Reproducible evaluation of classification methods in Alzheimer's disease: Framework and application to MRI and PET data.

A large number of papers have introduced novel machine learning and feature extraction methods for automatic classification of Alzheimer's disease (AD). However, while the vast majority of these works use the public dataset ADNI for evaluation, they are difficult to reproduce because different key components of the validation are often not readily available. These components include selected participants and input data, image preprocessing and cross-validation procedures. The performance of the different approaches is also difficult to compare objectively. In particular, it is often difficult to assess which part of the method (e.g. preprocessing, feature extraction or classification algorithms) provides a real improvement, if any. In the present paper, we propose a framework for reproducible and objective classification experiments in AD using three publicly available datasets (ADNI, AIBL and OASIS). The framework comprises: i) automatic conversion of the three datasets into a standard format (BIDS); ii) a modular set of preprocessing pipelines, feature extraction and classification methods, together with an evaluation framework, that provide a baseline for benchmarking the different components. We demonstrate the use of the framework for a large-scale evaluation on 1960 participants using T1 MRI and FDG PET data. In this evaluation, we assess the influence of different modalities, preprocessing, feature types (regional or voxel-based features), classifiers, training set sizes and datasets. Performances were in line with the state-of-the-art. FDG PET outperformed T1 MRI for all classification tasks. No difference in performance was found for the use of different atlases, image smoothing, partial volume correction of FDG PET images, or feature type. Linear SVM and L2-logistic regression resulted in similar performance and both outperformed random forests. The classification performance increased along with the number of subjects used for training. Classifiers trained on ADNI generalized well to AIBL and OASIS. 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://gitlab.icm-institute.org/aramislab/AD-ML.

Multilevel Survival Modeling With Structured Penalties for Disease Prediction From Imaging Genetics Data.

This paper introduces a framework for disease prediction from multimodal genetic and imaging data. We propose a multilevel survival model which allows predicting the time of occurrence of a future disease state in patients initially exhibiting mild symptoms. This new multilevel setting allows modeling the interactions between genetic and imaging variables. This is in contrast with classical additive models which treat all modalities in the same manner and can result in undesirable elimination of specific modalities when their contributions are unbalanced. Moreover, the use of a survival model allows overcoming the limitations of previous approaches based on classification which consider a fixed time frame. Furthermore, we introduce specific penalties taking into account the structure of the different types of data, such as a group lasso penalty over the genetic modality and a l2-penalty over the imaging modality. Finally, we propose a fast optimization algorithm, based on a proximal gradient method. The approach was applied to the prediction of Alzheimer's disease (AD) among patients with mild cognitive impairment (MCI) based on genetic (single nucleotide polymorphisms - SNP) and imaging (anatomical MRI measures) data from the ADNI database. The experiments demonstrate the effectiveness of the method for predicting the time of conversion to AD. It revealed how genetic variants and brain imaging alterations interact in the prediction of future disease status. The approach is generic and could potentially be useful for the prediction of other diseases.

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.