MOXIE: Discovering Alternative Explanations for Biomedical Image Classifiers

Post-hoc explanation methods are widely used to inspect image classifiers, but their reliability depends on design choices that are often treated as implementation details. We study this issue for LIME on document image classification, focusing on the segmentation step that defines the interpretable units being perturbed. Standard image-based LIME typically relies on natural-image superpixels, which are poorly aligned with document structure such as text regions, layout blocks, and identification codes. Using RVL-CDIP, we compare Quickshift and SLIC with document-aware segmentations based on OCR bounding boxes and regular grids. Our results show that segmentation strongly affects explanation consistency, correctness, and local fidelity. Document-aware segmentations produce more stable and faithful explanations, require fewer perturbations to converge, and expose shortcut behaviour based on document identification codes, a known RVL-CDIP bias that superpixel-based LIME often obscures. These findings show that reliable post-hoc explanation requires domain-aware interpretable representations, and that segmentation should be treated as part of the explanation method rather than as neutral preprocessing.

Deep neural networks for medical image diagnosis often achieve high predictive accuracy while relying on spurious or clinically irrelevant visual cues, limiting their trustworthiness in practice. Post-hoc explanation methods are widely used to visualize model decisions in the form of saliency maps; however, these explanations do not influence how models learn during training, allowing non-causal or confounding features to persist. This motivates the incorporation of explanation supervision directly into the training objective to guide model attention toward clinically meaningful regions and promote clinically grounded decision-making. This paper presents a systematic approach to integrate explanation loss into model training and analyzes how different explanation loss designs and supervision strengths influence both predictive performance and spatial faithfulness of explanations. To quantitatively assess interpretability, two complementary explanation performance metrics-annotation coverage and saliency precision-are introduced, enabling rigorous evaluation beyond qualitative visualization. Our experimental results reveal a clear trade-off between explanation quality and explanation loss coefficients. Furthermore, quantitative statistical analysis yields consistently improved explanation alignment while maintaining comparable accuracy. Experiments were conducted on annotated chest X-ray datasets; however, the proposed framework is applicable to a broad range of annotated biomedical imaging modalities. Overall, these findings demonstrate that explanation supervision is not a monolithic design choice and provide practical guidance for incorporating explanation loss into training objectives under noisy clinical annotations.

Deep learning models achieve remarkable predictive performance, yet their black-box nature limits transparency and trustworthiness. Although numerous explainable artificial intelligence (XAI) methods have been proposed, they primarily provide saliency maps or concepts (i.e., unstructured interpretability). Existing approaches often rely on auxiliary models (\eg, GPT, CLIP) to describe model behavior, thereby compromising faithfulness to the original models. We propose Interpretability to Explainability (I2X), a framework that builds structured explanations directly from unstructured interpretability by quantifying progress at selected checkpoints during training using prototypes extracted from post-hoc XAI methods (e.g., GradCAM). I2X answers the question of "why does it look there" by providing a structured view of both intra- and inter-class decision making during training. Experiments on MNIST and CIFAR10 demonstrate effectiveness of I2X to reveal prototype-based inference process of various image classification models. Moreover, we demonstrate that I2X can be used to improve predictions across different model architectures and datasets: we can identify uncertain prototypes recognized by I2X and then use targeted perturbation of samples that allows fine-tuning to ultimately improve accuracy. Thus, I2X not only faithfully explains model behavior but also provides a practical approach to guide optimization toward desired targets.