Farida Grinberg1,2, Xiang Gao1, Ezequiel Farrher1, and N. Jon Shah1,2
1Institute of Neuroscience and Medicine - 4, Forschungszentrum Juelich GmbH, Juelich, Germany, 2Department of Neurology, Faculty of Medicine, RWTH Aachen University, Aachen, Germany
Synopsis
Between-group comparisons of diffusion tensor and diffusion kurtosis
imaging metrics are important for elucidation of differences between pathology
and healthy state. However, thus far, the methodology of such comparisons has
not been well established. Frequently used methods, such as region-of-interest
analysis or atlas-based analysis are subject to errors due to partial volume effects,
whereas the track-based spatial statistics reduces consideration to a small
amount of voxels along the skeleton, thus diminishing useful information. In
this work we represent a simple, robust diffusion-kurtosis-informed template effectively
reducing partial volume effects in the atlas-based analysis using less
restrictive approach. Target Audience
This work is of useful for scientists and
radiologists interested in diffusion MRI, in particular, in methodology of
group comparisons.
Purpose
Diffusion tensor (DTI) and diffusion
kurtosis imaging (DKI) are powerful tools extensively used to investigate brain
microstructure and connectivity. The DTI/DKI metrics are often used for
between-group comparisons and studying the correlations with age or severity of
pathology. However, the methodology of group comparisons is not sufficiently well
established. Popular methods include region-of-interest (ROI) analysis [1], voxel-based
whole brain analysis [2], and the track-based spatial statistics (TBSS) [3]. Each
method suffers from specific problems reducing its statistical power or
sensitivity. In particular, difficulties of the ROI-based analysis are
associated with the necessity of manual (therefore, user biased) time-consuming
delineation of the ROIs and large inter-subject variability. To overcome these
difficulties, the atlas-based segmentation is used to automatically define the
ROIs by co-registration of the subject- and atlas-spaces. However, misregistration and various
distortions lead to significant partial volume effects (PVE) [4,5]. Therefore, automatic
atlas-based segmentation is prone to errors diminishing its accuracy. An alternative approach, TBSS, attempts to overcome misregistration problems by skeletonizing WM
and considering only the voxels of the mean fractional
anisotropy skeleton. However,
since the skeleton is formed only by a small fraction of voxels, potentially useful information occurs significantly reduced. The
purpose of this work was to develop a novel method that would reduce PVE in the
atlas-based analysis, on the one hand, but retain more voxels for between-group
comparisons, on the other. PVE are especially crucial when white matter (WM)
ROIs appear contaminated by voxels belonging to gray matter (GM) or
cerebrospinal fluid (CSF). Here, we propose a new diffusion-Kurtosis-Informed
Template (KIT) that allows one to reduce contamination of WM ROIs by PVE from neighbouring
GM and CSF regions by considering specific features of the diffusional kurtosis
histograms.
Materials and Methods
DKI measurements were performed with a whole-body 3T Siemens MAGNETOM scanner for 2 groups of healthy
subjects of different age. Typical DTI/DKI metrics (mean (MD), axial, and
radial diffusivity, fractional anisotropy, mean (MK), axial, and radial
kurtosis, kurtosis anisotropy were determined on the voxel-by-voxel basis in
the whole brain and averaged over 20 WM anatomic regions provided by JHU WM tractography atlas available in FSL.
Results and Discussion
KIT for atlas-based
comparison. Fig.1a shows the histogram of a typical MK map (Fig.2). The data
points are fitted by a sum of the 2 Gaussian distribution functions (see Eqs.
13,14 and Fig. 10 in Ref. [5]). Such a double-peak histogram is characteristic for brain regions containing
voxels in both WM and non-WM (GM and/or CSF) regions: the component with
smaller MK values is attributed to non-WM, the component with higher values to
WM [5]. The Gaussian shape of the MK distribution in WM (red curve, Fig. 1b) is
favourable for an easy and formalized determination of the MK value (MK_HHL)
at its half height (HH). We determine the KIT by selecting
the voxels for which the following conditions hold: a) FA > 0.2 and b) MK
> MK_HHL. The KIT is then applied for all evaluated metrics. The condition (a)
is widely used to roughly separate WM and non-WM. However, as the scatter plots
in Figs. 1c and 1d clearly show, this condition is insufficient to eliminate a
significant amount of voxels exhibiting low MK (see quadrant IV in Fig. 1c)
and/or high MD (see blue data points in Fig. 1d) paralleled by relatively high
FA (which can partially be encountered due to evaluation errors). These voxels very
likely belong to non-WM and should be excluded from comparisons. Voxels that
finally form the KIT are shown by data points in quadrant II in Fig. 1c and by
data points in red in Fig. 1d. The KIT is additionally visualised in Fig. 3 in
red, whereas the voxels eliminated by the constraint (b) are represented in
green. One can clearly see that the majority of the eliminated voxels are
really located at the interfaces of WM and non-WM regions justifying our simple
approach as robust and effective. We also demonstrated the efficiency of the KIT
by its application to an atlas-based comparison of 2 differently aged groups of
healthy subjects. We showed that both the magnitude of the between-group
differences of the DTI/DKI metrics and the corresponding significance levels
become greatly larger after an application of the proposed method.
Conclusion
We demonstrated a simple, robust, and efficient method to reduce PVE
in the atlas-based analysis, in general, and in between-group comparisons, in
particular, by using the novel diffusion-kurtosis informed template.
Acknowledgements
No acknowledgement found.References
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