Characterization of white matter degeneration in elderly subjects by magnetic resonance diffusion and FLAIR imaging correlation

Abstract

Fluid attenuated inversion recovery (FLAIR) and diffusion tensor imaging (DTI) techniques have been widely used to evaluate white matter (WM) alterations associated with aging, dementia and cerebral vascular disease. The relationship between FLAIR detected WM lesions (WML) and DTI detected WM integrity changes, however, remains unclear. To investigate this association, voxelwise correlations between 4 Tesla DTI and FLAIR images from elderly subjects were performed by relating WML volume and intensity in FLAIR to fractional anisotropy (FA) and mean diffusivity (MD) in DTI. Significant DTI-FLAIR correlations were found in regions overlapping with the WML of moderate intensities in FLAIR. No significant correlations were detected in periventricular regions where the FLAIR intensities are particularly high. The findings are consistent with a transitional model for WM degeneration from normal WM to cerebrospinal fluid (CSF). The results show that the correlation between DTI and FLAIR disappears when the FLAIR intensity of WML reaches its maximum at a certain lesion severity, and that the correlations may remerge with reversed signs when the lesion severity is further increased. These results suggest that the different stages of WM degeneration in elderly subjects can be better characterized by regional DTI-FLAIR correlations than single modality alone.

Fig. 1

(a) Effective T1 and T2 of WML at 4T respective as a function of increasing lesion severity represented as the free water-pool volume fraction f. (b) The joint (T1, T2) trajectory in the degeneration from normal WM (lower left) to pure CSF (upper right).

Fig. 2

(a) FLAIR intensity surface in the (T1, T2) rectangular area defined by normal WM and CSF relaxation times; (b) FLAIR intensity curve of WML with respect to the lesion progression (i.e. the partial volume fraction of free water pool) from normal WM (f=0) to pure CSF (f=1)as quantified by the volume fraction of CSF The blue curve is the results after proton density correction.

Fig. 3

DTI indices are plotted as the function of WML severities (represented by the free water pool volume fraction f) for b = 500~3000 (s/mm²). (a) Fractional anisotropy (FA) in noise free, (b) Mean diffusivity (MD) in noise free, (c) FA in SNR= 80:1 (b=0), and (d) MD in SNR=80:1 (b=0).

Fig. 4

Simulated DTI-FLAIR correlations (mean values and standard deviations of 20 independent trials, represented by blue and red bars, respectively) are illustrated for 10 successive intervals of WML severity (represented by the free water-pool volume fraction f) under the condition of b= 1000 s/mm² and realistic noise levels as estimated from in vivo data. (a) FLAIR intensities on 10 intervals of WML severity, (b) Correlation coefficients estimated between FA and FLAIR, and (c) Correlation coefficients estimated between MD and FLAIR.

Fig. 5

(a) Mean FA map (threshold at 0.35) is overlaid on the original T1 template, showing clear misregistration of WM at corpus callosum. (b) Mean FA map (threshold at 0.35) is overlaid on the adjusted T1 template showing less misregistration. (c) The mean WML map is overlaid on the adjusted T1 template to which the FLAIR images have been registered.

Fig. 6

Voxelwise correlations between DTI measurements and the total WML volume for all subjects. The upper row corresponds to the identical axial slice as use in Fig. 5, while the lower row uses a coronal slice. In columns (a) and (b), blue clusters are selected for negative correlations between FA and WML volume at threshold of p<0.001, overlaid on the background of mean FA and mean WML intensity image, respectively. In columns (c) and (d), red clusters are for positive correlations between MD and WML volume at threshold of p<0.001, overlaid respectively on the mean FA and mean WML intensity image.

Fig. 7

Correlations between DTI index (FA or MD) and WML intensity are estimated in each voxel across all subjects. The images in the upper and lower rows correspond to 2 axial slices in the normalized space, and the lower one is identical to the axial slice used in Fig. 6. The blue clusters in columns (a) and (b) are negative FA-WML intensity correlations selected at p<0.001, overlaid on the mean FA and mean WML maps, respectively. The red clusters in columns (b) and (c) represent the positive correlations between MD and WML intensity, overlaid on the mean FA and mean WML intensity maps.