Functional activation of pyruvate dehydrogenase in human brain using hyperpolarized [1- C]pyruvate.

Purpose: Pyruvate, produced from either glucose, glycogen, or lactate, is the dominant precursor of cerebral oxidative metabolism. Pyruvate dehydrogenase (PDH) flux is a direct measure of cerebral mitochondrial function and metabolism. Detection of [ C]bicarbonate in the brain from hyperpolarized [1- C]pyruvate using carbon-13 ( C) MRI provides a unique opportunity for assessing PDH flux in vivo.

Dual-phase imaging of cardiac metabolism using hyperpolarized pyruvate.

Purpose: Previous cardiac imaging studies using hyperpolarized (HP) [1- C]pyruvate were acquired at end-diastole (ED). Little is known about the interaction between cardiac cycle and metabolite content in the myocardium. In this study, we compared images of HP pyruvate and products at end-systole (ES) and ED.

Esterase-Catalyzed Production of Hyperpolarized C-Enriched Carbon Dioxide in Tissues for Measuring pH.

C Magnetic resonance imaging of hyperpolarized (HP) C-enriched bicarbonate (HCO) and carbon dioxide (CO) is a novel and sensitive technique for tissue pH mapping in vivo. Administration of the HP physiological buffer pair is attractive, but poor polarization and the short T of C-enriched inorganic bicarbonate salts are major drawbacks for this approach. Here, we report a new class of mixed anhydrides for esterase-catalyzed production of highly polarized CO and HCO in tissue.

Hyperpolarized δ-[1- C]gluconolactone as a probe of the pentose phosphate pathway.

The pentose phosphate pathway (PPP) is thought to be upregulated in trauma (to produce excess NADPH) and in cancer (to provide ribose for nucleotide biosynthesis), but simple methods for detecting changes in flux through this pathway are not available. MRI of hyperpolarized C-enriched metabolites offers considerable potential as a rapid, non-invasive tool for detecting changes in metabolic fluxes. In this study, hyperpolarized δ-[1- C]gluconolactone was used as a probe to detect flux through the oxidative portion of the pentose phosphate pathway (PPP ) in isolated perfused mouse livers.

MR Neurography of Brachial Plexus at 3.0 T with Robust Fat and Blood Suppression.

Purpose To develop and evaluate magnetic resonance (MR) neurography of the brachial plexus with robust fat and blood suppression for increased conspicuity of nerves at 3.0 T in clinically feasible acquisition times. Materials and Methods This prospective study was HIPAA compliant, with institutional review board approval and written informed consent.

Simultaneous steady-state and dynamic 13C NMR can differentiate alternative routes of pyruvate metabolism in living cancer cells.

Metabolic reprogramming facilitates cancer cell growth, so quantitative metabolic flux measurements could produce useful biomarkers. However, current methods to analyze flux in vivo provide either a steady-state overview of relative activities (infusion of (13)C and analysis of extracted metabolites) or a dynamic view of a few reactions (hyperpolarized (13)C spectroscopy). Moreover, although hyperpolarization has successfully quantified pyruvate-lactate exchanges, its ability to assess mitochondrial pyruvate metabolism is unproven in cancer.

Comparison of kinetic models for analysis of pyruvate-to-lactate exchange by hyperpolarized 13 C NMR.

The activity of specific enzyme-catalyzed reactions may be detected in vivo by (13) C NMR of hyperpolarized (HP) substrates. The signals from HP substrates and products, acquired over time, have been fitted to a number of different mathematical models to determine fluxes, but these models have not been critically compared. In this study, two-pool and three-pool first-order models were constructed to measure flux through lactate dehydrogenase in isolated glioblastoma cells by NMR detection of lactate and pyruvate following the addition of HP [1-(13) C]pyruvate.

Flux through hepatic pyruvate carboxylase and phosphoenolpyruvate carboxykinase detected by hyperpolarized 13C magnetic resonance.

In the heart, detection of hyperpolarized [(13)C]bicarbonate and (13)CO(2) by magnetic resonance (MR) after administration of hyperpolarized [1-(13)C]pyruvate is caused exclusively by oxidative decarboxylation of pyruvate via the pyruvate dehydrogenase complex (PDH). However, liver mitochondria possess alternative anabolic pathways accessible by [1-(13)C]pyruvate, which may allow a wider diagnostic range for hyperpolarized MR compared with other tissue. Metabolism of hyperpolarized [1-(13)C]pyruvate in the tricarboxylic acid (TCA) cycle was monitored in the isolated perfused liver from fed and fasted mice.

Transfer of hyperpolarization from long T1 storage nuclei to short T1 neighbors using FLOPSY-8.

Nuclei with long T1s are optimal targets for dynamic nuclear polarization (DNP). Therefore, most of the agents used in metabolic imaging and spectroscopy studies are based on carboxylic acid moieties that lack protons, a strong source of dipolar relaxation. Metabolic flux information encoded into spectra of small molecule metabolites in the form of the 13C isotopomer data cannot be accessed using standard 13C hyperpolarization methods because protonated carbons relax too quickly through T1 dipolar relaxation.

Inhibition of carbohydrate oxidation during the first minute of reperfusion after brief ischemia: NMR detection of hyperpolarized 13CO2 and H13CO3-.

Isolated rat hearts were studied by (31)P NMR and (13)C NMR. Hyperpolarized [1-(13)C]pyruvate was supplied to control normoxic hearts and production of [1-(13)C]lactate, [1-(13)C]alanine, (13)CO(2) and H(13)CO(-) (3) was monitored with 1-s temporal resolution. Hearts were also subjected to 10 min of global ischemia followed by reperfusion.

Hyperpolarized 13C allows a direct measure of flux through a single enzyme-catalyzed step by NMR.

(13)C NMR is a powerful tool for monitoring metabolic fluxes in vivo. The recent availability of automated dynamic nuclear polarization equipment for hyperpolarizing (13)C nuclei now offers the potential to measure metabolic fluxes through select enzyme-catalyzed steps with substantially improved sensitivity. Here, we investigated the metabolism of hyperpolarized [1-(13)C(1)]pyruvate in a widely used model for physiology and pharmacology, the perfused rat heart.

Dipolar cross-relaxation modulates signal amplitudes in the (1)H NMR spectrum of hyperpolarized [(13)C]formate.

The asymmetry in the doublet of a spin coupled to hyperpolarized (13)C has been used previously to measure the initial polarization of (13)C. We tested the hypothesis that a single observation of the (1)H NMR spectrum of hyperpolarized (13)C formate monitors (13)C polarization. Depending on the microwave frequency during the polarization process, in-phase or out-of-phase doublets were observed in the (1)H NMR spectrum.

Hyperpolarized (89)Y offers the potential of direct imaging of metal ions in biological systems by magnetic resonance.

Hyperpolarization of YCl and three Y-complexes was achieved by dynamic nuclear polarization of aqueous samples. The long T’s of Y make its application as an MR imaging probe extremely promising. In addition, the wide chemical shift range for various chelates of Y means that agents sensitive to their biological/chemical milieu could serve as exquisite sensors of important biological events.