Photonic integrated Mach-Zehnder interferometer with an on-chip reference arm for optical coherence tomography

Optical coherence tomography (OCT) is a noninvasive, three-dimensional imaging modality with several medical and industrial applications. Integrated photonics has the potential to enable mass production of OCT devices to significantly reduce size and cost, which can increase its use in established fields as well as enable new applications. Using silicon nitride (Si(3)N(4)) and silicon dioxide (SiO(2)) waveguides, we fabricated an integrated interferometer for spectrometer-based OCT. The integrated photonic circuit consists of four splitters and a 190 mm long reference arm with a foot-print of only 10 × 33 mm(2). It is used as the core of a spectral domain OCT system consisting of a superluminescent diode centered at 1320 nm with 100 nm bandwidth, a spectrometer with 1024 channels, and an x-y scanner. The sensitivity of the system was measured at 0.25 mm depth to be 65 dB with 0.1 mW on the sample. Using the system, we imaged human skin in vivo. With further optimization in design and fabrication technology, Si(3)N(4)/SiO(2) waveguides have a potential to serve as a platform for passive photonic integrated circuits for OCT

Choroidal Haller's and Sattler's Layer Thickness Measurement Using 3-Dimensional 1060-nm Optical Coherence Tomography

Objectives: To examine the feasibility of automatically segmented choroidal vessels in three-dimensional (3D) 1060-nmOCT by testing repeatability in healthy and AMD eyes and by mapping Haller's and Sattler's layer thickness in healthy eyes Methods: Fifty-five eyes (from 45 healthy subjects and 10 with non-neovascular age-related macular degeneration (AMD) subjects) were imaged by 3D-1060-nmOCT over a 36°x36° field of view. Haller's and Sattler's layer were automatically segmented, mapped and averaged across the Early Treatment Diabetic Retinopathy Study grid. For ten AMD eyes and ten healthy eyes, imaging was repeated within the same session and on another day. Outcomes were the repeatability agreement of Haller's and Sattler's layer thicknesses in healthy and AMD eyes, the validation with ICGA and the statistical analysis of the effect of age and axial eye length (AL) on both healthy choroidalsublayers. Results: The coefficients of repeatability for Sattler's and Haller's layers were 35% and 21% in healthy eyes and 44% and 31% in AMD eyes, respectively. The mean±SD healthy central submacular field thickness for Sattler's and Haller's was 87±56 µm and 141±50 µm, respectively, with a significant relationship for AL (P<.001). Conclusions: Automated Sattler's and Haller's thickness segmentation generates rapid 3D measurements with a repeatability correspondingto reported manual segmentation. Sublayers in healthy eyes thinnedsignificantly with increasing AL. In the presence of the thinned Sattler's layer in AMD, careful measurement interpretation is needed. Automatic choroidal vascular layer mapping may help to explain if pathological choroidal thinning affects medium and large choroidal vasculature in addition to choriocapillaris loss.Macular Vision Research FoundationMedical University of ViennaEuropean Union (project FUN OCT (FP7 HEALTH, contract no. 201880))European Union (FAMOS (FP7 ICT 317744))European Union (FWF-NFN ‘Photoacoustic imaging in biology and Medicine’, Oesterreichische Nationalbank Jubilaumsfonds projekt (14294))National Institutes of Health (U.S.) (NIH R01-EY011289-27)Deutsche Forschungsgemeinschaft (DFG-GSC80-SAOT)Deutsche Forschungsgemeinschaft (DFG-GSC80-SAOT, DFG-HO-1791/11-1)Carl Zeiss Meditec, Inc.FEMTOLASERS (Firm)Christian Doppler Societ

Imaging human cutaneous morphology and microcirculation using photoacoustic

Goldener Standard in der Dermatologie fuer die Bildgebung von Gewebem morphologie ist Histopathologie. Es ist invasiv, muehsam und zeitaufwendig, daher wird es nur in notwendigen Faellen durchgefuehrt. Optische Kohaerenztomographie (OCT) ist eine nicht-invasive und nicht-ionisierende Bildgebungstechnik, die tief aufgeloeste Informationen von Weichgewebe bis zu einer Tiefe von 1-2 mm liefert. Es handelt sich um eine interferometrische Technik, die auf dem Kohaerenz-Gating basiert, bei der ein Laserstrahl zeilenweise die untersuchende Probe abtastet, und der zurueck reflektierte Strahl liefert die strukturelle Information. Diese Technik basiert auf der raeumlichen Verteilung des Brechungsindex des Gewebes. Mit OCT ist eine in-vivo volumetrische Visualisierung der Probe moeglich. Es ist eine gut etablierte bildgebende Modalitaet in der Augenheilkunde seit mehr als einem Jahrzehnt und es gewinnt Akzeptanz in der Dermatologie in den letzten Jahren.^ ^ Photoakustische Tomographie (PAT) ist eine neuere, nicht-invasive Modalitaet, bei der die Probe durch einen Hochleistungs-Pulsar-Laser angeregt wird und im Gegenzug durch thermoelastische Expansion akustische Wellen erzeugt und aufgezeichnet werden. PAT visualisiert die raeumliche Verteilung von Chromophoren, die das Anregungslicht bis zu einigen Millimetern Tiefe absorbieren. Haemoglobin in den roten Blutkoerperchen ist ein starker endogener Chromophor, wenn es um die In-vivo-Bildgebung geht und daher mit PAT die volumetrische Vaskulaturkarte erhalten kann. Diese Kapazitaet von PAT geht ueber die Histopathologie und Dermatoskopie hinaus. Im ersteren erfaehrt das Gewebe oft ein gewisses Mass der Verformung, wodurch der urspruenglicher Zustand des Gewebes veraendert und die Gefaesse aus dem Blut abgelassen werden und im letzteren sind keine Tiefe aufgeloeste Informationen verfuegbar.^ Diese und andere Gruende ueberzeugen Kliniker und Wissenschaftler um mehr Aufmerksamkeit fuer PAT als eine andere nicht-invasive diagnostische Technik, Nachfolgend vermarkten einige Anbieter bereits PAT-Geraete fuer praeklinische oder klinische Anwendungen. Die laterale Aufloesung von PAT liegt in der Groessenordnung von vielen Mikrometern, jedoch in zehnerschritten und eignet sich daher nicht fuer die Bildgebung von Kapillaren mit einem Innendurchmesser von Mikrometern, die kleiner sind. Eine funktionelle Erweiterung von OCT, die empfindlich auf bewegte Partikel ist, naemlich OCT-Angiographie (OCTA), eignet sich fuer die Abbildung von Kapillaren. Ein multimodales Bildgebungssystem, welches PAT / OCT / OCTA verwendet, wuerde eine komplementaere Bildgebung ermoeglichen, die Morphologie und funktionelle Eigenschaften von Gewebe kombiniert. Im ersten Kapitel dieser Arbeit werden wissenschaftliche Hintergrund von OCT und PAT skizziert.^ Dann werden die Verbesserungen des bestehenden Dual-Modality-Imaging-Systems vorgestellt, die von Kandidaten umgesetzt wurden. Im zweiten Kapitel ist das erste Papier enthalten. Dort praesentieren wir die PAT / OCT-Visualisierung mehrerer Hautpathologien, bei denen die komplementaeren Informationen unseres Systems beispielloser Bilder der Pathologien an die Kliniker liefern. Im dritten Kapitel wird das OCTA eingefuehrt und dann folgt das zweite Papier, wo wir gezeigt haben wie OCTA Kapillarnetz in der Haut visualisierten. Im naechsten Kapitel diskutieren wir die Vor- und Nachteile des multimodalen Systems. Schliesslich sind die zukuenftigen Richtungen und die endgueltige Schlussfolgerungen im letzten Kapitel gegeben.Golden standard in dermatology for imaging tissue morphology is histopathology. It is invasive, laborious and time consuming, therefore it is performed only in necessary cases. Optical coherence tomography (OCT) is a non invasive and non ionizing imaging technique that provides depth resolved information of soft tissue up to 1-2 mm depth. It is an interferometric technique based on coherence gating in which a laser beam raster scans a sample and the back reflected beam provides the structural information based on the spatial distribution of the refractive index of the tissue. Using OCT in vivo real time volumetric visualization of specimen is possible. It is a well established imaging modality in ophthalmology for more than a decade and it is gaining acceptance in dermatology in recent years.^ ^ Photoacoustic tomography (PAT) is an emerging non-invasive modality in which sample is excited by high energy pulsar laser and in return through thermoelastic expansion acoustic waves are produced and recorded. PAT visualizes spatial distribution of chromophores that absorb the excitation light up to several millimeters in depth. Hemoglobin in the red blood cells is a strong endogenous chromophore when it comes to in vivo imaging and therefore using PAT one can obtain the volumetric vasculature map. This capacity of PAT goes beyond that of histopathology and dermatoscopy. In the former one the tissue often undergoes some degrees of deformation that the original condition of the tissue is changed and the vessels are drained from blood and in the later one no depth resolved information is available.^ These and other reasons are convincing clinicians and scientist to turn more attention to PAT as another noninvasive diagnostic technique and consecutively some vendors already commercialized PAT devices for preclinical or clinical applications. Lateral resolution of PAT is in the order of many tens of micrometers, and therefore is not suitable for imaging capillaries with inner diameter of few tens of micrometers to few micrometers. A functional extension of OCT that is sensitive to moving particle, namely OCT-Angiography (OCTA) fills the gap for imaging capillaries. A multimodal imaging system utilizing PAT/OCT/OCTA would enable complementary imaging combining morphology and functional properties of tissue. In the first chapter of this thesis, scientific background of OCT and PAT are outlined. Then the improvements to the existing dual-modality imaging system that were implemented by the candidate are presented. In the second chapter the first paper is included.^ There we present PAT/OCT visualization of several cutaneous pathologies where the complementary information offered by our system provided unprecedented images of the pathologies to clinicians. In the third chapter the OCTA is introduced and then it is followed by the second paper where we showed how OCTA succeeds in visualizing the capillary network in skin. In the next chapter we discuss the advantages and drawbacks of the multimodal system. Finally the future directions and the final conclusion are given in the last chapter.optical coherence tomography: imaging setup and applicationsubmitted by Behrooz ZabihianMedizinische Universität Wien, Diss., 201

EVALUATION OF SPECKLE REDUCTION WITH DENOISING FILTERING IN OPTICAL COHERENCE TOMOGRAPHY FOR DERMATOLOGY

ABSTRACT Optical Coherence Tomography (OCT) has shown a great potential as a complementary imaging tool in the diagnosis of skin diseases. Speckle noise is the most prominent artifact present in OCT images and could limit the interpretation and detection capabilities. In this work we evaluate various denoising filters with high edge-preserving potential for the reduction of speckle noise in 256 dermatological OCT Bscans. Our results show that the Enhanced Sigma Filter and the Block Matching 3-D (BM3D) as 2D denoising filters and the Wavelet Multiframe algorithm considering adjacent B-scans achieved the best results in terms of the enhancement quality metrics used. Our results suggest that a combination of 2D filtering followed by a wavelet based compounding algorithm may significantly reduce speckle, increasing signal-to-noise and contrast-to-noise ratios, without the need of extra acquisitions of the same frame

Visualization 4: In vivo dual-modality photoacoustic and optical coherence tomography imaging of human dermatological pathologies

3D-rendered video of fused PAT/OCT data of a patient with chronic hyperkeratotic hand eczema with a virtual cutout depicting the surface of the epidermis, a part of the capillary loop system, and the papillary dermis. The OCT data is presented with t Originally published in Biomedical Optics Express on 01 September 2015 (boe-6-9-3163

Choroidal Haller’s and Sattler’s Layer Thickness Measurement Using 3-Dimensional 1060-nm Optical Coherence Tomography

Objectives: To examine the feasibility of automatically segmented choroidal vessels in three-dimensional (3D) 1060-nmOCT by testing repeatability in healthy and AMD eyes and by mapping Haller’s and Sattler’s layer thickness in healthy eyes Methods: Fifty-five eyes (from 45 healthy subjects and 10 with non-neovascular age-related macular degeneration (AMD) subjects) were imaged by 3D-1060-nmOCT over a 36ux36u field of view. Haller’s and Sattler’s layer were automatically segmented, mapped and averaged across the Early Treatment Diabetic Retinopathy Study grid. For ten AMD eyes and ten healthy eyes, imaging was repeated within the same session and on another day. Outcomes were the repeatability agreement of Haller’s and Sattler’s layer thicknesses in healthy and AMD eyes, the validation with ICGA and the statistical analysis of the effect of age and axial eye length (AL) on both healthy choroidalsublayers. Results: The coefficients of repeatability for Sattler’s and Haller’s layers were 35% and 21% in healthy eyes and 44% and 31% in AMD eyes, respectively. The mean6SD healthy central submacular field thickness for Sattler’s and Haller’s was 87656 mm and 141650 mm, respectively, with a significant relationship for AL (P,.001). Conclusions: Automated Sattler’s and Haller’s thickness segmentation generates rapid 3D measurements with a repeatability correspondingto reported manual segmentation. Sublayers in healthy eyes thinnedsignificantly with increasing AL. In the presence of the thinned Sattler’s layer in AMD, careful measurement interpretation is needed. Automatic choroidal vascular layer mapping may help to explain if pathological choroidal thinning affects medium and large choroidal vasculature in addition to choriocapillaris loss

Visualization 1: Combined multi-modal photoacoustic tomography, optical coherence tomography (OCT) and OCT angiography system with an articulated probe for in vivo human skin structure and vasculature imaging

related to Fig. 4(e) Originally published in Biomedical Optics Express on 01 September 2016 (boe-7-9-3390