Measurement of brain lactate during visual stimulation using a long TE semi‐LASER sequence at 7 T

Estimation of metabolic changes during neuronal activation represents a challenge for in vivo MRS, especially for metabolites with low concentration and signal overlap, such as lactate. In this work, we aimed to evaluate the feasibility of detecting lactate during brain activation using a long urn:x-wiley:nbm:media:nbm4223:nbm4223-math-0001 (144 ms) semi‐LASER sequence at 7 T. urn:x-wiley:nbm:media:nbm4223:nbm4223-math-0002 spectra were acquired on healthy volunteers ( urn:x-wiley:nbm:media:nbm4223:nbm4223-math-0003) during a paradigm with 15 min of visual stimulation. Outer‐volume signals were further attenuated by the use of saturation slabs, and macromolecular signals in the vicinity of the inverted lactate peak were individually fitted with simulated Lorentzian peaks. All spectra were free of artefacts and highly reproducible across subjects. Lactate was accurately quantified with an average Cramér‐Rao lower bound of 8%. Statistically significant ( urn:x-wiley:nbm:media:nbm4223:nbm4223-math-0004, one‐tailed urn:x-wiley:nbm:media:nbm4223:nbm4223-math-0005‐test) increases in lactate ( urn:x-wiley:nbm:media:nbm4223:nbm4223-math-000610%) and glutamate ( urn:x-wiley:nbm:media:nbm4223:nbm4223-math-00073%) levels during stimulation were detected in the visual cortex. Lactate and glutamate changes were consistent with previous measurements. We demonstrated that quantification of a clear and non‐contaminated lactate peak obtained with a long TE sequence has the potential of improving the accuracy of functional MRS studies targeting non‐oxidative reaction pathways

Diffusion-weighted SPECIAL improves the detection of J-coupled metabolites at ultra-high magnetic field

A new sequence for single-voxel diffusion-weighted 1H MRS (DWS), named DW-SPECIAL, is proposed to improve the detection and subsequent estimation of the diffusion properties of strongly J-coupled metabolites. It combines the semi-adiabatic SPECIAL sequence with a stimulated echo (STE) diffusion block. Acquisitions with DW-SPECIAL and STE-LASER, the current gold-standard for rodent DWS experiments at high fields, were performed at 14.1T on phantoms and in vivo on the rat brain. The apparent diffusion coefficient and intra-stick diffusivity (Callaghan's model) were fitted and compared between the sequences for glutamate, glutamine (Gln), myo-inositol, taurine, total N-acetylaspartate, total choline, total creatine and the macromolecules. The shorter echo time achieved with DW-SPECIAL (18 ms against 33 ms with STE-LASER) substantially limited the metabolites' signal loss caused by J-evolution. In addition, DW-SPECIAL preserved the main advantages of STE-LASER: absence of cross-terms, diffusion time during a STE and limited sensitivity to B1 inhomogeneities. In vivo, compared to STE-LASER, DW-SPECIAL yielded the same spectral quality and reduced the Cramer Rao Lower Bounds (CRLB) for J-coupled metabolites, irrespective of the b-value. DW-SPECIAL also reduced the standard deviation of the metabolites' diffusion estimates based on individual animal fitting without loss of accuracy compared to the fit on the averaged decay. We conclude that due to its reduced echo time, DW-SPECIAL can serve as an alternative to STE-LASER when strongly J-coupled metabolites like Gln are investigated, thereby extending the range of accessible metabolites in the context of DWS acquisitions.Comment: Submitted to Magnetic Resonance in Medecin

Noise-reduction techniques for 1H-FID-MRSI at 14.1T: Monte-Carlo validation & in vivo application

Proton magnetic resonance spectroscopic imaging (1H-MRSI) is a powerful tool that enables the multidimensional non-invasive mapping of the neurochemical profile at high-resolution over the entire brain. The constant demand for higher spatial resolution in 1H-MRSI led to increased interest in post-processing-based denoising methods aimed at reducing noise variance. The aim of the present study was to implement two noise-reduction techniques, the Marchenko-Pastur principal component analysis (MP-PCA) based denoising and the low-rank total generalized variation (LR-TGV) reconstruction, and to test their potential and impact on preclinical 14.1T fast in vivo 1H-FID-MRSI datasets. Since there is no known ground truth for in vivo metabolite maps, additional evaluations of the performance of both noise-reduction strategies were conducted using Monte-Carlo simulations. Results showed that both denoising techniques increased the apparent signal-to-noise ratio SNR while preserving noise properties in each spectrum for both in vivo and Monte-Carlo datasets. Relative metabolite concentrations were not significantly altered by either methods and brain regional differences were preserved in both synthetic and in vivo datasets. Increased precision of metabolite estimates was observed for the two methods, with inconsistencies noted on lower concentrated metabolites. Our study provided a framework on how to evaluate the performance of MP-PCA and LR-TGV methods for preclinical 1H-FID MRSI data at 14.1T. While gains in apparent SNR and precision were observed, concentration estimations ought to be treated with care especially for low-concentrated metabolites.Comment: Brayan Alves and Dunja Simicic are joint first authors. Currently in revision for NMR in Biomedicin

Hyperpolarized 13C-glucose magnetic resonance highlights reduced aerobic glycolysis in vivo in infiltrative glioblastoma.

Glioblastoma (GBM) is the most aggressive brain tumor type in adults. GBM is heterogeneous, with a compact core lesion surrounded by an invasive tumor front. This front is highly relevant for tumor recurrence but is generally non-detectable using standard imaging techniques. Recent studies demonstrated distinct metabolic profiles of the invasive phenotype in GBM. Magnetic resonance (MR) of hyperpolarized 13C-labeled probes is a rapidly advancing field that provides real-time metabolic information. Here, we applied hyperpolarized 13C-glucose MR to mouse GBM models. Compared to controls, the amount of lactate produced from hyperpolarized glucose was higher in the compact GBM model, consistent with the accepted "Warburg effect". However, the opposite response was observed in models reflecting the invasive zone, with less lactate produced than in controls, implying a reduction in aerobic glycolysis. These striking differences could be used to map the metabolic heterogeneity in GBM and to visualize the infiltrative front of GBM

The Gaia satellite: a tool for Emission Line Stars and Hot Stars

The Gaia satellite will be launched at the end of 2011. It will observe at least 1 billion stars, and among them several million emission line stars and hot stars. Gaia will provide parallaxes for each star and spectra for stars till V magnitude equal to 17. After a general description of Gaia, we present the codes and methods, which are currently developed by our team. They will provide automatically the astrophysical parameters and spectral classification for the hot and emission line stars in the Milky Way and other close Local Group galaxies such as the Magellanic Clouds.Comment: SF2A2008, session GAIA, invited tal

Hyperpolarized ¹³C Magnetic Resonance Spectroscopy Reveals the Rate-Limiting Role of the Blood-Brain Barrier in the Cerebral Uptake and Metabolism of l-Lactate in Vivo.

The dynamics of l-lactate transport across the blood-brain barrier (BBB) and its cerebral metabolism are still subject to debate. We studied lactate uptake and intracellular metabolism in the mouse brain using hyperpolarized <sup>13</sup> C magnetic resonance spectroscopy (MRS). Following the intravenous injection of hyperpolarized [1- <sup>13</sup> C]lactate, we observed that the distribution of the <sup>13</sup> C label between lactate and pyruvate, which has been shown to be representative of their pool size ratio, is different in NMRI and C57BL/6 mice, the latter exhibiting a higher level of cerebral lactate dehydrogenase A ( Ldha) expression. On the basis of this observation, and an additional set of experiments showing that the cerebral conversion of [1- <sup>13</sup> C]lactate to [1- <sup>13</sup> C]pyruvate increases after exposing the brain to ultrasound irradiation that reversibly opens the BBB, we concluded that lactate transport is rate-limited by the BBB, with a 30% increase in lactate uptake after its disruption. It was also deduced from these results that hyperpolarized <sup>13</sup> C MRS can be used to detect a variation in cerebral lactate uptake of <40 nmol in a healthy brain during an in vivo experiment lasting only 75 s, opening new opportunities to study the role of lactate in brain metabolism

Fast high-resolution metabolite mapping in the rat brain using 1H-FID-MRSI at 14.1T

Magnetic resonance spectroscopic imaging (MRSI) enables the simultaneous non-invasive acquisition of MR spectra from multiple spatial locations inside the brain. While 1H-MRSI is increasingly used in the human brain, it is not yet widely applied in the preclinical settings, mostly because of difficulties specifically related to very small nominal voxel size in the rodent brain and low concentration of brain metabolites, resulting in low signal-to-noise ratio SNR. In this context, we implemented a free induction decay 1H-MRSI sequence (1H-FID-MRSI) in the rat brain at 14.1T. We combined the advantages of 1H-FID-MRSI with the ultra-high magnetic field to achieve higher SNR, coverage and spatial resolution in the rodent brain, and developed a custom dedicated processing pipeline with a graphical user interface: MRS4Brain toolbox. LCModel fit, using the simulated metabolite basis-set and in-vivo measured MM, provided reliable fits for the data at acquisition delays of 1.3 and 0.94 ms. The resulting Cram\'er-Rao lower bounds were sufficiently low (<40%) for eight metabolites of interest, leading to highly reproducible metabolic maps. Similar spectral quality and metabolic maps were obtained between 1 and 2 averages, with slightly better contrast and brain coverage due to increased SNR in the latter case. Furthermore, the obtained metabolic maps were accurate enough to confirm the previously known brain regional distribution of some metabolites. The acquisitions proved high repeatability over time. We demonstrated that the increased SNR and spectral resolution at 14.1T can be translated into high spatial resolution in 1H-FID-MRSI of the rat brain in 13 minutes, using the sequence and processing pipeline described herein. High-resolution 1H-FID-MRSI at 14.1T provided reproducible and high-quality metabolic mapping of brain metabolites with significantly reduced technical limitations.Comment: Dunja Simicic and Brayan Alves are joint first author