In this project, we propose to develop the Virtual Stomach - a comprehensive model of stomach anatomy and function for developing electroceutical treatment of digestive disorders and conditions. This project will complement another ongoing project (#: OD023847; PI: Powley), which focuses on ?the living stomach?, by bridging modeling and physiology to develop simulations that will predict parameters for neuromodulation of gastric conditions. Our integration of anatomy and physiology to models and simulations for translational applications will realize neuromodulation therapies. To accomplish our objective, the project consists of three major tasks. Briefly, we will represent knowledge about the stomach as an atlas and a knowledge graph (Task 1), model the stomach at cell, tissue and organ levels (Task 2), and simulate electromechanical function of the stomach and its responses to neuromodulation therapies (Task 3). Task 1: Building an atlas and knowledge graph representation of the stomach 1.1: Define cell/neurite types and standardize gastric ontology into a knowledge graph 1.2: Characterize synaptic inputs to gastric motor neurons by chemistry and origin 1.3: Delineate ICC relationships to vagal innervation 1.4: Embed structural and functional data onto the anatomical scaffold 1.5: Parcellate the stomach 1.6: Compare rat and human stomach for forward/backward translation Task 2: Modeling the rat and human stomach in multiple scales 2.1: Model gastric anatomy, incorporating major muscle layers 2.2: Model electrophysiology of interstitial cells of Cajal, smooth muscle cells, and their coupling 2.3: Model neural control circuits and innervation of interstitial cells of Cajal and smooth muscles 2.4: Model gastric slow wave propagation in relation to neural innervation 2.5: Model active-tension and passive constitution relationships of gastric smooth muscles Task 3: Simulating gastric electrophysiology and motility given neuromodulation 3.1: Simulate normal gastric slow wave activity and its neural control 3.2: Simulate gastric motility coupled to gastric slow wave and neural activity 3.3: Simulate neuromodulation protocols and their effects on gastric motility 3.4: Validate model simulations with experimental observations This Virtual Stomach will embed existing knowledge into a credible (see here ) and sustainable resource, be computable, learnable and testable end-to-end, and be searchable and reusable with data analytics. This model will provide a platform to standardize reporting and integration of research findings on stomach anatomy and physiology, enable rapid prototyping and testing of neuromodulation therapies in silico before and complementary to preclinical and clinical studies, and serve as a biophysical model of the living stomach suitable for closed-loop neuromodulation.
