Combined fMRI-MRS acquires simultaneous glutamate and BOLD-fMRI signals in the human brain

Abstract

Combined fMRI-MRS is a novel method to non-invasively investigate functional activation in the human brain using simultaneous acquisition of hemodynamic and neurochemical measures. The aim of the current study was to quantify neural activity using combined fMRI-MRS at 7 T. BOLD-fMRI and semi-LASER localization MRS data were acquired from the visual cortex of 13 participants during short blocks (64 s) of flickering checkerboards. We demonstrate a correlation between glutamate and BOLD-fMRI time courses (R=0.381, p=0.031). In addition, we show increases in BOLD-fMRI (1.43±0.17%) and glutamate concentrations (0.15±0.05 I.U., ~2%) during visual stimulation. In contrast, we observed no change in glutamate concentrations in resting state MRS data during sham stimulation periods. Spectral line width changes generated by the BOLD-response were corrected using line broadening. In summary, our results establish the feasibility of concurrent measurements of BOLD-fMRI and neurochemicals using a novel combined fMRI-MRS sequence. Our findings strengthen the link between glutamate and functional activity in the human brain by demonstrating a significant correlation of BOLD-fMRI and glutamate over time, and by showing ~2% glutamate increases during 64 s of visual stimulation. Our tool may become useful for studies characterizing functional dynamics between neurochemicals and hemodynamics in health and disease.

Neurochemical correlates of scene processing in the precuneus/posterior cingulate cortex: A multimodal fMRI and 1H‐MRS study

“…This might then in turn lead to different neurometabolite correlates of resting (i.e., as in Hu et al, ) versus active processing (i.e., scene tasks as in this study) in PCu/PCC. Further fMRI‐MRS studies (Ip et al, ) will be needed to explore this in more detail.…”

Optimized in vivo brain glutamate measurement using long‐echo‐time semi‐LASER at 7 T

“…These dependencies include the maximum available B 1 amplitude, pulse duration, and crusher gradient duration. Echo times as short as 36 ms (Reference ) and 38 ms (Reference ) have been achieved at 7 T. An even shorter echo time of 26 ms (Reference ) was achieved using 16 RF amplifiers (1 kW each), which provided greater B 1 amplitude, allowing for shorter adiabatic pulses. Trapezoidal adiabatic pulses, which can achieve more spectral bandwidth with less B 1 amplitude than hyperbolic secant adiabatic pulses, also allows for shorter pulse lengths and thus even shorter echo times.…”

“…Regardless of the available hardware, acquiring short-echo-time spectra has the added complication of a more pronounced macromolecule signal, which complicates the subsequent fitting and quantification of metabolites, particularly glutamate. In fact, Zhong and Ernst showed that the intensity of the macromolecule peak at 0.9 ppm doubled at T E = 8 ms compared with T E = 30 ms. 15 Several approaches can be used to estimate the macromolecule contribution including spline fitting (LCModel 45 ), measuring the macromolecule signal using inversion recovery techniques and including the lineshape as a basis function in the prior knowledge template, [41][42][43][44]46 use of a parameterized mathematical model of the macromolecules in the prior knowledge template, 6,24,47,48 or acquisition of a subject-specific metabolite-nulled macromolecule spectrum that is subtracted from the full spectrum. 11,49 Not surprisingly, Schaller et al 48 showed that the approach used to remove the macromolecule signal when using short echo times can significantly impact glutamate quantification, which contributes to variability in the glutamate measurement and complicates the comparison of glutamate levels from studies that use different methods for macromolecule signal removal.…”

Cortical excitability controls the strength of mental imagery

“…excitability was found (32). In addition, there is evidence for a strong link between BOLD-fMRI activity and glutamate concentration: using a combined fMRI-MRS approach where BOLD-fMRI activity and glutamate signals were recorded simultaneously, researchers found that the time courses of fMRI-BOLD activity and Glutamate concentration were strongly correlated (33). Evidence whether such a relationship also holds on a between-subject level is still missing, but seems plausible.…”