Magnetic resonance (MR) is one of the most versatile and useful physical effects used for human imaging, chemical analysis, and the elucidation of molecular structures. However, its full potential is rarely used, because only a small fraction of the nuclear spin ensemble is polarized, that is, aligned with the applied static magnetic field. Hyperpolarization methods seek other means to increase the polarization and thus the MR signal. A unique source of pure spin order is the entangled singlet spin state of dihydrogen, parahydrogen (pH ), which is inherently stable and long-lived. When brought into contact with another molecule, this "spin order on demand" allows the MR signal to be enhanced by several orders of magnitude. Considerable progress has been made in the past decade in the area of pH -based hyperpolarization techniques for biomedical applications. It is the goal of this Review to provide a selective overview of these developments, covering the areas of spin physics, catalysis, instrumentation, preparation of the contrast agents, and applications.

We report a simple and effective method to remove IrIMes homogeneous polarization transfer catalysts from solutions where NMR Signal Amplification By Reversible Exchange (SABRE) has been performed, while leaving intact the substrate’s hyperpolarized state. Following microTesla SABRE hyperpolarization of 15N spins in metronidazole, addition of SiO2 microparticles functionalized with 3-mercaptopropyl or 2-mercaptoethyl ethyl sulfide moieties provides removal of the catalyst from solution well within the hyperpolarization decay time at 0.3 T (T1>3 mins)—and enabling transfer to 9.4 T for detection of enhanced 15N signals in the absence of catalyst within the NMR-detection region. Successful catalyst removal from solution is supported by the inability to “re-hyperpolarize” 15N spins in subsequent attempts, as well as by 1H NMR and ICP-MS. Record-high 15N nuclear polarization of up to ~34% was achieved, corresponding to >100,000-fold enhancement at 9.4 T, and approximately 5/6th of the 15N hyperpolarization is retained after ~20-second-long purification procedure. Taken together, these results help pave the way for future studies involving in vivo molecular imaging using agents hyperpolarized via rapid and inexpensive parahydrogen-based methods.

We compare diffusion activation energy measurements in a hydrated perfluorosulfonate ionomer and aqueous solutions of triflic acid. These measurements provide insight into water transport dynamics on sub-nm length scales, and gauge the contribution of the polymer sidechain terminal group. Future membrane materials design will hinge on detailed understanding of transport dynamics.

Optimization of micellar molecular encapsulation systems, such as drug delivery vehicles, can be achieved through fundamental understanding of block copolymer micelle structure and dynamics. Herein, we present a study of PEO−PCL block copolymer spherical micelles that self-assemble at 1% wt/vol in D 2 O−THF-d 8 mixtures. Varying solvent composition as a function of cosolvent THF-d 8 at constant polymer concentration (1% wt/vol) allows sensitive study of how small molecule additives influence micelle structure and dynamics. We conduct nuclear magnetic resonance spectroscopy and diffusometry on two block copolymer (2k series: PEO 2k −PCL 3k ; 5k series: PEO 5k −PCL 8k ) spherical micelles that show drastically different behaviors. Unimers and micelles coexist in solution from 10−60 vol % THF-d 8 for the 2k series but only coexist at 60 vol % THF-d 8 for the 5k series. At ≥ 60 vol % THF-d 8 micelles disassemble into free unimers for both series. We observe relatively flat micelle diffusion coefficients (∼1 × 10 −10 m 2 /s) with increasing THF-d 8 below 60 vol % for both 2k and 5k series, with only small changes in micelle hydrodynamic radius (≈14 nm) over this range. We compare these results to a detailed SANS and microscopy study described in a companion paper. These fundamental molecular dynamics, unimer population, and diffusion results, as a function of polymer composition and solution environment, provide critical fodder for controlled design of block copolymer self-assembly.