Hanne Frenkel

Localized short-echo-time proton MR spectroscopy with full signal-intensity acquisition

We developed a short‐echo‐time (TE) sequence for proton localized spectroscopy by combining a 1D add‐subtract scheme with a doubly slice‐selective spin‐echo (SE) sequence. The sequence preserves the full magnetization available from the selected volume of interest (VOI). By reducing the number of radiofrequency (RF) pulses acting on transverse magnetization, we were able to minimize the TE to the level that is achievable with the stimulated echo acquisition mode (STEAM) technique, and also gained a twofold increase in sensitivity. The use of an adiabatic pulse in the add‐subtract localization improved the efficiency of excitation in spatially inhomogeneous RF fields, which are frequently encountered at high magnetic fields. The localization performance and sensitivity gains of this method, which is termed SPin ECho, full Intensity Acquired Localized (SPECIAL) spectroscopy, were demonstrated in vivo in rat brains. In conjunction with spectroscopic imaging, a 2‐μl spatial resolution was accomplished with a signal‐to‐noise ratio (SNR) above 30, which is usually sufficient for reliable quantification of a large number of metabolites (neurochemical profile). Magn Reson Med, 2006.

Non-invasive quantification of brain glycogen absolute concentration

The only currently available method to measure brain glycogen in vivo is 13C NMR spectroscopy. Incorporation of 13C‐labeled glucose (Glc) is necessary to allow glycogen measurement, but might be affected by turnover changes. Our aim was to measure glycogen absolute concentration in the rat brain by eliminating label turnover as variable. The approach is based on establishing an increased, constant 13C isotopic enrichment (IE). 13C‐Glc infusion is then performed at the IE of brain glycogen. As glycogen IE cannot be assessed in vivo, we validated that it can be inferred from that of N‐acetyl‐aspartate IE in vivo: After [1‐13C]‐Glc ingestion, glycogen IE was 2.2 ± 0.1 fold that of N‐acetyl‐aspartate (n = 11, R2 = 0.77). After subsequent Glc infusion, glycogen IE equaled brain Glc IE (n = 6, paired t‐test, p = 0.37), implying isotopic steady‐state achievement and complete turnover of the glycogen molecule. Glycogen concentration measured in vivo by 13C NMR (mean ± SD: 5.8 ± 0.7 μmol/g) was in excellent agreement with that in vitro (6.4 ± 0.6 μmol/g, n = 5). When insulin was administered, the stability of glycogen concentration was analogous to previous biochemical measurements implying that glycogen turnover is activated by insulin. We conclude that the entire glycogen molecule is turned over and that insulin activates glycogen turnover.

Characterization of sustained BOLD activation in the rat barrel cortex and neurochemical consequences

To date, only a couple of functional MR spectroscopy (fMRS) studies were conducted in rats. Due to the low temporal resolution of (1)H MRS techniques, prolonged stimulation paradigms are necessary for investigating the metabolic outcome in the rat brain during functional challenge. However, sustained activation of cortical areas is usually difficult to obtain due to neural adaptation. Anesthesia, habituation, high variability of the basal state metabolite concentrations as well as low concentrations of the metabolites of interest such as lactate (Lac), glucose (Glc) or γ-aminobutyric acid (GABA) and small expected changes of metabolite concentrations need to be addressed. In the present study, the rat barrel cortex was reliably and reproducibly activated through sustained trigeminal nerve (TGN) stimulation. In addition, TGN stimulation induced significant positive changes in lactate (+1.01 μmol/g, p<0.008) and glutamate (+0.92 μmol/g, p<0.02) and significant negative aspartate changes (-0.63 μmol/g, p<0.004) using functional (1)H MRS at 9.4 T in agreement with previous changes observed in human fMRS studies. Finally, for the first time, the dynamics of lactate, glucose, aspartate and glutamate concentrations during sustained somatosensory activation in rats using fMRS were assessed. These results allow demonstrating the feasibility of fMRS measurements during prolonged barrel cortex activation in rats.

Selective resonance suppression 1H-[13C] NMR spectroscopy with asymmetric adiabatic RF pulses.

Despite obvious improvements in spectral resolution at high magnetic field, the detection of 13C labeling by 1H‐[13C] NMR spectroscopy remains hampered by spectral overlap, such as in the spectral region of 1H resonances bound to C3 of glutamate (Glu) and glutamine (Gln), and C6 of N‐acetylaspartate (NAA). The aim of this study was to develop, implement, and apply a novel 1H‐[13C] NMR spectroscopic editing scheme, dubbed “selective Resonance suppression by Adiabatic Carbon Editing and Decoupling single‐voxel STimulated Echo Acquisition Mode” (RACED‐STEAM). The sequence is based on the application of two asymmetric narrow‐transition‐band adiabatic RF inversion pulses at the resonance frequency of the 13C coupled to the protons that need to be suppressed during the mixing time (TM) period, alternating the inversion band downfield and upfield from the 13C resonance on odd and even scans, respectively, thus suppressing the detection of 1H resonances bound to 13C within the transition band of the inversion pulse. The results demonstrate the efficient suppression of 1H resonances bound to C3 of Glu and Gln, and C4 of Glu, which allows the 1H resonances bound to C6 of NAA and C4 of Gln to be revealed. The measured time course of the resolved labeling into NAA C6 with the new scheme was consistent with the slow turnover of NAA. Magn Reson Med 61:260–266, 2009.