Changes in Normal-Appearing White Matter Precede Development of White Matter Lesions
Changes in Normal-Appearing White Matter Precede Development of White Matter Lesions
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DOI：
10.1161/strokeaha.112.680223
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发表时间：
2013-04-01
期刊：
影响因子：
8.3
通讯作者：
Vernooij, Meike W.
中科院分区：
文献类型：
--
作者：
de Groot, Marius;Verhaaren, Benjamin F. J.;Vernooij, Meike W.
背景和目的——尚不清楚白质病变 (WML) 是否在先前正常的大脑区域突然发生，或者在 WML 在 MRI 上变得明显之前是否已经存在组织变化。因此，我们研究了 WML 的发展是否先于正常白质 (NAWM) 的可量化变化。 方法 - 在来自普通人群的 689 名参与者（平均年龄 67 岁）中，我们使用相同的 1.5-T 扫描仪进行了 2 次 MRI 扫描（包括扩散张量成像和流体衰减反转恢复 [FLAIR] 序列），间隔 3.5 年。使用自动组织分割，我们在基线时识别出 NAWM。我们评估了哪些 NAWM 区域在后续过程中转化为 WML，并将新的 WML 区分为 WML 生长区域和从头 WML。使用 3 种方法比较转换为 WML 的区域和持续性 NAWM 区域的分数各向异性、平均扩散率和 FLAIR 强度：全脑分析、区域匹配方法和体素方法。结果 - 所有 3 种方法均表明，基线时低分数各向异性、高平均扩散率和相对较高的 FLAIR 强度与随访期间 WML 的发展相关。与持续性NAWM区域相比，转换为WML的NAWM区域具有显着较低的分数各向异性（0.337 vs 0.387；P < 0.001）、较高的平均扩散率（0.910x10(-3) mm(2)/s vs 0.729x10(-3) mm(2/)s；P < 0.001）以及相对较高的归一化FLAIR强度(1.233 对比 -0.340； P < 0.001）。这适用于 NAWM 发展为生长中的 WML 和从头开始的 WML。结论 - NAWM 中的白质变化是存在的，并且可以在 WML 发展之前通过扩散张量成像和 FLAIR 进行量化。这表明 WML 逐渐发展，视觉上可察觉的 WML 只是白质病理学的冰山一角。 （中风。2013；44：1037-1042。）
Background and Purpose-It is unknown whether white matter lesions (WML) develop abruptly in previously normal brain areas, or whether tissue changes are already present before WML become apparent on MRI. We therefore investigated whether development of WML is preceded by quantifiable changes in normal-appearing white matter (NAWM).Methods-In 689 participants from the general population (mean age 67 years), we performed 2 MRI scans (including diffusion tensor imaging and Fluid Attenuation Inversion Recovery [FLAIR] sequences) 3.5 years apart using the same 1.5-T scanner. Using automated tissue segmentation, we identified NAWM at baseline. We assessed which NAWM regions converted into WML during follow-up and differentiated new WML into regions of WML growth and de novo WML. Fractional anisotropy, mean diffusivity, and FLAIR intensity of regions converting to WML and regions of persistent NAWM were compared using 3 approaches: a whole-brain analysis, a regionally matched approach, and a voxel-wise approach.Results-All 3 approaches showed that low fractional anisotropy, high mean diffusivity, and relatively high FLAIR intensity at baseline were associated with WML development during follow-up. Compared with persistent NAWM regions, NAWM regions converting to WML had significantly lower fractional anisotropy (0.337 vs 0.387; P < 0.001), higher mean diffusivity (0.910x10(-3) mm(2)/s vs 0.729x10(-3) mm(2/)s; P < 0.001), and relatively higher normalized FLAIR intensity (1.233 vs -0.340; P < 0.001). This applied to both NAWM developing into growing and de novo WML.Conclusions-White matter changes in NAWM are present and can be quantified on diffusion tensor imaging and FLAIR before WML develop. This suggests that WML develop gradually, and that visually appreciable WML are only the tip of the iceberg of white matter pathology. (Stroke. 2013;44:1037-1042.)