BACKGROUND AND OBJECTIVES Large vessel vasculopathy (LVV), or moyamoya syndrome, increases the risk of stroke in patients with sickle cell disease (SCD), yet effective treatments are lacking. In atherosclerotic carotid disease, previous studies demonstrated elevated oxygen extraction fraction (OEF) as a predictor of ipsilateral stroke. In a SCD cohort, we examined hemispheric hemodynamic and oxygen metabolic dysfunction as tissue-based biomarkers of cerebral ischemic risk in patients with LVV. METHODS Children and adults with SCD were recruited from a SCD clinic associated with a tertiary medical center and underwent prospective brain MRI and MR angiography. LVV was defined as ≥75% stenosis in a major anterior circulation artery, excluding occlusion or previous revascularization surgery. Baseline characteristics, cerebral blood flow (CBF), normalized OEF (nOEF), infarct volume, white matter microstructure, and brain volume were compared in hemispheres with vs without LVV. In a cross-sectional analysis, mixed-effects linear multivariable models examined the effect of LVV on: (1) CBF and nOEF, as tissue markers of hemodynamic and oxygen metabolic stress, respectively, and (2) endpoints of cerebral ischemic injury including infarct volume, white matter microstructure, and brain volume. RESULTS Of 155 patients (22 [12-31] years, 57% female), 33 (21%) had ≥25% stenosis, 22 (14%) had ≥50% stenosis, 14 (9%) had 75%-99% stenosis, and 5 (3%) had 100% occlusion. After excluding hemispheres with previous revascularization surgery, LVV was present in 16 hemispheres from 11 patients. Hemispheres with (N = 16) vs without (N = 283) LVV had lower CBF (25.2 vs 32.1 mL/100 g/min, p = 0.01) and higher nOEF (0.99 vs 0.95, p = 0.02). On multivariable analysis, CBF was nonsignificantly lower (β = -0.16, p = 0.07) while nOEF remained higher in hemispheres with LVV (β = 0.04, p = 0.03). Moreover, LVV was associated with greater hemispheric infarct volume, microstructural disruption, and atrophy. DISCUSSION Beyond greater infarct burden, LVV was associated with hemispheric atrophy and white matter microstructural injury. As an indicator of active hypoxia, elevated nOEF likely represents a compensatory response to flow-limiting stenosis in hemispheres with LVV. The study is limited by a small number of patients with severe stenosis. Future studies are needed to evaluate the potential of tissue-based CBF and nOEF in assessing stroke risk and guide timely treatment of vasculopathy in SCD.

中文翻译：

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镰状细胞病引起的大血管病变儿童和成人的脑氧代谢应激。


背景和目的 大血管病变 （LVV） 或烟雾病综合征会增加镰状细胞病 （SCD） 患者发生中风的风险，但缺乏有效的治疗方法。在动脉粥样硬化性颈动脉疾病中，先前的研究表明氧提取分数 （OEF） 升高是同侧卒中的预测因子。在 SCD 队列中，我们检查了半球血流动力学和氧代谢功能障碍作为 LVV 患者脑缺血风险的基于组织的生物标志物。方法 从与三级医疗中心相关的 SCD 诊所招募患有 SCD 的儿童和成人，并接受前瞻性脑部 MRI 和 MR 血管造影。LVV 被定义为前大前循环动脉狭窄 ≥75%，不包括闭塞或既往血运重建手术。比较有 LVV 和无 LVV 的半球的基线特征、脑血流量 （CBF） 、标准化 OEF （nOEF） 、梗死体积、白质微观结构和脑体积。在横断面分析中，混合效应线性多变量模型检查了 LVV 对以下方面的影响： （1） CBF 和 nOEF，分别作为血流动力学和氧代谢应激的组织标志物，以及 （2） 脑缺血性损伤的终点，包括梗死体积、白质微观结构和脑体积。结果 155 例患者 （22 [12-31] 岁，57% 为女性），33 例 （21%） 狭窄 ≥25%，22 例 （14%） 狭窄 ≥50%，14 例 （9%） 狭窄 75%-99%，5 例 （3%） 闭塞 100%。在排除既往血运重建手术的半球后，11 例患者的 16 个半球存在 LVV。有 （N = 16） 与无 （N = 283） LVV 的半球具有较低的 CBF （25.2 vs 32.1 mL/100 g/min，p = 0.01） 和较高的 nOEF （0.99 vs 0.95，p = 0.02）。 在多变量分析中，CBF 无统计学意义地降低 （β = -0.16，p = 0.07），而 nOEF 在 LVV 的半球仍然较高 （β = 0.04，p = 0.03）。此外，LVV 与更大的半球梗死体积、微结构破坏和萎缩有关。讨论 除了更大的梗死负担外，LVV 还与半球萎缩和白质微结构损伤有关。作为活动性缺氧的指标，nOEF 升高可能代表 LVV 半球对限流性狭窄的代偿反应。该研究受到少数严重狭窄患者的限制。需要未来的研究来评估基于组织的 CBF 和 nOEF 在评估中风风险方面的潜力，并指导及时治疗 SCD 中的血管病变。