Background/Objectives: Deep transfer learning, leveraging convolutional neural networks (CNNs), has become a pivotal tool for brain tumor detection. However, key challenges include optimizing hyperparameter selection and enhancing the generalization capabilities of models. This study introduces a novel CART-ANOVA (Cartesian-ANOVA) hyperparameter tuning framework, which differs from traditional optimization methods by systematically integrating statistical significance testing (ANOVA) with the Cartesian product of hyperparameter values. This approach ensures robust and precise parameter tuning by evaluating the interaction effects between hyperparameters, such as batch size and learning rate, rather than relying solely on grid or random search. Additionally, it implements seven distinct classification schemes for brain tumors, aimed at improving diagnostic accuracy and robustness. Methods: The proposed framework employs a ResNet18-based knowledge transfer learning (KTL) model trained on a primary dataset, with 20% allocated for testing. Hyperparameters were optimized using CART-ANOVA analysis, and statistical validation ensured robust parameter selection. The model’s generalization and robustness were evaluated on an independent second dataset. Performance metrics, including precision, accuracy, sensitivity, and F1 score, were compared against other pre-trained CNN models. Results: The framework achieved exceptional testing accuracy of 99.65% for four-class classification and 98.05% for seven-class classification on the source 1 dataset. It also maintained high generalization capabilities, achieving accuracies of 98.77% and 96.77% on the source 2 datasets for the same tasks. The incorporation of seven distinct classification schemes further enhanced variability and diagnostic capability, surpassing the performance of other pre-trained models. Conclusions: The CART-ANOVA hyperparameter tuning framework, combined with a ResNet18-based KTL approach, significantly improves brain tumor classification accuracy, robustness, and generalization. These advancements demonstrate strong potential for enhancing diagnostic precision and informing effective treatment strategies, contributing to advancements in medical imaging and AI-driven healthcare solutions.
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