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This study targets the development of an explainable deep learning methodology for the automatic classification of coronary artery disease, utilizing SPECT MPI images. Deep learning is currently judged as non-transparent due to the model’s complex non-linear structure, and thus, it is considered a «black box», making it hard to gain a comprehensive understanding of its internal processes and explain its behavior. Existing explainable artificial intelligence tools can provide insights into the internal functionality of deep learning and especially of convolutional neural networks, allowing transparency and interpretation. This study seeks to address the identification of patients’ CAD status (infarction, ischemia or normal) by developing an explainable deep learning pipeline in the form of a handcrafted convolutional neural network. The proposed RGB-CNN model utilizes various pre- and post-processing tools and deploys a state-of-the-art explainability tool to produce more interpretable predictions in decision making. The dataset includes cases from 625 patients as stress and rest representations, comprising 127 infarction, 241 ischemic, and 257 normal cases previously classified by a doctor. The imaging dataset was split into 20% for testing and 80% for training, of which 15% was further used for validation purposes. Data augmentation was employed to increase generalization. The efficacy of the well-known Grad-CAM-based color visualization approach was also evaluated in this research to provide predictions with interpretability in the detection of infarction and ischemia in SPECT MPI images, counterbalancing any lack of …