Daniel Haenelt1,2, Nikolaus Weiskopf1, Lenka Vaculciakova1,2, Roland Mueller1, Shahin Nasr3,4, Jonathan Polimeni3,4, Roger Tootell3,4, Laurentius Huber5, Martin Sereno6, and Robert Trampel1
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, 2International Max Planck Research School on Neuroscience of Communication: Function, Structure, and Plasticity, Leipzig, Germany, 3Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, United States, 4Department of Radiology, Harvard Medical School, Boston, MA, United States, 5Department of Cognitive Neuroscience, Maastricht Brain Imaging Center, Maastricht, Netherlands, 6Department of Psychology, San Diego State University, San Diego, CA, United States
Synopsis
Functional
MRI studies classically rely on the use of GE-EPI sequences. However,
the GE-based signal is inherently sensitive to large veins,
which
impairs its use in high-resolution fMRI application. Other BOLD-
and CBV-based approaches like SE-EPI and SS-SI-VASO, respectively,
promise
a higher specificity at the expense of sensitivity.
In the present work, we tested if ocular dominance columns (ODCs) can
be detected using GE-EPI, SE-EPI and SS-SI-VASO at 7 T.
ODCs
could be reliably
mapped
using all three acquisition methods. Furthermore, we
could show for the first time ODCs
in
humans by exploiting
the functional CBV response
using SS-SI-VASO.
Introduction
With the advent of functional
magnetic resonance imaging at ultra-high magnetic fields (≥ 7 T), mapping of small physiological structures like ocular
dominance columns (ODCs) in the primary visual cortex (V1) became
possible in vivo. 1,2 However, using GE-EPI, which is
the choice in most fMRI applications, the acquired signal is
inherently sensitive to large draining veins 3, which
reduces its specificity towards the source of neural activation.
Other approaches like SE-EPI and especially SS-SI-VASO 4
promise higher specificity towards the microvasculature at the
expense of sensitivity by attenuating extravascular signal
contributions from larger veins and exploiting a more specific
contrast mechanism like cerebral blood volume (CBV), respectively. In
this study, we test if we can reliably detect ODCs in humans using
GE-EPI, SE-EPI and SS-SI-VASO. To the best of our knowledge, we show
for the first time ODCs in humans by measuring the functional CBV
response with SS-SI-VASO.Methods
Experiments
were performed on a 7 T whole-body MR scanner (Siemens Healthineers,
Germany) using a 32 channel
phased
array head RF coil (Nova Medical Inc, USA).
The study was carried out with approval from the local Ethics
Committee
and written
informed
consent was obtained.
One
participant was invited for 7 scanning sessions on different days.
While the first session was used for measurements of anatomical
reference and retinotopy 5,
ODCs
were measured in the remaining sessions with
each sequence type twice. ODCs
were localized by
alternate visual
stimulation
of
single eyes using
moving sparse random dot stereograms viewed through
in-house constructed
anaglyph
goggles. 6
In
each session, 10 functional runs
of 270 s length were acquired.
For
acquisition,
a
slab was positioned in an
oblique-coronal fashion over the posterior end of the occipital lobe.
For GE-EPI
/
SE-EPI
protocols, we used the CMRR MB sequence 7,8
without multiband acceleration,
TR = 3000 ms, TE = 24 ms / 38 ms, FA = 78 deg / 90 deg. SS-SI-VASO
was used with a 3D EPI readout 4,
TR = 2500
ms, TE = 25 ms, FA = 26 deg and TI = 650 ms. All protocols
had the same nominal isotropic
voxel
size (0.8
mm)3,
field-of-view
and
effective acceleration with GRAPPA = 3 and partial Fourier 6/8 along
the in-plane phase-encoding direction.
The
number of slices had to be reduced for SE-EPI due to SAR limitations.
SPM12
(Functional Imaging Laboratory, University College London, UK)
was
used for GLM analysis without spatial smoothing
(though
the
applicability of the same inferential statistics for VASO
might not be fulfilled).
To
correct for BOLD modulations
in the VASO time series, dynamic division of interleaved
acquired nulled
and not-nulled
volumes was performed. 4
Anatomical
data was automatically
segmented
using FreeSurfer (http://surfer.nmr.mgh.harvard.edu/).
For
profile sampling, reconstructed
surfaces were flattened
and
re-sampled
onto a cartesian grid.
Then, sampled
data from different
cortical depths were stacked together
to
form
a 3D array. 9
Since
ground truth for ODC detection
is
missing by relying only on fMRI data, we
performed a test-retest
analysis in a representative ROI and measured the vertex-wise
correlation between sessions, expecting
a high reliability within the stimulated
visual field of V1 (see fig. 3
for further explanation).Results
Fig. 1 shows thresholded
t-maps of ODCs (left eye > right eye) on the left
hemisphere close to the vertical meridians sampled at the central
cortical layer and represented on the pial surface. The expected
topography with ODCs radiating from the V1 border into the calcarine
sulcus 10 can be seen in all sessions. Due to lower
sensitivity of SE-EPI and SS-SI-VASO, the threshold was lowered which
increases the false positive rate (e.g. outside of V1). However,
several ODCs can be clearly seen within V1 and coincide across
sessions and sequence types (see green crosses in fig. 1). Note
that VASO shows the inverse contrast, since the MR signal of gray
matter tissue is reduced after neural activation due to vessel
dilation. The profile across cortical depth along the dashed green
line is shown in fig. 2. The columnar nature of ODCs can be seen
across sessions as well. To further examine the reliability of
activation patterns between sessions, a vertex-to-vertex correlation
within a defined patch in V1 was analyzed, shown in fig. 3.
While the expected trend of the regression line can be revealed in
all sessions, only GE-EPI and SE-EPI show a statistically significant
correlation.Discussion and conclusion
A robust pattern of ODCs could
be revealed across days and sequences in humans using BOLD- and
CBV-based fMRI approaches. While ODCs can be observed in each
session, a statistical comparison between GE-EPI and SS-SI-VASO
showed the expected negative correlation but without statistical
significance. This is not unexpected due to the lower sensitivity of
VASO and more subjects are needed to get a more conclusive picture.
The presented approach allows for in depth comparisons of these
different contrasts and acquisition methods in terms of their
sensitivity and specificity to neural activation. For example, the
inherent cortical depth-dependent vascular blurring can be studies as
previously proposed. 9 In conclusion, the study
demonstrates for the first time the feasibility of measuring ODCs in
humans using GE-EPI, SE-EPI and SS-SI-VASO.Acknowledgements
We thank the University of
Minnesota Center for Magnetic Resonance Research for the provision of
the multiband EPI sequence software. Furthermore, we thank Dr. Toralf
Mildner for insightful discussions. The research leading to these
results has received funding from the European Research Council under
the European Union's Seventh Framework Programme (FP7/2007-2013) /
ERC grant agreement n° 616905.References
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