PurposeProbe-based confocal laser endomicroscopy (pCLE) enables intraoperative tissue characterization with improved resection rates of brain tumours. Although a plethora of deep learning models have been developed for automating tissue characterization, their lack of transparency is a concern. To tackle this issue, techniques like Class Activation Map (CAM) and its variations highlight image regions related to model decisions. However, they often fall short of providing human-interpretable visual explanations for surgical decision support, primarily due to the shattered gradient problem or insufficient theoretical underpinning.MethodsIn this paper, we introduce XRelevanceCAM, an explanation method rooted in a better backpropagation approach, incorporating sensitivity and conservation axioms. This enhanced method offers greater theoretical foundation and effectively mitigates the shattered gradient issue when compared to other CAM variants.ResultsQualitative and quantitative evaluations are based on ex vivo pCLE data of brain tumours. XRelevanceCAM effectively highlights clinically relevant areas that characterize the tissue type. Specifically, it yields a remarkable 56% improvement over our closest baseline, RelevanceCAM, in the network’s shallowest layer as measured by the mean Intersection over Union (mIoU) metric based on ground-truth annotations (from 18 to 28.07%). Furthermore, a 6% improvement in mIoU is observed when generating the final saliency map from all network layers.ConclusionWe introduce a new CAM variation, XRelevanceCAM, for precise identification of clinically important structures in pCLE data. This can aid introperative decision support in brain tumour resection surgery, as validated in our performance study.