About 50% of cancer patients are treated with X-ray radiation therapy; however, with current treatment feedback, the effects and the efficacy of the treatment are generally detected several weeks/months after treatment completion. This makes the adjustment of the treatment based on early response, and identification of non-responding patients, nearly impossible. In this thesis a novel method combining optical coherence tomography and a gamut of image analysis methods is explored as a potential approach to detecting tissue variability. Applying texture analysis to the optical coherence tomography images may allow for the tracking of radiation therapy induced cell microstructural changes in cancer patients and help in the adjustment of treatment based on early response.

About 50% of cancer patients are treated with X-ray radiation therapy; however, with current treatment feedback, the effects and the efficacy of the treatment are generally detected several weeks/months after treatment completion. This makes the adjustment of the treatment based on early response, and identification of non-responding patients, nearly impossible. In this thesis a novel method combining optical coherence tomography and a gamut of image analysis methods is explored as a potential approach to detecting tissue variability. Applying texture analysis to the optical coherence tomography images may allow for the tracking of radiation therapy induced cell microstructural changes in cancer patients and help in the adjustment of treatment based on early response.

Laser-based photo-thermal therapies can provide minimally-invasive treatment of cancers. Their effectiveness is limited by light penetration depth in tissue due to its highly scattering properties. The highly disordered refractive index distribution in tissue leads to multiple-scattering of incident light. It has been hypothesized that mechanical compression has a great potential to enhance the capabilities of laser therapy by inducing localized water transport, decreasing the refractive index mismatch, and decreasing the scattering coefficient of tissue. To better understand this process, we investigated the refractive index change of ex-vivo dog skin during mechanical compression using a swept-source optical coherence tomography (OCT) device built in our lab. The Lorentz-Lorenz rule of mixtures was applied to evaluate the water and protein weight fraction of tissue simultaneously. Results show that the refractive index of skin increased from 1.38 to 1.52 during compression and water content decreased about 60%-70% when the skin sample was compressed by 70%. In addition, we conducted compression experiments on human finger, palm, back of hand, and front of forearm in vivo. OCT images of these skin sites before and after compression by 1 minute were compared. Optical thickness of epidermis and light penetration depth in the dermis were measured. The extended Huygens-Fresnel model was applied to measure the scattering coefficient μs of skin specimens. μs of skin was measured to be about 10-17 mm-1 before compression and decreased 60%-80% after compression, which increases the averaged light intensity by 2-7 dB and almost doubles light penetration depth in dermis. It is quite significant in laser therapies especially for treating epithelia cancers which originate at 1-2 mm beneath the tissue surface. In the OCT imaging of skin dehydration experiment, we conclude that dehydration is an important mechanism of mechanical clearing. / Master of Science

Στο συγκεκριμένο ερευνητικό πρωτόκολλο μελετήθηκαν οι πιθανές ένοχες βλάβες σε φλεβικά μοσχεύματα ασθενών με οξέα στεφανιαία σύνδρομα με τη μέθοδο της Οπτικής Συνεκτικής Τομογραφίας (OCT). • Οι αθηροσκληρωτικές βλάβες των φλεβικών μοσχευμάτων έχουν μελετηθεί in vivo με τη μέθοδο της αγγειοσκόπησης και της ενδαγγειακής υπερηχογραφίας (IVUS). Απεναντίας, η απεικόνιση των μοσχευμάτων με τη μέθοδο της OCT, η οποία χαρακτηρίζεται από σημαντικά μεγαλύτερη διακριτική ικανότητα σε σχέση με το IVUS και βελτιωμένη διεισδυτική ικανότητα συγκρινόμενη με την αγγειοσκόπηση, δεν έχει μελετηθεί συστηματικά. • Μέθοδος: Η απεικόνιση των ένοχων βλαβών των μοσχευμάτων πραγματοποιήθηκε, κατόπιν αγγειογραφίας τους, με τη μέθοδο χωρίς απόφραξη της OCT σε ασθενείς με ασταθή στηθάγχη (UA), έμφραγμα μυοκαρδίου με ανάσπαση του διαστήματος ST (STEMI) και έμφραγμα μυοκαρδίου χωρίς ανάσπαση του διαστήματος ST (non-STEMI). Ο ινώδης ιστός, ο λιπώδης ιστός, οι εναποθέσεις ασβεστίου, ο θρόμβος και η ρήξη της πλάκας ορίστηκαν σύμφωνα με τα κριτήρια απεικόνισης στοιχείων για την OCT, όπως περιγράφηκαν και στο γενικό μέρος. • Αποτελέσματα: Απεικονίστηκαν 28 φλεβικά μοσχεύματα (μέσης ηλικίας 14.6 ετών) σε 26 ασθενείς. Οι βλάβες χαρακτηρίστηκαν ως σύμπλοκες αγγειογραφικά σε ποσοστό 96.4%, ενώ εμφάνιζαν εξέλκωση σε ποσοστό 32.1% και θρόμβο σε ποσοστό 21.4%. Η OCT αποκάλυψε ινολιπώδη σύσταση σε όλες τις βλάβες, εναπόθεση ασβεστίου στο 32.1% των βλαβών, ρήξη πλάκας σε ποσοστό 60.7% και παρουσία θρόμβου σε ποσοστό 46.4%. Η παρουσία του θρόμβου ήταν προοδευτικά συχνότερη ανάμεσα στις ομάδες ανάλογα με το κλινικό τους σύνδρομο (UA έως STEMI, p=0.003, UA έναντι εμφράγματος μυοκαρδίου, p=0.006). Η λεπτή ινώδης κάψα καταγράφηκε οριακά συχνότερα στους ασθενείς με οξύ έμφραγμα μυοκαρδίου (UA έναντι εμφράγματος μυοκαρδίου, p=0.06, STEMI 100% έναντι non-STEMI 53.3% έναντι UA 20%, p=0.03). Βλάβες με στοιχεία ευθρυπτότητας, όπως απεικονίζονταν στην OCT παρουσιάζονταν σε ποσοστό 67.9%, χωρίς όμως συσχέτιση με την κλινική εικόνα. • Συμπέρασμα: Οι ένοχες βλάβες φλεβικών μοσχευμάτων μεγάλης ηλικίας ασθενών με οξέα στεφανιαία σύνδρομα, όπως αυτές απεικονίζονται στην OCT, εμφανίζουν ινολιπώδη σύσταση, σχετικά λεπτή ινώδη κάψα, ρήξη πλάκας και θρόμβο που συσχετίζονται με το κλινικό φάσμα των οξέων στεφανιαίων συνδρόμων. Αυτά οδηγούν στο συμπέρασμα ότι οι ίδιοι μηχανισμοί αθηροσκλήρωσης που οδηγούν στην εμφάνιση οξέων στεφανιαίων συνδρόμων στα γηγενή στεφανιαία αγγεία, είναι πιθανόν να ενέχονται και στην πρόκληση οξέων στεφανιαίων συνδρόμων λόγω αποτυχίας των φλεβικών μοσχευμάτων. / This study sought to assess, with optical coherence tomography (OCT), presumably culprit atherosclerotic lesions of saphenous vein grafts (SVGs) in patients with acute coronary syndromes (ACS). Background: Atherosclerotic lesions of SVGs have been studied in vivo with angioscopy and intravascular ultrasound. However, imaging with OCT, which has a higher resolution than intravascular ultrasound and better penetration than angioscopy, has not been conducted systematically. Methods Using a nonocclusive OCT technique, we performed angiography and OCT of culprit SVG lesions in patients with unstable angina (UA), ST-segment elevation myocardial infarction (STEMI), and non-STEMI. Fibrous and fatty tissue, calcification, thrombus, and plaque rupture were defined according to OCT objective criteria. Results: Twenty-eight SVGs (average age 14.6 years) in 26 patients were imaged. Lesions on angiography were complex (96.4%), with ulceration in 32.1% and thrombus in 21.4%. OCT disclosed a fibrofatty composition in all lesions, calcification in 32.1%, plaque rupture in 60.7%, and thrombus in 46.4%. Thrombus was progressively more frequent across groups (UA to STEMI, p=0.003; UA vs. myocardial infarction, p=0.006). A thin fibrous cap was marginally more frequent in myocardial infarction patients (UA vs. myocardial infarction, p=0.06; STEMI 100% vs. non-STEMI 53.3% vs. UA 20%, p=0.03). OCT features of friability were present in 67.9% of SVGs not correlating with clinical presentation. Conclusions: OCT of culprit lesions of old SVGs in patients with ACS demonstrates fibrofatty composition, relatively thin fibrous cap, plaque rupture, and thrombus, which correlate with the clinical spectrum of ACS. This suggests that similar mechanisms with native vessels’ atherosclerosis may be involved in SVG-related ACS.

La capacité de la tomographie par cohérence optique (OCT) à délivrer des images tomographiques de tissus biologiques in vivo, de manière non invasive et en temps réel, a suscité un intérêt croissant pour de nombreuses applications biomédicales, principalement en ophtalmologie pour l’imagerie de la rétine et du segment antérieur de l’œil. Toutefois, pour l’imagerie à haute résolution de tissus biologiques fortement diffusants, comme la sclérotique et la cornée œdémateuse, la technique nécessitait des améliorations technologiques. Dans cette thèse, un système d’OCT « Fourier-domain » (FD-OCT) à très haute résolution spatiale (< 4 µm), à la longueur d’onde de 1,3 µm, a été développé dans la Laboratoire Charles Fabry – Institute d’Optique Graduate School. Avec ce système original, nous avons réussi, pour la première fois, à visualiser correctement le canal de Schlemm de l’œil humain qui se trouve à une profondeur d’environ 0,8 mm dans le limbe de la cornée, milieu fortement diffusant. L’imagerie du canal de Schlemm est capitale afin d’envisager la chirurgie par laser du glaucome, qui consiste à inciser cette partie de l’œil afin d’améliorer l’écoulement de l’humeur aqueuse. Par ailleurs, en collaboration avec le Laboratoire d’Optique Appliquée de l’ENSTA ParisTech, nous avons démontré la possibilité de contrôler en temps réel par OCT des découpes par laser femtoseconde pratiquées dans la cornée humaine in vitro. Ces travaux ont montré que l’opération du Glaucome par laser femtoseconde, contrôlée par OCT, devrait être possible. / The ability of optical coherence tomography (OCT) to deliver tomographic images of biological tissues in vivo non-invasively and in real-time has been a growing interest in many biomedical applications, mainly in ophthalmology for imaging the retina and the anterior segment of the eye. However, developing high-resolution OCT for imaging strongly scattering biological tissues like sclera and edematous cornea has still been the main challenge. In this PhD work, an ultrahigh-resolution (< 4 µm) Fourier-domain OCT (FD-OCT) system optimized at 1.3 µm center wavelength was developed in Laboratoire Charles Fabry – Institut d’Optique Graduate School. Using this OCT system, we have, for the first time, properly visualized the Schlemm’s canal of the human eye that is located in the strongly scattering corneal limbus at depth of ~ 0.8 mm. Schlemm’s canal has been our target for OCT imaging because it plays an important role for the management of the aqueous humor that is responsible for causing glaucoma - an eye disease that can potentially lead to blindness. In collaboration with Laboratoire d’Optique Appliquée at ENSTA ParisTech, we have also demonstrated real-time OCT imaging of the femtosecond laser surgery in excised human cornea. These studies have thus shown that the surgery of glaucoma by femtosecond laser, monitored by OCT, would be possible.

<p>The goal of my Ph.D. thesis is to enhance the visualization of the peripheral retina using wide-field optical coherence tomography (OCT) in a clinical setting.</p><p>OCT has gain widespread adoption in clinical ophthalmology due to its ability to visualize the diseases of the macula and central retina in three-dimensions, however, clinical OCT has a limited field-of-view of 300. There has been increasing interest to obtain high-resolution images outside of this narrow field-of-view, because three-dimensional imaging of the peripheral retina may prove to be important in the early detection of neurodegenerative diseases, such as Alzheimer's and dementia, and the monitoring of known ocular diseases, such as diabetic retinopathy, retinal vein occlusions, and choroid masses.</p><p>Before attempting to build a wide-field OCT system, we need to better understand the peripheral optics of the human eye. Shack-Hartmann wavefront sensors are commonly used tools for measuring the optical imperfections of the eye, but their acquisition speed is limited by their underlying camera hardware. The first aim of my thesis research is to create a fast method of ocular wavefront sensing such that we can measure the wavefront aberrations at numerous points across a wide visual field. In order to address aim one, we will develop a sparse Zernike reconstruction technique (SPARZER) that will enable Shack-Hartmann wavefront sensors to use as little as 1/10th of the data that would normally be required for an accurate wavefront reading. If less data needs to be acquired, then we can increase the speed at which wavefronts can be recorded.</p><p>For my second aim, we will create a sophisticated optical model that reproduces the measured aberrations of the human eye. If we know how the average eye's optics distort light, then we can engineer ophthalmic imaging systems that preemptively cancel inherent ocular aberrations. This invention will help the retinal imaging community to design systems that are capable of acquiring high resolution images across a wide visual field. The proposed model eye is also of interest to the field of vision science as it aids in the study of how anatomy affects visual performance in the peripheral retina.</p><p>Using the optical model from aim two, we will design and reduce to practice a clinical OCT system that is capable of imaging a large (800) field-of-view with enhanced visualization of the peripheral retina. A key aspect of this third and final aim is to make the imaging system compatible with standard clinical practices. To this end, we will incorporate sensorless adaptive optics in order to correct the inter- and intra- patient variability in ophthalmic aberrations. Sensorless adaptive optics will improve both the brightness (signal) and clarity (resolution) of features in the peripheral retina without affecting the size of the imaging system.</p><p>The proposed work should not only be a noteworthy contribution to the ophthalmic and engineering communities, but it should strengthen our existing collaborations with the Duke Eye Center by advancing their capability to diagnose pathologies of the peripheral retinal.</p> / Dissertation

Insight Photonic Solutions Inc. has continued to develop their patented VT-DBR laser design; these wavelength tunable lasers promise marked image-quality and acquisition time improvements in SS-OCT applications. To be well suited for SS-OCT, tunable lasers must be capable of producing a highly linear wavelength sweep across a tuning range well-matched to the medium being imaged; many different tunable lasers used in SS-OCT are compared to identify the optimal solution. This work electrically and spectrally characterizes two completely new all-semiconductor VT-DBR designs to compare, as well. The Neptune VT-DBR, an O-band laser, operates around the 1310 nm range and is a robust solution for many OCT applications. The VTL-2 is the first 1060 nm VT-DBR laser to be demonstrated. It offers improved penetration through water over earlier designs which operate at longer wavelengths (e.g. - 1550 nm and 1310 nm), making it an optimal solution for the relatively deep imaging requirements of the human eye; the non-invasive nature of OCT makes it the ideal imaging technology for ophthalmology. Each laser has five semiconductor P-N junction segments that collectively enable precise akinetic wavelength-tuning (i.e. - the tuning mechanism has no moving parts). In an SS-OCT system utilizing one of these laser packages, the segments are synchronously driven with high speed current signals that achieve the desired wavelength, power, and sweep pattern of the optical output. To validate the laser’s fast tuning response time necessary for its use in SS-OCT, a circuit model of each tuning section is created; each laser section is modeled as a diode with a significant lead inductance. The dynamic resistance, effective capacitance, and lead inductance of this model are measured as a function of bias current and the response time corresponding to each bias condition is determined. Tuning maps, spectral linewidths, and side-mode suppression ratio (SMSR) measurements important to SS-OCT performance are also collected. Measured response times vary from 700 ps to 2 ns for the Neptune and 1.2 to 2.3 ns for the VTL-2. Linewidth measurements range from 9 MHz to 124 MHz for the Neptune and 300 kHz to 2 MHz for the VTL-2. SMSR measurements greater than 38 dB and 40 dB were observed for the Neptune and VTL-2, respectively. Collectively, these results implicate the VT-DBR lasers as ideal tunable sources for use in SS-OCT applications.

SWIFTS (Stationary Wave Integrated Fourier Transform Spectrometer) est une nouvelle technologie innovante de spectrométrie qui permet une réduction radicale de la taille des spectromètres à Transformée de Fourier, tout en conservant, et même en améliorant leurs performances. Grâce aux avancées de l'optique intégrée et des nanotechnologies, SWIFTS repose sur une méthode de détection optique originale, sans aucune partie mobile, où des nanoplots métalliques échantillonnent directement le champ évanescent d'une onde stationnaire dans un guide d'onde.Dans cette thèse, nous proposons de présenter le cheminement complet qui a mené, en partant du concept original, au développement puis à la mise en pratique de la technologie SWIFTS. Le document illustre notamment les caractérisations optiques, les choix technologiques et les optimisations entrepris pour la réalisation de spectromètres fonctionnels dans le domaine visible et proche-infrarouge. Des procédures de calibrages novatrices et complémentaires, basées sur du multiplexage fréquentiel et sur de l'interférométrie à faible cohérence temporelle, ont été développées pour déterminer avec précision les différentes irrégularités de fabrication et de comportement de l'appareil complètement intégré. Les spectromètres calibrés permettent à présent d'aborder des applications diverses en industrie et en recherche, de la caractérisation hautes performances de lasers, à l'interrogation de capteurs fibrés à réseaux de Bragg, aux techniques de spectrométries Raman et LIBS, et de tomographie optique OCT, jusqu'aux sciences de l'Univers (géophysique, astrophysique).SWIFTS est une innovation de rupture qui, de part sa miniaturisation obtenue sans compromis avec de hautes performances d'analyse spectrale, a la capacité de faire passer la spectrométrie du stade de la mesure complexe en laboratoire à celle d'un simple composant intégré pour des applications exigeantes. / SWIFTS (Stationary Wave Integrated Fourier Transform Spectrometer) is a new innovative technology of spectrometry that allows a drastic reduction of the size of Fourier transform spectrometers, while maintaining, and even improving their performance. With advances in integrated optics and nanotechnology, SWIFTS is based on an original method of optical detection, without any moving part, where metallic nanodots directly sample the evanescent field of a standing wave in a waveguide.In this thesis, we propose to present the complete process that led, starting from the original concept, to the development and the applications of the technology. The document illustrates the optical characterizations, the technological choices and the optimizations made for the realization of functional spectrometers in the visible and near-infrared range. Innovative and complementary procedures of calibrations, based on frequency multiplexing and low coherence interferometry, have been developed to accurately determine the various irregularities of the manufacturing and of the behavior of the integrated device. The calibrated spectrometers allow to address various applications in industry and research, such as high performance characterization of lasers, interrogation of fiber Bragg gratings sensors, Raman and LIBS spectrometry, optical coherence tomography OCT, and sciences of the Universe (geophysics, astrophysics).SWIFTS is a breakthrough innovation in spectrometry, without trade-off between miniaturization and high performance, that opens the way for product development based on the most demanding applications currently performed in research laboratories.

The early non-invasive diagnosis of epithelial tissue alterations in daily clinical routine is still challenging. Since optical coherence tomography (OCT) shows the potential to differentiate between benign and malignant tissue of primal endothelium, OCT could be beneficial for the early diagnosis of malignancies in routine health checks. In this research, a new handheld endoscopic scanning unit was designed and connected to a spectral domain OCT system of our workgroup for the in vivo imaging of the human oral mucosa.

In this work is describe anatomy and physiology of the cornea. The following are the primary non-inflamatory degeneration of the cornea. Then describe the physical principles diagnostic devices for cornea – keratometer, pachymeter, Michelson interferometr and optical coherence tomography (OCT). At the end of the theoretical introduction is describes the principle of laser correction surgery – LASIK. The practical part is divided into two main objectives. The first task is propose an algorithm for automatic detection of corneal surface and then calculation of corneal thickness and size of the chamber angle in Matlab. The aim of the second task is image flap analysis for boundary detection.