Janina Schellenberg1, Megan Hall2,3,4, Lisa Story2,3,4, Afra Wohlschläger1,5, and Jana Hutter2,3,6
1Technical University of Munich, Munich, Germany, 2Biomedical Engineering, King's College London, London, United Kingdom, 3Centre for the Developing Brain, King's College London, London, United Kingdom, 4Women’s Health, Guy's & St.Thomas' Hospital, London, United Kingdom, 5Department of Neuroradiology and TUM-NIC, Klinikum rechts der Isar, Munich, Germany, 6Smart Imaging Lab, Radiological Institute, University Hospital Erlangen, Erlangen, Germany
Synopsis
Keywords: Fetal, Brain, Multi-Echo Analysis
Motivation: fMRI of the fetus in the womb must overcome the challenges of fetal motion and heterogeneous tissue boundaries. Multi-Echo fMRI reduces signal dropout and thermal noise, improving contrast-to-noise ratio of the BOLD signal. This can produce higher quality fetal MRI and allow adequate functional assessment of fetal brain development.
Goal(s): This study aims to denoise ME-fMRI of the fetal brain with TE-dependent analysis (tedana) in a subset of 10 cases (gestational age >35weeks).
Approach: Multi-echo gradient echo EPI scans were acquired in 80 fetuses. The fetal brain is segmented and passed to the analysis.
Results: Credible BOLD components are successfully identified using tedana.
Impact: TE-dependent analysis denoises ME-fMRI data of fetuses which undergo motion during scanning and contain heterogeneous tissue boundaries.
This study assesses capabilities of ME-fMRI analysis to determine BOLD
components in the fetal brain,paving the way for future research and clinical
usage.
Introduction
An optimal intra-uterine environment is crucial for healthy fetal brain
development5,13. Neurodevelopment is vulnerable to maternal factors, such as nutrition,
stress and infection5,13. These affect the neurodevelopment of a fetus and are associated with
emotional, behavioural or cognitive problems in later life including impaired
brain growth, delayed verbal abilities and a higher risk of depression,
anxiety, ADHD or schizophrenia5,13. Currently, fetal brain development is evaluated
via ultrasound, able to detect structural pathologies but not suited to inform
on the function12,14,15.
Fetal motion and the multi-tissue environment in the uterus pose
challenges when analysing BOLD signals in fetuses4,6,7,15. Using multiple echoes to
process fMRI data reduces signal dropout and thermal noise, thereby improving
the contrast-to-noise ratio of the BOLD signal1,9,15. Exploring the
advantages of multi-echo fMRI in the context of the fetal brain fMRI carries
the potential to improve our understanding of fetal brain connectivity1,2.Methods
80 fetal MRI scans were
performed after informed consent was provided (MEERKAT, REC 21/LO/0742, Dulwich
Ethics Committee, 08/12/2021) on a 3T clinical Philips Achieva MRI scanner. MRI
data was acquired with a whole uterus single shot 2D multi-echo gradient echo
EPI sequence under free breathing. The voxel resolution was 3mm isotropic,
TEs=[ 10.2,, 54.3,98.4,142.5, 186.6]ms, flip angle=90. A B0 map was acquired
prior to the EPI scan and image-based shimming employed. The data was
reconstructed following normal vendor pipelines including EPI ghost correction
and gradient waveforms correction.
Fetal brain segmentations were performed manually for two control cases in late
gestation (36+6, 38 weeks). Two types of masks were obtained, a conservative
segmentation of the fetal brain (carefully avoiding amniotic fluid around the
fetal brain) and a more liberal mask. TE-dependent analysis (tedana) of the
multi-echo fMRI was used to denoise the data. TE-dependence analysis was
performed using the tedana workflow3, separately for each mask to assess its
dependence. A two-stage masking procedure was applied for optimal combination,
T2*/S0 estimation, denoising, and the component classification procedure. A
monoexponential model was fit to the data at each voxel using log-linear
regression to estimate T2* and S0 maps. Multi-echo data were then optimally
combined using the T2* combination method11. Principal component analysis based on the PCA
component estimation with a Moving Average process10 was applied to the
optimally combined data for dimensionality reduction. The metrics kappa and rho
were calculated as measures of TE-dependence and TE-independence, respectively.
Independent component analysis was then used to decompose the dimensionally
reduced dataset. Next, component selection was performed to identify BOLD
(TE-dependent), non-BOLD (TE-independent), and uncertain (low-variance)
components using the Kundu decision tree (v2.5)8.Results
ME-ICA of the fetal brain of case 1 with 38 weeks gestation with a conservative mask yields many accepted
BOLD components (20 out of 28) classified by the tedana workflow as “likely
BOLD”, with the two top components explaining 15.8% and 15.6% of the variance
respectively. ME-ICA with the liberal fetal brain mask detects fewer BOLD
components (12 out of 28). Here, the two components with the highest variances
are found at 17.7% and 17.1%.
ME-ICA of case 2 with 36+6 weeks gestation results in 13 total
components, of which 6 are classified as “likely BOLD” using a liberal fetal
brain mask. Here, the two highest variances of the accepted components hold the
values 23.8% and 21.3%. Applying the conservative mask yields 4 components,
none of which were classified as “likely BOLD”.Conclusion
The tedana workflow successfully decomposes the data into independent
components for both, the conservative and liberal masks, and classifies them as
likely or unlikely BOLD. Hence, initial results indicate that the choice of brain mask is an important factor.
This exploratory study is limited by the number of cases investigated
and by fetal motion occurring during scanning. However, application of the
tedana workflow shows promising results in determining BOLD components. Hence,
multi-echo fMRI has the potential to provide an improved analysis of the fetal
brain in its rather inhomogeneous and noisy environment.
The possibilities of multi-echo fMRI and the potential to achieve more
specific and higher quality functional analysis of the developing human brain
are exciting - including research questions addressing the influence of the
intra-uterine environment as well as a potential role in the clinical
assessment of complex neuropathologies. In the next steps, temporal realignment
of the data could improve the accuracy of the results. Currently, a larger
cohort of control cases as well as cases with pathologies will be investigated
with the tedana workflow.Acknowledgements
This research was supported by DFG Heisenberg funding [502024488].References
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