NMR with Hyperpolarized Spin Systems

The NMR signal in living tissue is fundamentally limited by the available thermal polarization of P ≈ 10^-6. Outside tissues, though, polarization levels can be manipulated to values of P ≈ 0.5 using hyperpolarization techniques, e.g. dynamic nuclear polarization (DNP), yielding a tremendous gain in NMR signal by about five orders of magnitude. Following the administration of substances carrying hyperpolarized spins, highest NMR signal is also exploitable in living tissue for the lifetime of polarized states (on the order of minutes), enabling NMR applications of unprecedented sensitivity.

One such application is metabolic MR using hyperpolarized ¹³C (see Figure): ¹³C-enriched, endogenous substrates (e.g. 1-¹³C-Pyruvate) are hyperpolarized and subsequently administered into living beings, where cellular metabolism 'transfers' the hyperpolarized ¹³C nuclei to other substances. As a consequence, the NMR signals of downstream metabolic products (e.g. 1-¹³C-Lactate) are also enhanced and become detectable. Utilizing dynamic ¹³C NMR techniques, each hyperpolarized metabolite can be identified by its individual ¹³C resonance frequency (chemical shift), and tracking the time course of hyperpolarized signals enables to quantify enzymatic activity (e.g. Lactate Dehydrogenase) in real time.
This way, the metabolic alterations of cancer tissues can be assessed, e.g., the increased activity of Lactate Dehydrogenase leading to an increased flux of Pyruvate to Lactate compared to healthy tissues. To realize assessment of cancer metabolism via hyperpolarized ¹³C also in humans, our research group currently establishes this cutting-edge technology using a SPINlab^TM DNP system for clinical application.