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Single-voxel proton MRS can be obtained with inversion-based, echo-based, and hybrid methods. Yet, standard localization methods do not guarantee quality. Therefore, knowing basic principles, such as influence factors on both volume definition and spectral quality, including radiofrequency pulses, gradients, chemical shift errors, water-suppression techniques, and outer volume suppression, is very important. In this chapter, we describe factors affecting performance of short echo-time single-voxel proton spectroscopy and currently available localization methods for 1H MRS.

The neurochemical profile of the striatum of R6/2 Huntington's disease mice was examined at different stages of pathogenesis using in vivo1H NMR spectroscopy at 9.4 T. Between 8 and 12 weeks, R6/2 mice exhibited distinct changes in a set of 17 quantifiable metabolites compared with littermate controls. Concentrations of creatine, glycerophosphorylcholine, glutamine and glutathione increased and N-acetylaspartate decreased at 8 weeks. By 12 weeks, concentrations of phosphocreatine, taurine, ascorbate, glutamate, and myo-inositol increased and phophorylethanolamine decreased. These metabolic changes probably reflected multiple processes, including compensatory processes to maintain homeostasis, active at different stages in the development of HD. The observed changes in concentrations suggested impairment of neurotransmission, neuronal integrity and energy demand, and increased membrane breakdown, gliosis, and osmotic and oxidative stress. Comparisons between metabolite concentrations from individual animals clearly distinguished HD transgenics from non-diseased littermates and identified possible markers of disease progression. Metabolic changes in R6/2 striata were distinctly different from those observed previously in the quinolinic acid and 3NP models of HD. Longitudinal monitoring of changes in these metabolites may provide quantifiable measures of disease progression and treatment effects in both mouse models of HD and patients. © 2007 The Authors.

Sequence-specific 1H NMR assignments are presented for a non-selfcomplementary 23-base-pair DNA duplex of molecular weight 15,000 daltons, containing the OR3 repressor binding site of bacteriophage lambda as the central core. The NMR techniques used were mainly phase-sensitive two-dimensional NOE and 2Q spectroscopy, the latter to overcome overlap problems within the spectral region of the deoxyribose spin-systems. Direct sequential NOE connectivities are observed between adenine 2 H and deoxyribose 1' protons. We propose the use of these connectivities as a check of the assignments of C1' and A2 protons, which have independently been derived via other assignment pathways.

Natural abundance 13C NMR spectra obtained from 144-cm3 volumes in the human brain contained well-resolved resonances of myo-inositol after 60 min of data accumulation. A mean concentration of 7.2 +/- 0.5 mumol/g (+/- SE, n = 7) was calculated from the comparison with phantoms. 13C NMR spectroscopy thus provides a complementary role in the quantitation of metabolites also observed in the crowded 1H spectrum.

The peak at 3.35 ppm in the 1H-NMR spectrum characteristic for scyllo- inositol may be a marker for cerebral pathology, although it has a well- known constant concentration relative to myo-inositol. Such a peak was observed with an intensity at least 300% above normal in the brain of a healthy volunteer. The scyllo-inositol signal was assigned based on the detection of a corresponding peak at 74.5 ppm in the 13C-NMR spectrum and on the demonstration of singlet characteristics of the proton signal. The presence of substantial brain concentrations of scyllo-inositol suggests that scyllo-inositol metabolism may be regulated independently from myo-inositol and that such concentrations are compatible with normal health.

Glucose is the major substrate that sustains normal brain function. When the brain glucose concentration approaches zero, glucose transport across the blood-brain barrier becomes rate limiting for metabolism during, for example, increased metabolic activity and hypoglycemia. Steady-state brain glucose concentrations in α-chloralose anesthetized rats were measured noninvasively as a function of plasma glucose. The relation between brain and plasma glucose was linear at 4.5 to 30 mmol/L plasma glucose, which is consistent with the reversible Michaelis-Menten model. When the model was fitted to the brain glucose measurements, the apparent Michaelis-Menten constant, Kt, was 3.3 ± 1.0 mmol/L, and the ratio of the maximal transport rate relative to CMRglc, Tmax/CMRglc, was 2.7 ± 0.1. This Kt is comparable to the authors' previous human data, suggesting that glucose transport kinetics in humans and rats are similar. Cerebral blood flow (CBF) was simultaneously assessed and constant above 2 mmol/L plasma glucose at 73 ± 6 mL 100 g-1 min-1. Extrapolation of the reversible Michaelis-Menten model to hypoglycemia correctly predicted the plasma glucose concentration (2.1 ± 0.6 mmol/L) at which brain glucose concentrations approached zero. At this point, CBF increased sharply by 57% ± 22%, suggesting that brain glucose concentration is the signal that triggers defense mechanisms aimed at improving glucose delivery to the brain during hypoglycemia.

For a rapid determination of saturation factors in surface coil NMR spectroscopy, the recently published (90 degrees-tau-180 degrees-tau-90 degrees-tau-) SUFIR sequence was modified with adiabatic pulse cycles. Signals were acquired after each of the two 90 degrees pulses and they were stored in different memory blocks. The deleterious offset-dependent saturation effects inherent in adiabatic 90 degrees excitation pulses were minimized by suitable combinations of adiabatic pulses that sweep from either side of the spectrum onto resonance, and by setting the carrier frequency in the middle of the spectrum. The practical use of the proposed method is illustrated with the determination of 31P NMR saturation factors in human calf muscle.

Elevated tissue lactate concentrations typically found in tumors can be measured by in vivo nuclear magnetic resonance (NMR) spectroscopy. In this study, lactate turnover in rat C6 glioma was determined from in vivo 1H NMR measurements of [3-13C]lactate buildup during steady-state hyperglycemia with [1-13C]glucose. With this tumor model, a narrow range of values was observed for the first-order rate constant that describes lactate efflux, k2 = 0.043 ± 0.007 (n = 12) SD min-1. For individual animals, the standard error in k2 was small (

The brain of a hibernating mammal withstands physiological extremes that would result in cerebral damage and death in a non-hibernating species such as humans. To examine the possibility that this neuroprotection results from alterations in cerebral metabolism, we used in vivo 1H NMR spectroscopy at high field (9.4 T) to measure the concentration of 18 metabolites (neurochemical profile) in the brain of 13-lined ground squirrels (Spermophilus tridecemlineatus) before, during, and after hibernation. Resolved in vivo1H NMR spectra were obtained even at low temperature in torpid hibernators (∼7°C). The phosphocreatine-to-creatine ratio was increased during torpor (+143%) indicating energy storage, and remained increased to a lesser extent during interbout arousal (IBA) (+83%). The total γ-aminobutyric acid concentration was increased during torpor (+135%) and quickly returned to baseline during IBA. Glutamine (Gln) was decreased (-54%) during torpor but quickly returned to normal levels during IBA and after terminal arousal in the spring. Glutamate (Glu) was also decreased during torpor (-17%), but remained decreased during IBA (-20% compared with fall), and returned to normal level in the spring. Our observation that Glu and Gln levels are depressed in the brain of hibernators suggests that the balance between anaplerosis and loss of Glu and Gln (because of glutamatergic neurotransmission or other mechanisms) is altered in hibernation. © 2007 The Authors.

Early detection of white matter lesions in childhood-onset cerebral adrenoleukodystrophy (ALD) is important as hematopoietic cell transplantation (HCT), currently the only effective treatment, is beneficial only if performed early in the disease course.

The continuous delivery of glucose to the brain is critically important to the maintenance of normal metabolic function. However, elucidation of the hormonal regulation of in vivo cerebral glucose metabolism in humans has been limited by the lack of direct, noninvasive methods with which to measure brain glucose. In this study, we sought to directly examine the effect of insulin on glucose concentrations and rates of glucose transport/metabolism in human brain using 1H-magnetic resonance spectroscopy at 4 Tesla. Seven subjects participated in paired hyperglycemic (16.3 ± 0.3 mmol/1) clamp studies performed with and without insulin. Brain glucose remained constant throughout (5.3 ± 0.3 μmol/g wet wt when serum insulin = 16 ± 7 pmol/1 vs. 5.5 ± 0.3 μmol/g wet wt when serum insulin = 668 ± 81 pmol/1, P = NS). Glucose concentrations in gray matter-rich occipital cortex and white matter-rich periventricular tissue were then simultaneously measured in clamps, where plasma glucose ranged from 4.4 to 24.5 mmol/1 and insulin was infused at 0.5 mU · kg-1 · min-1. The relationship between plasma and brain glucose was linear in both regions. Reversible Michaelis-Menten kinetics fit these data best, and no differences were found in the kinetic constants calculated for each region. These data support the hypothesis that the majority of cerebral glucose uptake/metabolism is an insulin-independent process in humans.

Many tissues exhibit metabolic compartmentation. In the brain, while there is no doubt on the importance of functional compartmentation between neurons and glial cells, there is still debate on the specific regulation of pathways of energy metabolism at different activity levels. Using 13C magnetic resonance spectroscopy (MRS) in vivo, we determined fluxes of energy metabolism in the rat cortex under α-chloralose anaesthesia at rest and during electrical stimulation of the paws. Compared to resting metabolism, the stimulated rat cortex exhibited increased glutamate–glutamine cycle (+67 nmol/g/min, +95%, P

In this study, hypothalamic activation was performed by dehydration-induced anorexia (DIA) and overnight food suppression (OFS) in female rats. The assessment of the hypothalamic response to these challenges by manganese-enhanced MRI showed increased neuronal activity in the paraventricular nuclei (PVN) and lateral hypothalamus (LH), both known to be areas involved in the regulation of food intake. The effects of DIA and OFS were compared by generating T-score maps. Increased neuronal activation was detected in the PVN and LH of DIA rats relative to OFS rats. In addition, the neurochemical profile of the PVN and LH were measured by 1H MRS at 14.1T. Significant increases in metabolite levels were measured in DIA and OFS relative to control rats. Statistically significant increases in γ-aminobutyric acid were found in DIA (p=0.0007) and OFS (p

Quantification of short-echo time proton magnetic resonance spectroscopy results in >18 metabolite concentrations (neurochemical profile). Their quantification accuracy depends on the assessment of the contribution of macromolecule (MM) resonances, previously experimentally achieved by exploiting the several fold difference in T-1. To minimize effects of hetero-geneities in metabolites T-1, the aim of the study was to assess MM signal contributions by combining inversion recovery (IR) and diffusion-weighted proton spectroscopy at high-magnetic field (14.1 T) and short echo time (=8 msec) in the rat brain. IR combined with diffusion weighting experiments (with delta/Delta = 1.5/200 msec and b-value = 11.8 msec/mu m(2)) showed that the metabolite nulled spectrum (inversion time = 740 msec) was affected by residuals attributed to creatine, inositol, taurine, choline, N-acetylaspartate as well as glutamine and glutamate. While the metabolite residuals were significantly attenuated by 50%, the MM signals were almost not affected (

In the past decade, magnetic resonance imaging (MRI) research has been focused on the acquisition of physiological and biochemical information noninvasively. Probably the most notable accomplishment in this general effort has been the introduction of the MR approaches to map brain function. This capability, often referred to as functional magnetic resonance imaging. orfMRI, is based on the sensitivity of MR signals to secondary metabolic and hemodynamic responses tliaî accompany increased neuronal activity. Despite this indirect link to neurotransmission, recent studies demonstrate that under appropriate conditions, these jMRl maps have accuracy at the scale of submillimeter neuronal organizations such as the orientation columns of the visual cortex, and are directly proportional in magnitude to electrical signals generated by the neurons. High magnetic fields have been critical in achieving such specificity in functional maps because they provide advantages through increased signal-to-noise ratio, diminishing blood-related contributions to mapping signals, and enhanced sensitivity to microvasculature. Equally important is MR spectroscopy studies, which, at high magnetic fields, provide for the first time the opportunity to measure local metabolic correlates of human brain function and neurotransmission rates. Together, these MR methods provide a complementary set of approaches for probing important aspects of the nervous system. © 2001 IEEE. Publisher Item Identifier S 0018-9219(01)07636-8.