1H 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 1H image quality and simultaneously enabled X‐nuclei imaging. Adaptation of 1H 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 23Na, 35Cl, 39K, and 17O. 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.
The aim of this study was to observe the effects of strophanthin induced inhibition of the Na-/K-ATPase in liver cells using a magnetic resonance (MR) compatible bioreactor. A microcavity array with a high density three-dimensional cell culture served as a functional magnetic resonance imaging (MRI) phantom for sodium multi quantum (MQ) spectroscopy. Direct contrast enhanced (DCE) MRI revealed the homogenous distribution of biochemical substances inside the bioreactor. NMR experiments using advanced bioreactors have advantages with respect to having full control over a variety of physiological parameters such as temperature, gas composition and fluid flow. Simultaneous detection of single quantum (SQ) and triple quantum (TQ) MR signals improves accuracy and was achieved by application of a pulse sequence with a time proportional phase increment (TQTPPI). The time course of the Na-/K-ATPase inhibition in the cell culture was demonstrated by the corresponding alterations of sodium TQ/SQ MR signals.
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.
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