Lidi Ma,1,2,* Shuting Liao,1,2,* Xiaolan Zhang,3,* Fan Zhou,1,2,* Zhijun Geng,1,2,* Jing Hu,3 Yunfei Zhang,4 Cheng Zhang,1,2 Tiebao Meng,1,2 Shutong Wang,5 Chuanmiao Xie1,2 

1Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou, People’s Republic of China; 3Shukun Technology Co., Ltd, Beijing, People’s Republic of China; 4Central Research Institute, United Imaging Healthcare, Shanghai, People’s Republic of China; 5Center of Hepato-Pancreato-Biliary Surgery, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Chuanmiao Xie, Department of Radiology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China, Email xchuanm@sysucc.org.cn Shutong Wang, Center of Hepato-Pancreato-Biliary Surgery, Center of Hepato-Pancreato-Biliary Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China, Email wangsht23@mail.sysu.edu.cn

Objective: To explore the value of intravoxel incoherent motion (IVIM) sequences in predicting intra-tumoral tertiary lymphoid structures (TLSs).
Materials and Methods: This prospective study pre-operatively enrolled hepatocellular carcinoma (HCC) patients who underwent magnetic resonance imaging including IVIM sequences, between January 2019 and April 2021. Intra-tumoral TLSs presence was assessed on pathological slide images. Clinical and radiological characteristics were collected. IVIM quantitative parameters and radiomics features were obtained based on the whole delineated tumor volume. By using feature selection techniques, 22 radiomics features, clinical-radiological features (lymphocyte count and satellite nodules), and IVIM parameters (apparent diffusion coefficient (ADC_90Percentile), perfusion fraction (f_Maximum)) were selected. The logistic regression algorithm was used to construct the prediction model based on the combination of these features. The diagnostic performance was assessed using the area under the receiver operating characteristic (AUC). The recurrence-free survival (RFS) was evaluated with Kaplan–Meier curves.
Results: A total of 168 patients were divided into training (n=128) and testing (n=40) cohorts (mean age: 56.83± 14.43 years; 149 [88.69%] males; 130 TLSs+). In testing cohort, the model combining multimodal features demonstrated a good performance (AUC: 0.86) and significantly outperformed models based on single-modality features. The model based on radiomics features (AUC: 0.80) had better performance than other features, including IVIM parameter maps (ADC_90Percentile and f_Maximum, AUC: 0.72) and clinical-radiological characteristics (satellite nodules and lymphocyte counts, AUC: 0.59). TLSs+ patients had higher RFS than TSLs- patients (all p < 0.05).
Conclusion: The nomogram based on the proposed model can be used as a pre-operative predictive biomarker of TLSs.
Critical Relevance Statement: The nomogram incorporating IVIM sequences may serve as a pre-operative predictive biomarker of intra-tumoral tertiary lymphoid structure (TLS) status.

Keywords: intravoxel incoherent motion, tertiary lymphatic structures, hepatocellular carcinoma, radiomics, recurrence-free survival