Beyond Protons (1H1): The Era of Multinuclear Magnetic Resonance Imaging

Sir,

Since its inception, clinical magnetic resonance imaging (MRI) has almost exclusively relied on proton (¹H) signal acquisition, owing to the high natural abundance and sensitivity of hydrogen in biological tissues. However, other nuclei—collectively termed X-nuclei—possess unique biochemical and physiologic signatures that can be directly interrogated by MRI, providing information inaccessible to conventional proton-based sequences. Recent technological advances in hardware, pulse sequence design, and hyperpolarization techniques are catalyzing the transition of multinuclear MRI from a research tool to targeted clinical applications.

Technical Foundations

Many X-nuclei, including ²³Na, ³¹P, ¹⁹F, ¹⁷O, ⁷Li, ³⁹K, and ³⁵Cl, have lower gyromagnetic ratios and natural abundances than ¹H, resulting in reduced signal-to-noise ratio (SNR) and often rapid relaxation. Optimized ultrashort echo time (UTE) and non-Cartesian k-space sampling schemes (e.g., 3D radial, cones) help capture short-T2 signals, while high-field systems (≥7 T) and dual-tuned or broadband radiofrequency coils improve sensitivity. Hyperpolarization techniques—spin-exchange optical pumping for ¹²⁹Xe and dissolution dynamic nuclear polarization for ¹³C—boost signal by several orders of magnitude, enabling real-time metabolic imaging.

Select Clinical Applications

²³Na MRI quantifies tissue sodium concentration, offering insight into cellular viability, cartilage glycosaminoglycan depletion, and renal corticomedullary gradients.[1] ³¹P spectroscopy measures high-energy phosphate metabolism and intracellular pH, aiding in the evaluation of cardiomyopathies and neuromuscular disorders.[2] Hyperpolarized ¹³C MRI, particularly using [1-¹³C]pyruvate, visualizes dynamic metabolic fluxes and has shown promise for early treatment-response assessment in brain and prostate tumors.[3]

Hyperpolarized ¹²⁹Xe MRI—recently cleared by the US FDA for ventilation imaging—maps pulmonary ventilation, alveolar–capillary barrier uptake, and red blood cell transfer, facilitating the assessment of asthma, chronic obstructive pulmonary disease, and interstitial lung disease.[4] [5] ¹⁹F MRI provides background-free “hot-spot” imaging for cell tracking and inflammation mapping, while ¹⁷O MRI allows direct measurement of cerebral oxygen consumption. ⁷Li MRI has demonstrated the ability to map in vivo brain lithium distribution, potentially guiding therapy in bipolar disorder.

Future Directions

The coming years are likely to see broader clinical adoption in three main areas:

1. Pulmonology: Regional ventilation and gas-exchange mapping with ¹²⁹Xe.

2. Oncology: Hyperpolarized ¹³C for metabolic characterization and early therapy response.

3. Nephrology: ²³Na mapping for functional assessment before structural changes occur.

Integration with routine ¹H imaging, vendor-neutral reconstruction pipelines, and standardized quantification protocols will be critical for multicenter reproducibility. Expansion of hyperpolarized agent portfolios and modular upgrades for existing scanners could make multinuclear imaging more accessible.

Conclusion

Multinuclear MRI extends the diagnostic potential of MRI by providing direct, noninvasive access to tissue biochemistry and physiology. Continued technical refinement, growing clinical evidence, and regulatory milestones position these techniques as key enablers of precision imaging in the next decade.

Conflict of Interest

None declared.

Note

Multinuclear MRI is transitioning from niche research to clinically impactful imaging, offering unique physiologic and metabolic insights that complement conventional proton MRI in precision medicine.

• References

• 1 Gast LV, Platt T, Nagel AM, Gerhalter T. Recent technical developments and clinical research applications of sodium (²³Na) MRI. Prog Nucl Magn Reson Spectrosc 2023; 138-139: 1-51
• 2 Tsampasian V, McHugh S, Dall'Armellina E. et al. ^31P MRS of myocardial energetics: systematic review. Front Cardiovasc Med 2023; 10: 1097022
• 3 Larson PEZ, Wang J, Wilson DM. et al. Current methods for hyperpolarized [1-¹³C]pyruvate MRI in human studies. Magn Reson Med 2024; 92 (03) 1035-1055
• 4 MacLeod JL, Khan HM, Franklin A, Myc L, Shim YM. Hyperpolarized xenon-129 MRI: narrative review of clinical studies, testing, and implementation. Diagnostics (Basel) 2025; 15 (04) 474
• 5 van Heeswijk RB, Piccini D, Bonanno G. et al. Cardiovascular molecular imaging with ^19F MRI. Circ Cardiovasc Imaging 2023; 16 (02) e014742

Publication History

Article published online:
12 January 2026