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Publication# Optimization of the Distance between Cylindrical Light Distributors Used for Interstitial Light Delivery in Biological Tissues

Résumé

Cylindrical light diffusers (CLDs) are often employed for the treatment of large tumors by interstitial photodynamic therapy (iPDT) and photoimmunotherapy (PIT), which involves careful treatment planning to maximize therapeutic dose coverage while minimizing the number of CLDs used. There is, however, a lack of general guidelines regarding optimal positioning of CLDs, in particular when they are inserted in parallel to treat head and neck squamous cell cancer (HNSCC). Therefore, the purpose of this study is to determine the CLD-CLD distances maximizing the necrosis for different geometries of CLD positions and shed light on the influence of different optical parameters on this distance, in particular when HNSCCs are treated by interstitial PIT with cetuximab-IR700 using up to seven CLDs. To that end, Monte-Carlo simulations of the light propagation around CLDs inserted perpendicularly in a semi-infinite tumor were performed to determine the volume receiving a fluence larger than a therapeutic threshold. An optimization algorithm was then used to calculate and maximize the necrosed tumor volumes. Tumor optical properties were derived from published data. Our findings suggest that optimal CLD positioning maximizing the volume of necrosed tumor during interstitial PIT for typical HNSCC optical properties corresponds to a CLD-CLD distance between 11.5- and 13-mm. Variations of the absorption and reduced scattering coefficients have the greatest influence on CLD placements, while tissue anisotropy factor, CLD insertion geometry, CLD length, and the angular dependence of the radiance emitted by the CLDs have minimal influence. At first approximation the influence of these optical parameters on optimal CLD-CLD distance are independent. Our data also suggests it is possible to derive new treatment plans using knowledge of previous treatment plans.

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Thérapie photodynamique

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Optimisation (mathématiques)

L'optimisation est une branche des mathématiques cherchant à modéliser, à analyser et à résoudre analytiquement ou numériquement les problèmes qui consistent à minimiser ou maximiser une fonction sur

Lumière

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Dans son sens le plus habituel, la lumière est le phénomène à l'origine d'une sensation visuelle. La physique montre qu'il s'agit d'ondes électromagnétiq

We have developed a new derivative-free algorithm based on Radial Basis Functions (RBFs). Derivative-free optimization is an active field of research and several algorithms have been proposed recently. Problems of this nature in the industrial setting are quite frequent. The reason is that in a number of applications the optimization process contains simulation packages which are treated as black boxes. The development of our own algorithm was originally motivated by an application in biomedical imaging: the medical image registration problem. The particular characteristics of this problem have incited us to develop a new optimization algorithm based on trust-region methods. However it has been designed to be generic and to be applied to a wide range of problems. The main originality of our approach is the use of RBFs to build the models. In particular we have adapted the existing theory based on quadratic models to our own models and developed new procedures especially designed for models based on RBFs. We have tested our algorithm called BOOSTERS against state-of-the-art methods (UOBYQA, NEWUOA, DFO). On the medical image registration problem, BOOSTERS appears to be the method of choice. The tests on problems from the CUTEr collection show that BOOSTERS is comparable to, but not better than other methods on small problems (size 2-20). It is performing very well for medium size problems (20-80). Moreover, it is able to solve problems of dimension 200, which is considered very large in derivative-free optimization. We have also developed a new class of algorithms combining the robustness of derivative-free algorithms with the faster rate of convergence characterizing Newtonlike-methods. In fact, they define a new class of algorithms lying between derivative-free optimization and quasi-Newton methods. These algorithms are built on the skeleton of our derivative-free algorithm but they can incorporate the gradient when it is available. They can be interpreted as a way of doping derivative-free algorithms with derivatives. If the derivatives are available at each iteration, then our method can be seen as an alternative to quasi-Newton methods. At the opposite, if the derivatives are never evaluated, then the algorithm is totally similar to BOOSTERS. It is a very interesting alternative to existing methods for problems whose objective function is expensive to evaluate and when the derivatives are not available. In this situation, the gradient can be approximated by finite differences and its costs corresponds to n additional function evaluations assuming that Rn is the domain of definition of the objective function. We have compared our method with CFSQP and BTRA, two gradient-based algorithms, and the results show that our doped method performs best. We have also a theoretical analysis of the medical image registration problem based on maximization of mutual information. Most of the current research in this field is concentrated on registration based on nonlinear image transformation. However, little attention has been paid to the theoretical properties of the optimization problem. In our analysis, we focus on the continuity and the differentiability of the objective function. We show in particular that performing a registration without extension of the reference image may lead to discontinuities in the objective function. But we demonstrate that, under some mild assumptions, the function is differentiable almost everywhere. Our analysis is important from an optimization point of view and conditions the choice of a solver. The usual practice is to use generic optimization packages without worrying about the differentiability of the objective function. But the use of gradient-based methods when the objective function is not differentiable may result in poor performance or even in absence of convergence. One of our objectives with this analysis is also that practitioners become aware of these problems and to propose them new algorithms having a potential interest for their applications.

Machine Learning is a modern and actively developing field of computer science, devoted to extracting and estimating dependencies from empirical data. It combines such fields as statistics, optimization theory and artificial intelligence. In practical tasks, the general aim of Machine Learning is to construct algorithms able to generalize and predict in previously unseen situations based on some set of examples. Given some finite information, Machine Learning provides ways to exract knowledge, describe, explain and predict from data. Kernel Methods are one of the most successful branches of Machine Learning. They allow applying linear algorithms with well-founded properties such as generalization ability, to non-linear real-life problems. Support Vector Machine is a well-known example of a kernel method, which has found a wide range of applications in data analysis nowadays. In many practical applications, some additional prior knowledge is often available. This can be the knowledge about the data domain, invariant transformations, inner geometrical structures in data, some properties of the underlying process, etc. If used smartly, this information can provide significant improvement to any data processing algorithm. Thus, it is important to develop methods for incorporating prior knowledge into data-dependent models. The main objective of this thesis is to investigate approaches towards learning with kernel methods using prior knowledge. Invariant learning with kernel methods is considered in more details. In the first part of the thesis, kernels are developed which incorporate prior knowledge on invariant transformations. They apply when the desired transformation produce an object around every example, assuming that all points in the given object share the same class. Different types of objects, including hard geometrical objects and distributions are considered. These kernels were then applied for images classification with Support Vector Machines. Next, algorithms which specifically include prior knowledge are considered. An algorithm which linearly classifies distributions by their domain was developed. It is constructed such that it allows to apply kernels to solve non-linear tasks. Thus, it combines the discriminative power of support vector machines and the well-developed framework of generative models. It can be applied to a number of real-life tasks which include data represented as distributions. In the last part of the thesis, the use of unlabelled data as a source of prior knowledge is considered. The technique of modelling the unlabelled data with a graph is taken as a baseline from semi-supervised manifold learning. For classification problems, we use this apporach for building graph models of invariant manifolds. For regression problems, we use unlabelled data to take into account the inner geometry of the input space. To conclude, in this thesis we developed a number of approaches for incorporating some prior knowledge into kernel methods. We proposed invariant kernels for existing algorithms, developed new algorithms and adapted a technique taken from semi-supervised learning for invariant learning. In all these cases, links with related state-of-the-art approaches were investigated. Several illustrative experiments were carried out on real data on optical character recognition, face image classification, brain-computer interfaces, and a number of benchmark and synthetic datasets.

Machine Learning is a modern and actively developing field of computer science, devoted to extracting and estimating dependencies from empirical data. It combines such fields as statistics, optimization theory and artificial intelligence. In practical tasks, the general aim of Machine Learning is to construct algorithms able to generalize and predict in previously unseen situations based on some set of examples. Given some finite information, Machine Learning provides ways to exract knowledge, describe, explain and predict from data. Kernel Methods are one of the most successful branches of Machine Learning. They allow applying linear algorithms with well-founded properties such as generalization ability, to non-linear real-life problems. Support Vector Machine is a well-known example of a kernel method, which has found a wide range of applications in data analysis nowadays. In many practical applications, some additional prior knowledge is often available. This can be the knowledge about the data domain, invariant transformations, inner geometrical structures in data, some properties of the underlying process, etc. If used smartly, this information can provide significant improvement to any data processing algorithm. Thus, it is important to develop methods for incorporating prior knowledge into data-dependent models. The main objective of this thesis is to investigate approaches towards learning with kernel methods using prior knowledge. Invariant learning with kernel methods is considered in more details. In the first part of the thesis, kernels are developed which incorporate prior knowledge on invariant transformations. They apply when the desired transformation produce an object around every example, assuming that all points in the given object share the same class. Different types of objects, including hard geometrical objects and distributions are considered. These kernels were then applied for images classification with Support Vector Machines. Next, algorithms which specifically include prior knowledge are considered. An algorithm which linearly classifies distributions by their domain was developed. It is constructed such that it allows to apply kernels to solve non-linear tasks. Thus, it combines the discriminative power of support vector machines and the well-developed framework of generative models. It can be applied to a number of real-life tasks which include data represented as distributions. In the last part of the thesis, the use of unlabelled data as a source of prior knowledge is considered. The technique of modelling the unlabelled data with a graph is taken as a baseline from semi-supervised manifold learning. For classification problems, we use this apporach for building graph models of invariant manifolds. For regression problems, we use unlabelled data to take into account the inner geometry of the input space. To conclude, in this thesis we developed a number of approaches for incorporating some prior knowledge into kernel methods. We proposed invariant kernels for existing algorithms, developed new algorithms and adapted a technique taken from semi-supervised learning for invariant learning. In all these cases, links with related state-of-the-art approaches were investigated. Several illustrative experiments were carried out on real data on optical character recognition, face image classification, brain-computer interfaces, and a number of benchmark and synthetic datasets.