Lactate in the brain has long been associated with ischaemia; however, more recent evidence shows that it can be found there under physiological conditions. In the brain, lactate is formed predominantly in astrocytes from glucose or glycogen in response to neuronal activity signals. Thus, neurons and astrocytes show tight metabolic coupling. Lactate is transferred from astrocytes to neurons to match the neuronal energetic needs, and to provide signals that modulate neuronal functions, including excitability, plasticity and memory consolidation. In addition, lactate affects several homeostatic functions. Overall, lactate ensures adequate energy supply, modulates neuronal excitability levels and regulates adaptive functions in order to set the 'homeostatic tone' of the nervous system.

A bacterial strain of Acinetobacter sp., which was capable of enzymatic production of pyruvate from lactate, was cultured in a 5-l reactor with a basal salt medium. After 14 h of fed-batch fermentation, 9.56 g l(-1) cell concentration in the broth was obtained with 20 g l(-1) (178 mM) sodium lactate and 4 g l(-1) NH(4)Cl in the medium; and the biotransformation ability was 2.51 units ml(-1). The cells were harvested from one reactor and then used for pyruvate production from lactate in the same reactor. l-lactate at a concentration about 527 mM was almost stoichiometrically converted to pyruvate in 28 h. After a total 42 h of cell culture and biotransformation, the transformative yield was about 0.72 g g(-1) pyruvate from lactate and the rate of pyruvate production was calculated as 1.33 g l(-1) h(-1) during the process. The results suggested this simple enzymatic production of pyruvate from lactate should be a promising process and may bring a yield higher than that by microbial fermentation. By this process, the recovery of pyruvate from such a simple reaction liquid is relatively easy and inexpensive to perform.

To characterize the variation in plasma lactate concentration among samples from commonly used blood sampling sites in conscious, healthy dogs.60 healthy dogs.Cross-sectional study using a replicated Latin square design. Each dog was assigned to 1 of 6 groups (n = 10) representing all possible orders for 3 sites (cephalic vein, jugular vein, and femoral artery) used to obtain blood. Samples were analyzed immediately, by use of direct amperometry for pH, PO2, Pco2, glucose, and lactate concentration.Significant differences in plasma lactate concentrations were detected among blood samples from the cephalic vein (highest), femoral artery, and jugular vein (lowest). Mean plasma lactate concentration in the first sample obtained, irrespective of sampling site, was lower than in subsequent samples. Covariation was identified among plasma lactate concentration, pH, and PCO2, but correlation coefficients were low.Plasma lactate concentrations differed among blood samples from various sites. A reference range for plasma lactate concentration was 0.3 to 2.5 mmol/L. Differences in plasma lactate concentrations among samples from various sites and with repeated sampling, in healthy dogs, are small. Use of the reference range may facilitate the clinical use of plasma lactate concentration in dogs.

H-MRS is a non-invasive technique used to assess the metabolic activity of brain tumors. The technique is useful for the preoperative prediction of tumor grade, which is important for treatment planning and accurate prognosis. We used H-MRS to study the lactate peak, which appears in various conditions, including hyperglycemia, ischemia, and hypoxia and lipid peak, which is associated with necrotic cells. The purpose of this study was to retrospectively examine the frequency and significance of lactate and lipid peaks in relation to brain tumor grade.Fifty-five patients diagnosed with neuroepithelial tumors of Grades I (3 cases), II (11 cases), III (15 cases), and IV (26 cases) were enrolled. Biopsies were excluded. Single voxel (TE = 144 ms) point resolved H-MRS spectroscopy sequences were retrospectively analyzed. An inverted doublet peak at 1.3 ppm was defined as lactate, a negative and positive peak was defined as combined lactate and lipid, and a clear upward peak was defined as lipid.Lactate peaks were detected in all grades of brain tumors and were least common in Grade II tumors (9.1%). The frequency of combined lactate-lipid peaks was 0% (Grades I and II), 8.3% (Grade III), and 44% (Grade IV). Grade IV tumors were significantly different to the other grades. There were three cases with a lipid peak. All were glioblastoma.The presence of a lac peak may be useful to largely rule out the Grade II tumors, and allow the subsequent differentiation of Grade I tumors from Grade III or IV tumors by conventional imaging. The presence of a lipid peak may be associated with Grade IV tumors.

To compare correlations of intramyocellular lipids (IMCL) measured by short and long echo-time proton magnetic resonance spectroscopy (1H-MRS) with indices of body composition and insulin resistance in obese and normal-weight women.We quantified IMCL of tibialis anterior (TA) and soleus (SOL) muscles in 52 premenopausal women (37 obese and 15 normal weight) using single-voxel 1H-MRS PRESS at 3.0 T with short (30 msec) and long (144 msec) echo times. Statistical analyses were performed to determine correlations of IMCL with body composition as determined by computed tomography (CT) and insulin resistance indices and to compare correlation coefficients from short and long echo-time data. Signal-to-noise ratio (SNR), linewidth, and coefficients of variation (CV) of short and long echo-time spectra were calculated.Short and long echo-time IMCL from TA and SOL significantly correlated with body mass index (BMI) and abdominal fat depots (r = 0.32 to 0.70, P = <0.05), liver density (r = -0.39 to -0.50, P < 0.05), and glucose area under the curve as a measure of insulin resistance (r = 0.47 to 0.49, P < 0.05). There was no significant difference between correlation coefficients of short and long echo-time spectra (P > 0.5). Short echo-time IMCL in both muscles showed significantly higher SNR (P < 0.0001) and lower CVs when compared to long echo-time acquisitions. Linewidth measures were not significantly different between groups.IMCL quantification using short and long echo-time 1H-MRS at 3.0 T is useful to detect differences in muscle lipid content in obese and normal-weight subjects. In addition, IMCL correlates with body composition and markers of insulin resistance in this population with no significant difference in correlations between short and long echo-times. Short echo-time IMCL quantification of TA and SOL muscles at 3.0 T was superior to long echo-time due to better SNR and better reproducibility.2010 Wiley-Liss, Inc.

Measurement of tissue lactate using (1) H MRS is often confounded by overlap with intense lipid signals at 1.3 ppm. Single-voxel localization using PRESS is also compromised by the large chemical shift displacement between voxels for the 4.1 ppm (-CH) resonance and the 1.3 ppm -CH3 resonance, leading to subvoxels with signals of opposite phase and hence partial signal cancellation. To reduce the chemical shift displacement to negligible proportions, a modified semi-LASER sequence was written ("FOCI-LASER", abbreviated as fLASER) using FOCI pulses to permit high RF bandwidth even with the limited RF amplitude characteristic of clinical MRI scanners. A further modification, MQF-fLASER, includes a selective multiple-quantum filter to detect lactate and reject lipid signals. The sequences were implemented on a Philips 3 T Achieva TX system. In a solution of brain metabolites fLASER lactate signals were 2.7 times those of PRESS. MQF-fLASER lactate was 47% of fLASER (the theoretical maximum is 50%) but still larger than PRESS lactate. In oil, the main 1.3 ppm lipid peak was suppressed to less than 1%. Enhanced suppression was possible using increased gradient durations. The minimum detectable lactate concentration was approximately 0.5 mM. Coherence selection gradients needed to be at the magic angle to avoid large water signals derived from intermolecular multiple-quantum coherences. In pilot patient measurements, lactate peaks were often observed in brain tumours, but not in cervix tumours; lipids were effectively suppressed. In summary, compared with PRESS, the fLASER sequence yields greatly superior sensitivity for direct detection of lactate (and equivalent sensitivity for other metabolites), while the single-voxel single-shot MQF-fLASER sequence surpasses PRESS for lactate detection while eliminating substantial signals from lipids. This sequence will increase the potential for in vivo lactate measurement as a biomarker in targeted anti-cancer treatments as well as in measurements of tissue hypoxia.© 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.

We present the first solid-state NMR experiments developed using optimal control theory. Taking heteronuclear dipolar recoupling in magic-angle-spinning NMR as an example, it proves possible to significantly improve the efficiency of the experiments while introducing robustness toward instrumental imperfections such as radio frequency inhomogeneity. The improvements are demonstrated by numerical simulations as well as practical experiments on a 13Calpha,15N-labeled powder of glycine. The experiments demonstrate a gain of 53% in the efficiency for 15N to 13Calpha coherence transfer relative to the typically double-cross-polarization experiments.

In this paper, we introduce optimal control algorithm for the design of pulse sequences in NMR spectroscopy. This methodology is used for designing pulse sequences that maximize the coherence transfer between coupled spins in a given specified time, minimize the relaxation effects in a given coherence transfer step or minimize the time required to produce a given unitary propagator, as desired. The application of these pulse engineering methods to design pulse sequences that are robust to experimentally important parameter variations, such as chemical shift dispersion or radiofrequency (rf) variations due to imperfections such as rf inhomogeneity is also explained.

We present the implementation of optimal control into the open source simulation package SIMPSON for development and optimization of nuclear magnetic resonance experiments for a wide range of applications, including liquid- and solid-state NMR, magnetic resonance imaging, quantum computation, and combinations between NMR and other spectroscopies. Optimal control enables efficient optimization of NMR experiments in terms of amplitudes, phases, offsets etc. for hundreds-to-thousands of pulses to fully exploit the experimentally available high degree of freedom in pulse sequences to combat variations/limitations in experimental or spin system parameters or design experiments with specific properties typically not covered as easily by standard design procedures. This facilitates straightforward optimization of experiments under consideration of rf and static field inhomogeneities, limitations in available or desired rf field strengths (e.g., for reduction of sample heating), spread in resonance offsets or coupling parameters, variations in spin systems etc. to meet the actual experimental conditions as close as possible. The paper provides a brief account on the relevant theory and in particular the computational interface relevant for optimization of state-to-state transfer (on the density operator level) and the effective Hamiltonian on the level of propagators along with several representative examples within liquid- and solid-state NMR spectroscopy.

核自旋单重态是一种特殊的自旋状态，其寿命远长于相应自旋的横向和纵向弛豫时间，能够被用于研究分子的慢扩散、慢运动、特征信号选择等过程.目前单重态的研究主要集中于孤立的两自旋体系.而本文以N-乙酰基天冬氨酸（NAA）分子中由亚甲基和次甲基的三个氢原子核构成的三自旋体系为研究对象，将亚甲基中的两个氢核制备成单重态.利用优化控制和数值计算方法，分别设计了包含和不包含次甲基氢核耦合的单重态制备脉冲，结果发现，不考虑次甲基氢耦合设计的优化脉冲，其在实际三自旋体系中的单重态制备效率会显著下降.另外，我们以单重态为起点，实现了针对次甲基和亚甲基的信号选择COSY谱和NOESY谱，结果表明基于单重态的二维谱能够有效避免谱峰重叠现象，提高谱图分辨率，并有助于提高分子结构解析的准确性.

核自旋单重态是一种特殊的量子态，其存在寿命能远长于纵向弛豫时间（T₁），能够被用于研究分子之间的慢扩散和慢运动等动力学过程．单重态的制备是其能成功应用的关键．目前文献中报道了多种制备单重态的方法，这些方法主要适用于孤立的两自旋体系，当单重态所涉及的核自旋受到其它自旋的耦合作用时，单重态的制备效率往往会降低．本文以三自旋体系为例，研究了不同耦合构型下单重态的制备效率受非单重态自旋耦合的影响，模拟结果表明当单重态自旋由弱耦合逐渐变为强耦合时，单重态的制备效率会在单重态自旋与非单重态自旋的耦合呈现对称性时保持一定的稳定性，此特性能够为复杂体系中选择合适的自旋制备单重态提供参考．我们利用N-乙酰-L-天门冬氨酸（NAA）分子的三个质子组成的自旋体系实验验证了以上结论，通过调节NAA分子的酸碱度，所选的三自旋体系能从弱耦合向强耦合转变，实验结果表明：当三自旋中单重态自旋处于强耦合时，单重态的制备效率明显高于弱耦合时的效率．