A Systematic Review of Diffusion Models for Medical Image-Based Diagnosis: Methods, Taxonomies, Clinical Integration, Explainability, and Future Directions

<b>Background and Objectives:</b> Diffusion models, as a recent advancement in generative modeling, have become central to high-resolution image synthesis and reconstruction. Their rapid progress has notably shaped computer vision and health informatics, particularly by enhancing medical imaging and diagnostic workflows. However, despite these developments, researchers continue to face challenges due to the absence of a structured and comprehensive discussion on the use of diffusion models within clinical imaging. <b>Methods:</b> This systematic review investigates the application of diffusion models in medical imaging for diagnostic purposes. It provides an integrated overview of their underlying principles, major application areas, and existing research limitations. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and included peer-reviewed studies published between 2013 and 2024. Studies were eligible if they employed diffusion models for diagnostic tasks in medical imaging; non-medical studies and those not involving diffusion-based methods were excluded. Searches were conducted across major scientific databases prior to the review. Risk of bias was assessed based on methodological rigor and reporting quality. Given the heterogeneity of study designs, a narrative synthesis approach was used. <b>Results:</b> A total of 68 studies met the inclusion criteria, spanning multiple imaging modalities and falling into eight major application categories: anomaly detection, classification, denoising, generation, reconstruction, segmentation, super-resolution, and image-to-image translation. Explainable AI components were present in 22.06% of the studies, clinician engagement in 57.35%, and real-time implementation in 10.30%. Overall, the findings highlight the strong diagnostic potential of diffusion models but also emphasize the variability in reporting standards, methodological inconsistencies, and the limited validation in real-world clinical settings. <b>Conclusions:</b> Diffusion models offer significant promise for diagnostic imaging, yet their reliable clinical deployment requires advances in explainability, clinician integration, and real-time performance. This review identifies twelve key research directions that can guide future developments and support the translation of diffusion-based approaches into routine medical practice.