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

Emerging technologies in endoscopic imaging

Endoscopic imaging is in part responsible for the recent drop in deaths from gastrointestinal cancers and also for detecting pre-cancerous and non-cancerous conditions and allowing them to be treated effectively, although techniques are far from perfect. Endoscopic imaging has evolved considerably from fiber optic systems 50 years ago to high resolution and high definition systems used at present. Moreover, image enhancement using filters and processors has led to the technique of ‘electronic chromoendoscopy’ to visualize mucosal blood vessels and surface pit patterns clearly. Magnification by optical zoom or confocal laser microscopy has enabled real time diagnosis and ‘virtual histology’. These techniques have contributed to the early detection, assessment and treatment of various gastrointestinal pathologies. The focus of future research is directed towards molecular targeted imaging

Multimodal optical systems for clinical oncology

This thesis presents three multimodal optical (light-based) systems designed to improve the capabilities of existing optical modalities for cancer diagnostics and theranostics. Optical diagnostic and therapeutic modalities have seen tremendous success in improving the detection, monitoring, and treatment of cancer. For example, optical spectroscopies can accurately distinguish between healthy and diseased tissues, fluorescence imaging can light up tumours for surgical guidance, and laser systems can treat many epithelial cancers. However, despite these advances, prognoses for many cancers remain poor, positive margin rates following resection remain high, and visual inspection and palpation remain crucial for tumour detection. The synergistic combination of multiple optical modalities, as presented here, offers a promising solution. The first multimodal optical system (Chapter 3) combines Raman spectroscopic diagnostics with photodynamic therapy using a custom-built multimodal optical probe. Crucially, this system demonstrates the feasibility of nanoparticle-free theranostics, which could simplify the clinical translation of cancer theranostic systems without sacrificing diagnostic or therapeutic benefit. The second system (Chapter 4) applies computer vision to Raman spectroscopic diagnostics to achieve spatial spectroscopic diagnostics. It provides an augmented reality display of the surgical field-of-view, overlaying spatially co-registered spectroscopic diagnoses onto imaging data. This enables the translation of Raman spectroscopy from a 1D technique to a 2D diagnostic modality and overcomes the trade-off between diagnostic accuracy and field-of-view that has limited optical systems to date. The final system (Chapter 5) integrates fluorescence imaging and Raman spectroscopy for fluorescence-guided spatial spectroscopic diagnostics. This facilitates macroscopic tumour identification to guide accurate spectroscopic margin delineation, enabling the spectroscopic examination of suspicious lesions across large tissue areas. Together, these multimodal optical systems demonstrate that the integration of multiple optical modalities has potential to improve patient outcomes through enhanced tumour detection and precision-targeted therapies.Open Acces

Multimodal Multispectral Optical Endoscopic Imaging for Biomedical Applications

Optical imaging is an emerging field of clinical diagnostics that can address the growing medical need for early cancer detection and diagnosis. Various human cancers are amenable to better prognosis and patient survival if found and treated during early disease onset. Besides providing wide-field, macroscopic diagnostic information similar to existing clinical imaging techniques, optical imaging modalities have the added advantage of microscopic, high resolution cellular-level imaging from in vivo tissues in real time. This comprehensive imaging approach to cancer detection and the possibility of performing an ‘optical biopsy’ without tissue removal has led to growing interest in the field with numerous techniques under investigation. Three optical techniques are discussed in this thesis, namely multispectral fluorescence imaging (MFI), hyperspectral reflectance imaging (HRI) and fluorescence confocal endomicroscopy (FCE). MFI and HRI are novel endoscopic imaging-based extensions of single point detection techniques, such as laser induced fluorescence spectroscopy and diffuse reflectance spectroscopy. This results in the acquisition of spectral data in an intuitive imaging format that allows for quantitative evaluation of tissue disease states. We demonstrate MFI and HRI on fluorophores, tissue phantoms and ex vivo tissues and present the results as an RGB colour image for more intuitive assessment. This follows dimensionality reduction of the acquired spectral data with a fixed-reference isomap diagnostic algorithm to extract only the most meaningful data parameters. FCE is a probe-based point imaging technique offering confocal detection in vivo with almost histology-grade images. We perform FCE imaging on chemotherapy-treated in vitro human ovarian cancer cells, ex vivo human cancer tissues and photosensitiser-treated in vivo murine tumours to show the enhanced detection capabilities of the technique. Finally, the three modalities are applied in combination to demonstrate an optical viewfinder approach as a possible minimally-invasive imaging method for early cancer detection and diagnosis

Fluorescence lifetime spectroscopy of tissue autofluorescence in normal and diseased colon measured ex vivo using a fiber-optic probe

We present an ex vivo study of temporally and spectrally resolved autofluorescence in a total of 47 endoscopic excision biopsy/resection specimens from colon, using pulsed excitation laser sources operating at wavelengths of 375 nm and 435 nm. A paired analysis of normal and neoplastic (adenomatous polyp) tissue specimens obtained from the same patient yielded a significant difference in the mean spectrally averaged autofluorescence lifetime −570 ± 740 ps (p = 0.021, n = 12). We also investigated the fluorescence signature of non-neoplastic polyps (n = 6) and inflammatory bowel disease (n = 4) compared to normal tissue in a small number of specimens

Endoskopske inovacije u dijagnostici i liječenju kolorektalnog karcinoma

Colonoscopy is the gold standard in diagnosis of colorectal cancer that in most instances arises from precursor lesion, adenomatous polyp. However, white ligh forward viewing colonoscopy is not a pefect method, up to a quarter of adenomas are being missed during standard procedures. Therefore, new techniques and technologies are being developed in order to increase adenoma detection rate, either through better resolution and magnification of the image (highdefinition, high-magnification endoscopes) or by augmenting the overview of colonic mucosa (Full Spectrum Endoscopy colonoscope, Third-Eye Retroscope). Besides adenoma detection, new technologies allow better tissue characterisation and in vivo discrimination between nonneoplastic and neoplastic lesions (conventional chromoendoscopy, virtual chromoendoscopy, confocal laser endomicroscopy, endocytoscopy). In additon to diagnostic procedures, therapeutic techniques are also evolving. Formerly, all of the flat or depressed colorectal lesions, encountered during colonoscopy, were reffered to surgery. Today, endoscopic mucosal resection is becoming a routine method for the treatment of early gastrointestinal mucosal lesions of less than 2 cm in diameter. For larger lesions, endoscopic submucosal dissection, a state-of-the-art technique, is indicated, but currently carried out only in tertiary centres. Endoscopic innovations are leading into new era of colorectal cancer diagnosis and management, hopefully resulting in decrease of incidence, morbidity and mortality.Kolonoskopija je zlatni standard u dijagnostici kolorektalnog karcinoma koji u većini slučajeva nastaje iz prekursorske lezije, adenoma. Međutim, standardna kolonoskopija nije savršena metoda; prema rezultatima tandem studija čak četvrtina adenoma ostaje neotkrivena. Stoga se razvijaju nove tehnike i tehnologije koje omogućuju bolju detekciju adenoma uvećanjem i boljom rezolucijom slike (‘’high-definition’’, ‘’high-magnification’’ endoskopi) te boljim pregledom sluznice debelog crijeva (‘’Full Spectrum Endoscopy’’ kolonoskop, ‘’Third-Eye Retroscope’’). Nove tehnologije također omogućuju i napredniju karakterizaciju kolorektalnih promjena i in vivo razlikovanje ne-neoplastičnih i neoplastičnih lezija (konvencionalna kromoendoskopija, virtualna kromoendoskopija, konfokalna laserska endomikroskopija, endocitoskopija). Osim dijagnostičkih, napreduju i terapijske endoskopske metode. Do sada su sve ne-polipoidne kolorektalne promjene liječene kirurški, a danas je endoskopska mukozna resekcija postala rutinska metoda za lezije do 2 cm u promjeru. U slučaju većih promjena inidicirana je endoskopska submukozna disekcija, state-of-the-art tehnika koja se trenutno izvodi samo u tercijarnim centrima. Inovacije u endoskopiji vode u novu eru dijagnostike i liječenja kolorektalnog karcinoma te nagoviještaju bolju prevenciju i smanjenje incidencije ove česte maligne bolesti