Simulated Colonic Feces Reveals Novel Contraction Patterns (2020)

Transport of colonic content is a complex physiologic process through which contents are received from the ileum, solidify during colonic passage, and are finally expelled from the rectum through the anus.1Yamada T et al. (eds). Textbook of Gastroenterology, 5th Edition. Blackwell, 2009. pp. 1717–1744.Google Scholar,2Gregersen H, Christensen J. Clinical mechanics in the Gut. An Introduction. Bentham Publishers, 2016.Google Scholar Colonic motility and transit are difficult to study where the mechanical loading and motion need to be quantified. Since the classic radiographic work of Cannon in 1902, it has been known that antiperistalsis is a common feature of colonic motility. More recently, the underlying slow wave patterns generated by the interstitial cells of Cajal and ripples on spatiotemporal diameter maps have been described in vitro.3Corsetti M. et al.Nat Rev Gastroenterol Hepatol. 2019; 16: 559-579Crossref PubMed Scopus (57) Google Scholar Many aspects of colonic motility are still unexplored because of lack of technology to measure physiologic and pathophysiologic processes. Pathophysiologically, constipation affects up to 25% of the population but remains poorly recognized and treated.4Rao S.S. et al.Gastroenterology. 2016; 150: 1430-1442Abstract Full Text Full Text PDF Scopus (198) Google Scholar,5Bharucha A.E. et al.Gastroenterology. 2006; 130: 1510-1518Abstract Full Text Full Text PDF PubMed Scopus (399) Google Scholar It is important to distinguish between slow-transit constipation and obstructed defecation.6Feyen B.J. et al.Curr Treat Options Gastroenterol. 2007; 10: 221-230Crossref PubMed Scopus (9) Google Scholar Patients with severe slow-transit constipation may be eligible for total or partial colon resection, but tests for identifying the segments of colon being affected are imprecise or cumbersome. Recently, we developed Fecobionics for studying anorectal physiology and pathophysiology.7Gregersen H. et al.Clin Gastroenterol Hepatol. 2018; 16: 981-983Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar,8Gregersen et al.Clin Transl Gastroenterology. 2019; 10: e00108Crossref PubMed Scopus (14) Google Scholar The compressible Fecobionics probe measures multiple pressures, orientation, anorectal angle, and shape changes during defecation.7Gregersen H. et al.Clin Gastroenterol Hepatol. 2018; 16: 981-983Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar,8Gregersen et al.Clin Transl Gastroenterology. 2019; 10: e00108Crossref PubMed Scopus (14) Google Scholar For the first time here, we advance the use of Fecobionics to the colon for mechanistic studies of colonic motility and transport function. We identify novel colonic contraction patterns never before reported in vivo, to our knowledge.3Corsetti M. et al.Nat Rev Gastroenterol Hepatol. 2019; 16: 559-579Crossref PubMed Scopus (57) Google Scholar Fecobionics is a device with shape and deformability mimicking feces.7Gregersen H. et al.Clin Gastroenterol Hepatol. 2018; 16: 981-983Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar,8Gregersen et al.Clin Transl Gastroenterology. 2019; 10: e00108Crossref PubMed Scopus (14) Google Scholar Fecobionics can be inserted anally for defecatory studies or endoscopically delivered to the proximal colon for advanced transit studies. The device provides several improvements to current diagnostic technologies, including (1) the mechanical properties of the device, which mimic normal stool; (2) objective electronic measurement of bending independently of direction/rotation or personal interpretation; and (3) integration of geometric data with multiple axial pressure measurements. Fecobionics integrates several existing technologies.5Bharucha A.E. et al.Gastroenterology. 2006; 130: 1510-1518Abstract Full Text Full Text PDF PubMed Scopus (399) Google Scholar,7Gregersen H. et al.Clin Gastroenterol Hepatol. 2018; 16: 981-983Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar It consists of a 10-cm-long and 10-mm-wide core of medical-grade resin that contains the Fecobionics electronics mounted on a flexible circuit board. A 1 × 3–cm cylindric encapsulated battery is tethered to support long-term colon transit studies. The core is surrounded by a silicone bag. Fecobionics contains 3 pressure transducers (front, rear, and inside the bag), 2 9-axis motion processor units for orientation and angle measurements, and electrodes and electronics for impedance cross-sectional area measurements (Figure 1).7Gregersen H. et al.Clin Gastroenterol Hepatol. 2018; 16: 981-983Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar The device transmits data in real time to an external receiver unit. Here, the Fecobionics probe was inserted through a cannula in the canine ascending colon. After the bag is filled with saline, the fill tube is removed. Recordings were made until the device was defecated. The experiments were approved by the Institutional Animal Care and Use Committee (protocol Calmi2-072). The supplementary videos show sequences captured from the graphical user interface during colonic passage of the Fecobionics device. The diagrams to the left show the color contour plots of the diameters of the bag (top) and pressures. The display speed is approximately 7 times faster than real time in Supplementary Video 1 and 5 times faster in Supplementary Video 2. Different contraction patterns are visible. One pattern exhibits coordinated changes in pressure corresponding to antegrade propagating contractions. Another pattern shows diameter waves crossing the bag in the oral or aboral directions without being detected by manometry. Supplementary Video 2 and Figure 2 show these types of waves more clearly. The 3-dimensional animation to the right in the videos shows the shape and orientation of Fecobionics. The orientation is to some extent affected by gross movements of the dog. Significant changes in shape are observed, which is consistent with mixing patterns of luminal contents. The retrograde contractions visible in the diameter map can also be observed in Supplementary Video 2 (red arrow from 33–41 seconds in the 3D animation). The propagating antegrade contractions are associated with mass movement of fluid in the bag in the aboral direction. The recordings are obtained in the proximal canine colon. The figures and videos clearly illustrate that Fecobionics records different types of contraction patterns in terms of pressure and dimensional changes, whereas only some are recorded by manometry. The waves reflect colonic slow wave activity (≈4 min–1) and have a striking resemblance to the ripples (low-amplitude shallow contractions), a myogenic motor pattern of antegrade and retrograde waves recorded by spatiotemporal mapping in colon segments in vitro.3Corsetti M. et al.Nat Rev Gastroenterol Hepatol. 2019; 16: 559-579Crossref PubMed Scopus (57) Google Scholar We have demonstrated colonic application of the Fecobionics system in canines. Compared to other technologies, the Fecobionics system provides integrated data for capturing the mechanical function (loading and deformation) of the colon. To the best of our knowledge, recordings of this type of data are novel and consistent with Cannon’s classic observations and the ripples measured in colon specimens in vitro.3Corsetti M. et al.Nat Rev Gastroenterol Hepatol. 2019; 16: 559-579Crossref PubMed Scopus (57) Google Scholar We believe that the waves help delay antegrade movement of feces and aid with mixing contents and absorption. Studies of the human colon can be conducted by using colonoscopic delivery of the device. Fecobionics has the potential to shift the current paradigm in clinical practice by providing measures of function and malfunction of the colon; that is, to detect locations in the colon with impaired function, such as segmental slow transit, and provide insight into mechanisms of functional colonic disorders. The clinical applications include diagnosis of the extent of colonic dysfunction; detection of whether activity remains in the constipated segments, requiring possible pharmacologic treatment; and determination of whether a patient is eligible for partial or total colon resection. Hans Gregersen, MD, PhD: Conceptionalization, Methodology, formal analysis, Writing- original draft preparation, Supervision, Funding acquisition Yanmin Wang, MD: Investigations, Resources, Writing- review and editing. Xiaomei Guo, MD: Investigations, Resources, Writing- review and editing. Fred Field, MSc: Investigations, Resources, Software, Validation, Writing- review and editing. Marjorie Nelson, MSc: Resources, Software, Validation, Writing- review and editing. William Combs, MSc: Resources, Software, Validation, Writing- review and editing. Mengjun Wang, MD: Investigations, resources, Writing- review and editing. Ghassan Kassab, MSc Eng: Conceptionalization, Methodology, Writing- review and editing, Supervision, Funding acquisition Hans Gregersen and Ghassan Kassab have filed patent applications. The remaining authors disclose no conflicts. Research reported in this publication was supported by the Office of the Director, National Institutes of Health, under award no. OT2OD025308.