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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK064775-08
Application #
8318772
Study Section
Special Emphasis Panel (ZRG1-SBIB-U (92))
Program Officer
Hamilton, Frank A
Project Start
2003-07-01
Project End
2015-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
8
Fiscal Year
2012
Total Cost
$261,389
Indirect Cost
$46,393
Name
Vanderbilt University Medical Center
Department
Surgery
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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Angeli, Timothy R; Du, Peng; Midgley, David et al. (2016) Acute Slow Wave Responses to High-Frequency Gastric Electrical Stimulation in Patients With Gastroparesis Defined by High-Resolution Mapping. Neuromodulation 19:864-871
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Du, Peng; O'Grady, Gregory; Paskaranandavadivel, Niranchan et al. (2016) Simultaneous anterior and posterior serosal mapping of gastric slow-wave dysrhythmias induced by vasopressin. Exp Physiol :
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Berry, Rachel; Paskaranandavadivel, Niranchan; Du, Peng et al. (2016) A novel retractable laparoscopic device for mapping gastrointestinal slow wave propagation patterns. Surg Endosc :
Paskaranandavadivel, Niranchan; Pan, Xingzheng; Du, Peng et al. (2015) Detection of the Recovery Phase of in vivo gastric slow wave recordings. Conf Proc IEEE Eng Med Biol Soc 2015:6094-7
Sathar, Shameer; Trew, Mark L; OGrady, Greg et al. (2015) A Multiscale Tridomain Model for Simulating Bioelectric Gastric Pacing. IEEE Trans Biomed Eng 62:2685-92
Cheng, L K (2015) Slow wave conduction patterns in the stomach: from Waller's foundations to current challenges. Acta Physiol (Oxf) 213:384-93

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