Semi-parametric time-domain quantification of HR-MAS data from prostate tissue.

High Resolution--Magic Angle Spinning (HR-MAS) spectroscopy provides rich biochemical profiles that require accurate quantification to permit biomarker identification and to understand the underlying pathological mechanisms. Meanwhile, quantification of HR-MAS data from prostate tissue samples is challenging due to significant overlap between the resonant peaks, the presence of short T2* metabolites such as citrate or polyamines (T2 from 25 to 100 msec) and macromolecules, and variations in chemical shifts and T2*s within a metabolite's spin systems. Since existing methods do not address these challenges completely, a new quantification method was developed and optimized for HR-MAS data acquired with an ultra short T(E) and over 30,000 data points. The proposed method, named HR-QUEST (High Resolution--QUEST), iteratively employs the QUEST time-domain semi-parametric strategy with a new model function that incorporates prior knowledge from whole and subdivided metabolite signals. With these features, HR-QUEST is able to independently fit the chemical shifts and T2*s of a metabolite's spin systems, a necessity for HR-MAS data. By using the iterative fitting approach, it is able to account for significant contributions from macromolecules and to handle shorter T2 metabolites, such as citrate and polyamines. After subdividing the necessary metabolite basis signals, the root mean square (RMS) of the residual was reduced by 52% for measured HR-MAS data from prostate tissue. Monte Carlo studies on simulated spectra with varied macromolecular contributions showed that the iterative fitting approach (6 iterations) coupled with inclusion of long T2 macromolecule components in the basis set improve the quality of the fit, as assessed by the reduction of the RMS of the residual and of the RMS error of the metabolite signal estimate, by 27% and 71% respectively. With this optimized configuration, HR-QUEST was applied to measured HR-MAS prostate data and reliably quantified 16 metabolites and reference signals with estimated Cramér Rao Bounds ≤5%.

Influence of measured and simulated basis sets on metabolite concentration estimates.

By quantification of brain metabolites, localized brain proton MRS can non-invasively provide biochemical information from distinct regions of the brain. Quantification of short-TE signals is usually based on a metabolite basis set. The basis set can be obtained by two approaches: (1) by measuring the signals of metabolites in aqueous solution; (2) by quantum-mechanically simulating the theoretical metabolite signals. The purpose of this study was to compare the effect of these two approaches on metabolite concentration estimates. Metabolite concentrations were quantified with the QUEST method, using both approaches. A comparison was performed with the aid of Monte Carlo studies, by using signals simulated from both basis sets. The best results were obtained when the basis set used for the fit was the same as that used to simulate the Monte Carlo signals. This comparison was also performed using in vivo short-TE signals acquired at 7 T from the central region of rat brains. The concentration estimates, with confidence intervals, obtained using both basis sets were in good agreement with values from the literature. The in vivo study showed that, in general, the differences between the estimates obtained with the two basis sets were not statistically significant or scientifically important. Consequently, a simulated basis set can be used in place of a measured basis set.