Homocarnosine and the measurement of neuronal pH in patients with epilepsy

Homocarnosine is a dipeptide of gamma‐aminobutyric acid (GABA) and histidine found uniquely in the brain, most likely in a subclass of GABAergic neurons. By comparison of spectra from the occipital lobe of patients receiving a homocarnosine elevation drug to normal subjects we have assigned two elevated resonances in the short TE 1 H MRS spectrum to homocarnosine. These resonances are partially resolved at 7.05 and 8.02 ppm in a short TE spectrum at 2.1 T when macromolecule resonances are removed by subtraction of a spectrum in which the metabolite resonances are nulled by inversion recovery. The chemical shift of both of these resonances is sensitive to pH i . By comparison with a titration curve the pH i was calculated from the downfield resonance to be 7.06 in the patient group which is similar to values reported using the P i resonance. Based on the in vivo results and theoretical considerations the potential sensitivity for using nonelevated homocarnosine to measure pH is similar to that of P i under physiological conditions.