Dynamic, multiphase magnetic resonance imaging of in vivo physiological processes with long-lived hyperpolarized 15N,d9-betaine

Hyperpolarized magnetic resonance imaging (HypMRI) offers valuable insights into dynamic physiological processes in vivo. However, the short signal lifetime of hyperpolarized ¹³C-labeled compounds commonly used in HypMRI studies restricts investigations to fast molecular reactions and rapid distributions. Here, we introduce hyperpolarized ¹⁵N,d₉-betaine (trimethyl-²H₉-¹⁵N-glycine) as an endogenous MRI contrast agent with a long-lived signal suited for comprehensive molecular tracking. With in vivo detectability exceeding 14 minutes and high polarization efficiency, ¹⁵N,d₉-betaine supports both real-time and delayed-phase MRI from a single dose, enabling flexible, multistage imaging. In preclinical models, renal ¹⁵N,d₉-betaine images were acquired with strong signal-to-noise ratios across resolutions. This extended imaging window facilitates tracking molecular distribution, assessing tissue perfusion, and monitoring cellular uptake relevant to betaine’s roles in cellular protection. By extending MRI capabilities across timescales, hyperpolarized ¹⁵N,d₉-betaine holds promise for applications like organ function assessment, disease monitoring, and real-time evaluation of therapeutic interventions, advancing noninvasive molecular imaging.