Hyperpolarized ¹⁵N caffeine, a potential probe of liver function and perfusion

Area of Science:

• Nuclear Magnetic Resonance (NMR) Spectroscopy
• Medical Imaging
• Pharmacology

Background:

• Hyperpolarization techniques significantly enhance NMR signal sensitivity.
• Caffeine, a widely consumed substance, has potential applications in medical imaging.
• Developing novel probes for liver function and perfusion assessment is crucial in diagnostics.

Purpose of the Study:

• To demonstrate the hyperpolarization of 15N-caffeine.
• To explore its potential as a probe for liver function and perfusion.
• To investigate the feasibility of using hyperpolarized 15N-caffeine in preclinical settings.

Main Methods:

• Amorphous [1,3-15N2]caffeine formulation for dissolution dynamic nuclear polarization.
• Augmented polarizer hardware for solid-state 15N MR signal monitoring.
• Liquid-state hyperpolarized 15N MR signal acquisition using a preclinical 3T magnet and custom RF coils.
• Estimation of 15N signal decay constants in vitro and in vivo (liver, brain) in rats at 3T and 9.4T.
• Assessment of protein binding effects using albumin.

Main Results:

• Achieved 3.5% polarization and ~200s T1 relaxation times for 15N-caffeine at 3T.
• Observed in vivo decay constants of 25-43s, with potential extension via competitive albumin binding.
• Failed to detect downstream caffeine metabolites in vivo in the liver, even with metabolic stimulation.
• Demonstrated signal persistence in the brain, suggesting potential as a perfusion agent due to high brain perfusion rates.

Conclusions:

• Successfully demonstrated the feasibility of hyperpolarizing 15N-caffeine.
• Further investigation is required to establish its role in probing liver metabolism.
• Exploratory findings suggest potential for 15N-caffeine as a perfusion imaging agent, particularly for brain.