Quantitative 2D in-vivo spectroscopy using the ERETIC method

Introduction In-vivo H spectroscopy is a valuable tool for clinical diagnostics of various diseases and provides deeper insight into basic metabolic and physiological processes in the brain. It has been recently demonstrated that the combination of 2D spectroscopy sequences like JPRESS [5] and prior knowledge based fitting (ProFit) [6] can improve the reliable and independent detection and quantification of small and strongly overlapping signals such as GABA, Glutamate (Glu), Glutamine (Gln) and GSH substantially as compared to conventional short-echo 1D MRS protocols at 3T. This is of special interest as neurotransmitter and antioxidants play a significant role in the pathophysiology of psychiatric and neurological disorders, which are still insufficiently understood. However, so far only metabolite ratios e.g. to creatine could be reported, while a fundamental requirement to use spectroscopy in a clinical setting and for most physiological studies is the ability to reliably detect concentration changes of individual metabolite signals from the measured spectrum. This is usually done by using internal or external reference signals of known concentrations. Both of these approaches exhibit certain disadvantages and have never been combined with 2D JPRESS so far. Finding a suitably stable internal reference which stays constant in any disease is also impossible. Using external reference signals requires additional measurements and therefore prolonging total scan time, which is especially problematic for 2D resolved spectroscopy sequences that suffer from long scan-times anyway. A more sophisticated technique which can circumvent some of the disadvantages of both methods is ERETIC (Electric REference To access In vivo Concentration). A reliable reference is produced by injecting an artificial signal of known amplitude, phase and duration [1, 2, 3, 4] into the measured spectrum. In this work a 2D JPRESS sequence was combined for the first time to our knowledge with the ERETIC reference in-vivo to bring the benefits of a stable reference signal to quantitative in-vivo 2D spectroscopy.