Synopsis

Non-proton MRI (X-nuclei MRI) can provide new information on living tissues that is not available with proton (¹H) MRI. Certain X-nuclei such as sodium (²³Na), phosphorus (³¹P), oxygen (¹⁷O), potassium (³⁹K), Chlorine (³⁵Cl), and others, play an important role in the body metabolism (such as ion homeostasis, propagation of action potential, energy metabolism) and can also be detected with magnetic resonance imaging.

Rationale

Non-proton nuclei MRI (also called X-nuclei MRI) can provide new information on living tissues that is not available with proton (¹H) MRI. Standard ¹H MRI can generate images of the human body with many different contrasts, such as T1-weighted, T2-weighted, proton density-weighted, T1 and T2 maps, diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), susceptibility weighted imaging (SWI), diffusion kurtosis imaging (DKI), dynamic contrast enhanced (DCE) MRI, and many more, that can provide structural/anatomical information on the tissues under investigation, to detect and monitor diseases. Proton MRI can also be adapted to be more sentive to 'functions' in the body (mostly in brain, but also in muscle), generally through the technique of blood-oxygen dependent level (BOLD) MRI, which detects changes in signal which are mainly due to transient increases of blood flow to areas with increased neuronal activation, which alter the local ratio between oxy- and deoxyhemoglobin.

Certain X-nuclei such as sodium (²³Na), phosphorus (³¹P), oxygen (¹⁷O), potassium (³⁹K), Chlorine (³⁵Cl), and others, play an important role in the body metabolism (such as ion homeostasis, propagation of action potential, energy metabolism) and can also be detected with magnetic resonance. Although these ions are in very low concentration in the body compared to the protons from water molecules (about 62% of the body atoms are hydrogen), and have different magnetic properties that can make them difficult to detect, X-nuclei MRI in a clinical environment is now possible due the recent technological advances of high-field MR systems (3 T, 7T, 9.4 T), multichannel-dual-tuned RF coils, efficient acquisition pulse sequences and image reconstruction algorithms.

In this presentation I will give an brief overview of X-nuclei MRI/MRS, of its challenges and potential clinical applications. I will mainly focus on ²³Na MRI, ³¹P MRS/MRI and ¹⁷O MRI as examples of potentially useful non-proton imaging methods that could give interesting new metabolic information in vivo in a non-invasive and quantitative manner.

X-Nuclei MRI/MRS

X-nuclei in biological tissues

• Ion homeostasis
• Natural abundance
• Energy metabolism

NMR properties of X-nuclei

• Spin and magnetic properties
• NMR sensitivity, signal strentgh and frequencies
• Relaxation times

Sodium ²³Na

• ²³Na NMR: spin 3/2, quadrupolar relaxation, biexponential relaxation
• Data acquisition: Ultrashort TE, non-Cartesian trajectories, resolution, SNR, multiple quantum filtering
• Data quantification: calibration, intracellular sodium concentration, cartilage sodium content

Phosphorus ³¹P

• ³¹P NMR: spin 1/2, metabolites, relaxation, chemical exchange, pH
• Data acquisition: CSI, UTE MRI, pulse selective, dynamic acquisition during exercise, satruration transfer
• Data quantification: calibration, pH, PCr, ATP, Pi

Oxygen ¹⁷O

• ¹⁷O NMR: spin 5/2, quadrupolar relaxation, biexponential relaxation
• Data acquisition: Ultrashort TE, non-Cartesian trajectories, resolution, SNR
• Data quantification: calibration, enriched 17O2 inhalation

Other nuclei

• Chlorine ³⁵Cl
• Potassium ³⁹K
• Lithium ⁷Li
• Fluorine ¹⁹F
• Hyperpolarized nuclei: ³He, ¹²⁹Xe, ¹³C

Potential clinical applications

Neurology

• Neurodegeneration in Alzheimer's disease
• Tumors
• Traumatic brain injury (TBI)
• Multiple Sclerosis (MS)

Musculosketal (MSK) and bone

• Cartilage: Osteoarthritis, cartilage repair
• Muscle: Diabetes, muscular dystrophy, muscular channelopathy, myotonic dystrophy, hypertension
• Bone

Breast cancer

Heart

Kidney

Therapy monitoring

Limitations and prospects

Limitations

• SNR
• Acquisition time
• Resolution
• Sensitivity and specificity
• Accuracy
• Repeatability and reproducibility

Prospects

• Compressed sensing
• MR fingerprinting (MRF)
• Denoising
• High-field MR systems
• New acquisition sequences

Acknowledgements

References

• G. Madelin, RR. Regatte. Biomedical applications of sodium MRI in vivo. J Magn Reson Imaging 38, 511-529, 2013
• G. Madelin, J-S. Lee, RR. Regatte, A. Jerschow. Sodium MRI: Methods and applications. Prog MNR Spectrosc 79, 14-47, 2014
• A. Jerschow. From nuclear structure to the quadrupolar NMR interaction and high-resolution spectroscopy, Prog NMR Spectrosc 46, 63–78, 2005
• C. Springer, Biological Systems: Spin-3/2 Nuclei, eMagRes (Encyclopedia of Magnetic Resonance), 2007
• G. Jaccard, S. Wimperis, G. Bodenhausen. Multiple quantum NMRspectroscopy of S=3/2 spins in isotropic phase: a new probe for multiexponential relaxation, J Chem Phys 85, 6282–6293, 1986
• FE. Boada FE, G. LaVerde, C. Jungreis, E. Nemoto, C. Tanase, I. Hancu. Loss of cell ion homeostasis and cell viability in the brain: what sodium MRI can tell us. Curr Top Dev Biol 70, 77-101, 2005
• R. Ouwerkerk. Sodium MRI. Methods Mol Biol 711, 175-201, 2011
• KE. Thulborn. Quantitative sodium MR imaging: A review of its evolving role in medicine. NeuroImage. In press, 2017
• AM. Nagel, F. Lehmann-Horn, M-A. Weber, K. Jurkat-Rott, MB. Wolf, A. Radbruch, R. Umathum, W. Semmler. In Vivo 35Cl MR Imaging in Humans: A Feasibility Study. Radiology 271(2), 585-595, 2014
• JC Soares, FE. Boada, MS. Keshavan. Brain lithium measurements with 7Li magnetic resonance spectroscopy (MRS): a literature review. Eur Neuropsychopharmacolgy 10(3), 151-158, 2000
• TB. Parish, DS. Fieno, SW. Fitzgerald, RM. Judd. Theoretical basis for sodium and potassium MRI of the human heart at 1.5 T. Magn Reson Med 38(4), 653-661, 1997
• X-H. Zhu, W. Chen. In vivo oxygen-17 NMR for imaging brain oxygen metabolism at high field. Prog MNR Spectrosc 59, 319-355, 2011
• I. Tirotta, V. Dichiarante, C. Pigliacelli, G. Cavallo, G. Terraneo, F. Baldelli Bombelli, P. Metrangolo, G. Resnati. 19F Magnetic Resonance Imaging (MRI): From Design of Materials to Clinical Applications. Chem Rev 115, 1106-1129, 2015
• S. Konstandin, AM. Nagel. Measurement techniques for magnetic resonance imaging of fast relaxing nuclei. Magn Reson Mater Phy 27, 5-19, 2014
• DML. Lilburn, GE. Pavlovskaya, T. Meersmann. Perspectives of hyperpolarized noble gas MRI beyond 3He. J Magn Reson 29, 173-186, 2013
• K. Golman, LE. Olsson, O. Axelsson, S. Mnasson, M. Karlsson, JS. Petersson. Molecular imaging using hyperpolarized 13C. Brit J Radiol 76, 118-127, 2003
• GJ. Kemp, M. Meyerspeer, E. Moser. Absolute quantification of phosphorus metabolite concentrations in human muscle in vivo by 31P MRS: a quantitative review. NMR Biomed 20, 555-565, 2007
• H. Hall, S. Cuellar-Baena, C. Dahlberg, R. Zandt, V. Denisov, D. Kirik. Magnetic Resonance Spectroscopic Methods for the Assessment of Metabolic Functions in the Diseased Brain. Curr Topics Behav Neurosci 11, 169–198, 2012