Fig. 23.1
Endoscopic and confocal laser endomicroscopy imaging of a mouse model of colitis. The mouse colitis was induced by ingestion of 3 % Dextran Sodium Sulfate (DSS). Imaging was performed with a small animal endoscope (Karl Storz, Germany) and confocal imaging of angiogenesis performed by using the AngioSpark™ nanoparticles in conjunction with near-infrared CLE (Mauna Kea Technologies, France). Mice with knockout (KO) of their protein kinase C iota (Prkci) gene were more susceptible to colitis compared with intact (f/f) mice. (Reproduced with permission from Calcagno SR, Li S, Shahid MW, Wallace MB, Leitges M, Fields AP, et al. Protein kinase c iota in the intestinal epithelium protects against dextran sodium sulfate-induced colitis. Inflamm Bowel Dis. 2011 Aug;17(8):1685–97.)
Inflammatory bowel disease offers a unique opportunity to explore the potential of molecular imaging for both detection and to guide therapy. Because of the increasing array of monoclonal antibody treatments for inflammatory bowel disease, there is significant potential for molecular imaging using fluorescent-labeled monoclonal antibodies to determine binding density and potentially to predict response to therapy [16]. In a proof of concept of this, Atrya et al. used topically applied fluorescent-labeled adalimumab followed by confocal imaging to assess adalimumab binding. They were able to show that patients with a strong binding of labeled adalimumab had significantly better short-term response to adalimumab therapy [17]. Molecular imaging has been evaluated for cancer and dysplasia detection. For example, molecular imaging probes that are activated by proteases such as cathepsin were found to be significantly upregulated when imaged by CLE in ulcerative colitis patients with dysplasia compared to those without dysplasia [18]. Raman spectroscopy, which evaluates subcellular biochemical changes in the tissue, has also been shown to be promising in detection of inflammatory bowel disease [19].
Other potential future applications include direct drug delivery, which would be most applicable in focal areas of inflammatory bowel disease such as Crohn’s disease associated strictures with isolated areas of inflammation.
Conclusion
Future areas for research include:
The need for randomized controlled trials demonstrating long-term benefit and prevention of colorectal cancer in patients undergoing surveillance, particularly with colonoscopy.
Methods to teach and train endoscopists to perform chromoendoscopy and to apply this in an outpatient clinical setting apart from tertiary care hospitals.
Methods to improve the convenience of chromoendoscopy such as using this through integrated water pumps associated with the endoscopic systems or dye delivery in a delayed release tablet.
Further evaluation of epithelial gaps and other methods to assess microscopic activity and their ability to predict the need for ongoing therapy.
Further confirmation of the role of confocal endomicroscopy outside of major tertiary care centers to determine if this can be used in practice and how to train endoscopists in image interpretation.
References
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Mowat C, Cole A, Windsor A, Ahmad T, Arnott I, Driscoll R, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut. [Practice Guideline Research Support, Non-U.S. Gov’t Review]. 2011;60(5):571–607.
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Sharaf RN, Shergill AK, Odze RD, Krinsky ML, Fukami N, Jain R, et al. Endoscopic mucosal tissue sampling. Gastrointest Endosc. 2013;78(2):216–24.PubMedCrossRef