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SNR optimized $$$^{31}$$$P fMRS to measure energy metabolism in the visual cortex
Arjan D. Hendriks1, Wybe J.M. van der Kemp1, Natalia Petridou1, and Dennis W.J. Klomp1

1Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands

Synopsis

Energy metabolism of the human visual cortex was investigated, by performing 31P fMRS. The used setup was optimized for high SNR by using a dedicated 31P RF coil at 7T and a visual stimulus with a large visual angle. Changes in the up-field peak of inorganic phosphate (Pi) are observed, revealing new promising opportunities to measure energy metabolism in the human visual cortex.

Introduction

The human brain consumes a great deal of energy, and it is known to be the main glucose demanding organ of the human body [1]. Neuronal activity can increase this energy demand, and can cause local pH changes via several mechanisms [2-3]. However, the energy metabolism of the brain is strongly regulated and intracellular pH levels are controlled, for example through buffer processes like the CO2/HCO3 system. Because of these regulatory mechanisms, the magnitude of the neuronal activity induced pH changes is very small, so with MRS it could possibly only be detected as a small shift in peak frequency or minimal change in peak amplitude of inorganic phosphate (Pi). At a field strength of 7 tesla the spectral resolution is high enough to measure shifts in pH, and, because of the increased SNR, potentially also the small changes in peak amplitude. The SNR can be further improved when 7T is combined with a method to enlarge the volume of activated tissue. A large volume of activated tissue would enable the use of a large spectroscopy voxel size, resulting in an additional increase in SNR [4]. In this study, energy metabolism of the visual cortex is investigated by performing 31P MRS at 7T with a large voxel size, an optimized RF coil, and a strong visual stimulus with a large visual angle. During visual stimulation, we expect that apart from the BOLD effect, a fraction of the Pi signal shifts in frequency, because the mitochondrial and/or extracellular Pi compartments get more acidic.

Aim

To gain insight into energy metabolism of the brain by using an SNR optimized 31P MRS setup at 7T with a strong visual stimulation and a large visual angle.

Methods

Two participants were scanned in a 7 Tesla Achieva system (Philips, Best, the Netherlands). A dedicated custom coil setup was used (Figure 1) with a large screen for projection of a stimulus with a large visual angle (Figure 2). The transmit/receive coil used was a quadrature birdcage coil, double tuned to both the 1H and 31P frequency. For each participant a total of 16 consecutive 31P CSI scans were made. Visual stimuli were projected in blocks of 4 scans (4 rest, 4 stimulus, 4 rest, 4 stimulus). Scan parameters of the 31P 3D CSI scan were TE/TR= 0.45/100 ms, 35x35x35 mm3 voxel, 280x280x280 mm3 FOV, matrix size 8x8x8, acquisition time of 2:09 min. The visual stimulus consisted of 8 Hz contrast reversing checkerboards of 8:20 min (4 scans) for the first participant. The second participant was stimulated with 8 Hz contrast reversing curved-lines oriented in different directions, targeted to stimulate more neurons with different orientation preference. After scanning, in post processing steps, the data was Hamming filtered and 1 voxel located in the visual cortex was selected from each 3D CSI scan. The resulting spectra of 1 block (4 scans) were phased, apodized and averaged.

Results

The acquired 31P MRS spectra are shown in Figure 3. Despite the lengthy and strong visual stimulation, only 4% change is visible in the PCr peak. Note that when excluding linewidth correction, a substantial BOLD effect is observed. The 31P spectra over time, for both the rest and stimulation scans, are shown in Figure 4. The intracellular Pi peak stays constant. However, the up-field (left) sub peak of Pi seems to disappear or shifts under the large Pi peak after stimulation.

Discussion and conclusion

The energy metabolism of the visual cortex is investigated with 31P MRS during visual stimulation with a large visual angle. Changes in the up-field peak of Pi are observed. Whether this up-field Pi peak is extracellular or mitochondrial Pi is yet undetermined. Despite the fact that the effect on total absolute Pi is minimal, the relative effect on the Piex/mi seems substantial. The amplitude of the effect is in agreement with the decrease of PCr, which matches the equilibrium condition. Overall, the SNR optimized 31P setup at 7T in combination with a stimulus with a large visual angle, revealed promising opportunities to detect changes in energy metabolism in the human visual cortex.

Acknowledgements

No acknowledgement found.

References

[1] P. Mergenthaler et al. (2013) Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends in Neurosciences, 36(10): 587-597

[2] V.A. Magnotta et al. (2012) Detecting activity-evoked pH changes in human brain. Proc Natl Acad Sci 22;109(21):8270-8273

[3] M. Chesler (2003) Regulation and Modulation of pH in the Brain. Physiol Rev 83: 1183–1221

[4] A.D. Hendriks et al. (2016) Pushing the limits of speed and accuracy for 7T GABA MR spectroscopy to reveal GABA level fluctuations in resting brain. Proceedings of the 24th ISMRM in Singapore pg.#3340

[5] D.L. Adams and J.C. Horton (2009) Ocular Dominance Columns: Enigmas and Challenges. Neuroscientist; 15: 62-77

Figures

Figure 1: The coil setup, which is equipped with a screen for visual stimulation. Displayed are (a) a photograph of the 31P transmit-receive coil, (b) a photograph of the coil when the screen is mounted and (c) a schematic overview of setup during signal acquisition. Note that no mirrors and/or prism glasses are required for this setup, which enhances the visual angle of view with respect to the projected stimulus.

Figure 2: The relation between the visual angle and the activated cortical volume. Displayed is (a) an illustration of the occipital lobe of the brain, highlighting the primairy visual cortex (calcarine sulcus). As described by literature [5], a larger visual angle of the participant, results in a larger volume of active tissue in the visual cortex. When considering MRS applications (b), a large screen with a large visual angle can be translated to a larger spectroscopy voxel size containing active tissue.

Figure 3: High SNR localized 31P MRS of the brain. Displayed is (a) the mean 31P spectrum during visual stimulation and its residual when subtracting the rest condition. Furthermore, (b,c) the PCr peak is shown during the different rest and stimulation conditions. Note that the 31P spectrum shows up-field Pi signal and substantial BOLD effect with minimal (<4%) effect on PCr during stimuli versus rest.

Figure 4: The 31P MR spectra of the visual cortex obtained from two subjects (a,b) at rest and during visual stimulation. While no effect is observed at the main Pi,i peak, a subtle effect on the up-field peak of Pi (Pimi/ex) is visible. The frequency shift of the Pimi/ex peak is particularly recognizable for subject 1.

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)
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