Method to correlate 1H MRSI and 18FDG-PET.

[18F]Fluorodeoxyglucose positron emission tomography (PET) is widely used to measure the cerebral metabolic rate of glucose consumption (CMRglc) in the study of normal and diseased brain (1–3). Because glucose is the sole substrate for normal brain metabolism, values of CM-Rglc likely reflect overall levels of brain metabolic activity. But whether CMRglc directly represents the metabolic activity of neurons, and not of other cells, has yet to be established. It is difficult to address this question, particularly in vivo in humans, with PET alone. PET data are acquired as averages over macroscopic volumes of tissue. Thus, the CMRglc values acquired by PET would be influenced by both neuronal metabolic rate and neuronal density in the tissue volume. Further, realistic tissue volumes contain not only neurons, but also other cells, in particular neuroglia, that consume glucose. There is growing evidence that glia actually consume glucose at a higher rate than neurons do (4). The issue is important because both aging and disease may reduce neuron populations and so affect the measurement of metabolic rates. Atrophy correction is only a partial solution because atrophy correction expresses cellular depletion in terms of gross tissue loss without regard to the type or density of cells present in the lost or in the remaining tissue. A method of indexing neuron density in vivo might permit more accurate assessment of these structural contributions to metabolic measurements, and therefore would improve the calculation of functional effects. The extent to which disease affects true metabolism could then be better understood. Proton magnetic resonance spectroscopic imaging of the brain (1H MRSI) detects the amino acid N-acetyl aspartate (NAA), which is found in high concentrations only in neurons and is virtually undetectable in other cells, including glia (5,6). NAA resonance intensity in the 1H MRSI spectrum is therefore related to neuron density and/or to NAA content per neuron. Thus, how CMRglc varies as a function of NAA concentration ([NAA]) should reflect the way in which brain glucose metabolism is affected by neuron density and/or by NAA content per neuron. The CMRglc-to-[NAA] relationship could be derived for an individual subject by plotting local CMRglc against local [NAA] across that subject’s brain. The CMGglc-to-[NAA] relationship might be expected to vary from subject to subject depending on factors such as subject cognitive status. However, there are limitations to this approach. First, although cortical gray matter is the tissue of primary interest in evaluating brain metabolic activity, PET and 1H MRSI data are often expressed in terms of whole, unsegmented brain tissue, rather than as values for cortical gray matter alone. Second, even if regional data are compared, the spatial resolution of MRSI is lower than that of PET, a source of possible signal infidelity. Therefore, the aims in this study were 1) to establish a method for the assessment of CMRglc and [NAA] in cortical gray matter, accounting for differences between PET and 1H MRSI image resolution; 2) to look for the quantitative relationship between gray matter CMRglc and [NAA] in individual cognitively normal, cognitively impaired, and demented subjects; and 3) to explore whether this CMRglc-to-[NAA] relation varies with cognitive status across subjects.