title: 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.
authors.affiliation: †Bruker Biospin Corp., Billerica, Massachusetts 01821, United States.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Hirsch
authors.affiliation: ‡Millikelvin Technologies, LLC, Braintree, Massachusetts 02184, United States.
authors.forename: Neal
authors.initials: N
authors.lastname: Kalechofsky
authors.affiliation: ‡Millikelvin Technologies, LLC, Braintree, Massachusetts 02184, United States.
authors.forename: Avrum
authors.initials: A
authors.lastname: Belzer
authors.affiliation: †Bruker Biospin Corp., Billerica, Massachusetts 01821, United States.
authors.forename: Melanie
authors.initials: M
authors.lastname: Rosay
authors.affiliation: †Bruker Biospin Corp., Billerica, Massachusetts 01821, United States.
authors.forename: James G
authors.initials: JG
authors.lastname: Kempf
mesh_terms: D019342:Acetic Acid / Q000737:chemistry*; D002247:Carbon Isotopes / Q000737:chemistry; D004867:Equipment Design; D005609:Free Radicals; D007773:Lactates / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008872:Microwaves; D015233:Models, Statistical; D010100:Oxygen / Q000737:chemistry; D011522:Protons; D019289:Pyruvic Acid / Q000737:chemistry*; D019354:Sodium Lactate / Q000737:chemistry*; D013696:Temperature; D014867:Water / Q000737:chemistry
chemical_list: D002247:Carbon Isotopes; D005609:Free Radicals; D007773:Lactates; D011522:Protons; D014867:Water; D019289:Pyruvic Acid; D019342:Acetic Acid; D010100:Oxygen; D019354:Sodium Lactate