Magnetic Resonance Imaging Tissue Signatures Associated With White Matter Changes Due to Sporadic Cerebral Small Vessel Disease Indicate That White Matter Hyperintensities Can Regress

Abstract

Background: White matter hyperintensities (WMHs) might regress and progress contemporaneously, but we know little about underlying mechanisms. We examined WMH change and underlying quantitative magnetic resonance imaging tissue measures over 1 year in patients with minor ischemic stroke with sporadic cerebral small vessel disease.

Methods and results: We defined areas of stable normal-appearing white matter, stable WMHs, progressing and regressing WMHs based on baseline and 1-year brain magnetic resonance imaging. In these areas we assessed tissue characteristics with quantitative T1, fractional anisotropy (FA), mean diffusivity (MD), and neurite orientation dispersion and density imaging (baseline only). We compared tissue signatures cross-sectionally between areas, and longitudinally within each area. WMH change masks were available for N=197. Participants' mean age was 65.61 years (SD, 11.10), 59% had a lacunar infarct, and 68% were men. FA and MD were available for N=195, quantitative T1 for N=182, and neurite orientation dispersion and density imaging for N=174. Cross-sectionally, all 4 tissue classes differed for FA, MD, T1, and Neurite Density Index. Longitudinally, in regressing WMHs, FA increased with little change in MD and T1 (difference estimate, 0.011 [95% CI, 0.006-0.017]; -0.002 [95% CI, -0.008 to 0.003] and -0.003 [95% CI, -0.009 to 0.004]); in progressing and stable WMHs, FA decreased (-0.022 [95% CI, -0.027 to -0.017] and -0.009 [95% CI, -0.011 to -0.006]), whereas MD and T1 increased (progressing WMHs, 0.057 [95% CI, 0.050-0.063], 0.058 [95% CI, 0.050 -0.066]; stable WMHs, 0.054 [95% CI, 0.045-0.063], 0.049 [95% CI, 0.039-0.058]); and in stable normal-appearing white matter, MD increased (0.004 [95% CI, 0.003-0.005]), whereas FA and T1 slightly decreased and increased (-0.002 [95% CI, -0.004 to -0.000] and 0.005 [95% CI, 0.001-0.009]).

Conclusions: Quantitative magnetic resonance imaging shows that WMHs that regress have less abnormal microstructure at baseline than stable WMHs and follow trajectories indicating tissue improvement compared with stable and progressing WMHs.

Keywords: MRI; cerebral small vessel disease; cerebrovascular disease; imaging; white matter hyperintensity.

Figure 1. Overview of white matter masks.

Areas of stable NAWM (A), stable WMHs (B), progressing WMHs (C), and regressing WMHs (D) over 1 year. ∩ indicates intersection; BL, baseline; NAWM, normal‐appearing white matter; and WMH, white matter hyperintensity.

Figure 2. Flow diagram of imaging data collected at baseline and 1‐year visit.

BL indicates baseline; FA, fractional anisotropy; MD, mean diffusivity; MRI, magnetic resonance imaging; NODDI, neurite orientation dispersion and density imaging; QT1, quantitative T1; WM, white matter; and WMH, white matter hyperintensity.

Figure 3. NODDI results at baseline in 4 tissue classes: stable NAWM, stable WMHs, and WMH change.

(Top Left) Neurite Density Index. (Top Right) Orientation Density Index. (Bottom Left) Free water fraction. Each boxplot indicates the median and interquartile range for each tissue class. Individual data points are overlaid as a beeswarm. NAWM indicates normal‐appearing white matter; NODDI, neurite orientation dispersion and density imaging; and WMH, white matter hyperintensity.

Figure 4. FA baseline (left) and 1‐year values (right) in stable NAWM, stable WMHs, and areas of WMH change.

Each boxplot indicates the median and interquartile range for each tissue class. Individual data points are overlaid as a beeswarm. FA indicates fractional anisotropy; NAWM, normal‐appearing white matter; and WMH, white matter hyperintensity.

Figure 5. MD (×10⁻³ mm²/s) at baseline (left) and at 1 year (right) in stable NAWM, stable WMHs, and WMH change.

Each boxplot indicates the median and interquartile range for each tissue class. Individual data points are overlaid as a beeswarm. MD indicates mean diffusivity; NAWM, normal‐appearing white matter; and WMH, white matter hyperintensity.

Figure 6. T1 (seconds) at baseline (left) and 1 year (right) in stable NAWM, stable WMHs, and WMH change.

Each boxplot indicates the median and interquartile range for each tissue class. Individual data points are overlaid as a beeswarm. NAWM indicates normal‐appearing white matter; and WMH, white matter hyperintensity.