From the Department of Neurology (Y.W., S.F., M.M.B., J.-M.L., H.A., A.L.F.), Division of Pediatric Hematology/Oncology (M.E.F.), Division of Pediatric Neurology (K.P.G.), and Mallinckrodt Institute of Radiology (C.E., J.S.S., M.R., K.D.V., Y.C., J.-M.L., H.A., A.L.F.), Washington University School of Medicine, St. Louis, MO.
Neurology. 2021 Aug 31;97(9):e902-e912. doi: 10.1212/WNL.0000000000012404. Epub 2021 Jun 25.
To determine the patient- and tissue-based relationships between cerebral hemodynamic and oxygen metabolic stress, microstructural injury, and infarct location in adults with sickle cell disease (SCD).
Control participants and patients with SCD underwent brain MRI to quantify cerebral blood flow (CBF), oxygen extraction fraction (OEF), mean diffusivity (MD), and fractional anisotropy (FA) within normal-appearing white matter (NAWM) and infarcts on fluid-attenuated inversion recovery. Multivariable linear regression examined the patient- and voxel-based associations between hemodynamic and metabolic stress (defined as elevated CBF and OEF, respectively), white matter microstructure, and infarct location.
Of 83 control participants and patients with SCD, adults with SCD demonstrated increased CBF (50.9 vs 38.8 mL/min/100 g, 0.001), increased OEF (0.35 vs 0.25, 0.001), increased MD (0.76 vs 0.72 × 10 mms, = 0.005), and decreased FA (0.40 vs 0.42, = 0.021) within NAWM compared to controls. In multivariable analysis, increased OEF (β = 0.19, = 0.035), but not CBF (β = 0.00, = 0.340), independently predicted increased MD in the SCD cohort; neither were predictors in controls. On voxel-wise regression, the SCD cohort demonstrated widespread OEF elevation, encompassing deep white matter regions of elevated MD and reduced FA, which spatially extended beyond high-density infarct locations from the SCD cohort.
Elevated OEF, a putative index of cerebral oxygen metabolic stress, may provide a metric of ischemic vulnerability that could enable individualization of therapeutic strategies in SCD. The patient- and tissue-based relationships between elevated OEF, elevated MD, and cerebral infarcts suggest that oxygen metabolic stress may underlie microstructural injury prior to the development of cerebral infarcts in SCD.
确定镰状细胞病（SCD）成人患者脑血流和氧代谢应激、微观结构损伤与梗死部位之间的患者和组织相关性。
对照组参与者和 SCD 患者接受脑部 MRI 检查，以定量评估正常外观的白质（NAWM）和液体衰减反转恢复的梗死区内脑血流（CBF）、氧提取分数（OEF）、平均扩散系数（MD）和各向异性分数（FA）。多元线性回归分析评估了血流动力学和代谢应激（分别定义为 CBF 和 OEF 升高）、白质微观结构和梗死部位之间的患者和体素相关性。
在 83 名对照组参与者和 SCD 患者中，SCD 成人患者的 CBF（50.9 与 38.8 mL/min/100 g， 0.001）、OEF（0.35 与 0.25， 0.001）、MD（0.76 与 0.72×10 mms， = 0.005）和 FA（0.40 与 0.42， = 0.021）均高于对照组。多元分析表明，SCD 组中，OEF 升高（β = 0.19， = 0.035），而 CBF 升高（β = 0.00， = 0.340）与 NAWM 中 MD 升高无关；在对照组中也没有预测作用。在体素回归分析中，SCD 组表现出广泛的 OEF 升高，包括 MD 升高和 FA 降低的深部白质区域，其空间范围超过了 SCD 组高密度梗死部位。
升高的 OEF，一种潜在的脑氧代谢应激指标，可能提供一种易缺血性的度量指标，从而能够在 SCD 中个体化治疗策略。OEF 升高、MD 升高和脑梗死之间的患者和组织相关性表明，氧代谢应激可能是 SCD 中脑梗死发生前微观结构损伤的基础。
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