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Conventional medical imaging technologies for cancer diagnosis utilize fixed geometric configuration of the source and the detector to image the target. In this dissertation, we hypothesize that dynamic utilization of source and detector geometry will lead to better performance of medical imaging devices. Interrogating a target in a three dimensional space requires cooperation and coordination between the source and detector positions. The goal of this dissertation is to develop a dynamic imaging method, which will improve the tumor characterization performance, and provide a control scheme appropriate for the dynamic interrogation. This dissertation proposes a bimodal dynamic imaging (BDI) method for improving tumor characterization and a hybrid hierarchical statistical control scheme for the autonomous control of the sources and detectors. The tactile imaging sensor has high specificity but low sensitivity in tumor characterization. The spectral sensor has high sensitivity but low specificity. The BDI system integrates the tactile sensing and the spectral sensing modalities with the capability of dynamic positioning of the source and detector to determine the mechanical and spectral properties of a tumor. The tactile sensing can estimate the mechanical properties of the tumor, such as size, depth, and elastic modulus, while the spectral sensing can determine the absorption coefficient of the tumor through diffuse optical imaging. These properties help us characterize the tumor, and differentiate cancerous tissues from healthy tissues. We designed and experimentally evaluated the BDI system for estimating the size, depth, elastic modulus, and absorption coefficient of embedded inclusions. The system performance in characterizing mechanical properties was then compared to that of the tactile imaging sensor. The proposed BDI method was experimentally validated using fabricated bimodal phantom. The experimental results showed that the tactile imaging system (TIS) estimated the tumor phantom size with 7.23% error; BDI measured the size with 0.8% error. The TIS depth estimation error was 41.83%; BDI reduced the depth measurement error to 20.00%. The TIS elastic modulus estimation error was 96.80%; the BDI method showed 74.79% error. Additionally, BDI estimated the absorption coefficient with 14%-25% estimation error. For further improvement the system performance, this bimodal imaging system is implemented on a dual-arm robot, Baxter, where the laser source and the tactile imaging sensors were mounted on the end-effectors. Each arm of Baxter robot has seven Degree-of- Freedom. This provides more flexibility in terms of interrogating the target compared to the fixed geometric configuration. We devised a hybrid statistical controller for maneuvering the source and the detector of the system. In this control architecture, a high-level supervisory controller was used for the functions at a higher level for coordinating two arms. At lower level, a full-state feedback statistical controller was used to facilitate the minimum position variation. A linear model for the dual-arm Baxter robot was derived for testing the proposed architecture. We performed the simulations of hybrid hierarchical statistical controller on the Baxter model for trajectory tracking. The simulation studies demonstrated accurate sequential task execution for the bimodal dynamic imaging system using a hybrid hierarchical statistical control. / Electrical and Computer Engineering

New advances in computational modeling and instrumentation in the past decade has enabled the use of electromagnetic radiation for non-invasive monitoring of the physio-logical state of biological tissues. The near infrared (NIR) light having the wavelength range of 600 nm -1000 nm has been the main contender in these emerging molecular imaging modalities. Assessment of accurate pathological condition of the tissue under investigation relies on the contrast in the molecular images, where the endogenous contrast may not be sufficient in these scenarios. The fluorescence (exogenous) contrast agents have been deployed to overcome these difficulties, where the preferential uptake by the tumor vasculature leads to high contrast,making this modality one of the biggest contenders in small-animal and soft-tissue molecular imaging modalities. In Fluorescence diffuse optical spectroscopy/imaging, this exogenous drug is excited by NIR laser light causing the emission of the fluorescence light. The emitted fluorescence light is typically dependent on the life time and concentration of the exogenous drug coupled with physiology associated with the tissue under investigation. As there is an excitation and emission of the light,the underlying physics of the problem is described by a coupled diffusion equations. These coupled diffusion equations are typically solved by advanced numerical methods, which tend to be computationally demanding. In this work, analytical solutions for these coupled partial differential equations (PDEs) for the regular geometries for both time-domain and frequency-domain cases were developed. Till now, the existing literature has not dealt with all regular geometries and derived analytical solutions were only for couple of geometries. Here a universally acceptable generic solution was developed based on Green’s function approach that is applicable to any regular geometry. Using this, the analytical solutions for the regular geometries that is encountered in diffuse fluorescence spectroscopy/imaging were obtained. These solutions can play an important role in determining the bulk fluorescence properties of the tissue, which could act as good initial guesses for the advanced image reconstruction techniques and/or can also facilitate the calibration of experimental fluorescence data by removing biases and source-detector variations. In the second part of this work, the developed analytical models for regular geometries were validated through comparison with the established numerical models that are traditionally used in the diffuse fluorescence spectroscopy/imaging. This comparison not only validated the developed analytical models, but also showed that analytical models are capable of providing bulk fluorescence properties with at least one order of magnitude less computational cost compared to the highly optimized traditional numerical models.

Diffuse optical tomography is a promising imaging modality that provides functional information of the soft biological tissues, with prime imaging applications including breast and brain tissue in-vivo. This modality uses near infrared light( 600nm-900nm) as the probing media, giving an advantage of being non-ionizing imaging modality. The image reconstruction problem in diffuse optical tomography is typically posed as a least-squares problem that minimizes the difference between experimental and modeled data with respect to optical properties. This problem is non-linear and ill-posed, due to multiple scattering of the near infrared light in the biological tissues, leading to infinitely many possible solutions. The traditional methods employ a regularization term to constrain the solution space as well as stabilize the solution, with Tikhonov type regularization being the most popular one. The choice of this regularization parameter, also known as hyper parameter, dictates the reconstructed optical image quality and is typically chosen empirically or based on prior experience. In this thesis, a simple back projection type image reconstruction algorithm is taken up, as they are known to provide computationally efficient solution compared to regularized solutions. In these algorithms, the hyper parameter becomes equivalent to filter factor and choice of which is typically dependent on the sampling interval used for acquiring data in each projection and the angle of projection. Determining these parameters for diffuse optical tomography is not so straightforward and requires usage of advanced computational models. In this thesis, a computationally efficient simplex Method based optimization scheme for automatically finding this filter factor is proposed and its performances is evaluated through numerical and experimental phantom data. As back projection type algorithms are approximations to traditional methods, the absolute quantitative accuracy of the reconstructed optical properties is poor .In scenarios, like dynamic imaging, where the emphasis is on recovering relative difference in the optical properties, these algorithms are effective in comparison to traditional methods, with an added advantage being highly computationally efficient. In the second part of this thesis, this hyper parameter choice for traditional Tikhonov type regularization is attempted with the help of Least-Squares QR-decompisition (LSQR) method. The established techniques that enable the automated choice of hyper parameters include Generalized Cross-Validation(GCV) and regularized Minimal Residual Method(MRM), where both of them come with higher over head of computation time, making it prohibitive to be used in the real-time. The proposed LSQR algorithm uses bidiagonalization of the system matrix to result in less computational cost. The proposed LSQR-based algorithm for automated choice of hyper parameter is compared with MRM methods and is proven to be computationally optimal technique through numerical and experimental phantom cases.

Le regroupement des neurones de propriétés similaires est à l’origine de modules permettant d’optimiser l’analyse de l’information. La conséquence est la présence de cartes fonctionnelles dans le cortex visuel primaire de certains mammifères pour de nombreux paramètres tels que l’orientation, la direction du mouvement ou la position des stimuli (visuotopie). Le premier volet de cette thèse est consacré à caractériser l’organisation modulaire dans le cortex visuel primaire pour un paramètre fondamental, la suppression centre / pourtour et au delà du cortex visuel primaire (dans l’aire 21a), pour l’orientation et la direction. Toutes les études ont été effectuées à l’aide de l’imagerie optique des signaux intrinsèques sur le cortex visuel du chat anesthésié. La quantification de la modulation par la taille des stimuli à permis de révéler la présence de modules de forte et de faible suppression par le pourtour dans le cortex visuel primaire (aires 17 et 18). Ce type d’organisation n’avait été observé jusqu’ici que dans une aire de plus haut niveau hiérarchique chez le primate. Une organisation modulaire pour l’orientation, similaire à celle observée dans le cortex visuel primaire a été révélée dans l’aire 21a. Par contre, contrairement à l’aire 18, l’aire 21a ne semblait pas être organisée en domaine de direction. L’ensemble de ces résultats pourront permettre d’alimenter les connaissances sur l’organisation anatomo-fonctionnelle du cortex visuel du chat mais également de mieux comprendre les facteurs qui déterminent la présence d’une organisation modulaire. Le deuxième volet abordé dans cette thèse s’est intéressé à l’amélioration de l’aspect quantitatif apporté par l’analyse temporelle en imagerie optique des signaux intrinsèques. Cette nouvelle approche, basée sur l’analyse de Fourier a permis d’augmenter considérablement le rapport signal / bruit des enregistrements. Toutefois, cette analyse ne s’est basée jusqu’ici que sur la quantification d’une seule harmonique ce qui a limité son emploi à la cartographie de l’orientation et de rétinotopie uniquement. En exploitant les plus hautes harmoniques, un modèle a été proposé afin d’estimer la taille des champs récepteurs et la sélectivité à la direction. Ce modèle a par la suite été validé par des approches conventionnelles dans le cortex visuel primaire. / The clustering of neurons of similar properties is at the basis of the brain modular architecture and is considered as a strategy to optimized processing. One consequence of this clustering is the presence of functional maps in the primary visual cortex of several mammals based on features such as orientation, direction of motion and stimulus position (retinotopy). The first section of this thesis was aimed at characterizing the modular organization of functions in primary and higher-order areas. First, we investigated the possibility that a fundamental cell property, the receptive field center / surround suppression, could be orderly represented in the primary visual cortex. Second, we determined the level of modular organization in area 21a for two key properties, orientation and direction of motion. All studies were based on the optical imaging of intrinsic signals in anesthetized cats. Results indicate the presence of high and low surround suppression modules in the primary visual cortex (areas 17 and 18). To date, such organization has been discovered only in a higher-order area in primate. A modular organization for orientation, similar to the one observed in areas 17 and 18 was observed in area 21a. On the other hand, in contrast to area 18, no direction modules were discovered in area 21a. Overall, the first part of this thesis increased our knowledge about the anatomo-fonctional organization of cat visual cortex. They will also be instrumental to better understand the factors leading to the presence of a modular organization in the cortex. The second section of this thesis was directed to the development of a novel quantitative tool for the temporal analysis of optical imaging intrinsic signals. This new approach, based on Fourier decomposition, allowed to greatly increase the signal to noise ratio of the recordings. Until now, this analysis was only been based on single harmonic quantification, limiting its application for orientation and rétinotopy mapping only. A model exploiting higher harmonics was then developed to estimate additional parameters such as the receptive field size and direction selectivity. Thereafter, this model was validated with success by conventional approaches on the primary visual cortex.

Jusqu'à récemment, les patients souffrant d'épilepsie réfractaire aux traitements médicamenteux étaient destinés à un avenir incertain. Le recours à la chirurgie comme traitement alternatif offre l'espoir de mener un jour une vie normale. Pour déterminer si un patient peut bénéficier d’une intervention chirurgicale, une évaluation complète est cruciale. Les méthodes d’évaluation préchirurgicale ont connu des progrès importants au cours des dernières décennies avec le perfectionnement des techniques d’imagerie cérébrale. Parmi ces techniques, la spectroscopie proche infrarouge (SPIR), aussi connue sous le nom d’imagerie optique, présente de nombreux avantages (coût, mobilité du participant, résolution spatiale et temporelle, etc.). L’objectif principal de cette étude est de développer un protocole d'évaluation préchirurgicale de la mémoire. Une tâche de mémoire verbale incluant l’encodage, le rappel immédiat et le rappel différé de listes de mots a été administrée à dix adultes sains lors d’un enregistrement en imagerie optique. Les résultats obtenus suggèrent l’activation bilatérale des aires préfrontales antérieures et dorsolatérales ainsi que des aires temporales antérieures et moyennes. Les aires préfrontales et temporales antérieures semblent modulées par les différents processus mnésiques et la position du rappel dans le temps. La première fois qu’une liste est rappelée, l’activité hémodynamique est plus élevée que lors des rappels subséquents, et ce, davantage dans l’hémisphère gauche que dans l’hémisphère droit. Cette étude constitue la première étape dans le processus de validation du protocole à des fins cliniques auprès de patients épileptiques. / Until recently, patients with epilepsy refractory to drug treatments were intended to an uncertain future. Surgery as an alternative treatment offers hope to, one day, lead a normal life. In order to determine if a patient may benefit from a surgical intervention, a complete evaluation is essential. With the advancements in brain imagery techniques over the last few decades, preoperative evaluation methods have seen important progress. Among these techniques, near infrared spectroscopy (NIRS), also known as optical imaging, presents numerous advantages (cost, participant mobility, spatial and temporal resolution, etc.). The purpose of this study is to develop a preoperative evaluation protocol for memory assessment. During a NIRS recording, a verbal memory task including encoding, immediate and delayed free-recall of a list of words was administered to ten healthy adults. The results obtained revealed bilateral activation of anterior and dorsolateral prefrontal areas as well as anterior and median temporal areas. Prefrontal and anterior temporal areas seemed to be regulated by different memory processes and the recall location in time. The first time that a list is recalled, increased hemodynamic activity is observed in comparison to subsequent recalls, with a greater activity in the left hemisphere than in the right hemisphere. This study constitutes the first step in the validation process of the protocol for clinical needs among epileptic patients.

Les objectifs de ce mémoire sont d’étudier la rétinotopie et les asymétries fonctionnelles du cortex visuel chez l’humain avec la spectroscopie proche de l’infrarouge fonctionnelle (SPIRf), tout en confirmant la fiabilité de cette technique. Tel qu’attendu, les résultats montrent une activation plus forte dans l’hémisphère controlatéral et dans le cortex haut/bas inverse à l’hémichamp stimulé. Nous avons également mesuré une activation significativement plus forte dans le cortex visuel supérieur (lorsque le champ visuel inférieur était stimulé) que l’activation dans le cortex visuel inférieur (lorsque le champ visuel supérieur était stimulé), surtout lorsque ces stimuli étaient présentés dans le champ visuel droit. Il s’agit de la première étude en SPIRf à observer les asymétries horizontale et verticale du cortex visuel et à ainsi confirmer l’existence de ces asymétries. Cette étude témoigne également de la fiabilité de la SPIRf comme technique d’imagerie pour cartographier le cerveau humain. / The present study aimed to further investigate retinotopic mapping and functional asymmetries within the human visual cortex using functional near-infrared spectroscopy (fNIRS), as well as the reliability of this technique. As expected, results showed a stronger visual cortical activation in the controlateral hemisphere and in the inverse upper/lower quadrant to the stimulation. We also measured significant stronger activations in the upper visual cortex (when lower hemifield stimuli were presented) compared to activations in the lower visual cortex (when upper hemifield stimuli were showed), especially when the visual stimulation was presented in the right visual field. This is the first study to confirm the vertical and horizontal asymmetries of the visual cortex with fNIRS technique. The present work also settles the reliability of this technique for functional mapping of the human brain.

Il est relativement bien établi que les crises focales entraînent une augmentation régionale du flot sanguin dans le but de soutenir la demande énergétique en hémoglobine oxygénée des neurones épileptiques. Des changements hémodynamiques précoces ont également été rapportés dans la région homologue controlatérale, bien que ceci ait été moins bien caractérisé. Dans cette étude, notre objectif est de mieux caractériser, lors de crises focales, la nature des changements hémodynamiques précoces dans la région homologue controlatérale au foyer épileptique. L'imagerie optique intrinsèque (IOI) et la microscopie deux-photons sont utilisées pour étudier les changements hémodynamiques dans la région homologue controlatérale au site de crises focales induites par l’injection de 4-aminopyridine (4-AP) dans le cortex somatosensitif ipsilatéral de souris. Dans l'étude d'IOI, des changements de l’oxyhémoglobine (HbO), de la désoxyhémoglobine (HbR) et du débit sanguin cérébral ont été observées dans la région homologue controlatérale au site de crises focales lors de toutes les crises. Toutefois, ces changements étaient hétérogènes, sans patron cohérent et reproduisible. Nos expériences avec la microscopie deux-photons n’ont pas révélé de changements hémodynamiques significatifs dans la région homotopique controlatérale lors de trains de pointes épileptiques. Nos résultats doivent être interprétés avec prudence compte tenu de plusieurs limitations: d’une part absence de mesures électrophysiologiques dans la région d’intérêt controlatérale au foyer simultanément à l’imagerie deux-photons et à l'IOI; d’autre part, lors des expériences avec le deux-photons, incapacité à générer de longues décharges ictales mais plutôt des trains de pointes, couverture spatiale limitée de la région d’intérêt controlatérale, et faible puissance suite au décès prématuré de plusieurs souris pour diverses raisons techniques. Nous terminons en discutant de divers moyens pour améliorer les expériences futures. / It has been well demonstrated that focal seizures are associated with a significant increase in regional cerebral blood flow to actively supply discharging neurons with oxygenated hemoglobin. There is also some evidence to suggest that focal seizures elicit early hemodynamic changes in the contralateral homotopic area, although this has been less well documented. In this study, we aim to better characterize the nature of early hemodynamic responses contralateral to the epileptic focus during seizures. We used intrinsic optical imaging (IOI) and two-photon laser microscopy to measure the hemodynamic changes in the homotopic contralateral area following focal seizures induced by an injection of 4-aminopyridine (4-AP) in the mouse somatosensory neocortex. In the study using IOI, oxyhemoglobin (HbO), deoxyhemoglobin (HbR) and cerebral blood flow (CBF) changes were observed in the homotopic area contralateral to the focus during all seizures. However, these changes were rather heterogenous, lacking any consistent or reproducible pattern. Our two-photon study showed no significant hemodynamic changes at the capillary level in the homotopic area contralateral to the ictal focus during epileptic spike trains. However, these findings must be interpreted cautiously in light of several limitations we encountered during the experiments. Specifically, we were unable to simultaneously record electrophysiology in the contralateral homotopic area. Furthermore, during our two-photon experiments, we failed to induce long ictal discharges (inducing only spike trains) had a limited sampling of the contralateral homotopic area and reduced power as a result of low mice survival rate. We conclude by providing alternatives to possibly improve future experiments.

Les techniques d'imagerie optique, dans la gamme de longueurs d'onde visible et proche infrarouge, permettent d'examiner très facilement les tissus biologiques de manière non invasive. Toutefois la forte diffusion des tissus biologiques limite fortement leur examen en profondeur. Examinés en rétrodiffusion (examen de la peau ou du col de l'uterus par exemple), non seulement les mesures sont polluées par la réflexion spéculaire, mais l'information sur la source volumique du signal est également perdue du fait de la forte diffusion. La prise en compte de la diffusion dans le modèle de propagation de la lumière permet d'évaluer cette distribution volumique du signal lumineux en fonction des propriétés optiques du milieu. Pour sophistiquer l'approche, nous introduisons un filtrage polarimétrique, basé sur l'utilisation de la lumière polarisée elliptiquement, particulièrement approprié à la géométrie de rétrodiffusion, permettant avant tout un sondage sélectif en profondeur tout en s'affranchissant de la réflexion spéculaire. Cette technique permet ainsi d'examiner les tissus à l'échelle mésoscopique (jusqu'à l'échelle du millimètre). / Optical imaging techniques using the visible and near-infrared wavelengths allow an easy and non-invasive way of analysing biological tissues. However, the high scattering of biological tissues significantly limits the depth of examination. Backscattering examination (of skin or of the cervix for example) shows not only that the measurements are polluted by mirror reflection, but also that information about the source of the signal is lost as a result of the high scattering. Including scattering in the light propagation model allows the evaluation of the volume distribution of the light signal as a function of the optical properties of the medium. In order to make the approach more sophisticated, we introduced a polarimetric filtering that uses elliptically polarised light. This is not only particularly appropriate for backscattering geometry, but also allows firstly to probe at selected depths and secondly to eliminate mirror reflection. Thus, this technique allows the examination of tissues at a mesoscopic scale (up to the milimeter scale).

L’imagerie optique par colorant potentiométrique est une méthode d’enregistrement de l’activité corticale prometteuse, mais dont le potentiel réel est limité par la présence d’artefacts et d’interférences dans les acquisitions. À partir de modèles existant dans la littérature, nous proposons un modèle génératif du signal basé sur un mélange additif de composantes, chacune contrainte dans une union d’espaces linéaires déterminés par son origine biophysique. Motivés par le problème de séparation de composantes qui en découle, qui est un problème inverse linéaire sous-déterminé, nous développons : (1) des régularisations convexes structurées spatialement, favorisant en particulier des solutions parcimonieuses ; (2) un nouvel algorithme proximal de premier ordre pour minimiser efficacement la fonctionnelle qui en résulte ; (3) des méthodes statistiques de sélection de paramètre basées sur l’estimateur non biaisé du risque de Stein. Nous étudions ces outils dans un cadre général, et discutons leur utilité pour de nombreux domaines des mathématiques appliqués, en particulier pour les problèmes inverses ou de régression en grande dimension. Nous développons par la suite un logiciel de séparation de composantes en présence de bruit, dans un environnement intégré adapté à l’imagerie optique par colorant potentiométrique. Finalement, nous évaluons ce logiciel sur différentes données, synthétiques et réelles, montrant des résultats encourageants quant à la possibilité d’observer des dynamiques corticales complexes. / Voltage-sensitive dye optical imaging is a promising recording modality for the cortical activity, but its practical potential is limited by many artefacts and interferences in the acquisitions. Inspired by existing models in the literature, we propose a generative model of the signal, based on an additive mixtures of components, each one being constrained within an union of linear spaces, determined by its biophysical origin. Motivated by the resulting component separation problem, which is an underdetermined linear inverse problem, we develop: (1) convex, spatially structured regularizations, enforcing in particular sparsity on the solutions; (2) a new rst-order proximal algorithm for minimizing e›ciently the resulting functional; (3) statistical methods for automatic parameters selection, based on Stein’s unbiased risk estimate.We study thosemethods in a general framework, and discuss their potential applications in variouselds of applied mathematics, in particular for large scale inverse problems or regressions. We develop subsequently a soŸware for noisy component separation, in an integrated environment adapted to voltage-sensitive dye optical imaging. Finally, we evaluate this soŸware on dišerent data set, including synthetic and real data, showing encouraging perspectives for the observation of complex cortical dynamics.