NMR line shapes have long been analyzed to study coupling constants and multiplicities, molecular structure and mobility, chemical exchange and other molecular properties. Line shape narrowing by complex shim procedures, sample spinning and/or other techniques has been extremely important for optimal suppression of line shape contributions not related to molecular properties. In biomedical in vivo NMR spectroscopy, relatively broad resonances were considered an inevitable annoyance reducing spectral resolution. Indeed, line widths in spectra from biological objects are affected by susceptibility gradients (as a result of tissue structures) that cannot be canceled by shim gradients.
In addition, line shapes of suitable resonances can be characteristically broadened due to specific physicochemical parameters varying across a measured volume of tissue (or other heterogeneous material). A case in point is the shape of the inorganic phosphate (Pi) 31P resonance as its chemical shift is a function of intracellular pH (pHi) [1,2]; or the H2 1H resonance of exogenous imidazole ethoxycarbonylpropionic acid (IEPA) whose chemical shift varies with extracellular pH (pHe) . Here, line shapes are not only broadened, but actually encode information on the statistical distribution of parameter values (pHi or pHe) within the measured pH-heterogeneous sample. We suggest to decode this information by statistical line shape analysis ("quantitative heterogeneity MRS", qhMRS), and present here the experimental proof of principle of our approach, applied to judiciously designed IEPA solutions (phantoms).
This was accomplished by calculating ≥ 8 quantitative descriptors (in addition to the curve maximum) characterizing each statistical distribution of pH values within a given volume or voxel. Based on the H2-IEPA resonance, our qhMRS technique enables integration of statistical pH heterogeneity analysis into 1H MRSI protocols.
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