Abstract

BackgroundThe accuracy of estimating microvascular invasion (MVI) preoperatively in hepatocellular carcinoma (HCC) by clinical observers is low. Most recent studies constructed MVI predictive models utilizing radiological and/or radiomics features extracted from computed tomography (CT) images. These methods, however, rely heavily on human experiences and require manual tumor contouring. We developed a deep learning-based framework for preoperative MVI prediction by using CT images of arterial phase (AP) with simple tumor labeling and without the need of manual feature extraction. The model was further validated on CT images that were originally scanned at multiple different hospitals.MethodsCT images of AP were acquired for 309 patients from China Medical University Hospital (CMUH). Images of 164 patients, who took their CT scanning at 54 different hospitals but were referred to CMUH, were also collected. Deep learning (ResNet-18) and machine learning (support vector machine) models were constructed with AP images and/or patients’ clinical factors (CFs), and their performance was compared systematically. All models were independently evaluated on two patient cohorts: validation set (within CMUH) and external set (other hospitals). Subsequently, explainability of the best model was visualized using gradient-weighted class activation map (Grad-CAM).ResultsThe ResNet-18 model built with AP images and patients’ clinical factors was superior than other models achieving a highest AUC of 0.845. When evaluating on the external set, the model produced an AUC of 0.777, approaching its performance on the validation set. Model interpretation with Grad-CAM revealed that MVI relevant imaging features on CT images were captured and learned by the ResNet-18 model.ConclusionsThis framework provide evidence showing the generalizability and robustness of ResNet-18 in predicting MVI using CT images of AP scanned at multiple different hospitals. Attention heatmaps obtained from model explainability further confirmed that ResNet-18 focused on imaging features on CT overlapping with the conditions used by radiologists to estimate MVI clinically.

Highlights

  • Hepatocellular carcinoma (HCC) is a common cancer existing globally and it is ranked as the fourth major cause for cancer-related death [1, 2]

  • The following inclusion criteria were used: (1) surgical resection or liver transplantation (LT) for initial microvascular invasion (MVI) diagnosis was performed; (2) hepatocellular carcinoma (HCC) was confirmed and MVI status was recorded in the pathological report; (3) clinical data, including age, gender, maximum tumor diameter (MTD), Child-Pugh score, alpha-fetoprotein (AFP), hepatitis B and C status, were available one week before surgery; (4) dynamic computed tomography (CT) images included pre-contrast enhancement, late arterial phase (AP) and portal venous phase (PVP) acquired within 3 months before surgery; and (5) presence of a single tumor and no gross venous invasion

  • A total of 164 HCC patients (127 men and 37 women) were obtained eventually. Since these patients were referred from 54 hospitals and took their first CT imaging outside of China Medical University Hospital (CMUH), they were eligible to be used for external validation of model performance

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Summary

Introduction

Hepatocellular carcinoma (HCC) is a common cancer existing globally and it is ranked as the fourth major cause for cancer-related death [1, 2]. It was reported that HCC with microvascular invasion (MVI) positive often recurs within 2 years [3] It was reported by several studies conducted research on MVI that MVI provides an independent risk factor for predicting tumor recurrence and overall survival rate after resection [6,7,8]. The accuracy of estimating microvascular invasion (MVI) preoperatively in hepatocellular carcinoma (HCC) by clinical observers is low. Most recent studies constructed MVI predictive models utilizing radiological and/ or radiomics features extracted from computed tomography (CT) images. These methods, rely heavily on human experiences and require manual tumor contouring. The model was further validated on CT images that were originally scanned at multiple different hospitals

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