This thesis describes the design, development, characterisation and clinical translation of three novel devices for optical endoscopic imaging. Over the past decade, rapid innovation in optics and photonics has led to the availability of low-cost and high-performance optical technologies that can be exploited for biomedical applications, but relatively few have been translated into clinic. The work presented outlines for the first time, a comprehensive analysis of the common barriers and unique challenges associated with the translation of optical imaging techniques. To assist developers streamline translation of optical imaging devices in future, a roadmap to clinical translation is outlined, and key translational characteristics are defined. Guided by these, subsequent development of endoscopic devices resulted in preparation and approval of endoscopes for first in human trials in the oesophagus, for early detection of cancer, and in the brain, for delineation of tumour during surgical resection. The thesis culminates in the presentation of results from the first in human use of a compact multispectral endoscope for imaging endogenous tissue contrast in the oesophagus. With continuation of the work as outlined at the end of this thesis, the novel techniques described have the potential to improve the standard of care in their respective indications.

Endoscopic techniques are widely used for screening, diagnostic and therapeutic maneuvers in all groups of patients and for a large spectrum of complaints. The availability of basic iterations of endoscopic techniques made screening programs for various diseases viable in most parts of the world, while the advent of modern techniques opens new perspectives for rapid and correct diagnosis. Going beyond normal human vision, innovative techniques opened the prospect of in-situ pathology. Endoscopic ultrasound has made incredible progress in recent years. Reaching the smaller orifices by endoscopy was a major step forward in the surveillance of previously inaccessible lesions. Investigatory techniques were complemented by advances in therapy, with novel applications in many major areas of medicine.

Combining a professional development course on diagnostic endoscopy from SPIE (the international society advancing light-based research) and the authors' graduate course on biomedical optics, this work is written for researchers in medical optics and biomedical engineering as well as graduate medical optics students. It uses extensive examples/case

Endoscopic techniques are widely used for screening, diagnostic and therapeutic maneuvers in all groups of patients and for a large spectrum of complaints. The availability of basic iterations of endoscopic techniques made screening programs for various diseases viable in most parts of the world, while the advent of modern techniques opens new perspectives for rapid and correct diagnosis. Going beyond normal human vision, innovative techniques opened the prospect of in-situ pathology. Endoscopic ultrasound has made incredible progress in recent years. Reaching the smaller orifices by endoscopy was a major step forward in the surveillance of previously inaccessible lesions. Investigatory techniques were complemented by advances in therapy, with novel applications in many major areas of medicine.

Evidence suggests that medical innovation is becoming increasingly dependent on interdisciplinary research and on the crossing of institutional boundaries. This volume focuses on the conditions governing the supply of new medical technologies and suggest that the boundaries between disciplines, institutions, and the private and public sectors have been redrawn and reshaped. Individual essays explore the nature, organization, and management of interdisciplinary R&D in medicine; the introduction into clinical practice of the laser, endoscopic innovations, cochlear implantation, cardiovascular imaging technologies, and synthetic insulin; the division of innovating labor in biotechnology; the government- industry-university interface; perspectives on industrial R&D management; and the growing intertwining of the public and proprietary in medical technology.

Significant progress in engineering has allowed the production of devices that can optically detect, differentiate and treat surface or near-surface cancers. The ability to differentiate cancerous from non-cancerous tissue in vitro using light represents a potentially significant advance in patient care, eliminating needless repeat procedures. With the help of advanced optical technologies, clinicians are able to identify cancers earlier, determine surgical margins at the time of surgery, and monitor treatment results without using expensive and insensitive imaging. This volume describes the state-of-the-art optical detection technologies in varying stages of cancer development. Written by an international panel of basic researchers, engineers and clinicians, the book is designed to give an up-to-date overview of the most recent advances for researchers and medical professionals who are interested in the biophotonic detection of cancer.

Endoscopy in Early Gastrointestinal Cancers, Volume 2: Treatment covers the detailed information of the indications, techniques and perioperative management of endoscopic resection including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Carcinoma of the gastrointestinal tract remained a major health issue worldwide, which is, however notoriously difficult to treat. Endoscopic resection for early neoplasia of the gastrointestinal tract had been developed for more than 25 years. Endoscopic submucosal dissection (ESD) is a recently developed technique pioneer by Japanese endoscopists. The principle of ESD is to achieve a complete resection of gastrointestinal neoplasia limited to mucosa with adequate circumferential margins. This novel endoscopic technique not only allows the achievement of en-bloc resection for early GI cancers, it also conveys a significantly lower rate of local recurrence as compared to EMR for early gastric cancers. There is an urge for the knowledge in applying these novel technologies for the treatment of early GI neoplasia worldwide. This book on the endoscopic treatment of early GI neoplasia, containing lots of illustrations, artwork and numerous short video clips, serves as a bridge between the recent development in endoscopy and the knowledge of gastroenterologist, endoscopist and surgeons.

The health of the human respiratory system depends critically on airway clearance via motile hair-like structures (cilia), which transport and eliminate unwanted particles trapped within mucus. Impairment of mucociliary clearance (MCC) can lead to life-threatening airway narrowing and lung infections, and is a major cause of morbidity and mortality in patients with cystic fibrosis, primary ciliary dyskinesia and chronic obstructive lung disease. However, no tool for microscopic in-vivo visualization of ciliary function is currently available, limiting studies of disease pathogenesis, refined diagnosis and phenotyping, and the development of novel therapeutics. In this thesis, a novel, 1-pm resolution, optical interferometric imaging technique termed Micro-OCT was incorporated into miniaturized common-path endoscopes and mucociliary transport was visualized in vivo for the first time. The first-generation Micro-OCT probe had a rigid design with outer diameter of 4 mm and a two-prism configuration providing beam splitting and sample beam shaping into an annular profile. Image quality of the probe allowed visualization of the periodic pattern of ciliary beating, measurement of airway surface liquid depth (ASL) and visualization of mucociliary transport. Unaltered ciliary function was demonstrated in a living, spontaneously breathing swine model. Newer generation common-path endoscope designs were demonstrated that improve, among other limitations, the stability of the reference reflector position and provide greater potential for miniaturization. The presented work opens unprecedented avenues for studying MCC and the effect of novel therapeutics within the complexity of a living organism. Further, it lays the groundwork for the development of a human probe with the potential to revolutionize diagnosis, phenotyping, and therapy management for all patients with respiratory disease involving the mucociliary escalator.

Gastrointestinal (GI) endoscopy has become indispensable in both diagnosis and treatment of GI disorders. It has been 10 years now since the first Endoscopy Forum Japan was held, and in that time, leading young endoscopists, including colleagues from Asia, Australia, Europe, and the United States, have participated in the forum, discussing issues at the forefront of the field. Through their efforts, GI endoscopy has advanced with many new methods for both diagnoses and treatments, and those achievements are included in this book. Contributing to the development of endoscopic medicine all over the world, this is a groundbreaking, edifying, and engrossing publication offering the most recent advances in the field, precisely presented and depicted with more than 250 color photographs. Novel technologies are described in detail and will be of interest to those in the field of medicine and in engineering as well.