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 13C 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 13C 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.
12 August 2010 in Angewandte Chemie International Edition
The Krebs (or tricarboxylic acid (TCA)) cycle has a central role in the regulation of brain energy regulation and metabolism, yet brain TCA cycle intermediates have never been directly detected in vivo. This study reports the first direct in vivo observation of a TCA cycle intermediate in intact brain, namely, 2-oxoglutarate, a key biomolecule connecting metabolism to neuronal activity. Our observation reveals important information about in vivo biochemical processes hitherto considered undetectable. In particular, it provides direct evidence that transport across the inner mitochondria membrane is rate limiting in the brain. The hyperpolarized magnetic resonance protocol designed for this study opens the way to direct and real-time studies of TCA cycle kinetics.
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.