Objectives White matter hyperintensity (WMH) is commonly observed in patients with intracranial artery stenosis (ICAS), such as atherosclerosis or moyamoya disease (MMD). However, the relationships between ICAS, cerebral blood flow (CBF), and WMH remain unclear. We aimed to investigate whether reduced CBF mediated the relationship between ICAS and WMH in MMD. Materials and methods We retrospectively analyzed prospectively collected data of patients with MMD who underwent 3T-MRI between June 2020 and July 2023. CBF in the territories of anterior cerebral artery (ACA), middle cerebral artery (MCA) and posterior cerebral artery (PCA) was quantified using arterial spin labeling, and the stage of ICAS was evaluated by MRA. We pooled the data from each hemisphere together. Results Sixty-five patients were included, with WMH mainly distributed within the MCA territory. Among 124 hemispheres with WMH, WMH volume increased with the increased stage of ICAS (p < 0.001). CBF in each arterial territory showed a negative correlation with WMH volume (ACA: r = −0.364; MCA: r = −0.406; PCA: r = −0.309; all p < 0.001). Linear mixed-effects models revealed that ICAS stage (β = 0.132, p = 0.026) and CBF in the MCA territory (β = −0.026, p = 0.019) were significantly associated with WMH volume. Mediation analysis showed that decreased CBF in the MCA territory mediated 40% of the effect of ICAS on WMH volume. Conclusions Hypoperfusion in the MCA territory partially mediated the association between ICAS and WMH, suggesting that enhancing perfusion could be a potential treatment strategy for WMH in MMD. Key Points <Emphasis Type="BoldItalic">Question</Emphasis> Whether cerebral blood flow mediates the relationship between intracranial artery stenosis and white matter hyperintensity remains unclear. <Emphasis Type="BoldItalic">Findings</Emphasis> In patients with moyamoya disease, cerebral blood flow in the middle cerebral artery territory mediates 40% of the effect of arterial stenosis on white matter hyperintensity. <Emphasis Type="BoldItalic">Clinical relevance</Emphasis> Improvement of cerebral blood flow in the middle cerebral artery territory could be a potential treatment strategy for white matter hyperintensity in moyamoya disease, thereby alleviating clinical manifestations such as cognitive dysfunction in patients. Graphical Abstract

Unraveling the links between intracranial artery stenosis, cerebral perfusion, and white matter hyperintensity in moyamoya disease

期刊论文
发表日期：

2025年7月30日

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Duo Xu,
Reng Ren,
Junwen Hu,
Lin Wang,
Biao Jiang,
Minming Zhang,
Xinfeng Yu

摘要

Objectives

White matter hyperintensity (WMH) is commonly observed in patients with intracranial artery stenosis (ICAS), such as atherosclerosis or moyamoya disease (MMD). However, the relationships between ICAS, cerebral blood flow (CBF), and WMH remain unclear. We aimed to investigate whether reduced CBF mediated the relationship between ICAS and WMH in MMD.

Materials and methods

We retrospectively analyzed prospectively collected data of patients with MMD who underwent 3T-MRI between June 2020 and July 2023. CBF in the territories of anterior cerebral artery (ACA), middle cerebral artery (MCA) and posterior cerebral artery (PCA) was quantified using arterial spin labeling, and the stage of ICAS was evaluated by MRA. We pooled the data from each hemisphere together.

Results

Sixty-five patients were included, with WMH mainly distributed within the MCA territory. Among 124 hemispheres with WMH, WMH volume increased with the increased stage of ICAS (p < 0.001). CBF in each arterial territory showed a negative correlation with WMH volume (ACA: r = −0.364; MCA: r = −0.406; PCA: r = −0.309; all p < 0.001). Linear mixed-effects models revealed that ICAS stage (β = 0.132, p = 0.026) and CBF in the MCA territory (β = −0.026, p = 0.019) were significantly associated with WMH volume. Mediation analysis showed that decreased CBF in the MCA territory mediated 40% of the effect of ICAS on WMH volume.

Conclusions

Hypoperfusion in the MCA territory partially mediated the association between ICAS and WMH, suggesting that enhancing perfusion could be a potential treatment strategy for WMH in MMD.

Key Points

Question Whether cerebral blood flow mediates the relationship between intracranial artery stenosis and white matter hyperintensity remains unclear.

Findings In patients with moyamoya disease, cerebral blood flow in the middle cerebral artery territory mediates 40% of the effect of arterial stenosis on white matter hyperintensity.

Clinical relevance Improvement of cerebral blood flow in the middle cerebral artery territory could be a potential treatment strategy for white matter hyperintensity in moyamoya disease, thereby alleviating clinical manifestations such as cognitive dysfunction in patients.

Graphical Abstract