Marvin Lerousseau

Tristan Lazard, Marvin Lerousseau, Etienne Decencière et al.

Whole slide images (WSI) are microscopy images of stained tissue slides routinely prepared for diagnosis and treatment selection in medical practice. WSI are very large (gigapixel size) and complex (made of up to millions of cells). The current state-of-the-art (SoTA) approach to classify WSI subdivides them into tiles, encodes them by pre-trained networks and applies Multiple Instance Learning (MIL) to train for specific downstream tasks. However, annotated datasets are often small, typically a few hundred to a few thousand WSI, which may cause overfitting and underperforming models. Conversely, the number of unannotated WSI is ever increasing, with datasets of tens of thousands (soon to be millions) of images available. While it has been previously proposed to use these unannotated data to identify suitable tile representations by self-supervised learning (SSL), downstream classification tasks still require full supervision because parts of the MIL architecture is not trained during tile level SSL pre-training. Here, we propose a strategy of slide level SSL to leverage the large number of WSI without annotations to infer powerful slide representations. Applying our method to The Cancer-Genome Atlas, one of the most widely used data resources in cancer research (16 TB image data), we are able to downsize the dataset to 23 MB without any loss in predictive power: we show that a linear classifier trained on top of these embeddings maintains or improves previous SoTA performances on various benchmark WSI classification tasks. Finally, we observe that training a classifier on these representations with tiny datasets (e.g. 50 slides) improved performances over SoTA by an average of +6.3 AUC points over all downstream tasks.

Marvin Lerousseau, Maria Vakalopoulou, Eric Deutsch et al.

Multiple instance learning (MIL) is the preferred approach for whole slide image classification. However, most MIL approaches do not exploit the interdependencies of tiles extracted from a whole slide image, which could provide valuable cues for classification. This paper presents a novel MIL approach that exploits the spatial relationship of tiles for classifying whole slide images. To do so, a sparse map is built from tiles embeddings, and is then classified by a sparse-input CNN. It obtained state-of-the-art performance over popular MIL approaches on the classification of cancer subtype involving 10000 whole slide images. Our results suggest that the proposed approach might (i) improve the representation learning of instances and (ii) exploit the context of instance embeddings to enhance the classification performance. The code of this work is open-source at {github censored for review}.

Marvin Lerousseau

This report summarizes work performed as part of an internship at INRIA, in partial requirement for the completion of a master degree in math and informatics. The goal of the internship was to develop a software environment to simulate electricity transmission in a power grid and actions performed by operators to maintain this grid in security. Our environment lends itself to automate the control of the power grid with reinforcement learning agents, assisting human operators. It is amenable to organizing benchmarks, including a challenge in machine learning planned by INRIA and RTE for 2019. Our framework, built on top of open-source libraries, is available at https://github.com/MarvinLer/pypownet. In this report we present intermediary results and its usage in the context of a reinforcement learning game.

Theophraste Henry, Alexandre Carre, Marvin Lerousseau et al.

Brain tumor segmentation is a critical task for patient's disease management. In order to automate and standardize this task, we trained multiple U-net like neural networks, mainly with deep supervision and stochastic weight averaging, on the Multimodal Brain Tumor Segmentation Challenge (BraTS) 2020 training dataset. Two independent ensembles of models from two different training pipelines were trained, and each produced a brain tumor segmentation map. These two labelmaps per patient were then merged, taking into account the performance of each ensemble for specific tumor subregions. Our performance on the online validation dataset with test time augmentation were as follows: Dice of 0.81, 0.91 and 0.85; Hausdorff (95%) of 20.6, 4,3, 5.7 mm for the enhancing tumor, whole tumor and tumor core, respectively. Similarly, our solution achieved a Dice of 0.79, 0.89 and 0.84, as well as Hausdorff (95%) of 20.4, 6.7 and 19.5mm on the final test dataset, ranking us among the top ten teams. More complicated training schemes and neural network architectures were investigated without significant performance gain at the cost of greatly increased training time. Overall, our approach yielded good and balanced performance for each tumor subregion. Our solution is open sourced at https://github.com/lescientifik/open_brats2020.

Théo Estienne, Maria Vakalopoulou, Enzo Battistella et al.

Image registration is one of the most challenging problems in medical image analysis. In the recent years, deep learning based approaches became quite popular, providing fast and performing registration strategies. In this short paper, we summarise our work presented on Learn2Reg challenge 2020. The main contributions of our work rely on (i) a symmetric formulation, predicting the transformations from source to target and from target to source simultaneously, enforcing the trained representations to be similar and (ii) integration of variety of publicly available datasets used both for pretraining and for augmenting segmentation labels. Our method reports a mean dice of $0.64$ for task 3 and $0.85$ for task 4 on the test sets, taking third place on the challenge. Our code and models are publicly available at https://github.com/TheoEst/abdominal_registration and \https://github.com/TheoEst/hippocampus_registration.

Marvin Lerousseau, Maria Vakalopoulou, Marion Classe et al.

Histopathological image segmentation is a challenging and important topic in medical imaging with tremendous potential impact in clinical practice. State of the art methods rely on hand-crafted annotations which hinder clinical translation since histology suffers from significant variations between cancer phenotypes. In this paper, we propose a weakly supervised framework for whole slide imaging segmentation that relies on standard clinical annotations, available in most medical systems. In particular, we exploit a multiple instance learning scheme for training models. The proposed framework has been evaluated on multi-locations and multi-centric public data from The Cancer Genome Atlas and the PatchCamelyon dataset. Promising results when compared with experts' annotations demonstrate the potentials of the presented approach. The complete framework, including $6481$ generated tumor maps and data processing, is available at https://github.com/marvinler/tcga_segmentation.

Théo Estienne, Maria Vakalopoulou, Enzo Battistella et al.

Deformable registration consists of finding the best dense correspondence between two different images. Many algorithms have been published, but the clinical application was made difficult by the high calculation time needed to solve the optimisation problem. Deep learning overtook this limitation by taking advantage of GPU calculation and the learning process. However, many deep learning methods do not take into account desirable properties respected by classical algorithms. In this paper, we present MICS, a novel deep learning algorithm for medical imaging registration. As registration is an ill-posed problem, we focused our algorithm on the respect of different properties: inverse consistency, symmetry and orientation conservation. We also combined our algorithm with a multi-step strategy to refine and improve the deformation grid. While many approaches applied registration to brain MRI, we explored a more challenging body localisation: abdominal CT. Finally, we evaluated our method on a dataset used during the Learn2Reg challenge, allowing a fair comparison with published methods.

Théo Estienne, Maria Vakalopoulou, Stergios Christodoulidis et al.

Explainability of deep neural networks is one of the most challenging and interesting problems in the field. In this study, we investigate the topic focusing on the interpretability of deep learning-based registration methods. In particular, with the appropriate model architecture and using a simple linear projection, we decompose the encoding space, generating a new basis, and we empirically show that this basis captures various decomposed anatomically aware geometrical transformations. We perform experiments using two different datasets focusing on lungs and hippocampus MRI. We show that such an approach can decompose the highly convoluted latent spaces of registration pipelines in an orthogonal space with several interesting properties. We hope that this work could shed some light on a better understanding of deep learning-based registration methods.

Marvin Lerousseau, Marion Classe, Enzo Battistella et al.

The vast majority of semantic segmentation approaches rely on pixel-level annotations that are tedious and time consuming to obtain and suffer from significant inter and intra-expert variability. To address these issues, recent approaches have leveraged categorical annotations at the slide-level, that in general suffer from robustness and generalization. In this paper, we propose a novel weakly supervised multi-instance learning approach that deciphers quantitative slide-level annotations which are fast to obtain and regularly present in clinical routine. The extreme potentials of the proposed approach are demonstrated for tumor segmentation of solid cancer subtypes. The proposed approach achieves superior performance in out-of-distribution, out-of-location, and out-of-domain testing sets.

Enzo Battistella, Maria Vakalopoulou, Roger Sun et al.

Precision medicine is a paradigm shift in healthcare relying heavily on genomics data. However, the complexity of biological interactions, the large number of genes as well as the lack of comparisons on the analysis of data, remain a tremendous bottleneck regarding clinical adoption. In this paper, we introduce a novel, automatic and unsupervised framework to discover low-dimensional gene biomarkers. Our method is based on the LP-Stability algorithm, a high dimensional center-based unsupervised clustering algorithm, that offers modularity as concerns metric functions and scalability, while being able to automatically determine the best number of clusters. Our evaluation includes both mathematical and biological criteria. The recovered signature is applied to a variety of biological tasks, including screening of biological pathways and functions, and characterization relevance on tumor types and subtypes. Quantitative comparisons among different distance metrics, commonly used clustering methods and a referential gene signature used in the literature, confirm state of the art performance of our approach. In particular, our signature, that is based on 27 genes, reports at least $30$ times better mathematical significance (average Dunn's Index) and 25% better biological significance (average Enrichment in Protein-Protein Interaction) than those produced by other referential clustering methods. Finally, our signature reports promising results on distinguishing immune inflammatory and immune desert tumors, while reporting a high balanced accuracy of 92% on tumor types classification and averaged balanced accuracy of 68% on tumor subtypes classification, which represents, respectively 7% and 9% higher performance compared to the referential signature.

Marvin Lerousseau, Eric Deutsh, Nikos Paragios

Cancer is a complex disease that provides various types of information depending on the scale of observation. While most tumor diagnostics are performed by observing histopathological slides, radiology images should yield additional knowledge towards the efficacy of cancer diagnostics. This work investigates a deep learning method combining whole slide images and magnetic resonance images to classify tumors. In particular, our solution comprises a powerful, generic and modular architecture for whole slide image classification. Experiments are prospectively conducted on the 2020 Computational Precision Medicine challenge, in a 3-classes unbalanced classification task. We report cross-validation (resp. validation) balanced-accuracy, kappa and f1 of 0.913, 0.897 and 0.951 (resp. 0.91, 0.90 and 0.94). For research purposes, including reproducibility and direct performance comparisons, our finale submitted models are usable off-the-shelf in a Docker image available at https://hub.docker.com/repository/docker/marvinler/cpm_2020_marvinler.

Antoine Marot, Benjamin Donnot, Camilo Romero et al.

For power grid operations, a large body of research focuses on using generation redispatching, load shedding or demand side management flexibilities. However, a less costly and potentially more flexible option would be grid topology reconfiguration, as already partially exploited by Coreso (European RSC) and RTE (French TSO) operations. Beyond previous work on branch switching, bus reconfigurations are a broader class of action and could provide some substantial benefits to route electricity and optimize the grid capacity to keep it within safety margins. Because of its non-linear and combinatorial nature, no existing optimal power flow solver can yet tackle this problem. We here propose a new framework to learn topology controllers through imitation and reinforcement learning. We present the design and the results of the first "Learning to Run a Power Network" challenge released with this framework. We finally develop a method providing performance upper-bounds (oracle), which highlights remaining unsolved challenges and suggests future directions of improvement.