Intraoperative Fourier domain optical coherence tomography for microsurgery guidance and assessment

In this dissertation, advanced high-speed Fourier domain optical coherence tomography (FD-OCT)systems were investigated and developed. Several real-time, high resolution functional Spectral-domain OCT (SD-OCT) systems capable of imaging and sensing blood flow and motion were designed and developed. The system were designed particularly for microsurgery guidance and assessment. The systems were tested for their ability to assessing microvascular anastomosis and vulnerable plaque development. An all fiber-optic common-path optical coherence tomography (CP-OCT) system capable of measuring high-resolution optical distances, was built and integrated into di fferent imaging modalities. First, a novel non-contact accurate in-vitro intra-ocular lens power measurement method was proposed and validated based on CP-OCT. Second, CP-OCT was integrated with a ber bundle based confocal microscope to achieve motion-compensated imaging. Distance between the probe and imaged target was monitored by the CP-OCT system in real-time.The distance signal from the CP-OCT system was routed to a high speed, high resolution linear motor to compensate for the axial motion of the sample in a closed-loop control. Finally a motion-compensated hand-held common-path Fourier domain optical coherence tomography probe was developed for image-guided intervention. Both phantom and ex vivo models were used to test and evaluate the probe. As the data acquisition speed of current OCT systems continue to increase, the means to process the data in real-time are in critically needed. Previous graphics processing unit accelerated OCT signal processing methods have shown their potential to achieve real-time imaging. In this dissertation, algorithms to perform real-time reference A-line subtraction and saturation artifact removal were proposed, realized and integrated into previously developed FD-OCT system CPU-GPU heterogeneous structure. Fourier domain phase resolved Doppler OCT (PRDOCT) system capable of real-time simultaneous structure and flow imaging based on dual GPUs was also developed and implemented. Finally, systematic experiments were conducted to validate the system for surgical applications. FD-OCT system was used to detect atherosclerotic plaque and drug effi ciency test in mouse model. Application of PRDOCT for both suture and cu ff based microvascular anastomosis guidance and assessment was extensively stuided in rodent model

Fabrication of Nanotopographic Ophthalmic Device

Corneal disease is the second most prevalent cause of blindness in the world. Keratoplasty or corneal transplant is available as the last treatment resort and extended drug delivery following the procedure are preferred to be delivered by a drug eluting contact lens. Patients using either device in the wounded eye are prone to microbial infection that could complicate the outcome of the sight recovery. Thus, nanotopography, a physical surface modification studied to have potential antimicrobial effect and wound healing promotion, is considered to be integrated in novel design of both devices. Due to the spherical nature of the eye, conventional nanotechnology could not produce such surface, or requires heavy cost and resources. In this thesis, I : 1) improve a nanopatterning technique for spherical surface and apply it on a novel cornea device, 2) validate its biological responses in vivo, 3) apply the patterning technique for a contact lens design with a new class of material, 4) analyze the economic and commercial benefits of both device in current ophthalmic market. This thesis consists universal protocol for adaptive patterning methods on various material platform and outline validation method for future regulatory works. This thesis shall set the foundation for a medical device startups that could restore sights for millions around the world

Motor learning induced neuroplasticity in minimally invasive surgery

Technical skills in surgery have become more complex and challenging to acquire since the introduction of technological aids, particularly in the arena of Minimally Invasive Surgery. Additional challenges posed by reforms to surgical careers and increased public scrutiny, have propelled identification of methods to assess and acquire MIS technical skills. Although validated objective assessments have been developed to assess motor skills requisite for MIS, they poorly understand the development of expertise. Motor skills learning, is indirectly observable, an internal process leading to relative permanent changes in the central nervous system. Advances in functional neuroimaging permit direct interrogation of evolving patterns of brain function associated with motor learning due to the property of neuroplasticity and has been used on surgeons to identify the neural correlates for technical skills acquisition and the impact of new technology. However significant gaps exist in understanding neuroplasticity underlying learning complex bimanual MIS skills. In this thesis the available evidence on applying functional neuroimaging towards assessment and enhancing operative performance in the field of surgery has been synthesized. The purpose of this thesis was to evaluate frontal lobe neuroplasticity associated with learning a complex bimanual MIS skill using functional near-infrared spectroscopy an indirect neuroimaging technique. Laparoscopic suturing and knot-tying a technically challenging bimanual skill is selected to demonstrate learning related reorganisation of cortical behaviour within the frontal lobe by shifts in activation from the prefrontal cortex (PFC) subserving attention to primary and secondary motor centres (premotor cortex, supplementary motor area and primary motor cortex) in which motor sequences are encoded and executed. In the cross-sectional study, participants of varying expertise demonstrate frontal lobe neuroplasticity commensurate with motor learning. The longitudinal study involves tracking evolution in cortical behaviour of novices in response to receipt of eight hours distributed training over a fortnight. Despite novices achieving expert like performance and stabilisation on the technical task, this study demonstrates that novices displayed persistent PFC activity. This study establishes for complex bimanual tasks, that improvements in technical performance do not accompany a reduced reliance in attention to support performance. Finally, least-squares support vector machine is used to classify expertise based on frontal lobe functional connectivity. Findings of this thesis demonstrate the value of interrogating cortical behaviour towards assessing MIS skills development and credentialing.Open Acces

Phototherapeutic Devices for the Treatment of Diabetic Retinopathy

Diabetic retinopathy is a microvascular disease of the retina and a leading cause of vision loss worldwide. In the non-proliferative phase, diabetes-induced degradation of the retinal blood supply leads to edema and progressive tissue hypoxia. In response, the retinal tissue expresses proangiogenic growth factors (e.g. vascular endothelial growth factor), which drive proliferation of aberrant blood vessels within the eye. These poorly formed vessels leak fluid and blood cells into the eye and grow into the vitreous, which puts traction on the retina and leads to detachment. Given the hypoxic etiology, retinal oxygen tension and metabolism have received considerable attention. Dark-adapted conditions drive the retina to a significantly lower oxygen tension compared to light- adapted conditions as rod cells consume more energy in order to boost sensitivity. While tolerable in the healthy retina, it has been hypothesized that increased nightly metabolism overwhelms the compromised oxygen supply in the diabetic retina, leading to hypoxia and pathological vascular endothelial growth factor expression. This thesis develops ocular devices that shine light onto the retina to modulate rod metabolism, reducing oxygen demand and mitigating nightly hypoxia. The phototherapeutic effect is characterized through mathematical modeling of retinal metabolism and in vivo testing. Implantable phototherapy devices are designed, fabricated, and evaluated. This thesis also develops overnight phototherapeutic contact lenses utilizing radioluminescence, chemiluminescence, and electroluminescence approaches. Phototherapy holds promise as a non-invasive, preventative therapy for the treatment of hypoxic retinal diseases such as diabetic retinopathy.</p

Surgical Ophthalmic Oncology

Designed as an easy-to-use, practical guide to tumors of the eye, lids, and orbit, this Open Access book comprehensively addresses surgical treatment and management of diseases related to ophthalmic oncology. Surgical Ophthalmic Oncology: A Collaborative Open Access Reference is an ideal reference for general ophthalmologists, surgeons, fellows and trainees around the world who encounter these diseases in the care of their patients. Notably, this book includes considerations for those ophthalmologists offering subspecialty care in environments with limited access to advanced technology and instrumentation. Individual chapters address diagnostic indications, pre-operative and post-operative concerns, and provide detailed explanations of surgical techniques required to manage various eye cancer ailments with help of ample illustrations. High-quality videos included throughout the book provide readers with the opportunity to review surgical steps in real-time as a learning tool. Chapters thoroughly cover tumors of eyelid, cornea and conjunctiva, orbit as well as intraocular tumors, while later chapters discuss ophthalmic radiation therapy. The book concludes with a section on ophthalmic pathology which details essential guidelines on relevant aspects from specimen collection and transport, to interpretation of the pathology report. Surgical Ophthalmic Oncology: A Collaborative Open Access Reference is a unique and necessary valuable resource for ophthalmologists, trainees, and related medical professionals working in underserved areas in providing quality care for patients suffering from ocular cancers. ; Open Access text that discusses Preferred Practice Guidelines for common surgeries performed on tumors of the eye and adnexa Written for general ophthalmologists providing oncology care and specialists practicing in areas with limited access to advanced technology and instrumentation Includes chapters on eyelid tumors, conjunctival and corneal tumors, intraocular tumors, brachytherapy, and ocular pathology Each chapter includes extensive color pictures and relevant video to assist the clinician in the various surgical procedures discusse

Towards clinical trials of a novel Bionic Eye: Building evidence of safety and efficacy

In the quest for therapeutic solutions for the visually impaired, electrical stimulation of the retina is, and has been, the focus of intense research. Some of these efforts have led to the development of the Phoenix99 Bionic Eye, a device which combines promising technological features with novel stimulation strategies. For medical devices, considerable challenges must be overcome before they’re allowed to be trialled in their target population. The requirements for a study to be performed include the demonstration of a positive risk-benefit ratio of the research. The present dissertation is an attempt to address how pre-clinical trials in animals can be used to understand and minimise risks. A positive risk-benefit ratio means that the potential benefits of the research outweigh the risks of the intervention. In the case of retinal prostheses, the risks include the surgical intervention, the immune response to the device, the safety of the electrical stimuli, and the effects of device ageing. In this work, successful demonstration of the surgical safety and biocompatibility of passive Phoenix99 devices during long-term implantation in sheep called for the evaluation of the chronic effects of the novel stimulation paradigms it can deliver. As preparation for this study, the techniques used to evaluate the safety and efficacy of the stimuli in animals were refined. A systematic approach to minimise the impact of anaesthesia on the experimental results is presented, as well as a novel in vivo retinal recording technique. To maximise the clinical relevance of all animal trials, a computer model for the prediction of thresholds was developed. Finally, in vitro device ageing was performed to deepen our understanding of the design’s potential for long-term implantation. Protocols for a long-term device safety study in sheep and for an acute human trial are also presented, thus taking concrete and sensible steps towards the first clinical use of the Phoenix99 Bionic Eye

Surgical Ophthalmic Oncology

Designed as an easy-to-use, practical guide to tumors of the eye, lids, and orbit, this Open Access book comprehensively addresses surgical treatment and management of diseases related to ophthalmic oncology. Surgical Ophthalmic Oncology: A Collaborative Open Access Reference is an ideal reference for general ophthalmologists, surgeons, fellows and trainees around the world who encounter these diseases in the care of their patients. Notably, this book includes considerations for those ophthalmologists offering subspecialty care in environments with limited access to advanced technology and instrumentation. Individual chapters address diagnostic indications, pre-operative and post-operative concerns, and provide detailed explanations of surgical techniques required to manage various eye cancer ailments with help of ample illustrations. High-quality videos included throughout the book provide readers with the opportunity to review surgical steps in real-time as a learning tool. Chapters thoroughly cover tumors of eyelid, cornea and conjunctiva, orbit as well as intraocular tumors, while later chapters discuss ophthalmic radiation therapy. The book concludes with a section on ophthalmic pathology which details essential guidelines on relevant aspects from specimen collection and transport, to interpretation of the pathology report. Surgical Ophthalmic Oncology: A Collaborative Open Access Reference is a unique and necessary valuable resource for ophthalmologists, trainees, and related medical professionals working in underserved areas in providing quality care for patients suffering from ocular cancers. ; Open Access text that discusses Preferred Practice Guidelines for common surgeries performed on tumors of the eye and adnexa Written for general ophthalmologists providing oncology care and specialists practicing in areas with limited access to advanced technology and instrumentation Includes chapters on eyelid tumors, conjunctival and corneal tumors, intraocular tumors, brachytherapy, and ocular pathology Each chapter includes extensive color pictures and relevant video to assist the clinician in the various surgical procedures discusse

Gold Nanorod-based Assemblies and Composites: Cancer Therapeutics, Sensors and Tissue Engineering Materials

abstract: Gold nanoparticles as potential diagnostic, therapeutic and sensing systems have a long history of use in medicine, and have expanded to a variety of applications. Gold nanoparticles are attractive in biological applications due to their unique optical, chemical and biological properties. Particularly, gold nanorods (GNRs) are increasingly used due to superior optical property in the near infrared (NIR) window. Light absorbed by the nanorod can be dissipated as heat efficiently or re-emitted by the particle. However, the limitations for clinical translation of gold nanorods include low yields, poor stability, depth-restricted imaging, and resistance of cancer cells to hyperthermia, are severe. A novel high-throughput synthesis method was employed to significantly increase in yields of solid and porous gold nanorods/wires. Stable functional nanoassemblies and nanomaterials were generated by interfacing gold nanorods with a variety of polymeric and polypeptide-based coatings, resulting in unique properties of polymer-gold nanorod assemblies and composites. Here the use of these modified gold nanorods in a variety of applications including optical sensors, cancer therapeutics, and nanobiomaterials were described.Dissertation/ThesisPh.D. Chemical Engineering 201

Textbook on Scar Management

This text book is open access under a CC BY 4.0 license. Written by a group of international experts in the field and the result of over ten years of collaboration, it allows students and readers to gain to gain a detailed understanding of scar and wound treatment – a topic still dispersed among various disciplines. The content is divided into three parts for easy reference. The first part focuses on the fundamentals of scar management, including assessment and evaluation procedures, classification, tools for accurate measurement of all scar-related elements (volume density, color, vascularization), descriptions of the different evaluation scales. It also features chapters on the best practices in electronic-file storage for clinical reevaluation and telemedicine procedures for safe remote evaluation. The second section offers a comprehensive review of treatment and evidence-based technologies, presenting a consensus of the various available guidelines (silicone, surgery, chemical injections, mechanical tools for scar stabilization, lasers). The third part evaluates the full range of emerging technologies offered to physicians as alternative or complementary solutions for wound healing (mechanical, chemical, anti-proliferation). Textbook on Scar Management will appeal to trainees, fellows, residents and physicians dealing with scar management in plastic surgery, dermatology, surgery and oncology, as well as to nurses and general practitioners ; Comprehensive reference covering the complete field of wounds and scar management: semiology, classifications and scoring Highly educational contents for trainees as well as professionals in plastic surgery, dermatology, surgery, oncology as well as nurses and general practitioners Fast access to information through key points, take home messages, highlights, and a wealth of clinical cases Book didactic contents enhanced by supplementary material and video