Diagnostic Efficacy of Quantitative Computed Tomography in CTD-ILA/ILD
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摘要:
目的：定量CT在结缔组织病相关间质性肺异常（CTD-ILA）和间质性肺疾病（CTD-ILD）中的诊断效能，建立基于定量CT的CTD患者筛查方法。方法：纳入CTD-ILD患者140例、CTD-ILA患者33例及对照组109例，使用3D-Slicer获得定量指标。结果：各组间定量CT指标均存在差异；ROC分析显示，F%、GGO%、SD及Kurtosis是鉴别对照组与CTD-ILA/ILD的敏感指标，其中SD在早期诊断CTD-ILA（AUC=0.862）、CTD-ILD（AUC=0.923）时表现最佳，进一步区分CTD-ILA与CTD-ILD时，SD（AUC=0.649）和F%（AUC=0.617）展现出较强区分能力；多元逐步logistic回归分析显示，F%、GGO%、SD和Kurtosis在区分对照组与CTD-ILA/ILD时具有统计学意义。结论：定量CT对于CTD-ILA/ILD早期诊断具有重要意义，基于定量CT构建CTD筛查流程有助实现患者精准管理。
Abstract:Objective: The aim of this study is to evaluate the diagnostic efficacy of quantitative computed tomography (CT) in differentiating between connective tissue disease-associated interstitial lung abnormalities (CTD-ILA) and connective tissue disease-associated interstitial lung disease (CTD-ILD), as well as to establish a screening protocol for connective tissue disease (CTD) patients based on quantitative CT. Methods: A total of 140 patients with CTD-ILD, 33 patients with CTD-ILA, and 109 healthy controls were enrolled. Quantitative indices were obtained using the 3D-Slicer software. Results: Significant differences in quantitative CT indices are observed among the groups. ROC analysis shows that the F%, GGO%, SD, and kurtosis are sensitive indicators for differentiating the control group from those with CTD-ILA/ILD. Notably, the best SD is demonstrated in the early diagnosis of both the CTD-ILA (AUC=0.862) and CTD-ILD (AUC=0.923) groups. Further distinguishing between CTD-ILA and CTD-ILD shows the strong discriminatory ability of the SD (AUC=0.649) and F% (AUC=0.617). Multivariable stepwise logistic regression analysis shows that F%, GGO%, SD, and kurtosis are statistically significant in differentiating the control group from the CTD-ILA/ILD groups. Conclusion: Quantitative CT is promising for the early diagnosis of CTD-ILA/ILD. Establishing a CTD screening protocol based on quantitative CT can facilitate precise patient management.
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图 1 CTD-ILA（a）和CTD-ILD（b）HRCT示例图
注：（a）一名59岁系统性红斑狼疮女性患者，按照指南诊断ILA，患者尚无呼吸系统症状。（b）一名66岁类风湿关节炎男性患者，按照指南诊断ILD，患者存在呼吸系统症状。
Figure 1. Representative HRCT images of CTD-ILA (a) and CTD-ILD (b)
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图 3 密度阈值分割法示例图
注：（a）为CT横断位图，（b）为定量CT分割结果图。蓝色代表正常肺组织（NL%），橙色表示磨玻璃样混浊区域（GGO%），粉红色表示纤维化区域（F%），红色表示血管。磨玻璃样混浊区和纤维化区的百分比之和被设置为异常病变区的百分比（AA%）。
Figure 3. Schematic illustration of density threshold segmentation methodology
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图 4 定量CT指标区分对照组与CTD-ILA ROC曲线
Figure 4. Receiver operating characteristic (ROC) curves of quantitative CT metrics for discriminating between control group and CTD-ILA patients
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图 5 定量CT指标区分对照组与CTD-ILD ROC曲线
Figure 5. Receiver operating characteristic (ROC) curves of quantitative CT metrics for differentiating between control group from CTD-ILD patients
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图 6 定量CT指标区分CTD-ILA与CTD-ILD ROC曲线
Figure 6. Receiver operating characteristic (ROC) curves of quantitative CT metrics for discriminating between CTD-ILA and CTD-ILD
表 1 患者临床资料表
Table 1 Demographic and clinical characteristics of study participants
项目 组别 统计检验 对照组（n=109） CTD-ILA（n=33） CTD-ILD（n=140） F/H p 性别（%） 14.52 0.001 男 19（17.3） 14（42.4） 53（37.9） 女 90（81.8） 19（57.6） 87（62.1） 年龄 40（19） 64（11） 62.5（14） 104.52 0.000 BMI 22.54（2.81） 21.89（3.08） 22.34（4.39） 0.29 0.864 病程 3（7） 5（11.25） 4（10.75） 3.25 0.187 CTD类型（%） 9.66 0.008 类风湿关节炎 63（57.3） 22（66.7） 67（47.9） 系统性红斑狼疮 24（21.8） 5（15.2） 10（7.1） 系统性硬化症 2（1.8） 2（6.1） 15（10.7） 干燥综合症 9（8.2） 2（6.1） 16（11.4） 皮肌炎 − 2（6.1） 8（5.7） 弥漫性结缔组织病 7（6.4） − 15（10.7） ANCA相关血管炎 4（3.6） 2（6.1） 9（6.4） CT分型（%） 1.12 0.291 普通型间质性肺炎 − 7（21.2） 41（29.3） 非特异性间质性肺炎 − 18（54.5） 71（50.7） 淋巴细胞性间质性肺炎 − 4（12.1） 22（15.7） 机化性肺炎 − 4（12.1） 6（4.3） 
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表 2 各组间定量CT指标差异
Table 2 Intergroup differences in quantitative CT metrics among controls, CTD-ILA, and CTD-ILD cohorts
项目 组别 统计检验 对照组（n=109） CTD-ILA（n=22） CTD-ILD（n=140） F/H p NL% 74（7） 68.0（7.5）* 65.5（9）* 89.82 0.000 GGO% 5.7（3.7） 11.3（8.75）* 12.65（9.1）* 76.00 0.000 F% 2.9（1.25） 5.2（3.4）* 6.6（4.98）* 113.72 0.000 AA% 8.8（4.9） 16.40（11.80）* 19.35（12.67）* 89.51 0.000 HAA 4.04（2.18） 9.25±5.26* 9.44（6.92）* 114.05 0.000 MLD −830.16（49.19） −777.08（59.02）* −768.19（93.69）* 70.18 0.000 SD 179.94（16.38） 205.52（25.83）* 220.19（41.43）* 139.60 0.000 Kurtosis 13.62±4.20 6.77（4.91）* 5.28（5.64）* 122.59 0.000 Skewness 3.27（0.71） 2.34（0.74）* 2.19±0.60* 115.41 0.000 注：*表示与对照组相比P＜0.05。NL%为正常肺区域的百分比；GGO%为磨玻璃密度区域的百分比；F%为纤维化区域的百分比；AA%为异常病变区域的百分比；HAA为高衰减区；MLA为平均肺衰减；SD为标准差；Kurtosis为峰值；Skewness为偏度。
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表 3 定量CT指标区分对照组与CTD-ILA的ROC曲线分析结果
Table 3 ROC curve analysis of quantitative CT metrics for discriminating control groups from CTD-ILA patients
项目 AUC1 P 最佳截断值 灵敏度 特异度 约登指数 NL% 0.770 0.001 < 71.50 0.758 0.743 0.501 GGO% 0.774 0.001 > 8.000 0.788 0.734 0.522 F% 0.814 0.001 > 4.050 0.758 0.807 0.565 AA% 0.785 0.001 > 12.20 0.788 0.762 0.549 HAA 0.830 0.001 > 6.121 0.788 0.835 0.623 MLD 0.763 0.001 > −800.9 0.697 0.798 0.495 SD 0.862 0.001 > 191.2 0.849 0.817 0.665 Kurtosis 0.821 0.001 < 9.615 0.727 0.844 0.571 Skewness 0.816 0.001 < 2.795 0.788 0.817 0.604 注：NL% 为正常肺区域的百分比；GGO%为磨玻璃密度区域的百分比；F%为纤维化区域的百分比；AA%为异常病变区域的百分比；HAA为高衰减区；MLA为平均肺衰减；SD为标准差； Kurtosis为峰值； Skewness为偏度。
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表 4 定量CT指标区分对照组与CTD-ILD的ROC曲线分析结果
Table 4 ROC curve analysis of quantitative CT metrics for differentiating control groups from CTD-ILD patients
项目 AUC2 P 最佳截断值 灵敏度 特异度 约登指数 NL% 0.844 0.000 < 71.50 0.829 0.743 0.572 GGO% 0.815 0.000 > 8.350 0.771 0.752 0.524 F% 0.886 0.000 > 4.050 0.727 0.807 0.535 AA% 0.843 0.000 > 11.30 0.857 0.716 0.573 HAA 0.885 0.000 > 6.205 0.727 0.844 0.571 MLD 0.801 0.000 > −798.2 0.636 0.826 0.462 SD 0.923 0.000 > 191.2 0.864 0.817 0.680 Kurtosis 0.896 0.000 < 11.74 0.818 0.706 0.525 Skewness 0.889 0.000 < 2.795 0.727 0.817 0.544 注：NL%为正常肺区域的百分比；GGO%为磨玻璃密度区域的百分比；F%为纤维化区域的百分比；AA%为异常病变区域的百分比；HAA为高衰减区；MLA为平均肺衰减；SD为标准差； Kurtosis为峰值； Skewness为偏度。
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表 5 定量CT指标区分CTD-ILA与CTD-ILD的ROC曲线分析结果
Table 5 ROC curve analysis of quantitative CT metrics for differentiating CTD-ILA from CTD-ILD
项目 AUC3 P 最佳截断值 灵敏度 特异度 约登指数 NL% 0.600 0.074 < 63.50 0.379 0.788 0.167 GGO% 0.544 0.435 > 12.10 0.536 0.576 0.112 F% 0.617 0.037 > 5.450 0.650 0.576 0.226 AA% 0.574 0.187 > 16.85 0.600 0.576 0.176 HAA 0.585 0.128 > 10.06 0.486 0.727 0.213 MLD 0.568 0.224 > −758.5 0.429 0.758 0.186 SD 0.649 0.008 > 219.1 0.529 0.758 0.286 Kurtosis 0.638 0.014 < 5.095 0.479 0.849 0.327 Skewness 0.614 0.042 < 1.932 0.364 0.879 0.243 注：NL%为正常肺区域的百分比；GGO%为磨玻璃密度区域的百分比；F%为纤维化区域的百分比；AA%为异常病变区域的百分比；HAA为高衰减区；MLA为平均肺衰减；SD为标准差； Kurtosis为峰值； Skewness为偏度。
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表 6 定量CT指标预测ILA与ILD多因素多元logistic回归结果
Table 6 Multivariate logistic regression analysis of quantitative CT metrics in predicting ILA vs. ILD
项目 β BE wald P OR 95% CI 下限 上限 ILA F% 0.620 0.225 7.629 0.006 1.859 1.197 2.887 GGO% −0.302 0.098 9.546 0.002 0.739 0.610 0.895 SD 0.015 0.006 6.784 0.009 1.016 1.004 1.027 Kurtosis −0.370 0.069 28.727 0.000 0.691 0.603 0.791 ILD F% 0.854 0.209 16.666 0.000 2.349 1.559 3.540 GGO% −0.454 0.092 24.385 0.000 0.635 0.530 0.760 SD 0.026 0.005 23.855 0.000 1.026 1.016 1.037 Kurtosis −0.439 0.062 50.962 0.000 0.645 0.571 0.727 注：NL%为正常肺区域的百分比；GGO%为磨玻璃密度区域的百分比；F%为纤维化区域的百分比；AA%为异常病变区域的百分比；HAA为高衰减区；MLA为平均肺衰减；SD为标准差； Kurtosis为峰值； Skewness为偏度。
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