Thermal heterogeneity within aqueous materials quantified by 1H NMR spectroscopy: Multiparametric validation in silico and in vitro

Abstract We recently suggested a new paradigm for statistical analysis of thermal heterogeneity in (semi-)aqueous materials by 1 H NMR spectroscopy, using water as a temperature probe. Here, we present a comprehensive in silico and in vitro validation that demonstrates the ability of this new technique to provide accurate quantitative parameters characterizing the statistical distribution of temperature values in a volume of (semi-)aqueous matter. First, line shape parameters of numerically simulated water 1 H NMR spectra are systematically varied to study a range of mathematically well-defined temperature distributions. Then, corresponding models based on measured 1 H NMR spectra of agarose gel are analyzed. In addition, dedicated samples based on hydrogels or biological tissue are designed to produce temperature gradients changing over time, and dynamic NMR spectroscopy is employed to analyze the resulting temperature profiles at sub-second temporal resolution. Accuracy and consistency of the previously introduced statistical descriptors of temperature heterogeneity are determined: weighted median and mean temperature, standard deviation, temperature range, temperature mode(s), kurtosis, skewness, entropy, and relative areas under temperature curves. Potential and limitations of this method for quantitative analysis of thermal heterogeneity in (semi-)aqueous materials are discussed in view of prospective applications in materials science as well as biology and medicine.