Deep neural networks show great promise for classifying brain diseases and making prognostic assessments based on neuroimaging data, but large, labeled training datasets are often required to achieve high predictive accuracy. Here we evaluated a range of transfer learning or pre-training strategies to create useful MRI representations for downstream tasks that lack large amounts of training data, such as Alzheimer’s disease (AD) classification. To test our proposed pretraining strategies, we analyzed 4,098 3D T1-weighted brain MRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort and independently validated with an out-of-distribution test set of 600 scans from the Open Access Series of Imaging Studies (OASIS3) cohort for detecting AD. First, we trained 3D and 2D convolutional neural network (CNN) architectures. We tested combinations of multiple pre-training strategies based on (1) supervised, (2) contrastive learning, and (3) self-supervised learning - using pre-training data within versus outside the MRI domain. In our experiments, the 3D CNN pre-trained with contrastive learning provided the best overall results - when fine-tuned on T1-weighted scans for AD classification - outperformed the baseline by 2.8% when trained with all of the training data from ADNI. We also show test performance as a function of the training dataset size and the chosen pre-training method. Transfer learning offered significant benefits in low data regimes, with a performance boost of 7.7%. When the pretrained model was used for AD classification, we were able to visualize an improved clustering of test subjects' diagnostic groups, as illustrated via a uniform manifold approximation (UMAP) projection of the high-dimensional model embedding space. Further, saliency maps indicate the additional activation regions in the brain scan using pretraining, that then maximally contributed towards the final prediction score.
Parkinson’s disease (PD) and Alzheimer’s disease (AD) are progressive neurodegenerative disorders that affect millions of people worldwide. In this work, we propose a deep learning approach to classify these diseases based on 3D T1- weighted brain MRI. We analyzed several datasets including the Parkinson's Progression Markers Initiative (PPMI), an independent dataset from the University of Pennsylvania School of Medicine (UPenn), the Alzheimer’s Disease Neuroimaging Initiative (ADNI), and the Open Access Series of Imaging Studies (OASIS) dataset. PPMI and ADNI were partitioned to train (70%), validate (20%), and test (10%) a 3D convolutional neural network (CNN) for PD and AD classification. The UPenn and OASIS datasets were used as independent test sets to evaluate the model performance during inference. We also implemented a random forest classifier as a baseline model by extracting key radiomics features from the same T1-weighted MRI scans. The proposed 3D CNN model was trained from scratch for the classification tasks. For AD classification, the 3D CNN model achieved an ROC-AUC of 0.878 on the ADNI test set and an average ROC-AUC of 0.789 on the OASIS dataset. For PD classification, the proposed 3D CNN model achieved an ROC-AUC of 0.667 on the PPMI test set and an average ROC-AUC of 0.743 on the UPenn dataset. We also found that model performance was largely maintained when using only 25% of the training dataset. The 3D CNN outperformed the random forest classifier for both the PD and AD tasks. The 3D CNN also generalized better on unseen MRI data from different imaging centers. Our results show that the proposed 3D CNN model was less prone to overfitting for AD than for PD classification. This approach shows promise for screening of PD and AD patients using only T1-weighted brain MRI, which is relatively widely available. This model with additional validation could also be used to help differentiate between challenging cases of AD and PD when they present with similarly subtle motor and non-motor symptoms.
Federated learning (FL) enables distributed computation of machine learning models over various disparate, remote data sources, without requiring to transfer any individual data to a centralized location. This results in an improved generalizability of models and efficient scaling of computation as more sources and larger datasets are added to the federation. Nevertheless, recent membership attacks show that private or sensitive personal data can sometimes be leaked or inferred when model parameters or summary statistics are shared with a central site, requiring improved security solutions. In this work, we propose a framework for secure FL using fullyhomomorphic encryption (FHE). Specifically, we use the CKKS construction, an approximate, floating point compatible scheme that benefits from ciphertext packing and rescaling. In our evaluation on large-scale brain MRI datasets, we use our proposed secure FL framework to train a deep learning model to predict a person’s age from distributed MRI scans, a common benchmarking task, and demonstrate that there is no degradation in the learning performance between the encrypted and non-encrypted federated models.
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