Efficient 23 Na triple-quantum signal imaging on clinical scanners: Cartesian imaging of single and triple-quantum 23 Na (CRISTINA).

PURPOSE: To capture the multiquantum coherence (MQC) 23 Na signal. Different phase-cycling options and sequences are compared in a unified theoretical layout, and a novel sequence is developed. METHODS: An open source simulation overview is provided with graphical explanations to facilitate MQC understanding and access to techniques. Biases such as B0 inhomogeneity and stimulated echo signal were simulated for 4 different phase-cycling options previously described. Considerations for efficiency and accuracy lead to the implementation of a 2D Cartesian single and triple quantum imaging of sodium (CRISTINA) sequence employing two 6-step cycles in combination with a multi-echo readout. CRISTINA was compared to simultaneous single-quantum and triple-quantum-filtered MRI of sodium (SISTINA) under strong static magnetic gradient. CRISTINA capabilities were assessed on 8 × 60 mL, 0% to 5% agarose phantom with 50 to 154 mM 23 Na concentration at 7 T. CRISTINA was demonstrated subsequently in vivo in the brain. RESULTS: Simulation of B0 inhomogeneity showed severe signal dropout, which can lead to erroneous MQC measurement. Stimulated echo signal was highest at the time of triple-quantum coherences signal maximum. However, stimulated echo signal is separated by Fourier Transform as an offset and did not interfere with MQC signals. The multi-echo readout enabled capturing both single-quantum coherences and triple-quantum coherences signal evolution at once. Signal combination of 2 phase-cycles with a corresponding B0 map was found to recover the signal optimally. Experimental results confirm and complement the simulations. CONCLUSION: Considerations for efficient MQC measurements, most importantly avoiding B0 signal loss, led to the design of CRISTINA. CRISTINA captures triple-quantum coherences and single-quantum coherences signal evolution to provide complete sodium signal characterization including T2∗ fast, T2∗ slow, MQC amplitudes, and sodium concentration.

X-nuclei imaging: Current state, technical challenges, and future directions.

1 H imaging is concerned with contrast generation among anatomically distinct soft tissues. X-nuclei imaging, on the other hand, aims to reveal the underlying changes in the physiological processes on a cellular level. Advanced clinical MR hardware systems improved 1 H image quality and simultaneously enabled X-nuclei imaging. Adaptation of 1 H methods and optimization of both sequence design and postprocessing protocols launched X-nuclei imaging past feasibility studies and into clinical studies. This review outlines the current state of X-nuclei MRI, with the focus on 23 Na, 35 Cl, 39 K, and 17 O. Currently, various aspects of technical challenges limit the possibilities of clinical X-nuclei MRI applications. To address these challenges, quintessential physical and technical concepts behind different applications are presented, and the advantages and drawbacks are delineated. The working process for methods such as quantification and multiquantum imaging is shown step-by-step. Clinical examples are provided to underline the potential value of X-nuclei imaging in multifaceted areas of application. In conclusion, the scope of the latest technical advance is outlined, and suggestions to overcome the most fundamental hurdles on the way into clinical routine by leveraging the full potential of X-nuclei imaging are presented. Level of Evidence: 1 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:355-376.

23 Na Triple-quantum signal of in vitro human liver cells, liposomes, and nanoparticles: Cell viability assessment vs. separation of intra- and extracellular signal.

BACKGROUND: Triple-quantum (TQ) filtered sequences have become more popular in sodium MR due to the increased usage of scanners with field strengths exceeding 3T. Disagreement as to whether TQ signal can provide separation of intra- and extracellular compartments persists. PURPOSE: To provide insight into TQ signal behavior on a cellular level. STUDY TYPE: Prospective. PHANTOM/SPECIMEN: Cell-phantoms in the form of liposomes, encapsulated 0 mM, 145 mM, 154 mM Na+ in a double-lipid membrane similar to cells. Poly(lactic-co-glycolic acid) nanoparticles encapsulated 154 mM Na+ within a single-layer membrane structure. Two microcavity chips with each 6 × 106 human HEP G2 liver cells were measured in an MR-compatible bioreactor. FIELD STRENGTH/SEQUENCE: Spectroscopic TQ sequence with time proportional phase-increments at 9.4T. ASSESSMENT: The TQ signal of viable, dead cells, and cell-phantoms was assessed by a fit in the time domain and by the amplitude in the frequency domain. STATISTICAL TESTS: The noise variance (σ) was evaluated to express the deviation of the measured TQ signal amplitude from noise. RESULTS: TQ signal >20σ was found for liposomes encapsulating sodium ions. Liposomal encapsulation of 0 mM Na+ and 154 mM Na+ encapsulation in the nanoparticles resulted in <2σ TQ signal. Cells under normal perfusion resulted in >9σ TQ signal. Compared with TQ signal under normal perfusion, a 56% lower TQ signal of was observed (25σ) during perfusion stop. TQ signal returned to 92% of the initial signal after reperfusion. DATA CONCLUSION: Our measurements indicate that TQ signal in liposomes was observed due to the trapping of ions within the double-lipid membrane rather than from the intraliposomal space. Transfer to the cell results suggests that TQ signal was observed from motion restriction equivalent to trapping. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:435-444.

Volumetric 23Na Single and Triple-Quantum Imaging at 7T: 3D-CRISTINA.

PURPOSE: To measure multi-quantum coherence (MQC) 23Na signals for noninvasive cell physiological information in the whole-brain, the 2D-CRISTINA method was extended to 3D. This experimental study investigated the use and results of a new sequence, 3D-CRISTINA, on a phantom and healthy volunteers. METHODS: The 3D Cartesian single and triple-quantum imaging of 23Na (3D-CRISTINA) was developed and implemented at 7T, favoring a non-selective volume excitation for increased signal-to-noise ratio (SNR) and lower energy deployment than its 2D counterpart. Two independent phase cycles were used in analogy to the 2D method. A comparison of 6-steps cycles and 12-steps cycles was performed. We used a phantom composed of different sodium and agarose concentrations, 50mM to 150mM Na+, and 0-5% agarose for sequence validation. Four healthy volunteers were scanned at 7T for whole brain MQC imaging. The sequence 3D-CRISTINA was developed and tested at 7T. RESULTS: At 7T, the 3D-CRISTINA acquisition allowed to reduce the TR to 230ms from the previous 390ms for 2D, resulting in a total acquisition time of 53min for a 3D volume of 4×4×8mm resolution. The phase cycle evaluation showed that the 7T acquisition time could be reduced by 4-fold with moderate single and triple-quantum signals SNR loss. The healthy volunteers demonstrated clinical feasibility at 7T and showed a difference in the MQC signals ratio of White Matter (WM) and Grey Matter (GM). CONCLUSION: Volumetric CRISTINA multi-quantum imaging allowed whole-brain coverage. The non-selective excitation enabled a faster scan due to a decrease in energy deposition which enabled a lower repetition time. Thus, it should be the preferred choice for future in vivo multi-quantum applications compared to the 2D method. A more extensive study is warranted to explore WM and GM MQC differences.

MRI Detection of Changes in Tissue Sodium Concentration in Brain Metastases after Stereotactic Radiosurgery: A Feasibility Study.

BACKGROUND AND PURPOSE: To date, treatment response to stereotactic radiosurgery (SRS) in brain metastases (BM) can only be determined by MRI evaluation of contrast-enhancing lesions in a long-time follow-up. Sodium MRI has been a subject of immense interest in imaging research as the measure of tissue sodium concentration (TSC) can give valuable quantitative information on cell viability. We aimed to analyze the longitudinal changes of TSC in BM measured with 23 Na MRI before and after SRS for assessment of early local tumor effects. METHODS: Seven patients with a total of 12 previously untreated BM underwent SRS with 22 Gy. In addition to a standard MRI protocol including dynamic susceptibility-weighted contrast-enhanced perfusion, a 23 Na MRI was performed at three time points: (I) 2 days before, (II) 5 days, and (III) 40 days after SRS. Nine BMs were evaluated. The absolute TSC in the BM, the respective peritumoral edemas, and the normal-appearing corresponding contralateral brain area were assessed and the relative TSC were correlated to the changes in BM longest axial diameters. RESULTS: TSC was elevated in nine BM at baseline before SRS with a mean of 73.4 ± 12.3 mM. A further increase in TSC was observed 5 days after SRS in all the nine BM with a mean of 86.9 ± 13 mM. Eight of nine BM showed a mean 60.6 ± 13.3% decrease in the longest axial diameter 40 days after SRS; at this time point, the TSC also had decreased to a mean 65.1 ± 7.9 mM. In contrast, one of the nine BM had a 13.4% increase in the largest axial diameter at time point III. The TSC of this BM showed a further TSC increase of 80.1 mM 40 days after SRS. CONCLUSION: Changes in TSC using 23 Na MRI shows the possible capability to detect radiobiological changes in BM after SRS.

Quantification of confounding factors in MRI-based dose calculations as applied to prostate IMRT.

Magnetic resonance (MR)-only radiotherapy treatment planning requires pseudo-CT (pCT) images to enable MR-based dose calculations. To verify the accuracy of MR-based dose calculations, institutions interested in introducing MR-only planning will have to compare pCT-based and computer tomography (CT)-based dose calculations. However, interpreting such comparison studies may be challenging, since potential differences arise from a range of confounding factors which are not necessarily specific to MR-only planning. Therefore, the aim of this study is to identify and quantify the contribution of factors confounding dosimetric accuracy estimation in comparison studies between CT and pCT. The following factors were distinguished: set-up and positioning differences between imaging sessions, MR-related geometric inaccuracy, pCT generation, use of specific calibration curves to convert pCT into electron density information, and registration errors. The study comprised fourteen prostate cancer patients who underwent CT/MRI-based treatment planning. To enable pCT generation, a commercial solution (MRCAT, Philips Healthcare, Vantaa, Finland) was adopted. IMRT plans were calculated on CT (gold standard) and pCTs. Dose difference maps in a high dose region (CTV) and in the body volume were evaluated, and the contribution to dose errors of possible confounding factors was individually quantified. We found that the largest confounding factor leading to dose difference was the use of different calibration curves to convert pCT and CT into electron density (0.7%). The second largest factor was the pCT generation which resulted in pCT stratified into a fixed number of tissue classes (0.16%). Inter-scan differences due to patient repositioning, MR-related geometric inaccuracy, and registration errors did not significantly contribute to dose differences (0.01%). The proposed approach successfully identified and quantified the factors confounding accurate MRI-based dose calculation in the prostate. This study will be valuable for institutions interested in introducing MR-only dose planning in their clinical practice.