Simultaneous Measurement of Cerebral Blood Flow and Energy Metabolites in Piglets Using Deuterium and Phosphorus Nuclear Magnetic Resonance

Abstract

This report demonstrates the feasibility of using deuterium (²H) and phosphorus (³¹P) nuclear magnetic resonance (NMR) spectroscopy to make multiple simultaneous determinations of changes in cerebral blood flow, brain intracellular pH, and phosphorylated metabolites for individual animals. In vivo spectra were obtained from the brains of newborn piglets immediately following an intracarotid bolus injection of deuterium oxide. Experiments were performed at magnetic field strengths of 1.9 T (²H NMR only) or 4.7 T (interleaved ²H and ³¹P NMR). The rate of clearance of deuterium signal was used to calculate cerebral perfusion rates (CBF_deuterium) during a stable control physiologic state and conditions known to alter blood flow. CBF_deuterium values measured at 1.9 T under conditions of control (normocarbia, normotension), hypercarbia, hypocarbia, and varying degrees of ischemia induced by hypotension showed a significant positive correlation with values measured simultaneously using radiolabeled microspheres (CBF_deuterium = 0.4 × CBF_microspheres + 8; r = 0.8). Simultaneous interleaved ²H and ³¹P NMR measurements under control conditions indicate that brain energy metabolites and intracellular pH remained at constant levels during the time course of the administration and clearance of deuterium oxide. Also, brain phosphorylated metabolites and intracellular pH did not differ significantly from their preinjection levels. Under control physiologic conditions, CBF_deuterium varied by ±6% and phosphorylated metabolite levels did not show a significant change with time, as measured from 15 blood flow determinations collected over 4 h. The results indicate that CBF_deuterium determinations have excellent reproducibility and do not affect brain energy metabolite levels. The procedures described here have the potential to bring a novel methodology to bear on investigating the relationship between cerebral perfusion and energy status during conditions such as ischemia or asphyxia.