An interpretable radiomics model for the diagnosis of panic disorder with or without agoraphobia using magnetic resonance imaging

Abstract

Background: Early and accurate diagnosis of panic disorder with or without agoraphobia (PDA) is crucial to reducing disease burden and individual suffering. However, its diagnosis is challenging for lack of validated biomarkers. This study aimed to investigate whether radiomic features extracted from T1-weighted images (T1) of major fear-circuit structures (amygdala, insula, and anterior cingulate cortex [ACC]) could differentiate patients with PDA from healthy controls (HCs).

Methods: The 213 participants (93 PDA, 120 HCs) were allocated to training (n = 149) and test (n = 64) sets after undergoing magnetic resonance imaging. Radiomic features (n = 1498) were extracted from T1 of the studied structures. Machine learning models were trained after feature selection and then validated in the test set. SHapley Additive exPlanations (SHAP) explored the model interpretability.

Results: We identified 29 radiomic features to differentiate participants with PDA from HCs. The area under the curve, accuracy, sensitivity, and specificity of the best performing radiomics model in the test set were 0.84 (95% confidence interval: 0.74-0.95), 81.3%, 75.0%, and 86.1%, respectively. The SHAP model explanation suggested that the energy features extracted from the bilateral long insula gyrus and central sulcus of the insula and right ACC were highly associated with the risk of PDA.

Limitations: This was a cross-sectional study with a relatively small sample size, and the causality of changes in radiomic features and their biological and clinical meanings remained to be elucidated.

Conclusions: Our findings suggest that radiomic features from the fear-circuit structures could unveil hidden microstructural aberrations underlying the pathogenesis of PDA that could help identify PDA.