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Multicenter Study
. 2016 Nov 29;87(22):2333-2339.
doi: 10.1212/WNL.0000000000003373. Epub 2016 Oct 28.

Cerebrovascular Reactivity and White Matter Integrity

Affiliations
Free PMC article
Multicenter Study

Cerebrovascular Reactivity and White Matter Integrity

Kevin Sam et al. Neurology. .
Free PMC article

Abstract

Objective: To compare the diffusion and perfusion MRI metrics of normal-appearing white matter (NAWM) with and without impaired cerebrovascular reactivity (CVR).

Methods: Seventy-five participants with moderate to severe leukoaraiosis underwent blood oxygen level-dependent CVR mapping using a 3T MRI system with precise carbon dioxide stimulus manipulation. Several MRI metrics were statistically compared between areas of NAWM with positive and negative CVR using one-way analysis of variance with Bonferroni correction for multiple comparisons.

Results: Areas of NAWM with negative CVR showed a significant reduction in fractional anisotropy by a mean (SD) of 3.7% (2.4), cerebral blood flow by 22.1% (8.2), regional cerebral blood volume by 22.2% (7.0), and a significant increase in mean diffusivity by 3.9% (3.1) and time to maximum by 10.9% (13.2) (p < 0.01), compared to areas with positive CVR.

Conclusions: Impaired CVR is associated with subtle changes in the tissue integrity of NAWM, as evaluated using several quantitative diffusion and perfusion MRI metrics. These findings suggest that impaired CVR may contribute to the progression of white matter disease.

Figures

Figure 1
Figure 1. Identification of normal-appearing white matter (NAWM)
(A) Example of a T1-weighted image from a participant with diffuse periventricular and deep white matter hyperintensities (WMHs). (B) Fluid-attenuated inversion recovery images highlight the hyperintensities seen in this participant. (C) The white matter (green) was segmented from other subdural structures such as CSF and gray matter. (D) Regions of hyperintensities are identified in yellow. (E) NAWM mask: a diamond-shaped structuring element was used to erode the white matter (C) in 5 iterations at the resolution of the T1-weighted image (A) to account for partial voluming effects. The WMHs were subtracted after erosion to give rise to a final NAWM mask (pink).
Figure 2
Figure 2. Identification of normal-appearing white matter (NAWM) with steal physiology
(A) Example of a mean diffusivity (MD) map from a participant with periventricular and deep white matter hyperintensities (WMHs). (B) The NAWM (green) is overlaid on the MD map. (C) Regions of positive cerebrovascular reactivity (CVR) (red) and negative CVR (steal physiology) in blue are overlaid on an MD map. (D) NAWM mask with only regions of positive CVR. (E) NAWM mask with only regions of negative CVR.
Figure 3
Figure 3. Regions of interest used to assess the influence of spatial location on MRI metrics
(A) Normal-appearing white matter (NAWM) mask with only regions of positive cerebrovascular reactivity (CVR). (B) NAWM mask with only regions of steal physiology (negative CVR). (C) Image B is left-right flipped about the y-axis in Montreal Neurologic Institute coordinates while retaining native structure. (D) Image C is overlaid on image A and overlapping voxels are retained, giving rise to a contralateral NAWM mask that has only positive CVR. (E) Image D is left-right flipped about the y-axis, giving rise to the original NAWM with steal physiology that also has contralateral positive CVR. (F) The 2 final masks, NAWM with steal physiology (E) and the corresponding contralateral homologous NAWM with positive CVR (D), are overlaid on a mean diffusivity map.
Figure 4
Figure 4. Comparison of MRI metrics between regions of normal-appearing white matter (NAWM) with positive cerebrovascular reactivity (CVR) and steal physiology
The values in MRI metrics are derived from paired comparisons of regions of positive CVR and their corresponding contralateral homologous regions of NAWM with steal physiology. Values are given as % change from NAWM with positive CVR. The regions of interest used for these measurements are taken from figure 3F, thereby accounting for differences in spatial location that may give rise to differences in MRI metrics. Fractional anisotropy (FA), cerebral blood flow (CBF), and relative cerebral blood volume (rCBV) values are significantly lower in NAWM with steal physiology compared to NAWM with positive CVR. Results from mean diffusivity (mD) and T2 metrics show significant increases in regions of steal physiology compared to NAWM with positive CVR. *Denotes significance compared to NAWM with positive CVR (p < 0.01). Bars indicate minimum and maximum, boxes indicate the interquartile range (25th–75th percentile), and the line within each box indicates the median. MTT = mean transit time; Tmax = time-to-maximum; TTP = time-to-peak.

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