Vascular Dysfunction in Leukoaraiosis

Abstract

Background and purpose: The pathogenesis of leukoaraiosis has long been debated. This work addresses a less well-studied mechanism, cerebrovascular reactivity, which could play a leading role in the pathogenesis of this disease. Our aim was to evaluate blood flow dysregulation and its relation to leukoaraiosis.

Materials and methods: Cerebrovascular reactivity, the change in the blood oxygen level-dependent 3T MR imaging signal in response to a consistently applied step change in the arterial partial pressure of carbon dioxide, was measured in white matter hyperintensities and their contralateral spatially homologous normal-appearing white matter in 75 older subjects (age range, 50-91 years; 40 men) with leukoaraiosis. Additional quantitative evaluation of regions of leukoaraiosis was performed by using diffusion (n = 75), quantitative T2 (n = 54), and DSC perfusion MRI metrics (n = 25).

Results: When we compared white matter hyperintensities with contralateral normal-appearing white matter, cerebrovascular reactivity was lower by a mean of 61.2% ± 22.6%, fractional anisotropy was lower by 44.9 % ± 6.9%, and CBF was lower by 10.9% ± 11.9%. T2 was higher by 61.7% ± 13.5%, mean diffusivity was higher by 59.0% ± 11.7%, time-to-maximum was higher by 44.4% ± 30.4%, and TTP was higher by 6.8% ± 5.8% (all P < .01). Cerebral blood volume was lower in white matter hyperintensities compared with contralateral normal-appearing white matter by 10.2% ± 15.0% (P = .03).

Conclusions: Not only were resting blood flow metrics abnormal in leukoaraiosis but there is also evidence of reduced cerebrovascular reactivity in these areas. Studies have shown that reduced cerebrovascular reactivity is more sensitive than resting blood flow parameters for assessing vascular insufficiency. Future work is needed to examine the sensitivity of resting-versus-dynamic blood flow measures for investigating the pathogenesis of leukoaraiosis.

Fig 1.

Calculation of ROIs used to control for differences in the spatial location of MR imaging metrics. A, Representative FLAIR image of a patient with periventricular and deep white matter hyperintensities. B, WMH are highlighted in yellow and overlaid on the FLAIR image. C, WMH (yellow) with the underlying FLAIR image removed. D, The WMH are left-right flipped about the y-axis (pink). This transformation is in Montreal Neurological Institute coordinates but retains the native structure (no warping of the brain). E, WMH (C) is subtracted from contralateral NAWM (pink). This is the final NAWM mask used in the statistical comparison between WMH and contralateral NAWM. F, Contralateral NAWM is left-right flipped and combined with the initial WMH ROI (C) by using a logical “and” operation; the resulting WMH mask includes only those voxels that have homologous NAWM in the contralateral hemisphere. This is the final WMH mask used in statistical comparisons between WMHs and contralateral NAWM. G, Final masks (E and F) overlaid on a FLAIR image.

Fig 2.

Relative values of MR imaging metrics in WMH compared with contralateral NAWM. The values of each MR imaging metric are given as a percentage change from NAWM. The ROIs used for these measurements are taken from Fig 1G. CVR, fractional anisotropy, CBF, and relative CBV values are significantly lower in WMH compared with NAWM, while MD, T2, MTT, time-to-maximum, and TTP are significantly higher in WMH compared with NAWM (asterisk, P < .01, compared with NAWM, and circle, P < .05, compared with NAWM). Bars indicate minimum and maximum; boxes, the interquartile range; and the line within each box, the median. FA indicates fractional anisotropy; Tmax, time-to-maximum; mD, mean diffusivity.