Dans un monde de plus en plus ouvert, les flux de personnes sont amenés à exploser dans les prochaines années. Fluidifier et contrôler ces flux, tout en respectant de fortes contraintes sécuritaires, apparaît donc comme un élément clef pour favoriser le dynamisme économique mondial. Cette gestion des flux passe principalement par la connaissance et la vérification de l’identité des personnes. Pour son aspect pratique et a priori sécurisé, la biométrie, et en particulier celle des empreintes digitales, s’est imposée comme une solution efficace, et incontournable. Néanmoins, elle souffre de deux sévères limitations. La première concerne les mauvaises performances obtenues avec des doigts détériorés. Ces détériorations peuvent être involontaires (travailleurs manuels par exemple), ou bien volontaires, à des fins d’anonymisation. La deuxième concerne les failles de sécurité des capteurs. En particulier, ils sont vulnérables à des attaques avec de fausses empreintes, réalisées par des personnes mal intentionnées dans un but d’usurpation d’identité. D’après nous, ces limitations sont dues à la faible quantité d’information exploitée par les capteurs usuels. Elle se résume souvent à une simple image de la surface du doigt. Pourtant, la complexité biologique des tissus humains est telle qu’elle offre une information très riche, unique, et difficilement reproductible. Nous avons donc proposé une approche d’imagerie, basée sur la Tomographique par Cohérence Optique, un capteur 3D sans contact, permettant de mesurer finement cette information. L’idée majeure de la thèse consiste à étudier divers moyens de l’exploiter, afin de rendre la biométrie plus robuste et vraiment sécurisée / In an increasingly open world, the flows of people are brought to explode in the coming years. Facilitating, streamlining, and managing these flows, by maintaining strict security constraints, therefore represent a key element for the global socio-economic dynamism. This flows management is mainly based on knowledge and verification of person identity. For its practicality and a priori secured, biometrics, in particular fingerprints biometrics, has become an effective and unavoidable solution.Nevertheless, it still suffers from two severe limitations. The first one concerns the poor performances obtained with damaged fingers. This damage can be involuntary (e.g. manual workers) or volunteers, for purposes of anonymity. The second limitation consists in the vulnerability of the commonly used sensors. In particular, they are vulnerable to copies of stolen fingerprints, made by malicious persons for identity theft purpose. We believe that these limitations are due to the small amount of information brought by the usual biometric sensors. It often consists in a single print of the finger surface. However, the biological complexity of human tissue provides rich information, unique to each person, and very difficult to reproduce. We therefore proposed an imaging approach based on Optical Coherence Tomography (OCT), a 3D contactless optical sensor, to finely measure this information. The main idea of the thesis is therefore to explore novel ways to exploit this information in order to make biometrics more robust and truly secured. In particular, we have proposed and evaluated different fingerprint imaging methods, based on the phase of the OCT signal

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20986号 / 医博第4332号 / 新制||医||1027(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 富樫 かおり, 教授 羽賀 博典, 教授 別所 和久 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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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.

Today, medical imaging is playing an important role in medicine as it provides the techniques and processes used to create images of the human body or parts thereof for clinical purposes (medical procedures seeking to reveal, diagnose or examine disease) or medical science (including the study of normal anatomy and function). Modalities are developing over time to achieve the highest possible resolution, speed of image acquisition, sensitivity, and specificity. In the past decade, advances in optics, fiber, as well as laser technology have enabled the development of noninvasive optical biomedical imaging technology that can also be applied to endoscopy to reach deeper locations in the human body. The purpose of this dissertation is to investigate a full system design and optimization of an optical coherence tomography (OCT) system to achieve high axial and lateral resolution together with an extended depth of focus for endoscopic in vivo imaging. In this research aimed at advancing endoscopic OCT imaging, two high axial resolution optical coherence tomography systems were developed: (1) a spectrometer-based frequency-domain (FD) OCT achieving an axial resolution of ~2.5 µm using a Ti:Sa femtosecond laser with a 120nm bandwidth centered at 800nm and (2) a swept-source based FD OCT employing a high speed Fourier domain mode locked (FDML) laser that achieves real time in vivo imaging with ~8 µm axial resolution at an acquisition speed of 90,000 A-scans/sec. A critical prior limitation of FD OCT systems is the presence of mirror images in the image reconstruction algorithm that could only be eliminated at the expense of depth and speed of imaging. A key contribution of this research is the development of a novel FD OCT imager that enables full range depth imaging without a loss in acquisition speed. Furthermore, towards the need for better axial resolution, we developed a mathematical model of the OCT signal that includes the effect on phase modulation of phase delay, group delay, and dispersion. From the mathematical model we saw that a Fourier domain optical delay line (FD ODL) incorporated into the reference arm of the OCT system represented a path to higher performance. Here we then present a method to compensate for overall system dispersion with a FDODL that maintains the axial resolution at the limit determined solely by the coherence length of a broadband source. In the development of OCT for endoscopic applications, the need for long depth of focus imaging is critical to accommodate the placement of the catheter anywhere within a vessel. A potential solution to this challenge is Bessel-beam imaging. In a first step, a Bessel-beam based confocal scanning optical microscopy (BCSOM) using an axicon and single mode fiber was investigated with a mathematical model and simulation. The BCSOM approach was then implemented in a FD OCT system that delivered high lateral resolution over a long depth of focus. We reported on the imaging in biological samples for the first time with a double-pass microoptics axicon that demonstrated clearly invariant SNR and 8 um lateral resolution images across a 4 mm depth of focus. Finally, we describe the design and fabrication of a catheter incorporated in the FD OCT. The design, conceived for a 5 mm outer diameter catheter, allows 360 degree scanning with a lateral resolution of about 5 um across a depth of focus of about 1.6 mm. The dissertation concludes with comments for related future work.

Time domain Optical Coherence Tomography (TD-OCT), first reported in 1991, makes use of the low temporal coherence properties of a NIR broadband laser to create depth sectioning of up to 2mm under the surface using optical interferometry and point to point scanning. Prior and ongoing work in OCT in the research community has concentrated on improving axial resolution through the development of broadband sources and speed of image acquisition through new techniques such as Spectral domain OCT (SD-OCT). In SD-OCT, an entire depth scan is acquired at once with a low numerical aperture (NA) objective lens focused at a fixed point within the sample. In this imaging geometry, a longer depth of focus is achieved at the expense of lateral resolution, which is typically limited to 10 to 20 [micro]m. Optical Coherence Microscopy (OCM), introduced in 1994, combined the advantages of high axial resolution obtained in OCT with high lateral resolution obtained by increasing the NA of the microscope placed in the sample arm. However, OCM presented trade-offs caused by the inverse quadratic relationship between the NA and the DOF of the optics used. For applications requiring high lateral resolution, such as cancer diagnostics, several solutions have been proposed including the periodic manual re-focusing of the objective lens in the time domain as well as the spectral domain C-mode configuration in order to overcome the loss in lateral resolution outside the DOF. In this research, we report for the first time, high speed, sub-cellular imaging (lateral resolution of 2 [micro]m) in OCM using a Gabor domain image processing algorithm with a custom designed and fabricated dynamic focus microscope interfaced to a Ti:Sa femtosecond laser centered at 800 nm within an SD-OCM configuration. It is envisioned that this technology will provide a non-invasive replacement for the current practice of multiple biopsies for skin cancer diagnosis. The research reported here presents three important advances to this technology all of which have been demonstrated in full functional hardware conceived and built during the course of this research. First, it has been demonstrated that the coherence gate created by the femtosecond laser can be coupled into a scanning optical microscope using optical design methods to include liquid lens technology that enables scanning below the surface of skin with no moving parts and at high resolution throughout a 2x2x2 mm imaging cube. Second, the integration the variable-focus liquid lens technology within a fixed-optics microscope custom optical design helped increase the working NA by an order of magnitude over the limitation imposed by the liquid lens alone. Thus, this design has enabled homogenous axial and lateral resolution at the micron-level (i.e., 2 [micro]m) while imaging in the spectral domain, and still maintaining in vivo speeds. The latest images in biological specimens clearly demonstrate sub-cellular resolution in all dimensions throughout the imaging volume. Third, this new modality for data collection has been integrated with an automated Gabor domain image registration and fusion algorithm to provide full resolution images across the data cube in real-time. We refer to this overall OCM method as Gabor domain OCM (GD-OCM). These advantages place GD-OCM in a unique position with respect to the diagnosis of cancer, because when fully developed, it promises to enable fast and accurate screening for early symptoms that could lead to prevention. The next step for this technology is to apply it directly, in a clinical environment. This step is underway and is expected to be reported by the next generation of researchers within this group.

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Paediatric glaucoma leads to a decreased thickness of the peripapillary retinal nerve fibre layer (pRNFL) and of the macula. These changes can be precisely quantified using spectral domain-optical coherence tomography (SD-OCT). Despite abundant reports in adults, studies on the diagnostic capacity of macular SD-OCT in paediatric glaucoma are rare. The aim of this study was to compare the glaucoma discriminative ability of pRNFL and macular segment thickness in paediatric glaucoma patients and healthy children. Data of 72 children aged 5–17 years (glaucoma: 19 (26.4%), healthy: 53 (73.6%)) examined with SD-OCT (SPECTRALIS®, Heidelberg Engineering) were analysed retrospectively. The thickness of pRNFL sectors and of macular segment subfields were compared between diseased and healthy participants. Areas under the receiver-operating characteristic curves (AUC), sensitivity, and specificity from logistic regression were used to evaluate the glaucoma discriminative capacity of single and combined pRNFL and macular segments’ thickness. The results revealed a reduced thickness of the pRNFL and of the three inner macular layers in glaucoma patients, which correlates highly with the presence of glaucoma. The highest glaucoma discriminative ability was observed for the combination of pRNFL sectors or inner macular segments (AUC: 0.83 and 0.85, respectively), although sensitivity remained moderate (both 63% at 95% specificity). In conclusion, while confirmation from investigations in larger cohorts is required, SD-OCT-derived pRNFL and macular thickness measurements seem highly valuable for the diagnosis of paediatric glaucoma.

The aim of this study was to compare the efficacy of trabeculectomy (TE), single XEN microstent implantation (solo XEN) or combined XEN implantation and cataract surgery (combined XEN) in primary open-angle glaucoma cases, naïve to prior surgical treatment, using a monocentric retrospective comparative cohort study. Intraocular pressure (IOP) and the number of IOP-lowering drugs (Meds) were monitored during the first 24 months after surgery. Further disease progression was monitored using peripapillary retinal nerve fiber layer (RNFL) thickness examinations using spectral domain optical coherence tomography (OCT) as well as visual acuity (VA) and visual field (VF) tests. In the TE group (52 eyes), the mean IOP decreased from 24.9 ± 5.9 to 13.9 ± 4.2 mmHg (p < 0.001) and Meds decreased from 3.2 ± 1.2 to 0.5 ± 1.1 (p < 0.001). In the solo XEN (38 eyes) and the combined XEN groups, the mean IOP decreased from 24.1 ± 4.7 to 15.7 ± 3.0 mmHg (p < 0.001) and 25.4 ± 5.6 to 14.7 ± 3.2 mmHg (p < 0.001), while Meds decreased from 3.3 ± 0.8 to 0.8 ± 1.2 (p < 0.001) and 2.7 ± 1.2 to 0.4 ± 1.0 (p < 0.001), respectively. The VF and VA indices showed no sign of further deterioration, the RNFL thickness further decreased in all treatment groups after surgery. TE and XEN led to comparable reductions in IOP and Meds. Although the VA and VF indices remained unaltered, the RNFL thickness continuously decreased in all treatment groups during the 24-month follow-up.