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No / We measured the wavefront aberrations of the eyes of five subjects with a Shack-Hartmann sensor sampling at 21.2 Hz and decomposed the measurements into Zernike aberration terms up to and including the fifth radial order. Coherence function analysis was used to determine the common frequency components between the aberrations within subjects. We found the results to be highly subject dependent. The coherence values were typically <0.4. Possible reasons for this are discussed. Coherence function analysis is a useful tool that can be used in future investigations to determine correlations between the aberration dynamics of the eye and other physiological mechanisms.

We explore a new laboratory technique in the field of urinalysis promising a combination of speed and selectivity in support of urinary tract infection diagnosis. Laboratory experimentation demonstrates long range surface plasmon polaritons (LRSPP) waveguides as a useful biosensor to selectively detect gram negative bacteria or gram positive bacteria in human urine. The biosensor can detect bacteria at concentration of 105 CFU/ml, the internationally recommended threshold for diagnostic of urinary tract infection (UTI). Using a negative control solution at bacterial concentration 1000x higher than the targeted bacteria in urine with a weak concentration of constituents, the power ratio between the negative control signals to the target bacteria signal is measured to be 5.4. Thus we report a conclusive demonstration of the LRSPP waveguide biosensor selectivity to the gram of bacteria in human urine. In addition, the biosensor may prove useful as an alternative urinalysis test method to determine the urine specific gravity, to estimate proteinuria, and to detect biofilm formation on surfaces.

Optical coherence imaging, including tomography (OCT) and microscopy (OCM), has been a growing research field in biomedical optical imaging in the last decade. In this imaging modality, a broadband light source, thus of short temporal coherence length, is used to perform imaging via interferometry. A challenge in optical coherence imaging, as in any imaging system towards biomedical diagnosis, is the quantification of image quality and optimization of the system components, both a primary focus of this research. We concentrated our efforts on the optimization of the imaging system from two main standpoints: axial point spread function (PSF) and practical steps towards compact low-cost solutions. Up to recently, the criteria for the quality of a system was based on speed of imaging, sensitivity, and particularly axial resolution estimated solely from the full-width at half-maximum (FWHM) of the axial PSF with the common practice of assuming a Gaussian source power spectrum. As part of our work to quantify axial resolution we first brought forth two more metrics unlike FWHM, which accounted for side lobes in the axial PSF caused by irregularities in the shape of the source power spectrum, such as spectral dips. Subsequently, we presented a method where the axial PSF was significantly optimized by suppressing the side lobes occurring because of the irregular shape of the source power spectrum. The optimization was performed through optically shaping the source power spectrum via a programmable spectral shaper, which consequentially led to suppression of spurious structures in the images of a layered specimen. The superiority of the demonstrated approach was in performing reshaping before imaging, thus eliminating the need for post-data acquisition digital signal processing. Importantly, towards the optimization and objective image quality assessment in optical coherence imaging, the impact of source spectral shaping was further analyzed in a task-based assessment method based on statistical decision theory. Two classification tasks, a signal-detection task and a resolution task, were investigated. Results showed that reshaping the source power spectrum was a benefit essentially to the resolution task, as opposed to both the detection and resolution tasks, and the importance of the specimen local variations in index of refraction on the resolution task was demonstrated. Finally, towards the optimization of OCT and OCM for use in clinical settings, we analyzed the detection electronics stage, which is a crucial component of the system that is designed to capture extremely weak interferometric signals in biomedical and biological imaging applications. We designed and tested detection electronics to achieve a compact and low-cost solution for portable imaging units and demonstrated that the design provided an equivalent performance to the commercial lock-in amplifier considering the system sensitivity obtained with both detection schemes.

L'amélioration de la visualisation in vivo des lésions précancéreuse (dysplasies) du col utérin est essentielle pour mieux identifier les zones à biopsier et pour optimiser la définition des limites d'exérèse chirurgicale. Dans ce but nous étudions une nouvelle technique d'imagerie polarimétrique en rétrodiffusion, que nous avons mise en oeuvre sur des échantillons ex vivo dans des configurations expérimentales variées afin d'optimiser le diagnostic in vivo. Comme cette optimisation passe par la compréhension des contrastes polarimétriques observés, nous avons réalisé de nombreuses simulations de la propagation de lumière polarisée dans des structures multicouche représentatives des tissus. Ces structures comprennent typiquement une couche comportant des diffuseurs dans une matrice homogène et représentant l'épithélium ou le tissu conjonctif superficiel, et un substrat lambertien totalement dépolarisant pour les couches plus profondes. Ces simulations ont été effectuées au moyen d'un code Monte Carlo que nous avons adapté à notre problématique. Nous avons ainsi montré que la contribution des noyaux cellulaires est très faible en rétrodiffusion. Pour le tissu conjonctif, les fibres de collagène, modélisées par des diffuseurs sphériques de 200 nm de rayon, donnent une contribution plus importante que les noyaux, mais ne reproduisent pas la réponse polarimétrique de type Rayleigh observée dans tous les tissus étudiés, qu'ils soient sains ou pathologiques. En revanche, l'inclusion de diffuseurs de taille nettement inférieure à la longueur d'onde, modélisés par des sphères de 50 nm, permet de reproduire cette réponse de manière très stable. Ces diffuseurs correspondent a priori aux protéines intracellulaires. Dans le cadre de ce modèle, les contrastes observés entre tissus sains et cancéreux s'expliquent essentiellement par une variation de la concentration de ces petits diffuseurs. Ce résultat, encore préliminaire, suggère que l'imagerie polarimétrique en rétrodiffusion peut être sensible non seulement à la morphologie, mais également à l'état physiologique du tissu, ce qui peut s'avérer important pour la détection sélective des dysplasies.

The common way to diagnose hard and soft tissue irregularities in the oral cavity is initially the visual inspection by an experienced dentist followed by further medical examinations, such as radiological imaging and/or histopathological investigation. For the diagnosis of oral hard and soft tissues, the detection of early transformations is mostly hampered by poor visual access, low specificity of the diagnosis techniques, and/or limited feasibility of frequent screenings. Therefore, optical noninvasive diagnosis of oral tissue is promising to improve the accuracy of oral screening. Considering this demand, a rigid handheld endoscopic scanner was developed for optical coherence tomography (OCT). The novelty is the usage of a commercially near-infrared endoscope with fitting optics in combination with an established spectral-domain OCT system of our workgroup. By reaching a high spatial resolution, in vivo images of anterior and especially posterior dental and mucosal tissues were obtained from the oral cavity of two volunteers. The convincing image quality of the endoscopic OCT device is particularly obvious for the imaging of different regions of the human soft palate with highly scattering fibrous layer and capillary network within the lamina propria.

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.