Purpose

Dynamic ¹⁷O-MRI enables metabolic imaging with reproducible quantification of the cerebral metabolic rate of oxygen (CMRO₂) consumption in healthy volunteers ¹ and patients with glioma ². This imaging technique requires inhalation of enriched ¹⁷O₂ gas. Data of three healthy volunteers were investigated with regard to hemispherical dependence of CMRO₂ quantification and robustness of the method. Mapping of task-related neuronal activity was investigated in one healthy volunteer employing finger tapping and dynamic ¹⁷O-MRI.

Methods

All experiments were performed on a 7-T whole-body MR system (Siemens, Erlangen, Germany). For the investigation of hemispherical dependence, three healthy volunteers (44±21 years, all men) were included in this study (n=3, 6 datasets). A home-built double-resonant ¹⁷O/¹H head coil was used to acquire dynamic ¹⁷O data as well as basic proton images. A 24-channel ¹H head coil (Nova Medical, Wilmington, Massachusetts) was used to obtain high spatial resolution anatomical data. Oxygen MRI data were acquired with a density-adapted radial sequence ³ with a Golden Angle distribution of projections ⁴ (nominal spatial resolution of (7.5mm)³, TR/TE=20ms/0.56ms, acquisition time t=40min). Administration of ca. 4.0L of 70%-enriched ¹⁷O₂ gas enabled the determination of the cerebral metabolic rate of oxygen (CMRO₂) consumption via three-phase inhalation experiment (baseline phase, ¹⁷O₂ inhalation phase, decay phase) ^1,5. The segmentation masks for gray matter (GM) and white matter (WM) were created automatically using the FSL-FAST algorithm tool ⁶ and were used for partial volume correction ⁷. All segmentation masks were subdivided into two compartments (left and right hemisphere) to investigate possible hemispherical dependence of CMRO₂ values. The CMRO₂ values for gray and white matter as well as their hemispherical dependence (left versus right hemisphere) were tested using Wilcoxon signed-rank tests with a level of significance of p<0.05. The experiment for mapping neuronal activity included dynamic ¹⁷O-MRI in one healthy volunteer (68 years, male). A finger-tapping paradigm was employed for stimulating the sensorimotor cortex. The chosen paradigm alternated blocks of resting and sequential right-hand finger-to-thumb tapping. A total of 40 images were acquired in 40 blocks of 60 seconds with the same experimental setup as for investigation of regional dependence.

Results

Dynamic ¹⁷O-signals relative to the baseline show similar increases in the left and right brain hemispheres (LH, RH) for both gray matter and white matter (Fig. 1A). Increased CMRO₂ in gray matter (2.38±0.15 μmol/g/min) was observed compared to white matter (0.63±0.05 μmol/g/min) (p=0.03) (Fig. 1B). Furthermore, the obtained CMRO₂ values in gray matter and white matter are consistent with previous studies in healthy volunteers (gray matter: 1.42-3.57 μmol/g/min, white matter: 0.67-0.75 μmol/g/min) ^1,5,8. The comparison between left and right hemispheric CMRO₂ in gray and white matter did not show any significant differences (p=0.50 and p=0.25) (Fig. 1B). The neuronal activity experiment with the finger-tapping paradigm (right-hand tapping) employing dynamic ¹⁷O-MRI yielded higher ¹⁷O-signal increases in the left sensorimotor cortex and adjacent brain tissue compared to the contralateral brain region as well as the experiment without finger tapping (Fig. 2).

Discussion

Dynamic ¹⁷O-MRI represents a non-invasive method to specifically quantify oxygen-dependent energy metabolism. Our findings for ¹⁷O-MRI of three healthy volunteers without sensomotoric stimulation showed that CMRO₂ was higher in gray matter compared to white matter, without significant differences between the left and right hemisphere. This indicates hemispherical independence of the employed dynamic ¹⁷O-MRI technique. The high increase in ¹⁷O-signal in brain regions related to sensomotoric stimulation during finger tapping suggests that dynamic ¹⁷O-MRI may enable visualization of task-related neuronal activity in the healthy human brain. This finding is in agreement with a previous study in which mapping of neuronal activity was shown to be feasible using visual stimulation ⁹.

Conclusion

Dynamic ¹⁷O-MRI demonstrates potential as a robust and non-invasive MRI technique that enables direct metabolic imaging in humans. The finger-tapping experiment in one healthy volunteer showed increased ¹⁷O-signal in the stimulated brain region. Therefore, dynamic ¹⁷O-MRI may permit visualization of physiological neuronal activity.

Acknowledgements

The authors would like to thank NUKEM Isotopes GmbH for their supply of ¹⁷O₂ gas and support of this project.