Normative modeling of choroid plexus volume across the adult lifespan: validation in multiple sclerosis and depression

The Choroid Plexus (ChP) is a vascular brain structure involved in vital brain functions. Most clinical studies have focused on analyzing ChP Volume (ChPV) in diseased populations, revealing a pattern of increased ChPV that might be related to neuroinflammatory processes. For full clinical translation, it is crucial to understand the normal variability of ChPV in relation to biological factors (such as age and gender) and brain anthropometric measures. Nonetheless, this has only been partially explored, and primarily in small size cohorts of healthy subjects. This study aims to develop and validate a normative modeling approach to describe the natural variation of ChPV across the adult lifespan. Age, gender, lateral ventricles volume, and total intracranial volume of 1,036 healthy subjects (age: 36-88 years) were used as independent regressors for a Bayesian hierarchical normative model, which was tested on two independent clinical cohorts of patients affected by depression (DEP) or multiple sclerosis (MS), respectively. The proposed model explains up to 40% of ChPV normal variability in healthy subjects and can detect ChPV alterations at the level of individual patients, replicating existing findings of altered ChPV in DEP and MS.Clinical Relevance- This work establishes a robust, portable normative benchmark for quantitative imaging of choroid plexus volume to be used as an individualized biomarker in neuroimaging studies, without additional collection of normative data.