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Co-Registered Multimodal Endoscope for Early Ovarian Cancer by David

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Co-Registered Multimodal Endoscope for Early Ovarian Cancer by David Co-registered Multimodal Endoscope for Early Ovarian Cancer by David Vega __________________________ Copyright © David Vega 2021 A Dissertation Submitted to the Faculty of the WYANT COLLEGE OF OPTICAL SCIENCES In Partial Fulfillment of the Requirements For the Degree of DOCTOR OF PHILOSOPHY In the Graduate College THE UNIVERSITY OF ARIZONA 2021 *$$)*&+!"**)++"&%&$$"++.)+"/+!+.!-)+!"**)++"&% ')')/ +"+# %)&$$%+!+"+'+*,#"##"% +!"**)++"&%)(,")$%+&)+! )&&+&)&!"#&*&'!/ +05/14/2021 + 05/14/2021 + "%#'')&-#%'+%&+!"*"**)++"&%"*&%+"% %+,'&%+!%"+0**,$"**"&% &+!"%#&'"*&+!"**)++"&%+&+! ),+&## !)/)+"/+!+ !-)+!"*"**)++"&%')'),%)$/")+"&%%)&$$% +!+"+'+*,#"##"% +!"**)++"&%)(,")$%+ +05/14/2021 "**)++"&%&$$"++!") 3 STATEMENT BY AUTHOR This dissertation has been submitted in partial fulfillment of the requirements for an advanced degree at the University of Arizona and is deposited in the University Library to be made available to borrowers under rules of the Library. Brief quotations from this dissertation are allowable without special permission, provided that an accurate acknowledgement of the source is made. Requests for permission for extended quotation from or reproduction of this manuscript in whole or in part may be granted by the head of the major department or the Dean of the Graduate College when in his or her judgment the proposed use of the material is in the interests of scholarship. In all other instances, however, permission must be obtained from the author. SIGNED: David Vega 4 DEDICATION A mi familia. To my family. 5 Table of Contents ABSTRACT 9 CHAPTER 1: INTRODUCTION 11 1.1 MOTIVATION 11 1.1.1. OVARIAN CANCER 12 1.1.2. DIAGNOSTIC IMAGING USED FOR OVARIAN CANCER DETECTION. 13 1.1.3. OVARIAN TISSUE ACCESS 13 1.2 ENDOSCOPES WITH VARYING FOV (MAGNIFICATION) 15 1.3 OPTICAL COHERENCE TOMOGRAPHY (OCT) 17 1.3.1 OPTICAL COHERENCE TOMOGRAPHY (OCT) AND OPTICAL COHERENCE MICROSCOPY (OCM) 17 1.3.2 TIME DOMAIN OCT (TD-OCT) 21 1.3.3 SPECTRAL DOMAIN OCT (SD-OCT) 26 1.3.4 OCT MECHANISM OF CONTRASTS IN TISSUE 34 1.4 MULTI-PHOTON MICROSCOPY (MPM) 36 1.4.1 MULTI-PHOTON MICROSCOPY (MPM) PRINCIPLES 36 1.4.2 MPM MECHANISMS OF CONTRAST IN TISSUE 38 1.5 NARROW-BAND REFLECTANCE IMAGING 45 1.5.1 REFLECTANCE MECHANISMS OF CONTRAST 45 1.5.2 HEMOGLOBIN ABSORPTION TO IDENTIFY AREAS OF INCREASED VASCULARITY 46 CHAPTER 2: PRESENT STUDY 48 2.1 ENABLING MULTIPLE OPTICAL PATHS FOR CO-REGISTERED IMAGING 48 2.2 CO-REGISTERED PROXIMAL SYSTEM 51 2.3 EN-FACE TRIPLE MODALITY CO-REGISTERED ENDOSCOPE (SALPINGOSCOPE) 53 CHAPTER 3: FUTURE WORK 56 4.1 MULTIPLE OPTICAL PATHS FOR CO-REGISTERED IMAGING FUTURE WORK 56 4.2 CO-REGISTERED PROXIMAL SYSTEM FUTURE WORK 56 4.3 EN-FACE TRIPLE MODALITY CO-REGISTERED ENDOSCOPE (SALPINGOSCOPE) FUTURE WORK 57 REFERENCES 59 APPENDIX A: USE OF EMBEDDED AND PATTERNED DICHROIC SURFACES WITH REFLECTIVE OPTICAL POWER TO ENABLE MULTIPLE OPTICAL PATHS IN A MICRO-OBJECTIVE 63 A.1 ACCEPTED MANUSCRIPT: USE OF EMBEDDED AND PATTERNED DICHROIC SURFACES WITH REFLECTIVE OPTICAL POWER TO ENABLE MULTIPLE OPTICAL PATHS IN A MICRO-OBJECTIVE 63 6 A.1.1 FILES STORAGE AND CONTRAST DATA 85 A.1.2 NON-SEQUENTIAL MODELING OF NON-CONVENTIONAL COMPONENTS 87 A.2 ACCEPTED ABSTRACT: MODEL AND EVALUATION OF FACE FORWARD ILLUMINATION FOR MULTIMODAL ENDOSCOPIC PROBES 94 A.2.1 REFLECTANCE MODALITY STRAY LIGHT STUDY 100 A.3 GENERATING VISUALIZATION OF SCANNING SYSTEMS WITH OPTICSTUDIO 114 APPENDIX B: PROXIMAL SUPPORTING SYSTEM FOR CO-REGISTERED MULTIMODAL IMAGING DESIGNED FOR REFLECTANCE, MULTIPHOTON, AND OPTICAL COHERENCE MICROSCOPY. 118 B.1 ACCEPTED MANUSCRIPT: A CO-REGISTERED MULTIMODAL IMAGING SYSTEM FOR REFLECTANCE, MULTIPHOTON, AND OPTICAL COHERENCE MICROSCOPY. 118 B.1.1 FILES STORAGE LOCATION 141 B.2 ELECTRONICS FOR SYSTEMS WITH MULTIPLE PHOTOMULTIPLIER TUBES 142 B.3 STANDARD OPERATING PROCEDURE B02-021B: ALIGNMENT & ASSEMBLY PROCEDURE OF OPTICAL COMPONENTS FOR THE MULTIPHOTON MICROSCOPE 145 B.4 STANDARD OPERATING PROCEDURE B02-022: SALPINGOSCOPE SPECTROMETER ALIGNMENT 172 APPENDIX C: TRIPLE MODALITY CO-REGISTERED ENDOSCOPE. 181 C.1 MANUSCRIPT: TRIPLE-MODALITY CO-REGISTERED ENDOSCOPE FEATURING WIDE-FIELD REFLECTANCE IMAGING, AND HIGH-RESOLUTION MULTIPHOTON AND OPTICAL COHERENCE MICROSCOPY. 181 C.1.1 FILES STORAGE LOCATION 215 C.2 STANDARD OPERATING PROCEDURE B16-011: SALPINGOSCOPE FIBER GLUING 216 C.3 STANDARD OPERATING PROCEDURE B02-024: SALPINGOSCOPE STOP-OBJECTIVE LENS GLUING 227 C.4 STANDARD OPERATING PROCEDURE B16-014: SALPINGOSCOPE FERRULE CONSTRUCTION 234 C.5 STANDARD OPERATING PROCEDURE B16-012: SALPINGOSCOPE HANDLE ASSEMBLY 253 C.6 STANDARD OPERATING PROCEDURE B02-023: CONNECTORIZING THE SALPINGOSCOPE 273 C.7 STANDARD OPERATING PROCEDURE B02-017A: SALPINGOSCOPE CLEANING - STERILIZATION 284 C.8 STANDARD OPERATING PROCEDURE B02-027: MULTIMODAL MICROSCOPE AND SALPINGOSCOPE OCT SPECTROMETER CALIBRATION AND ALIGNMENT 286 7 LIST OF FIGURES Figure 1. (Left) A-scan of backscattered light intensity vs axial position. (Right) B-scan where adjacent A-scans are taken at different locations of a transverse scan of the sample. .................. 17 Figure 2. (Left) A low NA imaging system providing a large DOF several times larger than the coherence length. (Right) A high NA imaging system providing a DOF of about one coherence length............................................................................................................................................. 20 Figure 3. Time Domain OCT basic diagram. ............................................................................... 21 Figure 4. Diagram of a balanced detection system in a TD-OCT configuration. ........................ 22 Figure 5. Interferogram showing the carrier in blue and the envelope in red. ............................. 23 Figure 6. Representation of multiple scatterers along the axial direction. ................................... 24 Figure 7. Full Idet is shown in blue. Envelope shown in red. ....................................................... 25 Figure 8. A-line extracted from the multiple scatterers. .............................................................. 26 Figure 9. Spectral Domain OCT basic diagram. .......................................................................... 27 Figure 10. Ophthalmic Spectral Domain OCT system diagram. ................................................. 28 Figure 11. Gaussian shaped spectrum as a function of wavenumber S(k) .................................. 28 Figure 12. Different frequency modulations produced by the echo delay between zR and zSn where zSn’ has a larger delay than zSn. The frequency modulation is imposed in a Gaussian shaped spectrum. ........................................................................................................................... 29 Figure 13. Representation of multiple scatterers along the axial direction using a delta function scaled by their respective reflectivity. .......................................................................................... 29 Figure 14. Representation of Idet at the detector plane. Cross-correlation terms and auto- correlation terms are present. ........................................................................................................ 31 Figure 15. Representation of Idet after spectrum DC term subtraction. ........................................ 31 Figure 16. Fourier transform showing the positive and the negative sides. The red side of the graph is usually not used. .............................................................................................................. 33 Figure 17. Fourier transform showing only the positive side with a threshold filter. .................. 34 Figure 18. Jablonski diagram for 1-photon absorption fluorescence excitation. Left axis represents the energy and bottom axis represents time. Blue squiggly arrow represents a high energy photon that is absorbed by the molecule. Blue arrow represents the transition of the electron to a possible excited electronic state. Green arrow represents energy dissipation between vibrational states. Red arrow represents the transition of the molecule to a ground electronic state where the energy is dissipated through electromagnetic emission represented with the red squiggly arrow. If the molecule does not come back to the true ground state after electromagnetic emission decay, it can further decay through energy dissipation until ground state is reached. .. 37 Figure 19. Jablonski diagram for 2-photon absorption fluorescence excitation. Left axis represents the energy and bottom axis represents time. Dark red squiggly arrow represents a high energy photon that is absorbed by the molecule that transition the electron to a possible excited 8 state. The molecule can then relax through non-radiative relaxation (green arrow) until it decays by emitting electromagnetic radiation (light red squiggly arrow). ............................................... 39 Figure 20. Jablonski diagram for 3-photon absorption fluorescence excitation. Dark red squiggly arrow represents a high energy photon that is absorbed by the molecule that transition the electron to a possible excited state. The molecule can then relax through non-radiative relaxation (green arrow) until it decays by emitting electromagnetic radiation (green squiggly arrow). ..... 41 Figure 21. Jablonski diagram for SHG. Dark red squiggly arrow represents a high energy photon that is absorbed by the molecule that transition the electron to a virtual excited state. The molecule can
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