Neuroimaging in Machine Learning for Brain Disorders

International audienceMedical imaging plays an important role in the detection, diagnosis and treatment monitoring of brain disorders. Neuroimaging includes different modalities such as magnetic resonance imaging (MRI), X-ray computed tomography (CT), positron emission tomography (PET) or single-photon emission computed tomography (SPECT).For each of these modalities, we will explain the basic principles of the technology, describe the type of information the images can provide, list the key processing steps necessary to extract features and provide examples of their use in machine learning studies for brain disorders

Individualised, interpretable and reproducible computer-aided diagnosis of dementia: towards application in clinical practice

Neuroimaging offers an unmatched description of the brain’s structure and physiology, but the information it provides is not easy to extract and interpret. A popular way to extract meaningful information from brain images is to use computational methods based on machine learning and deep learning to predict the current or future diagnosis of a patient. A large number of these approaches have been dedicated to the computer-aided diagnosis of dementia, and more specifically of Alzheimer's disease. However, only a few are translated to the clinic. This can be explained by different factors such as the lack of rigorous validation of these approaches leading to over-optimistic performance and their lack of reproducibility, but also the limited interpretability of these methods and their limited generalisability when moving from highly controlled research data to routine clinical data. This manuscript describes how we tried to address these limitations.We have proposed reproducible frameworks for the evaluation of Alzheimer's disease classification methods and developed two open-source software platforms for clinical neuroimaging studies (Clinica) and neuroimaging processing with deep learning (ClinicaDL). We have implemented and assessed the robustness of a visualisation method aiming to interpret convolutional neural networks and used it to study the stability of the network training. We concluded that, currently, combining a convolutional neural networks classifier with an interpretability method may not constitute a robust tool for individual computer-aided diagnosis. As an alternative, we have proposed an approach that detects anomalies in the brain by generating what would be the healthy version of a patient's image and comparing this healthy version with the real image. Finally, we have studied the performance of machine and deep learning algorithms for the computer-aided diagnosis of dementia from images acquired in clinical routine.La neuro-imagerie offre une description inégalée de la structure et de la physiologie du cerveau, mais les informations qu'elle fournit ne sont pas faciles à extraire et à interpréter. Une façon populaire d'extraire des informations pertinentes d'images cérébrales consiste à utiliser des méthodes basées sur l'apprentissage statistique et l'apprentissage profond pour prédire le diagnostic actuel ou futur d'un patient. Un grand nombre de ces approches ont été dédiées au diagnostic assisté par ordinateur de la démence, et plus spécifiquement de la maladie d'Alzheimer. Cependant, seules quelques-unes sont transposées en clinique. Cela peut s'expliquer par différents facteurs tels que l'absence de validation rigoureuse de ces approches conduisant à des performances trop optimistes et à leur manque de reproductibilité, mais aussi l'interprétabilité limitée de ces méthodes et leur généralisation limitée lors du passage de données de recherche hautement contrôlées à des données cliniques de routine. Ce manuscrit décrit comment nous avons tenté de remédier à ces limites.Nous avons proposé des cadres reproductibles pour l'évaluation des méthodes de classification de la maladie d'Alzheimer et développé deux plateformes logicielles open-source pour les études de neuroimagerie clinique (Clinica) et le traitement de la neuroimagerie par apprentissage profond (ClinicaDL). Nous avons implémenté et évalué la robustesse d'une méthode de visualisation visant à interpréter les réseaux neuronaux convolutifs et l'avons utilisée pour étudier la stabilité de l'entraînement du réseau. Nous avons conclu qu'actuellement, la combinaison de réseaux neuronaux convolutifs avec une méthode d'interprétabilité peut ne pas constituer un outil robuste pour le diagnostic individuel assisté par ordinateur. De façon alternative, nous avons proposé une approche qui détecte les anomalies dans le cerveau en générant ce qui serait la version saine de l'image d'un patient et en comparant cette version saine avec l'image réelle. Enfin, nous avons étudié les performances des algorithmes d'apprentissage statistique et profond pour le diagnostic assisté par ordinateur de la démence à partir d'images acquises en routine clinique

Machine learning for classification and prediction of brain diseases: recent advances and upcoming challenges

International audiencePurpose of review. Machine learning (ML) is an artificial intelligence technique that allows computers to perform a task without being explicitly programmed. ML can be used to assist diagnosis and prognosis of brain disorders. While the earliest papers date from more than ten years ago, research increases at a very fast pace. Recent findings. Recent works using ML for diagnosis have moved from classification of a given disease versus controls to differential diagnosis. Intense research has been devoted to the prediction of the future patient state. While a lot of earlier works focused on neuroimaging as data source, the current trend is on the integration of multimodal. In terms of targeted diseases, dementia remains dominant, but approaches have been developed for a wide variety of neurological and psychiatric diseases. Summary. ML is extremely promising for assisting diagnosis and prognosis in brain disorders. Nevertheless, we argue that key challenges remain to be addressed by the community for bringing these tools in clinical routine: good practices regarding validation and reproducible research need to be more widely adopted; extensive generalization studies are required; interpretable models are needed to overcome the limitations of black-box approaches

How can data augmentation improve attribution maps for disease subtype explainability?

International audienceAs deep learning has been widely used for computer aided-diagnosis, we wished to know whether attribution maps obtained using gradient back-propagation could correctly highlight the patterns of disease subtypes discovered by a deep learning classifier. As the correctness of attribution maps is difficult to evaluate directly on medical images, we used synthetic data mimicking the difference between brain MRI of controls and demented patients to design more reliable evaluation criteria of attribution maps. We demonstrated that attribution maps may mix the regions associated with different subtypes for small data sets while they could accurately characterize both subtypes using a large data set. We then proposed simple data augmentation techniques and showed that they could improve the coherence of the explanations for a small data set

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

International audienceIn 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

Transfer learning from synthetic to routine clinical data for motion artefact detection in brain T1-weighted MRI

International audienceClinical data warehouses (CDWs) contain the medical data of millions of patients and represent a great opportunity to develop computational tools. MRIs are particularly sensitive to patient movements during image acquisition, which will result in artefacts (blurring, ghosting and ringing) in the reconstructed image. As a result, a significant number of MRIs in CDWs are unusable because corrupted by these artefacts. Since their manual detection is impossible due to the number of scans, it is necessary to develop a tool to automatically exclude images with motion in order to fully exploit CDWs. In this paper, we propose a CNN for the automatic detection of motion in 3D T1-weighted brain MRI. Our transfer learning approach, based on synthetic motion generation, consists of two steps: a pre-training on research data using synthetic motion, followed by a fine-tuning step to generalise our pre-trained model to clinical data, relying on the manual labelling of 5500 images. The objectives were both (1) to be able to exclude images with severe motion, (2) to detect mild motion artefacts. Our approach achieved excellent accuracy for the first objective with a balanced accuracy nearly similar to that of the annotators (balanced accuracy>80%). However, for the second objective, the performance was weaker and substantially lower than that of human raters. Overall, our framework will be useful to take advantage of CDWs in medical imaging and to highlight the importance of a clinical validation of models trained on research data

Fourier Disentangled Multimodal Prior Knowledge Fusion for Red Nucleus Segmentation in Brain MRI

Early and accurate diagnosis of parkinsonian syndromes is critical to provide appropriate care to patients and for inclusion in therapeutic trials. The red nucleus is a structure of the midbrain that plays an important role in these disorders. It can be visualized using iron-sensitive magnetic resonance imaging (MRI) sequences. Different iron-sensitive contrasts can be produced with MRI. Combining such multimodal data has the potential to improve segmentation of the red nucleus. Current multimodal segmentation algorithms are computationally consuming, cannot deal with missing modalities and need annotations for all modalities. In this paper, we propose a new model that integrates prior knowledge from different contrasts for red nucleus segmentation. The method consists of three main stages. First, it disentangles the image into high-level information representing the brain structure, and low-frequency information representing the contrast. The high-frequency information is then fed into a network to learn anatomical features, while the list of multimodal low-frequency information is processed by another module. Finally, feature fusion is performed to complete the segmentation task. The proposed method was used with several iron-sensitive contrasts (iMag, QSM, R2*, SWI). Experiments demonstrate that our proposed model substantially outperforms a baseline UNet model when the training set size is very small

Predicting progression to Alzheimer’s disease from clinical and imaging data: a reproducible study

International audienceVarious machine learning approaches have been developed for predicting progression to Alzheimer’s disease (AD) in patients with mild cognitive impairment (MCI) from MRI and PET data. Objective comparison of these approaches is nearly impossible because of differences at all steps, from data management to image processing and evaluation procedures. Moreover, with a few exceptions, these papers rarely compare their results to that obtained with clinical/cognitive data only, a critical point to demonstrate the practical utility of neuroimaging in this context. We previously proposed a framework for the reproducible evaluation of ML algorithms for AD classification. This framework was applied to AD classification using unimodal neuroimaging data (T1 MRI and FDG PET). Here, we extend our previous work to the combination of multimodal clinical and neuroimaging data for predicting progression to AD among MCI patients. All the code is publicly available at: https://github.com/aramis-lab/AD-ML

Three simple ideas for predicting progression to Alzheimer's disease

International audienceIn spite of the amount of research done in the prediction of the progression of mild cognitive impaired (MCI) subjects to Alzheimer's disease (AD), there is still room for further improvement. Sophisticated methods have been proposed, some reaching classification accuracies of up to 85%. In the present paper, we propose a combination of simple ideas to determine if they allow to obtain similar accuracies when predicting MCI to AD conversion. We present three approaches making use of ADNI database. We set a performance baseline using only demographic and clinical data (gender, education level, APOE4, MMSE, CDR sum of boxes, ADASCog) that provides a balanced accuracy of 76% (AUC of 0.84). When using imaging data, an important finding is that when an SVM is trained for discriminating between cognitive normal (CN) subjects and AD patients, and the resulting classifier is applied to MCI subjects to predict conversion, performance using FDG PET data improves to 76% of balanced accuracy and an AUC of 0.82. The third approach, consisting of multimodal data, namely the combination of the scores obtained from SVM for T1w and FDG PET data, and the demographic and clinical data, provided the best prediction results (80% balanced accuracy, AUC of 0.88). These prediction accuracies, resulting from the combination simple ideas, are in line with state-of-the-art results, and provide a new baseline to compare more sophisticated methods against. All the code of the framework and the experiments will be publicly available at https://gitlab.icm-institute.org/aramislab/AD-ML