Rolf Gruetter

In vivo 1H NMR spectroscopy of rat brain at 1 ms echo time

Using optimized, asymmetric radiofrequency (RF) pulses for slice selection, the authors demonstrate that stimulated echo acquisition mode (STEAM) localization with ultra‐short echo time (1 ms) is possible. Water suppression was designed to minimize sensitivity to B1 inhomogeneity using a combination of 7 variable power RF pulses with optimized relaxation delays (VAPOR). Residual water signal was well below the level of most observable metabolites. Contamination by the signals arising from outside the volume of interest was minimized by outer volume saturation using a series of hyperbolic secant RF pulses, resulting in a sharp volume definition. In conjunction with FASTMAP shimming (Gruetter Magn Reson Med 1993;29:804–811), the short echo time of 1 msec resulted in highly resolved in vivo 1H nuclear magnetic resonance spectra. In rat brain the water linewidths of 11–13 Hz and metabolite singlet linewidths of 8–10 Hz were measured in 65 μl volumes. Very broad intense signals (Δν1/2 > 1 kHz), as expected from membranes, for example, were not observed, suggesting that their proton T2 are well below 1 msec. The entire chemical shift range of 1H spectrum was observable, including resolved resonances from alanine, aspartate, choline group, creatine, GABA, glucose, glutamate, glutamine, myo‐inositol, lactate, N‐acetylaspartate, N‐acetylaspartylglutamate, phosphocreatine, and taurine. At 9.4 T, peaks close to the water were observed, including the H‐1 of α‐D‐glucose at 5.23 ppm and a tentative H‐1 resonance of glycogen at 5.35 ppm. Magn Reson Med 41:649–656, 1999.

Simultaneous in vivo spectral editing and water suppression

Water suppression is typically performed in vivo by exciting the longitudinal magnetization in combination with dephasing, or by using frequency‐selective coherence generation. MEGA, a frequency‐selective refocusing technique, can be placed into any pulse sequence element designed to generate a Hahn spin‐echo or stimulated echo, to dephase transverse water coherences with minimal spectral distortions. Water suppression performance was verified in vivo using stimulated echo acquisition mode (STEAM) localization, which provided water suppression comparable with that achieved with four selective pulses in 3,1‐DRYSTEAM. The advantage of the proposed method was exploited for editing J‐coupled resonances. Using a double‐banded pulse that selectively inverts a J‐coupling partner and simultaneously suppresses water, efficient metabolite editing was achieved in the point resolved spectroscopy (PRESS) and STEAM sequences in which MEGA was incorporated. To illustrate the efficiency of the method, the detection of γ‐aminobutyric acid (GABA) was demonstrated, with minimal contributions from macromolecules and overlying singlet peaks at 4 T. The estimated occipital GABA concentration was consistent with previous reports, suggesting that editing for GABA is efficient when based on MEGA at high field strengths.

Field mapping without reference scan using asymmetric echo-planar techniques

Improvements in B0 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 T*2 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. Magn Reson Med 43:319–323, 2000.

In vivo 1H NMR spectroscopy of the human brain at 7 T

In vivo 1H NMR spectra from the human brain were measured at 7 T. Ultrashort echo‐time STEAM was used to minimize J‐modulation and signal attenuation caused by the shorter T2 of metabolites. Precise adjustment of higher‐order shims, which was achieved with FASTMAP, was crucial to benefit from this high magnetic field. Sensitivity improvements were evident from single‐shot spectra and from the direct detection of glucose at 5.23 ppm in 8‐ml volumes. The linewidth of the creatine methyl resonance was at best 9 Hz. In spite of the increased linewidth of singlet resonances at 7 T, the ability to resolve overlapping multiplets of J‐coupled spin systems, such as glutamine and glutamate, was substantially increased. Characteristic spectral patterns of metabolites, e.g., myo‐inositol and taurine, were discernible in the in vivo spectra, which facilitated an unambiguous signal assignment. Magn Reson Med 46:451–456, 2001.

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 Cramér‐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. Magn Reson Med, 2009.

Localized 13C NMR Spectroscopy in the Human Brain of Amino Acid Labeling from d‐[1‐13C]Glucose

Abstract: Cerebral metabolism of d[1‐13C]glucose was studied with localized 13C NMR spectroscopy during intravenous infusion of enriched [1‐13C]glucose in four healthy subjects. The use of three‐dimensional localization resulted in the complete elimination of triacylglycerol resonance that originated in scalp and subcutaneous fat. The sensitivity and resolution were sufficient to allow 4 min of time‐resolved observation of label incorporation into the C3 and C4 resonances of glutamate and C4 of glutamine, as well as C3 of aspartate with lower time resolution. [4‐13C]Glutamate labeled rapidly reaching close to maximum labeling at 60 min. The label flow into [3‐13C]glutamate clearly lagged behind that of [4‐13C]glutamate and peaked at t = 110–140 min. Multiplets due to homonuclear 13C‐13C coupling between the C3 and C4 peaks of the glutamate molecule were observed in vivo. Isotopomer analysis of spectra acquired between 120 and 180 min yielded a 13C isotopic fraction at C4 glutamate of 27 ± 2% (n = 4), which was slightly less than one‐half the enrichment of the C1 position of plasma glucose (63 ± 1%), p < 0.05. By comparison with an external standard the total amount of [4‐13C]glutamate was directly quantified to be 2.4 ± 0.1 µmol/ml‐brain. Together with the isotopomer data this gave a calculated brain glutamate concentration of 9.1 ± 0.7 µmol/ml, which agrees with previous estimates of total brain glutamate concentrations. The agreement suggests that essentially all of the brain glutamate is derived from glucose in healthy human brain.

MR Spectroscopy of the Human Brain With Enhanced Signal Intensity at Ultrashort Echo Times on a Clinical Platform at 3T and 7T

Recently, the spin‐echo full‐intensity acquired localized (SPECIAL) spectroscopy technique was proposed to unite the advantages of short TEs on the order of milliseconds (ms) with full sensitivity and applied to in vivo rat brain. In the present study, SPECIAL was adapted and optimized for use on a clinical platform at 3T and 7T by combining interleaved water suppression (WS) and outer volume saturation (OVS), optimized sequence timing, and improved shimming using FASTMAP. High‐quality single voxel spectra of human brain were acquired at TEs below or equal to 6 ms on a clinical 3T and 7T system for six volunteers. Narrow linewidths (6.6 ± 0.6 Hz at 3T and 12.1 ± 1.0 Hz at 7T for water) and the high signal‐to‐noise ratio (SNR) of the artifact‐free spectra enabled the quantification of a neurochemical profile consisting of 18 metabolites with Cramér‐Rao lower bounds (CRLBs) below 20% at both field strengths. The enhanced sensitivity and increased spectral resolution at 7T compared to 3T allowed a two‐fold reduction in scan time, an increased precision of quantification for 12 metabolites, and the additional quantification of lactate with CRLB below 20%. Improved sensitivity at 7T was also demonstrated by a 1.7‐fold increase in average SNR (= peak height/root mean square [RMS]‐of‐noise) per unit‐time. Magn Reson Med, 2009.

Temperature and SAR calculations for a human head within volume and surface coils at 64 and 300 MHz

To examine relationships between specific energy absorption rate (SAR) and temperature distributions in the human head during radio frequency energy deposition in MRI.

Sustained Neuronal Activation Raises Oxidative Metabolism to a New Steady-State Level: Evidence from 1H NMR Spectroscopy in the Human Visual Cortex

To date, functional 1H NMR spectroscopy has been utilized to report the time courses of few metabolites, primarily lactate. Benefiting from the sensitivity offered by ultra-high magnetic field (7 T), the concentrations of 17 metabolites were measured in the human visual cortex during two paradigms of visual stimulation lasting 5.3 and 10.6 mins. Significant concentration changes of approximately 0.2 μmol/g were observed for several metabolites: lactate increased by 23% ± 5% (P < 0.0005), glutamate increased by 3% ± 1% (P < 0.01), whereas aspartate decreased by 15% ± 6% (P < 0.05). Glucose concentration also manifested a tendency to decrease during activation periods. The lactate concentration reached the new steady-state level within the first minute of activation and came back to baseline only after the stimulus ended. The changes of the concentration of metabolites implied a rise in oxidative metabolism to a new steady-state level during activation and indicated that amino-acid homeostasis is affected by physiological stimulation, likely because of an increased flux through the malate—aspartate shuttle.

Clinical Proton MR Spectroscopy in Central Nervous System Disorders

A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units.