Knowledge-driven interpretative conditional diffusion model for contrast-free myocardial infarction enhancement synthesis

Synthesis of myocardial infarction enhancement (MIE) images without contrast agents (CAs) has shown great potential to advance myocardial infarction (MI) diagnosis and treatment. It provides results comparable to late gadolinium enhancement (LGE) images, thereby reducing the risks associated with CAs and streamlining clinical workflows. The existing knowledge-and-data-driven approach has made progress in addressing the complex challenges of synthesizing MIE images (i.e., invisible myocardial scars and high inter-individual variability) but still has limitations in the interpretability of kinematic inference, morphological knowledge integration, and kinematic-morphological fusion, thereby reducing the transparency and reliability of the model and causing information loss during synthesis. In this paper, we proposed a knowledge-driven interpretative conditional diffusion model (K-ICDM), which learns kinematic and morphological information from non-enhanced cardiac MR images (CINE sequence and T1 sequence) guided by cardiac knowledge, enabling the synthesis of MIE images. Importantly, our K-ICDM introduces three key innovations that address these limitations, thereby providing interpretability and improving synthesis quality. (1) A novel cardiac causal intervention that generates counterfactual strain to intervene in the inference process from motion maps to abnormal myocardial information, thereby establishing an explicit relationship and providing the clear causal interpretability. (2) A knowledge-driven cognitive combination strategy that utilizes cardiac signal topology knowledge to analyze T1 signal variations, enabling the model to understand how to learn morphological features, thus providing interpretability for morphology capture. (3) An information-specific adaptive fusion strategy that integrates kinematic and morphological information into the conditioning input of the diffusion model based on their specific contributions and adaptively learns their interactions, thereby preserving more detailed information. Experiments on a broad MI dataset with 315 patients show that our K-ICDM achieves state-of-the-art performance in contrast-free MIE image synthesis, improving structural similarity index measure (SSIM) by at least 2.1% over recent methods. These results demonstrate that our method effectively overcomes the limitations of existing methods in capturing the complex relationship between myocardial motion and scar distribution and integrating of static and dynamic sequences, thus enabling the accurate synthesis of subtle scar boundaries.