Spectroscopic assessment of alterations in macromolecule and small-molecule metabolites in human brain after stroke.

BACKGROUND AND PURPOSE: We sought to measure the temporal evolution and spatial distribution of lesion macromolecules and small molecules (lactate, N-acetyl compounds, creatine, and choline) in stroke patients by using short echo time in vivo proton MR spectroscopy. METHODS: Single-voxel spectra with TE=22 ms were obtained with and without inversion recovery suppression of small-molecule resonances from 30 examinations of 24 patients 3 to 214 days after stroke. Subtraction of the suppressed from the unsuppressed spectra yielded metabolite spectra without overlap from macromolecules. Two-dimensional spectroscopic images were acquired with macromolecule and small-molecule suppression from 5 additional patients. RESULTS: Macromolecule signals were elevated in lesions relative to normal brain and tended to increase in the subacute period, even as lactate peaks declined. Regions of increased lactate, increased macromolecule signal at 1.3 ppm, and decreased N-acetyl compounds were closely correlated in the 2D spectroscopic images. CONCLUSIONS: Short echo time spectra can be acquired in vivo in a manner that improves signal-to-noise ratio over long echo experiments and resolves overlapping macromolecule and small-molecule signals. The prominent macromolecule signals seen in the subacute period in association with persistently elevated lactate may represent mobile lipids in macrophages or other cells.

Proton spectroscopy of human stroke: assessment of transverse relaxation times and partial volume effects in single volume steam MRS.

Proton T2 relaxation times were measured in 13 stroke patients and 13 aged-matched normal subjects at 2.1 T. Spectra were acquired from an 8-cc volume using the STEAM sequence with echo times (TE) of 30.4 ms and 270.0 ms and repetition time of 2.8 s. Transverse relaxation times were estimated using two-point calculations. Percentage volume of infarct in the STEAM voxel was measured on spin-echo MRI encompassing the infarct and correlated with the peak amplitude of N-acetylated compounds (NA). T2 values of NA, creatine, and choline resonances showed no significant difference between patients and controls. T2 for lactate in patients was 780 +/- 257 ms, respectively (mean +/- SE, n = 7). In stroke patients, high inverse correlation was found between the absolute NA signal and partial volume of normal brain contributing to each spectrum (p < .001, r = 0.97). Together with unchanged T2, this suggests that NAA largely disappears from infarcted tissue within 24 hr postinfarct.

Metabolic assessment of a neuron-enriched fraction of rat cerebrum using high-resolution 1H and 13C NMR spectroscopy.

This study explored the utility of 1H and 13C magnetic resonance spectroscopy to study a neuron-enriched preparation made from rat cerebrum. The preparation contained high concentrations of N-acetylaspartate and gamma-aminobutyric acid and low concentrations of glutamine, indicating that it was in fact rich in neuronal cytosol. This was confirmed by immunohistochemical studies with antibodies to neuronal and glial markers. A method of metabolite quantification based on the creatine signal yielded metabolite concentrations similar to those of rat cerebrum, whereas concentrations based on the metabolite/protein ratio were five times lower, suggesting that much protein in the preparation was not associated with functioning cytoplasm. The metabolic competence of the preparation was assessed by quantitative measurements of its ability to convert 1-13C-glucose into lactate, glutamate, aspartate, and other metabolites under well oxygenated conditions for 30 min. Calculated from the creatine standard, the mean glycolytic rate was the same as in a synaptosomal preparation studied under similar conditions and the same as rat cerebrum in vivo. Tricarboxylic acid cycle flux occurred at half the rate observed in the synaptosomal preparation and 16% of the basal cerebral metabolic rate in vivo.