FlowLet: Conditional 3D brain MRI synthesis using wavelet flow matching.

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Abstract

Generative modeling for 3D brain MRI is challenged by a trade-off between anatomical fidelity, sample diversity, and computational efficiency. Diffusion-based approaches achieve strong visual quality but typically require hundreds to thousands of sampling steps, while latent-space compression can introduce reconstruction artifacts and degrade fine-grained anatomy. We introduce FlowLet, a conditional generative framework that performs Flow Matching in an invertible 3D wavelet domain. This representation enables multi-scale generation without learned latent compression, while deterministic ODE sampling allows fast inference. Age conditioning is modeled through complementary feature-wise modulation and spatially adaptive cross-attention, enabling explicit control over age-related morphological variation. Across multi-site neuroimaging datasets, FlowLet achieves competitive and, in several settings, superior global fidelity compared to diffusion-based baselines using as few as 10 sampling steps. Region-based evaluation across 95 cortical and subcortical brain regions demonstrates improved local anatomical plausibility beyond what is captured by global similarity metrics alone. In a downstream brain age prediction study, models augmented with FlowLet-generated data consistently reduce prediction error relative to real-only training and other generative baselines. Rather than focusing on a single dominant metric improvement, these results highlight a consistent trade-off between efficiency, controllability, and anatomically meaningful 3D brain MRI generation. The proposed framework is released as open-source to support reproducibility.

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