Singlet-Contrast Magnetic Resonance Imaging: Unlocking Hyperpolarization with Metabolism*.

Hyperpolarization-enhanced magnetic resonance imaging can be used to study biomolecular processes in the body, but typically requires nuclei such as 13 C, 15 N, or 129 Xe due to their long spin-polarization lifetimes and the absence of a proton-background signal from water and fat in the images. Here we present a novel type of 1 H imaging, in which hyperpolarized spin order is locked in a nonmagnetic long-lived correlated (singlet) state, and is only liberated for imaging by a specific biochemical reaction. In this work we produce hyperpolarized fumarate via chemical reaction of a precursor molecule with para-enriched hydrogen gas, and the proton singlet order in fumarate is released as antiphase NMR signals by enzymatic conversion to malate in D2 O. Using this model system we show two pulse sequences to rephase the NMR signals for imaging and suppress the background signals from water. The hyperpolarization-enhanced 1 H-imaging modality presented here can allow for hyperpolarized imaging without the need for low-abundance, low-sensitivity heteronuclei.

Role of the reaction intermediates in determining PHIP (parahydrogen induced polarization) effect in the hydrogenation of acetylene dicarboxylic acid with the complex [Rh (dppb)]+ (dppb: 1,4-bis(diphenylphosphino)butane).

This study deals with the parahydrogenation of the symmetric substrate acetylene dicarboxylic acid catalyzed by a Rh(I) complex bearing the chelating diphosphine dppb (1,4-bis(diphenylphosphino)butane). The two magnetically equivalent protons of the product yield a hyperpolarized emission signal in the (1)H-NMR spectrum. Their polarization intensity varies upon changing the reaction solvent from methanol to acetone. A detailed analysis of the hydrogenation pathway is carried out by means of density functional theory calculations to assess the structure of hydrogenation intermediates and their stability in the two solvents. The observed polarization effects have been accounted on the basis of the obtained structures. Insights into the lifetime of a short-lived reaction intermediate are also obtained.

Hyperpolarized agents for advanced MRI investigations.

The strong signal enhancement attainable by hyperpolarization methods has allowed the detection of heteronuclei in magnetic resonance imaging (MRI), allowing to obtain high quality images with very high signal to noise ratios in few seconds. The four methods to produce hyperpolarized molecules, i.e. the "brute force" approach, optical pumping of noble gases, parahydrogen induced polarization (PHIP) and dynamic nuclear polarization (DNP), are reported. The applications of hyperpolarized probes to MRI range from vascular imaging to interventional imaging and perfusion studies, up to the emerging and challenging field of molecular/metabolic imaging. In fact, the high signal intensities achievable by using hyperpolarized molecules make it possible to detect and image the metabolic products formed upon the administration of the hyperpolarized agent. The most striking examples are surveyed, including the use of hyperpolarized 13C-pyruvate in tumor diagnosis and stadiation, and in myocardium perfusion and activity studies, as well as the recently reported proposal of using 13C-bicarbonate as agent for pH-mapping in vivo.