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Sodium Magnetic Resonance Images of a female volunteer at 3T (6mm x 6mm in-plane resolution, 72mm slice thickness, captured in 50minutes for five segments)[1]

Sodium MRI (also known as 23Na-MRI) is a specialised magnetic resonance imaging technique that uses strong magnetic fields, magnetic field gradients, and radio waves to generate images of the distribution of sodium in the body, as opposed to more common forms of MRI that utilise protons (hydrogen atoms) present in water (1H-MRI).[2][3] Like the proton, sodium is naturally abundant in the body, and thus can be imaged directly without the need for contrast agents or hyperpolarization. Furthermore, sodium ions play a role in important biological processes via their contribution to concentration and electrochemical gradients across cellular membranes, making it of interest as an imaging target in health and disease.[4]

In contrast to conventional proton MRI, sodium MRI is complicated by the low concentrations of sodium nuclei relative to the concentration of H2O molecules in biological tissues[5] (10-45 mM) and the lower gyromagnetic ratio of the 23Na nucleus as compared to a 1H nucleus.[6][7] This causes low NMR sensitivity, meaning that a stronger magnetic field is required to obtain equivalent spatial resolution. The quadrupolar 23Na nucleus also has a faster transverse relaxation rate and multiple quantum coherences as compared to the 1H nucleus,[7] requiring specialized and high-performance MRI sequences to capture information before the contrast used to image the body is lost.

Biological significance

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Effects of hypoxic tumor microenvironment on intracellular pH

Tissue sodium concentration (TSC) is tightly regulated by healthy cells and is altered by energy status and cellular integrity, making it an effective marker for disease states.[5][7][8] Cells maintain a low intracellular Na+ concentration by actively pumping Na ions out via the Na+/K+ ATPase channel. Any challenge to the cell's metabolism which lowers ATP supply or compromises the cell's membrane integrity will drastically increase intracellular Na+ concentrations. After exhaustive exercise, for example, 23Na MRI can detect Na+ levels in tissues rising sharply, and can even visualize a sodium-rich meal in a patient's stomach. Malignant tumors in particular alter their metabolism drastically, often to account for hypoxic intratumor conditions, leading to an decrease in cytosolic pH. To compensate, Na+ ions from the extracellular space are exchanged for protons in the Na+/H+ antiport,[7] the loss of which often attenuates cancer growth.[9] Therefore, 23Na MRI is a useful clinical tool for detecting a number of disease states, including heart disease[10] and cancer, as well as monitoring therapy. For example, 23Na MRI has been shown to measure cellularity in ovarian cancer.[11] Tissue damage in stroke patients can also be evaluated using 23Na MRI, with one study showing that a change of 50% higher TSC than the TSC in healthy brain tissue is consistent with complete infarction,[12] and therefore can be used to determine tissue viability and treatment options for the patient. Tumor malignancy can also be evaluated based on the increases in TSC of rapidly proliferating cells. Malignant tumors have approximately 50-60% increased TSC relative to that of healthy tissues[12] – however, increases in TSC cannot be determined to be due to changes in extracellular volume, intracellular sodium content or neovascularization. Another interesting use of 23Na MRI is in evaluating multiple sclerosis, wherein accumulation of sodium in axons can lead to axon degeneration.[13] Preliminary studies have shown that there is a positive correlation between elevated TSC and disability.

Uses in prostate cancer

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Recently, work has been undertaken to assess the utility of using sodium MRI to characterize prostate cancer lesions in men.[14] In this study, patients were imaged with sodium MRI prior to surgical removal of the prostate. TSC was extracted from the images and compared to the Gleason score of imaged lesions. This work showed statistically significant increases in TSC as prostate cancer increased in aggression. This preliminary study suggests that sodium MRI can accurately characterize the stage of prostate cancer. This suggests the potential use of sodium MRI for better management and staging of patients with prostate cancer into treatment schemes.

Advantages

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23Na MRI measures cellular metabolic rate as well as disease-related change in tissues and organs.[15] It has improved from a 45 minute length to only 15 minutes at 1.5T.[7][12] For cartilage degeneration, proteoglycan degrades with negative charge, and positively charged sodium ion bonds with proteoglycan.[3] Both the proteoglycan and sodium level decrease, so a decrease in signal is observed by sodium MRI and can be used for monitoring of proteoglycan degeneration in cartilage.[3][16]

See also

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References

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  1. ^ Wetterling, Friedrich; Corteville, Dominique; Kalayciyan, Raffi; Rennings, Andre; Konstandin, Simon; Nagel, Armin; Stark, Helmut; Schad, Lothar (2012-06-22). "Whole body sodium MRI at 3T using an asymmetric birdcage resonator and short echo time sequence: first images of a male volunteer". Physics in Medicine and Biology. 57 (14): 4555–4567. Bibcode:2012PMB....57.4555W. doi:10.1088/0031-9155/57/14/4555. hdl:2262/108510. PMID 22722731.
  2. ^ Ouwerkerk, Ronald; Morgan, Russell H. (2007-10-01). "23Na MRI: From Research to Clinical Use". Journal of the American College of Radiology. 4 (10): 739–741. doi:10.1016/j.jacr.2007.07.001. ISSN 1546-1440. PMC 2084082. PMID 17903762.
  3. ^ a b c Borthakur, A; Shapiro, E. M; Beers, J; Kudchodkar, S; Kneeland, J. B; Reddy, R (2000-07-01). "Sensitivity of MRI to proteoglycan depletion in cartilage: comparison of sodium and proton MRI". Osteoarthritis and Cartilage. 8 (4): 288–293. doi:10.1053/joca.1999.0303. PMID 10903883.
  4. ^ Madelin, Guillaume (2012-12-18). "Sodium Magnetic Resonance Imaging: Biomedical Applications". arXiv:1212.4400 [physics.med-ph].
  5. ^ a b Romanzetti, Sandro; Mirkes, Christian C.; Fiege, Daniel P.; Celik, Avdo; Felder, Jörg; Shah, N. Jon (2014-08-01). "Mapping tissue sodium concentration in the human brain: a comparison of MR sequences at 9.4Tesla". NeuroImage. 96: 44–53. doi:10.1016/j.neuroimage.2014.03.079. ISSN 1095-9572. PMID 24721332. S2CID 17913668.
  6. ^ Madelin, Guillaume; Lee, Jae-Seung; Regatte, Ravinder R.; Jerschow, Alexej (2014-05-01). "Sodium MRI: Methods and applications". Progress in Nuclear Magnetic Resonance Spectroscopy. 79: 14–47. Bibcode:2014PNMRS..79...14M. doi:10.1016/j.pnmrs.2014.02.001. PMC 4126172. PMID 24815363.
  7. ^ a b c d e Madelin, Guillaume; Regatte, Ravinder R. (2013-09-01). "Biomedical Applications of Sodium MRI In Vivo". Journal of Magnetic Resonance Imaging. 38 (3): 511–529. doi:10.1002/jmri.24168. ISSN 1053-1807. PMC 3759542. PMID 23722972.
  8. ^ Ouwerkerk, Ronald (2011-01-01). "Sodium MRI". In Modo, Michel; Bulte, Jeff W.M. (eds.). Magnetic Resonance Neuroimaging. Methods in Molecular Biology. Vol. 711. Humana Press. pp. 175–201. doi:10.1007/978-1-61737-992-5_8. ISBN 9781617379918. PMID 21279602.
  9. ^ Alevizopoulos, Konstantinos; Calogeropoulou, Theodora; Lang, Florian; Stournaras, Christos (2014-01-01). "Na+/K+ ATPase inhibitors in cancer". Current Drug Targets. 15 (10): 988–1000. ISSN 1873-5592. PMID 25198786.
  10. ^ Bottomley, Paul A. (2016-02-01). "Sodium MRI in human heart: a review". NMR in Biomedicine. 29 (2): 187–196. doi:10.1002/nbm.3265. ISSN 1099-1492. PMC 4868405. PMID 25683054.
  11. ^ Deen, SS; Riemer, F; McLean, MA; Gill, AB; Kaggie, JD; Grist, JT; Crawford, R; Latimer, J; Baldwin, P; Earl, HM; Parkinson, CA; Smith, SA; Hodgkin, C; Moore, E; Jimenez-Linan, M; Brodie, CR; Addley, HC; Freeman, SJ; Moyle, PL; Sala, E; Graves, MJ; Brenton, JD; Gallagher, FA (2019). "Sodium MRI with 3D-cones as a measure of tumour cellularity in high grade serous ovarian cancer". European Journal of Radiology Open. 6: 156–162. doi:10.1016/j.ejro.2019.04.001. PMC 6477161. PMID 31032385.
  12. ^ a b c Ouwerkerk, Ronald; Bleich, Karen B.; Gillen, Joseph S.; Pomper, Martin G.; Bottomley, Paul A. (2003-05-01). "Tissue Sodium Concentration in Human Brain Tumors as Measured with 23Na MR Imaging". Radiology. 227 (2): 529–537. doi:10.1148/radiol.2272020483. ISSN 0033-8419. PMID 12663825.
  13. ^ Inglese, M.; Madelin, G.; Oesingmann, N.; Babb, J. S.; Wu, W.; Stoeckel, B.; Herbert, J.; Johnson, G. (2010-03-01). "Brain tissue sodium concentration in multiple sclerosis: a sodium imaging study at 3 tesla". Brain. 133 (3): 847–857. doi:10.1093/brain/awp334. ISSN 0006-8950. PMC 2842511. PMID 20110245.
  14. ^ Broeke, NC.; Peterson, J.; Lee, J.; Martin, PA.; Farag, A.; Gomez, J.; Moussa, M.; Gaed, M.; Chin, J.; Pautler, SE.; Ward, A.; Bauman, G.; Bartha, R.; Scholl, TJ. (2018-08-24). "Characterization of Clinical Human Prostate Cancer Lesions Using 3.0-T Sodium MRI Registered to Gleason-Graded Whole-Mount Histopathology". Journal of Magnetic Resonance Imaging. 49 (5): 1409–1419. doi:10.1002/jmri.26336. PMID 30430700. S2CID 53425193.
  15. ^ Madelin, Guillaume; Kline, Richard; Walvick, Ronn; Regatte, Ravinder R. (2014-04-23). "A method for estimating intracellular sodium concentration and extracellular volume fraction in brain in vivo using sodium magnetic resonance imaging". Scientific Reports. 4: 4763. Bibcode:2014NatSR...4E4763M. doi:10.1038/srep04763. PMC 4762219. PMID 24755879.
  16. ^ Newbould, R.D.; Miller, S.R.; Tielbeek, J.A.W.; Toms, L.D.; Rao, A.W.; Gold, G.E.; Strachan, R.K.; Taylor, P.C.; Matthews, P.M. (2012-01-01). "Reproducibility of sodium MRI measures of articular cartilage of the knee in osteoarthritis". Osteoarthritis and Cartilage. 20 (1): 29–35. doi:10.1016/j.joca.2011.10.007. ISSN 1063-4584. PMC 3270258. PMID 22040861.
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