La tomographie optique diffuse (TOD) est une technique d'imagerie médicale émergente utilisant la lumière proche infrarouge pour sonder les tissus biologiques. A partir de mesures non-invasives, cette technique permet d'obtenir les cartes en trois dimensions des coefficients d'absorption et de diffusion à l'intérieur des organes. Avec une approche multi-spectrale, la distribution spatiale des chromophores endogènes (hémoglobine, eau) peut aussi être obtenue. Pour certaines applications cliniques, il est souhaitable d'effectuer les mesures de TOD avec une sonde compacte qui regroupe tous les couples source-détecteur. Cependant, dans cette configuration, la sensibilité en profondeur est un défi majeur. Dans le cadre de cette thèse, nous proposons d'adresser ce challenge en utilisant des mesures résolues en temps. Une approche résolue en temps est développée pour optimiser la TOD dans le cas des mesures de réflectance à faibles distances source-détecteur. Cette approche inclut des aspects méthodologiques concernant le traitement des mesures résolues en temps par des algorithmes de TOD basés sur la transformée de Mellin-Laplace. Cette approche comporte aussi un volet instrumental qui consiste à optimiser la chaîne de détection sur deux points précis pour améliorer la détection et la localisation de contraste d'absorption en profondeur dans les milieux diffusants. Tout d'abord, l'impact de la réponse temporelle du détecteur est étudié avec des détecteurs de photons uniques disponibles dans le commerce (photomultiplicateurs classiques et hybrides). Dans un second temps, l'augmentation de la profondeur sondée avec de nouveaux détecteurs de photons uniques, les fast-gated single-photon avalanche diodes, est explorée au cours d'une collaboration avec le Politecnico de Milan. Pour finir, une étude illustre les performances de l'approche proposée en termes de résolution spatiale en profondeur pour différents arrangements des sources et détecteurs dans une sonde optique. Des sondes optiques dont la largeur est limitée à quelques centimètres ouvrent la voie à de nouvelles applications cliniques pour la TOD. Ces sondes peuvent accéder à des organes internes comme la prostate ou faciliter les examens médicaux sur des organes externes comme le sein ou le cerveau. / Diffuse optical tomography (DOT) is an emerging medical imaging technique using near-infrared light to probe biological tissues. This technique can retrieve three-dimensional maps of absorption and scattering coefficients inside organs from non-invasive measurements. With a multispectral approach, the spatial distribution of endogenous chromophores (hemoglobin, water) can even be obtained. For some clinical applications, it is desirable to carry out the measurements for DOT with a compact probe including all sources and detectors. However, the depth sensitivity is a real challenge in this configuration. We propose to tackle this challenge by using time-resolved measurements. A time-resolved approach is developed to perform DOT with reflectance measurements at short source-detector separation. This approach involves methodological aspects including the processing of time-resolved signals by DOT algorithms based on the Mellin-Laplace transform. Then, this approach consists in optimizing the detection chain on two aspects for enhancing the detection and localization of absorption contrast in depth in diffusive media. First, the impact of the temporal response of the detector is studied with commercially available single-photon detectors (classical and hybrid photomultipliers). Second, the enhancements in probed depth permitted with fast-gated single-photon avalanche diodes are explored in a joint work with the Politecnico di Milano. To finish, a study is carried out to illustrate the performance of the proposed approach with respect to spatial resolution in depth for different configurations of sources and detectors in the optical probe. Probes with a width limited to a few centimeters open the gate to multiple clinical interests. They could access intern organs like the prostate or facilitate the measurements on extern organs like the breast or the brain.

Time-Resolved diffuse optics is a powerful and safe technique to quantify the optical properties (OP) for highly scattering media such as biological tissues. The OP values are correlated with the compositions of the measured objects, especially for the tissue chromophores such as hemoglobin. The OP are mainly the absorption and the reduced scattering coefficients that can be quantified for highly scattering media using Time-Resolved Diffuse Optical Spectroscopy (TR-DOS) systems. The OP can be retrieved using Time-Resolved Diffuse Optical Imaging (TR-DOI) systems to reconstruct the distribution of the OP in measured media. Therefore, TR-DOS and TR-DOI can be used for functional monitoring of brain and muscles, and to diagnose some diseases such as detection and localization for breast cancer and blood clot. In general, TR-DOI systems are non-invasive, reliable, and have a high temporal resolution. TR-DOI systems have been known for their complexity, bulkiness, and costly equipment such as light sources (picosecond pulsed laser) and detectors (single photon counters). Also, TR-DOI systems acquire a large amount of data and suffer from the computational cost of the image reconstruction process. These limitations hinder the usage of TR-DOI for widespread potential applications such as clinical measurements. The goals of this research project are to investigate approaches to eliminate two main limitations of TR-DOI systems. First, building TR-DOS systems using custom-designed free-running (FR) and time-gated (TG) SPAD detectors that are fabricated in low-cost standard CMOS technology instead of the costly photon counting and timing detectors. The FR-TR-DOS prototype has demonstrated comparable performance (for homogeneous objects measurements) with the reported TR-DOS prototypes that use commercial and expensive detectors. The TG-TR-DOS prototype has acquired raw data with a low level of noise and high dynamic range that enable this prototype to measure multilayered objects such as human heads. Second, building and evaluating TR-DOI prototype that uses a computationally efficient algorithm to reconstruct high quality 3D tomographic images by analyzing a small part of the acquired data. This work indicates the possibility to exploit the recent advances in the technologies of silicon detectors, and computation to build low-cost, compact, portable TR-DOI systems. These systems can expand the applications of TR-DOI and TR-DOS into several fields such as oncology, and neurology. / Thesis / Doctor of Philosophy (PhD)