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A new type of adaptive optics (AO) based on the principles of digital holography (DH) is proposed and developed for the use in wide-field and confocal retinal imaging. Digital holographic adaptive optics (DHAO) dispenses with the wavefront sensor and wavefront corrector of the conventional AO system. DH is an emergent imaging technology that gives direct numerical access to the phase of the optical field, thus allowing precise control and manipulation of the optical field. Incorporation of DH in an ophthalmic imaging system can lead to versatile imaging capabilities at substantially reduced complexity and cost of the instrument. A typical conventional AO system includes several critical hardware pieces: spatial light modulator, lenslet array, and a second CCD camera in addition to the camera for imaging. The proposed DHAO system replaces these hardware components with numerical processing for wavefront measurement and compensation of aberration through the principles of DH. We first design an image plane DHAO system which is basically simulating the process the conventional AO system and replacing the hardware pieces and complicated control procedures by DH and related numerical processing. In this original DHAO system, CCD is put at the image plane of the pupil plane of the eye lens. The image of the aberration is obtained by a digital hologram or guide star hologram. The full optical field is captured by a second digital hologram. Because CCD is not at the conjugate plane of the sample, a numerical propagation is necessary to find the image of the sample after the numerical aberration compensation at the CCD plane. The theory, simulations and experiments using an eye model have clearly demonstrated the effectiveness of the DHAO. This original DHAO system is described in Chapter 2. Different from the conventional AO system, DHAO is a coherent imaging modality which gives more access to the optical field and allows more freedom in the optical system design. In fact, CCD does not have to be put at the image plane of the CCD. This idea was first explored by testing a Fourier transform DHAO system (FTDHAO). In the FTDHAO, the CCD can directly record the amplitude point spread function (PSF) of the system, making it easier to determine the correct guide star hologram. CCD is also at the image plane of the target. The signal becomes stronger than the image plane DHAO system, especially for the phase aberration sensing. Also, the numerical propagation is not necessary. In the FTDHAO imaging system, the phase aberration at the eye pupil can be retrieved by an inverse Fourier transform (FT) of the guide star hologram and the complex amplitude of the full field optical field at the eye pupil can be obtained by an inverse FT of the full field hologram. The correction takes place at the eye pupil, instead of the CCD plane. Taking FT of the corrected field at the eye pupil, the corrected image can be obtained. The theory, simulations, and experiments on FTDHAO are detailed in chapter 3. The successful demonstration of FTDHAO encourages us to test the feasibility of putting CCD at an arbitrary diffraction plane in the DHAO system. Through theoretical formulation by use of paraxial optical theory, we developed a correction method by correlation for the general optical system to perform the DHAO. In this method, a global quadratic phase term has to be removed before the correction operation. In the formulation, it is quite surprising to find that the defocus term can be eliminated in the correlation operation. The detailed formulations, related simulations, and experimental demonstrations are presented in Chapter 4. To apply the DHAO to the confocal retinal imaging system, we first transformed the conventional line-scanning confocal imaging system into a digital form. That means each line scan is turned into a digital hologram. The complex amplitude of the optical field from each slice of the sample and aberration of the optical system can be retrieved by digital holographic process. In Chapter 5, we report our experiments on this digital line-scanning confocal imaging system. This digital line-scanning confocal image absorbs the merits of the conventional line-scanning confocal imaging system and DH. High-contrast intensity images with low coherent noise, and the optical sectioning capability are made available due to the confocality. Phase profiles of the samples become accessible thanks to DH. The quantitative phase map is even better than that from the wide field DH. We then explore the possibility of applying DHAO to this newly developed digital line-scanning confocal imaging system. Since optical field of each line scan can be achieved by the DH, the aberration contained in this field can be eliminated if we are able to obtain the phase aberration. We have demonstrated that the phase aberration can be obtained by a guide star hologram in the wide field DHAO systems. We then apply this technique to acquire the aberration at the eye pupil, remove this aberration from the optical fields of the line scans and recover the confocal image. To circumvent the effect of phase aberration on the line illumination, a small collimated laser beam is shone on the cylindrical lens. Thus the image is solely blurred by the second passage through the aberrator. This way, we can clearly demonstrate the effect of DHAO on the digital line-scanning confocal image system. Simulations and experiments are presented in chapter 6, which clearly demonstrates the validity of this idea. Since line-scanning confocal imaging system using spatially coherent light sources has proven an effective imaging tool for retinal imaging, the presented digital adaptive optics line-scanning confocal imaging system is quite promising to become a compact digital adaptive optics laser scanning confocal ophthalmoscope.

Cancer is a world menace. After years of endeavor seeking the end of it, people started to realize that no matter how powerful the therapy could be, detection at early stage is always a cheaper, easier and more successful solution compared with curative methods for cancer developed onto its advanced stage. However, relatively few early-detection approaches have proven sufficiently effective and practical for mass use as a point-of-care tool. An early-cancer screening tool integrating the desired features of sensitive, informative, portable, and cost-effective is in need for the doctors. The progress in optical imaging and Micro-electro-mechanical system (MEMS) technology offers a promise for an innovative cancer screening alternative that is non-invasive, radiation-free, portable and potentially cost-effective. This dissertation investigates handheld instrumentation as multi-modalities of miniature imaging probes with various designs of MEMS devices, to obtain real-time images of epithelial tissue optical and physiological properties, combining the quantitative advantages of spectral analysis with the qualitative benefits of imaging to distinguish early cancer. This dissertation in sequence presents the handheld instruments in the fashions of Laser-scanning confocal microscopy (LSCM), optical diffuse reflectance imaging, nonlinear optical imaging modalities with their subsequent image-guided managements in oral cancer, skin cancer detection, circulating tumor cell (CTC) imaging, and imaging guided surgeries. One of the main challenges facing miniaturization lies in the mechanism of beam deflection across the sample. This dissertation introduces two generations of MEMS devices desgined, fabricated and incorporated in the imaging probes. A two-axis vertical comb driven silicon micromirror was used in the development of a handheld LSCM for oral cancer detection. Though obtaining numerous advantages, this first generation silicon MEMS micromirror suffers from small aperture size and high voltage requirement for actuation, which result in low collection efficiency in fluorescence imaging and medial safety concerns, respectively. Therefore a stainless steel scanner compatible with electrical discharge machining (EDM) process was fabricated with simplified process, low-voltage magnetic actuation and large fluorescence collection efficiency, with its capability demonstrated in the incorporation and embodiment of a handheld hyperspectral nonlinear imaging probe. Besides, software and controlling innovations for handheld imaging modalities are presented. A feedback controlling system for MEMS scanning status monitoring was developed for stabilized imaging rendering. For the sake of further improved imaging stability in handheld imaging and to enable on-site mosaic for large field viewing, a handheld mosaic system was developed and presented. / text

L’objet de cette thèse est le développement méthodologique et logiciel d’outils permettant de traiter les grands volumes de données multimodales et tomographiques produits sur Nanoscopium. La technique de microscopie en rayons X durs par balayage permet l’acquisition simultanée d’information par contraste d’absorption, de phase, de diffusion et de fluorescence X. L’association des techniques de balayage avec l’infrastructure d’acquisition rapide FLYSCAN permet de proposer aux futurs utilisateurs de la ligne Nanoscopium de faire des acquisitions tomographiques multimodales. Un des principaux enjeux de cette approche est le traitement en ligne des grands volumes de données générées durant l’acquisition. Le résultat principal de cette thèse est le logiciel MMXI, dédié au traitement et à la reconstruction des jeux de données multimodales 2D et 3D. Ce logiciel intègre un algorithme dédié à la lecture de gros volumes de données, différentes fonctions de réduction de données, deux algorithmes de reconstruction de phase (intégration dans l’espace de Fourrier et technique itérative) et des algorithmes de reconstruction tomographiques (rétroprojection filtré ou itérative). L’ensemble des méthodes implémentées, des applications permettant de valider ces développements ainsi que les perspectives d’évolution sont présentées dans ce manuscrit. / The subject of this thesis is the methodological and software development of tools for processing very large multimodal and tomographic datasets produced on Nanoscopium beamline in the SOLEIL synchrotron. Scanning hard X-ray imaging allows simultaneous acquisition of multimodal information, i.e. of images in which each pixel contains several types of data. Combining these scanning techniques with the FLYSCAN infrastructure, developed for fast data acquisition at Synchrotron SOLEIL, permits to perform multimodal tomographic imaging and tomographic reconstruction during routine user experiments. A main challenge of such imaging techniques is the online processing of the important amount of generated multimodal data. The main outcome of this thesis work is the MMX-I software which is dedicated to processing large 2D/3D multimodal dataset. This software includes an original algorithm for continuous reading of large data volumes, several reduction functions, two phase reconstruction algorithms (integration in Fourier space and iterative technics) and tomographic reconstruction technics (filtered back projection and iterative technics). Every implemented method as well as application allowing to validate the new developments and few evolution perspectives are presented in this thesis manuscript.