Prior Knowledge, Random Walks and Human Skeletal Muscle Segmentation

International audienceIn this paper, we propose a novel approach for segmenting the skeletal muscles in MRI automatically. In order to deal with the absence of contrast between the different muscle classes, we proposed a principled mathematical formulation that integrates prior knowledge with a random walks graph-based formulation. Prior knowledge is repre- sented using a statistical shape atlas that once coupled with the random walks segmentation leads to an efficient iterative linear optimization sys- tem. We reveal the potential of our approach on a challenging set of real clinical data

Automatic skeletal muscle segmentation through random walks and graph-based seed placement

International audienceIn this paper we propose a novel skeletal muscle segmentation method driven from discrete optimization. We introduce a graphical model that is able to automatically determine appropriate seed positions with respect to the different muscle classes. This is achieved by taking into account the expected local visual and geometric properties of the seeds through a pair-wise Markov Random Field. The outcome of this optimization process is fed to a powerful graphbased diffusion segmentation method (random walker) that is able to produce very promising results through a fully automated approach. Validation on challenging data sets demonstrates the potentials of our method

Discriminative Parameter Estimation for Random Walks Segmentation

The Random Walks (RW) algorithm is one of the most e - cient and easy-to-use probabilistic segmentation methods. By combining contrast terms with prior terms, it provides accurate segmentations of medical images in a fully automated manner. However, one of the main drawbacks of using the RW algorithm is that its parameters have to be hand-tuned. we propose a novel discriminative learning framework that estimates the parameters using a training dataset. The main challenge we face is that the training samples are not fully supervised. Speci cally, they provide a hard segmentation of the images, instead of a proba- bilistic segmentation. We overcome this challenge by treating the opti- mal probabilistic segmentation that is compatible with the given hard segmentation as a latent variable. This allows us to employ the latent support vector machine formulation for parameter estimation. We show that our approach signi cantly outperforms the baseline methods on a challenging dataset consisting of real clinical 3D MRI volumes of skeletal muscles.Comment: Medical Image Computing and Computer Assisted Interventaion (2013

Discriminative Parameter Estimation for Random Walks Segmentation: Technical Report

The Random Walks (RW) algorithm is one of the most e - cient and easy-to-use probabilistic segmentation methods. By combining contrast terms with prior terms, it provides accurate segmentations of medical images in a fully automated manner. However, one of the main drawbacks of using the RW algorithm is that its parameters have to be hand-tuned. we propose a novel discriminative learning framework that estimates the parameters using a training dataset. The main challenge we face is that the training samples are not fully supervised. Speci cally, they provide a hard segmentation of the images, instead of a proba-bilistic segmentation. We overcome this challenge by treating the optimal probabilistic segmentation that is compatible with the given hard segmentation as a latent variable. This allows us to employ the latent support vector machine formulation for parameter estimation. We show that our approach signi cantly outperforms the baseline methods on a challenging dataset consisting of real clinical 3D MRI volumes of skeletal muscles

Early Toxicities After High Dose Rate Proton Therapy in Cancer Treatments

Background: The conventional dose rate of radiation therapy is 0.01-0.05 Gy per second. According to preclinical studies, an increased dose rate may offer similar anti-tumoral effect while dramatically improving normal tissue protection. This study aims at evaluating the early toxicities for patients irradiated with high dose rate pulsed proton therapy (PT). Materials and methods: A single institution retrospective chart review was performed for patients treated with high dose rate (10 Gy per second) pulsed proton therapy, from September 2016 to April 2020. This included both benign and malignant tumors with ≥3 months follow-up, evaluated for acute (≤2 months) and subacute (>2 months) toxicity after the completion of PT. Results: There were 127 patients identified, with a median follow up of 14.8 months (3-42.9 months). The median age was 55 years (1.6-89). The cohort most commonly consisted of benign disease (55.1%), cranial targets (95.1%), and were treated with surgery prior to PT (56.7%). There was a median total PT dose of 56 Gy (30-74 Gy), dose per fraction of 2 Gy (1-3 Gy), and CTV size of 47.6 ml (5.6-2,106.1 ml). Maximum acute grade ≥2 toxicity were observed in 49 (38.6%) patients, of which 8 (6.3%) experienced grade 3 toxicity. No acute grade 4 or 5 toxicity was observed. Maximum subacute grade 2, 3, and 4 toxicity were discovered in 25 (19.7%), 12 (9.4%), and 1 (0.8%) patient(s), respectively. Conclusion: In this cohort, utilizing high dose rate proton therapy (10 Gy per second) did not result in a major decrease in acute and subacute toxicity. Longer follow-up and comparative studies with conventional dose rate are required to evaluate whether this approach offers a toxicity benefit

Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa: The EMBASSY Study

Background Late-onset Pompe disease is characterized by progressive skeletal myopathy followed by respiratory muscle weakness, typically leading to loss of ambulation and respiratory failure. In this population, enzyme replacement therapy (ERT) with alglucosidase alfa has been shown to stabilize respiratory function and improve mobility and muscle strength. Muscle pathology and glycogen clearance from skeletal muscle in treatment-naïve adults after ERT have not been extensively examined. Methods This exploratory, open-label, multicenter study evaluated glycogen clearance in muscle tissue samples collected pre- and post- alglucosidase alfa treatment in treatment-naïve adults with late-onset Pompe disease. The primary endpoint was the quantitative reduction in percent tissue area occupied by glycogen in muscle biopsies from baseline to 6 months. Secondary endpoints included qualitative histologic assessment of tissue glycogen distribution, secondary pathology changes, assessment of magnetic resonance images (MRIs) for intact muscle and fatty replacement, and functional assessments. Results Sixteen patients completed the study. After 6 months of ERT, the percent tissue area occupied by glycogen in quadriceps and deltoid muscles decreased in 10 and 8 patients, respectively. No changes were detected on MRI from baseline to 6 months. A majority of patients showed improvements on functional assessments after 6 months of treatment. All treatment-related adverse events were mild or moderate. Conclusions This exploratory study provides novel insights into the histopathologic effects of ERT in late-onset Pompe disease patients. Ultrastructural examination of muscle biopsies demonstrated reduced lysosomal glycogen after ERT. Findings are consistent with stabilization of disease by ERT in treatment-naïve patients with late-onset Pompe disease

Kinetic analysis of the nucleic acid chaperone activity of the Hepatitis C virus core protein

The multifunctional HCV core protein consists of a hydrophilic RNA interacting D1 domain and a hydrophobic D2 domain interacting with membranes and lipid droplets. The core D1 domain was found to possess nucleic acid annealing and strand transfer properties. To further understand these chaperone properties, we investigated how the D1 domain and two peptides encompassing the D1 basic clusters chaperoned the annealing of complementary canonical nucleic acids that correspond to the DNA sequences of the HIV-1 transactivation response element TAR and its complementary cTAR. The core peptides were found to augment cTAR-dTAR annealing kinetics by at least three orders of magnitude. The annealing rate was not affected by modifications of the dTAR loop but was strongly reduced by stabilization of the cTAR stem ends, suggesting that the core-directed annealing reaction is initiated through the terminal bases of cTAR and dTAR. Two kinetic pathways were identified with a fast pre-equilibrium intermediate that then slowly converts into the final extended duplex. The fast and slow pathways differed by the number of base pairs, which should be melted to nucleate the intermediates. The three peptides operate similarly, confirming that the core chaperone properties are mostly supported by its basic clusters

De la segmentation au moyen de graphes d’images de muscles striés squelettiques acquises par RMN

Segmentation of magnetic resonance images (MRI) of skeletal striated muscles is of crucial interest when studying myopathies. Diseases understanding, therapeutic followups of patients, etc. rely on discriminating the muscles in MRI anatomical images. However, delineating the muscle contours manually is an extremely long and tedious task, and thus often a bottleneck in clinical research. Typical automatic segmentation methods rely on finding discriminative visual properties between objects of interest, accurate contour detection or clinically interesting anatomical points. Skeletal muscles show none of these features in MRI, making automatic segmentation a challenging problem. In spite of recent advances on segmentation methods, their application in clinical settings is difficult, and most of the times, manual segmentation and correction is still the only option. In this thesis, we propose several approaches for segmenting skeletal muscles automatically in MRI, all related to the popular graph-based Random Walker (RW) segmentation algorithm. The strength of the RW method relies on its robustness in the case of weak contours and its fast and global optimization. Originally, the RW algorithm was developed for interactive segmentation: the user had to pre-segment small regions of the image – called seeds – before running the algorithm which would then complete the segmentation. Our first contribution is a method for automatically generating and labeling all the appropriate seeds, based on a Markov Random Fields formulation integrating prior knowledge of the relative positions, and prior detection of contours between pairs of seeds. A second contribution amounts to incorporating prior knowledge of the shape directly into the RW framework. Such formulation retains the probabilistic interpretation of the RW algorithm and thus allows to compute the segmentation by solving a large but simple sparse linear system, like in the original method. In a third contribution, we propose to develop a learning framework to estimate the optimal set of parameters for balancing the contrast term of the RW algorithm and the different existing prior models. The main challenge we face is that the training samples are not fully supervised. Specifically, they provide a hard segmentation of the medical images, instead of the optimal probabilistic segmentation, which corresponds to the desired output of the RW algorithm. We overcome this challenge by treating the optimal probabilistic segmentation as a latent variable. This allows us to employ the latent Support Vector Machine (latent SVM) formulation for parameter estimation. All proposed methods are tested and validated on real clinical datasets of MRI volumes of lower limbs.La segmentation d’images anatomiques de muscles striés squelettiques acquises par résonance magnétique nucléaire (IRM) présente un grand intérêt pour l’étude des myopathies. Elle est souvent un préalable nécessaire pour l’étude les mécanismes d’une maladie, ou pour le suivi thérapeutique des patients. Cependant, le détourage manuel des muscles est un travail long et fastidieux, au point de freiner les recherches cliniques qui en dépendent. Il est donc nécessaire d’automatiser cette étape. Les méthodes de segmentation automatique se basent en général sur les différences d’aspect visuel des objets à séparer et sur une détection précise des contours ou de points de repère anatomiques pertinents. L’IRM du muscle ne permettant aucune de ces approches, la segmentation automatique représente un défi de taille pour les chercheurs. Dans ce rapport de thèse, nous présentons plusieurs méthodes de segmentation d’images de muscles, toutes en rapport avec l’algorithme dit du marcheur aléatoire (MA). L’algorithme du MA, qui utilise une représentation en graphe de l’image, est connu pour être robuste dans les cas où les contours des objets sont manquants ou incomplets et pour son optimisation numérique rapide et globale. Dans sa version initiale, l’utilisateur doit d’abord segmenter de petites portions de chaque région de l’image, appelées graines, avant de lancer l’algorithme pour compléter la segmentation. Notre première contribution au domaine est un algorithme permettant de générer et d’étiqueter automatiquement toutes les graines nécessaires à la segmentation. Cette approche utilise une formulation en champs aléatoires de Markov, intégrant une connaissance à priori de l’anatomie et une détection préalable des contours entre des paires de graines. Une deuxième contribution vise à incorporer directement la connaissance à priori de la forme des muscles à la méthode du MA. Cette approche conserve l’interprétation probabiliste de l’algorithme original, ce qui permet de générer une segmentation en résolvant numériquement un grand système linéaire creux. Nous proposons comme dernière contribution un cadre d’apprentissage pour l’estimation du jeu de paramètres optimaux régulant l’influence du terme de contraste de l’algorithme du MA ainsi que des différents modèles de connaissance à priori. La principale difficulté est que les données d’apprentissage ne sont pas entièrement supervisées. En effet, l’utilisateur ne peut fournir qu’une segmentation déterministe de l’image, et non une segmentation probabiliste comme en produit l’algorithme du MA. Cela nous amène à faire de la segmentation probabiliste optimale une variable latente, et ainsi à formuler le problème d’estimation sous forme d’une machine à vecteurs de support latents (latent SVM). Toutes les méthodes proposées sont testées et validées sur des volumes de muscles squelettiques acquis par IRM dans un cadre clinique

Graph- based segmentation of skeletal striated muscles in NMR images

La segmentation d’images anatomiques de muscles striés squelettiques acquises par résonance magnétique nucléaire (IRM) présente un grand intérêt pour l’étude des myopathies. Elle est souvent un préalable nécessaire pour l’étude les mécanismes d’une maladie, ou pour le suivi thérapeutique des patients. Cependant, le détourage manuel des muscles est un travail long et fastidieux, au point de freiner les recherches cliniques qui en dépendent. Il est donc nécessaire d’automatiser cette étape. Les méthodes de segmentation automatique se basent en général sur les différences d’aspect visuel des objets à séparer et sur une détection précise des contours ou de points de repère anatomiques pertinents. L’IRM du muscle ne permettant aucune de ces approches, la segmentation automatique représente un défi de taille pour les chercheurs. Dans ce rapport de thèse, nous présentons plusieurs méthodes de segmentation d’images de muscles, toutes en rapport avec l’algorithme dit du marcheur aléatoire (MA). L’algorithme du MA, qui utilise une représentation en graphe de l’image, est connu pour être robuste dans les cas où les contours des objets sont manquants ou incomplets et pour son optimisation numérique rapide et globale. Dans sa version initiale, l’utilisateur doit d’abord segmenter de petites portions de chaque région de l’image, appelées graines, avant de lancer l’algorithme pour compléter la segmentation. Notre première contribution au domaine est un algorithme permettant de générer et d’étiqueter automatiquement toutes les graines nécessaires à la segmentation. Cette approche utilise une formulation en champs aléatoires de Markov, intégrant une connaissance à priori de l’anatomie et une détection préalable des contours entre des paires de graines. Une deuxième contribution vise à incorporer directement la connaissance à priori de la forme des muscles à la méthode du MA. Cette approche conserve l’interprétation probabiliste de l’algorithme original, ce qui permet de générer une segmentation en résolvant numériquement un grand système linéaire creux. Nous proposons comme dernière contribution un cadre d’apprentissage pour l’estimation du jeu de paramètres optimaux régulant l’influence du terme de contraste de l’algorithme du MA ainsi que des différents modèles de connaissance à priori. La principale difficulté est que les données d’apprentissage ne sont pas entièrement supervisées. En effet, l’utilisateur ne peut fournir qu’une segmentation déterministe de l’image, et non une segmentation probabiliste comme en produit l’algorithme du MA. Cela nous amène à faire de la segmentation probabiliste optimale une variable latente, et ainsi à formuler le problème d’estimation sous forme d’une machine à vecteurs de support latents (latent SVM). Toutes les méthodes proposées sont testées et validées sur des volumes de muscles squelettiques acquis par IRM dans un cadre clinique.Segmentation of magnetic resonance images (MRI) of skeletal striated muscles is of crucial interest when studying myopathies. Diseases understanding, therapeutic followups of patients, etc. rely on discriminating the muscles in MRI anatomical images. However, delineating the muscle contours manually is an extremely long and tedious task, and thus often a bottleneck in clinical research. Typical automatic segmentation methods rely on finding discriminative visual properties between objects of interest, accurate contour detection or clinically interesting anatomical points. Skeletal muscles show none of these features in MRI, making automatic segmentation a challenging problem. In spite of recent advances on segmentation methods, their application in clinical settings is difficult, and most of the times, manual segmentation and correction is still the only option. In this thesis, we propose several approaches for segmenting skeletal muscles automatically in MRI, all related to the popular graph-based Random Walker (RW) segmentation algorithm. The strength of the RW method relies on its robustness in the case of weak contours and its fast and global optimization. Originally, the RW algorithm was developed for interactive segmentation: the user had to pre-segment small regions of the image – called seeds – before running the algorithm which would then complete the segmentation. Our first contribution is a method for automatically generating and labeling all the appropriate seeds, based on a Markov Random Fields formulation integrating prior knowledge of the relative positions, and prior detection of contours between pairs of seeds. A second contribution amounts to incorporating prior knowledge of the shape directly into the RW framework. Such formulation retains the probabilistic interpretation of the RW algorithm and thus allows to compute the segmentation by solving a large but simple sparse linear system, like in the original method. In a third contribution, we propose to develop a learning framework to estimate the optimal set of parameters for balancing the contrast term of the RW algorithm and the different existing prior models. The main challenge we face is that the training samples are not fully supervised. Specifically, they provide a hard segmentation of the medical images, instead of the optimal probabilistic segmentation, which corresponds to the desired output of the RW algorithm. We overcome this challenge by treating the optimal probabilistic segmentation as a latent variable. This allows us to employ the latent Support Vector Machine (latent SVM) formulation for parameter estimation. All proposed methods are tested and validated on real clinical datasets of MRI volumes of lower limbs