Prospects for Theranostics in Neurosurgical Imaging: Empowering Confocal Laser Endomicroscopy Diagnostics via Deep Learning

Confocal laser endomicroscopy (CLE) is an advanced optical fluorescence imaging technology that has the potential to increase intraoperative precision, extend resection, and tailor surgery for malignant invasive brain tumors because of its subcellular dimension resolution. Despite its promising diagnostic potential, interpreting the gray tone fluorescence images can be difficult for untrained users. In this review, we provide a detailed description of bioinformatical analysis methodology of CLE images that begins to assist the neurosurgeon and pathologist to rapidly connect on-the-fly intraoperative imaging, pathology, and surgical observation into a conclusionary system within the concept of theranostics. We present an overview and discuss deep learning models for automatic detection of the diagnostic CLE images and discuss various training regimes and ensemble modeling effect on the power of deep learning predictive models. Two major approaches reviewed in this paper include the models that can automatically classify CLE images into diagnostic/nondiagnostic, glioma/nonglioma, tumor/injury/normal categories and models that can localize histological features on the CLE images using weakly supervised methods. We also briefly review advances in the deep learning approaches used for CLE image analysis in other organs. Significant advances in speed and precision of automated diagnostic frame selection would augment the diagnostic potential of CLE, improve operative workflow and integration into brain tumor surgery. Such technology and bioinformatics analytics lend themselves to improved precision, personalization, and theranostics in brain tumor treatment.Comment: See the final version published in Frontiers in Oncology here: https://www.frontiersin.org/articles/10.3389/fonc.2018.00240/ful

In vivo histologically equivalent evaluation of gastric mucosal topologic morphology in dogs by using confocal endomicroscopy

Background: Confocal endomicroscopy (CEM) is an endoscopic technology permitting in vivo cellular and subcellular imaging. CEM aids real-time clinical assessment and diagnosis of various gastrointestinal diseases in people. CEM allows in vivo characterization of small intestinal mucosal morphology in dogs. Objective: To determine the feasibility of CEM to evaluate gastric mucosal morphology in dogs and to characterize the appearance in healthy dogs. Animals: Fourteen clinically healthy research colony dogs. Methods: Experimental study. Under general anesthesia, dogs underwent standard endoscopic evaluation and CEM of the gastric mucosa. In the initial 6 dogs, fluorescent contrast was provided with the fluorophore acriflavine (0.05% solution), applied topically. Subsequently, 8 dogs were assessed using a combination of fluorescein (10% solution, 15\ua0mg/kg IV), followed by acriflavine administered topically. For each fluorophore, a minimum of 5 sites were assessed. Results: Confocal endomicroscopy provided high quality in vivo histologically equivalent images of the gastric mucosa, but reduced flexibility of the endoscope tip limited imaging of the cranial stomach in some dogs. Intravenous administration of fluorescein allowed assessment of cellular cytoplasmic and microvasculature features. Topical application of acriflavine preferentially stained cellular nucleic acids, allowing additional evaluation of nuclear morphology. Identification of Helicobacter-like organisms was possible in 13 dogs. Conclusion and Clinical Importance: Confocal endomicroscopy provides in vivo images allowing assessment of gastric mucosal morphology during endoscopy, potentially permitting real-time diagnosis of gastrointestinal disease. \ua9 2014 by the American College of Veterinary Internal Medicine

In Vivo confocal endomicroscopy of small intestinal mucosal morphology in dogs

Background: Confocal endomicroscopy (CEM) is an endoscopic technology that permits in vivo cellular and subcellular imaging of the gastrointestinal mucosa. Objective: To determine the feasibility of CEM to evaluate small intestinal mucosal topologic morphology in dogs and to characterize the appearance in healthy dogs. Animals: Fourteen clinically healthy research colony dogs. Methods: Experimental study. Dogs were anesthetized for standard endoscopic evaluation of the small intestine followed by CEM. Two fluorophores were used to provide contrast: fluorescein (10% solution, 15 mg/kg IV) before administration of topical acriflavine (0.05% solution) via an endoscopy spray catheter. A minimum of 5 sites within the small intestine were assessed and at each location, sequential adjustment of imaging depth allowed collection of a three-dimensional volume equivalent to an 'optical biopsy'. CEM-guided pinch biopsies were obtained for histologic examination. Results: CEM provided high-quality in vivo cellular and subcellular images. Intravenous administration of fluorescein provided sufficient contrast to allow assessment of the vasculature, cellular cytoplasmic features and goblet cell numbers, and distribution. Topical application of acriflavine preferentially stained cellular nucleic acids, allowing evaluation of nuclear morphology. Quality of captured images was occasionally affected by motion artifact, but improved with operator experience. Conclusion and Clinical Importance: CEM provides in vivo images that allow for cellular and subcellular assessment of intestinal mucosal morphology during endoscopy. This has implications for aiding in vivo diagnosis of gastrointestinal disease. \ua9 2013 by the American College of Veterinary Internal Medicine

Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease

Loss of intestinal barrier function plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Shedding of intestinal epithelial cells is a potential cause of barrier loss during inflammation. The objectives of the study were (1) to determine whether cell shedding and barrier loss in humans can be detected by confocal endomicroscopy and (2) whether these parameters predict relapse of IBD

Fluorescence multi-scale endoscopy and its applications in the study and diagnosis of gastro-intestinal diseases: set-up design and software implementation

Proceedings of: IPA 2015 / SPIE Biophotonics South America. Rio de Janeiro, Brazil, 22-26 May, 2015Endoscopy is frequently used in the diagnosis of several gastro-intestinal pathologies as Crohn disease, ulcerative colitis or colorectal cancer. It has great potential as a non-invasive screening technique capable of detecting suspicious alterations in the intestinal mucosa, such as inflammatory processes. However, these early lesions usually cannot be detected with conventional endoscopes, due to lack of cellular detail and the absence of specific markers. Due to this lack of specificity, the development of new endoscopy technologies, which are able to show microscopic changes in the mucosa structure, are necessary. We here present a confocal endomicroscope, which in combination with a wide field fluorescence endoscope offers fast and specific macroscopic information through the use of activatable probes and a detailed analysis at cellular level of the possible altered tissue areas. This multi-modal and multi-scale imaging module, compatible with commercial endoscopes, combines near-infrared fluorescence (NIRF) measurements (enabling specific imaging of markers of disease and prognosis) and confocal endomicroscopy making use of a fiber bundle, providing a cellular level resolution. The system will be used in animal models exhibiting gastro-intestinal diseases in order to analyze the use of potential diagnostic markers in colorectal cancer. In this work, we present in detail the set-up design and the software implementation in order to obtain simultaneous RGB/NIRF measurements and short confocal scanning times.The authors acknowledge support from EC FP7 IMI project PREDICT-TB, the EC FP7 CIG grant HIGH-THROUGHPUT TOMO, the Spanish MINECO project grant FIS2013-41802-R MESO-IMAGING, and TOPUS S2013/MIT-3024 project from the regional government of MadridPublicad

Detection of colonic dysplasia in patients with ulcerative colitis using a targeted fluorescent peptide and confocal laser endomicroscopy: A pilot study

Targeted molecular probes have been used to detect sporadic colonic dysplasia during confocal laser endomicroscopy (CLE) with promising results. This is a feasibility pilot study aiming to assess the potential role of CLE combined with a fluorescent-labeled peptide to stain and detect dysplasia associated with Ulcerative Colitis

Confocal laser endomicroscopy is a new imaging modality for recognition of intramucosal bacteria in inflammatory bowel disease in vivo

Interaction of bacteria with the immune system within the intestinal mucosa plays a key role in the pathogenesis of inflammatory bowel disease (IBD). The aim of the current study was to develop a fluorescein-aided confocal laser endomicroscopy (CLE) method to visualise intramucosal enteric bacteria in vivo and to determine the involved mucosal area in the colon and ileum in patients with ulcerative colitis (UC) and Crohn's disease (CD)

Double-clad fiber with a tapered end for confocal endomicroscopy

We present a double-clad fiber coupler (DCFC) for use in confocal endomicroscopy to reduce speckle contrast, increase signal collection while preserving optical sectioning. The DCFC is made by incorporating a double-clad tapered fiber (DCTF) to a fused-tapered DCFC for achromatic transmission (from 1265 nm to 1325 nm) of > 95% illumination light trough the single mode (SM) core and collection of > 40% diffuse light through inner cladding modes. Its potential for confocal endomicroscopy is demonstrated in a spectrally-encoded imaging setup which shows a 3 times reduction in speckle contrast as well as 5.5 × increase in signal collection compared to imaging with a SM fiber