Influence of Residual Quadrupolar Interaction on Quantitative Sodium Brain Magnetic Resonance Imaging of Patients With Multiple Sclerosis.

OBJECTIVES: The purpose of this work was to evaluate the influence of residual quadrupolar interaction on the determination of human brain apparent tissue sodium concentrations (aTSCs) using quantitative sodium magnetic resonance imaging ( 23 Na MRI) in healthy controls (HCs) and patients with multiple sclerosis (MS). Especially, it was investigated if the more detailed examination of residual quadrupolar interaction effects enables further analysis of the observed 23 Na MRI signal increase in MS patients. MATERIALS AND METHODS: 23 Na MRI with a 7 T MR system was performed on 21 HC and 50 MS patients covering all MS subtypes (25 patients with relapsing-remitting MS, 14 patients with secondary progressive MS, and 11 patients with primary progressive MS) using 2 different 23 Na pulse sequences for quantification: a commonly used standard sequence (aTSC Std ) as well as a sequence with shorter excitation pulse length and lower flip angle for minimizing signal loss resulting from residual quadrupolar interactions (aTSC SP ). Apparent tissue sodium concentration was determined using the same postprocessing pipeline including correction of the receive profile of the radiofrequency coil, partial volume correction, and relaxation correction. Spin dynamic simulations of spin-3/2 nuclei were performed to aid in the understanding of the measurement results and to get deeper insight in the underlying mechanisms. RESULTS: In normal-appearing white matter (NAWM) of HC and all MS subtypes, the aTSC SP values were approximately 20% higher than the aTSC Std values ( P < 0.001). In addition, the ratio aTSC SP /aTSC Std was significantly higher in NAWM than in normal-appearing gray matter (NAGM) for all subject cohorts ( P < 0.002). In NAWM, aTSC Std values were significantly higher in primary progressive MS compared with HC ( P = 0.01) as well as relapsing-remitting MS ( P = 0.03). However, in contrast, no significant differences between the subject cohorts were found for aTSC SP . Spin simulations assuming the occurrence of residual quadrupolar interaction in NAWM were in good accordance with the measurement results, in particular, the ratio aTSC SP /aTSC Std in NAWM and NAGM. CONCLUSIONS: Our results showed that residual quadrupolar interactions in white matter regions of the human brain have an influence on aTSC quantification and therefore must be considered, especially in pathologies with expected microstructural changes such as loss of myelin in MS. Furthermore, the more detailed examination of residual quadrupolar interactions may lead to a better understanding of the pathologies themselves.

Influence of image contrasts and reconstruction methods on the classification of multiple sclerosis-like lesions in simulated sodium magnetic resonance imaging.

PURPOSE: To evaluate the classifiability of small multiple sclerosis (MS)-like lesions in simulated sodium (23 Na) MRI for different 23 Na MRI contrasts and reconstruction methods. METHODS: 23 Na MRI and 23 Na inversion recovery (IR) MRI of a phantom and simulated brain with and without lesions of different volumes (V = 1.3-38.2 nominal voxels) were simulated 100 times by adding Gaussian noise matching the SNR of real 3T measurements. Each simulation was reconstructed with four different reconstruction methods (Gridding without and with Hamming filter, Compressed sensing (CS) reconstruction without and with anatomical 1 H prior information). Based on the mean signals within the lesion volumes of simulations with and without lesions, receiver operating characteristics (ROC) were determined and the area under the curve (AUC) was calculated to assess the classifiability for each lesion volume. RESULTS: Lesions show higher classifiability in 23 Na MRI than in 23 Na IR MRI. For typical parameters and SNR of a 3T scan, the voxel normed minimal classifiable lesion volume (AUC > 0.9) is 2.8 voxels for 23 Na MRI and 19 voxels for 23 Na IR MRI, respectively. In terms of classifiability, Gridding with Hamming filter and CS without anatomical 1 H prior outperform CS reconstruction with anatomical 1 H prior. CONCLUSION: Reliability of lesion classifiability strongly depends on the lesion volume and the 23 Na MRI contrast. Additional incorporation of 1 H prior information in the CS reconstruction was not beneficial for the classification of small MS-like lesions in 23 Na MRI.

Quantitative 7T sodium magnetic resonance imaging of the human brain using a 32-channel phased-array head coil: Application to patients with secondary progressive multiple sclerosis.

Apparent tissue sodium concentrations (aTSCs) determined by 23 Na brain magnetic resonance imaging (MRI) have the potential to serve as a biomarker in pathologies such as multiple sclerosis (MS). However, the quantification is hindered by the intrinsically low signal-to-noise ratio of 23 Na MRI. The purpose of this study was to improve the accuracy and reliability of quantitative 23 Na brain MRI by implementing a dedicated postprocessing pipeline and to evaluate the applicability of the developed approach for the examination of MS patients. 23 Na brain MRI measurements of 13 healthy volunteers and 17 patients with secondary progressive multiple sclerosis (SPMS) were performed at 7 T using a dual-tuned 23 Na/1 H birdcage coil with a receive-only 32-channel phased array. The aTSC values were determined for normal appearing white matter (NAWM) and normal appearing gray matter (NAGM) in healthy subjects and SPMS patients. Signal intensities were normalized using the mean cerebrospinal fluid (CSF) sodium concentration determined in 37 separate patients receiving a spinal tap for routine diagnostic purposes. Five volunteers underwent MRI examinations three times in a row to assess repeatability. Coefficients of variation (CoVs) were used to quantify the repeatability of the proposed method. aTSC values were compared regarding brain regions and subject cohort using the paired-samples Wilcoxon rank-sum test. Laboratory CSF sodium concentration did not differ significantly between patients without and with MS (p = 0.42). The proposed quantification workflow for 23 Na MRI was highly repeatable with CoVs averaged over all five volunteers of 1.9% ± 0.9% for NAWM and 2.2% ± 1.6% for NAGM. Average NAWM aTSC was significantly higher in patients with SPMS compared with the control group (p = 0.009). Average NAGM aTSC did not differ significantly between healthy volunteers and MS patients (p = 0.98). The proposed postprocessing pipeline shows high repeatability and the results can serve as a baseline for further studies establishing 23 Na brain MRI as a biomarker in diseases such as MS.

Motion-corrected 23 Na MRI of the human brain using interleaved 1 H 3D navigator images.

PURPOSE: To evaluate the feasibility of motion correction for sodium (23 Na) MRI based on interleaved acquired 3D proton (1 H) navigator images. METHODS: A 3D radial density-adapted sequence for interleaved 23 Na/1 H MRI was implemented on a 7 Tesla whole-body MRI system. The 1 H data obtained during the 23 Na acquisition were used to reconstruct 140 navigator image volumes with a nominal spatial resolution of (2.5 mm)3 and a temporal resolution of 6 s. The motion information received from co-registration was then used to correct the 23 Na image dataset, which also had a nominal spatial resolution of (2.5 mm)3 . The approach was evaluated on six healthy volunteers, whose motion during the scans had different intensities and characteristics. RESULTS: Interleaved acquisition of two nuclei did not show any relevant influence on image quality (SNR of 13.0 for interleaved versus 13.2 for standard 23 Na MRI and 176.4 for interleaved versus 178.0 for standard 1 H MRI). The applied motion correction increased the consistency between two consecutive scans for all examined volunteers and improved the image quality for all kinds of motion. The SD of the differences ranged between 2.30% and 6.96% for the uncorrected and between 2.13% and 2.67% for the corrected images. CONCLUSION: The feasibility of interleaved acquired 1 H navigator images to be used for retrospective motion correction of 23 Na images was successfully demonstrated. The approach neither affected the 23 Na image quality nor elongated the scan time and can therefore be an important tool to improve the accuracy of quantitative 23 Na MRI.

Longitudinal Sodium MRI of Multiple Sclerosis Lesions: Is there Added Value of Sodium Inversion Recovery MRI.

BACKGROUND: Sodium enhancement has been demonstrated in multiple sclerosis (MS) lesions. PURPOSE: To investigate sodium MRI with and without an inversion recovery pulse in acute MS lesions in an MS relapse and during recovery. STUDY TYPE: Prospective. SUBJECTS: Twenty-nine relapsing-remitting MS patients with an acute relapse were included. FIELD STRENGTH/SEQUENCE: A 3D density-adapted radial sodium sequence at 3 T using a dual-tuned (23 Na/1 H) head coil. ASSESSMENT: Full-brain images of the tissue sodium concentration (TSC1, n = 29) and a sodium inversion recovery sequence (SIR1, n = 20) at the beginning of the anti-inflammatory therapy and on medium-term follow-up visits (days 27-99, n = 12 [TSC], n = 5 [SIR]) were measured. Regions of interest (RoIs) with contrast enhancement (T1 CE+) and without change in T1-weighted imaging (FL + T1n) were normalized (nTSC and nSIR). To gain insight on the origin of the TSC enhancement at time point 1, it is investigated whether the nTSC enhancement of the lesions is accompanied by a change of the respective nSIR. Potential prognostic value of nSIR1 is examined referring to the nTSC progression. STATISTICAL TESTS: nTSC and nSIR were compared regarding the type of lesion and the time point using a one-way ANOVA. Pearson's correlation coefficient was calculated for nTSC over nSIR and for nTSC1-nTSC2 over nSIR1. A P-value <0.05 was considered statistically significant. RESULTS: At the first measurement, all lesion types showed increased nTSC, while nSIR was decreased in the FL + T1 n and the T1 CE+ lesions in comparison to the normal-appearing white matter. For acute lesions, the difference between nTSC at baseline and nTSC at time point 2 showed a significant correlation with the baseline nSIR. DATA CONCLUSION: At time point 1, nTSC is increased, while nSIR is unchanged or decreased in the lesions. The mean sodium IR signal at baseline correlates with recovery or progression of an acute lesion. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 4.

Direct imaging of white matter ultrashort T2∗ components at 7 Tesla.

PURPOSE: To demonstrate direct imaging of the white matter ultrashort T2∗ components at 7 Tesla using inversion recovery (IR)-enhanced ultrashort echo time (UTE) MRI. To investigate its characteristics, potentials and limitations, and to establish a clinical protocol. MATERIAL AND METHODS: The IR UTE technique suppresses long T2∗ signals within white matter by using adiabatic inversion in combination with dual-echo difference imaging. Artifacts arising at 7 T from long T2∗ scalp fat components were reduced by frequency shifting the IR pulse such that those frequencies were inverted likewise. For 8 healthy volunteers, the T2∗ relaxation times of white matter were then quantified. In 20 healthy volunteers, the UTE difference and fraction contrast were evaluated. Finally, in 6 patients with multiple sclerosis (MS), the performance of the technique was assessed. RESULTS: A frequency shift of -1.2 ppm of the IR pulse (i.e. towards the fat frequency) provided a good suppression of artifacts. With this, an ultrashort compartment of (68 ± 6) % with a T2∗ time of (147 ± 58) µs was quantified with a chemical shift of (-3.6 ± 0.5) ppm from water. Within healthy volunteers' white matter, a stable ultrashort T2∗ fraction contrast was calculated. For the MS patients, a significant fraction reduction in the identified lesions as well as in the normal-appearing white matter was observed. CONCLUSIONS: The quantification results indicate that the observed ultrashort components arise primarily from myelin tissue. Direct IR UTE imaging of the white matter ultrashort T2∗ components is thus feasible at 7 T with high quantitative inter-subject repeatability and good detection of signal loss in MS.

3D sodium (23 Na) magnetic resonance fingerprinting for time-efficient relaxometric mapping.

PURPOSE: To develop a framework for 3D sodium (23 Na) MR fingerprinting (MRF), based on irreducible spherical tensor operators with tailored flip angle (FA) pattern and time-efficient data acquisition for simultaneous quantification of T1 , T2l∗ , T2s∗ , and T2∗ in addition to ΔB0 . METHODS: 23 Na-MRF was implemented in a 3D sequence and irreducible spherical tensor operators were exploited in the simulations. Furthermore, the Cramér Rao lower bound was used to optimize the flip angle pattern. A combination of single and double echo readouts was implemented to increase the readout efficiency. A study was conducted to compare results in a multicompartment phantom acquired with MRF and reference methods. Finally, the relaxation times in the human brain were measured in four healthy volunteers. RESULTS: Phantom experiments revealed a mean difference of 1.0% between relaxation times acquired with MRF and results determined with the reference methods. Simultaneous quantification of the longitudinal and transverse relaxation times in the human brain was possible within 32 min using 3D 23 Na-MRF with a nominal resolution of (5 mm)3 . In vivo measurements in four volunteers yielded average relaxation times of: T1,brain = (35.0 ± 3.2) ms, T2l,brain∗ = (29.3 ± 3.8) ms and T2s,brain∗ = (5.5 ± 1.3) ms in brain tissue, whereas T1,CSF = (61.9 ± 2.8) ms and T2,CSF∗ = (46.3 ± 4.5) ms was found in cerebrospinal fluid. CONCLUSION: The feasibility of in vivo 3D relaxometric sodium mapping within roughly ½ h is demonstrated using MRF in the human brain, moving sodium relaxometric mapping toward clinically relevant measurement times.

Feasibility of deuterium magnetic resonance spectroscopy of 3-O-Methylglucose at 7 Tesla.

Deuterium Magnetic Resonance Spectroscopy (DMRS) is a non-invasive technique that allows the detection of deuterated compounds in vivo. DMRS has a large potential to analyze uptake, perfusion, washout or metabolism, since deuterium is a stable isotope and therefore does not decay during biologic processing of a deuterium labelled substance. Moreover, DMRS allows the distinction between different deuterated substances. In this work, we performed DMRS of deuterated 3-O-Methylglucose (OMG). OMG is a non-metabolizable glucose analog which is transported similar to D-glucose. DMRS of OMG was performed in phantom and in vivo measurements using a preclinical 7 Tesla MRI system. The chemical shift (3.51 ± 0.1 ppm) and relaxation times were determined. OMG was injected intravenously and spectra were acquired over a period of one hour to monitor the time evolution of the deuterium signal in tumor-bearing rats. The increase and washout of OMG could be observed. Three different exponential functions were compared in terms of how well they describe the OMG washout. A mono-exponential model with offset seems to describe the observed time course best with a time constant of 1910 ± 770 s and an offset of 2.5 ± 1.2 mmol/l (mean ± std, N = 3). Chemical shift imaging could be performed with a voxel size of 7.1 mm x 7.1 mm x 7.9 mm. The feasibility of DMRS with deuterium labelled OMG could be demonstrated. These data might serve as basis for future studies that aim to characterize glucose transport using DMRS.

Combined imaging of potassium and sodium in human skeletal muscle tissue at 7 T.

PURPOSE: To validate the feasibility of quantitative combined potassium (39 K) and sodium (23 Na) MRI in human calf muscle tissue, as well as to evaluate the reproducibility of the apparent tissue potassium concentration (aTPC) and apparent tissue sodium concentration (aTSC) determination in healthy muscle tissue. METHODS: Quantitative 23 Na and 39 K MRI acquisition protocols were implemented on a 7 T MR system. A double-resonant 23 Na/39 K birdcage RF coil was used. Measurements of human lower leg were performed in a total acquisition time of TANa = 10:54 min/TAK = 8:06 min and using a nominal spatial resolution of 2.5 × 2.5 × 15 mm3 /7.5 × 7.5 × 30 mm3 for 23 Na/39 K MRI. Two aTSC and aTPC examinations in muscle tissue were performed during the same day on 10 healthy subjects. RESULTS: The proposed acquisition and postprocessing workflow for 23 Na and 39 K MRI data sets provided reproducible aTSC and aTPC measurements. In human calf muscle tissue, the coefficient of variation between scan and re-scan was 5.7% for both aTSC and aTPC determination. Overall, mean values of aTSC = (17 ± 1) mM and aTPC = (85 ± 5) mM were measured. Moreover, for 39 K in calf muscle tissue, T2∗ components of T2f∗ = (1.2 ± 0.2) ms and T2s∗ = (7.9 ± 0.9) ms, as well as a residual quadrupolar interaction of ωq¯ = (143 ± 17) Hz, were determined. The fraction of the fast component was f = (58 ± 4)%. CONCLUSION: Using the presented measurement and postprocessing approach, a reproducible aTSC and aTPC determination using 23 Na and 39 K MRI at 7 T in human skeletal muscle tissue is feasible in clinically acceptable acquisition durations.

23Na MRI of human skeletal muscle using long inversion recovery pulses.

23Na inversion recovery (IR) imaging allows for a weighting toward intracellular sodium in the human calf muscle and thus enables an improved analysis of pathophysiological changes of the muscular ion homeostasis. However, sodium signal-to-noise ratio (SNR) is low, especially when using IR sequences. 23Na has a nuclear spin of 3/2 and therefore experiences a strong electrical quadrupolar interaction. This results in very short relaxation times as well as in possible residual quadrupolar splitting. Consequently, relaxation effects during a radiofrequency pulse can no longer be neglected and even allow for increasing SNR as has previously been shown for human brain and knee. The aim of this work was to increase the SNR in 23Na IR imaging of the human calf muscle by using long inversion pulses instead of the usually applied short pulses. First, the influence of the inversion pulse length (1 to 20 ms) on the SNR as well as on image contrast was simulated for different model environments and verified by phantom measurements. Depending on the model environment (agarose 4% and 8%, xanthan 2% and 3%), SNR values increased by a factor of 1.15 up to 1.35, while NaCl solution was successfully suppressed. Thus, image contrast between the non-suppressed model compartments changes with IR pulse length. Finally, in vivo measurements of the human calf muscle of ten healthy volunteers were conducted at 3 Tesla. On average, a 1.4-fold increase in SNR could be achieved by increasing the inversion pulse length from 1 ms to 20 ms, leaving all other parameters - including the scan time - constant. This enables 23Na IR MRI with improved spatial resolution or reduced acquisition time.