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PURPOSE To effectively grade hepatocellular carcinoma (HCC) based on deep features derived from diffusion weighted images (DWI) with multiple b-values using convolutional neural networks (CNN). MATERIALS AND METHODS Ninety-eight subjects with 100 pathologically confirmed HCC lesions from July 2012 to October 2018 were included in this retrospective study, including forty-seven low-grade and fifty-three high-grade HCCs. DWI was performed for each subject with a 3.0T MR scanner in a breath-hold routine with three b-values (0,100, and 600sec/mm2 ). First, logarithmic transformation was performed on original DWI images to generate log maps (logb0, logb100 and logb600). Then, a resampling method was performed to extract multiple 2D axial planes of HCCs from the log map to increase the dataset for training. Subsequently, 2D CNN was used to extract deep features of the log map for HCCs. Finally, fusion of deep features derived from three b-value log maps was conducted for HCC malignancy classification. Specifically, a deeply supervised loss function was devised to further improve the performance of lesion characterization. The data set was split into two parts: the training and validation set (60 HCCs) and the fixed test set (40 HCCs). Four-fold cross validation with 10 repetitions was performed to assess the performance of deep features extracted from single b-value images for HCC grading using the training and validation set. Receiver operating characteristic curve (ROC) and area under the curve (AUC) values were used to assess the characterization performance of the proposed deep feature fusion method to differentiate low-grade and high-grade in the fixed test set. RESULTS The proposed fusion of deep features derived from logb0, logb100 and logb600 with deeply supervised loss function generated the highest accuracy for HCC grading (80%), thus outperforming the method of deep feature derived from the ADC map directly (72.5%), the original b0 (65%), b100 (68%) and b600 (70%) images. Furthermore, AUC values of the deep features of the ADC map, the deep feature fusion with concatenation, and the proposed deep feature fusion with deeply supervised loss function were 0.73, 0.78 and 0.83, respectively. CONCLUSION The proposed fusion of deep features derived from the logarithm of the three b-value images yields high performance for HCC grading, thus providing a promising approach for the assessment of DWI in lesion characterization. This article is protected by copyright. All rights reserved.