Summary:To determine the distribution of cerebral glucose and lactate between the intracell ular and the extracellular space of the rat brain in vivo, the diffusion characteristic of glucose and lactate was compared with that of metabolites known to be mainly intracellular (N-acetylaspartate, choline, creatine, glu tamate, myo-inositol, and taurine) using a pulsed-field-gradient I H nuclear magnetic resonance technique. The detection of a glucose signal at large diffusion weighting provided direct ex perimental evidence of intracellular glucose in the rat brain. At large diffusion weighting, the apparent diffusion coefficient (ADC) of glucose and lactate was similar to that of the intra cellular metabolites such as N-acetylaspartate, creatine, and glutamate. At small diffusion weighting, the ADC of glucose It is generally assumed that the distribution volume of glucose (Ole) in the brain is similar to that of water (Lund-Andersen, 1979; Ojedde, 1992), demonstrated by biochemical extraction studies and indirect kinetic evi dence (Ojedde and Diemer, 1983; Holden et aI., 1991; Oruetter et aI., 1996), and that Ole phosphorylation is rate-limiting for metabolism (Furler et aI., 1991). Recent noninvasive studies suggest that Ole from blood initially enters a substantial compartment fast (Knudsen et aI., 1990; Hasselbaleh et aI., 1996) and that the brain Ole concentration is a linear function of the Ole concentra tion in the blood (Oruetter et aI., 1998a). These studies Received September 13, 1999; final revision received December 17, 1999; accepted December 20, 1999. Supported by National Institutes of Health Grants CA64338 and RR08079, the W. M. Keck Foundation, and the Whitaker Foundation (R.G.).Address correspondence and reprint requests to Josef Pfeuffer, PhD, Center for Magnetic Resonance Research, University of Minnesota Medical School, 202 1 Sixth Street S.E., Minneapolis, MN 55455, U.S.A.Abbreviations used: ADC, apparent diffusion coefficient; Cho, cho line-containing compounds; Cr, creatine; Glc, glucose; Glu, glutamate; Ins, myo-inositol; Lac, lactate; MM, macromolecule; NAA, N-acetyl aspartate; NAAG, N-acetylaspartylglutamate; NMR, nuclear magnetic resonance; PCr, phosphocreatine; T, temperature; Tau, taurine; TE, echo time; TM, middle interval; TR, repetition time.
736and lactate was increased, which was explained by a decreased relative contribution of intracellular glucose to the total signal. The calculated extracellular volume fraction of glucose (0.19 ± 0.05) and lactate (0.17 ± 0.06) was consistent with a substantial fraction of glucose and lactate signals being intracellular. The findings were direct in vivo evidence that the largest concen tration gradient of glucose is at the blood-brain barrier and that glucose is evenly distributed in the brain in vivo between the intracellular and extracellular space.