Research Collaboration Visit to the Auckland Bioengineering Institute, New Zealand.

尽管经过了世纪的研究，但心律失常的机制仍知之甚少。即使是现代实验方法也不能提供足够的时间和空间分辨率来追踪心脏组织样本中纤颤发展的细节，更不用说体内心脏了。人类遗传学的进展提供了某些基因对细胞活性影响的信息，但不能解释纤维性颤动产生的机制。因此，对于一些遗传性心脏病来说，第一个症状是死亡。结合数学模型和最新的心脏电活动的真实计算机模拟，我们对心脏纤颤和心脏性猝死的理解大大提高了，而随着我们接近全心脏模型的最终目标，计算机模拟或实际上计算机“测试”的影响预计会显著增加。通过心脏的心脏动作电位传播的生物解剖学和解剖学上的真实模拟由于每个细胞的大量方程和所需的巨大空间和时间尺度而在计算上是昂贵的。因此，通过通用数学模型分析可以获得的任何见解都是非常有价值的，因为它往往揭示通用机制，而不像直接的计算机模拟，直接的计算机模拟提供的答案只对特定的参数和初始条件的选择有效，并取决于计算机模型的准确性。请注意，尽管经过几十年的稳步发展，计算机模型在宏观尺度上仍然具有定性而不是定量的预测能力，例如，在涉及整个心脏或整个心室的情况下。我们在耗散涡动力学渐近分析方面的最新进展揭示了可激发层厚度急剧变化时涡相互作用的新现象。心脏折返与尖锐解剖特征（例如，梳状肌和心房中的终嵴）的这种相互作用可能导致与首次定位的位置相比，已建立的折返定位发生相当大的位移。在Belousov-Zhabotinski反应的实验中，已经证实了由与层中的急剧厚度变化的相互作用引起的涡旋漂移的渐近理论预测，并且在计算机模拟中用各种细胞激发模型进行了验证，从极其简化的"概念"模型到现实的离子动力学模型，以及从人工理想化几何形状到现实的人体心房解剖结构的组织几何形状。更好地理解这种现象可能在临床上具有重要意义，例如选择用于治疗心房颤动的个体消融策略。迄今为止，仅在单个人类心房模型上验证了所识别的新现象，并且理解这种效应在多大程度上是普遍的需要在各种心脏MRI解剖模型上进行广泛的测试，在实验测试和临床意义可以考虑之前。拟议项目的目的是参观新西兰奥克兰生物工程研究所，该研究所是心脏和心血管系统研究的国际领导者，结合了仪器开发、实验测量和建模。ABI心血管磁共振（CMR）成像组获得了最详细的心脏几何形状和组织微结构模型。这次访问将建立比远距离可行的更密切的合作，并提供在最新的解剖学和生物解剖学现实模型中对新现象进行详尽测试的可能性。申请人参加心脏生理学研讨会（2016年8月23日，韩国首尔）将获得额外的好处，这将是一个与该领域的世界领导者讨论我们最近的发现和未来研究方向的独特机会。

Despite over a century's study, the mechanisms of cardiac arrhythmias are poorly understood. Even modern experimental methods do not provide sufficient temporal and spacial resolution to trace down fine details of fibrillation development in samples of cardiac tissue, not to mention the heart in vivo. Advances in human genetics provide information on the impact of certain genes on cellular activity, but do not explain the resultant mechanisms by which fibrillation arises. Thus, for some genetic cardiac diseases, the first presenting symptom is death.Combination of mathematical modelling and the latest realistic computer simulations of electrical activity in the heart have much advanced our understanding of heart fibrillation and sudden cardiac death, and the impact of in-silico modelling, or indeed in-silico "testing", is expected to increase significantly as we approach the ultimate goal of the whole-heart modelling. Biophysically and anatomically realistic simulation of cardiac action potential propagation through the heart is computationally expensive due to the huge number of equations per cell and the vast spacial and temporal scales required. Therefore any insights that can be obtained through generic mathematical model analysis is very valuable, as it tends to reveal generic mechanisms, unlike direct computer simulations, which provide answers valid only for a specific choice of parameters and initial conditions and depend on the computer model accuracy. Note that despite of the decades of steady progress, computer models still have qualitative rather than quantitative predictive power on the macroscopic scale, e.g. where whole heart or a whole chamber of the heart are concerned. Our recent progress in asymptotic analysis of dissipative vortices dynamics has revealed a new phenomenon of the vortices interaction with sharp variations of thickness in excitable layer. Such interaction of cardiac re-entry with sharp anatomical features, as e.g. pectinate muscles and terminal crest in atria, can cause considerable displacement of established localisation of re-entry compared to where it was first localised. The asymptotic theory prediction of the vortices drift caused by interaction with sharp thickness variations in a layer has been confirmed in experiments with Belousov-Zhabotinski reaction, and verified in computer simulations with a variety of cell excitation models, from extremely simplified "conceptual" models to realistic ionic kinetics models, and for tissue geometries from artificial idealised geometries to a realistic anatomy of human atria. A better underestanding of this phenomenon may have significant implications in clinics, say for chosing an individual ablation strategy for treatment of atrial fibrillation.Validation of the identified new phenomenon has so far been done only on a single model of human atrium, and understanding of to what extent the effect is universal requires extensive testing on a wide variety of cardiac MRI anatomy models, before experimental testing and clinical implications can be considered. The aim of the proposed project is to visit the Auckland Bioengineering Institute (ABI), New Zealand, which is an international leader in the heart and cardiovascular system research that combines instrumentation development, experimental measurements and modelling. ABI cardiovascular magnetic resonance (CMR) imaging group obtains most detail models of heart geometry and tissue microstructure. This visit will forge a closer collaboration than it is feasible from a distance, and provide a possibility of exhaustive testing of the new phenomenon in the most up-to-date anatomically and biophysically realistic models. An extra benefit will be provided by the applicant's participation in Cardiac Physiome Workshop (23 August 2016, Seoul, Korea), which will be a unique opportunity to discuss our recent findings and future directions of research with the world leaders in the field.