Wang Junjun, Zhuang Liying, Fu Fengli, Mo Yejia, Zhai Lihao, Xu Qi, Mou Caiyun
Department of Neurology, Zhejiang Hospital, Hangzhou, China.
Department of Radiology, Zhejiang Hospital, Hangzhou, China.
Front Hum Neurosci. 2025 Jul 28;19:1633355. doi: 10.3389/fnhum.2025.1633355. eCollection 2025.
Different white matter hyperintensities (WMHs) distribution patterns exhibit distinct clinical implications, but their underlying mechanisms remain unclear. This study explores vascular risk factors and neuroimaging features to elucidate their heterogeneity.
We retrospectively analyzed WMHs patients who underwent multimodal MRI at Zhejiang Hospital. Neuroimaging features included gray matter volume, white matter microstructure (Fractional anisotropy, FA), and cerebral blood flow (CBF) were assessed. Vascular risk factors and imaging features were compared across four different WMHs distribution patterns [multi-spots, peri-basal ganglia, anterior subcortical (SC) patches, and posterior SC patches]. Mediation analysis was performed to explore the role of imaging features on WMHs related cognitive impairment.
A total of 163 patients were included in the final analysis. Among the four WMHs distribution patterns, hypertension was significantly more prevalent in patients with anterior SC patches [48 [85.7%] vs. 71 [66.4%], = 0.008]. All WMH distribution patterns except multi-spots exhibited reduced gray matter volume (Bonferroni < 0.0125). Notably, only patients with anterior SC patches exhibited a reduction in white matter FA (0.342 ± 0.049 vs. 0.370 ± 0.043, < 0.001). Furthermore, patients with posterior SC patches displayed significantly lower CBF in both gray matter (42.65 ± 11.76 vs. 48.02 ± 10.97, = 0.003) and white matter (35.25 ± 8.81 vs. 38.86 ± 8.07, = 0.007). Mediation analysis revealed that white matter microstructural injury mediated the association between anterior SC patches WMHs and cognitive impairment [β = -0.371, Bootstrap 95% CI [-0.939, -0.006]].
This study demonstrates heterogeneity in vascular risk factors, gray matter volume, microstructural injury, and hypoperfusion across different WMHs patterns, underscoring the importance of subtype-specific mechanistic and therapeutic research.
不同的脑白质高信号（WMHs）分布模式具有不同的临床意义，但其潜在机制仍不清楚。本研究探讨血管危险因素和神经影像学特征以阐明其异质性。
我们回顾性分析了在浙江医院接受多模态磁共振成像（MRI）的WMHs患者。评估了神经影像学特征，包括灰质体积、白质微观结构（分数各向异性，FA）和脑血流量（CBF）。比较了四种不同WMHs分布模式[多发点、基底节周围、前皮质下（SC）斑块和后SC斑块]的血管危险因素和影像学特征。进行中介分析以探讨影像学特征在与WMHs相关的认知障碍中的作用。
最终分析共纳入163例患者。在四种WMHs分布模式中，前SC斑块患者的高血压患病率显著更高[48例（85.7%）对71例（66.4%），P = 0.008]。除多发点外，所有WMHs分布模式均表现出灰质体积减少（Bonferroni校正P < 0.0125）。值得注意的是，仅前SC斑块患者的白质FA降低（0.342±0.049对0.370±0.043，P < 0.001）。此外，后SC斑块患者的灰质（42.65±11.76对48.02±10.97，P = 0.003）和白质（35.25±8.81对38.86±8.07，P = 0.007）的CBF均显著降低。中介分析显示，白质微观结构损伤介导了前SC斑块WMHs与认知障碍之间的关联[β = -0.371，Bootstrap 95%CI[-0.939，-0.006]]。
本研究证明了不同WMHs模式在血管危险因素、灰质体积、微观结构损伤和灌注不足方面存在异质性，强调了亚型特异性机制和治疗研究的重要性。
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