Multiscale modelling of the microstructural evolution of nervous tissues through high-performance computing

该项目旨在解决英国在神经系统疾病医疗保健方面的一个关键社会挑战。据估计，神经系统疾病是英国残疾的主要原因，每年造成约五分之一的死亡。越来越多的证据表明力学在神经系统疾病中的关键作用，实验表明，神经退行性疾病，如多发性硬化症，阿尔茨海默病和脱髓鞘，导致神经组织微观结构的变化。例如，自闭症与结构可塑性相关的变化有关，这些变化导致树突棘（树突的微小突起，与其他神经元的相邻轴突形成功能性接触）形状和数量的改变。从建模的角度来看，已作出努力，了解这种神经系统疾病的机制，通过不同的理论和计算方法，并阐明创新的治疗策略。虽然在神经组织的功能和功能障碍的研究方面取得了进展，但仍需要解决许多共同的挑战，并且仍然缺少基于多尺度和多物理学框架将各个信息联系在一起的现实计算模拟。该提案中开发的方法将提供新的数学基础设施，并通过解释各个尺度下电化学机械相互作用之间的关系如何通过数学建模和高性能计算促进其演变，从而对神经组织产生基本的科学认识。该提案产生的成果和知识将对科学界，特别是对医疗保健最有益，因为它旨在了解有关神经系统疾病进展的一些机制，并揭示可用于构思新治疗策略的新信息。一个长期目标是加强科学界，通过可获得但复杂的计算机软件向生物医学转让技术。

This project seeks to address a key UK societal challenge in healthcare concerning neurological disorders. It is estimated that neurological conditions are a leading cause of disability in the UK and cause around one-fifth of all deaths yearly. Growing evidence points to the pivotal role of mechanics in neurological disorders and experiments show that neurodegenerative diseases, such as multiple sclerosis, Alzheimer's disease, and demyelination, lead to changes in nervous tissue microstructure. For instance, autism has been linked to structural plasticity-associated changes leading to alterations in dendritic spines' (tiny protrusions from dendrites, which form functional contacts with neighbouring axons of other neurons) shape and number. From the modelling point of view, efforts have been made to understand the mechanisms underlying such neurological conditions through different theoretical and computational approaches and to elucidate innovative treatment strategies. While advances have been made in the investigation of the function and dysfunction of nervous tissues, many common challenges still need to be addressed and realistic computational simulations based on a multiscale and multiphysics framework tying together the individual pieces of information are still missing. The methodologies developed in this proposal will provide new mathematical infrastructures and generate a fundamental scientific understanding of the nerve tissue by explaining how the relationship among electro-chemo-mechanical interactions at individual scales contributes to its evolution through mathematical modelling and high-performance computing. The outcomes and knowledge generated by the proposal will be of most benefit to the scientific community and, particularly, to healthcare as it aims at understanding some of the mechanisms concerning the progression of neurological disorders and shed light on new information that can be useful for the conception of novel treatment strategies. A long-term goal is to reinforce the scientific community in terms of the technological transfer towards biomedicine through accessible, but sophisticated, computer software.