Multi-modal MRI for objective diagnosis and outcome prediction in depression

The low treatment effectiveness in major depressive disorder (MDD) may be caused by the subjectiveness in clinical examination and the lack of quantitative tests. Objective biomarkers derived from magnetic resonance imaging (MRI) may support clinical experts during decision-making. Numerous studies have attempted to identify such MRI-based biomarkers. However, the majority is uni-modal (based on a single MRI modality) and focus on either MDD diagnosis or outcome. Uncertainty remains regarding whether key features or classification models for diagnosis may also be used for outcome prediction. Therefore, we aim to find multi-modal predictors of both, MDD diagnosis and outcome. By addressing these research questions using the same dataset, we eliminate between-study confounding factors. Various structural (T₁-weighted, T₂-weighted, diffusion tensor imaging (DTI)) and functional (resting-state and task-based functional MRI) scans were acquired from 32 MDD and 31 healthy control (HC) subjects during the first visit at the investigational site (baseline). Depression severity was assessed at baseline and 6 months later. Features were extracted from the baseline MRI images with different modalities. Binary 6-months negative and positive outcome (NO; PO) classes were defined based on relative (to baseline) change in depression severity. Support vector machine models were employed to separate MDD from HC (diagnosis) and NO from PO subjects (outcome). Classification was performed through a uni-modal (features from a single MRI modality) and multi-modal (combination of features from different modalities) approach.

Our results show that DTI features yielded the highest uni-modal performance for diagnosis and outcome prediction: mean diffusivity (AUC (area under the curve) = 0.701) and the sum of streamline weights (AUC = 0.860), respectively. Multi-modal ensemble classifiers with T₁-weighted, resting-state functional MRI and DTI features improved classification performance for both diagnosis and outcome (AUC = 0.746 and 0.932, respectively). Feature analyses revealed that the most important features were located in frontal, limbic and parietal areas. However, the modality or location of these features was different between diagnostic and prognostic models.

Our findings suggest that combining features from different MRI modalities predict MDD diagnosis and outcome with higher performance. Furthermore, we demonstrated that the most important features for MDD diagnosis were different and located in other brain regions than those for outcome. This longitudinal study contributes to the identification of objective biomarkers of MDD and its outcome. Follow-up studies may further evaluate the generalizability of our models in larger or multi-center cohorts.