Accelerated multiple-quantum-filtered sodium magnetic resonance imaging using compressed sensing at 7 T.

PURPOSE: Multiple-quantum-filtered (MQF) sodium magnetic resonance imaging (MRI), such as enhanced single-quantum and triple-quantum-filtered imaging of 23Na (eSISTINA), enables images to be weighted towards restricted sodium, a promising biomarker in clinical practice, but often suffers from clinically infeasible acquisition times and low image quality. This study aims to mitigate the above limitation by implementing a novel eSISTINA sequence at 7 T with the application of compressed sensing (CS) to accelerate eSISTINA acquisitions without a noticeable loss of information. METHODS: A novel eSISTINA sequence with a 3D spiral-based sampling scheme was implemented at 7 T for the application of CS. Fully sampled datasets were obtained from one phantom and ten healthy subjects, and were then retrospectively undersampled by various undersampling factors. CS undersampled reconstructions were compared to fully sampled and undersampled nonuniform fast Fourier transform (NUFFT) reconstructions. Reconstruction performance was evaluated based on structural similarity (SSIM), signal-to-noise ratio (SNR), weightings towards total and compartmental sodium, and in vivo quantitative estimates. RESULTS: CS-based phantom and in vivo images have less noise and better structural delineation while maintaining the weightings towards total, non-restricted (predominantly extracellular), and restricted (primarily intracellular) sodium. CS generally outperforms NUFFT with a higher SNR and a better SSIM, except for the SSIM in TQ brain images, which is likely due to substantial noise contamination. CS enables in vivo quantitative estimates with <15% errors at an undersampling factor of up to two. CONCLUSIONS: Successful implementation of an eSISTINA sequence with an incoherent sampling scheme at 7 T was demonstrated. CS can accelerate eSISTINA by up to twofold at 7 T with reduced noise levels compared to NUFFT, while maintaining major structural information, reasonable weightings towards total and compartmental sodium, and relatively reliable in vivo quantification. The associated reduction in acquisition time has the potential to facilitate the clinical applicability of MQF sodium MRI.

Two Decades of Brain Tumour Imaging with O-(2-[18F]fluoroethyl)-L-tyrosine PET: The Forschungszentrum Jülich Experience.

O-(2-[18F]fluoroethyl)-L-tyrosine (FET) is a widely used amino acid tracer for positron emission tomography (PET) imaging of brain tumours. This retrospective study and survey aimed to analyse our extensive database regarding the development of FET PET investigations, indications, and the referring physicians' rating concerning the role of FET PET in the clinical decision-making process. Between 2006 and 2019, we performed 6534 FET PET scans on 3928 different patients against a backdrop of growing demand for FET PET. In 2019, indications for the use of FET PET were as follows: suspected recurrent glioma (46%), unclear brain lesions (20%), treatment monitoring (19%), and suspected recurrent brain metastasis (13%). The referring physicians were neurosurgeons (60%), neurologists (19%), radiation oncologists (11%), general oncologists (3%), and other physicians (7%). Most patients travelled 50 to 75 km, but 9% travelled more than 200 km. The role of FET PET in decision-making in clinical practice was evaluated by a questionnaire consisting of 30 questions, which was filled out by 23 referring physicians with long experience in FET PET. Fifty to seventy per cent rated FET PET as being important for different aspects of the assessment of newly diagnosed gliomas, including differential diagnosis, delineation of tumour extent for biopsy guidance, and treatment planning such as surgery or radiotherapy, 95% for the diagnosis of recurrent glioma, and 68% for the diagnosis of recurrent brain metastases. Approximately 50% of the referring physicians rated FET PET as necessary for treatment monitoring in patients with glioma or brain metastases. All referring physicians stated that the availability of FET PET is essential and that it should be approved for routine use. Although the present analysis is limited by the fact that only physicians who frequently referred patients for FET PET participated in the survey, the results confirm the high relevance of FET PET in the clinical diagnosis of brain tumours and support the need for its approval for routine use.

Compressed Sensing in Sodium Magnetic Resonance Imaging: Techniques, Applications, and Future Prospects.

Sodium (23 Na) yields the second strongest nuclear magnetic resonance (NMR) signal in biological tissues and plays a vital role in cell physiology. Sodium magnetic resonance imaging (MRI) can provide insights into cell integrity and tissue viability relative to pathologies without significant anatomical alternations, and thus it is considered to be a potential surrogate biomarker that provides complementary information for standard hydrogen (1 H) MRI in a noninvasive and quantitative manner. However, sodium MRI suffers from a relatively low signal-to-noise ratio and long acquisition times due to its relatively low NMR sensitivity. Compressed sensing-based (CS-based) methods have been shown to accelerate sodium imaging and/or improve sodium image quality significantly. In this manuscript, the basic concepts of CS and how CS might be applied to improve sodium MRI are described, and the historical milestones of CS-based sodium MRI are briefly presented. Representative advanced techniques and evaluation methods are discussed in detail, followed by an expose of clinical applications in multiple anatomical regions and diseases as well as thoughts and suggestions on potential future research prospects of CS in sodium MRI. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 1.

Putaminal y-Aminobutyric Acid Modulates Motor Response to Dopaminergic Therapy in Parkinson's Disease.

BACKGROUND: Motor response to dopaminergic therapy is a characteristic of patients with Parkinson's disease (PD). Whether nondopaminergic neurotransmitters contribute to treatment response is uncertain. OBJECTIVES: The aim of this study is to determine whether putaminal y-aminobutyric acid (GABA) levels are associated with dopaminergic motor response. METHODS: We assessed putaminal GABA levels in 19 PD patients and 13 healthy controls (HCs) utilizing ultra-high field proton magnetic resonance spectroscopy. Motor performance was evaluated using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale, Part III, in the ON and OFF states. Statistical analysis comprised group comparisons, correlation analysis, and multiple linear regression. RESULTS: In PD, GABA levels were significantly higher compared to HCs (1.50 ± 0.26 mM vs. 1.26 ± 0.31 mM, P = 0.022). Furthermore, GABA levels were independent predictors of absolute and relative dopaminergic treatment response. CONCLUSIONS: Our findings indicate that elevated putaminal GABA levels are associated with worse dopaminergic response in PD, emphasizing the essential role of nondopaminergic neurotransmitters in motor response. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Iterative Restoration of the Fringe Phase (REFRASE) for QSM.

In quantitative susceptibility mapping (QSM), reconstructed results can be critically biased by misinterpreted or missing phase data near the edges of the brain support originating from the non-local relationship between field and susceptibility. These data either have to be excluded or corrected before further processing can take place. To address this, our iterative restoration of the fringe phase (REFRASE) approach simultaneously enhances the accuracy of multi-echo phase data QSM maps and the extent of the area available for evaluation. Data loss caused by strong local phase gradients near the surface of the brain support is recovered within the original phase data using harmonic and dipole-based fields extrapolated from a robust support region toward an extended brain mask. Over several iterations, phase data are rectified prior to the application of further QSM processing steps. The concept is successfully validated on numerical phantoms and brain scans from a cohort of volunteers. The increased extent of the mask and improved numerical stability within the segmented globus pallidus confirm the efficacy of the presented method in comparison to traditional evaluation.

Relaxometry and quantification in sodium MRI of cerebral gliomas: A FET-PET and MRI small-scale study.

Sodium MRI is a promising method for assessing the metabolic properties of brain tumours. In a recent study, a strong relationship between semi-quantitative abnormalities in sodium MRI and the mutational status of the isocitrate dehydrogenase enzyme (IDH) with untreated cerebral gliomas was observed. Here, sodium relaxometry in brain tumour tissue was investigated in relation to molecular markers in order to reveal quantitative sodium tissue parameters and the differences between healthy tissue and brain tumour. The previous semi-quantitative approach is extended by use of suitable relaxometry methods accompanied by numerical simulation to achieve detailed quantitative analysis of intra- and extracellular sodium concentration using an enhanced SISTINA sequence at 4 T. Using optimised techniques, biexponential sodium relaxation times in tumour (T*2f , T*2s ) and in healthy contralateral brain tissue (T*2f,CL , T*2s,CL ) were estimated in 10 patients, along with intracellular sodium molar fractions (χ, χCL ), volume fractions (η, ηCL ) and concentrations (ρin , ρin,CL ). The total sodium tissue concentrations (ρT , ρT,CL ) were also estimated. The ratios T*2f /T*2f,CL (P = .05), η/ηCL (P = .02) and χ/χCL (P = .02) were significantly lower in IDH mutated than in IDH wildtype gliomas (n = 4 and n = 5 patients, respectively). The Wilcoxon rank-sum test was used to compare sodium MRI parameters in patients with and without IDH mutation. Thus, quantitative analysis of relaxation rates, intra- and extracellular sodium concentrations, intracellular molar and volume fractions based on enhanced SISTINA confirmed a relationship between abnormalities in sodium parameters and the IDH mutational status in cerebral gliomas, hence catering for the potential to provide further insights into the status of the disease.

An in vivo multimodal feasibility study in a rat brain tumour model using flexible multinuclear MR and PET systems.

BACKGROUND: In addition to the structural information afforded by 1H MRI, the use of X-nuclei, such as sodium-23 (23Na) or phosphorus-31 (31P), offers important complementary information concerning physiological and biochemical parameters. By then combining this technique with PET, which provides valuable insight into a wide range of metabolic and molecular processes by using of a variety of radioactive tracers, the scope of medical imaging and diagnostics can be significantly increased. While the use of multimodal imaging is undoubtedly advantageous, identifying the optimal combination of these parameters to diagnose a specific dysfunction is very important and is advanced by the use of sophisticated imaging techniques in specific animal models. METHODS: In this pilot study, rats with intracerebral 9L gliosarcomas were used to explore a combination of sequential multinuclear MRI using a sophisticated switchable coil set in a small animal 9.4 T MRI scanner and, subsequently, a small animal PET with the tumour tracer O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET). This made it possible for in vivo multinuclear MR-PET experiments to be conducted without compromising the performance of either multinuclear MR or PET. RESULTS: High-quality in vivo images and spectra including high-resolution 1H imaging, 23Na-weighted imaging, detection of 31P metabolites and [18F]FET uptake were obtained, allowing the characterisation of tumour tissues in comparison to a healthy brain. It has been reported in the literature that these parameters are useful in the identification of the genetic profile of gliomas, particularly concerning the mutation of the isocitrate hydrogenase gene, which is highly relevant for treatment strategy. CONCLUSIONS: The combination of multinuclear MR and PET in, for example, brain tumour models with specific genetic mutations will enable the physiological background of signal alterations to be explored and the identification of the optimal combination of imaging parameters for the non-invasive characterisation of the molecular profile of tumours.

Comparison of [18F]Fluoroethyltyrosine PET and Sodium MRI in Cerebral Gliomas: a Pilot Study.

PURPOSE: Positron emission tomography (PET) using O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) improves the diagnostics of cerebral gliomas compared with conventional magnetic resonance imaging (MRI). Sodium MRI is an evolving method to assess tumor metabolism. In this pilot study, we explored the relationship of [18F]FET-PET and sodium MRI in patients with cerebral gliomas in relation to the mutational status of the enzyme isocitrate dehydrogenase (IDH). PROCEDURES: Ten patients with untreated cerebral gliomas and one patient with a recurrent glioblastoma (GBM) were investigated by dynamic [18F]FET-PET and sodium MRI using an enhanced simultaneous single-quantum- and triple-quantum-filtered imaging of 23Na (SISTINA) sequence to estimate total (NaT), weighted non-restricted (NaNR, mainly extracellular), and restricted (NaR, mainly intracellular) sodium in tumors and normal brain tissue. [18F]FET uptake and sodium parameters in tumors with a different IDH mutational status were compared. After biopsy or resection, histology and the IDH mutational status were determined neuropathologically. RESULTS: NaT (p = 0.05), tumor-to-brain ratios (TBR) of NaT (p = 0.02), NaNR (p = 0.003), and the ratio of NaT/NaR (p < 0.001) were significantly higher in IDH-mutated than in IDH-wild-type gliomas (n = 5 patients each) while NaR was significantly lower in IDH-mutated gliomas (p = 0.01). [18F]FET parameters (TBR, time-to-peak) were not predictive of IDH status in this small cohort of patients. There was no obvious relationship between sodium distribution and [18F]FET uptake. The patient with a recurrent GBM exhibited an additional radiation injury with strong abnormalities in sodium MRI. CONCLUSIONS: Sodium MRI appears to be more strongly related to the IDH mutational status than are [18F]FET-PET parameters. A further evaluation of the combination of the two methods in a larger group of high- and low-grade gliomas seems promising.

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.

Relaxometry and quantification in simultaneously acquired single and triple quantum filtered sodium MRI.

PURPOSE: Sodium imaging delivers valuable information about in vivo metabolism and pathophysiology. Image quantification can benefit the diagnosis and characterization of existing pathologies and the clinical course of a disease. An enhanced SISTINA sequence is proposed for sodium imaging and for the estimation of sodium tissue parameters for a 2-compartment model of the brain, such as relaxation times in intracellular space and tissue, intracellular volume fraction, and intracellular molar fraction. The aim of the research is to demonstrate how a 2-compartment model can be parameterized to sufficiently describe tissue sodium concentrations and dynamics by performing relaxometry with such a sequence. METHODS: Multiple quantum filtered sodium signals were detected using an enhanced SISTINA sequence (consisting of 3 consecutive RF pulses) by placing a readout train between the first and second RF pulse, and 1 after the third pulse. Semiautomatic segmentation using singular value decomposition and manual segmentation was applied to the images. RESULTS: Analysis was performed on 40 healthy volunteers in a 4T scanner, yielding bi-exponential relaxation times of brain tissue, intracellular sodium molar and volume fraction, intracellular sodium concentration, as well as sodium tissue concentration in the scope of a considered model. Two models with either purely mono-exponential or bi-exponential relaxing extracellular sodium were used with and without a potential contribution of triple quantum-filtered signal from extracellular space. CONCLUSION: An estimation of relaxation properties and concentrations limited to the assumed model is possible from a single sequence. The achieved results agree well with those reported in literature.

Design and use of a folded four-ring double-tuned birdcage coil for rat brain sodium imaging at 9.4 T.

A folded four-ring quadrature birdcage coil was designed and constructed with a double-tune configuration of an outer high-pass coil for 1H (400 MHz) and inner low-pass coil for 23Na (105.72 MHz at 9.4 T). The coil was evaluated on the bench and in the scanner, comparing its performance with that of single-tuned coils and a large four-ring coil. All coils were tuned and matched and the isolation between two quadrature ports was found to be better than -13.7 dB for 1H and -27 dB for 23Na. Signal-to-noise ratios (SNRs) were calculated and 23Na flip angle maps were acquired. 23Na SNR of the folded four-ring reached ∼93% of that obtained with the single-tuned coil. A set of in vivo1H and 23Na axial images to cover the whole rat brain were obtained. The performance of the folded four-ring coil and its benefit for 23Na imaging experiments have been demonstrated. This proposed four-ring coil could avoid length restrictions, e.g. the shoulders, by folding the outer rings vertically. This facilitates the construction of double-tuned four-ring birdcage coils just to fit the head, leading to higher filling factors and better SNR.

Imaging of sodium in the brain: a brief review.

Sodium-based MRI plays a vital role in the study of metabolism and can unveil valuable information about emerging and existing pathology--in particular in the human brain. Sodium is the second most abundant MR active nucleus in living tissue and, due to its quadrupolar nature, has magnetic properties not common to conventional proton MRI, which can reveal further insights, such as information on the compartmental distribution of intra- and extracellular sodium. Nevertheless, the use of sodium nuclei for imaging comes at the expense of a lower sensitivity and significantly reduced relaxation times, making in vivo sodium studies feasible only at high magnetic field strength and by the use of dedicated pulse sequences. Hybrid imaging combining sodium MRI and positron emission tomography (PET) simultaneously is a novel and promising approach to access information on dynamic metabolism with much increased, PET-derived specificity. Application of this new methodology is demonstrated herein using examples from tumour imaging.

Evidence for the light hole in GaAs/AlGaAs quantum wells from optically-pumped NMR and Hanle curve measurements.

Optically-pumped (69)Ga NMR (OPNMR) and optically-detected measurements of polarized photoluminescence (Hanle curves) show a characteristic feature at the light hole-to-conduction band transition in a GaAs/AlxGa1-xAs multiple quantum well sample. OPNMR data are often depicted as a "profile" of the OPNMR integrated signal intensity plotted versus optical pumping photon energy. What is notable is the inversion of the sign of the measured (69)Ga OPNMR signals when optically pumping this light hole-to-conduction band energy in OPNMR profiles at multiple external magnetic fields (B0=4.7T and 3T) for both σ(+) and σ(-) irradiation. Measurements of Hanle curves at B0=0.5T of the same sample exhibit similar phase inversion behavior of the Hanle curves at the photon energy for light hole excitation. The zero-field value of the light-hole state in the quantum well can be predicted for the quantum well structure using the positions of each of these signal-inversion features, and the spin splitting term in the equation for the transition energy yields consistent values at 3 magnetic fields for the excitonic g-factor (g(ex)). This study demonstrates the application of OPNMR and optical measurements of the photoluminescence to detect the light hole transition in semiconductors.