Deep learning based on intratumoral heterogeneity predicts histopathologic grade of hepatocellular carcinoma.

Objectives: The potential of medical imaging to non-invasively assess intratumoral heterogeneity (ITH) is increasingly being recognized. This study aimed to investigate the value of the ITH-based deep learning model for preoperative prediction of histopathologic grade in hepatocellular carcinoma (HCC).

Materials And Methods: A total of 858 patients from primary cohort and two external cohorts were included. 3.0T or 1.5T axial portal venous phase MRI images were collected. We conducted radiomics feature-driven K-means clustering for automatic partition to reveal ITH. 2.5D and 3D deep learning models based on ResNet architecture were trained to extract deep learning hidden features of each subregion. The selected features were used to train Random Forest classifier, which constructed the feature-fusion model.

Results: The extracted voxel-level radiomics features were unsupervised clustered by K-means to generate three subregions. In the 2.5D deep learning, the feature-fusion model based on ITH had superior predictive efficacy than the whole-tumor model (AUC: 0.82 vs. 0.72; p = 0.004). Even in the validation and external test sets, this model maintained a high AUC of 0.78-0.83, and net reclassification indices indicated that it could improve prediction by 25-28%. Regarding the prognostic value, overall survival (OS) and recurrence-free survival (RFS) could be significantly stratified by the 2.5D feature-fusion model, and multivariable Cox regressions indicated its signature was identified as a risk predictor for OS and RFS (p < 0.05).

Conclusion: The ITH-based feature-fusion model provided a non-invasive method for classifying tumor differentiation in HCC, which may serve as a promising strategy for stratification management.