Anatomy-Guided Surface Diffusion Model for Alzheimer's Disease Normative Modeling

Normative modeling has emerged as a pivotal approach for characterizing heterogeneity and individual variance in neurodegenerative diseases, notably Alzheimer's disease (AD). One of the challenges of cortical normative modeling is the anatomical structure mismatch due to folding pattern variability. Traditionally, registration is applied to address this issue and recently deep generative models are employed to generate anatomically aligned samples for analyzing disease progression; however, these models are predominantly applied to volume-based data, which often falls short in capturing intricate morphological changes on the brain cortex. As an alternative, surface-based analysis has been proven to be more sensitive in disease modeling such as AD. Yet, like volume-based data, it also suffers from the mismatch problem. To address these limitations, we propose a novel generative normative modeling framework by transferring the conditional diffusion generative model to the spherical domain. Furthermore, the proposed model generates normal feature map distributions by explicitly conditioning on individual anatomical segmentation to ensure better geometrical alignment which helps to reduce variance between subjects in normative analysis. We find that our model can generate samples that are better anatomically aligned than registered reference data and through ablation study and normative assessment experiments, the samples are able to better measure individual differences from the normal distribution and increase sensitivity in differentiating cognitively normal (CN), mild cognitive impairment (MCI), and Alzheimer's disease (AD) patients.