The Anatomy of Synthesis: Simulating Changes in the Human Brain over Time through Diffeomorphic Deformations

Anirudh Kaushik

Abstract

The human brain undergoes continuous structural changes throughout the lifespan, driven by a complex interplay of aging processes, environmental influences, and disease-related mechanisms. Patterns of structural change—particularly atrophy associated with tissue loss and shrinkage—emerge gradually over time and are observable using medical imaging techniques. While these changes are shaped by common biological mechanisms, they are also highly individualized, influenced by factors such as lifestyle, and neurological conditions like Alzheimer’s Disease (AD), Parkinson’s disease, tumors, and stroke. Understanding the progression of these changes—both at the individual level and across populations—is critical for advancing our knowledge of healthy aging and the dynamics of neurodegenerative disease.

To study how brain structure evolves over time, researchers rely on longitudinal neuroimaging: repeated imaging of the same individuals at multiple timepoints. Unlike cross-sectional imaging, which captures a single snapshot per subject, longitudinal scans provide a temporal sequence that enables direct observation of anatomical trajectories. These sequences allow for the measurement of rates of change, identification of early biomarkers, and modeling of disease progression in a subject-specific manner.

However, acquiring complete longitudinal datasets in practice remains challenging. Subject dropout, missed clinical visits, and protocol variability often result in missing scans, interrupting the temporal continuity required for accurate modeling. These gaps limit the effectiveness of methods that rely on temporally complete inputs and can bias downstream analyses. Imputing the missing scan to complete the subject’s imaging timeline is therefore a critical step toward enabling robust longitudinal modeling and improving our understanding of neurodegenerative processes.

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