Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized ¹³C magnetic resonance.

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, <sup>13</sup> C magnetic resonance spectroscopy (MRS) allows following the fate of <sup>13</sup> C-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 <sup>13</sup> C MRS. In particular, the dynamic <sup>13</sup> C-labeling of pyruvate and lactate formed from <sup>13</sup> C-glucose was observed in real time. An ad-hoc synthesis to produce [2,3,4,6,6- <sup>2</sup> H <sub>5</sub> , 3,4- <sup>13</sup> C <sub>2</sub> ]-D-glucose was developed to improve the <sup>13</sup> C signal-to-noise ratio as compared to experiments performed following [U- <sup>2</sup> H <sub>7</sub> , U- <sup>13</sup> C]-D-glucose injections. The main advantage of only labeling C3 and C4 positions is the absence of <sup>13</sup> C- <sup>13</sup> C 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

Evolution of magnetic polarons and spin-carrier interactions through the metal-insulator transition in Eu1−x_{1-x}Gdx_{x}O

Raman scattering studies as functions of temperature, magnetic field, and Gd-substitution are used to investigate the evolution of magnetic polarons and spin-carrier interactions through the metal-insulator transition in Eu$_{1-x}$Gd$_{x}$O. These studies reveal a greater richness of phase behavior than have been previously observed using transport measurements: a spin-fluctuation-dominated paramagnetic (PM) phase regime for T $>$ T$^{*}$ $>$ T$_{C}$, a two-phase regime for T $<$ T$^{*}$ in which magnetic polarons develop and coexist with a remnant of the PM phase, and an inhomogeneous ferromagnetic phase regime for T $<$ T$_{C}$

Hyperpolarized ¹³C Magnetic Resonance Spectroscopy Reveals the Rate-Limiting Role of the Blood-Brain Barrier in the Cerebral Uptake and Metabolism of l-Lactate in Vivo.

The dynamics of l-lactate transport across the blood-brain barrier (BBB) and its cerebral metabolism are still subject to debate. We studied lactate uptake and intracellular metabolism in the mouse brain using hyperpolarized &lt;sup&gt;13&lt;/sup&gt; C magnetic resonance spectroscopy (MRS). Following the intravenous injection of hyperpolarized [1- &lt;sup&gt;13&lt;/sup&gt; C]lactate, we observed that the distribution of the &lt;sup&gt;13&lt;/sup&gt; C label between lactate and pyruvate, which has been shown to be representative of their pool size ratio, is different in NMRI and C57BL/6 mice, the latter exhibiting a higher level of cerebral lactate dehydrogenase A ( Ldha) expression. On the basis of this observation, and an additional set of experiments showing that the cerebral conversion of [1- &lt;sup&gt;13&lt;/sup&gt; C]lactate to [1- &lt;sup&gt;13&lt;/sup&gt; C]pyruvate increases after exposing the brain to ultrasound irradiation that reversibly opens the BBB, we concluded that lactate transport is rate-limited by the BBB, with a 30% increase in lactate uptake after its disruption. It was also deduced from these results that hyperpolarized &lt;sup&gt;13&lt;/sup&gt; C MRS can be used to detect a variation in cerebral lactate uptake of &lt;40 nmol in a healthy brain during an in vivo experiment lasting only 75 s, opening new opportunities to study the role of lactate in brain metabolism

Spin dependent scattering of a domain-wall of controlled size

Magnetoresistance measurements in the CPP geometry have been performed on single electrodeposited Co nanowires exchange biased on one side by a sputtered amorphous GdCo layer. This geometry allows the stabilization of a single domain wall in the Co wire, the thickness of which can be controlled by an external magnetic field. Comparing magnetization, resistivity, and magnetoresistance studies of single Co nanowires, of GdCo layers, and of the coupled system, gives evidence for an additional contribution to the magnetoresistance when the domain wall is compressed by a magnetic field. This contribution is interpreted as the spin dependent scattering within the domain wall when the wall thickness becomes smaller than the spin diffusion length.Comment: 9 pages, 13 figure

Quantifying normal human brain metabolism using hyperpolarized [1– 13 C]pyruvate and magnetic resonance imaging

Hyperpolarized 13 C Magnetic Resonance Imaging ( 13 C-MRI) provides a highly sensitive tool to probe tissue metabolism in vivo and has recently been translated into clinical studies. We report the cerebral metabolism of intravenously injected hyperpolarized [1– 13 C]pyruvate in the brain of healthy human volunteers for the first time. Dynamic acquisition of 13 C images demonstrated 13 C-labeling of both lactate and bicarbonate, catalyzed by cytosolic lactate dehydrogenase and mitochondrial pyruvate dehydrogenase respectively. This demonstrates that both enzymes can be probed in vivo in the presence of an intact blood-brain barrier: the measured apparent exchange rate constant (k PL ) for exchange of the hyperpolarized 13 C label between [1– 13 C]pyruvate and the endogenous lactate pool was 0.012 ± 0.006 s −1 and the apparent rate constant (k PB ) for the irreversible flux of [1– 13 C]pyruvate to [ 13 C]bicarbonate was 0.002 ± 0.002 s −1 . Imaging also revealed that [1– 13 C]pyruvate, [1– 13 C]lactate and [ 13 C]bicarbonate were significantly higher in gray matter compared to white matter. Imaging normal brain metabolism with hyperpolarized [1– 13 C]pyruvate and subsequent quantification, have important implications for interpreting pathological cerebral metabolism in future studies

Design and performance of a DNP prepolarizer coupled to a rodent MRI scanner

For most of the last forty years, the techniques of Dynamic Nuclear Polarization (DNP) have been confined to particle-physics laboratories building polarized targets, but recently it has been shown that samples similar to a solid target can be transformed into room temperature liquid solutions while retaining a high nuclear polarization. This method of "hyperpolarization" is of interest in NMR/MRI/MRS. We describe a 3.35 T DNP/9.4 T MRI installation based on a continuous-flow cryostat, using a standard wide-bore low-field NMR magnet as prepolarizer magnet and a widely available radical as polarizing agent. The interfacing to a rodent scanner requires that the infusion of the polarized solution in the animal be remotely controlled, because of limited access inside the magnet bore. Physiological constraints on the infusion rate can be a serious source of polarization loss, and the discussion of efficiency is therefore limited to that of the prepolarizer itself, i.e., the spin temperatures obtained in the solid state. To put our results in context, we summarize data obtained in targets with different types of radicals, and provide a short review of the DNP mechanisms needed in their discussion. (C) 2007 Wiley Periodicals, Inc

Heterogeneity and Strategic Choices: The Case of Stock Repurchases

Strategic decisions are fundamentally tough choices. Theory suggests that managers are likely to display bounded rationality. Empirics on the other hand assume rationality in choice behavior. Recognizing this inherent disconnect between theory and empirics, we try to account for behavioral biases using a theoretically consistent choice model. The traditional approach to modeling strategic choice has been to use discrete choice models and make inference on the conditional mean effects. We argue that the conditional mean effect does not capture behavioral biases. The focus should be on the conditional variance. Explicitly modeling the conditional variance (in the discrete choice framework) provides us with valuable information on individual level variation in decision-making. We demonstrate the effect of ignoring the role of variance in choice modeling in the context of firm’s decisions to conduct open market repurchases. We show that when taking into account the heterogeneity in choices, manager’s choices of conducting open market repurchases displays considerable heterogeneity and that not accounting for such heterogeneity might lead to wrong conclusions on the mean effects