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In Frontiers in physiology

Objectives: To determine the association between radiomics signature (Rad-signature) of pericoronary tissue (PCT) in coronary computed tomography angiography (CCTA) and CT-derived fractional flow reserve (CT-FFR), and explore the influential factors of functional ischemia. Methods: We retrospectively included 350 patients who underwent CCTA from 2 centers, consisting of the training (n = 134), validation (n = 66), and testing (with CCTA and invasive coronary angiography, n = 150) groups. After evaluating coronary stenosis level in CCTA (anatomical CT), pericoronary fat attenuation index (FAI), and CT-FFR, we extracted 1,691 radiomic features from PCT. By accumulating and weighting the most contributive features to functional ischemia (CT-FFR ≤ 0.8) the Rad-signature was established using Boruta integrating with a random forest algorithm. Another 45 patients who underwent CCTA and invasive FFR were included to assure the performance of Rad-signature. Results: A total of 1046 vessels in 350 patients were analyzed, and functional ischemia was identified in 241/1046 (23.0%) vessels and 179/350 (51.1%) patients. From the 47 features highly relevant to functional ischemia, the top-8 contributive features were selected to establish Rad-signature. At the vessel level, the area under the curve (AUC) of Rad-signature to discriminate functional ischemia was 0.83, 0.82, and 0.82 in the training, validation, and testing groups, higher than 0.55, 0.55, and 0.52 of FAI (p < 0.001), respectively, and was higher than 0.72 of anatomical CT in the testing group (p = 0.017). The AUC of the combined model (Rad-signature + anatomical CT) was 0.86, 0.85, and 0.83, respectively, significantly higher than that of anatomical CT and FAI (p < 0.05). In the CCTA-invasive FFR group, using invasive FFR as the standard, the mean AUC of Rad-signature was 0.83 ± 0.02. At the patient level, multivariate logistic regression analysis showed that Rad-signature of left anterior descending (LAD) [odds ratio (OR) = 1.72; p = 0.012] and anatomical CT (OR = 3.53; p < 0.001) were independent influential factors of functional ischemia (p < 0.05). In the subgroup of nonobstructive (stenosis <50% in invasive coronary angiography) and obstructive (≥50%) cases of the testing group, the independent factor of functional ischemia was FAI of LAD (OR = 1.10; p = 0.041) and Rad-signature of LAD (OR = 2.45; p = 0.042), respectively. Conclusion: The machine-learning-derived Rad-signature of PCT in CCTA demonstrates significant association with functional ischemia.

Feng Yan, Xu Zhihan, Zhang Lin, Zhang Yaping, Xu Hao, Zhuang Xiaozhong, Zhang Hao, Xie Xueqian


coronary computed tomography angiography, fractional flow reserve, functional ischemia, machine learning, radiomics