3T sodium MR imaging in Alzheimer's disease shows stage-dependent sodium increase influenced by age and local brain volume.

INTRODUCTION: Application of MRI in clinical routine mainly addresses structural alterations. However, pathological changes at a cellular level are expected to precede the occurrence of brain atrophy clusters and of clinical symptoms. In this context, 23Na-MRI examines sodium changes in the brain as a potential metabolic parameter. Recently, we have shown that 23Na-MRI at ultra-high-field (7 T) was able to detect increased tissue sodium concentration (TSC) in Alzheimer's disease (AD). In this work, we aimed at assessing AD-pathology with 23Na-MRI in a larger cohort and on a clinical 3T MR scanner. METHODS: We used a multimodal MRI protocol on 52 prodromal to mild AD patients and 34 cognitively healthy control subjects on a clinical 3T MR scanner. We examined the TSC, brain volume, and cortical thickness in association with clinical parameters. We further compared TSC with intra-individual normalized TSC for the reduction of inter-individual TSC variability resulting from physiological as well as experimental conditions. Normalized TSC maps were created by normalizing each voxel to the mean TSC inside the brain stem. RESULTS: We found increased normalized TSC in the AD cohort compared to elderly control subjects both on global as well as on a region-of-interest-based level. We further confirmed a significant association of local brain volume as well as age with TSC. TSC increase in the left temporal lobe was further associated with the cognitive state, evaluated via the Montreal cognitive assessment (MoCA) screening test. An increase of normalized TSC depending on disease stage reflected by the Clinical Dementia Rating (CDR) was found in our AD patients in temporal lobe regions. In comparison to classical brain volume and cortical thickness assessments, normalized TSC had a higher discriminative power between controls and prodromal AD patients in several regions of the temporal lobe. DISCUSSION: We confirm the feasibility of 23Na-MRI at 3T and report an increase of TSC in AD in several regions of the brain, particularly in brain regions of the temporal lobe. Furthermore, to reduce inter-subject variability caused by physiological factors such as circadian rhythms and experimental conditions, we introduced normalized TSC maps. This showed a higher discriminative potential between different clinical groups in comparison to the classical TSC analysis. In conclusion, 23Na-MRI represents a potential translational imaging marker applicable e.g.for diagnostics and the assessment of intervention outcomes in AD even under clinically available field strengths such as 3T. Implication of 23Na-MRI in association with other metabolic imaging marker needs to be further elucidated.

Magnetic field strength dependent SNR gain at the center of a spherical phantom and up to 11.7T.

PURPOSE: The SNR at the center of a spherical phantom of known electrical properties was measured in quasi-identical experimental conditions as a function of magnetic field strength between 3 T and 11.7 T. METHODS: The SNR was measured at the center of a spherical water saline phantom with a gradient-recalled echo sequence. Measurements were performed at NeuroSpin at 3, 7, and 11.7 T. The phantom was then shipped to Maastricht University and then to the University of Minnesota for additional data points at 7, 9.4, and 10.5 T. Experiments were carried out with the exact same type of birdcage volume coil (except at 3 T, where a similar coil was used) to attempt at isolating the evolution of SNR with field strength alone. Phantom electrical properties were characterized over the corresponding frequency range. RESULTS: Electrical properties were found to barely vary over the frequency range. Removing the influence of the flip-angle excitation inhomogeneity was crucial, as expected. After such correction, measurements revealed a gain of SNR growing as B0 1.94 ± 0.16 compared with B0 2.13 according to ultimate intrinsic SNR theory. CONCLUSIONS: By using quasi-identical experimental setups (RF volume coil, phantom, electrical properties, and protocol), this work reports experimental data between 3 T and 11.7 T, enabling the comparison with SNR theories in which conductivity and permittivity can be assumed to be constant with respect to field strength. According to ultimate SNR theory, these results can be reasonably extrapolated to the performance of receive arrays with greater than about 32 elements for central SNR in the same spherical phantom.

What can 7T sodium MRI tell us about cellular energy depletion and neurotransmission in Alzheimer's disease?

The pathophysiological processes underlying the development and progression of Alzheimer's disease (AD) on the neuronal level are still unclear. Previous research has hinted at metabolic energy deficits and altered sodium homeostasis with impaired neuronal function as a potential metabolic marker relevant for neurotransmission in AD. Using sodium (23 Na) magnetic resonance (MR) imaging on an ultra-high-field 7 Tesla MR scanner, we found increased cerebral tissue sodium concentration (TSC) in 17 biomarker-defined AD patients compared to 22 age-matched control subjects in vivo. TSC was highly discriminative between controls and early AD stages and was predictive for cognitive state, and associated with regional tau load assessed with flortaucipir-positron emission tomography as a possible mediator of TSC-associated neurodegeneration. TSC could therefore serve as a non-invasive, stage-dependent, metabolic imaging marker. Setting a focus on cellular metabolism and potentially disturbed interneuronal communication due to energy-dependent altered cell homeostasis could hamper progressive cognitive decline by targeting these processes in future interventions.

Feasibility and characterization of a safe susceptibility-matched endorectal coil for MR spectroscopy.

When using endorectal coils, local radiofrequency (RF) heating may occur in the surrounding tissue. Furthermore, most endorectal coils create a susceptibility artifact detrimental to both anatomical magnetic resonance imaging (MRI) and spectroscopy (MRS) acquisitions. We aimed at assessing the safety and MRS performance of a susceptibility-matched endorectal coil for further rectal wall analysis. Experiments were performed on a General Electric MR750 3 T scanner. A variable number of miniaturized passive RF traps were incorporated in the reception cable. The assessment of RF heating and coil sensitivity was conducted on a 1.5% agar-agar phantom doped with NaCl. Several susceptibility-matched materials such as Ultem, perfluorocarbon and barium sulfate were then compared with an external coil. Finally, Ultem was used as a solid support for an endorectal coil and compared with a reference coil. Phantom experiments exhibited a complete suppression of both the RF heating phenomenon and the coil sensitivity artifact. Ultem was the material that produced the smallest image distortion. The full width at half maximum of MR spectra acquired using the susceptibility-matched endorectal coil showed at least 30% narrowing compared with a reference endorectal coil. A susceptibility-matched endorectal coil with RF traps incorporated was validated on phantoms. This coil appears to be a promising device for future in vivo experiments.

Accumulation of Lithium in the Hippocampus of Patients With Bipolar Disorder: A Lithium-7 Magnetic Resonance Imaging Study at 7 Tesla.

BACKGROUND: Lithium (Li) is a first-line treatment for bipolar disorder (BD). To study its cerebral distribution and association with plasma concentrations, we used 7Li magnetic resonance imaging at 7T in euthymic patients with BD treated with Li carbonate for at least 2 years. METHODS: Three-dimensional 7Li magnetic resonance imaging scans (N = 21) were acquired with an ultra-short echo-time sequence using a non-Cartesian k-space sampling scheme. Lithium concentrations ([Li]) were estimated using a phantom replacement approach accounting for differential T1 and T2 relaxation effects. In addition to the determination of mean regional [Li] from 7 broad anatomical areas, voxel- and parcellation-based group analyses were conducted for the first time for 7Li magnetic resonance imaging. RESULTS: Using unprecedented spatial sensitivity and specificity, we were able to confirm the heterogeneity of the brain Li distribution and its interindividual variability, as well as the strong correlation between plasma and average brain [Li] ([Li]B ≈ 0.40 × [Li]P, R = .74). Remarkably, our statistical analysis led to the identification of a well-defined and significant cluster corresponding closely to the left hippocampus for which high Li content was displayed consistently across our cohort. CONCLUSIONS: This observation could be of interest considering 1) the major role of the hippocampus in emotion processing and regulation, 2) the consistent atrophy of the hippocampus in untreated patients with BD, and 3) the normalization effect of Li on gray matter volumes. This study paves the way for the elucidation of the relationship between Li cerebral distribution and its therapeutic response, notably in newly diagnosed patients with BD.

Tissue sodium concentration and sodium T1 mapping of the human brain at 3 T using a Variable Flip Angle method.

PURPOSE: The state-of-the-art method to quantify sodium concentrations in vivo consists in a fully relaxed 3D spin-density (SD) weighted acquisition. Nevertheless, most sodium MRI clinical studies use short-TR SD acquisitions to reduce acquisition durations. We present a clinically viable implementation of the Variable Flip Angle (VFA) method for robust and clinically viable quantification of total sodium concentration (TSC) and longitudinal relaxation rates in vivo in human brain at 3 T. METHODS: Two non-Cartesian steady-state spoiled ultrashort echo time (UTE) scans, performed at optimized flip angles, repetition time and pulse length determined under specific absorption rate constraints, are used to simultaneously compute T1 and total sodium concentration (TSC) maps using the VFA method. Images are reconstructed using the non-uniform Fast Fourier Transform algorithm and TSC maps are corrected for possible inhomogeneity of coil transmission and reception profiles. Fractioned acquisitions are used to correct for potential patient motion. TSC quantifications obtained using the VFA method are validated at first in comparison with a fully-relaxed SD acquisition in a calibration phantom. The robustness of similar VFA acquisitions are compared to the short-TR SD approach in vivo on seven healthy volunteers. RESULTS: The VFA method resulted in consistent TSC and T1 estimates across our cohort of healthy subjects, with mean TSC of 38.1 ±â€¯5.0 mmol/L and T1 of 39.2 ±â€¯4.4 ms. These results are in agreement with previously reported values in literature TSC estimations and with the predictions of a 2-compartment model. However, the short-TR SD acquisition systematically underestimated the sodium concentration with a mean TSC of 31 ±â€¯4.5 mmol/L. CONCLUSION: The VFA method can be applied successfully to image sodium at 3 T in about 20 min and provides robust and intrinsically T1-corrected TSC maps.

Simultaneous multi-parametric mapping of total sodium concentration, T1, T2 and ADC at 7 T using a multi-contrast unbalanced SSFP.

PURPOSE: Quantifying multiple NMR properties of sodium could be of benefit to assess changes in cellular viability in biological tissues. A proof of concept of Quantitative Imaging using Configuration States (QuICS) based on a SSFP sequence with multiple contrasts was implemented to extract simultaneously 3D maps of applied flip angle (FA), total sodium concentration, T1, T2, and Apparent Diffusion Coefficient (ADC). METHODS: A 3D Cartesian Gradient Recalled Echo (GRE) sequence was used to acquire 11 non-balanced SSFP contrasts at a 6 × 6 × 6 mm3 isotropic resolution with carefully-chosen gradient spoiling area, RF amplitude and phase cycling, with TR/TE = 20/3.2 ms and 25 averages, leading to a total acquisition time of 1 h 18 min. A least-squares fit between the measured and the analytical complex signals was performed to extract quantitative maps from a mono-exponential model. Multiple sodium phantoms with different compositions were studied to validate the ability of the method to measure sodium NMR properties in various conditions. RESULTS: Flip angle maps were retrieved. Relaxation times, ADC and sodium concentrations were estimated with controlled precision below 15%, and were in accordance with measurements from established methods and literature. CONCLUSION: The results illustrate the ability to retrieve sodium NMR properties maps, which is a first step toward the estimation of FA, T1, T2, concentration and ADC of 23Na for clinical research. With further optimization of the acquired QuICS contrasts, scan time could be reduced to be suitable with in vivo applications.