Multiparametric quantification of the heterogeneity of free Ca 2+ concentration by 19 F MR spectroscopy.

For biological tissue that is heterogeneous with respect to free intracellular Ca2+ concentration ([Ca2+ ]i ), the lineshape of the 19 F MRS resonance of injected [Ca2+ ]-sensitive 4-FBAPTA or BAPTA-FF reflects the statistical distribution of [Ca2+ ]i values. While conventional 19 F MRS of these fluorinated Ca2+ reporter molecules only provides one [Ca2+ ]i value per spectrum, our specially designed lineshape analysis reveals at least eight quantitative statistical parameters (descriptors) characterizing the [Ca2+ ]i distribution within the observed tissue volume. To this end, the [Ca2+ ]-sensitive 19 F MRS resonance is transformed into a [Ca2+ ]i curve. Subsequently, the digital points of this [Ca2+ ]i profile are used to build a histogram using dedicated algorithms. The following statistical descriptors are computed from this histogram: weighted mean and median, standard deviation, range, mode(s), kurtosis, skewness, and entropy. Our new method is thoroughly validated through in silico and experimental models. The potential of combining statistical [Ca2+ ] information with spatial resolution is demonstrated by simulated statistical CSI maps. This proof of principle should form the basis of future in vivo studies in physiology and medicine, notably in heart and muscle research.