RESUMO
BACKGROUND: The integration of the information encoded in multiparametric MRI images can enhance the performance of machine-learning classifiers. In this study, we investigate whether the combination of structural and functional MRI might improve the performances of a deep learning (DL) model trained to discriminate subjects with Autism Spectrum Disorders (ASD) with respect to typically developing controls (TD). MATERIAL AND METHODS: We analyzed both structural and functional MRI brain scans publicly available within the ABIDE I and II data collections. We considered 1383 male subjects with age between 5 and 40 years, including 680 subjects with ASD and 703 TD from 35 different acquisition sites. We extracted morphometric and functional brain features from MRI scans with the Freesurfer and the CPAC analysis packages, respectively. Then, due to the multisite nature of the dataset, we implemented a data harmonization protocol. The ASD vs. TD classification was carried out with a multiple-input DL model, consisting in a neural network which generates a fixed-length feature representation of the data of each modality (FR-NN), and a Dense Neural Network for classification (C-NN). Specifically, we implemented a joint fusion approach to multiple source data integration. The main advantage of the latter is that the loss is propagated back to the FR-NN during the training, thus creating informative feature representations for each data modality. Then, a C-NN, with a number of layers and neurons per layer to be optimized during the model training, performs the ASD-TD discrimination. The performance was evaluated by computing the Area under the Receiver Operating Characteristic curve within a nested 10-fold cross-validation. The brain features that drive the DL classification were identified by the SHAP explainability framework. RESULTS: The AUC values of 0.66±0.05 and of 0.76±0.04 were obtained in the ASD vs. TD discrimination when only structural or functional features are considered, respectively. The joint fusion approach led to an AUC of 0.78±0.04. The set of structural and functional connectivity features identified as the most important for the two-class discrimination supports the idea that brain changes tend to occur in individuals with ASD in regions belonging to the Default Mode Network and to the Social Brain. CONCLUSIONS: Our results demonstrate that the multimodal joint fusion approach outperforms the classification results obtained with data acquired by a single MRI modality as it efficiently exploits the complementarity of structural and functional brain information.
RESUMO
Machine Learning (ML) is nowadays an essential tool in the analysis of Magnetic Resonance Imaging (MRI) data, in particular in the identification of brain correlates in neurological and neurodevelopmental disorders. ML requires datasets of appropriate size for training, which in neuroimaging are typically obtained collecting data from multiple acquisition centers. However, analyzing large multicentric datasets can introduce bias due to differences between acquisition centers. ComBat harmonization is commonly used to address batch effects, but it can lead to data leakage when the entire dataset is used to estimate model parameters. In this study, structural and functional MRI data from the Autism Brain Imaging Data Exchange (ABIDE) collection were used to classify subjects with Autism Spectrum Disorders (ASD) compared to Typical Developing controls (TD). We compared the classical approach (external harmonization) in which harmonization is performed before train/test split, with an harmonization calculated only on the train set (internal harmonization), and with the dataset with no harmonization. The results showed that harmonization using the whole dataset achieved higher discrimination performance, while non-harmonized data and harmonization using only the train set showed similar results, for both structural and connectivity features. We also showed that the higher performances of the external harmonization are not due to larger size of the sample for the estimation of the model and hence these improved performance with the entire dataset may be ascribed to data leakage. In order to prevent this leakage, it is recommended to define the harmonization model solely using the train set.