Contrast-enhanced to non-contrast-enhanced image translation to exploit a clinical data warehouse of T1-weighted brain MRI.

BACKGROUND: Clinical data warehouses provide access to massive amounts of medical images, but these images are often heterogeneous. They can for instance include images acquired both with or without the injection of a gadolinium-based contrast agent. Harmonizing such data sets is thus fundamental to guarantee unbiased results, for example when performing differential diagnosis. Furthermore, classical neuroimaging software tools for feature extraction are typically applied only to images without gadolinium. The objective of this work is to evaluate how image translation can be useful to exploit a highly heterogeneous data set containing both contrast-enhanced and non-contrast-enhanced images from a clinical data warehouse. METHODS: We propose and compare different 3D U-Net and conditional GAN models to convert contrast-enhanced T1-weighted (T1ce) into non-contrast-enhanced (T1nce) brain MRI. These models were trained using 230 image pairs and tested on 77 image pairs from the clinical data warehouse of the Greater Paris area. RESULTS: Validation using standard image similarity measures demonstrated that the similarity between real and synthetic T1nce images was higher than between real T1nce and T1ce images for all the models compared. The best performing models were further validated on a segmentation task. We showed that tissue volumes extracted from synthetic T1nce images were closer to those of real T1nce images than volumes extracted from T1ce images. CONCLUSION: We showed that deep learning models initially developed with research quality data could synthesize T1nce from T1ce images of clinical quality and that reliable features could be extracted from the synthetic images, thus demonstrating the ability of such methods to help exploit a data set coming from a clinical data warehouse.

Data Augmentation in High Dimensional Low Sample Size Setting Using a Geometry-Based Variational Autoencoder.

In this paper, we propose a new method to perform data augmentation in a reliable way in the High Dimensional Low Sample Size (HDLSS) setting using a geometry-based variational autoencoder (VAE). Our approach combines the proposal of 1) a new VAE model, the latent space of which is modeled as a Riemannian manifold and which combines both Riemannian metric learning and normalizing flows and 2) a new generation scheme which produces more meaningful samples especially in the context of small data sets. The method is tested through a wide experimental study where its robustness to data sets, classifiers and training samples size is stressed. It is also validated on a medical imaging classification task on the challenging ADNI database where a small number of 3D brain magnetic resonance images (MRIs) are considered and augmented using the proposed VAE framework. In each case, the proposed method allows for a significant and reliable gain in the classification metrics. For instance, balanced accuracy jumps from 66.3% to 74.3% for a state-of-the-art convolutional neural network classifier trained with 50 MRIs of cognitively normal (CN) and 50 Alzheimer disease (AD) patients and from 77.7% to 86.3% when trained with 243 CN and 210 AD while improving greatly sensitivity and specificity metrics.

ClinicaDL: An open-source deep learning software for reproducible neuroimaging processing.

BACKGROUND AND OBJECTIVE: As deep learning faces a reproducibility crisis and studies on deep learning applied to neuroimaging are contaminated by methodological flaws, there is an urgent need to provide a safe environment for deep learning users to help them avoid common pitfalls that will bias and discredit their results. Several tools have been proposed to help deep learning users design their framework for neuroimaging data sets. Software overview: We present here ClinicaDL, one of these software tools. ClinicaDL interacts with BIDS, a standard format in the neuroimaging field, and its derivatives, so it can be used with a large variety of data sets. Moreover, it checks the absence of data leakage when inferring the results of new data with trained networks, and saves all necessary information to guarantee the reproducibility of results. The combination of ClinicaDL and its companion project Clinica allows performing an end-to-end neuroimaging analysis, from the download of raw data sets to the interpretation of trained networks, including neuroimaging preprocessing, quality check, label definition, architecture search, and network training and evaluation. CONCLUSIONS: We implemented ClinicaDL to bring answers to three common issues encountered by deep learning users who are not always familiar with neuroimaging data: (1) the format and preprocessing of neuroimaging data sets, (2) the contamination of the evaluation procedure by data leakage and (3) a lack of reproducibility. We hope that its use by researchers will allow producing more reliable and thus valuable scientific studies in our field.

Clinica: An Open-Source Software Platform for Reproducible Clinical Neuroscience Studies.

We present Clinica (www.clinica.run), an open-source software platform designed to make clinical neuroscience studies easier and more reproducible. Clinica aims for researchers to (i) spend less time on data management and processing, (ii) perform reproducible evaluations of their methods, and (iii) easily share data and results within their institution and with external collaborators. The core of Clinica is a set of automatic pipelines for processing and analysis of multimodal neuroimaging data (currently, T1-weighted MRI, diffusion MRI, and PET data), as well as tools for statistics, machine learning, and deep learning. It relies on the brain imaging data structure (BIDS) for the organization of raw neuroimaging datasets and on established tools written by the community to build its pipelines. It also provides converters of public neuroimaging datasets to BIDS (currently ADNI, AIBL, OASIS, and NIFD). Processed data include image-valued scalar fields (e.g., tissue probability maps), meshes, surface-based scalar fields (e.g., cortical thickness maps), or scalar outputs (e.g., regional averages). These data follow the ClinicA Processed Structure (CAPS) format which shares the same philosophy as BIDS. Consistent organization of raw and processed neuroimaging files facilitates the execution of single pipelines and of sequences of pipelines, as well as the integration of processed data into statistics or machine learning frameworks. The target audience of Clinica is neuroscientists or clinicians conducting clinical neuroscience studies involving multimodal imaging, and researchers developing advanced machine learning algorithms applied to neuroimaging data.

Deep learning for brain disorders: from data processing to disease treatment.

In order to reach precision medicine and improve patients' quality of life, machine learning is increasingly used in medicine. Brain disorders are often complex and heterogeneous, and several modalities such as demographic, clinical, imaging, genetics and environmental data have been studied to improve their understanding. Deep learning, a subpart of machine learning, provides complex algorithms that can learn from such various data. It has become state of the art in numerous fields, including computer vision and natural language processing, and is also growingly applied in medicine. In this article, we review the use of deep learning for brain disorders. More specifically, we identify the main applications, the concerned disorders and the types of architectures and data used. Finally, we provide guidelines to bridge the gap between research studies and clinical routine.

Predicting the progression of mild cognitive impairment using machine learning: A systematic, quantitative and critical review.

We performed a systematic review of studies focusing on the automatic prediction of the progression of mild cognitive impairment to Alzheimer's disease (AD) dementia, and a quantitative analysis of the methodological choices impacting performance. This review included 172 articles, from which 234 experiments were extracted. For each of them, we reported the used data set, the feature types, the algorithm type, performance and potential methodological issues. The impact of these characteristics on the performance was evaluated using a multivariate mixed effect linear regressions. We found that using cognitive, fluorodeoxyglucose-positron emission tomography or potentially electroencephalography and magnetoencephalography variables significantly improved predictive performance compared to not including them, whereas including other modalities, in particular T1 magnetic resonance imaging, did not show a significant effect. The good performance of cognitive assessments questions the wide use of imaging for predicting the progression to AD and advocates for exploring further fine domain-specific cognitive assessments. We also identified several methodological issues, including the absence of a test set, or its use for feature selection or parameter tuning in nearly a fourth of the papers. Other issues, found in 15% of the studies, cast doubts on the relevance of the method to clinical practice. We also highlight that short-term predictions are likely not to be better than predicting that subjects stay stable over time. These issues highlight the importance of adhering to good practices for the use of machine learning as a decision support system for the clinical practice.

Convolutional neural networks for classification of Alzheimer's disease: Overview and reproducible evaluation.

Numerous machine learning (ML) approaches have been proposed for automatic classification of Alzheimer's disease (AD) from brain imaging data. In particular, over 30 papers have proposed to use convolutional neural networks (CNN) for AD classification from anatomical MRI. However, the classification performance is difficult to compare across studies due to variations in components such as participant selection, image preprocessing or validation procedure. Moreover, these studies are hardly reproducible because their frameworks are not publicly accessible and because implementation details are lacking. Lastly, some of these papers may report a biased performance due to inadequate or unclear validation or model selection procedures. In the present work, we aim to address these limitations through three main contributions. First, we performed a systematic literature review. We identified four main types of approaches: i) 2D slice-level, ii) 3D patch-level, iii) ROI-based and iv) 3D subject-level CNN. Moreover, we found that more than half of the surveyed papers may have suffered from data leakage and thus reported biased performance. Our second contribution is the extension of our open-source framework for classification of AD using CNN and T1-weighted MRI. The framework comprises previously developed tools to automatically convert ADNI, AIBL and OASIS data into the BIDS standard, and a modular set of image preprocessing procedures, classification architectures and evaluation procedures dedicated to deep learning. Finally, we used this framework to rigorously compare different CNN architectures. The data was split into training/validation/test sets at the very beginning and only the training/validation sets were used for model selection. To avoid any overfitting, the test sets were left untouched until the end of the peer-review process. Overall, the different 3D approaches (3D-subject, 3D-ROI, 3D-patch) achieved similar performances while that of the 2D slice approach was lower. Of note, the different CNN approaches did not perform better than a SVM with voxel-based features. The different approaches generalized well to similar populations but not to datasets with different inclusion criteria or demographical characteristics. All the code of the framework and the experiments is publicly available: general-purpose tools have been integrated into the Clinica software (www.clinica.run) and the paper-specific code is available at: https://github.com/aramis-lab/AD-DL.

Ensemble Learning of Convolutional Neural Network, Support Vector Machine, and Best Linear Unbiased Predictor for Brain Age Prediction: ARAMIS Contribution to the Predictive Analytics Competition 2019 Challenge.

We ranked third in the Predictive Analytics Competition (PAC) 2019 challenge by achieving a mean absolute error (MAE) of 3.33 years in predicting age from T1-weighted MRI brain images. Our approach combined seven algorithms that allow generating predictions when the number of features exceeds the number of observations, in particular, two versions of best linear unbiased predictor (BLUP), support vector machine (SVM), two shallow convolutional neural networks (CNNs), and the famous ResNet and Inception V1. Ensemble learning was derived from estimating weights via linear regression in a hold-out subset of the training sample. We further evaluated and identified factors that could influence prediction accuracy: choice of algorithm, ensemble learning, and features used as input/MRI image processing. Our prediction error was correlated with age, and absolute error was greater for older participants, suggesting to increase the training sample for this subgroup. Our results may be used to guide researchers to build age predictors on healthy individuals, which can be used in research and in the clinics as non-specific predictors of disease status.