###### Abstract  
**Background:** Microvascular invasion (MVI) is a necessary step in the metastatic evolution of hepatocellular carcinoma liver tumors. Predicting the onset of MVI in the initial stages of the tumors could improve patient survival and the quality of life. In this study, the possibility of using radiomic features to predict the presence/absence of MVI was evaluated. **Methods:** Multiphase contrast-enhanced computed tomography (CECT) images were collected from 49 patients, and the radiomic features were extracted from the tumor region and the zone of transition. The most-relevant features were selected; the dataset was balanced, and the presence/absence of MVI was classified. The dataset was split into training and test sets in three ways using cross-validation: the first applied feature selection and dataset balancing outside cross-validation; the second applied dataset balancing outside and feature selection inside; the third applied the entire pipeline inside the cross-validation procedure. **Results:** The features from the tumor areas on CECT showed both the portal and the arterial phases to be the most predictive. The three pipelines showed receiver operating characteristic area under the curve (ROC AUC) scores of 0.89, 0.84, and 0.61, respectively. **Conclusions:** The results obtained confirmed the efficiency of multiphase CECT and the ZOT in detecting MVI. The results showed a significant difference in the performance of the three pipelines, highlighting that a non-rigorous pipeline design could lead to model performance and generalization capabilities that are too optimistic. radiomics; artificial intelligence; machine learning; medical imaging; survival +
Footnote †: journal: Medical and Surgical Sciences
by a high rate of recurrence [4], which negatively impacts overall survival [5; 6]. For example, the cumulative tumor recurrence rates of HCCs \(\leq 3\) cm at three years after ablation in patients in the low-, middle-, and high-risk groups were 68.2%, 100%, and 100%, respectively [7]. Five-year HCC recurrence complicates 35% of cases after LT and 70% of cases after hepatic resection [8; 9; 10; 11]. Vascular invasion, both macroinvasion and microvascular invasion (MVI), has been universally recognized as a predictor of recurrence and poor overall survival after treatment for HCC [4; 12]. For example, vascular invasion is currently considered to be more informative than the Milan Criteria in predicting the prognosis [5; 6; 13]. The pre-treatment clinical significance of the two forms of vascular infiltration is clearly different. Macrovascular infiltration can be correctly diagnosed by imaging in the pre-treatment phase, thus allowing correctly classifying those patients in the advanced stage and directing them to the best treatment (systemic therapy) [2]. Conversely, the presence of MVI can be confirmed only post-operatively by histopathological analysis [13; 14; 15]. Therefore, its utility in the pre-treatment selection of patients to undergo the different types of treatment is not possible since, even with state-of-the-art treatment, its diagnosis still remains post-procedural. Moreover, in patients having the same Barcelona clinical liver cancer stage, such as patients in the very early or the early stages, who are fit for surgery or ablation and have the same tumor burden, it is important to differentiate those with the MVI of HCC in order to choose the best treatment for each patient. For example, since MVI has been proven to be one of the most-relevant prognostic factors for HCC recurrence after surgical treatment [16; 17], in recent years, much effort has been made to identify reliable imaging findings in order to reach an accurate pre-procedural diagnosis of MVI in HCC patients [16; 18; 19]. Unfortunately, to date, these criteria for a preoperative radiological diagnosis of MVI in HCC have not been widely recognized and have not been reported in the current guidelines for the management of HCC [2].