MorphoGen: Efficient Unconditional Generation of Long-Range Projection Neuronal Morphology via a Global-to-Local Framework

Abstract

Capturing the spatial patterns of neurons and generating high-fidelity morphological data remain critical challenges in developing biologically realistic large-scale brain network models. Existing methods fail to reconcile anatomical complexity with diversity and computational scalability. We propose MorphoGen, a hierarchical framework integrating global structure prediction through denoising diffusion probabilistic models (DDPMs) with local neurites optimization. The pipeline initiates with DDPM-generated coarse-grained neuronal point clouds, followed by skeletonization and growth-guided linking to derive plausible tree-like structures, and culminates in natural neural fibers refinement via a pragmatic smoothing network. Comprehensive evaluations across three distinct long-range projection neuron datasets demonstrate that the proposed method improves 1-Nearest Neighbor Accuracy by approximately 12% on average compared to state-of-the-art baseline, reduces average training time by around 55%, and aligns the distributions of several morphometrics with real data. This work establishes a novel global-to-local paradigm for neuronal morphology generation, offering a more direct and efficient approach compared to current branch-sequential modeling methods. Code is available at https://github.com/Brainsmatics/MorphoGen.