Purpose This assesses the potential of measuring lactate in the human brain using three non‐editing MRS methods at 7T and compares the accuracy and precision of the methods. Methods 1H MRS data were measured in the right dorsolateral prefrontal cortex using a semi‐adiabatic spin‐echo full‐intensity acquired localized sequence with three different protocols: (I) TE = 16 ms, (II) TE = 110 ms, and (III) TE = 16 ms, TI = 300 ms. T1 and T2 relaxation times of lactate were also measured. Simulated spectra were generated for three protocols with known concentrations, using a range of spectral linewidths and SNRs to assess the effect of data quality on the measurement precision and accuracy. Results Lactate was quantified in all three protocols with mean Cramér‐Rao lower bound of 8% (I), 13% (II), and 7% (III). The T1 and T2 relaxation times of lactate were 1.9 ± 0.2 s and 94 ± 13 ms, respectively. Simulations predicted a spectral linewidth‐associated underestimation of lactate measurement. Simulations, phantom and in vivo results showed that protocol II was most affected by this underestimation. In addition, the estimation error was insensitive to a broad range of spectral linewidth with protocol I. Within‐session coefficient of variances of lactate were 6.1 ± 7.9% (I), 22.3 ± 12.3% (II), and 5.1 ± 5.4% (III), respectively. Conclusion We conclude that protocols I and III have the potential to measure lactate at 7T with good reproducibility, whereas the measurement accuracy and precision depend on spectral linewidth and SNR, respectively. Moreover, simulation is valuable for the optimization of measurement protocols in future study design and the correction for measurement bias.

Carbon-13 nuclear magnetic resonance spectroscopy in combination with the infusion of 13C-labeled precursors is a unique approach to study in vivo brain energy metabolism. Incorporating the maximum information available from in vivo localized 13C spectra is of importance to get broader knowledge on cerebral metabolic pathways. Metabolic rates can be quantitatively determined from the rate of 13C incorporation into amino acid neurotransmitters such as glutamate and glutamine using suitable mathematical models. The time course of multiplets arising from 13C-13C coupling between adjacent carbon atoms was expected to provide additional information for metabolic modeling leading to potential improvements in the estimation of metabolic parameters.The aim of the present study was to extend two-compartment neuronal/glial modeling to include dynamics of 13C isotopomers available from fine structure multiplets in 13C spectra of glutamate and glutamine measured in vivo in rats brain at 14.1 T, termed bonded cumomer approach. Incorporating the labeling time courses of 13C multiplets of glutamate and glutamine resulted in elevated precision of the estimated fluxes in rat brain as well as reduced correlations between them.

Disclosure statement: the authors disclose no conflicts of interest. HIGHLIGHTS:➔ Magnetic resonance spectroscopy reveals altered chemistry in the aging rat brain ➔ Age-and sex-dependent differences in metabolites and macromolecules are present ➔ Metabolites and macromolecules are markers of processes involved in healthy aging ➔ This study clarifies normative progression of brain chemistry and metabolism in vivo ➔ Improved understanding will inform future studies in pathological aging ABSTRACT:Normal aging is associated with numerous biological changes including altered brain metabolism and tissue chemistry. In vivo characterization of the neurochemical profile during aging is possible using magnetic resonance spectroscopy, a powerful non-invasive technique capable of quantifying brain metabolites involved in physiological processes that become impaired with age. A prominent macromolecular signal underlies those of brain metabolites and is particularly visible at high fields;parameterization of this signal into components improves quantification and expands the number of biomarkers comprising the neurochemical profile. The present study reports, for the first time, the simultaneous absolute quantification of brain metabolites and individual macromolecules in aging male and female Fischer 344 rats, measured longitudinally using proton magnetic resonance spectroscopy at 7T. We identified age-and sex-related changes in neurochemistry, with prominent differences in metabolites implicated in anaerobic energy metabolism, antioxidant capacity, and neuroprotection, as well as numerous macromolecule changes. These findings contribute to our understanding of the neurobiological processes associated with healthy aging, critical for the proper identification and management of pathological aging trajectories.

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