Longitudinal quantification of metabolites and macromolecules reveals age- and sex-related changes in the healthy Fischer 344 rat brain

In vivo macromolecule signals in rat brain 1H‐MR spectra at 9.4T: Parametrization, spline baseline estimation, and T2 relaxation times

“…J‐coupled metabolites (eg, Glx and Tau) were fitted with larger linewidths to account for the J‐splitting appearance. This approach is an accepted approximation for the removal of the residual metabolites at short TE and UHF, 10 , 11 , 44 with the main improvement that in this manuscript more metabolite residuals were reliably identified 11 , 23 , 45 (ie, NAA ‐ 2.49 ppm, Tau ‐ 3.42 ppm, Glx ‐ 3.75 ppm, Ins ‐ 4.05 ppm; see Table 1 ). The identified metabolite residuals were removed from all MM spectra acquired with TE = 2.8 ‐ 40 ms. For the MM spectra acquired with TE ≥ 60 ms (section 2.2.5.)…”

“…Detailed steps for constructing reliable PK are also provided. Furthermore, additional metabolite residuals were identified and reliably removed from MM spectra compared with previous preclinical 10 , 45 (Ins‐4.05 ppm) and clinical (tCr‐3.0 ppm, Ins‐3.6 ppm, and Tau‐3.25 ppm) 9 , 11 , 23 , 34 studies (Table 1 ).…”

“… 3 , 11 , 13 , 21 , 22 , 23 , 24 , 35 , 48 , 49 At UHF, 9 to 24 MM peaks can be distinguished based on the nomenclature used, 3 , 9 , 11 with some peaks needing further investigations. These peaks have been previously fitted using mainly singlets, 9 , 11 , 34 , 45 while some studies used several peaks to fit individual MM components without specific PK, which were then grouped in a limited number of components to avoid over‐parametrization. 13 , 48 , 49 Even though MM signals can be modeled using singlets, they have complex spectral patterns.…”

“…There are few studies evaluating the impact of parametrized MM with PK on metabolite concentrations, together with the assessment of the best soft constraints while still keeping enough flexibility to estimate MM changes. 11 , 45 , 50 …”

“… 34 However, a small MM contribution cannot be excluded. In contrast to previous studies, 11 , 45 , 50 each of the 10 MM components was parametrized by fitting with several Lorentzian functions to consider various unknown constituents that might be contained in one broad resonance. This approach reduced the overlap between MM resonances that might arise when broad functions are used.…”