Pitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: a report of the international immuno‐oncology biomarker working group

The clinical significance of the tumor-immune interaction in breast cancer (BC) has been well established, and tumor-infiltrating lymphocytes (TILs) have emerged as a predictive and prognostic biomarker for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2 negative) breast cancer (TNBC) and HER2-positive breast cancer. How computational assessment of TILs can complement manual TIL-assessment in trial- and daily practices is currently debated and still unclear. Recent efforts to use machine learning (ML) for the automated evaluation of TILs show promising results. We review state-of-the-art approaches and identify pitfalls and challenges by studying the root cause of ML discordances in comparison to manual TILs quantification. We categorize our findings into four main topics; (i) technical slide issues, (ii) ML and image analysis aspects, (iii) data challenges, and (iv) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns, or design choices in the computational implementation. To aid the adoption of ML in TILs assessment, we provide an in-depth discussion of ML and image analysis including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial- and routine clinical management of patients with TNBC

2D electromagnetic imaging by full waveform inversion : Multiparameter approach on synthetic cases and real data

Le radar géologique est une méthode d'investigation géophysique basée sur la propagation d'ondes électromagnétiques dans le sous-sol. Avec des fréquences allant de 5 MHz à quelques GHz et une forte sensibilité aux propriétés électriques, le géoradar fournit des images de réflectivité dans des contextes et à des échelles très variés : génie civil, géologie, hydrogéologie, glaciologie, archéologie. Cependant, dans certains cas, la compréhension fine des processus étudiés dans la subsurface nécessite une quantification des paramètres physiques du sous-sol. Dans ce but, l'inversion des formes d'ondes complètes, méthode initialement développée pour l'exploration sismique qui exploite l'ensemble des signaux enregistrés, pourrait s'avérer efficace. Dans cette thèse, je propose ainsi des développements méthodologiques par une approche d'inversion multiparamètres (permittivité diélectrique et conductivité), pour des configurations en transmission, en deux dimensions.Ces développements sont ensuite appliqués à un jeu de données réelles acquises entre forages.Dans une première partie, je présente tout d'abord la méthode numérique utilisée pour modéliser la propagation des ondes électromagnétiques dans un milieu 2D hétérogène, élément indispensable pour mener à bien le processus d'imagerie. Ensuite, j’introduis puis étudie le potentiel des méthodes d’optimisation locale standards (gradient conjugué non linéaire, l-BFGS, Newton tronqué dans ses versions Gauss-Newton et Exact-Newton) pour découpler la permittivité diélectrique et la conductivité électrique. Je montre notamment qu’un découplage effectif n’est possible qu’avec un modèle initial suffisamment précis et la méthode la plus sophistiquée (Newton tronqué). Comme dans le cas général, ce modèle initial n’est pas disponible, il s’avère nécessaire d'introduire un facteur d'échelle qui répartit le poids relatif de chaque classe de paramètres dans l'inversion. Dans un milieu réaliste avec une acquisition entre puits, je montre que les différentes méthodes d'optimisation donnent des résultats similaires en matière de découplage de paramètres. C'est finalement la méthode l-BFGS qui est retenue pour l'application aux données réelles, en raison de coûts de calcul plus faibles.Dans une deuxième partie, j'applique cette méthodologie à des données réelles acquises entre deux forages localisés dans des formations carbonatées, à Rustrel (France, 84). Cette inversion est réalisée en parallèle d'une approche synthétique à l'aide d'un modèle représentatif du site étudié et des configurations d'acquisition similaires. Ceci permet de pouvoir comprendre, contrôler et valider les observations et conclusions obtenues sur les données réelles. Cette démarche montre que la reconstruction de la permittivité est très robuste. A contrario, l'estimation de la conductivité souffre de deux couplages majeurs, avec la permittivité diélectrique, d'une part, et avec l'amplitude de la source estimée, d'autre part. Les résultats obtenus sont confrontés avec succès à des données indépendantes (géophysique depuis la surface, analyse sur échantillons de roche), et permet de bénéficier d'une image haute-résolution des formations géologiques. Enfin, une analyse 3D confirme que les structures 3D à fort contraste de propriétés, telles que la galerie enfouie sur notre site, nécessiteraient une approche de modélisation 3D, notamment pour mieux expliquer les amplitudes observées.Ground Penetrating Radar (GPR) is a geophysical investigation method based on electromagnetic waves propagation in the underground. With frequencies ranging from 5 MHz to a few GHz and a high sensitivity to electrical properties, GPR provides reflectivity images in a wide variety of contexts and scales: civil engineering, geology, hydrogeology, glaciology, archeology. However, in some cases, a better understanding of some subsurface processes requires a quantification of the physical parameters of the subsoil. For this purpose, inversion of full waveforms, a method initially developed for seismic exploration that exploits all the recorded signals, could prove effective. In this thesis, I propose methodological developments using a multiparameter inversion approach (dielectric permittivity and conductivity), for two-dimensional transmission configurations. These developments are then applied to a real data set acquired between boreholes.In a first part, I present the numerical method used to model the propagation of electromagnetic waves in a heterogeneous 2D environment, a much-needed element to carry out the process of imaging. Then, I introduce and study the potential of standard local optimization methods (nonlinear conjugate gradient, l-BFGS, Newton truncated in its Gauss-Newton and Exact-Newton versions) to fight the trade-off effects related to the dielectric permittivity and to the electrical conductivity. In particular, I show that effective decoupling is possible only with a sufficiently accurate initial model and the most sophisticated method (truncated Newton). As in the general case, this initial model is not available, it is necessary to introduce a scaling factor which distributes the relative weight of each parameter class in the inversion. In a realistic medium and for a cross-hole acquisition configuration, I show that the different optimization methods give similar results in terms of parameters decoupling. It is eventually the l-BFGS method that is used for the application to the real data, because of lower computation costs.In a second part, I applied the developed Full waveform inversion methodology to a set of real data acquired between two boreholes located in carbonate formations, in Rustrel (France, 84). This inversion is carried out together with a synthetic approach using a model representative of the studied site and with a similar acquisition configuration. This approach enables us to monitor and validate the observations and conclusions derived from data inversion. It shows that reconstruction of dielectrical permittivity is very robust. Conversely, conductivity estimation suffers from two major couplings: the permittivity and the amplitude of the estimated source. The derived results are successfully compared with independent data (surface geophysics and rock analysis on plugs) and provides a high resolution image of the geological formation. On the other hand, a 3D analysis confirms that 3D structures presenting high properties contrasts, such as the buried gallery present in our site, would require a 3D approach, notably to better explain the observed amplitudes

Imagerie électromagnétique 2D par inversion des formes d'ondes complètes : Approche multiparamètres sur cas synthétiques et données réelles

Ground Penetrating Radar (GPR) is a geophysical investigation method based on electromagnetic waves propagation in the underground. With frequencies ranging from 5 MHz to a few GHz and a high sensitivity to electrical properties, GPR provides reflectivity images in a wide variety of contexts and scales: civil engineering, geology, hydrogeology, glaciology, archeology. However, in some cases, a better understanding of some subsurface processes requires a quantification of the physical parameters of the subsoil. For this purpose, inversion of full waveforms, a method initially developed for seismic exploration that exploits all the recorded signals, could prove effective. In this thesis, I propose methodological developments using a multiparameter inversion approach (dielectric permittivity and conductivity), for two-dimensional transmission configurations. These developments are then applied to a real data set acquired between boreholes.In a first part, I present the numerical method used to model the propagation of electromagnetic waves in a heterogeneous 2D environment, a much-needed element to carry out the process of imaging. Then, I introduce and study the potential of standard local optimization methods (nonlinear conjugate gradient, l-BFGS, Newton truncated in its Gauss-Newton and Exact-Newton versions) to fight the trade-off effects related to the dielectric permittivity and to the electrical conductivity. In particular, I show that effective decoupling is possible only with a sufficiently accurate initial model and the most sophisticated method (truncated Newton). As in the general case, this initial model is not available, it is necessary to introduce a scaling factor which distributes the relative weight of each parameter class in the inversion. In a realistic medium and for a cross-hole acquisition configuration, I show that the different optimization methods give similar results in terms of parameters decoupling. It is eventually the l-BFGS method that is used for the application to the real data, because of lower computation costs.In a second part, I applied the developed Full waveform inversion methodology to a set of real data acquired between two boreholes located in carbonate formations, in Rustrel (France, 84). This inversion is carried out together with a synthetic approach using a model representative of the studied site and with a similar acquisition configuration. This approach enables us to monitor and validate the observations and conclusions derived from data inversion. It shows that reconstruction of dielectrical permittivity is very robust. Conversely, conductivity estimation suffers from two major couplings: the permittivity and the amplitude of the estimated source. The derived results are successfully compared with independent data (surface geophysics and rock analysis on plugs) and provides a high resolution image of the geological formation. On the other hand, a 3D analysis confirms that 3D structures presenting high properties contrasts, such as the buried gallery present in our site, would require a 3D approach, notably to better explain the observed amplitudes.Le radar géologique est une méthode d'investigation géophysique basée sur la propagation d'ondes électromagnétiques dans le sous-sol. Avec des fréquences allant de 5 MHz à quelques GHz et une forte sensibilité aux propriétés électriques, le géoradar fournit des images de réflectivité dans des contextes et à des échelles très variés : génie civil, géologie, hydrogéologie, glaciologie, archéologie. Cependant, dans certains cas, la compréhension fine des processus étudiés dans la subsurface nécessite une quantification des paramètres physiques du sous-sol. Dans ce but, l'inversion des formes d'ondes complètes, méthode initialement développée pour l'exploration sismique qui exploite l'ensemble des signaux enregistrés, pourrait s'avérer efficace. Dans cette thèse, je propose ainsi des développements méthodologiques par une approche d'inversion multiparamètres (permittivité diélectrique et conductivité), pour des configurations en transmission, en deux dimensions.Ces développements sont ensuite appliqués à un jeu de données réelles acquises entre forages.Dans une première partie, je présente tout d'abord la méthode numérique utilisée pour modéliser la propagation des ondes électromagnétiques dans un milieu 2D hétérogène, élément indispensable pour mener à bien le processus d'imagerie. Ensuite, j’introduis puis étudie le potentiel des méthodes d’optimisation locale standards (gradient conjugué non linéaire, l-BFGS, Newton tronqué dans ses versions Gauss-Newton et Exact-Newton) pour découpler la permittivité diélectrique et la conductivité électrique. Je montre notamment qu’un découplage effectif n’est possible qu’avec un modèle initial suffisamment précis et la méthode la plus sophistiquée (Newton tronqué). Comme dans le cas général, ce modèle initial n’est pas disponible, il s’avère nécessaire d'introduire un facteur d'échelle qui répartit le poids relatif de chaque classe de paramètres dans l'inversion. Dans un milieu réaliste avec une acquisition entre puits, je montre que les différentes méthodes d'optimisation donnent des résultats similaires en matière de découplage de paramètres. C'est finalement la méthode l-BFGS qui est retenue pour l'application aux données réelles, en raison de coûts de calcul plus faibles.Dans une deuxième partie, j'applique cette méthodologie à des données réelles acquises entre deux forages localisés dans des formations carbonatées, à Rustrel (France, 84). Cette inversion est réalisée en parallèle d'une approche synthétique à l'aide d'un modèle représentatif du site étudié et des configurations d'acquisition similaires. Ceci permet de pouvoir comprendre, contrôler et valider les observations et conclusions obtenues sur les données réelles. Cette démarche montre que la reconstruction de la permittivité est très robuste. A contrario, l'estimation de la conductivité souffre de deux couplages majeurs, avec la permittivité diélectrique, d'une part, et avec l'amplitude de la source estimée, d'autre part. Les résultats obtenus sont confrontés avec succès à des données indépendantes (géophysique depuis la surface, analyse sur échantillons de roche), et permet de bénéficier d'une image haute-résolution des formations géologiques. Enfin, une analyse 3D confirme que les structures 3D à fort contraste de propriétés, telles que la galerie enfouie sur notre site, nécessiteraient une approche de modélisation 3D, notamment pour mieux expliquer les amplitudes observées

2D frequency-domain full-waveform inversion of GPR data: Permittivity and conductivity imaging

International audienceFull waveform inversion of Ground Penetrating Radar data is a promising and challenging technique. As both dielectric permittivity and electrical conductivity should be recovered, the associated inverse problem is intrinsically multi-parameter. It requires to properly account for the influence of the Hessian matrix to mitigate the trade-offs between constitutive parameters. Recently, a first step in this direction was performed with the l-BFGS quasi-Newton method, which is based on an approximation of the inverse Hessian computed from previous gradient estimations. We propose to go further in solving locally the Newton equation related to the optimization workflow. For this purpose, we implement the truncated Newton method where the computation of the gradient and Hessian-vector products are respectively based on first-order and second-order adjoint state methods. On a synthetic case study, using the TE mode with borehole and surface acquisitions, we compare our results with those obtained using the l-BFGS method and we show an improvement in the precision of reconstructed parameters. A better decoupling between the two parameters is obtained with the truncated Newton method

Study of catalyst deactivation during 1,3-butanediol dehydration to produce butadiene

Catalyst deactivation and mechanism of coke formation during the gas phase dehydration of 1,3-butanediol were studied on solid acids of different nature: Al2O3, SiO2/Al2O3, HZSM5 and tungstophosphoric acid (TPA) supported on SiO2. All the catalysts deactivated on stream with a significant coke content ranged between 9% and 14% C. Fresh and spent catalysts as well as carbonaceous deposits were thoroughly characterized using different techniques such as N2 physisorption, FTIR spectroscopy, FTIR of adsorbed pyridine, DSC-TGA, GC-MS and MALDI-TOF MS (matrix-assisted laser desorption/ionization time of flight mass spectrometry). The IR spectra of spent and washed (after direct extraction with CH2Cl2) samples and the superficial soluble coke characterized by MALDI-TOF MS showed the different nature of coke formed in each catalyst with carbonaceous products of higher molecular weights on HZSM5 and TPA/SiO2 than on Al2O3 and SiO2/Al2O3. After catalyst dissolution using hydrofluoric acid and extraction with CH2Cl2 both total soluble and insoluble coke were analyzed. Insoluble coke was only detected on TPA/SiO2 and it was attributed to the strength of its Brønsted acid sites. GC-MS chromatograms of total soluble coke showed the presence of aromatic and polyromantic species, that were very alkylated in the case of HZSM5. Particularly, the well differentiated nature of coke on HZSM5 including alkylnaftalenes and alkylantracenes suggested the coke formation by a shape selectivity mechanism.Fil: Rodríguez, Andrea Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigaciones en Catálisis y Petroquímica "Ing. José Miguel Parera". Universidad Nacional del Litoral. Instituto de Investigaciones en Catálisis y Petroquímica "Ing. José Miguel Parera"; ArgentinaFil: Sad, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigaciones en Catálisis y Petroquímica "Ing. José Miguel Parera". Universidad Nacional del Litoral. Instituto de Investigaciones en Catálisis y Petroquímica "Ing. José Miguel Parera"; ArgentinaFil: Cruchade, Hugo. Université de Poitiers; FranciaFil: Pinard, Ludovic. Université de Poitiers; FranciaFil: Padro, Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigaciones en Catálisis y Petroquímica "Ing. José Miguel Parera". Universidad Nacional del Litoral. Instituto de Investigaciones en Catálisis y Petroquímica "Ing. José Miguel Parera"; Argentin

Full-waveform inversion of GPR data acquired between boreholes in Rustrel carbonates

ACTInternational audienceFull waveform inversion (FWI) of seismic or Ground Penetrating Radar data provides high-resolution quantitative images of the constitutive parameters of the rock/soil which control seismic/GPR wave propagation. We developed a 2D inversion tool in the frequency domain adapted to the multi-parameter physics controlling GPR propagation in isotropic non dispersive media, i.e. dielectric permittivity and electrical conductivity. This inversion engine was previously tested using synthetic 2D data to mitigate the trade-off between the two parameter classes. In this paper, we present the required processing techniques and first inversion results obtained on a real GPR dataset acquired in carbonates with a cross-hole configuration. The presence of the 2m diameter underground gallery at depth constitutes a nice target to test the robustness, efficiency and resolution of the inversion in such high-contrasts context. Starting from a time tomographic image for the dielectric permittivity and from a homogeneous conductivity, we show that FWI is efficient to retrieve high resolution images of dielectric permittivity but struggles with electrical conductivity. As a quality control, we compare real and synthetic radargrams computed from the tomography and final images, showing the efficiency of the process to reconstruct some events but also underlying some issues, particularly on large incidence angles amplitude traces. © 2016 The Authors, published by EDP Sciences

Simultaneous GPR Reconstruction of Electrical Conductivity and Permittivity

International audienceGround-penetrating radar (GPR) is a non-invasive prospecting technique based on the electromagnetic waves sampling of the near surface. Building quantitative images through these waves requires the reconstruction of both electrical permittivity and conductivity. This multi-parameter reconstruction is performed through the minimization of a misfit function measuring the discrepancy between observed and synthetic data. The minimization is achieved with a local descent method based on the Newton equation. Both the gradient and the product of the Hessian matrix with a model vector are necessary for avoiding any trade-off between parameter classes, especially when high contrasts are encountered by electromagnetic waves. This presentation is devoted to the design of these two key ingredients needed when updating the model, based on efficient first- and second-order adjoint methods. We formulate the problem in the frequency domain and we show that we need two forward modeling for the gradient and two additional forward modeling for the product of the Hessian matrix and a model vector. Our formulation is such that these quantities are obtained through solution fields, regardless of the numerical scheme used to obtain them

Full-waveform inversion of GPR data acquired between boreholes in Rustrel carbonates

Full waveform inversion (FWI) of seismic or Ground Penetrating Radar data provides high-resolution quantitative images of the constitutive parameters of the rock/soil which control seismic/GPR wave propagation. We developed a 2D inversion tool in the frequency domain adapted to the multi-parameter physics controlling GPR propagation in isotropic non dispersive media, i.e. dielectric permittivity and electrical conductivity. This inversion engine was previously tested using synthetic 2D data to mitigate the trade-off between the two parameter classes. In this paper, we present the required processing techniques and first inversion results obtained on a real GPR dataset acquired in carbonates with a cross-hole configuration. The presence of the 2 m diameter underground gallery at depth constitutes a nice target to test the robustness, efficiency and resolution of the inversion in such high-contrasts context. Starting from a time tomographic image for the dielectric permittivity and from a homogeneous conductivity, we show that FWI is efficient to retrieve high resolution images of dielectric permittivity but struggles with electrical conductivity. As a quality control, we compare real and synthetic radargrams computed from the tomography and final images, showing the efficiency of the process to reconstruct some events but also underlying some issues, particularly on large incidence angles amplitude traces

Green-aromatic production in typical conditions of fluidized catalytic cracking

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Catalytic Routes for Direct Methane Conversion to Hydrocarbons and Hydrogen: Current State and Opportunities

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