Project ID BE-MI2026_17

ThemeBE-MI

Co Supervisor 1A Dr Thomas Eykyn Faculty of Life Sciences & Medicine, School of Biomedical Engineering & Imaging Sciences, Department of Imaging Chemistry & BiologyEmail

Co Supervisor 1B Dr Özlem Ipek Faculty of Life Sciences & Medicine, School of Biomedical Engineering & Imaging Sciences, Imaging Physics and EngineeringEmail

High-field NMR and MRI of 23Na and 2H for metabolic imaging in cancer

Magnetic resonance imaging (MRI) is a cornerstone of diagnostic medicine, offering unparalleled capabilities to visualize tissue structure and function. Advances in high-field scanners have expanded the scope of MRI beyond protons (¹H) to other nuclei such as sodium (²³Na) and deuterium (²H), opening new avenues to study metabolism alongside structural imaging. Our previous work demonstrated a link between glucose metabolism and intracellular sodium concentrations ([Na]) in breast cancer, highlighting the potential of multinuclear imaging for probing tumour energetics.

This project aims to develop high-field spectroscopic imaging techniques using ²³Na and ²H MRI for metabolic imaging in cancer, leveraging a Bruker 9.4 T preclinical scanner and a Siemens Terra.X 7 T clinical scanner at St Thomas’ Hospital. Prototype RF coils for ²H and ²³Na have been constructed, and preliminary images have been acquired on both platforms (Figure 1). The project will focus on advancing RF coil design, hardware engineering, pulse sequences, and MR physics to translate these promising approaches towards human studies.

Year 1:
Prototype coils will be optimized for sensitivity and re-engineered for seamless integration with the scanners. Imaging protocols for ²³Na and ²H will be validated in phantoms mimicking in vivo tissue concentrations and relaxation properties. The physics of quadrupolar nuclei (I > 1/2) will be explored, and MRI sequences—including FLASH, RARE, UTE, and various k-space sampling strategies (Cartesian vs centric)—will be optimized for in vivo imaging. Multiple quantum filtering and other quantum-mechanical properties will be exploited to generate novel contrast sensitive to anisotropic tissue architecture.

Year 2:
Preclinical MRI studies will be conducted in a human MDA-MB-231 breast cancer xenograft model using immunocompromised NOD/SCID/gamma mice. Glycolytic flux will be imaged using [6,6’-²H]glucose with ²H MRI, while intracellular sodium concentrations will be assessed with ²³Na MRI. Treatment response to Na⁺/K⁺-ATPase inhibition (ouabain) and sodium channel blockade (lidocaine) will be evaluated, linking ion transport and metabolism in vivo.

Years 3–4:
Clinical RF coils will be validated in healthy volunteers on the Siemens scanner. Transmit/receive characteristics and SAR profiles will be simulated and experimentally verified. A comprehensive MRI protocol combining anatomical imaging (T1- and T2-weighted) with metabolic imaging using ²³Na and ²H will be optimized, establishing a critical foundation for translation to cancer patients.

3-Month Rotation Project:
Optimization of ²H imaging protocols in phantoms mimicking in vivo tissue parameters on the 9.4 T scanner, to support subsequent preclinical and clinical studies.

Representative Publications

Disrupting Na+ ion homeostasis and Na+/K+ ATPase activity in breast cancer cells directly modulates glycolysis in vitro and in vivo, Michaels AM, Zoccarato A, Hoare Z, Firth G, Chung YJ, Kuchel PW, Shah AM, Shattock MJ, Southworth R, Eykyn TR, (2024) Cancer Metab. https://doi.org/10.1186/s40170-024-00343-5.
Elevated Na is a dynamic and reversible modulator of mitochondrial metabolism in the heart: Intracellular Na reversibly alters myocardial metabolism and energetics, Chung YJ, Hoare Z, Baark F, Yu CS, Gun J, Fuller W, Southworth R, Katschinski DM, Murphy MP, Eykyn TR, Shattock MJ, (2024) Nat Commun. https://doi.org/10.1038/s41467-024-48474-z.
Multiple quantum nuclear magnetic resonance of 23Na+ ions dissolved in uniformly stretched and compressed hydrogels, Elliott SJ, Eykyn TR, Kuchel PW, (2023) J Chem Phys. https://doi.org/10.1063/5.0158608.
2: Nutritional Ketosis Increases NAD+/NADH Ratio in Healthy Human Brain: An in Vivo Study by 31P-MRS, Xin L, Ipek O, Beaumont M, Shevlyakova M, Christinat N, Masoodi M, Greenberg N, Gruetter R, Cuenoud B, (2018) Front Nutr. doi: 10.3389/fnut.2018.00062.
A Double-Quadrature Radiofrequency Coil Design for Proton-Decoupled Carbon-13 Magnetic Resonance Spectroscopy in Humans at 7T, Roig ES, Magill AW, Donati G, Meyerspeer M, Xin L, Ipek O, Gruetter R, (2015) Magn Reson Med. https://doi.org/10.1002/mrm.25171.
A combined 32-channel receive-loops/8-channel transmit-dipoles coil array for whole-brain MR imaging at 7T, Clément J, Gruetter R, Ipek O, (2019) Magn Reson Med. https://doi.org/10.1002/mrm.27808.