Developments in molecular and advanced endoscopic imaging in esophageal cancer

Esophageal cancer, including esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), shows high incidence and poor prognosis. The early detection and endoscopic treatment of (pre)malignant lesions of esophageal cancer significantly improve disease outcomes of patients. However, the high-definition white-light endoscopy followed by random biopsy is reported with a non-ignorable miss rate. The development of advanced endoscopic techniques, such as fluorescence molecular endoscopy (FME) and endocytoscopy, can aid endoscopists in diagnosing early (pre)malignant lesions in vivo. FME realizes wide-field molecular imaging under endoscopy, which serves as a red flag technique for endoscopists by fluorescently highlighting the disease-specific molecule. In Chapter 3 and 4, we identified suitable target proteins and developed near-infrared fluorescent tracers for FME to detect ESCC and EAC at an early stage. In Chapter 6, we investigated the feasibility of assessing pathological response of EAC patients after neoadjuvant chemoradiotherapy by Bevacizumab-800CW guided FME.Endocytoscopy is a pin-point imaging technique that provides endoscopists with magnified optical cellular morphology and subcellular characteristics, referred to as an optical biopsy. In Chapter 5, we developed a classification criteria, an online training module for clinicians and a computer-aided diagnosis (CAD) algorithm based on in vivo images of fourth-generation endocytoscopy to distinguish dysplastic from non-dysplastic Barrett's esophagus tissue. We further investigated the interaction of this CAD algorithm with the clinicians

Volumetric laser endomicroscopy and its application to Barrett's esophagus: results from a 1,000 patient registry.

Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291

Role of artificial intelligence in the diagnosis of oesophageal neoplasia: 2020 an endoscopic odyssey

The past decade has seen significant advances in endoscopic imaging and optical enhancements to aid early diagnosis. There is still a treatment gap due to the underdiagnosis of lesions of the oesophagus. Computer aided diagnosis may play an important role in the coming years in providing an adjunct to endoscopists in the early detection and diagnosis of early oesophageal cancers, therefore curative endoscopic therapy can be offered. Research in this area of artificial intelligence is expanding and the future looks promising. In this review article we will review current advances in artificial intelligence in the oesophagus and future directions for development

Volumetric laser endomicroscopy and its application to Barrett\u27s esophagus: results from a 1,000 patient registry.

Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett\u27s esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291

Today's Mistakes and Tomorrow's Wisdom in Endoscopic Imaging of Barrett's Esophagus

Background: Esophageal adenocarcinoma (EAC) is one of the main causes of cancer-related deaths worldwide and its incidence is rising. Barrett's esophagus (BE) can develop low- and high-grade dysplasia which can progress to EAC overtime. The golden standard to detect dysplastic BE (DBE) or EAC is surveillance with high-definition white-light endoscopy (HD-WLE) and random biopsies according to the Seattle protocol. However, this method is time-consuming and associated with a remarkable miss rate. Therefore, there is great need for the development of novel reliable techniques to optimize surveillance strategies and improve detection rates.Summary: Optical chromoendoscopy (OC) techniques like narrow-band imaging have shown improved detection of DBE and EAC compared to HD-WLE and random biopsies. Most recent OC techniques, including the iSCAN optical enhancement system and linked color imaging, showed improved characterization of DBE and EAC retrospectively. Fluorescence molecular endoscopy (FME) presented promising results to highlight DBE and EAC. Moreover, with the establishment of well-performing delineation computer-aided detection (CAD) algorithms and the first real-time CAD system for EAC, we expect clinical application of CAD in the near future.Key Messages: Despite impressive progress made in the development of advanced endoscopic techniques, combined HD-WLE/OC followed by random biopsies remains the golden standard for BE surveillance. Surveillance depends on appropriate mucosal cleansing, sufficient inspection time, and competence of the performing gastroenterologist to improve detection of EAC. In addition, to facilitate the clinical implementation of advanced endoscopic techniques, multicenter prospective clinical studies are demanded for OC and FME. Meanwhile, further optimization of CAD algorithms, the education of gastroenterologists, and analysis of the interaction between the clinician and the computer should be performed.</p

Endoscopic optical coherence tomography for clinical studies in the gastrointestinal tract

Thesis (Ph. D.)--Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2013.Cataloged from PDF version of thesis.Includes bibliographical references.Optical coherence tomography (OCT) performs micrometer-scale, cross-sectional and three dimensional imaging by measuring the echo time delay of backscattered light. OCT imaging is performed using low-coherence interferometry. With the development of Fourier domain detection techniques and fiber-optic based OCT endoscopes, high speed internal body imaging was enabled, which makes OCT suitable for clinical research in the human gastrointestinal (GI) tract. Endoscopic OCT imaging is challenging because fast and stable optical scanning must be implemented inside a small imaging probe to acquire useable volumetric information from internal human bodies. Although several studies have shown the use of endoscopic OCT in human gastrointestinal tracts as a real-time surveillance tool, the capability of OCT has not yet been fully explored in endoscopic applications and OCT is not well accepted as a standard imaging modality for GI clinics due to hardware limitations and lack of comprehensive clinical evidences. This thesis presents a number of clinical studies using endoscopic OCT that provide solutions to clinical problems in the GI tract supported by statistically significant results and the development of ultrahigh speed endoscopic OCT system that enables advanced OCT imaging applications. In collaboration with medical partners, the structural features in the diseased esophagus identified from OCT images are compared before and immediately after different ablative therapies, and features that predict the treatment response are investigated. Working in collaboration with industrial partners, an ultrahigh speed endoscopic OCT imaging system is constructed for clinical research in gastroenterology. Distally actuated imaging catheters are developed, enabling the visualization of the detailed three-dimensional (3D) structure in the gastrointestinal tract. Finally, clinical pilot studies are conducted and demonstrate the utility of the ultrahigh speed endoscopic OCT imaging for broader surveillance coverage, pathology detection, and dye-less contrast enhancement. The convergence of 3D spatial resolution, imaging speed, field of view, and minimally invasive access enabled by endoscopic OCT are unmatched by most other biomedical imaging techniques. Though still in its early stage of clinical validation, endoscopic OCT may have a profound impact on human healthcare and industrial inspection by enabling visualization and quantification of 3D microstructure in situ and in real time.by Tsung-Han Tsai.Ph.D

Swept source optical coherence microscopy for pathological assessment of cancerous tissues

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2013.Cataloged from PDF version of thesis.Includes bibliographical references.Optical coherence microscopy (OCM) combines optical coherence tomography (OCT) with confocal microscopy and enables depth resolved visualization of biological specimens with cellular resolution. OCM offers a suitable alternative to confocal imaging by providing enhanced contrast due to the additional coherence gate to the inherent confocal gate, increasing the field of view and imaging depth, and eliminating the need of external contrast agents. In the past, development of OCT systems have been focused on time domain and spectral/Fourier domain methods which offer high axial resolution and imaging speeds. However, recent advances in the OCT technology have pushed the development into the direction of swept source OCT technologies, and development of the OCM technology is likely to follow this path. This thesis describes construction, characterization and preliminary imaging results of a swept source OCM (SS-OCM) system utilizing a novel light source, Vertical Cavity Surface-Emission Laser (VCSEL). This swept source laser can reach sweep rates exceeding 1 MHz and provide wide tuning ranges, which will enable both imaging speeds approaching to time domain OCM (TD-OCM) systems, and axial resolution approaching to spectral/Fourier domain OCM (SD-OCM) systems. Several other advantages of SS-OCM compared to TD-OCM and SD-OCM that make this technology a promising alternative to the latter imaging methods are presented. Furthermore, practical concepts in the system development and signal processing, such as compensation for the scan curvatures, methods for calibration of the spectrums, selection of suitable color maps for display, and other related topics are also discussed in the text. In addition to technical description of the OCM system development, an in depth analysis of several clinical applications that will be likely to benefit from this imaging modality is also presented. Real time intraoperative feedback is required in order to reduce the morbidity and the rate of additional operations for the surgical management of several forms of cancer, where a benchtop OCM system residing in the pathology laboratory can be immensely beneficial. Furthermore, with the novel scanning mechanisms that have been developed in the recent years it is possible to translate this imaging modality to an in vivo setting where an OCM probe can be inserted through the working channel of an endoscope and generate cellular resolution images in real time without the need of external contrast agents. Endoscopic management and clinical challenges for a spectrum of lower gastrointestinal (GI) diseases is discussed where an in vivo OCM imaging probe can play an important role in the diagnosis and evaluation of the extend of the particular disease. A review of alternative imaging modalities, such as chromoendoscopy, narrow band imaging (NBI) and confocal laser endomicroscopy (CLE) is also included which outlines the relative strengths and limitations of these imaging modalities for the clinical management of lower GI diseases.by Osman Oguz Ahsen.S.M

Fast widefield techniques for fluorescence and phase endomicroscopy

Thesis (Ph.D.)--Boston UniversityEndomicroscopy is a recent development in biomedical optics which gives researchers and physicians microscope-resolution views of intact tissue to complement macroscopic visualization during endoscopy screening. This thesis presents HiLo endomicroscopy and oblique back-illumination endomicroscopy, fast widefield imaging techniques with fluorescence and phase contrast, respectively. Fluorescence imaging in thick tissue is often hampered by strong out-of-focus background signal. Laser scanning confocal endomicroscopy has been developed for optically-sectioned imaging free from background, but reliance on mechanical scanning fundamentally limits the frame rate and represents significant complexity and expense. HiLo is a fast, simple, widefield fluorescence imaging technique which rejects out-of-focus background signal without the need for scanning. It works by acquiring two images of the sample under uniform and structured illumination and synthesizing an optically sectioned result with real-time image processing. Oblique back-illumination microscopy (OBM) is a label-free technique which allows, for the first time, phase gradient imaging of sub-surface morphology in thick scattering tissue with a reflection geometry. OBM works by back-illuminating the sample with the oblique diffuse reflectance from light delivered via off-axis optical fibers. The use of two diametrically opposed illumination fibers allows simultaneous and independent measurement of phase gradients and absorption contrast. Video-rate single-exposure operation using wavelength multiplexing is demonstrated