Physics-Informed Conditional Diffusion for Motion-Robust Retinal Temporal Laser Speckle Contrast Imaging

Retinal laser speckle contrast imaging (LSCI) is a noninvasive optical modality for monitoring retinal blood flow dynamics. However, conventional temporal LSCI (tLSCI) reconstruction relies on sufficiently long speckle sequences to obtain stable temporal statistics, which makes it vulnerable to acquisition disturbances and limits effective temporal resolution. A physically informed reconstruction framework, termed RetinaDiff (Retinal Diffusion Model), is proposed for retinal tLSCI that is robust to motion and requires only a few frames. In RetinaDiff, registration based on phase correlation is first applied to stabilize the raw speckle sequence before contrast computation, reducing interframe misalignment so that fluctuations at each pixel primarily reflect true flow dynamics. This step provides a physics prior corrected for motion and a high quality multiframe tLSCI reference. Next, guided by the physics prior, a conditional diffusion model performs inverse reconstruction by jointly conditioning on the registered speckle sequence and the corrected prior. Experiments on data acquired with a retinal LSCI system developed in house show improved structural continuity and statistical stability compared with direct reconstruction from few frames and representative baselines. The framework also remains effective in a small number of extremely challenging cases, where both the direct 5-frame input and the conventional multiframe reconstruction are severely degraded. Overall, this work provides a practical and physically grounded route for reliable retinal tLSCI reconstruction from extremely limited frames. The source code and model weights will be publicly available at https://github.com/QianChen113/RetinaDiff.