Supplementary Material for: Relation between cerebral small vessel function at 7T MRI and small vessel disease burden in a general ageing population

Introduction There is a need for measures of early stages of cerebral small vessel diseases (cSVDs). Recently, using 7T MRI, abnormalities of small vessel function were reported in patients with clinically manifest cSVD. The question is if such abnormalities are also present in early, covert stages of cSVD. We therefore studied the relation between cerebral small vessel function measures on 7T MRI and the burden of covert cSVD in the general ageing population. Methods Two hundred participants (mean age (years) ± SD: 71 ± 5, 43% women) without a history of stroke or dementia from the Rotterdam Study were included. Small vessel measures at 7T MRI, including perforating artery blood flow velocity and pulsatility and cerebrovascular reactivity (CVR) to carbon dioxide, were related to markers of cSVD burden at 1.5T MRI, including white matter hyperintensity volume and microbleed, enlarged perivascular spaces, and lacune presence, using linear and logistic regression analyses. We also included cognitive performance as a clinical indicator of covert cSVD. Results Across the population, neither perforating artery flow measures nor CVR were significantly associated with cSVD lesion burden or cognition, with small point estimates and no consistent direction of effects. Yet, within individuals, CVR was lower inside white matter hyperintensities compared to normal-appearing white matter (CVRNAWM=0.54±0.48%; CVRWMH=0.24±0.94%; p = 0.006). Conclusion Although these data confirm that vascular function is affected within WMH, we did not observe relations between small vessel function measures at 7T MRI and the burden of covert cSVD in this population-based sample. Apparently, these measures have limited sensitivity to early stages of cSVD.引言 目前亟需针对脑小血管病（cerebral small vessel diseases, cSVDs）早期阶段的评估手段。近期有研究借助7T磁共振成像（7T MRI），在临床确诊的cSVD患者中发现了小血管功能异常。当前的核心问题是，此类功能异常是否也存在于cSVD的早期隐匿阶段。为此，本研究在普通老年人群中探究了7T MRI下的脑小血管功能评估指标与隐匿性cSVD负荷之间的关联。 研究方法 本研究纳入了来自鹿特丹研究（Rotterdam Study）的200名无卒中或痴呆病史的受试者，其平均年龄为71±5岁，女性占比43%。本研究采用线性回归与logistic回归分析，将7T MRI下的脑小血管功能指标，包括穿支动脉血流速度、搏动性参数以及二氧化碳脑血管反应性（CVR），与1.5T磁共振成像（1.5T MRI）下的隐匿性cSVD负荷标志物，包括白质高信号体积、脑微出血、扩大的血管周围间隙以及腔隙性梗死灶存在情况，进行关联分析。此外，本研究还将认知表现作为隐匿性cSVD的临床评估指标。 研究结果 在全人群中，穿支动脉血流相关指标与CVR均未与cSVD病变负荷或认知表现呈现显著关联，其点估计值较小且效应方向无一致性。但在个体内部，白质高信号区域的CVR较正常表观白质更低（正常表观白质CVR=0.54±0.48%；白质高信号区域CVR=0.24±0.94%；p=0.006）。 结论 尽管本研究数据证实了白质高信号（white matter hyperintensity, WMH）区域内的血管功能确实受到影响，但在该基于人群的样本中，我们未观察到7T MRI下的脑小血管功能指标与隐匿性cSVD负荷之间存在关联。由此可见，此类评估指标对cSVD早期阶段的检测灵敏度较为有限。