MGRD: Compact morphology-gated residual diffusion for variance-aware cross-domain neurite forecasting

Tsung Yeh Hsieh, Cosmin Anitescu, Chunghwan Kim, Victoria A. Webster-Wood, Yongjie Jessica Zhang

Tracking neurite morphology over time helps characterize structural changes during neuronal development and deterioration, but long-term time-lapse imaging is resource-intensive and difficult to scale. Forecasting future morphology could reduce this burden. Existing neurite digital-twin models such as gated spatiotemporal attention (gSTA) produce a single deterministic forecast without representing variability among plausible futures. We introduce Morphology-Gated Residual Diffusion (MGRD), a compact stochastic surrogate that jointly forecasts twenty future neurite-morphology frames from ten observed frames while conditioning on morphology features derived from the latest observation. On controlled phase-field trajectories, MGRD reduces trajectory-wise mean MAE by 9.7% relative to a matched control while updating 4.46 times fewer parameters. On human iPSC-derived neuron microscopy, MGRD improves all four reported metrics over gSTA, including a 39.6% reduction in trajectory-wise mean MAE and a 45.3% increase in skeleton F1. Without mouse-domain retraining or fine-tuning, MGRD also improves MAE and skeleton F1 on mouse cortical-neurosphere microscopy across 10-40-min sampling…