Hyperpolarized NMR Spectroscopy: d‐DNP, PHIP, and SABRE Techniques

Abstract

The intensity of NMR signals can be enhanced by several orders of magnitude by using various techniques for the hyperpolarization of different molecules. Such approaches can overcome the main sensitivity challenges facing modern NMR/magnetic resonance imaging (MRI) techniques, whilst hyperpolarized fluids can also be used in a variety of applications in material science and biomedicine. This Focus Review considers the fundamentals of the preparation of hyperpolarized liquids and gases by using dissolution dynamic nuclear polarization (d-DNP) and parahydrogen-based techniques, such as signal amplification by reversible exchange (SABRE) and parahydrogen-induced polarization (PHIP), in both heterogeneous and homogeneous processes. The various new aspects in the formation and utilization of hyperpolarized fluids, along with the possibility of observing NMR signal enhancement, are described.

15N Hyperpolarization of Dalfampridine at Natural Abundance for Magnetic Resonance Imaging

“…[2,3] This drug is approved by the regulating agencies in the US, Canada, and Europe, andi ti sm arketed as Ampyraa nd Fampyra.T he distribution of the drug inside the body,t he biochemicalpathways of its transformation,aswellasits metabolic profile are important information for determining the effectivenesso ft he drug. [7][8][9][10][11] Parahydrogen servesa sasourceo fh yperpolarization in this method, and two SABRE approaches have been developed. [4] This is due to the fact that populationdifferenceo fn uclear spin states (termed nuclear spin polarization P)i ss mall.…”

“…The directu se of at hermally polarized signal of 15 Nn uclei for in vivo MRI applicationsi sv ery challenging because of the very low natural abundance of the 15 Ni sotope (0.365 %) and the lowerg yromagnetic ratio of 15 Nn uclei compared to 1 H ( % 1:10), resulting in low detection sensitivity.Asaresult, alimited number of 15 NM RI studies with non-isotopically enriched molecules were reported to date. [7][8][9][10][11] Parahydrogen servesa sasourceo fh yperpolarization in this method, and two SABRE approaches have been developed. [7][8][9][10][11] Parahydrogen servesa sasourceo fh yperpolarization in this method, and two SABRE approaches have been developed.…”

Front Cover: Simulating Non‐linear Chemical and Physical (CAP) Dynamics of Signal Amplification By Reversible Exchange (SABRE) (Chem. Eur. J. 32/2019)

“…We simulated the relaxation kinetics of af ree 15 Ns ubstrate by using Equation (13) with the following parameters:t he values of T 1 for the bound substrates, substrates in solution and hydride protons were 10, 60 and1s, respectively (see Tables S1-S4 in the Supporting Information), k d = 50 s À1 , k a = 1000 m À1 s À1 , k ex = 200 m À1 s À1 , W out = 10 s À1 ,H 2 ½ = 50 mm, f pH 2 = 25 %a nd S 0 ½ = 100 mm for three different concentrations of Ir 0 ½ :3 0, 10 and 1mm.T he para enrichment fraction f pH2 of 25 %m eans that hydrogen gas at room temperature thermal equilibrium was supplied to the system;t hus, no pH 2 -induced hyperpolarization occurred. The relaxation was investigated at two different static magnetic fields: B = 1Tand 1 mT ( Figure 3).…”

“…In this work we calculated the 15 Np olarizationo ft he free substrate as af unction of H 2 ½ and k ex ( Figure 7A)a nd H 2 ½ and W out ( Figure 7B). We found that the polarization level can be strongly improvedb yi ncreasing the rate of H 2 exchange with the transient complex, that is, the product H 2 ½ k ex [ Figure 7A,r eaction (3)].…”

“…The hyperpolarization (HP) of nuclear spins promises to revolutionize medical diagnostics [1][2][3][4][5][6][7][8][9][10] and chemical analysis [11][12][13][14][15] alike. Amongo thers, signal amplification by reversible exchange (SABRE), discovered in 2008, [16] is an up-and-coming technique with unique properties,i ncluding continuous hyperpolarization.…”