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: 1-¹³C-pyruvic acid, 1-¹³C-sodium lactate, and 1-¹³C-acetic acid. The ¹³C solution NMR signal of pyruvic acid was enhanced 1600-fold at <i>B</i> = 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/<i>B</i>. Our brute-force process ejects the frozen, solid sample from the low-<i>T</i>, high-<i>B</i> polarizer, passing it through low field (<i>B</i> < 100 G) to facilitate “thermal mixing”. That equilibrates ¹H and ¹³C in hundreds of milliseconds, providing ¹³C HP from ¹H Boltzmann polarization attained at high <i>B</i>/<i>T</i>. 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 ¹³C 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 ¹³C shifts and <i>J</i>-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