Prediction of multiple pH compartments by deep learning in magnetic resonance spectroscopy with hyperpolarized 13C-labelled zymonic acid

Background Hyperpolarization enhances the sensitivity of nuclear magnetic resonance experiments by between four and five orders of magnitude. Several hyperpolarized sensor molecules have been introduced that enable high sensitivity detection of metabolism and physiological parameters. However, hyperpolarized magnetic resonance spectroscopy imaging (MRSI) often suffers from poor signal-to-noise ratio and spectral analysis is complicated by peak overlap. Here, we study measurements of extracellular pH (pH(e)) by hyperpolarized zymonic acid, where multiple pH(e) compartments, such as those observed in healthy kidney or other heterogeneous tissue, result in a cluster of spectrally overlapping peaks, which is hard to resolve with conventional spectroscopy analysis routines. Methods We investigate whether deep learning methods can yield improved pH(e) prediction in hyperpolarized zymonic acid spectra of multiple pH(e) compartments compared to conventional line fitting. As hyperpolarized C-13-MRSI data sets are often small, a convolutional neural network (CNN) and a multilayer perceptron (MLP) were trained with either a synthetic or a mixed (synthetic and augmented) data set of acquisitions from the kidneys of healthy mice. Results Comparing the networks' performances compartment-wise on a synthetic test data set and eight real kidney data shows superior performance of CNN compared to MLP and equal or superior performance compared to conventional line fitting. For correct prediction of real kidney pH(e) values, training with a mixed data set containing only 0.5% real data shows a large improvement compared to training with synthetic data only. Using a manual segmentation approach, pH maps of kidney compartments can be improved by neural network predictions for voxels including three pH compartments. Conclusion The results of this study indicate that CNNs offer a reliable, accurate, fast and non-interactive method for analysis of hyperpolarized C-13 MRS and MRSI data, where low amounts of acquired data can be complemented to achieve suitable network training.