Proton magnetic resonance spectroscopy with metabolite nulling reveals regional differences of macromolecules in normal human brain

Abstract

Purpose: To quantify the macromolecular content in different anatomic brain regions and to evaluate an age dependency of the macromolecular concentrations. Material and Methods:A short echo time Stimulated Echo Acquisition Mode (STEAM) sequence was used without and with inversion recovery metabolite nulling in 8 -12 healthy volunteers. Quantitation was achieved by an extended LCModel, and macromolecular resonances at 0.9, 1.4, 2.1, and 3.0 ppm were evaluated. Results:In the cerebellum, the 1.4, 2.1, and 3.0 ppm resonances were highest compared to all other regions (P Ͻ 0.02); the 0.9 ppm resonance was significantly higher than that of pons (P Ͻ 0.01). In the motor cortex, the 0.9, 1.4, and 2.1 ppm resonances were higher than those of white matter and pons (P Ͻ 0.02). Pons and white matter did not differ significantly from each other. A significant correlation of the macromolecular concentrations with the age could not be found. Conclusion:There were higher macromolecular concentrations in the cerebellum and motor cortex than in pons or white matter. These were probably due to the higher portions of gray matter in these volumes of interest (VOIs) than in the other regions. SHORT ECHO TIME PROTON MAGNETIC resonance spectroscopy (MRS) of the brain allows for the detection of so-called macromolecules with a molecular weight of above 3500 Da, forming a broad substructure below the signal from metabolites with lower molecular weights (1-6). Several approaches have been made to evaluate the macromolecular contributions in the baseline of the spectra to achieve a reliable quantitation of the metabolites (6 -10). Other studies pointed out a potential pathologic relevance of increased macromolecular resonances, e.g., in stroke, brain tumors or multiple sclerosis (3,(11)(12)(13). Although a correlation of metabolite concentrations with anatomic regions is well known (14 -19), there is only one work concerning regional alterations of the macromolecules with respect to supratentorial gray and white matter (6). More knowledge about variations of the macromolecules within different supra-and infratentorial anatomic regions of the brain is essential to avoid misinterpretations of macromolecular signals in healthy and pathological conditions. This study was focused on the macromolecular content of different anatomic brain regions, such as the cerebellum, motor cortex, pons, and parietal white matter in healthy subjects. Correlations between the macromolecular concentration and age were analyzed and compared with the work of Hofmann et al (6). The metabolite concentrations obtained from the different regions were compared to the literature. Possible factors influencing the measurements of the macromolecules such as relaxation effects and partial volume problems were considered. To evaluate the quality of the quantification method, the results for the macromolecular concentrations of the metabolite-nulled and not-nulled spectra were compared. MATERIALS AND METHODS SubjectsTwelve healthy male volunteers, aged 28 -62 years (median a...

MRS signal quantitation: A review of time- and frequency-domain methods

“…The latter is often preferred in recent publications (see, e.g., [126,63,140,141]). This can be explained by the fact that adding macromolecular profiles adds more prior knowledge [2] X X X QUEST [28] X X Elster et al's [38] X X TDFD Fit [85] X X X CFIT [3] X LCModel [18] X X X Young/Soher et al's [132,48,71] X X…”

“…However, recent studies [125][126][127] show that strong correlation between the macromolecular concentration/composition and the location of the voxel in the brain have been found. Hoffmann et al [125] also found significant correlation with age but not with gender, while no significant correlation with age could be detected by Mader et al [126] (the correlation with gender was not studied in the latter reference). Similarly, several conditions such as stroke [128], brain tumors [63] and multiple sclerosis [129] show an altered macromolecule profile.…”

“…On the other hand, the baseline can be modeled in the quantitation step. In parametric models, the profiles of the baseline components, obtained from measurements [126,63,[140][141][142][143][144] or from theoretical considerations [145], are added to the database of metabolites. The authors of these papers conclude that including the baseline components in the basis set of metabolite profiles provides more accurate results.…”

The Impact of Gabapentin Administration on Brain GABA and Glutamate Concentrations: A 7T 1H-MRS Study

“…However, macromolecule contamination remains a challenge for accurate quantification of brain metabolites using short echo-time spectroscopy. Methods currently under development include using double inversion recovery for metabolite-nulling to obtain macromolecular spectra, which can be used for subtraction or as prior knowledge for fitting (Kassem and Bartha, 2003;Mader et al, 2002). Further validation may be needed to test efficiency of macromolecule removal using these methods.…”

In vivo 1H NMR spectroscopy of individual human brain metabolites at moderate field strengths

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