Hyperpolarized singlet lifetimes of pyruvate in human blood and in the mouse

Abstract

Hyperpolarized NMR is a promising technique for non-invasive imaging of tissue metabolism in vivo. However, the pathways that can be studied are limited by the fast T1 decay of the nuclear spin order. In metabolites containing pairs of coupled nuclear spins-1/2, the spin order may be maintained by exploiting the non-magnetic singlet (spin-0) state of the pair. This may allow preservation of the hyperpolarization in vivo during transport to tissues of interest, such as tumors, or to detect slower metabolic reactions. We show here that in human blood and in a mouse in vivo at millitesla fields the 13C singlet lifetime of [1,2-13C2]pyruvate was significantly longer than the 13C T1, although it was shorter than the T1 at field strengths of several tesla. We also examine the singlet-derived NMR spectrum observed for hyperpolarized [1,2-13C2]lactate, originating from the metabolism of [1,2-13C2]pyruvate. © 2013 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.

Imaging of Extracellular pH Using Hyperpolarized Molecules

“…They form either a triplet or singlet nuclear spin state, with the lifetime of the singlet state being potentially much longer than T 1 , since it is not affected by dipolar relaxation mechanisms. Although long‐lived states cannot be directly observed by NMR, magnetization can be transferred from the triplet to the singlet state for storage and later on be recovered for the experiment by chemical reactions, specific pulse sequences or at low μ‐tesla magnetic fields ,. This concept has not yet been applied to pH‐sensitive molecules, but it was already used in vivo and could potentially increase the available signal intensity of hyperpolarized pH imaging molecules as well.…”

Optimizing dissolution dynamic nuclear polarization

“…The same issue also arises during the infusion of hyperpolarized molecules into the blood stream, during the time lag before reaching the targeted organs for in vivo applications, as well as during the signal acquisition. Multiple strategies have been explored and developed in the last years for minimizing losses of polarization, such as the use of fast fluid transfer devices [19], the rapid elimination of the free radicals [20][21][22], or the storage of hyperpolarization in the form of long-lived states (LLS) [23][24][25][26][27][28].…”

Expeditious dissolution dynamic nuclear polarization without glassing agents

“…The frozen sample, which settled to the bottom of the solution, was decanted and transferred to a Teflon sample cup using a spatula; the transfer (~3 s) also allowed the evaporation of any remaining isopentane. Complete evaporation of isopentane was confirmed by solution 13 C NMR measurements after polarization experiments.…”

“…Each sample was placed inside the cryostat and cooled to ≤1.2 K. Polarization of 13 C-labeled substrate at thermal equilibrium was measured after cooling for at least 5 h via an NMR coil in the cryostat (buildup of polarization was measured via small tip angle pulses to verify that thermal equilibrium was established). The sample was then hyperpolarized for 2 h via microwave irradiation (140.31 GHz for trityl-containing samples and 140.71 GHz for TEMPO-containing samples at~50 mW; Virginia Diodes Inc., Charlottesville, VA, USA) whilst monitoring polarization via 13 C NMR using a small tip angle pulse every 5 min.…”