Michaël Bernier1, Guillaume Gilbert2, Stephen C Cunnane3,4,5, and Kevin Whittingstall6
1Nuclear medecine and radiobiology, Université de Sherbrooke, Sherbrooke, QC, Canada, 2MR Clinical Science, Philips Healthcare Canada, Markham, ON, Canada, 3Research center of aging, CSSS-IUGS, Sherbrooke, QC, Canada, 4Department of Pharmacology and Physiology, Université de Sherbrooke, Sherbrooke, QC, Canada, 5Department of Medecine, Université de Sherbrooke, Sherbrooke, QC, Canada, 6Diagnostic radiology, Université de Sherbrooke, Sherbrooke, QC, Canada
Synopsis
The structural nature of BOLD and CBV
fluctuations during resting-state remains unclear. To address this, we first
developed a simultaneous multi-slice VASO-BOLD EPI sequence at 3T and isolated
resting-state VASO- and BOLD- based networks. We then performed ToF and SWI to
quantify the arterial and venous contributions in each network. Overall, both
BOLD and VASO showed similar networks which were spatially localized near large
veins. Also, similar proportions of vasculature were observed throughout all
networks. These results suggest that simultaneous BOLD-CBV acquisitions are
feasible at 3T and that their resting state networks are spatially and
structurally similar.
Introduction
Resting-state
fMRI networks are often used to study the impact of brain disease or healthy
aging on brain dynamics1. Since the BOLD contrast
combines the cerebral metabolic rate of oxygen (CMRO2) with effects from cerebral
blood flow and volume (CBF and CBV), important questions arise regarding the true origin
of these networks, or more specifically, whether some simply reflect the heterogeneous
layout of cortical veins and/or arteries. Recently, a simultaneous whole-brain vascular space occupancy (VASO)2 and BOLD acquisition was
reported at 7T3. Based on this, we sought to develop
a similar acquisition at 3T using a simultaneous VASO-BOLD EPI sequence. Image quality of the
sequence was first assessed using a known cognitive task. We then used the same
VASO-BOLD acquisition to investigate the similarities and differences between
CBV- and BOLD-based resting-state networks obtained by machine-learning
decomposition. We finally compared this to maps of arterial and venous density computed
from Time of Flight angiography (ToF) and susceptibility weighting images (SWI) to investigate the vasculature of these networks.Methods
Image acquisition was performed in healthy young adults (N=12, 18-30
years old) on a Philips 3T scanner. Each session started with an anatomical
T1-weighted MPRAGE acquisition (TR/TE 7.8/3.54 msec, voxel size of 1 mm³),
followed by a resting-state VASO-BOLD acquisition (5 min, 240x240x100 FOV, TR/TI1/TI2/TE
3000/675/1825/20 msec, voxel size of 3x3x5 mm, 5-slice EPI readout with Multiband
SENSE acceleration of 4, for a total of 20 slices). The VASO-BOLD acquisition
was also tested on one participant using an alternating finger-tapping task (4min30,
30 secs on/off). Vascular brain structure (veins/arteries) was then assessed
using a ToF angiography acquisition (200x200x120 FOV, TR/TE 23/3.6 msec, voxel
size of 0.625x0.625x1.3 mm) and a high-resolution multi-echo SWI sequence
(230x230x160 FOV, TR 28 msec, TE 6.9/12.6/18.3/24.0 msec, voxel size of 0.6x0.6x1.2mm).
BOLD and VASO signal analysis were carried out using a pipeline consisting of motion
correction, band-pass temporal filtering (0.005 to 0.1 Hz), spatial smoothing
using non-local mean denoising4 and temporal normalisation
(signal from -1.0 to 1.0) using AFNI5. Residual BOLD was finally regressed
out of the VASO signal using a point-by-point divisions (VASO/BOLD)6. Both ToF and SWI were
preprocessed using an in-house algorithm based on a Frangi measure of
vesselness and vessels enhancement diffusion filtering7,8, then thresholded to obtain both
whole-brain artery and vein maps. VASO and BOLD, SWI and ToF signals and maps
were all registered to MNI standard space using ANTs non-linear registration9. The mean of all participants’
veins and arteries was computed to form a multi-subject venous and arterial
atlas. The multi-subjects VASO and BOLD were respectively decomposed into 20
functionally defined maps using the multi-subject dictionary learning algorithm10 implemented in Nilearn11, similar to but more
consistent, stable and less noisy than independent component analysis12. The VASO components were
matched to the BOLD components to finally retain 16 positive matches. From
these components, the percentage of veins and arteries was then reported as the
proportion of non-zero voxels in each component map.Results
Figure 1 illustrates the proof-of-concept of our 3T simultaneous VASO-BOLD
acquisition during a finger-tapping task, where both CBV and BOLD activations
in the motor cortex are similar (percent change: 8% vs 6% respectively). Figure
2 illustrates both venous (blue) and arterial (red) vessels computed from the
mean of all participants’ SWI and ToF, respectively. Figure 3 shows the 16 BOLD-based
and VASO-based network components, as well as their respective proportion of
venous and arterial voxels (Whole head: veins 28%, arteries 5.6%; BOLD
networks: veins 36.1 +/- 8.2%, arteries 4.5 +/- 4.4%; CBV networks: veins 34.3
+/- 5.9%, arteries 4.0 +/- 3.8%). In all cases, BOLD and CBV networks were
highly similar and were for the most part localized near the larger veins.Discussion & conclusion
We
report reliable and highly similar brain networks detected from simultaneous
multi-slice EPI VASO and BOLD across the brain. These results are in agreement
with a previous study reporting a less consistent but similar parity across
networks13. The improved correspondence
observed in our results may be due to the use of a simultaneous multi-slice
VASO-BOLD approach compared to separate 3D-GRASE VASO and EPI BOLD acquisitions
which may be biased by slight changes in brain state. Even if our venous and
arterial atlas revealed no significant distinction between the vascular
composition of the networks, it was demonstrated that the resting state
fluctuations observed by either VASO or BOLD occur in regions with a higher
than average venous contribution, which is not the case for the arterial
contribution. Acknowledgements
The authors would like to acknowledge the funding agencies which have supported this research; Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grants (PGSD3-475005-2015), Canada Foundation for Innovation (CFI), Canada Research Chairs (CRC), QBIN (Quebec Bio-Imaging Network), Université de Sherbrooke FMSS graduate scholarship programs. We also thank to Dr. Jun Hua and his team for their help regarding the VASO sequences.References
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