Voxel-wise partial volume correction method for accurate estimation of tissue sodium concentration in 23 Na-MRI at 7 T.

Sodium is crucial for the maintenance of cell physiology, and its regulation of the sodium-potassium pump has implications for various neurological conditions. The distribution of sodium concentrations in tissue can be quantitatively evaluated by means of sodium MRI (23 Na-MRI). Despite its usefulness in diagnosing particular disease conditions, tissue sodium concentration (TSC) estimated from 23 Na-MRI can be strongly biased by partial volume effects (PVEs) that are induced by broad point spread functions (PSFs) as well as tissue fraction effects. In this work, we aimed to propose a robust voxel-wise partial volume correction (PVC) method for 23 Na-MRI. The method is based on a linear regression (LR) approach to correct for tissue fraction effects, but it utilizes a 3D kernel combined with a modified least trimmed square (3D-mLTS) method in order to minimize regression-induced inherent smoothing effects. We acquired 23 Na-MRI data with conventional Cartesian sampling at 7 T, and spill-over effects due to the PSF were considered prior to correcting for tissue fraction effects using 3D-mLTS. In the simulation, we found that the TSCs of gray matter (GM) and white matter (WM) were underestimated by 20% and 11% respectively without correcting tissue fraction effects, but the differences between ground truth and PVE-corrected data after the PVC using the 3D-mLTS method were only approximately 0.6% and 0.4% for GM and WM, respectively. The capability of the 3D-mLTS method was further demonstrated with in vivo 23 Na-MRI data, showing significantly lower regression errors (ie root mean squared error) as compared with conventional LR methods (p < 0.001). The results of simulation and in vivo experiments revealed that 3D-mLTS is superior for determining under- or overestimated TSCs while preserving anatomical details. This suggests that the 3D-mLTS method is well suited for the accurate determination of TSC, especially in small focal lesions associated with pathological conditions.

Correlation of quantitative conductivity mapping and total tissue sodium concentration at 3T/4T.

PURPOSE: To investigate the correlation between electrical conductivity and sodium concentration, both measured in vivo, in the human brain. METHODS: Conductivity measurements were performed on samples with different sodium (Na+ ) and agarose concentrations using a dielectric probe, and the correlation between conductivity and Na+ content was evaluated. Subsequently, brain conductivity and total Na+ content maps were measured in 8 healthy subjects using phase-based MREPT and sodium MRI, respectively. After co-registration and spatial normalization to the 1 mm 152 MNI brain atlas, the relationship between conductivity and tissue sodium concentration (TSC) was examined within different brain regions. RESULTS: The conductivities of agarose gels increased linearly with NaCl concentration, while remaining almost independent of agarose content. When measured in healthy subjects, conductivities showed positive correlation with total tissue sodium concentration (R = 0.39, P < 0.005). The same trend was found in gray matter (R = 0.36, P < 0.005) and in white matter (R = 0.28, P < 0.05). CONCLUSION: Tissue conductivity shows a positive correlation with total sodium concentration. Conductivity might serve as a novel technique to visualize the total tissue electrolyte concentration, although refinements in the consideration of e.g., tissue water content, would be necessary to improve the quantitative value.

Atrophy of calf muscles by unloading results in an increase of tissue sodium concentration and fat fraction decrease: a 23Na MRI physiology study.

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

Partial volume correction for in vivo (23)Na-MRI data of the human brain.

The concentration of sodium is a functional cell parameter and absolute quantification can be interesting for diagnostical purposes. The accuracy of sodium magnetic resonance imaging ((23)Na-MRI) is strongly biased by partial volume effects (PVEs). Hence our purpose was to establish a partial volume correction (PVC) method for (23)Na-MRI. The existing geometric transfer matrix (GTM) correction method was transferred from positron emission tomography (PET) to (23)Na-MRI and tested in a phantom study. Different parameters, as well as accuracy of registration and segmentation were evaluated prior to first in vivo measurements. In vivo sodium data-sets of the human brain were obtained at B0=7T with a nominal spatial resolution of (3mm)(3) using a density adapted radial pulse sequence. A volunteer study with four healthy subjects was performed to measure partial volume (PV) corrected tissue sodium concentration (TSC) which was verified by means of an intrinsic correction control. In the phantom study the PVC algorithm yielded a good correction performance and reduced the discrepancy between the measured sodium concentration value and the expected value in the smallest compartments of the phantom by 11% to a mean PVE induced discrepancy of 5.7% after correction. The corrected in vivo data showed a reduction of PVE bias for the investigated compartments for all volunteers, resulting in a mean reduction of discrepancy between two separate CSF compartments from 36% to 7.6%. The absolute TSC for two separate CSF compartments (sulci, lateral ventricles), gray and white brain matter after correction were 129±8mmol/L, 138±4mmol/L, 48±1mmol/L and 43±3mmol/L, respectively. The applied PVC algorithm reduces the PV-bias in quantitative (23)Na-MRI. Accurate, high-resolution anatomical data is required to enable appropriate PVC. The algorithm and segmentation approach is robust and leads to reproducible results.

Recent technical developments and clinical research applications of sodium (23Na) MRI.

Sodium is an essential ion that plays a central role in many physiological processes including the transmembrane electrochemical gradient and the maintenance of the body's homeostasis. Due to the crucial role of sodium in the human body, the sodium nucleus is a promising candidate for non-invasively assessing (patho-)physiological changes. Almost 10 years ago, Madelin et al. provided a comprehensive review of methods and applications of sodium (23Na) MRI (Madelin et al., 2014) [1]. More recent review articles have focused mainly on specific applications of 23Na MRI. For example, several articles covered 23Na MRI applications for diseases such as osteoarthritis (Zbyn et al., 2016, Zaric et al., 2020) [2,3], multiple sclerosis (Petracca et al., 2016, Huhn et al., 2019) [4,5] and brain tumors (Schepkin, 2016) [6], or for imaging certain organs such as the kidneys (Zollner et al., 2016) [7], the brain (Shah et al., 2016, Thulborn et al., 2018) [8,9], and the heart (Bottomley, 2016) [10]. Other articles have reviewed technical developments such as radiofrequency (RF) coils for 23Na MRI (Wiggins et al., 2016, Bangerter et al., 2016) [11,12], pulse sequences (Konstandin et al., 2014) [13], image reconstruction methods (Chen et al., 2021) [14], and interleaved/simultaneous imaging techniques (Lopez Kolkovsky et al., 2022) [15]. In addition, 23Na MRI topics have been covered in review articles with broader topics such as multinuclear MRI or ultra-high-field MRI (Niesporek et al., 2019, Hu et al., 2019, Ladd et al., 2018) [16-18]. During the past decade, various research groups have continued working on technical improvements to sodium MRI and have investigated its potential to serve as a diagnostic and prognostic tool. Clinical research applications of 23Na MRI have covered a broad spectrum of diseases, mainly focusing on the brain, cartilage, and skeletal muscle (see Fig. 1). In this article, we aim to provide a comprehensive summary of methodological and hardware developments, as well as a review of various clinical research applications of sodium (23Na) MRI in the last decade (i.e., published from the beginning of 2013 to the end of 2022).

Imaging of Sodium MRI for Therapy Evaluation of Brain Metastase with Cyberknife at 7T: A Case Report.

Herein we describe the case of an elderly patient who presented with a recent history of impaired vision of the right eye around three months due to brain lesions. He was diagnosed with liver cancer and underwent surgery three months prior. The pathological result is hepatocellular carcinoma. Magnetic resonance imaging (MRI) revealed the diagnosis of brain to be metastatic. The patient selected CyberKnife (Accuray Incorporated, Sunnyvale, USA) radiosurgery for the brain lesion since his physical conditions are not suitable for craniotomy. We adapt the imaging of sodium MRI and proton diffusion mapping at 7T MR system to evaluate the efficacy following CyberKnife early stage treatment. To date, we find the tissue sodium concentration (TSC) changes with the time whereas the proton MRI has no significant change within one month. The time course of sodium concentration in the tumor showed a dramatic increase in the treated brain tumor compared to the pretreatment sodium concentration and 48 hours after stereotactic radiosurgery (SRS), which is correlated to the period of the radiotherapy-induced cellular necrosis. This case demonstrates the possibility of sodium MRI as a biomarker for monitoring early radiotherapy for assessing tumor cellularity.