Fuyixue Wang1,2, Zijing Dong1,3, Qiyuan Tian1, Jingyuan Chen1, Anna Izabella Blazejewska1, Timothy G. Reese1, Jonathan R. Polimeni1,2, and Kawin Setsompop1,2
1A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, 2Harvard-MIT Health Sciences and Technology, MIT, Cambridge, MA, United States, 33Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA, United States
Synopsis
BOLD fMRI based on T2 contrast has the promise to provide
exclusively microvascular specificity, which would optimize the ability of fMRI
signals to accurately reflect and localize neuronal activity. However, it is
challenging in practice to achieve pure T2 weighting. Here we employ a new
highly-efficient acquisition and reconstruction framework based on EPI,
Echo-Planar Time-resolved Imaging (EPTI), and extend it to generate blurring- and distortion-free data with purely T2 weighting. We evaluate the technique
through a cortical-depth analysis of activation in human visual cortex and
demonstrate that it achieves the desired microvascular specificity.
Introduction
Recent studies have suggested that fMRI can be a veridical
representation of neuronal activity if one can measure fMRI signals exclusively
from the microvasculature. This has led to a renewed interest in evaluating
alternative fMRI signals other than standard GE BOLD1-2, such as CBV using
non-contrast CBV methods for humans3-4, however the vascular origins of these
signals and how they evolve over time is incompletely understood.
While it is known that spin-echo BOLD has exclusively
microvascular sensitivity, it is not commonly used5 in part because of
practical issues—it is extremely difficult to achieve the desired pure T2-weighting,
which may be underappreciated2. Common techniques such as spin-echo EPI do
not provide pure T2-weighted BOLD because the long echo-train length (ETL)
imparts T2′ contamination and an undesirable sensitivity to large blood vessels6-7. 3D-GRASE8-9, a powerful method to generate T2-BOLD, has been applied
to high-resolution fMRI2,9,10. However, the refocusing train in 3D-GRASE
generates stimulated echoes, introducing T1-weighting that affects
the signal2,11, complicating interpretation.
Here we propose to utilize a new acquisition technique,
Echo-Planar Time-resolved Imaging (EPTI)12(Fig.1), to provide reconstruct pure
spin-echo images with suitably short ETL to eliminate T2′ contamination,
providing the desired microvascular specificity. Using a cortical-depth
analysis we demonstrate that T2-BOLD with EPTI provides the expected
microvascular specificity, and that a graded re-introduction of T2’ effects
gradually re-introduces contributions from macrovascular signals.Methods
Data acquisition: The data was acquired using spin-echo
acquisition using 3 EPTI-shot with Rseg=32. Fifty-six echo images can be
obtained with a TE increment of 1.08ms. Other imaging parameters: FOV=168×96×22mm3,
TR=8.8s, zoomed FOV along PE (AP) with saturation pulse applied. Data were acquired
with visual stimulus presentation following a standard block-design paradigm.
Image reconstruction: EPTI data were reconstructed
using B0-informed k-t GRAPPA to generate a series of distortion-free images at each
echo timepoint. The GRAPPA kernel causes small local temporal smoothing, with a
FWHM of the correlation of 7–8ms12. This will cause a small amount of T2′
contamination, however it is still within the range of ETLs that would provide
microvasculature-dominated BOLD6. The data was also reconstructed using
subspace reconstruction that takes advantages of the signal model prior which
should provide purer T2 contrast without the need to interpolate along t as in
GRAPPA.
Conventional EPI data simulation: EPTI data at
different TEs were used to simulate conventional EPI acquisition with different ETL (Fig.2), to simulate cases with different T2* contribution, in
order to investigate if a graded re-introduction of T2’ effects re-introduces
contributions from macrovascular signals.
Data analysis: Same-session MPRAGE data were used as
an anatomical reference and processed with FreeSurfer. GLM analysis was used to
identify activated voxels. We performed a standard cortical depth analysis13 of the fMRI data.
7T feasibility data: To evaluate image quality and feasibility of
T2-BOLD at 7T, pilot BOLD-weighted EPTI data were acquired on a MAGNETOM Terra
(Siemens Healthineers) equipped with the product 32-channel head-only receive
coil array (Nova Medical).Results
Robust visual responses
were detected within the visual cortex (Fig.3). The cortical-depth analysis of the two
T2*-BOLD activations (from the same EPTI acquisition, TE=56 and 90ms) exhibited
the expected bias to large vessels, manifesting as a depth profile that peaked
at the pial surface, while the slope of the T2-BOLD profile was substantially
reduced (same EPTI acquisition, TE=73ms). The peak response of the T2-BOLD was
also observed at the pial surface, however because these data were acquired at
3T we do expect intravascular BOLD contributions which should introduce some
sensitivity to large pial vessels, therefore this peak at the surface may
reflect partial volume effects with those large veins.
Next we reconstructed
the data using the subspace reconstruction approach to further drive down the
T2’ contamination. The resulting cortical depth analysis applied to these data,
shown in Fig.4, was consistent with that of the standard reconstruction. Profiles from the three selected EPTI echo images along with the simulated conventional SE EPI data with different ETLs, achieved by using different width of data along t, were shown. To
test whether the reduced slopes in the presumptive T2-BOLD data is simply due
to its lower sensitivity, we normalized the z-scores to the value measured at
the mid-cortical depth (Fig. 4b). The slopes of the profiles after
normalization are still distinct, with a decreased slope with decreasing T2*
contribution (shorter and shorter ETL), as predicted.
To demonstrate the
feasibility of this approach at 7T, where intravascular contributions are
negligible and microvascular specificity of T2-BOLD is enhanced14-15, we
acquired pilot 0.8mm-iso BOLD-weighted EPTI data at 7T (Fig. 5). High image
quality was achieved, indicating that this technique can be applied at 7T as
well.Discussion and Conclusions
We have demonstrated the
ability of EPTI to generate purely T2-weighted BOLD for high-resolution fMRI
with high spatial and moderate temporal resolution. As T2’ contamination is
gradually reintroduced we see increased influence of the microvasculature,
reproducing findings of a previous study in the macaque visual cortex6. T2-BOLD fMRI experiments utilizing this
sequence at 7T where we expect greater microvascular specificity are currently
underway.Acknowledgements
This work was supported in part by the NIH NIBIB
(grants P41-EB015896, R01-EB019437 and R21-NS106706), by the BRAIN Initiative (NIH NIMH grant
R01-MH111419), and by the MGH/HST Athinoula A. Martinos Center for Biomedical
Imaging; and was made possible by the
resources provided by NIH Shared Instrumentation Grants S10-RR019371.References
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