Diversity in blood flow control to the brain: moving from individualized modelling towards personalized treatment of the injured brain

大脑血流控制的多样性：从个性化建模转向受伤大脑的个性化治疗

• 批准号: EP/K036157/1
• 负责人: David Simpson
• 金额: $ 41.48万
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FK036157%2F1
• 关键词: Diversity; blood; flow; control; brain

The brain, more than any other organ in the body, requires a constant supply of blood in order to maintain its function. When blood pressure drops, small arteries dilate to restore flow levels, and when pressure rises, they constrict to protect the most delicate blood vessels and avoid bleeding in the brain. This control system can however become impaired for example following stroke, head trauma, in dementia or following premature birth and this has been associated with worse outcomes for the patient. Failure of the control system also has important implications for the management of patient's blood pressure: changes in blood pressure could be dangerous without the protection of this 'autoregulatory' system.This project aims to improve methods for measuring cerebral autoregulation and to gain a deeper understanding of the complex relationship between blood pressure and blood flow in healthy individuals and patients following stroke. While much work has been done in this field, experimental and technical challenges in assessing the control function has so far led to only limited benefit to patients. The control system is highly complex and, typical of such biological systems, there are multiple complementary physiological mechanisms working in parallel. There are indications that even in healthy individuals there are differences in the manner and the extent to which they control the flow. Impairment may also affect different mechanisms to a varying extent in different individuals. This has important implications for grading an individual's autoregulation, as the conventional approach, based on a single number to quantifying the strength of autoregulation, is likely to be inadequate. This project sets out in a new direction for the field, by focussing on the diversity of ways in which brain blood flow may operate in different individuals, rather than studying average group behaviour, which has so far been the predominant approach. It also breaks new ground methodologically by integrating the study of blood flow control with that of blood pressure control, based on the complementary roles these have in ensuring that the brain receives sufficient blood.We will thus investigate a sample of healthy volunteers in detail. We will repeatedly record blood pressure and flow, heart-rate and carbon dioxide levels during spontaneous fluctuations at rest, and during challenges in a range of protocols (periodic squatting, raising the upper body of volunteers, applying random pressure changes to a cuff around the thighs, breathing air with 5% CO2). Using advanced data analysis methods (signal processing and mathematical modelling), some of which will be developed and optimized as part of this project, we will quantify the simultaneous control of blood pressure and flow and aim to identify characteristic differences between individuals and sub-groups. Building on the differences observed in the healthy subjects, we will also study a group of patients during the first days and weeks after they have suffered a stroke. We aim to quantify the impairments in blood flow and blood pressure control, with a view to improving understanding of the evolution of this condition, and how this might impact the management of their blood pressure in the acute and chronic phase. Correct functioning of these control systems is thought to be key in making effective clinical decisions, but currently there are no clear guidelines due to a lack of understanding of the impairments in each individual patient and also the methods for their measurement.The overarching aim of this multicentre and multidisciplinary project is thus to lay the foundations for a personalized approach to managing blood pressure control after stroke, based on characterising individuals' blood pressure and flow control, and thus to protect patients' brains from further damage.

大脑比体内任何其他器官都多，需要持续的血液供应才能维持其功能。当血压下降时，小动脉会扩张以恢复流量水平，当压力升高时，它们会收缩以保护最细腻的血管并避免大脑流血。但是，这种控制系统可能会受到损害，例如中风后，头部外伤，痴呆症或过早出生后，这与患者的结局差有关。控制系统的失败对患者血压的管理也具有重要意义：如果没有这种“自动调节”系统的保护，血压的变化可能是危险的。该项目旨在改善衡量大脑自动调节的方法，并在Stroke后健康的个体和患者中对血压和血液流动之间的复杂关系进行更深入的了解。尽管该领域已经完成了许多工作，但在评估控制功能方面的实验和技术挑战迄今仅导致对患者的好处有限。控制系统是高度复杂的，并且是这种生物系统的典型特征，并且有多种并行起作用的互补生理机制。有迹象表明，即使在健康的个体中，他们控制流动的方式和程度也存在差异。在不同个体中，损伤也可能在不同程度上影响不同的机制。这对于对个体的自动调节进行评分具有重要意义，因为基于单个数字来量化自动调节强度的常规方法可能是不足的。该项目通过重点关注脑血流可能在不同个体中起作用的方式的多样性，而不是研究平均群体行为，这是迄今为止主要的方法，这是脑血流可能起作用的多样性，从而朝着该领域的新方向朝着新的方向发展。它还基于这些互补作用在确保大脑接受足够的血液方面的互补作用，通过将血流控制的研究与血压控制的研究相结合，从而在方法论上打破了新的地面。因此，我们将详细研究健康志愿者的样本。我们将在静止时自发波动期间以及在一系列方案中的挑战期间反复记录血压和流动，心率和二氧化碳水平（周期性蹲下，增加志愿者的上身，将随机压力变化，对大腿周围的袖口施加随机压力，以5％的CO2呼吸空气）。使用先进的数据分析方法（信号处理和数学建模），其中一些将作为本项目的一部分进行开发和优化，我们将同时量化血压和流动的同时控制，并旨在确定个体和子组之间的特征差异。在健康受试者中观察到的差异的基础上，我们还将在中风后的头几天和几周内研究一组患者。我们旨在量化血流和血压控制的损害，以提高人们对这种情况演变的了解，以及这可能如何影响急性和慢性期在血压的管理。认为这些控制系统的正确功能被认为是做出有效临床决策的关键，但是由于缺乏对每个患者的损害的了解以及其测量方法的理解，因此目前尚无明确的指南。因此，该多中心和多学科项目的总体目的是为了在造成血液控制的基础上，以使血液控制的基础和流动型的基础，并奠定了疾病的基础。 损害。

项目成果

Estimation of confidence limits for descriptive indexes derived from autoregressive analysis of time series: Methods and application to heart rate variability.

• DOI: 10.1371/journal.pone.0183230
• 发表时间: 2017
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Beda A;Simpson DM;Faes L
• 通讯作者: Faes L

Structural Identifiability Analysis of Fractional Order Models with Applications in Battery Systems

分数阶模型的结构可辨识性分析及其在电池系统中的应用

• DOI: 10.48550/arxiv.1511.01402
• 发表时间: 2015
• 作者: Alavi S

Estimating confidence intervals for cerebral autoregulation: a parametric bootstrap approach.

估计大脑自动调节的置信区间：参数引导方法。

• DOI: 10.1088/1361-6579/ac27b8
• 发表时间: 2021
• 期刊: Physiological measurement
• 影响因子: 3.2
• 作者: Bryant JED

Assessment of dynamic cerebral autoregulation in humans: Is reproducibility dependent on blood pressure variability?

• DOI: 10.1371/journal.pone.0227651
• 发表时间: 2020-01-10
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Elting, Jan Willem;Sanders, Marit L.;Claassen, Jurgen A. H. R.
• 通讯作者: Claassen, Jurgen A. H. R.

White paper on transfer function analysis: a consensus guideline

传递函数分析白皮书：共识指南

• 发表时间: 2015
• 作者: Claassen JA