Time-Resolved fMRI-fMRS measures simultaneous Neurotransmitters and BOLD-fMRI signals in the human brain at 7T 2021 Minnesota Workshop on High and Ultra-high Field Imaging https://bit.ly/3kE66qk

1. Time-Resolved fMRI-fMRS measures simultaneous Neurotransmitters and BOLD-fMRI signals in the human brain at 7T
Uzay E Emir1
, Renée S. Koolschijn2
, Helen Barron2
, Betina Ip2
1
Purdue University, 2
University of Oxford
The blood-oxygenation level dependent (BOLD)-fMRI response, one of the most widely used measures of functional activity, reflects a
spectrum of energy and blood-flow dependent processes [1] that are not completely understood. 1H-MRS is a non-invasive measure of
absolute concentrations of neurochemicals that has been exploited to identify biomarkers of normal and neurological conditions [2].
Recently, we have developed and implemented a novel functional MR-sequence that simultaneously recorded BOLD-fMRI and 1H-MRS
(combined fMRI-MRS) to quantify simultaneous changes in neurochemicals and brain activity using BOLD-fMRI [3]. In this work, we will
present two novel applications of this advanced combined and time-resolved fMRI-MRS technique
at 7T.
Methods
Two experiments were conducted under IRB ethical approval at 7T using a whole-body MR system
(Siemens, Erlangen) with a Nova Medical 32-channel receive array head-coil. For the binocular
rivalry experiment (Figure 1), Thirteen participants (7 females, 29.2 ± 6.0 years) took part in the
study with a block design experiment paradigm [4]. For the memory recall experiment, twenty-two
(mean age of 22.8 ± 0.74 years, 4 males) took part in the study with an event-related design
experimental paradigm (Figure 2) [5]. A dielectric pad containing a suspension of Barium Titanate
(BaTiO3) was placed behind the occiput of each subject to improve the transmit-field efficiency.
A 2 x 2 x 2 cm MRS VOI was positioned in the occipital lobe. fMRI volumes and MRS spectra
were acquired in the same TR of 4s over a 512 s scan (3D EPI, resolution= 4.3 x 4.3 x 4.3 mm;
flip angle = 5°, repetition time TRepi= 83 ms, TE= 25 ms, FOV= 240 mm) [3]. Functional MRS data
were acquired using the semi-LASER pulse sequence (TE = 36 ms, TRmrs = 4 s) [3]. Metabolites
were quantified using LCModel.
Results
The combined fMRI-MRS sequence acquired robust BOLD-fMRI responses (Fig. 2a) and MRS
spectra (Figure 3). In the first experiment, we related the behaviorally derived eye dominance
index (EDI), measured in the binocular rivalry experiment, to interocular GABA. EDI was
significantly correlated with interocular GABA (Figure 3b, Spearman’s Rank Correlation r = 0.62,
uncorrected p= 0.037). In the second experiment, using time-resolved fMRI-fMRS in humans, we
show that recall of a visual cue is accompanied by a dynamic increase in the ratio between
glutamate and GABA in visual cortex (Figure 4).
Discussion and Conclusion
In summary, we tested the feasibility of a novel combined fMRI-MRS method by measuring
responses to a visual stimulus in the human visual cortex and showed reliable changes in
glutamate and GABA and BOLD-fMRI. In addition, using time-resolved fMRI-fMRS, we report a
transient increase in glu/GABA ratio in V1. Thus, our combined fMRI-MRS method has the
potential to address questions about cortical function in the living human brain that cannot be answered by separate application of either
technique alone.
References
1. Logothetis, N.K., et al., Neurophysiological investigation of the basis of the fMRI signal. Nature, 2001. 412(6843): p. 150-7.
2. Oz, G., et al., Clinical proton MR spectroscopy in central nervous system disorders. Radiology, 2014. 270(3): p. 658-79.
3. Ip, I.B., Berrington, A., Hess, A.T., Parker, A.J., Emir, U.E., Bridge, H., 2017. Combined fMRI-MRS acquires simultaneous glutamate
and BOLD-fMRI signals in the human brain. NeuroImage 155, 113–119.
4- I. Betina Ip, Claudia Lunghi, Uzay E. Emir, Andrew J. Parker, Holly Bridge bioRxiv 2020.09.10.291047; doi:
https://doi.org/10.1101/2020.09.10.291047
5- Renée S. Koolschijn, Anna Shpektor, I. Betina Ip, William T. Clarke, David Dupret, Uzay E. Emir, Helen C. Barron bioRxiv
2020.11.27.401299; doi: https://doi.org/10.1101/2020.11.27.401299
Figure 1 The combined fMRI-
MRS monocular visual
stimulation paradigm.
Figure 2 Using fMRI-fMRS data
to assess changes in BOLD
signal and glu/GABA ratio during
an event related experimental
design
Figure 3 (a) The interocular GABA metric was calculated to
show the difference in GABAergic inhibition between
activation of the DE or NDE eye. (b) Eye dominance was
highly correlated with interocular GABA.
Figure 4 Memory recall and inference involves a transient
break in glu/GABA ratio, time-Resolved fMRI-fMRS
measures simultaneous Neurotransmitters and BOLD-fMRI
signals