Marta Gaviraghi1, Giovanni Savini2, Gloria Castellazzi1,3, Nicolò Rolandi4, Simone Sacco5,6, Egidio D’Angelo4,7, Fulvia Palesi4, Paolo Vitali2, and Claudia A.M. Gandini Wheeler-Kingshott2,4,8
1Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy, 2Neuroradiology Unit, Brain MRI 3T Research Center, IRCCS Mondino Foundation, Pavia, Italy, 33Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, United Kingdom, 4Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy, 5UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, United States, 6Department of Clinical Surgical Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy, 7Brain Connectivity Center (BCC), IRCCS Mondino Foundation, Pavia, Italy, 8Brain MRI 3T Research Center, IRCCS Mondino Foundation, Pavia, Italy
Synopsis
Dentate
nuclei (DN) segmentation is necessary for assessing whether DN are affected by pathologies
through quantitative analysis of parameter maps, e.g. calculated from diffusion
weighted imaging (DWI). This study developed a fully automated segmentation
method using non-DWI (b0) images. A Convolution Neural Network was optimised on
heathy subjects’ data with high spatial resolution and was used to segment the
DN of Temporal Lobe Epilepsy (TLE) patients, using standard DWI. Statistical
comparison of microstructural metrics from DWI analysis, as well as volumes of
each DN, revealed altered and lateralised changes in TLE patients compared to
healthy controls.
Introduction
Cerebellar nuclei (CN)
have a fundamental role in the central nervous system. Indeed, they are the
main output channel of the cerebellum 1, but their involvement
in pathologies remains unclear. It is possible to study the CN using
quantitative magnetic resonance images (MRI) that reflect biophysical
properties of tissues. Often it is useful to segment specific regions2 to extract, for example, microstructural parameters from
diffusion weighted images (DWI)-derived maps; hence, it is desirable to have
segmentations in DWI-space.
Manual
segmentation is the gold standard method for segmenting the dentate nuclei
(DN), i.e. the CN with the largest volume, but it is time-consuming and has
high rater-dependent variability. To overcome these limitations, automatic
segmentation is desirable.3 In this study,
therefore, a method was developed to automatically segment the DN from non-DWI
(i.e. b0) images and was applied to DWI-derived maps of patients with Temporal
Lobe Epilepsy (TLE).Methods
Automatic DN
segmentation
The b0s of 76
heathy subjects (43 Females, age 29.41±3.62 y), from the Human Connectome
Project (HCP), were manually segmented and considered as ground truth (GT). HCP
data were used because of the higher spatial resolution compared to standard
research protocols (acquisition parameters in Table 1).
Three
automatic segmentation methods were tested: SUIT (A spatially unbiased atlas
template of the cerebellum and brainstem), OPAL (Optimized Patch Match for
Label fusion) and CNN (Convolution Neural Network).
Performance
was tested comparing automatic DN regions against GT using the Dice Similarity
Coefficient (DSC), which calculates the overlap between two binary masks.
SUIT
is currently the only existing automatic method for DN segmentation and is
based on registration to an atlas.4
OPAL
is based on Patch Match, a multi-template method that needs a database of b0s
and corresponding GTs used as reference templates.5
CNN
is based on dilated convolutions, which expand receptive fields without
increasing the number of parameters. The architecture used here was inspired to
that used for spinal cord segmentation6 optimised as
reported in Figure 1.
In order to
remove false positives, a final step masked the outcome of OPAL and CNN with a
region of interest obtained from dilating twice the SUIT segmentation of the
DN.
Proof of principle of clinical translation
86
subjects were recruited for a TLE study (Table 1). Subjects were divided in
three groups: 34 healthy subjects (17 Females, 32.65±8.46 y), 25 subjects with
left-TLE (14 Females, 32.36±11.02 y) and 27 subjects with right-TLE (17
Females, 38.89±9.41 y). The volumes of right and left DN were extracted with
the three automated methods, after resampling the TLE b0s to match the HCP-data
resolution using FLIRT.7
For each DN,
average values obtained from microstructure DWI-derived maps were calculated.
These included diffusion tensor metrics (axial diffusivity, AD, radial diffusivity,
RD, mean diffusivity, MD and fractional anisotropy, FA) and diffusion kurtosis
tensor (axial kurtosis, AK, radial kurtosis, RK, mean kurtosis, MK).
Lateralization of volumes and metrics between right and left values was
hypothesized and tested using an Asymmetry Index (AI) 8:
$$ AI=(mean(DN right)-mean(DN left))/((mean(DN rigth)+mean(DN left))/2)
$$
As the three groups of
subjects have a statistically different age, the statistical comparison of the
metrics used a general linear model with age as covariate. Instead, as gender
and handedness are homogeneous in the three groups, these were not included in
the model.Results and Discussion
All methods extracted the DN
from all b0s of HCP subjects with DSCs equal to: 0.49±0.08 for SUIT, 0.790.1 for OPAL
and 0.85±0.05 for CNN. Figure 2 shows examples of segmentations from the methods
compared to GT.
SUIT is worse than the other
methods and the comparison of segmentations obtained with OPAL and CNN revealed
a greater precision of CNN (Figure 3).
CNN has a further advantage,
given the greater transferability than OPAL. Indeed, OPAL requires that the database
of b0s and associated GTs are available to perform the DN segmentations.
Contrarily, CNN needs a database only for the training step, but then once the
network has learned the association between images and segmentations, the
reference images are no longer needed.
The CNN developed here can be
useful in clinical studies as there is further evidence of the key role of the
cerebellum and CN in supporting healthy brain functioning. Here, the DN of
subjects with TLE were segmented. Some studies have shown that patients with
TLE have cerebellar atrophy 9 and even that , in animal models of epilepsy, neurostimulation of the CN can block
epileptic seizures. 10-11
The comparison of quantitative
metrics, measured in each DN separately, between patients with right or
left-TLE and healthy controls showed that there are statistically significant
differences as reported in Figure 4.Conclusion
We have demonstrated the
successful delineation of the DN in health and pathology using a fully automated
method. The CNN implemented is able to segment images with a different spatial
resolution compared to that of the training set. CNN offers a method that does
not need the original training data for transferring to other studies.Acknowledgements
Data were provided by the Human Connectome Project,
WU-Minn Consortium (Principa lInvestigators: David Van Essen and KamilUgurbil;
1U54MH091657) funded by the 16 NIH Institutes and Centers that support the
NIHBlueprint for Neuroscience Research; and by the McDonnell Center for Systems
Neuroscience atWashington University.
3TLE is a multicentric research project granted by
Italian Health Ministry (NET2013-02355313): Magnetic resonance imaging in
drug-refractory temporal lobe epilepsy: standardization of advanced structural
and functional protocols at 3T, to identify hippocampal and extra-hippocampal
abnormalities.
Acknowledgments to the UCL-UCLH Biomedical Research Centre for ongoing
funding; the European Union’s Horizon 2020 research and innovation programme
under grant agreement No. 634541, Spinal Research (UK), Wings for Life
(Austria), Craig H. Neilsen Foundation (USA) (jointly funding the INSPIRED
study), Wings for Life (#169111), the UK Multiple Sclerosis Society (grants
892/08 and 77/2017).
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