Vahid Malekian1, Nadège Corbin1,2, Michael Moutoussis1,3, and Martina F. Callaghan1
1Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom, 2Centre de Résonance Magnétique des Systèmes Biologiques, CNRS‐University Bordeaux, Bordeaux, France, 3Max Planck University College London Centre for Computational Psychiatry and Ageing Research, London, United Kingdom
Synopsis
Keywords: Data Acquisition, fMRI
Multi-echo
fMRI can boost BOLD sensitivity relative to conventional single-echo fMRI,
especially in high-susceptibility brain regions like orbito-frontal cortex
(OFC). Another option is to optimise slice-tilts, z-shimming and k-space
traversal to minimise susceptibility effects. In this study, we sought to
determine if multi-echo EPI, which requires the use of parallel imaging to
achieve reasonable echo times, would remain optimal in OFC when compared to an
OFC-optimised single echo alternative. The relative performance is quantified
via BOLD contrast-to-noise ratio and an additional comparison is made by
incorporating the TE Dependent ANAlysis (TEDANA) denoising approach. Multi-echo
increased BOLD CNR, particularly following denoising.
Introduction
Orbitofrontal
cortex (OFC) is involved in many cognitive tasks including memory, decision-making
and emotional/social behaviours1. Unfortunately, susceptibility-induced
B0-field inhomogeneity in this region accentuates signal dropout, and
distortion, in 2D gradient-echo echo-planar imaging (EPI). In comparing a range
of different sequence options, Kirilina et al.2 found that a
multi-echo acquisition3 could combat signal dropout and bolster BOLD
sensitivity, specifically in the OFC – an improvement preserved at the group
level. However, this was relative to standard 2D-EPI. A well-established
alternative for recovering BOLD sensitivity is to integrate slice tilts and
z-shimming gradients specifically optimised for the OFC region4. In
this study, we sought to determine if multi-echo EPI, which requires parallel
imaging to achieve reasonable echo times (TE), would remain optimal in OFC relative
to an OFC-optimised single-echo alternative.Material & Methods
Data acquisition: 9 participants were scanned at 3T
(Siemens Prisma) using a 64 channel coil. Time series data with 3mm isotropic
resolution were acquired with both a multi-echo and an OFC-optimised protocol
(Table 1) while the participants engaged in a decision-making task. In brief,
the OFC-optimised protocol had a TE of 30ms, a slice tilt of −30° and a
z-shimming gradient moment of -1.4 mt/m*ms to mitigate signal dropout4,5.
The multi-echo acquisition comprised three echoes with TE of 17.5ms, 35.6ms and
53.7ms. This extended the repetition
time, TR, (3.84s relative to 3.36s) and necessitated an in-plane acceleration
factor of 2. Matching the total acquisition
time led to 150 and 172 volumes for the multi-echo and OFC-optimised protocols respectively.
B0-field
mapping and a T1-weighted MPRAGE were also acquired.
Data
processing: Two
participants were excluded during quality assessment due to excessive motion (exceeding
the voxel dimension) during data acquisition.
All
pre-processing and analyses were performed using FSL6 and MATLAB (Figure
1). First, slice-timing and motion correction were applied to the OFC-optimised
and multi-echo data. Next, the multi-echo data were combined either as a simple
average over TE7, or by using the TE-Dependent ANAlysis (TEDANA)
denoising approach8,9. Finally, drift removal with a cut-off
frequency of 0.01 Hz and distortion correction using the B0-field mapping data
were applied to both datasets.
The
BOLD sensitivity of each dataset was estimated in grey matter (GM) and the OFC
for each participant in native space. Both regions of interest (ROIs) were
defined in MNI space and transformed to native space via inverse transformation
(Figure 1). The OFC was defined according to Kirilina et al.2 as a spherical
ROI, of 10 mm diameter, centred on coordinates (3,51,−14) (Figure 2a). The GM mask
was defined as those voxels with > 50% probability of being GM according to a
canonical tissue probability map (Figure 2b).
Analysis: CNRBOLD was calculated using equation (1)7,
where Si is the voxel’s
signal amplitude at TEi and
n is the number of echoes. Following
TEDANA denoising, CNRBOLD was calculated using the average TE.
$$CNR_{BOLD}=\frac{mean(\frac{\sum_1^nTE_{i}.S_{i}}{n})}{std(\frac{\sum_1^nS_{i}}{n})} \;\;\;\;\;\;\;\;\;\;\;\;\;(1)$$Results
In
GM, the median CNRBOLD across the cohort was 19% higher for the multi-echo
relative to the OFC-optimised data (3.02 and 2.35 respectively). However, the
multi-echo data also had a larger inter-quartile range (IQR of 0.60, versus
0.26 for OFC-optimised data). TEDANA denoising further increased the CNRBOLD
(median±IQR=4.12±0.69).
The
median CNRBOLD was reduced for both sequences in the OFC, but
remained 16% higher for the multi-echo data (2.35, versus 2.73 for
OFC-optimised). However, in this ROI the IQR was more comparable (1.12, versus
1.07 for OFC-optimised). The TEDANA denoising further increase CNRBOLD
(median±IQR=4.14±0.85).
Figure
4 shows the group-level CNRBOLD map for each approach. The green
cursor indicates the centre of the OFC ROI. This qualitative assessment aligns
with the quantitative assessment. Multi-echo
offers a modest gain over the OFC-optimised approach, with further gains
following TEDANA denoising.Discussion
This
study builds on previous work that showed multi-echo acquisitions can increase
BOLD sensitivity in the OFC by acquiring data with shorter TE and reduced signal
dropout. Here we show that this is the case even when compared to a 2D-EPI
acquisition optimised for imaging the OFC, and particularly so when the
multi-echo nature of the data is exploited for denoising to detect and remove
TE-independent (i.e. non-BOLD) components8.
This
gain in BOLD sensitivity occurs despite the use of in-plane acceleration necessary
to acquire multiple echoes with sufficiently short inter-echo spacing and TR to
not overly degrade temporal efficiency. This acceleration will incur a √2
reduction in SNR, plus any g-factor penalty, and leads to greater sensitivity
to motion occurring between the acquisition of calibration data and the ongoing
time series data. However, it is also worth
noting that the shorter readout used with in-plane acceleration provides the
benefit of reducing any susceptibility-induced distortion, which will be
particularly beneficial in the OFC.
In
conclusion, the multi-echo approach continued to outperform single-echo 2D-EPI
in the OFC even after incorporating optimal slice tilt and z-shim settings for
this region. The benefits were further
amplified, across the entire GM, by exploiting the multi-echo nature of the
data to perform denoising. Acknowledgements
The Wellcome Trust funded the
“Neuroscience in Psychiatry Project” (NSPN). All NSPN members were supported by
the Wellcome Strategic Award, ref. 095844/7/11/Z. The Max Planck – UCL Centre
for Computational Psychiatry and Aging is a joint initiative of the Max Planck
Society and UCL. M.M. received support from the National Institute for Health
Research (NIHR) UCLH Biomedical Research Centre. The Wellcome Centre for Human
Neuroimaging is supported by core funding from the Wellcome [203147/Z/16/Z]. This
research was funded in whole, or in part, by the Wellcome Trust
[203147/Z/16/Z].References
1. Rolls
ET. The functions of the orbitofrontal cortex. Brain and cognition. 2004 Jun
1;55(1):11-29.
2. Kirilina,
E., Lutti, A., Poser, B.A., Blankenburg, F. and Weiskopf, N., 2016. The quest
for the best: The impact of different EPI sequences on the sensitivity of
random effect fMRI group analyses. Neuroimage, 126, pp.49-59.
3. Poser,
B.A. and Norris, D.G., 2009. Investigating the benefits of multi-echo EPI for
fMRI at 7 T. Neuroimage, 45(4), pp.1162-1172.
4. Weiskopf,
N., Hutton, C., Josephs, O. and Deichmann, R., 2006. Optimal EPI parameters for
reduction of susceptibility-induced BOLD sensitivity losses: a whole-brain
analysis at 3 T and 1.5 T. Neuroimage, 33(2), pp.493-504.
5. Volz,
S., Callaghan, M.F., Josephs, O. and Weiskopf, N., 2019. Maximising BOLD
sensitivity through automated EPI protocol optimisation. Neuroimage, 189,
pp.159-170.
6. Jenkinson,
M., Beckmann, C.F., Behrens, T.E., Woolrich, M.W. and Smith, S.M., 2012. Fsl.
Neuroimage, 62(2), pp.782-790.
7. Kettinger,
Á., Hill, C., Vidnyánszky, Z., Windischberger, C. and Nagy, Z., 2016.
Investigating the group-level impact of advanced dual-echo fMRI combinations.
Frontiers in neuroscience, 10, p.571.
8. Kundu,
P., Inati, S.J., Evans, J.W., Luh, W.M. and Bandettini, P.A., 2012.
Differentiating BOLD and non-BOLD signals in fMRI time series using multi-echo
EPI. Neuroimage, 60(3), pp.1759-1770.
9. DuPre,
E., Salo, T., Ahmed, Z., Bandettini, P.A., Bottenhorn, K.L., Caballero-Gaudes,
C., Dowdle, L.T., Gonzalez-Castillo, J., Heunis, S., Kundu, P. and Laird, A.R.,
2021. TE-dependent analysis of multi-echo fMRI with* tedana. Journal of Open
Source Software, 6(66), p.3669.