SA-CycleGAN-2.5D: Self-Attention CycleGAN with Tri-Planar Context for Multi-Site MRI Harmonization

TL;DR

This paper introduces SA-CycleGAN-2.5D, a novel deep learning framework for multi-site MRI harmonization that effectively models global intensity correlations and preserves tumor details, significantly reducing scanner bias across datasets.

Contribution

It proposes a 2.5D tri-planar architecture with self-attention and spectral normalization, enabling global intensity bias modeling and stable training for MRI harmonization.

Findings

Reduces Maximum Mean Discrepancy by 99.1%

Decreases domain classifier accuracy to near-chance levels

Ablation confirms global attention's statistical importance

Abstract

Multi-site neuroimaging analysis is fundamentally confounded by scanner-induced covariate shifts, where the marginal distribution of voxel intensities $P(\mathbf{x})$ varies non-linearly across acquisition protocols while the conditional anatomy $P(\mathbf{y}|\mathbf{x})$ remains constant. This is particularly detrimental to radiomic reproducibility, where acquisition variance often exceeds biological pathology variance. Existing statistical harmonization methods (e.g., ComBat) operate in feature space, precluding spatial downstream tasks, while standard deep learning approaches are theoretically bounded by local effective receptive fields (ERF), failing to model the global intensity correlations characteristic of field-strength bias. We propose SA-CycleGAN-2.5D, a domain adaptation framework motivated by the $H\Delta H$-divergence bound of Ben-David et al., integrating three architectural innovations: (1) A 2.5D tri-planar manifold injection preserving through-plane gradients $\nabla_z$ at $O(HW)$ complexity; (2) A U-ResNet generator with dense voxel-to-voxel self-attention, surpassing the $O(\sqrt{L})$ receptive field limit of CNNs to model global scanner field biases; and (3) A spectrally-normalized discriminator constraining the Lipschitz constant ($K_D \le 1$) for stable adversarial optimization. Evaluated on 654 glioma patients across two institutional domains (BraTS and UPenn-GBM), our method reduces Maximum Mean Discrepancy (MMD) by 99.1% ($1.729 \to 0.015$) and degrades domain classifier accuracy to near-chance (59.7%). Ablation confirms that global attention is statistically essential (Cohen's $d = 1.32$, $p < 0.001$) for the harder heterogeneous-to-homogeneous translation direction. By bridging 2D efficiency and 3D consistency, our framework yields voxel-level harmonized images that preserve tumor pathophysiology, enabling reproducible multi-center radiomic analysis.