Skre Ingeborg S, Karlsson Magnus, Sánchez-Heredia Juan Diego, Olin Rie B, Lerche Mathilde H
Center for Hyperpolarization in Magnetic Resonance, Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark.
Technical University of Cartagena (UPCT), Cartagena, Spain.
Sci Adv. 2025 Jul 4;11(27):eadx8417. doi: 10.1126/sciadv.adx8417. Epub 2025 Jul 2.
Hyperpolarized magnetic resonance imaging (HypMRI) offers valuable insights into dynamic physiological processes in vivo. However, the short signal lifetime of hyperpolarized C-labeled compounds commonly used in HypMRI studies restricts investigations to fast molecular reactions and rapid distributions. Here, we introduce hyperpolarized N,d-betaine (trimethyl-H-N-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, N,d-betaine supports both real-time and delayed-phase MRI from a single dose, enabling flexible, multistage imaging. In preclinical models, renal N,d-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 N,d-betaine holds promise for applications like organ function assessment, disease monitoring, and real-time evaluation of therapeutic interventions, advancing noninvasive molecular imaging.
超极化磁共振成像(HypMRI)为体内动态生理过程提供了有价值的见解。然而,HypMRI研究中常用的超极化碳标记化合物的短信号寿命限制了对快速分子反应和快速分布的研究。在此,我们引入超极化N,d-甜菜碱(三甲基-H-N-甘氨酸)作为一种内源性MRI造影剂,其具有适合全面分子追踪的长寿命信号。N,d-甜菜碱的体内可检测性超过14分钟且极化效率高,单次给药即可支持实时和延迟期MRI,实现灵活的多阶段成像。在临床前模型中,在不同分辨率下均以高信噪比采集了肾脏N,d-甜菜碱图像。这个扩展的成像窗口有助于追踪分子分布、评估组织灌注以及监测与甜菜碱在细胞保护中的作用相关的细胞摄取。通过跨时间尺度扩展MRI能力,超极化N,d-甜菜碱在器官功能评估、疾病监测和治疗干预实时评估等应用方面具有潜力,推动了无创分子成像的发展。