Guillaume Madelin

Biomedical applications of sodium MRI in vivo.

In this article we present an up‐to‐date overview of the potential biomedical applications of sodium magnetic resonance imaging (MRI) in vivo. Sodium MRI is a subject of increasing interest in translational imaging research as it can give some direct and quantitative biochemical information on the tissue viability, cell integrity and function, and therefore not only help the diagnosis but also the prognosis of diseases and treatment outcomes. It has already been applied in vivo in most human tissues, such as brain for stroke or tumor detection and therapeutic response, in breast cancer, in articular cartilage, in muscle, and in kidney, and it was shown in some studies that it could provide very useful new information not available through standard proton MRI. However, this technique is still very challenging due to the low detectable sodium signal in biological tissue with MRI and hardware/software limitations of the clinical scanners. The article is divided in three parts: 1) the role of sodium in biological tissues, 2) a short review on sodium magnetic resonance, and 3) a review of some studies on sodium MRI on different organs/diseases to date.J. Magn. Reson. Imaging 2013;38:511–529.

Sodium inversion recovery MRI of the knee joint in vivo at 7T.

The loss of proteoglycans (PG) in the articular cartilage is an early signature of osteoarthritis (OA). The ensuing changes in the fixed charge density in the cartilage can be directly linked to sodium concentration via charge balance. Sodium ions in the knee joint appear in two pools: in the synovial fluids or joint effusion where the ions are in free motion and bound within the cartilage tissue where the Na(+) ions have a restricted motion. The ions in these two compartments have therefore different T₁ and T₂ relaxation times. The purpose of this study is to demonstrate the feasibility of a fluid-suppressed 3D ultrashort TE radial sodium sequence by implementing an inversion recovery (IR) preparation of the magnetization at 7T. This method could allow a more accurate and more sensitive quantification of loss of PG in patients with OA. It is shown that adiabatic pulses offer significantly improved performance in terms of robustness to B₁ and B₀ inhomogeneities when compared to the hard pulse sequence. Power deposition considerations further pose a limit to the RF inversion power, and we demonstrate in simulations and experiments how a practical compromise can be struck between clean suppression of fluid signals and power deposition levels. Two IR sequences with different types of inversion pulses (a rectangular pulse and an adiabatic pulse) were tested on a liquid phantom, ex vivo on a human knee cadaver and then in vivo on five healthy volunteers, with a (Nyquist) resolution of ∼3.6 mm and a signal-to-noise ratio of ∼30 in cartilage without IR and ∼20 with IR. Due to specific absorption rate limitations, the total acquisition time was ∼17 min for the 3D radial sequence without inversion or with the rectangular IR, and 24:30 min for the adiabatic IR sequence. It is shown that the adiabatic IR sequence generates a more uniform fluid suppression over the whole sample than the rectangular IR sequence.

Compressed Sensing Sodium MRI of Cartilage at 7T: Preliminary Study

Sodium MRI has been shown to be highly specific for glycosaminoglycan (GAG) content in articular cartilage, the loss of which is an early sign of osteoarthritis (OA). Quantitative sodium MRI techniques are therefore under development in order to detect and assess early biochemical degradation of cartilage, but due to low sodium NMR sensitivity and its low concentration, sodium images need long acquisition times (15-25 min) even at high magnetic fields and are typically of low resolution. In this preliminary study, we show that compressed sensing can be applied to reduce the acquisition time by a factor of 2 at 7 T without losing sodium quantification accuracy. Alternatively, the nonlinear reconstruction technique can be used to denoise fully-sampled images. We expect to even further reduce this acquisition time by using parallel imaging techniques combined with SNR-improved 3D sequences at 3T and 7 T.

Sodium MRI: Methods and applications

Sodium NMR spectroscopy and MRI have become popular in recent years through the increased availability of high-field MRI scanners, advanced scanner hardware and improved methodology. Sodium MRI is being evaluated for stroke and tumor detection, for breast cancer studies, and for the assessment of osteoarthritis and muscle and kidney functions, to name just a few. In this article, we aim to present an up-to-date review of the theoretical background, the methodology, the challenges, limitations, and current and potential new applications of sodium MRI.

Articular cartilage: evaluation with fluid-suppressed 7.0-T sodium MR imaging in subjects with and subjects without osteoarthritis.

PURPOSE To assess the potential use of sodium magnetic resonance (MR) imaging of cartilage, with and without fluid suppression by using an adiabatic pulse, for classifying subjects with versus subjects without osteoarthritis at 7.0 T. MATERIALS AND METHODS The study was approved by the institutional review board and was compliant with HIPAA. The knee cartilage of 19 asymptomatic (control subjects) and 28 symptomatic (osteoarthritis patients) subjects underwent 7.0-T sodium MR imaging with use of two different sequences: one without fluid suppression (radial three-dimensional sequence) and one with fluid suppression (inversion recovery [IR] wideband uniform rate and smooth truncation [WURST]). Fluid suppression was obtained by using IR with an adiabatic inversion pulse (WURST pulse). Mean sodium concentrations and their standard deviations were measured in the patellar, femorotibial medial, and lateral cartilage regions over four consecutive sections for each subject. The minimum, maximum, median, and average means and standard deviations were calculated over all measurements for each subject. The utility of these measures in the detection of osteoarthritis was evaluated by using logistic regression and the area under the receiver operating characteristic curve (AUC). Bonferroni correction was applied to the P values obtained with logistic regression. RESULTS Measurements from IR WURST were found to be significant predicators of all osteoarthritis (Kellgren-Lawrence score of 1-4) and early osteoarthritis (Kellgren-Lawrence score of 1 or 2). The minimum standard deviation provided the highest AUC (0.83) with the highest accuracy (>78%), sensitivity (>82%), and specificity (>74%) for both all osteoarthritis and early osteoarthritis groups. CONCLUSION Quantitative sodium MR imaging at 7.0 T with fluid suppression by using adiabatic IR is a potential biomarker for osteoarthritis.

A method for estimating intracellular sodium concentration and extracellular volume fraction in brain in vivo using sodium magnetic resonance imaging

In this feasibility study we propose a method based on sodium magnetic resonance imaging (MRI) for estimating simultaneously the intracellular sodium concentration (C1, in mM) and the extracellular volume fraction (α) in grey and white matters (GM, WM) in brain in vivo. Mean C1 over five healthy volunteers was measured ~11 mM in both GM and WM, mean α was measured ~0.22 in GM and ~0.18 in WM, which are in close agreement with standard values for healthy brain tissue (C1 ~ 10–15 mM, α ~ 0.2). Simulation of ‘fluid’ and ‘solid’ inclusions were accurately detected on both the C1 and α 3D maps and in the C1 and α distributions over whole GM and WM. This non-invasive and quantitative method could provide new biochemical information for assessing ion homeostasis and cell integrity in brain and help the diagnosis of early signs of neuropathologies such as multiple sclerosis, Alzheimers disease, brain tumors or stroke.

Reproducibility and repeatability of quantitative sodium magnetic resonance imaging in vivo in articular cartilage at 3 T and 7 T

Osteoarthritis is a degenerative disease of articular cartilage that may be associated with a loss of glycosaminoglycans. Quantitative sodium magnetic resonance imaging is highly specific to glycosaminoglycan content and could be used to assess the biochemical degradation of cartilage in early osteoarthritis. However, the reproducibility and repeatability of this technique are not well documented. The aim of this study is to test the reproducibility and repeatability of sodium quantification in cartilage in vivo using intraday and interday acquisitions at 3 T and 7 T, with a radial 3D sequence, with and without fluid suppression. Fluid suppression was obtained by adiabatic inversion recovery (IR WURST) and is expected to improve the sensitivity of the method to glycosaminoglycan content. The root mean square of coefficients of variation are all in the range of 7.5–13.6%. No significant intermagnet, intersequence, intraday, and interday differences in the coefficients of variation were observed. Sodium quantification using IR WURST gave values closer to those reported in the literature for healthy cartilage (220–310 mM) than radial 3D. In conclusion, IR WURST was more accurate in context of sodium measurement, with a reproducibility and repeatability comparable to other compositional magnetic resonance imaging techniques of cartilage. Magn Reson Med, 2012.

Sodium relaxation times in the knee joint in vivo at 7T

The sodium concentration correlates directly with the concentration of proteoglycans (PG) in cartilage, the loss of which is an early signature of osteoarthritis (OA). As a result, quantitative sodium MRI is a promising technique for assessing the degradation of articular cartilage in patients with OA. Sodium relaxation times can also provide information on the degradation of cartilage: it has already been shown on bovine cartilage that T1 and T2long are longer and T2short shorter when the PG concentration decreases. In this study, sodium T1, T2short∗ and T2long∗ relaxation maps were measured in vivo at 7 T on 8 healthy volunteers and in 4 different regions of the cartilage in the knee joint. The patellar, femoro‐tibial medial, lateral, and femoral condyle cartilage have an average T1 ∼ 20 ms, but different T2short∗ (from 0.5 ms to 1.4 ms) and T2long∗ (from 11.4 ms to 14.8 ms). Statistically significant differences in T1, T2short∗ and T2long∗ were observed between the different regions in cartilage (p ≪ 10− 5). Statistical differences in T1 were also observed between male and female data (p ≪ 10− 5). These relaxation times measurements can further be applied as correction factors for sodium concentration maps in vivo and can also be useful as complementary information to quantitative sodium MRI in the quest for detecting early OA. These measurements were done on low resolution sodium images in order to acquire sufficient quality data for fitting (5 images for T1 and 9 images for T2∗ ) while keeping the total time of acquisition of the data reasonable for the volunteer’s comfort (1 h 15 min). Copyright

Design of a nested eight-channel sodium and four-channel proton coil for 7T knee imaging

The critical design aim for a sodium/proton coil is to maximize sodium sensitivity and transmit field homogeneity while simultaneously providing adequate proton sensitivity and homogeneity. While most dual‐frequency coils use lossy high‐impedance trap circuits or PIN diodes to allow dual‐resonance, we explored a nested‐coil design for sodium/proton knee imaging at 7 T. A stand‐alone eight‐channel sodium receive array was implemented without standard dual‐resonance circuitry to provide improved sodium signal‐to‐noise ratio. A detunable sodium birdcage was added for homogeneous sodium excitation and a four‐channel proton transmit‐receive array was added to provide anatomical reference imaging and B0 shimming capabilities. Both additional modules were implemented with minimal disturbance to the eight‐channel sodium array by managing their respective resonances and geometrical arrangement. In vivo sodium signal‐to‐noise ratio was 1.2–1.7 times greater in the developed eight‐channel array than in a mononuclear sodium birdcage coil, whereas the developed four‐channel proton array provided signal‐to‐noise ratio similar to that of a commercial mononuclear proton birdcage coil. Magn Reson Med, 2013.

Comparison of a 28-channel receive array coil and quadrature volume coil for morphologic imaging and T2 mapping of knee cartilage at 7T

To compare a new birdcage‐transmit, 28‐channel receive array (28‐Ch) coil and a quadrature volume coil for 7T morphologic MRI and T2 mapping of knee cartilage.