Yunjie Tong1, Kimberly P Lindsey1, Lia M Hocke2, Gordana Vitaliano1, Dionyssios Mintzopoulos1, and Blaise B Frederick1
1McLean Hospital/Harvard Medical School, Belmont, MA, United States, 2Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
Synopsis
Previously, we have demonstrated that we can
extract systemic low frequency oscillation (sLFO) from resting state (RS) fMRI
data and map its dynamic patterns as it moves through the brain. We have
hypothesized that the dynamic patterns represent the cerebral blood flow. In
this study, we tested this hypothesis by conducting both Dynamic Susceptibility
Contrast scan (bolus tracking) and RS fMRI scan in health subjects. By
comparing the flow patterns of the bolus with that of sLFO, we found that the
flow of sLFO does represent the blood flow, however, mostly in the capillaries
and veins.Purpose
Previously, we have demonstrated that we can extract systemic low frequency
oscillation (sLFO) from resting state (RS) fMRI data. This sLFO is present
throughout the brain; temporally-shifted versions of the signal appear in
different voxels. A dynamic flow of sLFO can therefore be derived from the RS
data
1,2. We hypothesized
that the flow pattern of sLFO reflects the passage of cerebral blood through
the brain. We tested this hypothesis by conducting a Dynamic
Susceptibility Contrast (DSC) MRI scan (i.e. bolus tracking)
3 following the resting state
scans on 8 healthy subjects.
Methods
The studies were conducted in 8 healthy
participants. The RS scan was conducted before the DSC scan. In the RS scan, multiband
EPI data were obtained (University of Minnesota sequence cmrr_mbep2d_bold R010
4,5)
with the following parameters: TR/TE = 720/32 ms, 500 time points, matrix 86 x
86 on a 212 x 212 mm FOV, multiband factor=8, 64 2.5-mm slices with no gap. This
was followed by a Gd-DSC scan (TR/TE = 1510/21ms, 120 time points, flip angle =
60°, 1.8x1.8 mm inplane resolution, 29 3.5mm slices with a 0.5 mm gap). Twenty
seconds after the beginning of this scan, 20 ml of Prohance was injected into
the antecubital vein at 4 ml/s, followed by a flush of 20ml of saline using an
Medrad Spectris Solaris power injector. The flow pattern of sLFO was derived from
the RS data of each subject with the following steps: 1) a seed time series was
extracted from superior sagittal sinus, and 2) used to cross-correlate with all
the other voxels. The time lag of maximum correlation coefficient of each voxel
represents the relative arrival time of the sLFO at that voxel. A time lag map
was generated for each subject. Similarly, the arrival time of the Gd contrast bolus
at each voxel was estimated by the time to peak (TTP) value of the DSC time
course. These two time lag maps are compared. Finally, dynamic movies can be
generated from the time lag maps. Each non-overlapping consecutive frame of the
movie consists of voxels whose time lags are within a 0.72s time window. A 4-second
movies were made by concatenating all these frames in sequence.
Results
The time lag maps derived from RS data and DSC are
robust among all the subjects. The averaged time lag maps are shown in Figure
1(a) and (b) respectively. Since the signal to noise ratio of sLFO in RS data
is much smaller than the bolus contrast in DSC, time lag map of RS has more
noise. In Figure 1(a), early time lags can be found in symmetric central
regions, such as motor cortex. Late time lags are mainly concentrated in white
matter and draining veins. Compared to RS time lag maps, DSC map showed much
more uniform region in most of the gray matter. The voxel with late time lags
are concentrated in white matter and draining veins, like that of RS time lag
map. The dynamic movie frames of two flows are shown in Figure 2. Red
represents the flow of sLFO (RS) in the brain, while blue represents the flow
of the Gd contrast bolus (DSC). Both similarities and differences can be
observed. To a large extent, the flow of sLFO matches the contrast flow (DSC).
The discrepancy is most likely due to the fact that fMRI is only sensitive to
blood in capillaries and veins (due to high deoxyhemoglobin concentration
6), while DSC is sensitive to blood in all the
vessels (due to exogenous contrast (i.e. Gd) in all vessels). In other word, DSC
observes much faster blood flows than that of RS even from the same voxels,
resulting in shorter time lags (e.g. uniform blue in the Figure 1(b)).
Conclusions
In this study, we tested the hypothesis that sLFO extracted
from RS data travel with the blood flow, arriving in different parts of the
brain with different delays. By comparing the flow patterns of the injected bolus
with that of sLFO, we found that the flow of sLFO reflects blood flow in the
brain, to large extent. However, since the contrast mechanism of fMRI is BOLD,
which is primarily sensitive to deoxyhemoglobin concentration, the sLFO method
reflects mostly the blood flow in the capillaries and veins. The results from
this study can be used to develop new and simple perfusion methods without exogenous
contrast; because of the higher sensitivity to venous blood, this perfusion
method offers complementary information to DSCMRI.
Acknowledgements
The
work was supported by the National Institutes of Health, Grants K25 DA031769
(YT), R21 DA032746 (BdeBF). We thank Drs. Scott Lukas, Steven Lowen and Sinem
Erdogan for their helpful discussions. References
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