Abstract
BACKGROUND AND PURPOSE: Radiotherapy (RT) of head and neck cancer can cause severe toxicities. Early identification of individuals at risk could enable personalized treatment. This study evaluated whether convolutional neural networks (CNNs) applied to Magnetic Resonance (MR) images acquired early after irradiation can predict radiation-induced tissue changes associated with toxicity in mice. Patient/material and methods: Twenty-nine C57BL/6JRj mice were included (irradiated: n = 14; control: n = 15). Irradiated mice received 65 Gy of fractionated RT to the oral cavity, swallowing muscles and salivary glands. T2-weighted MR images were acquired 3-5 days post-irradiation. CNN models (VGG, MobileNet, ResNet, EfficientNet) were trained to classify sagittal slices as irradiated or control (n = 586 slices). Predicted class probabilities were correlated with five toxicity endpoints assessed 8-105 days post-irradiation. Model explainability was assessed with VarGrad heatmaps, to verify that predictions relied on clinically relevant image regions. RESULTS: The best-performing model (EfficientNet B3) achieved 83% slice-level accuracy (ACC) and correctly classified 28 of 29 mice. Higher predicted probabilities of the irradiated class were strongly associated with oral mucositis, dermatitis, reduced saliva production, late submandibular gland fibrosis and atrophy of salivary gland acinar cells. Explainability heatmaps confirmed that CNNs focused on irradiated regions. INTERPRETATION: The high CNN classification ACC, the regions highlighted by the explainability analysis and the strong correlations between model predictions and toxicity suggest that CNNs, together with post-irradiation magnetic resonance imaging, may identify individuals at risk of developing toxicity.