Translation of hyperpolarized [(13)C,(15)N(2)]urea MRI for novel human brain perfusion studies

超极化[(13)C,(15)N(2)]尿素MRI在新型人脑灌注研究中的应用

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Abstract

This study developed a new approach to produce sterile, hyperpolarized [(13)C,(15)N(2)]urea as a novel molecular imaging probe and applied it for first-ever healthy brain volunteer studies. Hyperpolarized [(13)C,(15)N(2)]urea, as a small, metabolically inert molecule, offers significant advantages for perfusion imaging due to its endogenous nature and excellent safety profile. The developed methods achieved a hyperpolarized [(13)C,(15)N(2)]urea solution (132 ± 6 mM) with 27.4 ± 5.6% polarization and a T(1) = 50.4 ± 0.2 s. In healthy brain volunteer studies, high-resolution (13)C imaging captured blood flow with a spatial resolution of 7.76 × 7.76 × 15 (or 10) mm(3) over ~1 min following hyperpolarized [(13)C,(15)N(2)]urea injection, visualizing detailed vascular structures. Time-to-peak and centroid analyses showed consistent arterial and venous signal patterns across subjects. Findings suggest hyperpolarized [(13)C,(15)N(2)]urea may have applications beyond brain imaging, including the non-invasive perfusion assessment in various organs, cancer microenvironment, and renal function, paving the way for clinical translation.

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