Quantification issues of in vivo¹H NMR spectroscopy of the rat brain investigated at 16.4 T

Abstract

The accuracy and precision of the quantification of metabolite concentrations in in vivo (1) H NMR spectroscopy are affected by linewidth and signal-to-noise ratio (SNR). To study the effect of both factors in in vivo (1) H NMR spectra acquired at ultrahigh field, a reference spectrum was generated by summing nine in vivo (1) H NMR spectra obtained in rat brain with a STEAM sequence at 16.4 T. By progressive deterioration of linewidth and SNR, 6400 single spectra were generated. In an accuracy study, the variation in the mean concentrations of five metabolites was mainly dependent on SNR, whereas 11 metabolites were predominantly susceptible to the linewidth. However, the standard deviations of the concentrations obtained were dependent almost exclusively on the SNR. An insignificant correlation was found between most of the heavily overlapping metabolite peaks, indicating independent and reliable quantification. Two different approaches for the consideration of macromolecular signals were evaluated. The use of prior knowledge derived by parameterization of a metabolite-nulled spectrum demonstrated improved fitting quality, with reduced Cramér-Rao lower bounds, compared to the calculation of a regularized spline baseline.

Follow-up analyses on the effects of long-term use of high fat diet on hippocampal metabolite concentrations in Wistar rats: Comparing Tarquin quantification of 7.0T rat metabolites to LCModel

“…For TARQUIN, we evaluated two macromolecular basis sets for: 1) based on LCModel (to allow more direct comparison with LC Model), further reffered to as LCModel-like basis set and 2) based on work by Hong and colleagues [5], further reffered to as Hong-like basis set; it consists of 16 macromolecules. Both basis sets are included in supplementary material.…”

Temperature dependence of 1H NMR chemical shifts and its influence on estimated metabolite concentrations

“…The similarities and differences between AQSES, which was used in this study, and other quantification methods have been described by Poullet et al [11]. The extensive use of prior knowledge allows the quantification of 20 or more metabolites, at least for high magnetic field strengths and excellent B 0 homogeneity [5,[14][15][16][17][18][19]. However, even under favorable experimental conditions and if correct prior knowledge is used, the separate quantification of some metabolites is difficult.…”

“…However, a separate quantification of Cr and PCr is hampered independent of line width, even for small temperature changes from 37 °C. While the simulations were performed for 7 T, small changes of chemical shifts due to pyrexia or anaesthesia should also be taken into account at higher B 0 to avoid quantification errors, even in case of an excellent separation between the CH 2 signals of Cr and PCr [16][17][18]. Alternatively, the CH 3 and CH 2 signals of Cr and PCr could be modelled as separate singlet signals.…”

1H MRS characterization of neurochemical profiles in orthotopic mouse models of human brain tumors

“…Spectra from rat and mouse brains collected at 9.4 T have been used to measure the concentration of 18 and 16 small metabolites respectively (1,2). The number of metabolites that can be reliably detected increases with field strength (3,4). The sensitivity of high field 1 H in vivo MRS is sufficient to detect differences in the neurochemical profiles of post-natal mice from 10 through 90 days of age (3), between mouse strains (5), and between tumors derived from cultured human tumor cell lines or directly implanted human tumor cells (6).…”