Simultaneous acquisition of oxygen extraction fraction and cerebral blood flow during brain activation
Yayan Yin1, Yaoyu Zhang1, Yang Fan2, Bing Wu2, and Jia-Hong Gao1

1Center for MRI Research, Peking University, Beijing, People's Republic of China, 2MR Research China, GE Healthcare, Beijing, People's Republic of China


The development of neuroimaging methods to obtain oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) is crucial for understanding mechanisms underlying physiological function and neuronal activity. In the present study, a novel technique termed FAIR-MGESSE combined flow sensitive alternating inversion recovery (FAIR) and multiecho gradient echo sampling of the spin echo (MGESSE) techniques. It is proposed for acquiring OEF and ASL maps in a single repetition time to determine the relative change in CMRO2 in human subjects. Relative changes in CBF, OEF and CMRO2 were measured during the visual task and the results agree well with expectations.


According to the Fick’s first law, the amplitude of the cerebral metabolic rate of oxygen (CMRO2) response to task-based stimulation is determined by changes in cerebral blood flow (CBF) and oxygen extraction fraction (OEF). From a neuroscience perspective, measuring CMRO2 in response to task-based stimulation should enable new advances in understanding functional architecture and connectivity, due to its close relationship to underlying neuronal activity. Current methods in obtaining relative changes in CMRO2 require the inhalation of gas1-3. It is not ideal for task-based functional studies. Another alternative approach to estimate the CMRO2 is by obtaining the OEF and CBF without gas inhalation. However, no MRI technique has been developed which can simultaneously measure CBF and OEF. In this work, a novel method named FAIR-MGESSE is proposed to fill this gap. A distinctive benefit of this effective technique is that relative CBF and OEF can be measured simultaneously voxel by voxel in a single repetition time (TR), which subsequently leads to the derivation of CMRO2. A visual stimulus fMRI study was carried out for its verification.


The pulse sequence diagram of FAIR-MGESSE is shown in Fig. 1: after an inversion recovery, arterial spin labeling perfusion contrast will be obtained in the first EPI readout; and the following series of EPI readouts were used to measure OEF after a nonselective inversion pulse. FAIR-MGESSE was implemented on a 3T GE MR750 MRI scanner. Five healthy adult subjects (24-27 y) were recruited for a visual stimulus study. The stimulus consisted of two minute presentations of an 8Hz flashing radial checkerboard (with central fixation point), interleaved with two minutes of the fixation point alone (2 OFF epochs and 1 ON epoch) and the scan parameters used were: inversion slab thickness=78mm, TI=1000ms, TR=3000ms, 11 slices without space, 4x4x6mm3. TE=66ms, dTE=20.6ms, dTE1 was as short as possible. 3D T1-weighted images for TR/TE/alpha=6.6ms/2.9ms/12°, 1x1x1mm3. 1mm isotropic 3D T1-weighted images were also obtained. The acquired FAIR-MGESSE data was corrected for motion, co-registered to the 3D T1 anatomical image, all images were spatially normalized to standard MNI space and the normalized FAIR-MGESSE images were smoothed. The perfusion image was obtained by subtracting the adjacent slab-selective and nonselective images from the first echo in the sequence.R2 was estimated from one pair of the gradient echo images (the 2th and 4th gradient echoes) that were acquired symmetrically about the spin echo as:$$R_{2}=ln\left(\frac{S(TE-dTE)}{S(TE+dTE)}\right)/2dTE$$ Similarly, the reversible relaxation rate,R2′, can be estimated from the last four gradient echo images by: $$S(t)=S_{0}\cdot exp(-R_{2}\cdot t)\cdot exp(-R_{2}^{'}\cdot |TE-t|)$$ Furthermore,λ (the fractional cerebral venous blood volume) can be obtained from the real spin echo signaland S0(TE) and extrapolated spin echo signals S(TE) from above equation by: $$\lambda=\ln(S(TE))-\ln(S_{0}(TE))$$ then OEF can be calculated by:$$R_{2}^{'}=\lambda\cdot 4/3\pi\cdot\gamma\cdot \triangle\chi_{0}\cdot Hct\cdot B_{0}\cdot OEF$$ where γ is the gyromagnetic ratio; Hct is the fractional hematocrit, a constant Hct of 0.42 was employed for all subjects and a small vessel Hct to large vessel Hct ratio of 0.854; Δχ0is the susceptibility difference between the fully oxygenated and fully deoxygenated blood, which has been measured to be 0.18 ppm per unit Hct5. Maps of the t-statistics for ASL and OEF were thresholded at voxel-level P < 0.001 with cluster-level FWE correction of P < 0.05. Only common activation areas that passed the statistically significant threshold for ASL and OEF maps was used for calculating the average values of the $$$\triangle OEF/OEF^{base}$$$ and $$$\triangle CBF/CBF^{base}$$$, respectively. Under conditions of constant arterial oxygen content, $$$\triangle CMRO_{2}/CMRO_{2}^{base}$$$ was calculated by: $$\frac{\triangle CMRO_{2}}{CMRO_{2}^{base}}=(1+\frac{\triangle CBF}{CBF^{base}})\cdot (1+\frac{\triangle OEF}{OEF^{base}})-1$$


The activation maps for the ASL and OEF revealed significant changes during the visual stimulus, and the activation maps of a typical subject is shown in Fig.2 (five primary slices are shown). The measured relative OEF, CBF and CMRO2 of all the subjects are summarized in Table 1. From five subjects the $$$\triangle OEF/OEF^{base}$$$,$$$\triangle CBF/CBF^{base}$$$ and $$$\triangle CMRO_{2}/CMRO_{2}^{base}$$$ were (mean±s.d.) -0.2785±0.042, 0.5815±0.0938 and 0.1403±0.0854, respectively.

Discussion and conclusion

In this work, a new method named FAIR-MGESSE that acquires relative CBF, OEF and CMRO2 of multislices of the brain voxel by voxel during functional challenges was proposed and tested in a fMRI study. Our estimates of relative changes in CBF, OEF and CMRO2 fell within the expected physiological range and were comparable with previous reports6,7. Due to its short scan time, relatively high spatial and temporal resolution and simultaneous measurement of multiple physiological parameters, it is might be a highly potential method to effectively assess CMRO2 in future functional studies.



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Fig.1. Schematic diagram of the pulse sequence that performs concurrent acquisitions of seven images. An adiabatic inversion pulse (combined with slab selection gradients) was used for alternating slab-selective and non-slab-selective inversion, followed by an inversion time delay (TI) for perfusion image with gradient-echo echo-planar imaging (EPI), and a six-sampling spin echo EPI acquisition for OEF map fitting.

Fig.2. The functional maps of the ASL and OEF for a single subject at 8Hz stimulus frequency (five primary slices are shown). The activation area (in color) were generated by setting the threshold at voxel-level P < 0.001 with cluster-level FWE correction of P < 0.05 superimposed onto a standard template.

Tbale 1. Summary of relative changes in OEF, CBF and CMRO2 during visual task for five human subjects

Proc. Intl. Soc. Mag. Reson. Med. 25 (2017)