cartilage repair surgery (matrix-associated autologous chondrocyte transplantation and microfracture therapy). MATERIALS AND METHODS: One female patient (67.3 years), and 11 male patients (median age, 28.8 years; interquartile range [IQR], 24.6-32.3 years) were examined with a 7-T whole-body system, with approval of the local ethics committee after written informed consent was obtained. A modified three-dimensional gradient-echo sequence and a 28-channel knee coil were used for gagCEST imaging. (23)Na imaging was performed with a circularly polarized knee coil by using a modified gradient-echo sequence. Statistical analysis of differences and Spearman correlation were applied. RESULTS: The median of asymmetries in gagCEST z-spectra summed over all offsets from 0 to 1.3 ppm was 7.99% (IQR, 6.33%-8.79%) in native cartilage and 5.13% (IQR, 2.64%-6.34%) in repair tissue. A strong correlation (r = 0.701; 95% confidence interval: 0.21, 0.91) was found between ratios of signal intensity from native cartilage to signal intensity from repair tissue obtained with gagCEST or (23)Na imaging. The median of dimensionless ratios between native cartilage and repair tissue was 1.28 (IQR, 1.20-1.58) for gagCEST and 1.26 (IQR, 1.21-1.48) for (23)Na MR imaging. CONCLUSION: The high correlation between the introduced gagCEST method and (23)Na imaging implies that gagCEST is a potentially useful biomarker for glycosaminoglycans.

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.

Muscle Na+ channelopathies: MRI detects intracellular 23Na accumulation during episodic weakness.

BACKGROUND: Muscle channelopathies such as paramyotonia, hyperkalemic periodic paralysis, and potassium-aggravated myotonia are caused by gain-of-function Na+ channel mutations. METHODS: Methods: Implementation of a three-dimensional radial 23Na magnetic resonance (MR) sequence with ultra-short echo times allowed the authors to quantify changes in the total muscular 23Na signal intensity. By this technique and T2-weighted 1H MRI, the authors studied whether the affected muscles take up Na+ and water during episodes of myotonic stiffness or of cold- or exercise-induced weakness. RESULTS: A 22% increase in the 23Na signal intensity and edema-like changes on T2-weighted 1H MR images were associated with cold-induced weakness in all 10 paramyotonia patients; signal increase and weakness disappeared within 1 day. A 10% increase in 23Na, but no increase in the T2-weighted 1H signal, occurred during cold- or exercise-induced weakness in seven hyperkalemic periodic paralysis patients, and no MR changes were observed in controls or exercise-induced stiffness in six potassium-aggravated myotonia patients. Measurements on native muscle fibers revealed provocation-induced, intracellular Na+ accumulation and membrane depolarization by -41 mV for paramyotonia, by -30 mV for hyperkalemic periodic paralysis, and by -20 mV for potassium-aggravated myotonia. The combined in vivo and in vitro approach showed a close correlation between the increase in 23Na MR signal intensity and the membrane depolarization (r = 0.92). CONCLUSIONS: The increase in the total 23Na signal intensity reflects intracellular changes, the cold-induced Na+ shifts are greatest and osmotically relevant in paramyotonia patients, and even osmotically irrelevant Na+ shifts can be detected by the implemented 23Na MR technique.