Voorter Paulien H M, Stringer Michael S, van Dinther Maud, Kerkhofs Daniëlle, Dewenter Anna, Blair Gordon W, Thrippleton Michael J, Jaime Garcia Daniela, Chappell Francesca M, Janssen Esther, Kopczak Anna, Staals Julie, Ingrisch Michael, Duering Marco, Doubal Fergus N, Dichgans Martin, van Oostenbrugge Robert J, Jansen Jacobus F A, Wardlaw Joanna M, Backes Walter H
Department of Radiology and Nuclear Medicine (P.H.M.V., J.F.A.J., W.H.B.), Maastricht University Medical Center, the Netherlands.
Mental Health and Neuroscience Research Institute (P.H.M.V., R.J.v.O., J.F.A.J., W.H.B.), Maastricht University, the Netherlands.
Stroke. 2025 Jan;56(1):128-137. doi: 10.1161/STROKEAHA.124.047910. Epub 2024 Dec 9.
White matter hyperintensities (WMHs) are established structural imaging markers of cerebral small vessel disease. The pathophysiologic condition of brain tissue varies over the core, the vicinity, and the subtypes of WMH and cannot be interpreted from conventional magnetic resonance imaging. We aim to improve our pathophysiologic understanding of WMHs and the adjacently injured normal-appearing white matter in terms of microstructural and microvascular alterations using quantitative magnetic resonance imaging in patients with sporadic and genetic cerebral small vessel disease.
Structural T-weighted imaging, multishell diffusion imaging, and dynamic contrast-enhanced magnetic resonance imaging were performed at 3T in 44 participants with sporadic cerebral small vessel disease and 32 participants with monogenic cerebral small vessel disease (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; 59±12 years, 41 males) between June 2017 and May 2020 as part of the prospective, multicenter (Edinburgh, the United Kingdom; Maastricht, the Netherlands; and Munich, Germany), observational INVESTIGATE-SVDs study (Imaging Neurovascular, Endothelial and Structural Integrity in Preparation to Treat Small Vessel Diseases). The mean diffusivity, free water content, and perfusion (all derived from multishell diffusion imaging), as well as the blood-brain barrier leakage and plasma volume fraction (derived from dynamic contrast-enhanced magnetic resonance imaging), were compared between deep and periventricular WMH types using paired tests. Additional spatial analyses were performed inside and outside the WMH types to determine the internal heterogeneity and the extent of the penumbras, that is, adjacent white matter at risk for conversion to WMH.
Periventricular WMH had higher mean diffusivity, higher free water content, and more plasma volume compared with deep WMH (<0.001, =0.01, and <0.001, respectively). No differences were observed in perfusion (=0.94) and blood-brain barrier leakage (=0.65) between periventricular and deep WMHs. The spatial analyses inside WMH and the adjacent white matter revealed a gradual gradient in white matter microstructure, free water content, perfusion, and plasma volume but not in blood-brain barrier leakage.
We showed different pathophysiological heterogeneity of the 2 WMH types. Periventricular WMHs display more severe damage and fluid accumulation compared with deep WMH, whereas deep WMHs reflect stronger hypoperfusion in the lesion's core.
URL: https://www.isrctn.com; Unique identifier: ISRCTN10514229.
脑白质高信号（WMHs）是已确立的脑小血管病的结构成像标志物。脑组织的病理生理状况在WMHs的核心、周边及亚型之间存在差异，无法从传统磁共振成像中得到解读。我们旨在通过对散发性和遗传性脑小血管病患者进行定量磁共振成像，从微观结构和微血管改变方面，加深对WMHs及其相邻的外观正常但已受损白质的病理生理理解。
2017年6月至2020年5月期间，在3T条件下，对44例散发性脑小血管病患者和32例单基因脑小血管病（大脑常染色体显性动脉病伴皮质下梗死和白质脑病；年龄59±12岁，男性41例）患者进行了结构T加权成像、多壳层扩散成像和动态对比增强磁共振成像，作为前瞻性、多中心（英国爱丁堡；荷兰马斯特里赫特；德国慕尼黑）观察性研究INVESTIGATE - SVDs研究（为治疗小血管病准备的神经血管、内皮和结构完整性成像）的一部分。使用配对t检验比较深部和脑室周围WMH类型之间的平均扩散率、自由水含量和灌注（均来自多壳层扩散成像），以及血脑屏障渗漏和血浆体积分数（来自动态对比增强磁共振成像）。在WMH类型内部和外部进行了额外的空间分析，以确定内部异质性和半暗带范围，即有转化为WMH风险的相邻白质。
与深部WMH相比，脑室周围WMH具有更高的平均扩散率、更高的自由水含量和更多的血浆体积（分别为<0.001、=0.01和<0.001）。脑室周围和深部WMH在灌注（=0.94）和血脑屏障渗漏（=0.65）方面未观察到差异。对WMH内部和相邻白质的空间分析显示，白质微观结构、自由水含量、灌注和血浆体积存在逐渐变化的梯度，但血脑屏障渗漏不存在。
我们展示了两种WMH类型不同的病理生理异质性。与深部WMH相比，脑室周围WMH表现出更严重的损伤和液体蓄积，而深部WMH在病变核心反映出更强的灌注不足。
