Automatic Segmentation of Intramedullary Multiple Sclerosis Lesions

Contexte: La moelle épinière est un composant essentiel du système nerveux central. Elle contient des neurones responsables d’importantes fonctionnalités et assure la transmission d’informations motrices et sensorielles entre le cerveau et le système nerveux périphérique. Un endommagement de la moelle épinière, causé par un choc ou une maladie neurodégénérative, peut mener à un sérieux handicap, pouvant entraîner des incapacités fonctionnelles, de la paralysie et/ou de la douleur. Chez les patients atteints de sclérose en plaques (SEP), la moelle épinière est fréquemment affectée par de l’atrophie et/ou des lésions. L’imagerie par résonance magnétique (IRM) conventionnelle est largement utilisée par des chercheurs et des cliniciens pour évaluer et caractériser, de façon non-invasive, des altérations micro-structurelles. Une évaluation quantitative des atteintes structurelles portées à la moelle épinière (e.g. sévérité de l’atrophie, extension des lésions) est essentielle pour le diagnostic, le pronostic et la supervision sur le long terme de maladies, telles que la SEP. De plus, le développement de biomarqueurs impartiaux est indispensable pour évaluer l’effet de nouveaux traitements thérapeutiques. La segmentation de la moelle épinière et des lésions intramédullaires de SEP sont, par conséquent, pertinentes d’un point de vue clinique, aussi bien qu’une étape nécessaire vers l’interprétation d’images RM multiparamétriques. Cependant, la segmentation manuelle est une tâche extrêmement chronophage, fastidieuse et sujette à des variations inter- et intra-expert. Il y a par conséquent un besoin d’automatiser les méthodes de segmentations, ce qui pourrait faciliter l’efficacité procédures d’analyses. La segmentation automatique de lésions est compliqué pour plusieurs raisons: (i) la variabilité des lésions en termes de forme, taille et position, (ii) les contours des lésions sont la plupart du temps difficilement discernables, (iii) l’intensité des lésions sur des images MR sont similaires à celles de structures visiblement saines. En plus de cela, réaliser une segmentation rigoureuse sur l’ensemble d’une base de données multi-centrique d’IRM est rendue difficile par l’importante variabilité des protocoles d’acquisition (e.g. résolution, orientation, champ de vue de l’image). Malgré de considérables récents développements dans le traitement d’images MR de moelle épinière, il n’y a toujours pas de méthode disponible pouvant fournir une segmentation rigoureuse et fiable de la moelle épinière pour un large spectre de pathologies et de protocoles d’acquisition. Concernant les lésions intramédullaires, une recherche approfondie dans la littérature n’a pas pu fournir une méthode disponible de segmentation automatique. Objectif: Développer un système complètement automatique pour segmenter la moelle épinière et les lésions intramédullaires sur des IRM conventionnelles humaines. Méthode: L’approche présentée est basée de deux réseaux de neurones à convolution mis en cascade. La méthode a été pensée pour faire face aux principaux obstacles que présentent les données IRM de moelle épinière. Le procédé de segmentation a été entrainé et validé sur une base de données privée composée de 1943 images, acquises dans 30 différents centres avec des protocoles hétérogènes. Les sujets scannés comportent 459 sujets sains, 471 patients SEP et 112 avec d’autres pathologies affectant la moelle épinière. Le module de segmentation de la moelle épinière a été comparé à une méthode existante reconnue par la communauté, PropSeg. Résultats: L’approche basée sur les réseaux de neurones à convolution a fourni de meilleurs résultats que PropSeg, atteignant un Dice médian (intervalle inter-quartiles) de 94.6 (4.6) vs. 87.9 (18.3) %. Pour les lésions, notre segmentation automatique a permis d'obtenir un Dice de 60.0 (21.4) % en le comparant à la segmentation manuelle, un ratio de vrai positifs de 83 (34) %, et une précision de 77 (44) %. Conclusion: Une méthode complètement automatique et innovante pour segmenter la moelle épinière et les lésions SEP intramédullaires sur des données IRM a été conçue durant ce projet de maîtrise. La méthode a été abondamment validée sur une base de données clinique. La robustesse de la méthode de segmentation de moelle épinière a été démontrée, même sur des cas pathologiques. Concernant la segmentation des lésions, les résultats sont encourageants, malgré un taux de faux positifs relativement élevé. Je crois en l’impact que peut potentiellement avoir ces outils pour la communauté de chercheurs. Dans cette optique, les méthodes ont été intégrées et documentées dans un logiciel en accès-ouvert, la “Spinal Cord Toolbox”. Certains des outils développés pendant ce projet de Maîtrise sont déjà utilisés par des analyses d’études cliniques, portant sur des patients SEP et sclérose latérale amyotrophique.----------ABSTRACT Context: The spinal cord is a key component of the central nervous system, which contains neurons responsible for complex functions, and ensures the conduction of motor and sensory information between the brain and the peripheral nervous system. Damage to the spinal cord, through trauma or neurodegenerative diseases, can lead to severe impairment, including functional disabilities, paralysis and/or pain. In multiple sclerosis (MS) patients, the spinal cord is frequently affected by atrophy and/or lesions. Conventional magnetic resonance imaging (MRI) is widely used by researchers and clinicians to non-invasively assess and characterize spinal cord microstructural changes. Quantitative assessment of the structural damage to the spinal cord (e.g. atrophy severity, lesion extent) is essential for the diagnosis, prognosis and longitudinal monitoring of diseases, such as MS. Furthermore, the development of objective biomarkers is essential to evaluate the effect of new therapeutic treatments. Spinal cord and intramedullary MS lesions segmentation is consequently clinically relevant, as well as a necessary step towards the interpretation of multi-parametric MR images. However, manual segmentation is highly time-consuming, tedious and prone to intra- and inter-rater variability. There is therefore a need for automated segmentation methods to facilitate the efficiency of analysis pipelines. Automatic lesion segmentation is challenging for various reasons: (i) lesion variability in terms of shape, size and location, (ii) lesion boundaries are most of the time not well defined, (iii) lesion intensities on MR data are confounding with those of normal-appearing structures. Moreover, achieving robust segmentation across multi-center MRI data is challenging because of the broad variability of data features (e.g. resolution, orientation, field of view). Despite recent substantial developments in spinal cord MRI processing, there is still no method available that can yield robust and reliable spinal cord segmentation across the very diverse spinal pathologies and data features. Regarding the intramedullary lesions, a thorough search of the relevant literature did not yield available method of automatic segmentation. Goal: To develop a fully-automatic framework for segmenting the spinal cord and intramedullary MS lesions from conventional human MRI data. Method: The presented approach is based on a cascade of two Convolutional Neural Networks (CNN). The method has been designed to face the main challenges of ‘real world’ spinal cord MRI data. It was trained and validated on a private dataset made up of 1943 MR volumes, acquired in different 30 sites with heterogeneous acquisition protocols. Scanned subjects involve 459 healthy controls, 471 MS patients and 112 with other spinal pathologies. The proposed spinal cord segmentation method was compared to a state-of-the-art spinal cord segmentation method, PropSeg. Results: The CNN-based approach achieved better results than PropSeg, yielding a median (interquartile range) Dice of 94.6 (4.6) vs. 87.9 (18.3) % when compared to the manual segmentation. For the lesion segmentation task, our method provided a median Dice-overlap with the manual segmentation of 60.0 (21.4) %, a lesion-based true positive rate of 83 (34) % and a lesion-based precision de 77 (44) %. Conclusion: An original fully-automatic method to segment the spinal cord and intramedullary MS lesions on MRI data has been devised during this Master’s project. The method was validated extensively against a clinical dataset. The robustness of the spinal cord segmentation has been demonstrated, even on challenging pathological cases. Regarding the lesion segmentation, the results are encouraging despite the fairly high false positive rate. I believe in the potential value of these developed tools for the research community. In this vein, the methods are integrated and documented into an open-source software, the Spinal Cord Toolbox. Some of the tools developed during this Master’s project are already integrated into automated analysis pipelines of clinical studies, including MS and Amyotrophic Lateral Sclerosis patients

SoftSeg: Advantages of soft versus binary training for image segmentation

Most image segmentation algorithms are trained on binary masks formulated as a classification task per pixel. However, in applications such as medical imaging, this "black-and-white" approach is too constraining because the contrast between two tissues is often ill-defined, i.e., the voxels located on objects' edges contain a mixture of tissues. Consequently, assigning a single "hard" label can result in a detrimental approximation. Instead, a soft prediction containing non-binary values would overcome that limitation. We introduce SoftSeg, a deep learning training approach that takes advantage of soft ground truth labels, and is not bound to binary predictions. SoftSeg aims at solving a regression instead of a classification problem. This is achieved by using (i) no binarization after preprocessing and data augmentation, (ii) a normalized ReLU final activation layer (instead of sigmoid), and (iii) a regression loss function (instead of the traditional Dice loss). We assess the impact of these three features on three open-source MRI segmentation datasets from the spinal cord gray matter, the multiple sclerosis brain lesion, and the multimodal brain tumor segmentation challenges. Across multiple cross-validation iterations, SoftSeg outperformed the conventional approach, leading to an increase in Dice score of 2.0% on the gray matter dataset (p=0.001), 3.3% for the MS lesions, and 6.5% for the brain tumors. SoftSeg produces consistent soft predictions at tissues' interfaces and shows an increased sensitivity for small objects. The richness of soft labels could represent the inter-expert variability, the partial volume effect, and complement the model uncertainty estimation. The developed training pipeline can easily be incorporated into most of the existing deep learning architectures. It is already implemented in the freely-available deep learning toolbox ivadomed (https://ivadomed.org)

Automatic multiclass intramedullary spinal cord tumor segmentation on MRI with deep learning

Spinal cord tumors lead to neurological morbidity and mortality. Being able to obtain morphometric quantification (size, location, growth rate) of the tumor, edema, and cavity can result in improved monitoring and treatment planning. Such quantification requires the segmentation of these structures into three separate classes. However, manual segmentation of three-dimensional structures is time consuming, tedious and prone to intra- and inter-rater variability, motivating the development of automated methods. Here, we tailor a model adapted to the spinal cord tumor segmentation task. Data were obtained from 343 patients using gadolinium-enhanced T1-weighted and T2-weighted MRI scans with cervical, thoracic, and/or lumbar coverage. The dataset includes the three most common intramedullary spinal cord tumor types: astrocytomas, ependymomas, and hemangioblastomas. The proposed approach is a cascaded architecture with U-Net-based models that segments tumors in a two-stage process: locate and label. The model first finds the spinal cord and generates bounding box coordinates. The images are cropped according to this output, leading to a reduced field of view, which mitigates class imbalance. The tumor is then segmented. The segmentation of the tumor, cavity, and edema (as a single class) reached 76.7 ± 1.5% of Dice score and the segmentation of tumors alone reached 61.8 ± 4.0% Dice score. The true positive detection rate was above 87% for tumor, edema, and cavity. To the best of our knowledge, this is the first fully automatic deep learning model for spinal cord tumor segmentation. The multiclass segmentation pipeline is available in the Spinal Cord Toolbox (https://spinalcordtoolbox.com/). It can be run with custom data on a regular computer within seconds

2D multi-class model for gray and white matter segmentation of the cervical spinal cord at 7T

8 pages, 5 figuresThe spinal cord (SC), which conveys information between the brain and the peripheral nervous system, plays a key role in various neurological disorders such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS), in which both gray matter (GM) and white matter (WM) may be impaired. While automated methods for WM/GM segmentation are now largely available, these techniques, developed for conventional systems (3T or lower) do not necessarily perform well on 7T MRI data, which feature finer details, contrasts, but also different artifacts or signal dropout. The primary goal of this study is thus to propose a new deep learning model that allows robust SC/GM multi-class segmentation based on ultra-high resolution 7T T2*-w MR images. The second objective is to highlight the relevance of implementing a specific data augmentation (DA) strategy, in particular to generate a generic model that could be used for multi-center studies at 7T

Benefits of linear conditioning for segmentation using metadata

Medical images are often accompanied by metadata describing the image (vendor, acquisition parameters) and the patient (disease type or severity, demographics, genomics). This metadata is usually disregarded by image segmentation methods. In this work, we adapt a linear conditioning method called FiLM (Feature-wise Linear Modulation) for image segmentation tasks. This FiLM adaptation enables integrating metadata into segmentation models for better performance. We observed an average Dice score increase of 5.1% on spinal cord tumor segmentation when incorporating the tumor type with FiLM. The metadata modulates the segmentation process through low-cost affine transformations applied on feature maps which can be included in any neural network's architecture. Additionally, we assess the relevance of segmentation FiLM layers for tackling common challenges in medical imaging: training with limited or unbalanced number of annotated data, multi-class training with missing segmentations, and model adaptation to multiple tasks. Our results demonstrated the following benefits of FiLM for segmentation: FiLMed U-Net was robust to missing labels and reached higher Dice scores with few labels (up to 16.7%) compared to single-task U-Net. The code is open-source and available at www.ivadomed.org