Brute-Force Hyperpolarization for NMR and MRI

Abstract

Hyperpolarization (HP) of nuclear spins is critical for ultrasensitive nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). We demonstrate an approach for >1500-fold enhancement of key small-molecule metabolites: 1-(13)C-pyruvic acid, 1-(13)C-sodium lactate, and 1-(13)C-acetic acid. The (13)C solution NMR signal of pyruvic acid was enhanced 1600-fold at B = 1 T and 40 °C by pre-polarizing at 14 T and ∼2.3 K. This "brute-force" approach uses only field and temperature to generate HP. The noted 1 T observation field is appropriate for benchtop NMR and near the typical 1.5 T of MRI, whereas high-field observation scales enhancement as 1/B. Our brute-force process ejects the frozen, solid sample from the low-T, high-B polarizer, passing it through low field (B < 100 G) to facilitate "thermal mixing". That equilibrates (1)H and (13)C in hundreds of milliseconds, providing (13)C HP from (1)H Boltzmann polarization attained at high B/T. The ejected sample arrives at a room-temperature, permanent magnet array, where rapid dissolution with 40 °C water yields HP solute. Transfer to a 1 T NMR system yields (13)C signals with enhancements at 80% of ideal for noted polarizing conditions. High-resolution NMR of the same product at 9.4 T had consistent enhancement plus resolution of (13)C shifts and J-couplings for pyruvic acid and its hydrate. Comparable HP was achieved with frozen aqueous lactate, plus notable enhancement of acetic acid, demonstrating broader applicability for small-molecule NMR and metabolic MRI. Brute-force avoids co-solvated free-radicals and microwaves that are essential to competing methods. Here, unadulterated samples obviate concerns about downstream purity and also exhibit slow solid-state spin relaxation, favorable for transporting HP samples.

Rapid-melt Dynamic Nuclear Polarization

“…For measurement, the sample was transferred to a field of 1 T and rapidly dissolved and measured at 40°C [22]. Although higher polarization can be obtained at higher fields and lower temperatures, there are also limitations to these approaches.…”

NMR Hyperpolarization Techniques of Gases

“…The development of SEOP is rooted in the pioneering work of Kastler, [31] who was recognized with the Nobel Prize in physics for demonstrating that electronic spin order can be created in alkali metal vapors using circularly polarized laser light. Later Bouchiat, Carver, and Varnum [32] showed that the addition of 3 He to the gas mixture permitted helium nuclear spins to be polarized by spin-exchange collisions with the optically pumped alkali vapor atoms-work that was extended to 129 Xe by Grover. [33] The rich physics of SEOP has been extensively explored by Happer, Cates, Chupp, Walker, and many others (e.g.…”

“…Although the vast majority of SEOP experiments have employed the spin I=1/2 noble gas isotopes 129 Xe and 3 He, the quadrupolar species 21 Ne (I=3/2), [36] 83 Kr (I=9/2), [37] and 131 Xe [38] (I=3/2) can also be polarized via this method. For the alkali metal vapor, Rb is most-commonly employed for practical reasons-including its low melting point [39] (facilitating vaporization) and the availability of high-powered lasers resonant with its D1 transition [40] ; however, K and Cs are also utilized (particularly for 3 He [41] and 129 Xe, [42] respectively).…”

“…For the alkali metal vapor, Rb is most-commonly employed for practical reasons-including its low melting point [39] (facilitating vaporization) and the availability of high-powered lasers resonant with its D1 transition [40] ; however, K and Cs are also utilized (particularly for 3 He [41] and 129 Xe, [42] respectively). Technological developments for SEOP have been extensively reviewed elsewhere, [35] and only a brief description is given here.…”

“…[1] This process of significant polarization enhancement-well above that achieved at thermal equilibrium-is termed hyperpolarization. Hyperpolarization of solids, liquids, and gases [2] has been demonstrated via a number of techniques including Brute Force Polarization (BFP), [3] Spin Exchange Optical Pumping (SEOP), [4] Dynamic Nuclear Polarization (DNP), [1c] Chemically-Induced Dynamic Nuclear Polarization (CIDNP) [5] photo-CIDNP, [6] Parahydrogen Induced Polarization (PHIP), [7] and Signal Amplification By Reversible Exchange (SABRE). [8] .…”