Dana Ramadan1, Jonas Bause1, Sebastian Mueller1, Dario Bosch1,2, Ruediger Stirnberg3, Philipp Ehses3, and Klaus Scheffler1,2
1High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Tübingen, Germany, 2Department of Biomedical Magnetic Resonance, University of Tübingen, Tübingen, Germany, 3German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Synopsis
Keywords: fMRI Analysis, fMRI (resting state), High-Field MRI
Motivation: GRE-EPI, the most widely used sequence for BOLD fMRI, is highly biased towards large draining veins that follow the cortical curvature and influence the surrounding magnetic field in an orientation-dependent manner increasing with field strength.
Goal(s): This work aims to investigate large vein biases resulting in cortical orientation-dependent signal variations in GRE-EPI and bSSFP resting-state fMRI signals.
Approach: We compared 2D and 3D GRE-EPI with 3D bSSFP rs-fMRI signal fluctuations in their dependence on the cortical orientation to B0 in five subjects at 9.4 Tesla.
Results: Unlike GRE-EPI, intra- and inter-subject comparisons revealed no dependence of bSSFP on the cortical orientation to B0.
Impact: Fluctuations
in the GRE-EPI signal are highly dependent on the cortical orientation and
depth. This was not observed with bSSFP, demonstrating the potentially higher
specificity of bSSFP for smaller veins, closer to brain activation at field
strengths ≥ 7 Tesla.
Introduction
Veins
filled with paramagnetic deoxygenated blood introduce perturbations to the
magnetic field of the surrounding tissue, which are highest when perpendicular
to the main axis of B01 and increase with increasing field
strengths. Large vessels are assumed
to follow the cortical curvature, while smaller vessels are oriented randomly.
Therefore, the cortical orientation to B0 is considered a valid estimate for
the large vessel orientation to B02,3.
Gradient echo
(GRE) echo-planar imaging (EPI) is known to be sensitive to large draining
veins, which is considered a drawback due to the distance from the capillary
bed and thus the low specificity of the signal4,5. Previous work has shown the strong
cortical orientation dependence of 2D simultaneous multi-slice (SMS) GRE-EPI3,
and preliminary results have shown the dependence of 3D GRE-EPI and
balanced steady-state free precession (bSSFP) on the cortical orientation in
two subjects6. Aiming to understand the signal
specificity of bSSFP, we compare all three sequences in their signal dependence
on cortical orientation to B0 in five additional subjects.Materials & Methods
Data acquisition
A graphical
overview of the methods is shown in Figure 1. Resting-state fMRI data were
collected from five subjects at a whole-body 9.4T MRI scanner with a 16Tx/31Rx
coil7 after informed consent. Four runs
of 112 frames of 3D bSSFP8 and segmented 3D GRE-EPI9 and one run of 197 frames of 2D SMS
GRE-EPI were acquired with 1.1mm isotropic resolution. The volume TR (TRvol) was kept
at 3000ms/1700ms for the 3D/2D sequences, respectively. A T1-weighted MPRAGE
was acquired with 0.7mm isotropic resolution using a universal pulse for
excitation10. Acquisition parameters are shown in
Table 1.
Analysis
After
removing the first two/three volumes from the images acquired with the 3D/2D
sequences, respectively, motion correction was performed in SPM12. The
coefficient of variation ($$$CV=\frac{1}{tSNR_{eff}}=\frac{\sigma}{\mu}\sqrt{TR_{vol}}$$$) was
calculated as a measure for signal fluctuation (Figure 2B). The MPRAGE image,
along with the calculated cortical orientation and cortical ribbon, were
transformed to the functional space. This included an additional warping step in
FSL11,12 (6.0.5.2) performed only on the anatomical data co-registered to the EPI
data. In the other case, the anatomical data were directly co-registered to the
mean bSSFP image.
The
cortical orientation, defined as the angle between the surface normal and
$$$\overrightarrow{B_0}$$$
($$$\theta_{B_0}$$$), was calculated and converted into voxel space in FreeSurfer3 (v7.4.0) (Figure 2C). To see the effect in
different cortical depths, LayNii13 (v.2.1.0) was used to partition the cortical
ribbon into five equi-distant depths (Figure 2D).Results
The results
are summarized in Figure 3 for 3D bSSFP (top), 3D GRE-EPI (middle) and 2D
GRE-EPI (bottom). The CV is plotted on $$$\theta_{B_0}$$$ in the entire cortical
ribbon and in the 5 equi-distant depths (1 closest to cerebrospinal fluid [CSF]
and 5 closest to white matter [WM]). In the GRE-EPI plots a clear decrease of
signal fluctuation with increasing $$$\theta_{B_0}$$$ (parallelism to B0) is observed.
Furthermore, with increasing proximity to WM, this effect is diminished,
especially in 2D GRE-EPI. None of these effects are visible in the bSSFP plots.Discussion
The expected
strong dependence of the GRE-EPI signal on the cortical orientation relative to
B0 was demonstrated. This dependence
thus implies a substantial signal contribution from large veins. Supporting
this hypothesis, this effect is reduced, but is not eliminated at deeper
cortical depths (depth5). The resting-state signal acquired with bSSFP does not
show any of these effects. This suggests a higher specificity of bSSFP to
smaller veins, which was expected based on simulations of a previous work14. Our results are comparable to
those of Viessmann et al.3, who investigated the cortical
orientation dependence of 2D SMS EPI with similar settings at 7 Tesla. Thus,
direct translation of our results to this field strength appears to be
reasonable.
To further substantiate this hypothesis, we aim to explore the impact of masking out voxels closer to pial veins on the cortical orientation effect. A decreasing signal dependence on the cortical orientation would indicate a high dependence on large veins. Here, only one session for each subject is shown and one run is acquired with the 2D sequence as opposed to four with the 3D sequences. Test-retest reliability has not been demonstrated and is in progress (example for S1 shown in Figure 4). Thermal and physiological noise regression effects were investigated, but did not impact the overall outcome (results not shown).Conclusion
The bSSFP
sequence shows no dependence on the cortical orientation relative to $$$\overrightarrow{B_0}$$$, while
the opposite is true for 2D SMS and 3D GRE-EPI. This suggests a higher signal
specificity of bSSFP and must be further investigated with task fMRI.Acknowledgements
D.R. and S.M. are financially supported by the grant FKZ 01GQ2101 of the Federal Ministry of Education and Research, Germany.References
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