From the Departments of Anesthesiology and Critical Care Medicine (M.P.K., C.L., M.W., J.H., R.A.B., A.T.), and Radiology (J.I.B., M.O., H.H., A.V.); Data Science and Biostatistics Unit (H.L., A.M., H.G.), Department of Biomedical and Health Informatics, and Department of Neurosurgery (S.-S.L.), Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
Neurology. 2022 Dec 5;99(23):e2615-e2626. doi: 10.1212/WNL.0000000000201189.
Diffusion MRI can quantify the extent of hypoxic-ischemic brain injury after cardiac arrest. Our objective was to determine the association between the adult-derived threshold of apparent diffusion coefficient (ADC) <650 × 10 mm/s in >10% of brain tissue and an unfavorable outcome after pediatric cardiac arrest. Since ADC decreases exponentially as a function of increasing age, we determined the association between (1) having >10% of brain tissue below a novel age-dependent ADC threshold, and (2) age-normalized whole-brain mean ADC and unfavorable outcome.
This was a retrospective study of patients aged ≤18 years who had cardiac arrest and a clinically obtained brain MRI within 7 days. The primary outcome was unfavorable neurologic status at hospital discharge based on the Pediatric Cerebral Performance Category score. ADC images were extracted from 3-direction diffusion imaging. We determined whether each patient had >10% of voxels with an ADC below prespecified thresholds. We computed the whole-brain mean ADC for each patient.
One hundred thirty-four patients were analyzed. Patients with ADC <650 × 10 mm/s in >10% of voxels had 15 times higher odds (95% CI 5-65) of an unfavorable outcome compared with patients with ADC <650 × 10 mm/s (area under the receiver operating characteristic curve [AUROC] 0.72 [95% CI 0.63-0.80]). These ADC criteria had a sensitivity and specificity of 0.49 and 0.94, respectively, and positive and negative predictive values of 0.93 and 0.52, respectively, for an unfavorable outcome. The age-dependent ADC threshold that yielded optimal sensitivity and specificity for unfavorable outcomes was <300 × 10 mm/s below each patient's predicted whole-brain mean ADC. The sensitivity, specificity, and positive and negative predictive values for this ADC threshold were 0.53, 0.96, 0.96, and 0.54, respectively (odds ratio [OR] 26.4 [95% CI 7.5-168.3]; AUROC 0.74 [95% CI 0.66-0.83]). Lower age-normalized whole-brain mean ADC was also associated with an unfavorable outcome (OR 0.42 [0.24-0.64], AUROC 0.76 [95% CI 0.66-0.82]).
Quantitative diffusion thresholds on MRI within 7 days after cardiac arrest were associated with an unfavorable outcome in children. The age-independent ADC threshold was highly specific for predicting an unfavorable outcome. However, the specificity and sensitivity increased when using age-dependent ADC thresholds. Age-dependent ADC thresholds may improve prognostic accuracy and require further investigation in larger cohorts.
This study provides Class III evidence that quantitative diffusion-weighted imaging within 7 days postarrest can predict an unfavorable clinical outcome in children.
弥散 MRI 可定量评估心脏骤停后缺氧缺血性脑损伤的程度。我们的目的是确定成人获得的表观扩散系数（ADC）<650×10mm/s 的阈值>10%的脑组织与儿科心脏骤停后不良结局之间的相关性。由于 ADC 随年龄的增加呈指数下降，因此我们确定了以下两种情况之间的相关性：（1）>10%的脑组织的 ADC 值低于新的年龄依赖性 ADC 阈值；（2）年龄归一化的全脑平均 ADC 值与不良结局。
这是一项回顾性研究，纳入了年龄≤18 岁的心脏骤停患者，且在发病后 7 天内获得了临床脑 MRI。主要结局是基于小儿脑功能分类评分的出院时不良神经状态。从 3 个方向的弥散成像中提取 ADC 图像。我们确定每个患者是否有>10%的体素 ADC 值低于预设阈值。我们计算了每个患者的全脑平均 ADC 值。
共分析了 134 例患者。与 ADC <650×10mm/s 的患者相比，ADC <650×10mm/s 的患者中>10%的脑区 ADC 值较低的患者不良结局的可能性高 15 倍（95%CI 5-65）（受试者工作特征曲线下面积 [AUROC] 0.72 [95%CI 0.63-0.80]）。这些 ADC 标准的敏感性和特异性分别为 0.49 和 0.94，阳性和阴性预测值分别为 0.93 和 0.52，用于预测不良结局。为获得最佳敏感性和特异性，年龄依赖性 ADC 阈值为每个患者预测的全脑平均 ADC 值以下<300×10mm/s。该 ADC 阈值的敏感性、特异性、阳性和阴性预测值分别为 0.53、0.96、0.96 和 0.54（比值比 [OR] 26.4 [95%CI 7.5-168.3]；AUROC 0.74 [95%CI 0.66-0.83]）。较低的年龄归一化全脑平均 ADC 也与不良结局相关（OR 0.42 [0.24-0.64]，AUROC 0.76 [95%CI 0.66-0.82]）。
心脏骤停后 7 天内 MRI 的定量弥散阈值与儿童不良结局相关。独立于年龄的 ADC 阈值对预测不良结局具有高度特异性。然而，当使用年龄依赖性 ADC 阈值时，特异性和敏感性会增加。年龄依赖性 ADC 阈值可能会提高预后准确性，需要在更大的队列中进一步研究。
这项研究提供了 III 级证据，表明心脏骤停后 7 天内的定量弥散加权成像可以预测儿童的不良临床结局。
