Data_Sheet_1_Increase in Brain Volume After Aneurysmal Subarachnoid Hemorrhage Leads to Unfavorable Outcome: A Retrospective Study Quantified by CT Scan.doc

Background and Purpose: Primary brain swelling occurs in aneurysmal subarachnoid hemorrhage (aSAH) patients. The absence of a dynamic quantitative method restricts further study of primary brain swelling. This study compared differences in the change rate of brain volume (CRBV) between patients with and without primary brain swelling in the early stage of aSAH. Moreover, the relationship between CRBV and clinical outcomes was evaluated.
Methods: Patients hospitalized within 24 h after aSAH were included in this retrospective study. Utilizing a qualitative standard established before the study to recognize primary brain swelling through brain CT after aSAH, clinical outcomes after 3 months of SAH were evaluated with a modified Rankin scale (mRS). The brain volume (BV) of each patient was calculated with a semiautomatic threshold algorithm of 3D-slicer, and the change in brain volume (CIBV) was obtained by subtracting the two extreme values (CIBV = BVmax – BVmin). The CRBV was obtained by CIBV/BVmin × 100%. The CRBV values that predicted unfavorable prognoses were estimated.
Results: In total, 130 subjects were enrolled in the study. The mean CRBV in the non-swelling group and swelling group were 4.37% (±4.77) and 11.87% (±6.84), respectively (p < 0.05). CRBV was positively correlated with the length of hospital stay, blood in the ambient cistern, blood in the lateral ventricle, and lateral ventricular volume (Spearman ρ = 0.334; p < 0.001; Pearson ρ = 0.269, p = 0.002; Pearson ρ = 0.278, p = 0.001; Pearson ρ = 0.233, p = 0.008, respectively). Analysis of variance showed significant differences in CIBV, CRBV, blood in the ambient cistern, blood in the lateral ventricle, and lateral ventricular volume among varying modified Fisher scale (mFisher), with higher admission mFisher scale, indicating larger values of these variables. After adjusting for risk factors, the model showed that for every 1% increase in the CRBV, the probability of poor clinical prognosis increased by a factor of 1.236 (95% CI = 1.056–1.446). In the stratified analysis, the odds of worse clinical outcomes increased with increases in the CRBV. Receiver operating characteristic curve analysis showed that HH grade, mFisher scale, and score of CRBV (SCRBV) had diagnostic performance for predicting unfavorable clinical outcomes.
Conclusion: Primary brain swelling increases brain volume after aSAH. The CRBV quantified by 3D-Slicer can be used as a volumetric representation of the degree of brain swelling. A larger CRBV in the early stage of aSAH is associated with poor prognosis. The CRBV can be used as a neuroimaging biomarker of early brain injury after bleeding and may be an effective predictor of patients' clinical prognoses.

背景与目的：动脉瘤性蛛网膜下腔出血（aneurysmal subarachnoid hemorrhage, aSAH）患者可发生原发性脑肿胀（primary brain swelling）。目前缺乏动态定量检测方法，限制了对原发性脑肿胀的进一步研究。本研究比较了aSAH早期伴与不伴原发性脑肿胀患者的脑体积变化率（change rate of brain volume, CRBV）差异，并评估了CRBV与临床预后的相关性。

方法：本回顾性研究纳入了aSAH发病后24小时内住院的患者。采用研究前期确立的定性标准，通过aSAH后颅脑CT影像识别原发性脑肿胀；采用改良Rankin量表（modified Rankin scale, mRS）评估SAH后3个月的临床预后。使用3D-Slicer的半自动阈值算法计算每位患者的脑体积（brain volume, BV），通过两个极值相减得到脑体积变化量（change in brain volume, CIBV，即CIBV = BVmax – BVmin）。脑体积变化率CRBV由公式CIBV/BVmin × 100%计算得出，并估算了可预测不良预后的CRBV临界值。

结果：本研究共纳入130名受试者。非肿胀组与肿胀组的平均CRBV分别为4.37%（±4.77）与11.87%（±6.84），组间差异具有统计学意义（p < 0.05）。CRBV与住院时长、环池积血、侧脑室积血及侧脑室体积均呈正相关（Spearman ρ=0.334，p<0.001；Pearson ρ=0.269，p=0.002；Pearson ρ=0.278，p=0.001；Pearson ρ=0.233，p=0.008）。方差分析显示，不同改良Fisher量表（modified Fisher scale, mFisher）分组间的CIBV、CRBV、环池积血、侧脑室积血及侧脑室体积均存在显著差异，入院时mFisher量表评分越高，上述指标数值越大。校正危险因素后，模型显示CRBV每升高1%，临床预后不良的概率增加1.236倍（95%置信区间：1.056~1.446）。分层分析显示，临床不良预后的比值比随CRBV升高而升高。受试者工作特征曲线（Receiver Operating Characteristic, ROC）分析显示，HH分级、mFisher量表及CRBV评分（score of CRBV, SCRBV）对预测不良临床预后具有诊断效能。

结论：原发性脑肿胀可增加aSAH后的脑体积。通过3D-Slicer量化得到的CRBV可作为脑肿胀程度的体积表征指标。aSAH早期较高的CRBV与不良预后显著相关。CRBV可作为出血后早期脑损伤的神经影像学生物标志物，或可成为预测患者临床预后的有效指标。