Hamed Y. Mesri^{1}, Szabolcs David^{1}, Max A. Viergever^{1}, and Alexander A. Leemans^{1}

Diffusional Kurtosis Imaging (DKI) is an extension to Diffusion Tensor Imaging (DTI), which allows the quantification of non-Gaussian water diffusion and the quantification of parameters related to microstructural changes. In this work, we used high-quality datasets from the Human Connectome Project and non-parametric statistical inference to evaluate the performance of the DKI measures for group-wise studies. To this end, we used the gender information to group the subjects and study the differences. Our results demonstrated that DKI metrics could reveal the differences more accurately compared to DTI metrics.

BACKGROUND AND PURPOSE

Subjects:

The subjects for this study were taken from the HCP 500 subject release, out of which 410 subjects (244 females and 166 males) aged between 22 and 36 years had their full DKI data available.

Diffusion data:

We used the preprocessed multi-shell diffusion-weighted MRI data (b=1000, 2000 and 3000 s/mm^{2}) with 90 unique gradient directions and 6 b=0 acquisitions per shell (288 volumes in total). Estimation of DKI parameters was implemented using the REKINDLE^{6} approach in ExploreDTI^{7} with constraints on kurtosis tensor^{8}. Correction for diffusion gradient nonlinearities was performed^{9-11} and the gradient field tensor for each subject was used to correct the magnitude and direction of the diffusion-sensitizing gradients at each brain voxel^{9,10,12}. DTI and DKI metrics were then calculated for each understudied subject.

Parcellation of brain regions using the FreeSurfer^{13} toolbox with “wmparc” atlas had already been performed by the HCP team. 179 brain regions common among all the subjects were identified in total out of which 165 regions were ultimately considered. Regions consisting of CSF (ventricles) and the right and left vessels were excluded due to huge flow and noise-related artifacts. The parcellation masks were then used to calculate the mean and standard deviation of all the DTI and DKI for each subject. The mean and standard deviation per regions were inspected to ensure that all the regions consist of normal diffusion values.

Comparison of gender differences was carried out on the mean values per region using non-parametric two-sample permutation based t-tests^{14,15} in Permutation Analysis of Linear Models (PALM) version alpha104 with 10000 permutations. To eliminate the nuisance effect of volume on the statistical analyses^{16}, volume was considered as a covariate of no-interest. Tests were applied to all the 8 DTI and DKI scalars. Calculation speed was accelerated using the tail approximation^{17}. P-values were corrected for multiple comparisons with family-wise error-rate adjustment by considering multiple contrasts and metrics^{15}. Corrected p-values and effect sizes (Cohen’s D) were provided for every region per metric. The significance of a test was determined at corrected p-value (P_{corr}) < 0.05. The effect sizes are standardized measures which quantify the strength of the group-wise differences and can be used to compare the performance of tests for different metrics.

Fig.1 shows the voxel-wise scalar maps for a representative subject from the HCP dataset. Fig.2 shows the corresponding regional averages of the scalars for the same subject, which indicates the distribution of average DKI metrics for different regions.

Fig.3 depicts the effect sizes for the regions with significant differences between groups. Positive and negative values indicate larger average values for male and female groups respectively.

Fig.4 demonstrates the range of average values for the regions listed in Fig.3 sorted by the highest absolute effect size for each metrics. From the table in Fig.3, it can be inferred that on average the effect sizes for DKI metrics are larger than for the DTI counterparts. The values in Fig.3 also indicate that if a region is significant with a DTI metric it is also significant with a DKI metric. There are some regions for which no significant difference was shown with DTI metrics, while DKI metrics indicated a significant difference, e.g. region number 21 Right Amygdala.

Fig.5 shows the significant regions for the gender comparison for different metrics. The color of each region is scaled with the corresponding effect size for the corresponding statistical test.

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Fig.1: Voxel-wise parameter maps for DTI and DKI metrics from a representative 26 years old female subject from the HCP dataset.

Fig.2: Regional average parameter maps for DTI and DKI metrics from the same subject as in Fig.1. The regions were delineated using FreeSurfer toolbox with “wmparc” atlas.

Fig.3: Highest effect sizes for all the DKI and DTI metrics for regions resulting in significant differences between females and males. Positive and negative values indicate larger average values for male and female groups respectively. In general DKI-based tests show higher effect sizes in comparison to DTI-based metrics.

Fig.4: Range of the DKI and DTI
metrics for regions resulting in the highest effect sizes for each metrics as
presented in Fig.3.

Fig.5: Significant regions for gender comparisons with different metrics. The color of each region is scaled with the corresponding effect size for the statistical test. Positive and negative values indicate larger average values for male and female groups respectively.