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UC Riverside UC Riverside Electronic Theses and Dissertations UC Riverside UC Riverside Electronic Theses and Dissertations Title The Feasibility of a Transparent Cranial Implant for Chronic Structural and Functional Brain Imaging Permalink https://escholarship.org/uc/item/2kj0728r Author Halaney, David Lloyd Publication Date 2021 Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California UNIVERSITY OF CALIFORNIA RIVERSIDE The Feasibility of a Transparent Cranial Implant for Chronic Structural and Functional Brain Imaging A Dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Mechanical Engineering by David L. Halaney March 2021 Dissertation Committee: Dr. Guillermo Aguilar, Chairperson Dr. Lorenzo Mangolini Dr. Suveen Mathaudhu Copyright by David L. Halaney 2021 The Dissertation of David L. Halaney is approved: Committee Chairperson University of California, Riverside Acknowledgments I would like to thank all of the researchers and mentors with whom I have had the pleasure of working on this and other related projects. Each of my Dissertation Committee members has provided me with extensive professional guidance and has taught me a great deal about scientific research. I would especially like to thank Dr. Guillermo Aguilar, the chairman of my committee and my primary PhD advisor, from whom I have learned so much. I would also like to thank Dr. Thomas E. Milner for his mentorship and guidance throughout this program and my entire career. I would like to thank my parents, whose love and guidance have led me to where I am today. Above all, I would like to thank my wife, Sarah Halaney, and my children, Spencer Thompson, Sterling Thompson, and Roselyn Halaney, for their unwavering support, encouragement and love during this PhD program; they made this accomplishment possible. iv ABSTRACT OF THE DISSERTATION The Feasibility of a Transparent Cranial Implant for Chronic Structural and Functional Brain Imaging by David L. Halaney Doctor of Philosophy, Graduate Program in Mechanical Engineering University of California, Riverside, March 2021 Dr. Guillermo Aguilar, Chairperson A variety of medical conditions (e.g., traumatic brain injury, cerebral edema, stroke, brain tumors) necessitate surgical craniectomy to access the brain, followed by the placement of a cranial implant to replace the excised cranial bone. Cranial implants provide mechanical protection to the brain, and are made from a variety of materials ranging from polymers to metals and ceramics. Despite this variety of implant options, all current cranial implants for patient use lack optical transparency which could allow for brain imaging or therapy without additional open-skull procedures. The “Window to the Brain” is a novel transparent cranial implant made from a tough, biocompatible ceramic called nanocrystalline-Yttria Stabilized Zirconia. Preliminary studies have shown that this material allows for acute brain imaging in vivo, but its suitability for chronic use has not been established. In this dissertation, I investigated (1) the stability of the optical access provided by the window for chronic brain imaging in vivo; (2) functional and structural v imaging techniques across the window; (3) laser bacterial antifouling strategies for use with the window; (4) characterization of the window’s optical properties which impact imaging. This work provides answers to some of the key remaining questions regarding the feasibility of a transparent cranial implant for chronic structural and functional brain imaging based on nc-YSZ. vi Table of Contents List of Figures……………………………………………………………...……….……vii Chapter 1: Introduction…………………………………………………………….........1 Chapter 2: Evaluation of a Transparent Cranial Implant as a Permanent Window for Cerebral Blood Flow Imaging.………….……………………………………………….6 Background……………………………………………………………………..…6 Methods……………………………………………………………………….…..8 Implant Fabrication and Preparation…………………...………………....8 Animals…..…………………………………...…………………………..9 Surgical Procedures…….………………..………………………………..9 Laser Speckle Imaging...…………...…………………………………….11 Experimental Design…..………………………………………………....12 Image Processing and Data Analysis……………………………..………12 Results..……………………………………………………………………….….15 Experiment 1: LSI Image Quality Over Time………………….…………15 Experiment 2: LSI Image Quality through Skull vs. Chronic Implant……17 Discussion……………....………….………………………………...………......19 Conclusion……………………………………………………………………….26 Acknowledgments……………….……………………..…………...……………27 Chapter 3. Chronic Brain Imaging across a Transparent Nanocrystalline Yttria- Stabilized-Zirconia Cranial Implant………….……………………………….....……28 Background………………………………………………………………………28 vii Methods……………………………………………………………………….….30 Implant Fabrication and Preparation……..………………………………30 Animals…………………………………………………………………..30 Surgical Procedures and Post-Surgical Monitoring and Care……………30 Laser Speckle Imaging……………………….………………..……....…31 Optical Coherence Tomography Imaging………………………………..33 Cross-Sectional OCT Intensity Images……………..…….……...35 OCT Angiography Images...……………………………………..36 Results………....………………..………....……………………….………….…39 Discussion…………………………………………...………………..……….....46 Conclusion………………………….……………………………………………48 Acknowledgments…………………………………...…………..……………….49 Chapter 4. Optical Access to Arteriovenous Cerebral Microcirculation Through a Transparent Cranial Implant……………………………………………...…...…........50 Background………………………………………………………………………50 Methods……………………………………………………………………….….54 Transparent Stabilized‐Zirconia Cranial Implant………..……...………..54 Animals…………………………….………………….…………………55 Surgical Procedures..……………….………………….…………………55 MSRI and LSI…..………………….………………….…………………55 Vein‐Artery Separation Using MSRI………………….…………………57 viii Rebuilding Arteriovenous Cerebral Blood Flowmetry Map Based on MSRI‐ LSI………………………………….………………….…………………58 Quantitative Analysis of the LSI Resolution and Contrast………………60 Results………....………………..…………………....……………………….….62 MSRI Images of the Brain: Comparison of Through‐Skull and Through‐ Implant Images…...……….…...................................................................62 Comparison of the Improved LSI Image Quality: Through‐Implant Versus Through‐Skull……………..……………………………………………..65 Assessing Arteriovenous Blood Flow Through‐Implant…………………67 Discussion…………………………………………...…………………………...68 Conclusion……………………………………………………………………….74 Acknowledgments…………………………………...…………..……………….74 Chapter 5. Enhanced Near Infrared Optical Access to the Brain with a Transparent Cranial Implant and Scalp Optical Clearing………………...……………...….....…..76 Background………………………………………………………………….…...76 Methods………………………………………………………………………......79 Implant Fabrication and Preparation………………………......................79 Scalp and Skull Samples…………………………....……....…....…..…..79 Surgical Procedure…………………………....……………………..…...80 Optical Clearing……......…………………….………………..……........80 Tissue Characterization…………...….…………………………………..80 Experimental Method……………...……………..……...…………...…..82 ix Results and Discussion..………………..…………………………………….......83 Conclusions……………………………………………………………………....89 Acknowledgments…………………………………...…………..…………….....90 Chapter 6. Evaluation of Laser Bacterial Anti-Fouling of Transparent Nanocrystalline Yttria-Stabilized-Zirconia Cranial Implant….………….….....…....91 Background………………………………………………………………………91 Methods……………………………………………………………………….….93 Implant Fabrication and Preparation……………....……....……………..93 Bacterial Inoculation…..……………………..………….……………….94 Laser Device………………………..….………………..……...………..96 Temperature Measurements..………………………………….……...….96 Bioluminescence Imaging System……………………..……..…….........97 Statistical Analysis……………...……………………..……..……..........97 Results ……………......………………..……………………………….…….….98 Discussion…………………………...…………....…………………...……......100 Conclusions……………………………………………………………………..106 Acknowledgments…………………………………...…………..……….……..107 Chapter 7. Characterization of Ageing Resistant Transparent Nanocrystalline Yttria- Stabilized Zirconia Implants ……………………………………………….….....…..108 Background……………………………………………………………………..108 Methods…………………………………………………………………………110 Implant Fabrication and Preparation……………....……....……………110 x Ageing Test…………………………………..………….……………...112 Material Characterization…………..….………………..……...……….113 Optical Characterization……………………………………….……......115 Mechanical Characterization…………………………..……..……........116 Results ……………......………………..……………………………….………117 Densified Samples…………………………………………….…….......117 Material Characterization……………….……….…………..…....….....117 Optical Characterization………………………………………………...117 Hardness Characterization……………………………………………...119 Discussion…………………………...…………....…………………...……......120 Conclusions……………………………………………………………………..124 Acknowledgments…………………………………...…………..……….……..124 Chapter 8. Group Refractive Index of nc-YSZ Transparent Cranial Implants…………………………………………………………………..………........126 Background……………………………………………………………………..126 Methods…………………………………………………………………………128 Implant Fabrication and Preparation……………....……....……………128 OCT Imaging………………………………..………….…………..…..129 Experimental Setup for Temperature-Dependent Measurements………129 Group Refractive Index of Water…..………………………….……......132 Method 1: Image-based Analysis………………………..……..…….......132 Method 2: Spectral Phase Function based Analysis……………………..134 xi Results ……………......………………..……………………………….………136 Discussion…………………………...…………....…………………...……......138 Conclusions……………………………………………………………………..140 Acknowledgments…………………………………...…………..……….……..141 Chapter 9. Recommendations for Future Work………………………………….….142
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