Muñoz Maniega Susana, Chappell Francesca M, Valdés Hernández Maria C, Armitage Paul A, Makin Stephen D, Heye Anna K, Thrippleton Michael J, Sakka Eleni, Shuler Kirsten, Dennis Martin S, Wardlaw Joanna M
1 Division of Neuroimaging Sciences, University of Edinburgh, Edinburgh, UK.
2 Department of Cardiovascular Science, University of Sheffield, Sheffield, UK.
J Cereb Blood Flow Metab. 2017 Feb;37(2):644-656. doi: 10.1177/0271678X16635657. Epub 2016 Jul 21.
White matter hyperintensities accumulate with age and occur in patients with stroke, but their pathogenesis is poorly understood. We measured multiple magnetic resonance imaging biomarkers of tissue integrity in normal-appearing white matter and white matter hyperintensities in patients with mild stroke, to improve understanding of white matter hyperintensities origins. We classified white matter into white matter hyperintensities and normal-appearing white matter and measured fractional anisotropy, mean diffusivity, water content (T1-relaxation time) and blood-brain barrier leakage (signal enhancement slope from dynamic contrast-enhanced magnetic resonance imaging). We studied the effects of age, white matter hyperintensities burden (Fazekas score) and vascular risk factors on each biomarker, in normal-appearing white matter and white matter hyperintensities, and performed receiver-operator characteristic curve analysis. Amongst 204 patients (34.3-90.9 years), all biomarkers differed between normal-appearing white matter and white matter hyperintensities ( P < 0.001). In normal-appearing white matter and white matter hyperintensities, mean diffusivity and T1 increased with age ( P < 0.001), all biomarkers varied with white matter hyperintensities burden ( P < 0.001; P = 0.02 signal enhancement slope), but only signal enhancement slope increased with hypertension ( P = 0.028). Fractional anisotropy showed complex age-white matter hyperintensities-tissue interactions; enhancement slope showed white matter hyperintensities-tissue interactions. Mean diffusivity distinguished white matter hyperintensities from normal-appearing white matter best at all ages. Blood-brain barrier leakage increases with hypertension and white matter hyperintensities burden at all ages in normal-appearing white matter and white matter hyperintensities, whereas water mobility and content increase as tissue damage accrues, suggesting that blood-brain barrier leakage mediates small vessel disease-related brain damage.
脑白质高信号随年龄增长而累积，且见于中风患者，但对其发病机制了解甚少。我们测量了轻度中风患者正常脑白质和脑白质高信号中多种组织完整性的磁共振成像生物标志物，以增进对脑白质高信号起源的理解。我们将脑白质分为脑白质高信号和正常脑白质，并测量了分数各向异性、平均扩散率、含水量（T1弛豫时间）和血脑屏障渗漏（动态对比增强磁共振成像的信号增强斜率）。我们研究了年龄、脑白质高信号负荷（ Fazekas评分）和血管危险因素对正常脑白质和脑白质高信号中每种生物标志物的影响，并进行了受试者工作特征曲线分析。在204例患者（年龄34.3 - 90.9岁）中，正常脑白质和脑白质高信号之间的所有生物标志物均存在差异（P < 0.001）。在正常脑白质和脑白质高信号中，平均扩散率和T1随年龄增加（P < 0.001），所有生物标志物随脑白质高信号负荷而变化（P < 0.001；信号增强斜率P = 0.02），但只有信号增强斜率随高血压增加（P = 0.028）。分数各向异性显示出年龄 - 脑白质高信号 - 组织之间的复杂相互作用；增强斜率显示出脑白质高信号 - 组织之间的相互作用。在所有年龄段，平均扩散率区分脑白质高信号和正常脑白质的效果最佳。在正常脑白质和脑白质高信号中，血脑屏障渗漏在所有年龄段均随高血压和脑白质高信号负荷增加，而水流动性和含量随组织损伤累积而增加，这表明血脑屏障渗漏介导了与小血管疾病相关的脑损伤。
