Simultaneous, trimodal MR-PET-EEG at 3T in humans: Glutamate drives energy consumption in the default mode network
Irene Neuner1,2,3, Jörg Mauler1, Ravichandran Rajkumar1,2,3, Ezequiel Farrher1, Elena Rota Kops1, Lutz Tellmann1, Jürgen Scheins1, Frank Boers1, Karl Josef Langen1,3,4, Hans Herzog1,2,3, and N. Jon Shah1,3,5

1Institute of Neuroscience and Medicine 4 (INM 4), Forschungszentrum Juelich GmbH, Juelich, Germany, 2Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany, 3JARA-BRAIN, Translational Medicine, Aachen, Germany, 4Department of Nuclear Medicine, RWTH Aachen University, Aachen, Germany, 5Department of Neurology, RWTH Aachen University, Aachen, Germany

Synopsis

Within the scope of this explorative pilot trial we focus on the role of GABA and glutamate within the default mode network with regard to energy consumption. In one simultaneous session MR, FDG-PET and EEG data were recorded at a 3T hybrid MR-BrainPET scanner (Siemens, Germany) equipped with a 32 channel MR-compatible EEG system (Brain Products, Germany) in 11 healthy volunteers. The Pearson correlation showed a statistically significant positive correlation between glutamate ratio and mean CMRGlu in the DMN (r = 0.678, n = 11, p = 0.022) but none to GABA.

Aim

The brain is a very efficient, fast acting and complex network. A large number of different brain areas have their own dedicated task and function but continuously share information with each other on a millisecond basis1. As a complex network, the brain relies for its function on different aspects of connectivity in the structural domain and functional domain. For the functional domain temporal patterns of neuronal activity, concentrations of transmitters and energy metabolism shape important aspects of brain activity. Within the scope of this explorative pilot trial, we focused on the functional aspect and aimed to investigate the role of GABA and glutamate within the cardinal resting state network, the default mode network, with regard to metabolic activity and energy consumption.

Methods

In one session MR, FDG-PET and EEG data were recorded simultaneously on a 3T hybrid MR-BrainPET scanner (Siemens, Germany) equipped with a 32 channel MR-compatible EEG system (Brain Products, Germany) in 11 healthy, male volunteers (mean age: 25.2 years SD: 1.2).

MR and EEG data acquisition

MP-RAGE (TR = 2250 ms, TE= 3.03 ms, 176 sagittal slices á 1 mm, GRAPPA factor 2). EPI sequence parameters for rs-fMRI were (TR: 2.2 s, TE: 30 ms, FOV: 200 mm, in plane resolution 3 mm, 165 volumes). Single-voxel spectra of the posterior cingulate cortex (PCC) and precuneus were consecutively measured using the point resolved spectroscopy (PRESS) sequence (TE1 = 14 ms, TE = 105 ms, TR = 2.5 s, NA = 128, 25 mm × 25 mm × 25 mm voxel size, RF pulse centred at 2.4 ppm, 16 step phase cycling). One extra complete phase cycle was measured without the water suppression RF pulse to record a water peak reference for eddy current correction and absolute metabolite concentration calibration. Before spectroscopy measurements, the B0 field was shimmed by running FASTESTMAP2 iteratively to ensure the FWHM of the reference water peak to be below 0.05 ppm. The GABA ratios (relative to Cr+PCr) and the glutamate ratios were investigated in the PCC and in the precuneus. During data acquisition volunteers were requested to close their eyes and relax but instructed not to fall asleep. EEG data were recorded simultaneously using a 32-channel MR compatible EEG system.

PET data acquisition

Approx. 200 MBq FDG were injected as a single bolus with the volunteer lying in the scanner at the start of the trimodal imaging study. PET data were acquired in list mode and iteratively reconstructed, with all necessary corrections, into 153 slices with 256 x 256 voxels sized 1.25 mm3. MR-based, template-based attenuation correction was applied.

Results

The paired-samples t-test showed that the mean CMRGlu within the DMN mask was higher than outside the DMN mask (t(10) = 13.773, p < 0.001). The Pearson correlation showed a statistically significant positive correlation between glutamate ratio and mean CMRGlu in the DMN (r = 0.678, n = 11, p = 0.022) but none to GABA. This activity of the default mode was not coupled to a special EEG frequency band.

Discussion

The trimodal approach, recording PET data, MR data and EEG data simultaneously was successful. The high neuronal activity of the structures within the default mode network occurs on the basis of a high glucose consumption rate within the default node network. The regional metabolic rate of glucose as assessed via 18FDG-PET is largely influence by glial uptake of glucose in response to neuronal glutamate release 3,4.These prior findings fit well with the observation in our data that the glutamate levels assessed in the precuneus and PCC correlate significantly and positively with the measured glucose consumption rate within the DMN. Thus, glutamate seems to be coupled to / to steer the metabolic demands of neuronal activity but not the vascular response. There was no correlation between glutamate and BOLD amplitude. A close link between glutamate and mean glucose consumption rate as assessed in vivo in humans in our simultaneous approach extends prior work in vitro and in anesthesized cats 5. These findings are in line with the observation that the major part of brain energy consumption is dedicated to excitatory activity 5, 6.

Acknowledgements

This trimodal imaging approach was supported by the EU-FP7 funded project TRIMAGE (Nr. 602621). We thank Dr. Jorge Arrubla for his support in data acquisition and processing. We thank Cornelia Frey, Silke Frensch and Suzanne Schaden for their excellent technical assistance.

References

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Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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