Fluorescence In Vivo Endomicroscopy
Conclusion FIVE enables interrogation of living systems in stunning
morphological detail. Advances in fluorophores have provided functional and molecular targeted imaging capabilities that enable the capture of specific cellular events impossible to rec- reate in vitro. Tis includes longitudinal studies of physiologi- cal and pathological processes and cellular, subcellular, and molecular events in vivo that have not previously been seen. Te unexpected nature of some FIVE findings illustrates important roles it can play in the understanding of systems biology, and how it can provide answers to important questions that cannot be visualized by other instruments.
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Figure 12: Bacteria in the mucus surrounding microvilli in mouse ileum. Con- trast agent, 0.5% acriflavine applied topically. Image courtesy of Professor Alastair J.M. Watson, MD, FRCP, LRSM Professor of Translational Medicine, University of East Anglia.
and characterization of lesions and may be used for prediction of responses to targeted therapy. Virtual biopsy with FIVE can generate hundreds of images in a short period of time. Hence, deep-learning computational models are proposed for iden- tifying images of interest. Izadyyazdanabadi and others have developed deep-learning algorithms to automatically detect and separate diagnostic images for glioblastoma [63,64] (Fig- ure 11). Such computational models for detecting histological features from FIVE images allow for rapid and detailed diag- nosis of diseases. In a further study, these authors developed AlexNet, a deep-learning architecture that can classify images as diagnostic or non-diagnostic [65]. AlexNet was highly reli- able when trained on 8,572 nondiagnostic and 8,223 diagnos- tic images from 74 FIVE-aided brain tumor surgery patients. Findings of these studies have demonstrated that FIVE, when used with AlexNet, can achieve a brain virtual histology model that reliably captures and quickly recognizes diagnostic images. More initiatives are needed to develop AlexNet-like algorithms for other tissue types to increase the efficiency of FIVE. An interesting FIVE application is in studying the gastro-
intestinal microbiome (Figure 12). Recent work suggests the interactions between microorganisms significantly affects gas- trointestinal, immune system, and brain function. For example, Moussata [32] elucidated the role of intramucosal bacteria in inflammatory bowel disease. Being able to study these interac- tions in vivo provides a novel tool for investigating this excit- ing new area of research. Another field where the ability to image cellular interactions in vivo opens new possibilities for understanding is integration of transplanted cells into living organisms. Bergenheim et al. imaged the incorporation of trans- planted intestinal stem cells into the gastrointestinal mucosa.
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www.microscopy-today.com
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