Development of a virtual gut model to aid in operative innovation during intestinal surgery

Introduction: Intestinal surgery is a common medical necessity carrying the risk for both morbidity and mortality. There is a lack of virtual operative models for predicting outcomes following novel experimental surgical techniques, particularly ones that account for nutrient absorption. Animal models offer an avenue for first line testing for surgical innovation but are not perfect physiological analogues to humans. Animal testing also presents significant financial and ethical burdens. Existing scientific literature has studied luminal fluid and solute mixing extensively. Model concerns include the fluid type (Newtonian vs non-Newtonian), fluid motion (laminate and turbulent as limiting cases), and modeling method. In our work, we are developing a computationally efficient small intestine model specifically designed for rapid adjustment of anatomic proportions, based on the physiological expectations of a patient, including small intestine length, lumen diameter, and dysmotility. Our model uses a type of lattice-Boltzmann model in which we use multiple models from prior literature to create a segmented, heuristic model allowing for modeling of different locations and types of surgical intervention, output fluid flow rates, and nutritional absorption. The mock interventions establish preliminary efficacy of novel surgical interventions, minimizing utilization of animal models and future risk to human patients.

Materials and

Methods: We began with an extensive literature review of over 25 articles in intestinal peristaltic modeling, with special emphasis on models with either closed form or approximation functions. We collected published and unpublished luminal data for normal and SBS adult and neonatal intestinal geometries to create a baseline of the known anatomic and physiologic norms of the human small intestine. Our intestine model is based around an n-section model created in Matlab and Simulink. In the model, each section represents approximately 1 cm for a linearly connected (meaning no loops or branches) intestine, and thus is 575 connected segments for an average length adult intestine. The number of sections can be increased or decreased depending upon the observed intestinal length. The model supports diameter changes and branching which would be seen in bowel anastomosis or procedures such as the Bianchi procedure. The primary physical dimension for each section is the diameter, which narrows slightly with progression from start to end of the intestine. The classic “c” shape of the duodenum is included as a perturbative term as a position-varying gravitational vector force. The model includes the bowel wall thickness as part of an indirect model on the expected flexure of the intestine, as are the electrical nerve signals for peristalsis. At the microscopic level, the dimensions and structure used for the villi in each section serve to change the fluid mechanics and nutrient uptake. Finally, the model sections are connected mathematically to incorporate propulsion of the chyme.

Results, Conclusions, and Discussions: Our model’s simulated nutritional absorption is based on the described absorption of a complex glucose with a model target absorption rate of 80 mmol/h for 25cm of intestine. The modeled enteric contents are the same composition as the fluid used in the study that got this absorption rate acknowledging, however, that this does not represent the composition of normal dietary intake. We use the approximation that the intestine produces 1.5 L of fluid in addition to the ingested fluids. Our model includes simulated gastric fluid production over time and peristaltic-aided nutrient uptake of a 240 mL protein drink that progresses through the model. We observed that for equal segment properties, the nutrient uptake in the jejunum was highest at the proximal portion of the duodenum and tapered approximately exponentially until exiting at the ileum. The model result does not match empirical findings that the absorption is roughly constant along the intestinal pathway. By adjusting the parameters for diameter and peristaltic activity we obtain a solution for nearly constant uptake of nutrients.

We have developed a heuristic virtual gut model as an avenue for pre-operative surgical innovation. The model can provide high-resolution predictions of intestinal motility and nutrient uptake which can be tested via methods such as functional MRI measurements. The end goal is to provide risk- and cost-reductions before pioneering a study in animal models.

The intestine is a vastly complex organ structure from an anatomic, secretive, absorptive, neuromuscular, and neuroendocrine perspective. Developing a perfect in silico replica has been in progress for nearly two decades and will likely take decades of further research to quantify physiological values which at this time are not clearly elucidated. An easily parametrized model aids in anticipating the effects of bowel resection or reconstruction. We anticipate that the proportional changes seen pre- and post-manipulation of the virtual gut model will provide valuable insight into the outcome of procedures even if the absolute numbers are currently of limited generalizability.

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