Administration and (1)H MRS detection of histidine in human brain: application to in vivo pH measurement

Measurement of histidine in vivo offers the potential for tissue pH measurement using routinely performed (1)H MR spectroscopy. In the brain, however, histidine concentrations are generally too low for reliable measurement. By using oral loading of histidine, this study demonstrates that brain concentrations can be significantly increased, enabling detection of histidine by localized (1)H MR measurements and making in vivo pH measurement possible. In studies carried out on healthy human subjects at 1.5 T, a consistent spectral quality downfield from water was achieved using a PRESS sequence at short echo times. Measurements at different TE values helped to characterize the downfield spectral region. Histidine loading of 400 mg/kg of body weight increased brain histidine levels by approximately 0.8 mM, with maximum histidine concentration reached 4 to 7 hr after consumption. The pH calculated from histidine resonances was 6.96, and a hyperventilation study demonstrated the potential for measuring altered pH.