Field mapping without reference scan using asymmetric echo-planar techniques

Improvements in B(o) mapping and shimming were achieved by measuring the static field information in multiple subsequent echoes generated by an asymmetric echo-planar readout gradient train. With careful compensation, eddy current effects were shown to affect the adjustment of the shim coils minimally. In addition to reducing the time required for field mapping by two-fold, the sensitivity was simultaneously optimized irrespective of the prevalent T2/* present, thereby minimizing the error of the static field measurement to below 0.1 Hz. With adiabatic low flip-angle excitation, the time required for field mapping was below 1 second. (C) 2000 Wiley-Liss, Inc

Methodology of H NMR Spectroscopy of the Human Brain at Very High Magnetic Fields

An ultrashort-echo-time stimulated echo-acquisition mode (STEAM) pulse sequence with interleaved outer volume suppression and VAPOR (variable power and optimized relaxation delays) water suppression was redesigned and optimized for human applications at 4 and 7 T, taking into account the specific requirements for spectroscopy at high magnetic fields and limitations of currently available hardware. In combination with automatic shimming, automated parameter adjustments and data processing, this method provided a user-friendly tool for routine (1)H nuclear magnetic resonance (NMR) spectroscopy of the human brain at very high magnetic fields. Effects of first- and second-order shimming, single-scan averaging, frequency and phase corrections, and eddy currents were described. LCModel analysis of an in vivo (1)H NMR spectrum measured from the human brain at 7 T allowed reliable quantification of more than fifteen metabolites noninvasively, illustrating the potential of high-field NMR spectroscopy. Examples of spectroscopic studies performed at 4 and 7 T demonstrated the high reproducibility of acquired spectra quality

Extracellular-intracellular distribution of glucose and lactate in the rat brain assessed noninvasively by diffusion-weighted 1H nuclear magnetic resonance spectroscopy in vivo

To determine the distribution of cerebral glucose and lactate between the intracellular and the extracellular space of the rat brain in vivo, the diffusion characteristic of glucose and lactate was compared with that of metabolites known to be mainly intracellular (N-acetylaspartate, choline, creatine, glutamate, myo-inositol, and taurine) using a pulsed-field-gradient 1H nuclear magnetic resonance technique. The detection of a glucose signal at large diffusion weighting provided direct experimental evidence of intracellular glucose in the rat brain. At large diffusion weighting, the apparent diffusion coefficient (ADC) of glucose and lactate was similar to that of the intracellular metabolites such as N-acetylaspartate, creatine, and glutamate. At small diffusion weighting, the ADC of glucose and lactate was increased, which was explained by a decreased relative contribution of intracellular glucose to the total signal. The calculated extracellular volume fraction of glucose (0.19 ± 0.05) and lactate (0.17 ± 0.06) was consistent with a substantial fraction of glucose and lactate signals being intracellular. The findings were direct in vivo evidence that the largest concentration gradient of glucose is at the blood-brain barrier and that glucose is evenly distributed in the brain in vivo between the intracellular and extracellular space

Noninvasive measurements of [1-13C]glycogen concentrations and metabolism in rat brain in vivo

Using a specific 13C NMR localization method, 13C label incorporation into the glycogen C1 resonance was measured while infusing [1- 13C]glucose in intact rats. The maximal concentration of [1-13C]glycogen was 5.1 ± 0.6 μmol g-1 (mean ± SE, n = 8). During the first 60 rain of acute hyperglycemia, the rate of 13C label incorporation (synthase flux) was 2.3 ± 0.7 μmol g-1 h-1 (mean ± SE, n = 9 rats), which was higher (p 0.05 for correlation). The results implied that net glycogen synthesis of ~3 μmol g-1 had occurred, similar to previous reports. When infusing unlabeled glucose before [1-13C]glucose in three studies, the rate of glycogen C1 accumulation was 0.46 ± 0.08 μmol g-1 h-1. The results suggest that steady-state glycogen turnover rates during hyperglycemia are ~1% of glucose consumption

A localization method for the measurement of fast relaxing 13C NMR signals in humans at high magnetic fields

Nuclear magnetic resonance (NMR) signals with short T1 and T2, such as the 13C signal of glycogen, are difficult to localize in three dimensions without major signal loss. A pulse sequence that accomplishes the spatial localization of 1H-decoupled 13C NMR signals on a whole-body scanner within the Food and Drug Administration guidelines for specific absorption rates was designed. The method uses an optimized three-dimensional outer volume suppression scheme combined with one-dimensional image-selected in vivo spectroscopy and surface coil detection. The localization performance of the sequence was validated at 4 T with double chambered phantoms and 13C magnetic resonance imaging. Localized 13C spectra were acquired from human brain and muscle. © Springer-Verlag 2005

In vivo 1H NMR spectroscopy of the human brain at high magnetic fields: Metabolite quantification at 4T vs. 7T

A comprehensive comparative study of metabolite quantification from the human brain was performed on the same 10 subjects at 4T and 7T using MR scanners with identical consoles, the same type of RF coils, and identical pulse sequences and data analysis. Signal-to-noise ratio (SNR) was increased by a factor of 2 at 7T relative to 4T in a volume of interest selected in the occipital cortex using half-volume quadrature radio frequency (RF) coils. Spectral linewidth was increased by 50% at 7T, which resulted in a 14% increase in spectral resolution at 7T relative to 4T. Seventeen brain metabolites were reliably quantified at both field strengths. Metabolite quantification at 7T was less sensitive to reduced SNR than at 4T. The precision of metabolite quantification and detectability of weakly represented metabolites were substantially increased at 7T relative to 4T. Because of the increased spectral resolution at 7T, only one-half of the SNR of a 4T spectrum was required to obtain the same quantification precision. The Cramé r-Rao lower bounds (CRLB), a measure of quantification precision, of several metabolites were lower at both field strengths than the intersubject variation in metabolite concentrations, which resulted in a strong correlation between metabolite concentrations of individual subjects measured at 4T and 7T. © 2009 Wiley-Liss, Inc

Metabolic changes in quinolinic acid-lesioned rat striatum detected noninvasively by in vivo 1H NMR spectroscopy

Intrastriatal injection of quinolinic acid (QA) provides an animal model of Huntington disease. In vivo 1H NMR spectroscopy was used to measure the neurochemical profile non-invasively in seven animals 5 days after unilateral injection of 150 nmol of QA. Concentration changes of 16 metabolites were measured from 22 μl volume at 9.4 T. The increase of glutamine ((+25 ± 14)%, mean ± SD, n = 7) and decrease of glutamate (-12 ± 5)%, N-acetylaspartate (-17 ± 6)%, taurine (-14 ± 6)% and total creatine (-9 ± 3%) were discernible in each individual animal (P < 0.005, paired t-test). Metabolite concentrations in control striata were in excellent agreement with biochemical literature. The change in glutamate plus glutamine was not significant, implying a shift in the glutamate-glutamine interconversion, consistent with a metabolic defect at the level of neuronal-glial metabolic trafficking. The most significant indicator of the lesion, however, were the changes in glutathione ((-19 ± 9)%, P < 0.002)), consistent with oxidative stress. From a comparison with biochemical literature we conclude that high-resolution in vivo 1H NMR spectroscopy accurately reflects the neurochemical changes induced by a relatively modest dose of QA, which permits one to longitudinally follow mitochondrial function, oxidative stress and glial-neuronal metabolic trafficking as well as the effects of treatment in this model of Huntington disease. © 2001 Wiley-Liss, Inc

Elevated Pontine and Putamenal GABA Levels in Mild-Moderate Parkinson Disease Detected by 7 Tesla Proton MRS

Background: Parkinson disease (PD) is characterized by the degeneration of nigrostriatal dopaminergic neurons. However, postmortem evidence indicates that the pathology of lower brainstem regions, such as the pons and medulla, precedes nigral involvement. Consistently, pontomedullary damage was implicated by structural and PET imaging in early PD. Neurochemical correlates of this early pathological involvement in PD are unknown. Methodology/Principal Finding: To map biochemical alterations in the brains of individuals with mild-moderate PD we quantified neurochemical profiles of the pons, putamen and substantia nigra by 7 tesla (T) proton magnetic resonance spectroscopy. Thirteen individuals with idiopathic PD (Hoehn &amp; Yahr stage 2) and 12 age- and gender-matched healthy volunteers participated in the study. c-Aminobutyric acid (GABA) concentrations in the pons and putamen were significantly higher in patients (N = 11, off medications) than controls (N = 11, p,0.001 for pons and p,0.05 for putamen). The GABA elevation was more pronounced in the pons (64%) than in the putamen (32%). No other neurochemical differences were observed between patients and controls. Conclusion/Significance: The GABA elevation in the putamen is consistent with prior postmortem findings in patients with PD, as well as with in vivo observations in a rodent model of PD, while the GABA finding in the pons is novel. The more significant GABA elevation in the pons relative to the putamen is consistent with earlier pathological involvement of th

Proton MRS of the unilateral substantia nigra in the human brain at 4 tesla: Detection of high GABA concentrations

Parkinson's disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra (SN), the cause of which is unknown. Characterization of early SN pathology could prove beneficial in the treatment and diagnosis of PD. The present study shows that with the use of short-echo (5 ms) Stimulated-Echo Acquisition Mode (STEAM) spectroscopy and LCModel, a neurochemical profile consisting of 10 metabolites, including γ-aminobutyric acid (GABA), glutamate (Glu), and glutathione (GSH), can be measured from the unilateral SN at 4 tesla. The neurochemical profile of the SN is unique and characterized by a fourfold higher GABA/Glu ratio compared to the cortex, in excellent agreement with established neurochemistry. The presence of elevated GABA levels in SN was validated with the use of editing, suggesting that partial volume effects were greatly reduced. These findings establish the feasibility of obtaining a neurochemical profile of the unilateral human SN by single-voxel spectroscopy in small volumes. © 2006 Wiley-Liss, Inc