Quantifying global-brain metabolite level changes with whole-head proton MR spectroscopy at 3 T

Abstract

BACKGROUND AND PURPOSE To assess the sensitivity of non-localized, whole-head 1H-MRS to an individual’s serial changes in total-brain NAA, Glx, Cr and Cho concentrations – metabolite metrics often used as surrogate markers in neurological pathologies. MATERIALS AND METHODS In this prospective study, four back-to-back (single imaging session) and three serial (successive sessions) non-localizing, ~3 minute 1H-MRS (TE/TR/TI= 5/104/940 ms) scans were performed on 18 healthy young volunteers: 9 women, 9 men: 29.9±7.6 [mean±standard deviation (SD)] years old. These were analyzed by calculating a within-subject coefficient of variation (CV=SD/mean) to assess intra- and inter-scan repeatability and prediction intervals. This study was Health Insurance Portability and Accountability Act-compliant. All subjects gave Institutional Review Board-approved written, informed consent. RESULTS The intra-scan CVs for the NAA, Glx, Cr and Cho were: 3.9±1.8%, 7.3±4.6%, 4.0±3.4% and 2.5±1.6%, and the corresponding inter-scan (longitudinal) values were: 7.0±3.1%, 10.6±5.6%, 7.6±3.5% and 7.0±3.9%. This method is shown to have 80% power to detect changes of 14%, 27%, 26% and 19% between two serial measurements in a given individual. CONCLUSIONS Subject to the assumption that in neurological disorders NAA, Glx, Cr and Cho changes represent brain-only pathology and not muscles, bone marrow, adipose tissue or epithelial cells, this approach enables us to quantify them, thereby adding specificity to the assessment of the total disease load. This will facilitate monitoring diffuse pathologies with faster measurement, more extensive (~90%) spatial coverage and sensitivity than localized 1H-MRS.

Glutamatergic Dysfunction and Glutamatergic Compounds for Major Psychiatric Disorders: Evidence From Clinical Neuroimaging Studies

“…Typically, MRS is used to measure signals within a predefined region of interest (i.e., a voxel), although the technique is still being updated to acquire biochemical signals from the whole brain (8). Using 1 H-MRS, and depending on the chemical environment, each proton may be visualized at a specific chemical shift (peak position along the chemical shift axis).…”

Whole brain neuronal abnormalities in focal quantified with proton MR spectroscopy

“…(b) That this global metabolic metric may be a more sensitive marker than global morphological ones. However, these patients were not scanned prior to the onset of their disease, nor followed afterwards (at sufficiently large time intervals to be sensitive to WB NAA change) (Davitz et al, 2017). It is, therefore, impossible to determine from our data whether the NAA deficits preceded the disease onset, or occurred afterwards.…”

“…The fit basis set (synthesized by the VeSPA-Simulation application using the MRS sequence actual RF pulses and timings) comprised total-NAA [NAA+ NAA-glutamate at 7:1 ratio (Pouwels and Frahm, 1997)], Cho, Cr, glutamate+glutamine (Glx) and myo- inositol (mI). [Note that the last two were only included in the simulation to more accurately account for the total spectral lineshape; however, because the mI peak is partially suppressed by the bandwidth of the 1331 readout pulse of the sequence (Soher et al, 2014) and the Glx coefficient of variation is ~30% larger than the major metabolites’ (Davitz et al, 2017), both were excluded from the results]. S ij were scaled into absolute amounts, Q ij , against a 2 L sphere of Q i vitro = 25, 20, and 6 millimoles NAA, Cr and Cho in water at physiological ionic strength: Qij=Qivitro⋅SijSiR⋅Vk180°VR180°millimoles, where S iR is the VeSPA-Analysis derived sphere’s metabolites’ signals; and V j 1 80° , V R 180° subject and sphere RF voltages for non-selective 1 ms 180° pulses.…”

A Longitudinal, Observational Study of the Effect of Dimethyl Fumarate on Hippocampal Metabolites in RRMS using 1H-MR Spectroscopy

“…Reduced level of NAA in the grey matter of MS patients has also been recently demonstrated [31] further supporting the importance of NAA as a disease marker. Increased levels of mI have been detected by others in the CSF from MS patients [32] and also in the T1-weighted hypo-intense chronic MS lesions [33], the latter thought to be associated with astrogliosis around the lesion [34].…”