Multiscale Multiphysiology Models of the Brain

大脑的多尺度多生理学模型

基本信息

批准号：
1951446
负责人：
Daniela Calvetti
金额：
$ 30万
依托单位：
Case Western Reserve University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1951446&HistoricalAwards=false
关键词：
Multiscale Multiphysiology Models Brain

项目摘要

This project will develop mathematical models to study the link between electrophysiology, metabolism, and hemodynamics in the human brain. The human brain, accounting for only 2% of total body weight, consumes about 20% of the oxygen supply to produce energy needed to support its functions. Brain functions depend in a crucial way on the vascular system delivering oxygen and metabolites where needed and removing waste products in a timely fashion. Several questions related to the coordination of blood flow and brain activity level are still waiting for a definite answer, for example why an oversupply of oxygenated blood is delivered to activated brain regions. Understanding the coupling between brain electrophysiological activity and cerebral blood flow is crucial in many brain studies, and a model explaining the mechanism connecting cerebral electrophysiology and hemodynamics will be the key to interpret experimental data. The metabolic processes guaranteeing brain functions require a coordination between different types of brain cells, neurons and astrocytes, and are the crucial link between electrophysiology and hemodynamics. Multiscale, multi-physiology mathematical models are necessary to evaluate the feasibility of proposed interaction mechanisms, test novel oxygen transport paradigms, and understand the interplay between local and global brain phenomena. This project will open a mathematical window on the interactions and feedback of different human brain functions, with potential to uncover metabolic or vascular causes behind some brain disease states. Students will be trained through involvement in the research project. The integrated spatially distributed mathematical models developed as part of the project will be used to understand the signaling mechanisms linking neural activation to changes in the cerebral metabolism and hemodynamics, with a particular interest in the role of oxygen in normal brain activity and in the presence of cortical spreading depolarization waves related to migraine and traumatic brain injury. The new predictive computational models for the electric, metabolic, and blood flow dynamics of brain activation under normal and abnormal conditions will be based on ordinary and partial differential equations and will account for multiple spatial and temporal time scales. Modeling challenges arise from the need to interface brain functions at widely different spatial and temporal scales, involving quantities as different as electric charges and biochemical species concentrations. The design of a model capable of relating phenomena occurring in the gap junctions to changes at the organ level, e.g., in the concentrations of biochemical species or hemodynamic response, will be a great asset for the mathematical modeling community and may serve as a template for a variety of spatial and temporal multiscale paradigms. The models will depend on a multitude of parameters, whose estimation will be carried out within a Bayesian framework utilizing the tools developed for computational inverse problems. An important contribution of the project will be the quantification of uncertainty in the model predictions, which will indicate how much variability can be expected.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该项目将开发数学模型，以研究人脑的电生理学，代谢和血液动力学之间的联系。人脑仅占体重的2％，消耗了约20％的氧气供应，以产生支持其功能所需的能量。大脑功能以至关重要的方式取决于需要在需要的情况下提供氧气和代谢产物的血管系统，并及时消除废物产品。与血流和大脑活动水平的协调有关的几个问题仍在等待明确的答案，例如，为什么将含氧血液过度供应到激活的大脑区域。在许多大脑研究中，了解脑电生理活性和脑血流量之间的耦合至关重要，并且解释连接大脑电生理学和血液动力学的机制的模型将是解释实验数据的关键。确保大脑功能的代谢过程需要在不同类型的脑细胞，神经元和星形胶质细胞之间进行协调，并且是电生理学与血液动力学之间的关键联系。多尺度，多物理学数学模型对于评估提出的相互作用机制的可行性，测试新型的氧气传输范式以及了解局部和全球脑现象之间的相互作用所必需。该项目将打开有关不同人脑功能的相互作用和反馈的数学窗口，并有可能在某些脑部疾病状态下发现代谢或血管原因。学生将通过参与研究项目而接受培训。作为该项目的一部分开发的集成的空间分布式数学模型将用于了解将神经激活与脑代谢和血液动力学变化联系起来的信号传导机制，并特别感兴趣氧气在正常脑活动中的作用以及与迁移和迁移脑损伤相关的皮质扩散波动的作用。在正常和异常条件下的电气，代谢和血流动力学的新的预测计算模型将基于普通和部分微分方程，并将考虑多个空间和时间尺度。建模挑战是由于需要在空间和时间尺度上界面脑功能的界面功能，涉及与电荷和生化物种浓度不同的数量。能够将差距连接中发生现象与器官水平的变化相关的模型的设计，例如，在生化物种或血流动力学反应的浓度下，将是数学建模社区的重要资产，并且可以用作各种空间和时间颞叶式标准的模板。这些模型将取决于多种参数，其估计将在贝叶斯框架内使用用于计算反问题的工具进行。该项目的一个重要贡献是量化模型预测中的不确定性，这将表明可以预期多少可变性。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子和更广泛影响的评估审查标准来通过评估来获得支持的。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Modeling surface pH measurements of oocytes

模拟卵母细胞表面 pH 测量

DOI：
10.1088/2057-1976/ac71d0
发表时间：
2022
期刊：
Biomedical Physics & Engineering Express
影响因子：
1.4
作者：
Bocchinfuso, A;Calvetti, D;Somersalo, E
通讯作者：
Somersalo, E

Bayesian hierarchical dictionary learning

DOI：
10.1088/1361-6420/acad21
发表时间：
2022-12
期刊：
Inverse Problems
影响因子：
2.1
作者：
Nathan Waniorek;D. Calvetti;E. Somersalo
通讯作者：
Nathan Waniorek;D. Calvetti;E. Somersalo

On the fast track: Rapid construction of stellar stream paths

快车道上：快速构建恒星流路径

DOI：
10.1093/mnras/stad1166
发表时间：
2023
期刊：
Monthly Notices of the Royal Astronomical Society
影响因子：
4.8
作者：
Starkman, Nathaniel;Bovy, Jo;Webb, Jeremy J;Calvetti, Daniela;Somersalo, Erkki
通讯作者：
Somersalo, Erkki

Modeling Epidemic Spread among a Commuting Population Using Transport Schemes