Diffusion-weighted image analysis along the perivascular space (DWI-ALPS) for evaluating interstitial fluid status: age dependence in normal subjects

Abstract

Purpose: The purpose of this study was to evaluate the interstitial fluid status in a wide range of age groups using diffusion-weighted image analysis along the perivascular space (DWI-ALPS) method, which is a simplified variation of diffusion tensor image analysis along the perivascular space (DTI-ALPS).

Materials and methods: This retrospective study included data from 128 patients who underwent clinical magnetic resonance imaging (MRI) studies, including DWI, and were found to have no abnormal findings in the brain on MRI. Three motion-probing gradients of the DWI were applied in an orthogonal direction to the imaging plane. Apparent diffusion coefficient images in the x-, y-, and z-axes were retrospectively generated, and composite color images were created to locate the projection and association fiber area on the slice including the body of the lateral ventricle. ALPS indices were calculated, and correlations with age were evaluated using linear and second-degree regression analysis. Linear regression analysis was also performed for a subgroup of patients older than 40 years. In addition, an analysis of variance (ANOVA) test among the generations was performed.

Results: The linear regression analysis between age and the ALPS index showed a correlation coefficient of -0.20 for all age group and -0.51 for the subgroup older than 40 years. The second-degree regression analysis showed a correlation coefficient of 0.39. ANOVA showed that the 40's generation showed a statistically significant higher value of ALPS index compared to all other generations except for the 30's generation. While, the 70's generation showed a statistically significant lower value of the ALPS index compared to all other generations.

Conclusions: The analysis of the DWI-APLS method showed a correlation between age and the ALPS index in second-degree distribution which peaked in the 40's generation. This finding in normal subjects may be fundamental in the analysis of disease cases. We tried to evaluate the glymphatic system status in a wide range of age groups using diffusion-weighted image analysis along the perivascular space (DWI-ALPS) method, and the results showed a correlation between age and the ALPS index in second-degree distribution which peaked in the 40's generation.

Keywords: DTI–ALPS method; DWI–ALPS method; Diffusion image; Glymphatic system; MRI.

Fig. 1

Calculation of the DWI–ALPS index. Apparent diffusion coefficient (ADC) images in the x-axis (a), y-axis (b), and z-axis (c) were retrospectively created from the b = 0 images and diffusion-weighted images (DWI) of the x-, y-, and z-axes. Color composite images were created as follows: x = red, y = green, and z = blue (d). On the slice including the body of the lateral ventricle of the composite color image (d), we identified the projection fiber area (R. Proj and L. Proj on d) and association fiber areas (R.Assoc and L. Assoc on d). For these ROIs, we measured ADC values along the x-, y-, and z-axes to calculate the DWI–ALPS index, which is given by the ratio of the mean of the x-axis ADC in the area of the projection fiber (ADCxproj) and the x-axis diffusivity in the area of association fibers (ADCxassoc) to the mean of the y-axis diffusivity in the area of projection fiber (ADCyproj) and z-axis diffusivity in the area of association fibers (ADCzassoc) as follows: DWI-ALPS index = mean (ADCxproj, ADCxassoc)/mean (ADCyproj, ADCzassoc)

Fig. 2

Correlation of the measured ALPS index by two independent observers. Regression lines and 95% CIs (gray areas) are shown. The correlation coefficient between the measurements from the two observers was 0.85

Fig. 3

DWI–ALPS index-to-age plot in normal subjects. a is the DWI–ALPS index-to-age plot. The red line shows the linear regression line of the whole subject (r = −0.20), while the green line shows linear regression line of the subject older than 40 years (r = −0.51). The blue line shows the secondary regression line (r = 0.39). The 95% confidence intervals are shown as gray area. b Is the boxplot of the DWI–ALPS index of age groups (10’s to 80’s) including the minimum, lower quartile, median, upper quartile, and maximum, and open circles indicate outliers. The ANOVA test showed a statistically significant higher DWI-ALPS index in the age group of 40’s and lower index in the age group of 70–79