Michel Dojat

Benjamin Lambert, Florence Forbes, Senan Doyle et al.

Volumetry is one of the principal downstream applications of 3D medical image segmentation, for example, to detect abnormal tissue growth or for surgery planning. Conformal Prediction is a promising framework for uncertainty quantification, providing calibrated predictive intervals associated with automatic volume measurements. However, this methodology is based on the hypothesis that calibration and test samples are exchangeable, an assumption that is in practice often violated in medical image applications. A weighted formulation of Conformal Prediction can be framed to mitigate this issue, but its empirical investigation in the medical domain is still lacking. A potential reason is that it relies on the estimation of the density ratio between the calibration and test distributions, which is likely to be intractable in scenarios involving high-dimensional data. To circumvent this, we propose an efficient approach for density ratio estimation relying on the compressed latent representations generated by the segmentation model. Our experiments demonstrate the efficiency of our approach to reduce the coverage error in the presence of covariate shifts, in both synthetic and real-world settings. Our implementation is available at https://github.com/benolmbrt/wcp_miccai

Benjamin Lambert, Florence Forbes, Alan Tucholka et al.

The full acceptance of Deep Learning (DL) models in the clinical field is rather low with respect to the quantity of high-performing solutions reported in the literature. Particularly, end users are reluctant to rely on the rough predictions of DL models. Uncertainty quantification methods have been proposed in the literature as a potential response to reduce the rough decision provided by the DL black box and thus increase the interpretability and the acceptability of the result by the final user. In this review, we propose an overview of the existing methods to quantify uncertainty associated to DL predictions. We focus on applications to medical image analysis, which present specific challenges due to the high dimensionality of images and their quality variability, as well as constraints associated to real-life clinical routine. We then discuss the evaluation protocols to validate the relevance of uncertainty estimates. Finally, we highlight the open challenges of uncertainty quantification in the medical field.

Benjamin Lambert, Florence Forbes, Senan Doyle et al.

Deep Learning models are easily disturbed by variations in the input images that were not observed during the training stage, resulting in unpredictable predictions. Detecting such Out-of-Distribution (OOD) images is particularly crucial in the context of medical image analysis, where the range of possible abnormalities is extremely wide. Recently, a new category of methods has emerged, based on the analysis of the intermediate features of a trained model. These methods can be divided into 2 groups: single-layer methods that consider the feature map obtained at a fixed, carefully chosen layer, and multi-layer methods that consider the ensemble of the feature maps generated by the model. While promising, a proper comparison of these algorithms is still lacking. In this work, we compared various feature-based OOD detection methods on a large spectra of OOD (20 types), representing approximately 7800 3D MRIs. Our experiments shed the light on two phenomenons. First, multi-layer methods consistently outperform single-layer approaches, which tend to have inconsistent behaviour depending on the type of anomaly. Second, the OOD detection performance highly depends on the architecture of the underlying neural network.

Benjamin Lambert, Pauline Roca, Florence Forbes et al.

The burden of liver tumors is important, ranking as the fourth leading cause of cancer mortality. In case of hepatocellular carcinoma (HCC), the delineation of liver and tumor on contrast-enhanced magnetic resonance imaging (CE-MRI) is performed to guide the treatment strategy. As this task is time-consuming, needs high expertise and could be subject to inter-observer variability there is a strong need for automatic tools. However, challenges arise from the lack of available training data, as well as the high variability in terms of image resolution and MRI sequence. In this work we propose to compare two different pipelines based on anisotropic models to obtain the segmentation of the liver and tumors. The first pipeline corresponds to a baseline multi-class model that performs the simultaneous segmentation of the liver and tumor classes. In the second approach, we train two distinct binary models, one segmenting the liver only and the other the tumors. Our results show that both pipelines exhibit different strengths and weaknesses. Moreover we propose an uncertainty quantification strategy allowing the identification of potential false positive tumor lesions. Both solutions were submitted to the MICCAI 2023 Atlas challenge regarding liver and tumor segmentation.

Nicolas Pinon, Geoffroy Oudoumanessah, Robin Trombetta et al.

Neural network-based anomaly detection remains challenging in clinical applications with little or no supervised information and subtle anomalies such as hardly visible brain lesions. Among unsupervised methods, patch-based auto-encoders with their efficient representation power provided by their latent space, have shown good results for visible lesion detection. However, the commonly used reconstruction error criterion may limit their performance when facing less obvious lesions. In this work, we design two alternative detection criteria. They are derived from multivariate analysis and can more directly capture information from latent space representations. Their performance compares favorably with two additional supervised learning methods, on a difficult de novo Parkinson Disease (PD) classification task.

Benjamin Lambert, Florence Forbes, Senan Doyle et al.

Deep neural networks have become the gold-standard approach for the automated segmentation of 3D medical images. Their full acceptance by clinicians remains however hampered by the lack of intelligible uncertainty assessment of the provided results. Most approaches to quantify their uncertainty, such as the popular Monte Carlo dropout, restrict to some measure of uncertainty in prediction at the voxel level. In addition not to be clearly related to genuine medical uncertainty, this is not clinically satisfying as most objects of interest (e.g. brain lesions) are made of groups of voxels whose overall relevance may not simply reduce to the sum or mean of their individual uncertainties. In this work, we propose to go beyond voxel-wise assessment using an innovative Graph Neural Network approach, trained from the outputs of a Monte Carlo dropout model. This network allows the fusion of three estimators of voxel uncertainty: entropy, variance, and model's confidence; and can be applied to any lesion, regardless of its shape or size. We demonstrate the superiority of our approach for uncertainty estimate on a task of Multiple Sclerosis lesions segmentation.

Benjamin Lambert, Florence Forbes, Senan Doyle et al.

Deep Learning models are easily disturbed by variations in the input images that were not seen during training, resulting in unpredictable behaviours. Such Out-of-Distribution (OOD) images represent a significant challenge in the context of medical image analysis, where the range of possible abnormalities is extremely wide, including artifacts, unseen pathologies, or different imaging protocols. In this work, we evaluate various uncertainty frameworks to detect OOD inputs in the context of Multiple Sclerosis lesions segmentation. By implementing a comprehensive evaluation scheme including 14 sources of OOD of various nature and strength, we show that methods relying on the predictive uncertainty of binary segmentation models often fails in detecting outlying inputs. On the contrary, learning to segment anatomical labels alongside lesions highly improves the ability to detect OOD inputs.

Benjamin Lambert, Florence Forbes, Senan Doyle et al.

The volume of a brain lesion (e.g. infarct or tumor) is a powerful indicator of patient prognosis and can be used to guide the therapeutic strategy. Lesional volume estimation is usually performed by segmentation with deep convolutional neural networks (CNN), currently the state-of-the-art approach. However, to date, few work has been done to equip volume segmentation tools with adequate quantitative predictive intervals, which can hinder their usefulness and acceptation in clinical practice. In this work, we propose TriadNet, a segmentation approach relying on a multi-head CNN architecture, which provides both the lesion volumes and the associated predictive intervals simultaneously, in less than a second. We demonstrate its superiority over other solutions on BraTS 2021, a large-scale MRI glioblastoma image database.

Stenzel Cackowski, Emmanuel L. Barbier, Michel Dojat et al.

ImUnity is an original deep-learning model designed for efficient and flexible MR image harmonization. A VAE-GAN network, coupled with a confusion module and an optional biological preservation module, uses multiple 2D-slices taken from different anatomical locations in each subject of the training database, as well as image contrast transformations for its self-supervised training. It eventually generates 'corrected' MR images that can be used for various multi-center population studies. Using 3 open source databases (ABIDE, OASIS and SRPBS), which contain MR images from multiple acquisition scanner types or vendors and a large range of subjects ages, we show that ImUnity: (1) outperforms state-of-the-art methods in terms of quality of images generated using traveling subjects; (2) removes sites or scanner biases while improving patients classification; (3) harmonizes data coming from new sites or scanners without the need for an additional fine-tuning and (4) allows the selection of multiple MR reconstructed images according to the desired applications. Tested here on T1-weighted images, ImUnity could be used to harmonize other types of medical images.

Jacopo Iollo, Geoffroy Oudoumanessah, Carole Lartizien et al.

A key challenge in maximizing the benefits of Magnetic Resonance Imaging (MRI) in clinical settings is to accelerate acquisition times without significantly degrading image quality. This objective requires a balance between under-sampling the raw k-space measurements for faster acquisitions and gathering sufficient raw information for high-fidelity image reconstruction and analysis tasks. To achieve this balance, we propose to use sequential Bayesian experimental design (BED) to provide an adaptive and task-dependent selection of the most informative measurements. Measurements are sequentially augmented with new samples selected to maximize information gain on a posterior distribution over target images. Selection is performed via a gradient-based optimization of a design parameter that defines a subsampling pattern. In this work, we introduce a new active BED procedure that leverages diffusion-based generative models to handle the high dimensionality of the images and employs stochastic optimization to select among a variety of patterns while meeting the acquisition process constraints and budget. So doing, we show how our setting can optimize, not only standard image reconstruction, but also any associated image analysis task. The versatility and performance of our approach are demonstrated on several MRI acquisitions.

Geoffroy Oudoumanessah, Carole Lartizien, Michel Dojat et al.

Anomaly detection in medical imaging is a challenging task in contexts where abnormalities are not annotated. This problem can be addressed through unsupervised anomaly detection (UAD) methods, which identify features that do not match with a reference model of normal profiles. Artificial neural networks have been extensively used for UAD but they do not generally achieve an optimal trade-o$\hookleftarrow$ between accuracy and computational demand. As an alternative, we investigate mixtures of probability distributions whose versatility has been widely recognized for a variety of data and tasks, while not requiring excessive design e$\hookleftarrow$ort or tuning. Their expressivity makes them good candidates to account for complex multivariate reference models. Their much smaller number of parameters makes them more amenable to interpretation and e cient learning. However, standard estimation procedures, such as the Expectation-Maximization algorithm, do not scale well to large data volumes as they require high memory usage. To address this issue, we propose to incrementally compute inferential quantities. This online approach is illustrated on the challenging detection of subtle abnormalities in MR brain scans for the follow-up of newly diagnosed Parkinsonian patients. The identified structural abnormalities are consistent with the disease progression, as accounted by the Hoehn and Yahr scale.

Dwight Nwaigwe, Lucrezia Carboni, Martial Mermillod et al.

Artificial neural networks are prone to being fooled by carefully perturbed inputs which cause an egregious misclassification. These \textit{adversarial} attacks have been the focus of extensive research. Likewise, there has been an abundance of research in ways to detect and defend against them. We introduce a novel approach of detection and interpretation of adversarial attacks from a graph perspective. For an input image, we compute an associated sparse graph using the layer-wise relevance propagation algorithm \cite{bach15}. Specifically, we only keep edges of the neural network with the highest relevance values. Three quantities are then computed from the graph which are then compared against those computed from the training set. The result of the comparison is a classification of the image as benign or adversarial. To make the comparison, two classification methods are introduced: 1) an explicit formula based on Wasserstein distance applied to the degree of node and 2) a logistic regression. Both classification methods produce strong results which lead us to believe that a graph-based interpretation of adversarial attacks is valuable.

Benjamin Lambert, Maxime Louis, Senan Doyle et al.

Automatic segmentation of brain abnormalities is challenging, as they vary considerably from one pathology to another. Current methods are supervised and require numerous annotated images for each pathology, a strenuous task. To tackle anatomical variability, Unsupervised Anomaly Detection (UAD) methods are proposed, detecting anomalies as outliers of a healthy model learned using a Variational Autoencoder (VAE). Previous work on UAD adopted a 2D approach, meaning that MRIs are processed as a collection of independent slices. Yet, it does not fully exploit the spatial information contained in MRI. Here, we propose to perform UAD in a 3D fashion and compare 2D and 3D VAEs. As a side contribution, we present a new loss function guarantying a robust training. Learning is performed using a multicentric dataset of healthy brain MRIs, and segmentation performances are estimated on White-Matter Hyperintensities and tumors lesions. Experiments demonstrate the interest of 3D methods which outperform their 2D counterparts.