Signal enhancement of hyperpolarized ¹⁵N sites in solution—increase in solid‐state polarization at 3.35 T and prolongation of relaxation in deuterated water mixtures

Abstract

Hyperpolarized 15 N sites have been found to be promising for generating long-lived hyperpolarized states in solution, and present a promising approach for utilizing dissolution-dynamic nuclear polarization (dDNP)-driven hyperpolarized MRI for imaging in biology and medicine. Specifically, 15 N sites with directly bound protons were shown to be useful when dissolved in D 2 O. The purpose of the current study was to further characterize and increase the visibility of such 15 N sites in solutions that mimic an intravenous injection during the first cardiac pass in terms of their H 2 O: D 2 O composition. The T 1 values of hyperpolarized 15 N in [ 15 N 2 ]urea and [ 15 N]NH 4 Cl demonstrated similar dependences on the H 2 O:D 2 O composition of the solution, with a T 1 of about 140 s in 100% D 2 O, about twofold shortening in 90% and 80% D 2 O, and about threefold shortening in 50% D 2 O. [ 13 C]urea was found to be a useful solid-state 13 C marker for qualitative monitoring of the 15 N polarization process in a commercial pre-clinical dDNP device. Adding trace amounts of Gd 3+ to the polarization formulation led to higher solid-state polarization of [ 13 C]urea and to higher polarization levels of [ 15 N 2 ]urea in solution.

Directly Bound Deuterons Increase X‐Nuclei Hyperpolarization using Dynamic Nuclear Polarization

“…The prolonged solid‐state T 1 s of the deuterated sites likely leads to favorable polarization buildup conditions. In our hands, other compounds with 13 C that were protonated and showed short T 1 s in solution (of the order of a few seconds) did not show significant buildup in the polarizer [13] . Such molecules were investigated as possible 13 C solid‐state markers for polarization of other X‐nuclei in the same polarizer and include, for example, [2‐ 13 C]glycerol and [ 13 C 3 ]glycerol [13] .…”

“…The process of 13 C polarization enhancement in the solid-state under dynamic nuclear polarization (DNP) conditions (< 40 K, in the presence of free radicals and microwave (MW) irradiation( consists of multiple mechanisms, the different contributions from which are condition and formulation dependent. [1] This means that the combination of the molecule bearing the 13 C nuclei, the vitrifying solution, the radical, the temperature, and the irradiation frequency are all part of this process, and each may affect the polarization buildup time, the T 1 in the solidstate, and the maximal polarization that may be achieved.…”

“…Previously, the factors influencing this process in several compounds and formulations involving 13 C hyperpolarization in the solid-state were characterized. [2] For biomedical applications, the utility of 13 C-labeled compounds for dissolution DNP (dDNP) studies is of interest.…”

“…Previously, the factors influencing this process in several compounds and formulations involving 13 C hyperpolarization in the solid-state were characterized. [2] For biomedical applications, the utility of 13 C-labeled compounds for dissolution DNP (dDNP) studies is of interest. The dDNP approach allows enhancement of the liquid-state polarization of 13 C sites by > 10,000 fold [1a] and thus allows monitoring of metabolic processes in biological preparations and in vivo in human subjects in real time.…”

“…[2] For biomedical applications, the utility of 13 C-labeled compounds for dissolution DNP (dDNP) studies is of interest. The dDNP approach allows enhancement of the liquid-state polarization of 13 C sites by > 10,000 fold [1a] and thus allows monitoring of metabolic processes in biological preparations and in vivo in human subjects in real time. [3] Specifically, studies have been focused on 13 C sites that are directly bound to deuterons (D), as a means to prolong the 13 C T 1 in solution, in sites that would otherwise (i. e., when protonated) be inaccessible to dDNP due to the fast decay of their hyperpolarized state in solution (a few seconds).…”