Realistic models of gastrointestinal bioelectromagnetism

描述(申请人提供)：随着简化论生物医学在分子水平上成功地阐明了更多的细节，数学建模框架将变得越来越重要，以应对这种数据爆炸，并将完整的整个器官功能与利用这种分子知识的潜在生物物理详细机制联系起来。这项拟议的研究有两个主要的长期目标。首先是继续开发可扩展的基于解剖学和生物物理学的建模框架，该框架可用于整合胃肠道(GI)系统的生理、解剖和医学知识。第二个目标是将这个综合建模框架集中在影响美国相当数量的人的三种主要胃肠道疾病上，即肠缺血、糖尿病胃轻瘫和肠易激综合征(IBS)。先前的研究表明，使用多通道超导量子干涉装置(SQUID)磁力仪记录胃肠道电活动的磁场可以提供对胃肠道平滑肌生理状态的非侵入性和非接触性评估。我们将结合多通道鱿鱼和皮肤电极测量以及基于解剖学的综合计算机模型来研究肠缺血、胃轻瘫和IBS对胃肠电活动的无创影响。我们假设，由此产生的解剖和生理生物物理特性的整合将作为更完整地了解胃肠道系统的基础，并将有助于检测和诊断，并最终有助于胃肠道疾病的治疗。这必然是一个合作项目，最初涉及五个主要小组(范德比尔特大学的Living State物理小组、范德比尔特大学的外科系、内华达大学的生理和细胞生物学系、梅奥诊所的肠道神经科学计划和奥克兰生物工程研究所)，并将基于生物物理的综合建模专业知识与胃肠道系统功能的生理、临床和研究专业知识结合起来 公共卫生相关性：目前没有非侵入性诊断程序来评估许多电生理性胃肠道疾病，尽管它们很普遍。该项目旨在研究与三种常见胃肠道疾病相关的生物电磁场，这三种疾病影响着相当大一部分人：肠缺血、胃轻瘫和肠易激综合征。我们的目标是解决我们对这些情况的认识上的重大差距，并最终希望开发一种方法来非侵入性地确定胃肠道电活动的潜在生理和病理生理学机制。

DESCRIPTION (provided by applicant): 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.