As reductionist biomedical science succeeds in elucidating ever more detail at the molecular level, a mathematical modeling framework will become increasingly important to cope with this explosion of data and to relate integrated whole organ function to underlying biophysically detailed mechanisms that exploit this molecular knowledge. The proposed research has two primary long term objectives. The first is to continue development of an extensible anatomically and biophysically based modeling framework that can be used to integrate the physiological, anatomical and medical knowledge of the gastrointestinal (GI) system. The second objective is to focus this integrative modeling framework on three major diseases of the GI tract that affect a significant number of people in the United States, namely intestinal ischemia, diabetic gastro paresis and irritable bowel syndrome (IBS). Prior research has shown that recordings of the magnetic field from gastrointestinal electrical activity using multichannel Superconducting QUantum Interference Device (SQUID) magnetometers provides a noninvasive and noncontact assessment of the physiological state of the GI smooth muscle. We will combine multichannel SQUID and cutaneous electrode measurements with anatomically based integrative computer models to investigate the inter- and intra-subject effects of intestinal ischemia, gastro paresis and IBS on GI electrical activity noninvasively. We hypothesize that the resulting integration of anatomical and physiological biophysical properties will serve as a basis for a more complete understanding of the gastrointestinal system and will aid in the detection and diagnosis and, ultimately, in the treatment of gastrointestinal disorders. This is necessarily a collaborative project that initially involves five main groups (the Living State Physics Group at Vanderbilt University, the Department of Surgery at Vanderbilt University, the Department of Physiology and Cell Biology, University of Nevada, the Enteric Neuroscience Program at Mayo Clinic and the Auckland Bioengineering Institute) and combines expertise in integrated biophysically based modeling with physiological, clinical and research expertise in the function of the gastrointestinal system

Public Health Relevance

Currently there are no non-invasive diagnostic procedures for assessing many electrophysiological GI disorders despite their prevalence. This project aims to investigate the bioelectromagnetic fields associated with three common gastrointestinal conditions that affect a significant proportion of the population: intestinal ischemia, gastro paresis and irritable bowel syndrome. We aim to address significant gaps in our knowledge about each of these conditions and ultimately wish to develop a method to non-invasively determine underlying physiological and pathophysiological mechanisms of gastrointestinal electrical activity. Narrative Currently there are no non-invasive diagnostic procedures for assessing many electrophysiological GI disorders despite their prevalence. This project aims to investigate the bioelectromagnetic fields associated with three common gastrointestinal conditions that affect a significant proportion of the population: intestinal ischemia, gastroparesis and irritable bowel syndrome. We aim to address significant gaps in our knowledge about each of these conditions and ultimately wish to develop a method to non-invasively determine underlying physiological and pathophysiological mechanisms of gastrointestinal electrical activity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK064775-10
Application #
8704335
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Hamilton, Frank A
Project Start
2003-07-01
Project End
2015-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
10
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Surgery
Type
Schools of Medicine
DUNS #
City
Nashville
State
TN
Country
United States
Zip Code
37212
Mayne, Terence P; Paskaranandavadivel, Niranchan; Erickson, Jonathan C et al. (2018) Improved Visualization of Gastrointestinal Slow Wave Propagation Using a Novel Wavefront-Orientation Interpolation Technique. IEEE Trans Biomed Eng 65:319-326
Lin, Anthony Y; Du, Peng; Dinning, Philip G et al. (2017) High-resolution anatomic correlation of cyclic motor patterns in the human colon: Evidence of a rectosigmoid brake. Am J Physiol Gastrointest Liver Physiol 312:G508-G515
Paskaranandavadivel, Niranchan; OGrady, Gregory; Cheng, Leo K (2017) Time-Delay Mapping of High-Resolution Gastric Slow-Wave Activity. IEEE Trans Biomed Eng 64:166-172
Angeli, T R; Du, P; Paskaranandavadivel, N et al. (2017) High-resolution electrical mapping of porcine gastric slow-wave propagation from the mucosal surface. Neurogastroenterol Motil 29:
Berry, Rachel; Paskaranandavadivel, Niranchan; Du, Peng et al. (2017) A novel retractable laparoscopic device for mapping gastrointestinal slow wave propagation patterns. Surg Endosc 31:477-486
Zifan, Ali; Kumar, Dushyant; Cheng, Leo K et al. (2017) Three-Dimensional Myoarchitecture of the Lower Esophageal Sphincter and Esophageal Hiatus Using Optical Sectioning Microscopy. Sci Rep 7:13188
Du, Peng; Calder, Stefan; Angeli, Timothy R et al. (2017) Progress in Mathematical Modeling of Gastrointestinal Slow Wave Abnormalities. Front Physiol 8:1136
Du, Peng; Paskaranandavadivel, Niranchan; Angeli, Timothy R et al. (2016) The virtual intestine: in silico modeling of small intestinal electrophysiology and motility and the applications. Wiley Interdiscip Rev Syst Biol Med 8:69-85
Berry, Rachel; Miyagawa, Taimei; Paskaranandavadivel, Niranchan et al. (2016) Functional physiology of the human terminal antrum defined by high-resolution electrical mapping and computational modeling. Am J Physiol Gastrointest Liver Physiol 311:G895-G902
Erickson, Jonathan C; Putney, Joy; Hilbert, Douglas et al. (2016) Iterative Covariance-Based Removal of Time-Synchronous Artifacts: Application to Gastrointestinal Electrical Recordings. IEEE Trans Biomed Eng 63:2262-2272

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