New Techniques in Gastrointestinal Endoscopy

As result of progress, endoscopy has became more complex, using more sophisticated devices and has claimed a special form. In this moment, the gastroenterologist performing endoscopy has to be an expert in macroscopic view of the lesions in the gut, with good skills for using standard endoscopes, with good experience in ultrasound (for performing endoscopic ultrasound), with pathology experience for confocal examination. It is compulsory to get experience and to have patience and attention for the follow-up of thousands of images transmitted during capsule endoscopy or to have knowledge in physics necessary for autofluorescence imaging endoscopy. Therefore, the idea of an endoscopist has changed. Examinations mentioned need a special formation, a superior level of instruction, accessible to those who have already gained enough experience in basic diagnostic endoscopy. This is the reason for what these new issues of endoscopy are presented in this book of New techniques in Gastrointestinal Endoscopy

Ex Vivo and In Vivo Noninvasive Imaging of Epidermal Growth Factor Receptor Inhibition on Colon Tumorigenesis Using Activatable Near-Infrared Fluorescent Probes

Near-infrared fluorescence (NIRF) imaging combined with enzyme-activatable NIRF probes has yielded promising results in cancer detection

Seeing the Big Picture: System Architecture Trends in Endoscopy and LED-Based hyperspectral Subsystem Intergration

Early-stage colorectal lesions remain difficult to detect. Early development of neoplasia tends to be small (less than 10 mm) and flat and difficult to distinguish from surrounding mucosa. Additionally, optical diagnosis of neoplasia as benign or malignant is problematic. Low rates of detection of these lesions allow for continued growth in the colorectum and increased risk of cancer formation. Therefore, it is crucial to detect neoplasia and other non-neoplastic lesions to determine risk and guide future treatment. Technology for detection needs to enhance contrast of subtle tissue differences in the colorectum and track multiple biomarkers simultaneously. This work implements one such technology with the potential to achieve the desired multi-contrast outcome for endoscopic screenings: hyperspectral imaging. Traditional endoscopic imaging uses a white light source and a RGB detector to visualize the colorectum using reflected light. Hyperspectral imaging (HSI) acquires an image over a range of individual wavelength bands to create an image hypercube with a wavelength dimension much deeper and more sensitive than that of an RGB image. A hypercube can consist of reflectance or fluorescence (or both) spectra depending on the filtering optics involved. Prior studies using HSI in endoscopy have normally involved ex vivo tissues or xiv optics that created a trade-off between spatial resolution, spectral discrimination and temporal sampling. This dissertation describes the systems design of an alternative HSI endoscopic imaging technology that can provide high spatial resolution, high spectral distinction and video-rate acquisition in vivo. The hyperspectral endoscopic system consists of a novel spectral illumination source for image acquisition dependent on the fluorescence excitation (instead of emission). Therefore, this work represents a novel contribution to the field of endoscopy in combining excitation-scanning hyperspectral imaging and endoscopy. This dissertation describes: 1) systems architecture of the endoscopic system in review of previous iterations and theoretical next-generation options, 2) feasibility testing of a LED-based hyperspectral endoscope system and 3) another LED-based spectral illuminator on a microscope platform to test multi-spectral contrast imaging. The results of the architecture point towards an endoscopic system with more complex imaging and increased computational capabilities. The hyperspectral endoscope platform proved feasibility of a LED-based spectral light source with a multi-furcated solid light guide. Another LED-based design was tested successfully on a microscope platform with a dual mirror array similar to telescope designs. Both feasibility tests emphasized optimization of coupling optics and combining multiple diffuse light sources to a common output. These results should lead to enhanced imagery for endoscopic tissue discrimination and future optical diagnosis for routine colonoscopy

Capsule endoscopy compatible fluorescence imager demonstrated using bowel cancer tumours

We demonstrate a proof of concept highly miniaturised fluorescence imager and its application to detecting cancer in resected human colon cancer tissues. Fluorescence imaging modalities have already been successfully implemented in traditional endoscopy. However, the procedure still causes discomfort and requires sedation. Wireless fluorescence capsule endoscopy has the potential to improve diagnostic accuracy with less inconvenience for patients. In this paper we present a 5 mm x 6 mm x 5 mm optical block that is small enough to integrate into a capsule endoscope. The block integrates ultrathin filters for optical isolation and was successfully integrated with a sensitive CMOS SPAD array to detect green fluorescence from Flavin Adenine Dinucleotide (FAD), which is an endogenous fluorophore responsible for autofluorescence in human tissues, and fluorescence from the cancer selective molecular probe ProteoGREENTM-gGlu used to label colorectal cancer cells. In vitro studies were validated using a commercial ModulusTM Microplate reader. The potential use of the device in capsule endoscopy was further validated by imaging healthy and malignant resected human tissues from the colon to detect changes in autofluorescence signal that are crucial for cancer diagnosis

Diagnosis and Treatment of Small Bowel Disorders

Over the last few decades, remarkable progress has been made in understanding the aetiology and pathophysiology of diseases and many new theories emphasize the importance of the small bowel ‘ecosystem’ in the pathogenesis of acute and chronic illness. Emerging factors such as microbiome, stem cells, innate intestinal immunity and the enteric nervous system along with mucosal and endothelial barriers have key role in the development of gastrointestinal and extra-intestinal diseases. Therefore, the small intestine is considered key player in metabolic disease development, including diabetes mellitus, and other diet-related disorders such as celiac and non-celiac enteropathies. Another major field is drug metabolism and its interaction with microbiota. Moreover, the emergence of gut-brain, gut-liver and gut-blood barriers points toward the important role of small intestine in the pathogenesis of common disorders, such as liver disease, hypertension and neurodegenerative disease. However, the small bowel remains an organ that is difficult to fully access and assess and accurate diagnosis often poses a clinical challenge. Eventually, the therapeutic potential remains untapped. Therefore, it is due time to direct our interest towards the small intestine and unravel the interplay between small-bowel and other gastrointestinal (GI) and non-GI related maladies

In vivo testing of gold nanoparticles using the Caenorhabditis elegans model organism

Gold nanoparticles (AuNPs) are present in many man-made products and cosmetics, and are also used by the food and medical industries. Tight regulations regarding the use of mammalian animals for product testing can hamper the study of the specific interactions between engineered nanoparticles and biological systems. Invertebrate models, such as the nematode Caenorhabditis elegans (C. elegans), can offer alternative approaches during the early phases of nanoparticle discovery. Here, we thoroughly evaluated the biodistribution of 11-nm and 150-nm citrate-capped AuNPs in the model organism C. elegans at multiple scales, moving from micrometric to nanometric resolution and from the organismal to cellular level. We confirmed that the nanoparticles were not able to cross the intestinal and dermal barriers. We investigated the effect of AuNPs on the survival and reproductive performance of C. elegans, and correlated these effects with the uptake of AuNPs in terms of their number, surface area, and metal mass. In general, exposure to 11-nm AuNPs resulted in a higher toxicity than the larger 150-nm AuNPs. NP aggregation inside C. elegans was determined using absorbance microspectroscopy, which allowed the plasmonic properties of AuNPs to be correlated with their confinement inside the intestinal lumen, where anatomical traits, acidic pH and the presence of biomolecules play an essential role on NP aggregation. Finally, quantitative PCR of selected molecular markers indicated that exposure to AuNPs did not significantly affect endocytosis and intestinal barrier integrity. Statement of significance This work highlights how the simple, yet information-rich, animal model C. elegans is ideally suited for preliminary screening of nanoparticles or chemicals mitigating most of the difficulties associated with mammalian animal models, namely the ethical issues, the high cost, and time constraints. This is of particular relevance to the cosmetic, food, and pharmaceutical industries, which all have to justify the use of animals, especially during the discovery, development and initial screening phases. This work provides a detailed and thorough analysis of 11-nm and 150-nm AuNPs at multiple levels of organization (the whole organism, organs, tissues, cells and molecules).Peer ReviewedPostprint (author's final draft

Biochromoendoscopy: molecular imaging with capsule endoscopy for detection of adenomas of the GI tract

Current capsule endoscopy (CE) provides minimally invasive technology for gastrointestinal imaging, but has limited ability to discriminate different polyp types. Near Infrared Fluorescent (NIRF) probes activated by biomarkers upregulated in adenomas (e.g., cathepsin B) are potentially powerful tools to distinguish premalignant or malignant lesions from benign or inflammatory lesions

Current engineering developments for robotic systems in flexible endoscopy

The past four decades have seen an increase in the incidence of early-onset gastrointestinal cancer. Because early-stage cancer detection is vital to reduce mortality rate, mass screening colonoscopy provides the most effective prevention strategy. However, conventional endoscopy is a painful and technically challenging procedure that requires sedation and experienced endoscopists to be performed. To overcome the current limitations, technological innovation is needed in colonoscopy. In recent years, researchers worldwide have worked to enhance the diagnostic and therapeutic capabilities of endoscopes. The new frontier of endoscopic interventions is represented by robotic flexible endoscopy. Among all options, self-propelling soft endoscopes are particularly promising thanks to their dexterity and adaptability to the curvilinear gastrointestinal anatomy. For these devices to replace the standard endoscopes, integration with embedded sensors and advanced surgical navigation technologies must be investigated. In this review, the progress in robotic endoscopy was divided into the fundamental areas of design, sensing, and imaging. The article offers an overview of the most promising advancements on these three topics since 2018. Continuum endoscopes, capsule endoscopes, and add-on endoscopic devices were included, with a focus on fluid-driven, tendon-driven, and magnetic actuation. Sensing methods employed for the shape and force estimation of flexible endoscopes were classified into model- and sensor-based approaches. Finally, some key contributions in molecular imaging technologies, artificial neural networks, and software algorithms are described. Open challenges are discussed to outline a path toward clinical practice for the next generation of endoscopic devices

pH-dependent ileocolonic drug delivery, part II:Preclinical evaluation of novel drugs and novel excipients

Novel drugs and novel excipients in pH-dependent ileocolonic drug delivery systems have to be tested in animals. Which animal species are suitable and what in vivo methods are used to verify ileocolonic drug delivery