Identifying gray matter alterations in Cushing's disease using machine learning: An interpretable approach

Cushing's Disease (CD) is a rare clinical syndrome characterized by excessive secretion of adrenocorticotrophic hormone, leading to significant functional and structural brain alterations as observed in Magnetic Resonance Imaging (MRI). While traditional statistical analysis has been widely employed to investigate these MRI changes in CD, it has lacked the ability to predict individual-level outcomes.

To address this problem, this paper has proposed an interpretable machine learning (ML) framework, including model-level assessment, feature-level assessment, and biology-level assessment to ensure a comprehensive analysis based on structural MRI of CD.

The ML framework has effectively identified the changes in brain regions in the stage of model-level assessment, verified the effectiveness of these altered brain regions to predict CD from normal controls in the stage of feature-level assessment, and carried out a correlation analysis between altered brain regions and clinical symptoms in the stage of biology-level assessment.

The experimental results of this study have demonstrated that the Insula, Fusiform gyrus, Superior frontal gyrus, Precuneus, and the opercular portion of the Inferior frontal gyrus of CD showed significant alterations in brain regions. Furthermore, our study has revealed significant correlations between clinical symptoms and the frontotemporal lobes, insulin, and olfactory cortex, which also have been confirmed by previous studies.

The ML framework proposed in this study exhibits exceptional potential in uncovering the intricate pathophysiological mechanisms underlying CD, with potential applicability in diagnosing other diseases.