Decoding MRI-informed brain age using mutual information.

Objective: We aimed to develop a standardized method to investigate the relationship between estimated brain age and regional morphometric features, meeting the criteria for simplicity, generalization, and intuitive interpretability.

Methods: We utilized T1-weighted magnetic resonance imaging (MRI) data from the Cambridge Centre for Ageing and Neuroscience project (N = 609) and employed a support vector regression method to train a brain age model. The pre-trained brain age model was applied to the dataset of the brain development project (N = 547). Kraskov (KSG) estimator was used to compute the mutual information (MI) value between brain age and regional morphometric features, including gray matter volume (GMV), white matter volume (WMV), cerebrospinal fluid (CSF) volume, and cortical thickness (CT).

Results: Among four types of brain features, GMV had the highest MI value (8.71), peaking in the pre-central gyrus (0.69). CSF volume was ranked second (7.76), with the highest MI value in the cingulate (0.87). CT was ranked third (6.22), with the highest MI value in superior temporal gyrus (0.53). WMV had the lowest MI value (4.59), with the insula showing the highest MI value (0.53). For brain parenchyma, the volume of the superior frontal gyrus exhibited the highest MI value (0.80).

Conclusion: This is the first demonstration that MI value between estimated brain age and morphometric features may serve as a benchmark for assessing the regional contributions to estimated brain age. Our findings highlighted that both GMV and CSF are the key features that determined the estimated brain age, which may add value to existing computational models of brain age.

Critical relevance statement: Mutual information (MI) analysis reveals gray matter volume (GMV) and cerebrospinal fluid (CSF) volume as pivotal in computing individuals' brain age.

Key points: Mutual information (MI) interprets estimated brain age with morphometric features. Gray matter volume in the pre-central gyrus has the highest MI value for estimated brain age. Cerebrospinal fluid volume in the cingulate has the highest MI value. Regarding brain parenchymal volume, the superior frontal gyrus has the highest MI value. The value of mutual information underscores the key brain regions related to brain age.