Wavelet-Fusion Diffusion Model for Multimodal Brain MRI Synthesis with Modality and Metadata Conditioning

Multimodal MRI provides complementary information for neuroimaging analysis, where different imaging modalities capture distinct anatomical, tissue, and pathological features that support the development and evaluation of downstream AI applications. Although large-scale structural MRI resources are increasingly available, their modality coverage is often uneven across public and pooled neuroimaging datasets. This uneven modality coverage is further complicated by heterogeneity across sites, scanners, and acquisition protocols, as well as demographic and clinical variables that are often sparse, inconsistently recorded, or unavailable across studies. Synthetic MRI generation can help address this imbalance by synthesizing target-modality volumes for dataset augmentation and controlled synthetic cohort creation. However, many existing MRI synthesis approaches are trained on narrow modality sets or relatively homogeneous cohorts, limiting their applicability to large pooled neuroimaging resources where modality availability, acquisition protocols, and metadata coverage vary substantially across datasets. Diffusion models have become an attractive approach for MRI synthesis because of their strong sample fidelity and diversity, but sampling directly in 3D voxel space is computationally expensive and slow at inference. Latent diffusion improves practicality by synthesizing MRI in a learned, 3D latent space, although generation quality depends on the autoencoder's reconstruction fidelity and the resulting latent distribution. Our approach combines a Wavelet-Fusion variational autoencoder (WF-VAE) latent compressor with a conditional 3D U-Net diffusion model trained in the learned latent space using explicit modality and metadata conditioning. Our proposed Wavelet-Fusion Diffusion Model (WFDM) achieved the strongest distributional alignment among the evaluated synthetic MRI generators.

A Hormetic Approach to the Value-Loading Problem: Preventing the Paperclip Apocalypse?

The value-loading problem is a significant challenge for researchers aiming to create artificial intelligence (AI) systems that align with human values and preferences. This problem requires a method to define and regulate safe and optimal limits of AI behaviors. In this work, we propose HALO (Hormetic ALignment via Opponent processes), a regulatory paradigm that uses hormetic analysis to regulate the behavioral patterns of AI. Behavioral hormesis is a phenomenon where low frequencies of a behavior have beneficial effects, while high frequencies are harmful. By modeling behaviors as allostatic opponent processes, we can use either Behavioral Frequency Response Analysis (BFRA) or Behavioral Count Response Analysis (BCRA) to quantify the hormetic limits of repeatable behaviors. We demonstrate how HALO can solve the 'paperclip maximizer' scenario, a thought experiment where an unregulated AI tasked with making paperclips could end up converting all matter in the universe into paperclips. Our approach may be used to help create an evolving database of 'values' based on the hedonic calculus of repeatable behaviors with decreasing marginal utility. This positions HALO as a promising solution for the value-loading problem, which involves embedding human-aligned values into an AI system, and the weak-to-strong generalization problem, which explores whether weak models can supervise stronger models as they become more intelligent. Hence, HALO opens several research avenues that may lead to the development of a computational value system that allows an AI algorithm to learn whether the decisions it makes are right or wrong.