A time-domain algorithm for NMR spectral normalization

Recently, a new method for quantitatively comparing NMR spectra of control and treated samples, in order to examine the possible occurring variations in cell metabolism and/or structure in response to numerous physical, chemi cal, and biological agents, was proposed. This method is based upon the uti lization of the maximum superposition normalization algorithm (MaSNAl) oper ative in the frequency domain and based upon maximizing, by an opportune si gn variable measure, the spectral region in which control and treated spect ra are superimposed. Although the frequency-domain MaSNAl algorithm was ver y precise in normalizing spectra, it showed some limitations in relation to the signal-to-noise ratio and to the degree of diversity of the two spectr a being analyzed. In particular, it can rarely be applied to spectra with a small number of visible signals not buried in the noise such as generally in vivo spectra. In this paper, a time-domain normalization algorithm is pr esented. Specifically, it consists in minimizing the rank of a Hankel matri x constructed with the difference of the two free induction decay signals. The algorithm, denoted MiRaNAl (minimum rank normalization algorithm), was tested by Monte Carlo simulations as well as experimentally by comparing tw o samples of known contents both with the new algorithms and with an older method using a standard. Finally, the algorithm was applied to real spectra of cell samples showing how it can be used to obtain qualitative and quant itative biological information. (C) 2000 Academic Press.