Cardiogenetics 2025, 15(3), 19; https://doi.org/10.3390/cardiogenetics15030019 (registering DOI) - 15 Jul 2025
Abstract
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Background: Leigh’s Disease is a rare mitochondrial disorder primarily affecting the central nervous system, with frequent secondary cardiac manifestations such as hypertrophic and dilated cardiomyopathies. Early detection of cardiac complications is crucial for patient management, but manual interpretation of cardiac MRI is labour-intensive
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Background: Leigh’s Disease is a rare mitochondrial disorder primarily affecting the central nervous system, with frequent secondary cardiac manifestations such as hypertrophic and dilated cardiomyopathies. Early detection of cardiac complications is crucial for patient management, but manual interpretation of cardiac MRI is labour-intensive and subject to inter-observer variability. Methodology: We propose an integrated deep learning framework using cardiac MRI to automate the detection of cardiac abnormalities associated with Leigh’s Disease. Four CNN architectures—Inceptionv3, a custom 3-layer CNN, DenseNet169, and EfficientNetB2—were trained on preprocessed MRI data (224 × 224 pixels), including left ventricular segmentation, contrast enhancement, and gamma correction. Morphological features (area, aspect ratio, and extent) were also extracted to aid interpretability. Results: EfficientNetB2 achieved the highest test accuracy (99.2%) and generalization performance, followed by DenseNet169 (98.4%), 3-layer CNN (95.6%), and InceptionV3 (94.2%). Statistical morphological analysis revealed significant differences in cardiac structure between Leigh’s and non-Leigh’s cases, particularly in area (212,097 vs. 2247 pixels) and extent (0.995 vs. 0.183). The framework was validated using ROC (AUC = 1.00), Brier Score (0.000), and cross-validation (mean sensitivity = 1.000, std = 0.000). Feature embedding visualisation using PCA, t-SNE, and UMAP confirmed class separability. Grad-CAM heatmaps localised relevant myocardial regions, supporting model interpretability. Conclusions: Our deep learning-based framework demonstrated high diagnostic accuracy and interpretability in detecting Leigh’s disease-related cardiac complications. Integrating morphological analysis and explainable AI provides a robust and scalable tool for early-stage detection and clinical decision support in rare diseases.
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