Hyperpolarized substrates prepared via dissolution dynamic nuclear polarization have been proposed as magnetic resonance imaging (MRI) agents for cancer or cardiac failure diagnosis and therapy monitoring through the detection of metabolic impairments in vivo. The use of potentially toxic persistent radicals to hyperpolarize substrates was hitherto required. We demonstrate that by shining UV light for an hour on a frozen pure endogenous substance, namely the glucose metabolic product pyruvic acid, it is possible to generate a concentration of photo-induced radicals that is large enough to highly enhance the 13 C polarization of the substance via dynamic nuclear polarization. These radicals recombine upon dissolution and a solution composed of purely endogenous products is obtained for performing in vivo metabolic hyperpolarized 13 C MRI with high spatial resolution. Our method opens the way to safe and straightforward preclinical and clinical applications of hyperpolarized MRI because the filtering procedure mandatory for clinical applications and the associated pharmacological tests necessary to prevent contamination are eliminated, concurrently allowing a decrease in the delay between preparation and injection of the imaging agents for improved in vivo sensitivity.is a very powerful imaging modality in terms of temporal and spatial resolution of anatomical structures. The modality is widespread, well established in clinical environments, and paramagnetic agents are used extensively for enhanced contrast or perfusion examination. MR is also a unique technique to obtain in vivo metabolic maps using the spectroscopic information that can be extracted from the time-domain acquisitions. In particular, it is possible to monitor the biochemical transformations of specific substrates that are delivered to subjects. Because it gives access to the kinetics of the conversion of substrates into metabolites, MR spectroscopy (MRS) of the carbon nuclei ( 13 C) is one of the most powerful techniques to investigate intermediary metabolism (1).The well-known weakness of MR as a spectroscopic technique is its relatively low sensitivity. It can be offset by so-called hyperpolarization methods, in particular the one based on dynamic nuclear polarization (DNP) (2), which is now commonly referred to as dissolution DNP and was first proposed about a decade ago (3). The hyperpolarized substrates obtained following dissolution DNP are biomolecules in aqueous solution with a largely out-ofequilibrium nuclear spin polarization corresponding to an enhancement of several orders of magnitude compared with the thermal equilibrium polarization attainable in MRI scanners. A basic requirement for DNP is the presence of unpaired electron spins in the sample to be hyperpolarized. These polarizing agents are usually incorporated in the form of persistent radicals. An inherent limit of any hyperpolarization method is that the intrinsic longitudinal nuclear spin relaxation will annihilate the polarization enhancement in the course of time to reach t...

Multidimensional acquisitions play a central role in the progress and applications of nuclear magnetic resonance (NMR) spectroscopy. Such experiments have been collected traditionally as an array of one-dimensional scans, with suitably incremented delay parameters that encode along independent temporal domains the nD spectral distribution being sought. During the past few years, an ultrafast approach to nD NMR has been introduced that is capable of delivering any type of multidimensional spectrum in a single transient. This method operates by departing from the canonical nD NMR scheme and by replacing its temporal encoding with a series of spatial manipulations derived from magnetic resonance imaging. The present survey introduces the main principles of this subsecond approach to spectroscopy, focusing on the applications that have hitherto been demonstrated for single-scan two-dimensional NMR in different areas of chemistry.

The mammalian brain relies primarily on glucose as a fuel to meet its high metabolic demand. Among the various techniques used to study cerebral metabolism, 13C magnetic resonance spectroscopy (MRS) allows following the fate of 13C-enriched substrates through metabolic pathways. We herein demonstrate that it is possible to measure cerebral glucose metabolism in vivo with sub-second time resolution using hyperpolarized 13C MRS. In particular, the dynamic 13C-labeling of pyruvate and lactate formed from 13C-glucose was observed in real time. An ad-hoc synthesis to produce [2,3,4,6,6-2H5, 3,4-13C2]-D-glucose was developed to improve the 13C signal-to-noise ratio as compared to experiments performed following [U-2H7, U-13C]-D-glucose injections. The main advantage of only labeling C3 and C4 positions is the absence of 13C-13C coupling in all downstream metabolic products after glucose is split into 3-carbon intermediates by aldolase. This unique method allows direct detection of glycolysis in vivo in the healthy brain in a noninvasive manner.

An approach enabling the acquisition of 2D nuclear magnetic resonance (NMR) spectra within a single scan has been recently proposed. A promising application opened up by this "ultrafast" data acquisition format concerns the monitoring of chemical transformations as they happen, in real time. The present paper illustrates some of this potential with two examples: (i) following an H/D exchange process that occurs upon dissolving a protonated protein in D2O, and (ii) real-time in situ tracking of a transient Meisenheimer complex that forms upon rapidly mixing two organic reactants inside the NMR observation tube. The first of these measurements involved acquiring a train of 2D 1H-15N HSQC NMR spectra separated by ca. 4 s; following an initial dead time, this allowed us to monitor the kinetics of hydrogen exchange in ubiquitin at a site-resolved level. The second approach enabled us to observe, within ca. 2 s after the triggering of the reaction, a competition between thermodynamic and kinetic controls via changes in a series of 2D TOCSY patterns. The real-time dynamic experiments hereby introduced thus add to an increasing family of fast characterization techniques based on 2D NMR; their potential and limitations are briefly discussed.