Amide proton signals as pH indicator for in vivo MRS and MRI of the brain-Responses to hypercapnia and hypothermia

Using proton MRS and MRI of mouse brain at 9.4 T, this work provides the first in vivo evidence of pH-dependent concurrent changes of three amide signals and related metabolic responses to hypercapnia and hypothermia. During hypercapnia, amide proton MRS signals of glutamine at 6.8-6.9 ppm and 7.6 ppm as well as of unspecific compounds at 8.1-8.3 ppm increase by at least 50% both at 37 °C and 22 °C. These changes reflect a reduced proton exchange with water. They are strongly correlated with intracellular pH which ranges from 6.75 ± 0.10 to 7.13 ± 0.06 as determined from a shift in creatine phosphokinase equilibrium. In MRI, saturation transfer from aliphatic as well as aromatic and/or amide protons alters slightly during hypercapnia and significantly during hypothermia. The asymmetry in magnetization transfer ratios decreased slightly during hypercapnia and hypothermia. Regardless of pH or temperature, saturation transfer from aliphatic protons between − 2 and − 4 ppm frequency offset to water protons is significantly greater than that from aromatic/amide protons at corresponding offsets between + 2 and + 4 ppm. Irradiation of aliphatic compounds at − 3.5 ppm frequency offset from water predominantly saturates lipids and water associated with myelin. Taken together, the results indicate that, for the B1 power used in this study, dipolar coupling between aliphatic and water protons rather than proton exchange is the dominant factor in Z-spectra and magnetization transfer ratio asymmetry of the brain in vivo.