Rationale and Objectives
The objective of this study was to determine how metabolite values (total N-acetyl aspartate [tNAA], glutamate plus glutamine [Glx], total choline [tCho], myoinositol [mI], and total creatine [tCr]) vary across brain regions in healthy subjects. This study was implemented to create an internal reference database for patients with psychiatric disorders and epilepsy.
Materials and Methods
Using the multivoxel technique with a voxelwise phantom calibration on a 3-T magnetic resonance imaging scanner, metabolite levels of 29 healthy controls (13 men, 16 women; average age, 29 years) were obtained from the hippocampi, basal ganglia, insula cortex, cingulum, and precuneus. Additionally, gray and white matter metabolite values were obtained from the frontal and parietal lobes.
Results
No significant effect of gender was noticed. The total magnitude of variation was greatest for Glx, followed by tNAA, mI, tCho, and tCr. Glx/tCr, Glx, and tCr were increased in gray matter, while tNAA/tCr, tCho/tCr, respectively tNAA and tCho, were elevated in white matter. These findings indicate (1) anterior-to-posterior increases of tNAA/tCr and Glx/tCr, respectively tNAA and Glx, along the midline in gray matter (cingulum); (2) increased tNAA/tCr, respectively tNAA, in white matter in the fiber tracts of the precentral region; (3) an accentuated anterior-to-posterior increase of tCr in the insula cortex; and (4) an anterior-to-posterior decrease of tCho/tCr and tCho in white matter.
Conclusions
There are significant metabolic differences within tissue types and within tissue types at different locations; therefore, the spectra and metabolite values presented should provide a useful internal reference for both clinical and research studies.
Detailed knowledge about regional variation in brain metabolites is essential for an accurate interpretation of the results of proton magnetic resonance spectroscopy ( 1 H-MRS) in various brain diseases, such as epilepsy and psychiatric disorders . As for most laboratory tests, it is a prerequisite for an assessment of true metabolic disturbances and may contribute to a better functional understanding of certain diseases.
Commonly distinguishable metabolites include total N-acetyl aspartate (tNAA), total choline (tCho), myoinositol (mI), glutamate (Glu) plus glutamine (Gln) (Glu + Gln = Glx), and total creatine (tCr). In clinical settings, metabolite ratios are often used rather than absolute metabolite values because of variations in susceptibility, coil loading, tissue composition, and changes in receiver gain . Earlier proton magnetic resonance spectroscopic studies of the human brain have implemented the single-voxel technique, acquiring a single spectrum from a definite volume of tissue as an integral . This acquisition is fairly fast (3 minutes), and a spectrum is easily obtained, but it provides limited information about the regional distribution of brain metabolites. Multivoxel techniques acquire spectra simultaneously over a wide brain region, thus enabling the analysis of metabolite distribution and eventually covering the whole brain . The multivoxel technique refers to chemical shift imaging, which combines features of magnetic resonance imaging and MRS, yielding data from multiple adjacent voxels covering a large volume of interest in a single measurement.
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Materials and methods
Subjects
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Multivoxel MRS
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![Figure 1, Arrangement of three multivoxel spectra (a–f) into symmetric pairs on each side of the midline including the centrum semiovale (white matter), the cingulum (Ci), the precuneus (PC), the insula cortex (I), the basal ganglia (thalamus [T] and putamen [P]), and the hippocampus (H). (b,d,f) Reference lines and correct positioning. Pre, precentral gyrus.](https://storage.googleapis.com/dl.dentistrykey.com/clinical/MultivoxelMagneticResonanceSpectroscopyofCerebralMetabolitesinHealthyAdultsat3Tesla/0_1s20S1076633209004292.jpg)
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Postprocessing
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Statistical Analysis
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Results
Influence of Sex on Brain Metabolites in Different Brain Regions
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Right and Left Hemispheric Metabolite Differences
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Metabolite Differences Between Gray and White Matter
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Total and Regional Metabolite Magnitudes of Variation
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Intraregional Metabolite Variation in Gray and White Matter and Hippocampus
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Table 1
Summary of Significant Intraregional Variations in Gray and White Matter and the Hippocampus
Metabolite Ratios to Cr Individual Metabolite Values Voxel tNAA/tCr Glx/tCr tCho/tCr mI/tCr tNAA Glx tCho mI tCr Cingulum ( k = 6) ↑ 81% ↑ 77% ↓ 96% ↑ 92% ↑ 71% ↓ 96% Thalamus ( k = 1) Insula cortex ( k = 3) ↑ 95% ↑ 85% ↑ 90% ↑ 85% Hippocampus ( k = 3) ↑ 94% White matter (centrum semiovale) ( k = 15) CR ↑ 88% ↓ 85% CR ↑ 83% ↓ 62% CR ↑ 88% CR ↑ 88%
CR ↑, significant increase in the fiber tracts of the precentral region; Glx, glutamate plus glutamine; mI, myoinositol; tCho, total choline; tCr, total creatine; tNAA, total N-acetyl aspartate; ↑, significant increase from anterior to posterior; ↓, significant decrease from anterior to posterior.
Analysis of variance with Bonferroni’s correction with P i < P / k ( P = .05); k is the number of comparisons. The percentages of subjects showing the trend in the individual values are shown.
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Interregional Metabolite Variation
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Discussion
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Conclusion
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