Dynamic Colon Model (DCM): A Cine-MRI Informed Biorelevant In Vitro Model of the Human Proximal Large Intestine Characterized by Positron Imaging Techniques
Konstantinos Stamatopoulos,
Sharad Karandikar,
Mark Goldstein,
Connor O’Farrell,
Luca Marciani,
Sarah Sulaiman,
Caroline L. Hoad,
Mark J. H. Simmons,
Hannah K. Batchelor
Affiliations
Konstantinos Stamatopoulos
School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Sharad Karandikar
Department of Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, UK
Mark Goldstein
Department of Radiology, University Hospitals Birmingham NHS Foundation Trust, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, UK
Connor O’Farrell
School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Luca Marciani
Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK
Sarah Sulaiman
Nottingham Digestive Diseases Centre and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham NG7 2UH, UK
Caroline L. Hoad
Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham NG7 2QX, UK
Mark J. H. Simmons
School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Hannah K. Batchelor
Institute of Clinical Sciences, College of Medical and Dental Sciences, Medical School Building, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
This work used in vivo MRI images of human colon wall motion to inform a biorelevant Dynamic Colon Model (DCM) to understand the interplay of wall motion, volume, viscosity, fluid, and particle motion within the colon lumen. Hydrodynamics and particle motion within the DCM were characterized using Positron Emission Tomography (PET) and Positron Emission Particle Tracking (PEPT), respectively. In vitro PET images showed that fluid of higher viscosity follows the wall motion with poor mixing, whereas good mixing was observed for a low viscosity fluid. PEPT data showed particle displacements comparable to the in vivo data. Increasing fluid viscosity favors the net forward propulsion of the tracked particles. The use of a floating particle demonstrated shorter residence times and greater velocities on the liquid surface, suggesting a surface wave that was moving faster than the bulk liquid. The DCM can provide an understanding of flow motion and behavior of particles with different buoyancy, which in turn may improve the design of drug formulations, whereby fragments of the dosage form and/or drug particles are suspended in the proximal colon.