Brute-Force
Hyperpolarization for NMR and MRI
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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-<sup>13</sup>C-pyruvic acid, 1-<sup>13</sup>C-sodium
lactate, and 1-<sup>13</sup>C-acetic acid. The <sup>13</sup>C 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 <sup>1</sup>H and <sup>13</sup>C in hundreds of
milliseconds, providing <sup>13</sup>C HP from <sup>1</sup>H 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 <sup>13</sup>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 <sup>13</sup>C 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