Tomographic Mapping of Brain Intracellular pH and Extracellular Water Space in Stroke Patients

Functional images of regional intracellular pH (pH_i) and of fractional volume of extracellular water (FVECW) were obtained in 10 patients with recent hemispheric infarction (between 10 and 19 days after onset of symptoms) using positron emission tomography (PET). The volume of extracellular water relative to that of total water was evaluated in each pixel of the PET scan 7–8 h after injection of ⁷⁶Br. The pH_i image was calculated from the data obtained after injection of [¹¹C]5,5-dimethyl-2,4-oxazolidinedione and from the FVECW image. Regional CBF, oxygen extraction, and oxygen metabolism were also measured in the same patients. In normal hemisphere, mean ± SD values for FVECW and pH_i were 0.12 ± 0.01 and 6.86 ± 0.11, respectively. FVECW was increased in the infarcted area in most patients. pH_i was increased in the infarct in seven patients and unchanged in three. The increase in pH_i was not correlated with changes in FVECW, CBF, or CMRO₂, but there was a significant correlation with the decrease in oxygen extraction fraction in the same region. Thus, the decreased H⁺ content in the infarcted area was correlated with the occurrence of perfusion in excess of metabolic demand. An alkaline shift in pH_i enhances the glycolysis rate and could explain why the glucose metabolism is less affected than the oxygen metabolism in recent cerebral infarction. The pH_i measured in the infarct could represent mainly the pH_i of phagocytic cells that use aerobic glycolysis to synthesize hydrogen peroxide.